[House Hearing, 110 Congress]
[From the U.S. Government Publishing Office]





                WHY DOES THE U.S. DEPARTMENT OF VETERANS
                  AFFAIRS CONTINUE TO GIVE A SUICIDE-
                     INDUCING DRUG TO VETERANS WITH
                    POST TRAUMATIC STRESS DISORDER?

=======================================================================

                                HEARING

                               before the

                     COMMITTEE ON VETERANS' AFFAIRS
                     U.S. HOUSE OF REPRESENTATIVES

                       ONE HUNDRED TENTH CONGRESS

                             SECOND SESSION

                               __________

                              JULY 9, 2008

                               __________

                           Serial No. 110-96

                               __________

       Printed for the use of the Committee on Veterans' Affairs








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                     COMMITTEE ON VETERANS' AFFAIRS

                    BOB FILNER, California, Chairman

CORRINE BROWN, Florida               STEVE BUYER, Indiana, Ranking
VIC SNYDER, Arkansas                 CLIFF STEARNS, Florida
MICHAEL H. MICHAUD, Maine            JERRY MORAN, Kansas
STEPHANIE HERSETH SANDLIN, South     HENRY E. BROWN, Jr., South 
Dakota                               Carolina
HARRY E. MITCHELL, Arizona           JEFF MILLER, Florida
JOHN J. HALL, New York               JOHN BOOZMAN, Arkansas
PHIL HARE, Illinois                  GINNY BROWN-WAITE, Florida
SHELLEY BERKLEY, Nevada              MICHAEL R. TURNER, Ohio
JOHN T. SALAZAR, Colorado            BRIAN P. BILBRAY, California
CIRO D. RODRIGUEZ, Texas             DOUG LAMBORN, Colorado
JOE DONNELLY, Indiana                GUS M. BILIRAKIS, Florida
JERRY McNERNEY, California           VERN BUCHANAN, Florida
ZACHARY T. SPACE, Ohio               STEVE SCALISE, Louisiana
TIMOTHY J. WALZ, Minnesota
DONALD J. CAZAYOUX, Jr., Louisiana

                   Malcom A. Shorter, Staff Director

Pursuant to clause 2(e)(4) of Rule XI of the Rules of the House, public 
hearing records of the Committee on Veterans' Affairs are also 
published in electronic form. The printed hearing record remains the 
official version. Because electronic submissions are used to prepare 
both printed and electronic versions of the hearing record, the process 
of converting between various electronic formats may introduce 
unintentional errors or omissions. Such occurrences are inherent in the 
current publication process and should diminish as the process is 
further refined.


                            C O N T E N T S

                               __________

                              July 9, 2008

                                                                   Page
Why Does the U.S. Department of Veterans Affairs Continue to Give 
  a Suicide-Inducing Drug to Veterans with Post Traumatic Stress 
  Disorder?......................................................     1

                           OPENING STATEMENTS

Chairman Bob Filner..............................................     1
    Prepared statement of Chairman Filner........................    82
Hon. Steve Buyer, Ranking Republican Member......................     4
    Prepared statement of Congressman Buyer......................    83
Hon. John J. Hall................................................     7
Hon. Cliff Stearns...............................................     8
Hon. Phil Hare...................................................     9
Hon. Steve Scalise...............................................    10
    Prepared statement of Congressman Scalise....................    85
Hon. Jerry McNerney..............................................    10
Hon. Timothy J. Walz.............................................    11
Hon. Harry E. Mitchell, prepared statement of....................    85
Hon. John T. Salazar, prepared statement of......................    85

                               WITNESSES

U.S. Department of Veterans Affairs:
    Hon. James B. Peake, M.D., Secretary.........................    33
      GPrepared statement of Secretary Peake.....................    92
    John D. Daigh, Jr., M.D., CPA, Assistant Inspector General 
      for Healthcare Inspections, Office of Inspector General....    72
      GPrepared statement of Dr. Daigh...........................   108
U.S. Department of Health and Human Services, Paul Seligman, 
  M.D., M.P.H, Associate Director of Safety Policy and 
  Communication, Center for Drug Evaluation and Research, Food 
  and Drug Administration........................................    40
    Prepared statement of Dr. Seligman...........................   101

                                 ______

Elliott, James G., Silver Spring, MD.............................    12
    Prepared statement of Mr. Elliott............................    86
Pfizer Inc., New York, NY, Ponni Subbiah, M.D., M.P.H., Vice 
  President, Medical Affairs.....................................    69
    Prepared statement of Dr. Subbiah............................   105
Soldiers for the Truth Foundation, Lieutenant Colonel Roger G. 
  Charles, USMC (Ret.), Vice-Chairman, Board of Trustees, and 
  Editor, DefenseWatch, on behalf of Eilhys England Hackworth, 
  Chairperson, Board of Trustees, Soldiers for the Truth 
  Foundation.....................................................    12
    Prepared statement of Lieutenant Colonel Charles.............    90

                       SUBMISSION FOR THE RECORD

Koocher, Gerald P., Ph.D., Professor and Dean, School of Health 
  Sciences, Simmons College, Boston, MA, statement...............   117

                   MATERIAL SUBMITTED FOR THE RECORD

Resolution:

    Adopted Resolution of the Committee Naming the Democratic 
      Membership of the Standing Subcommittee on Health for the 
      110th Congress.............................................   119

Newspaper Articles:
    ``VA Testing Drugs on War Veterans, Experiments Raise Ethical 
      Questions,'' The Washington Times, by Audrey Hudson, June 
      17, 2008...................................................   119
    ``Congress Demands VA Investigation, Obama, Pelosi, and 
      Others Hit Drug Testing, The Washington Times, by Audrey 
      Hudson and S.A. Miller, June 18, 2008......................   123
    ``Veterans as `Lab Rats','' The Washington Times Editorial, 
      June 18, 2008..............................................   124
    ``VA Reports More Chantix Effects, Study Participants Had 26 
      `Serious' Events, The Washington Times, by Audrey Hudson 
      and Amy Fagan, June 19, 2008...............................   125
    ``Doctors Raised Chantix Worries Last Year, Quiet 
      Investigation Preceded Warnings by Months,'' The Washington 
      Times, by Audrey Hudson and Amy Fagan, July 8, 2008........   127

Post Hearing Follow-up, Questions and Responses for the Record:

    Christine O. Hill, Acting Assistant Secretary, Office of the 
      Assistant Secretary for Congressional and Legislative 
      Affairs, U.S. Department of Veterans Affairs, to Hon. Bob 
      Filner, Chairman, Committee on Veterans' Affairs, letter 
      dated July 18, 2008, and attached report entitled, 
      ``Quality of Care Concern, Veterans Integrated Service 
      Network 5, Veterans Affairs Medical Center, Washington, 
      DC,'' Interim Report 2008-D-963, Office of the Medical 
      Inspector, Veterans Health Administration, U.S. Department 
      of Veterans Affairs, July 18, 2008, responding to a request 
      from Congresswoman Berkley for follow-up information [The 
      attached report will be retained in the Committee files due 
      to confidential personal information included in the 
      report.]...................................................   129
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      James Elliott, Silver Spring, MD, letter dated July 14, 
      2008, and Mr. Elliott's responses..........................   129
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      Lieutenant Colonel Roger Charles, USMC (Ret.), Vice-
      Chairman, Soldiers for the Truth, letter dated July 14, 
      2008, and Colonel Charles' responses.......................   130
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      Hon. James B. Peake, M.D., Secretary, U.S. Department of 
      Veterans Affairs, letter dated July 14, 2008, and VA 
      responses..................................................   131
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      Paul Seligman, M.D., M.P.H., Associate Director of Safety 
      Policy and Communication, Center for Drug Evaluation and 
      Research, Food and Drug Administration, letter dated July 
      14, 2008, and response from Stephen R. Mason, Acting 
      Assistant Commissioner for Legislation, Food and Drug 
      Administration, U.S. Department of Health and Human 
      Services, letter dated September 16, 2008..................   136
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      Ponni Subbiah, M.D., M.P.H., Vice President, Medical 
      Affairs, Pfizer Inc., letter dated July 14, 2008, and 
      response letter dated August 20, 2008 [The attachment to 
      the letter will be retained in the Committee files due to 
      confidential personal information included in the 
      attachment.]...............................................   140
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      John D. Daigh, Jr., M.D., CPA, Assistant Inspector General 
      for Healthcare Inspections, Office of Inspector General, 
      U.S. Department of Veterans Affairs, letter dated July 14, 
      2008, and response from Hon. George J. Opfer, Inspector 
      General, U.S. Department of Veterans Affairs, letter dated 
      August 22, 2008............................................   144
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      Gerald P. Koocher, Ph.D., ABPP, Dean and Professor, School 
      of Health Sciences, Simmons College, Boston, MA, letter 
      dated July 14, 2008, and Mr. Koocher's response............   146
    Hon. Bob Filner, Chairman, Committee on Veterans' Affairs, to 
      Hon. James B. Peake, M.D., Secretary, U.S. Department of 
      Veterans Affairs, letter dated July 29, 2008, formally 
      requesting a list of patients given the smoking-cessation 
      drug Chantix, and response letter dated September 26, 2008 
      [The attachments to the letter will be retained in the 
      Committee files due to confidential personal information 
      included in attachment.]...................................   148
 
                    WHY DOES THE U.S. DEPARTMENT OF
                   VETERANS AFFAIRS CONTINUE TO GIVE
                  A SUICIDE-INDUCING DRUG TO VETERANS
                  WITH POST TRAUMATIC STRESS DISORDER?

                              ----------                              


                        WEDNESDAY, JULY 9, 2008

                     U.S. House of Representatives,
                            Committee on Veterans' Affairs,
                                                    Washington, DC.

    The Committee met, pursuant to notice, at 10:05 a.m., in 
Room 334, Cannon House Office Building, Hon. Bob Filner 
[Chairman of the Committee] presiding.
    Present: Representatives Filner, Brown of Florida, Snyder, 
Herseth Sandlin, Mitchell, Hall, Hare, Berkley, Salazar, 
Rodriguez, McNerney, Space, Walz, Cazayoux, Buyer, Stearns, 
Boozman, Lamborn, Buchanan, and Scalise.

              OPENING STATEMENT OF CHAIRMAN FILNER

    The Chairman. This meeting of the House Committee on 
Veterans' Affairs will come to order. And we have an important 
hearing today, but before we get started, we have a couple of 
housekeeping things that need to be done.
    First, I ask unanimous consent that all Members may have 
five legislative days in which to revise and extend their 
remarks. Hearing no objection, so ordered.
    We also have to consider a resolution to designate a new 
Democratic Subcommittee assignment to include our newest Member 
of the Committee, Don Cazayoux.
    [The resolution appears on p. 119.]
    The Chairman. Don, make sure we do it right, okay?
    Don agreed to fill the vacancy on the Subcommittee on 
Health, which was made available when Mike Doyle resigned from 
the Committee. The Democratic Members of the Committee agreed 
to the assignment on June 17th, and now it is before the full 
Committee to approve the actions of the Democratic Caucus. The 
list of the Democratic Members of the Subcommittee on Health 
are in front of you, and I would ask for a motion to approve 
the resolution.
    Mr. Buyer. I so move.
    Ms. Berkley. I second it.
    The Chairman. We want to buy in Mr. Buyer on this. Motion 
made by Mr. Buyer, seconded by Ms. Berkley. All those in favor, 
say aye.
    Opposed?
    The motion carries unanimously.
    Mr. Cazayoux, we welcome you to the Subcommittee on Health. 
We are looking forward to your participation.
    Mr. Cazayoux. Thank you.
    The Chairman. And from talking to you, I know--as a 
representative of a rural area, there are a lot of problems 
with access and we intend to be looking at this as a Committee, 
and in the areas that you represent.
    Mr. Cazayoux. Thank you, Mr. Chairman and Members, as well 
as Ranking Member Buyer and Subcommittee Chairman Michaud.
    I'm honored to serve on this Subcommittee. Obviously, it is 
a Committee I believe is essential for helping secure benefits 
for those who have put their bodies on the line every day, and 
I'm honored to be able to serve and I'll work hard as a Member 
of this Subcommittee to ensure that the veterans of this 
country achieve and are assured of the benefits that they 
deserve.
    But thank you so much.
    The Chairman. Thank you, sir, and welcome to the Committee. 
The Subcommittee will probably be meeting this week.
    We thank all the Members of the Committee, our witnesses 
and those of you who are here to watch the proceedings. Like 
many people in this country, I was appalled when The Washington 
Times published articles revealing that the U.S. Department of 
Veterans Affairs (VA) was, and continues to use, the drug 
Chantix' in Cooperative Studies Program (CSP) 519 
that is smoking cessation treatment for veterans with post 
traumatic stress disorder (PTSD).
    [The Washington Times articles appear on p. 119.]
    The Chairman. Some veterans with PTSD, enrolled in the VA 
smoking cessation study were being, and continue to be, 
administered Chantix'. The drug did receive Food and 
Drug Administration (FDA) approval in May of 2006. However, on 
November 20, 2007, the FDA issued an early communication about 
an ongoing safety review of Chantix'. It revealed 
that FDA had received reports of ``suicidal thoughts and 
aggressive and erratic behavior in patients who have taken 
Chantix'.''
    At this point, I believe a prudent course of action would 
have been for the VA to suspend the study and immediately 
notify all patients of the possible danger. The loss of any 
veteran to suicide is a tragedy. Since December 2007, this 
Committee has held two hearings regarding the issue of veteran 
suicide; and that is why I fail to understand why the VA did 
not react when the FDA issued the early communication 
concerning the dangerous side effects of Chantix'.
    A few months later, in February of 2008, the FDA issued a 
Public Health Advisory stating, ``Chantix' may cause 
worsening of current psychiatric illness, even if it is 
currently under control and may cause an old psychiatric 
illness to occur. Symptoms may include anxiety, nervousness, 
tension, depressed mood, unusual behaviors and thinking about 
or attempted suicide.'' According to the records, the VA waited 
until the end of February 2008, that is, a month later, to send 
the letter and new consent form to study participants to notify 
them of the dangers associated with Chantix'.
    The letter informed patients that they may experience an 
increase in psychiatric symptoms such as anxiety, nervousness, 
tension, depression, as well as untoward changes in behavior. 
It failed to mention in that letter that Chantix' 
may lead to suicide ideation or attempted suicide. That fact 
was buried in a consent form, and we have to put this in the 
context of issues that we have had with the VA on statistics 
about suicide, of taking the issue seriously.
    We had two hearings where there seemed to be an attempt to 
downplay the numbers, a real lack of speed in giving this 
Committee information that the VA had; and downplaying, in 
fact, the sense that if you have 1,000 suicide attempts per 
month of veterans in your care, something is wrong. That is the 
context in which we are viewing this particular situation.
    Whatever warning was issued was too late for Mr. Elliott, 
an Army veteran of Operation Iraqi Freedom. In February, as he 
will soon tell us he suffered a psychotic episode that led to a 
confrontation with the police.
    And, Mr. Elliott, I appreciate you being here today. I know 
it is not easy to talk about these things, and we appreciate 
your interest in helping other veterans as well as yourself.
    As I said, there are a series of incidents that have given 
us concern about this. Suicides in Dallas, for example; e-mails 
suggesting that VA providers downgrade the diagnosis of PTSD to 
adjustment disorder, to an e-mail downplaying the epidemic of 
suicides in the VA. They have caused all of us on this 
Committee to question the VA's accountability measures and the 
Department's dedication to addressing the mental health needs 
of our returning servicemembers.
    So we want to look at not only the exact procedures for 
handling human research subjects and determining whether they 
were followed in design and execution of this smoking cessation 
study and explore whether there was adequate oversight of the 
study. I'd like also to find out about VA's responsibility to 
respond to the FDA advisories and VA's decision to continue to 
use Chantix', a suicide-inducing drug, on veterans 
with PTSD.
    But I think in a larger sense we use this hearing today to 
ask the VA to take responsibility and to hold people 
accountable for the numerous issues that have been identified 
over the last few months. Both e-mails that have become public 
because of legal action--not because they were just given to 
us--were explained by the VA with the term they were 
``unfortunate.'' These were more than unfortunate; these 
involve life and death of the soldiers and veterans under our 
care.
    The Texas e-mail said: ``Given that we are having more and 
more compensation-seeking veterans, I'd like to suggest that 
you refrain from giving a diagnosis of PTSD straight up, 
consider adjustment disorder.'' Four patients committed suicide 
in Dallas, and the psychiatric ward was forced to close. We 
keep hearing these things time and time again, but do not see 
any action or any sense of responsibility. Talk is cheap, 
especially when it comes to the safety and well-being of our 
veterans.
    We have seen a pattern in all of these. It is deny, deny, 
deny. And then, when caught and confronted, it is cover up, 
cover up, cover up, and then minimizing the importance of the 
issue or showing that this particular veteran is merely an 
anomaly. No one is held accountable and the system goes on.
    When questioned on this and in the various articles that 
have appeared, the VA immediately wants to defend the process 
that is being followed. This is not about the process. It is 
about the veteran. And the question really today is, when will 
the VA stop being the veteran's adversary in these processes 
and start being the veteran's advocate? We're talking about our 
veterans, our children. We want them defended.
    I would recognize for an opening statement, Mr. Buyer.
    [The prepared statement of Chairman Filner appears on p. 
82.]

             OPENING STATEMENT OF HON. STEVE BUYER

    Mr. Buyer. Thank you, Mr. Chairman for yielding.
    By way of opening, I'd like for you to know I'm very 
bothered by the title of the hearing. You've titled this 
hearing ``Why Does the VA Continue to Give a Suicide-Inducing 
Drug to Veterans With PTSD?``
    Now, calling an FDA-approved drug, Chantix', a 
suicide-inducing drug, I believe, is inflammatory and it is 
misleading. And I believe by titling this hearing as you have 
done misses the mark. The issue I believe before us on which we 
should focus is Human Subject Research Protection and whether 
the protocols of the Common Rule have been followed by the VA.
    Now, at the end of your opening, I agree with you; when you 
then finally began to focus that we really need to look at the 
execution of procedures, I agree. And the response to these 
advisory opinions that come out of the FDA--in other words, how 
does the VA respond, what is the VA's response to these 
advisory opinions and how is it followed through, and focus on 
accountability and responsibility, I agree with you and join on 
that.
    With the possible exceptions of Drs. Boozman and Snyder, I 
doubt that anyone on this Committee, including myself, has the 
expertise to determine which drugs should be used by the VA and 
what drugs should be placed on a formulary. We defer to the 
experts on these matters. And Chantix' is an FDA-
approved drug since May of 2006, and it is used by over 7 
million people worldwide to help them stop smoking.
    Again, what I think the Committee should investigate is 
whether the veterans who volunteered to be research subjects 
were treated properly. The VA Office of Inspector General (OIG) 
briefed our Committee staff prior to this hearing, and we know 
what their preliminary findings are.
    I'm very disappointed that long-standing problems with the 
VA research program have apparently not been corrected. Those 
problems relate to strict human research subject protections 
that require fully informed consent of patients before they 
participate in any research study. It appears VA may have 
failed to disclose important facts veterans need to make 
informed decisions before participating in these studies. If 
they were not provided full information about the possible 
risks for their involvement in the VA smoking cessation study, 
this is a major problem, one that is made worse because this 
would not be the first time that the VA has found themselves in 
this position on not giving proper informed consent in VA 
research.
    During the 108th Congress, while serving here as Chairman 
of the Oversight and Investigations Subcommittee, I introduced 
H.R. 1585 to establish the Office of Research Oversight within 
the Department of Veterans Affairs. The language of this bill 
became law, Public Law 108-170. The provisions of this law 
established within the Veterans Health Administration (VHA) an 
Office of Research and Oversight to monitor, review, and 
investigate matters of medical research compliance and 
assurance in the VA, including matters relating to the 
protection and safety of human subjects and VA employees 
participating in VA medical research programs.
    Now, Mr. Chairman, I recall, when the Committee passed 
this, the VA fought us on this. So with your opening about 
you're challenged by the VA, not only did they fight us on this 
bill, we had also sought that this be an independent office, 
and they didn't want that at all. So we ended up having to 
compromise on some of the legislation.
    What gave rise to the legislation was an OIG report 
entitled, ``The Alleged Research Improprieties, Informed 
Consent Issues at the Jerry L. Pettis Memorial Veterans Affairs 
in Loma Linda, California,'' issued on October 7, 1999, along 
with several hearings that followed on VA research and informed 
consent issues.
    The Committee then was briefed on potential research 
misconduct at the Albany VA in 2003, and we were informed by 
the VA Inspector General that the VHA was conducting an inquiry 
into the matter. We monitored that situation and there was an 
actual criminal prosecution from that. And so--the Committee, I 
think, took very appropriate action to create this office; so 
the purpose of the legislation was to avoid the occurrence of 
situations like the unfortunate one we are discussing here 
today.
    So, Mr. Chairman, ``In August 2003, the VA initiated a 
Cooperative Studies Program integrating practice guidelines for 
smoking cessation into mental healthcare for post traumatic 
stress disorder,'' end quote. This research project was to 
compare effectiveness of integrating smoking cessation with 
mental health treatment versus keeping them as separate 
treatment programs. The protocol medications for this research 
project included the nicotine patch and nicotine gum. In 
January 2007, the VA modified the protocol by adding 
Chantix'.
    After FDA's approval of the drug for public use as of 
today, the VA has approximately 32,000 patients on 
Chantix', and the Department of Defense has 
approximately 67,000 patients on Chantix'. On June 
17, 2008, an article appeared in the front page of The 
Washington Times detailing the use of the drug, 
Chantix', in the VA study and the subsequent effects 
that may have been caused by this drug in one veteran in 
particular. That same day, I wrote a letter to the VA, as well 
as the VA Inspector General, requesting an investigation and 
immediate briefing on the allegations detailed in The 
Washington Times article.
    On June 18th, I, along with Committee staff and 
representatives from Congresswoman Brown-Waite's office, 
attended a briefing by the Principal Deputy Under Secretary for 
Health, the Chief of Research and Development, the Chief 
Officer of the Office of Research and Oversight and the Acting 
Deputy Chief Research and Development Officer. At this 
briefing, we were provided a chronology of the events leading 
up to The Washington Times article.
    The Committee staff again met with Dr. Kupersmith and Dr. 
O'Leary on June 19th and requested documentation of all amended 
informed consent forms for all study subjects, as well as all 
adverse drug reactions and serious adverse events related to 
this study that have been reported to VA's Cooperative Study 
Center in Albuquerque, New Mexico.
    To date, neither the Committee staff nor I have seen the 
amended consent forms. I ask the Secretary to be prepared to 
explain the absence of these forms during the question-and-
answer period during the testimony here today.
    Because of the preliminary findings, on July 3, 2008, I 
further requested a nationwide investigation by the Office of 
Inspector General on human research subject protections. I will 
have much more to say about this when Dr. Daigh of the 
Inspector General's Office testifies.
    The FDA and Pfizer are going to be testifying to inform the 
Committee about Chantix'. They are the only 
witnesses here today that can be considered experts or 
authorities on drug safety and Chantix'. I caution 
my colleagues that this Committee lacks the expertise, as well 
as the jurisdiction over the FDA and drug safety. This is a 
topic more appropriately addressed by the Committee on Energy 
and Commerce.
    To attack a legal drug as being unsafe and to characterize 
it as suicide-inducing, I believe is irresponsible and 
inflammatory. We should be careful in making sensational public 
statements about the safety of an FDA-regulated drug without 
full information about such drug when it could be also an 
enormous benefit in saving lives in the cessation of smoking.
    There are many, many drugs, and we all take some of these 
drugs that have tremendous side effects. For example, there is 
a drug that all of us take every day, Mr. Chairman. It is 
called aspirin. One of the side effects of aspirin is 
anticlotting action that can cause an unwanted side effect 
called bleeding on the brain. Now, do we want to say--title a 
hearing, ``Why Is the VA Giving a Bleeding on the Brain 
Inducing Drugs to Veterans?``
    So you could go down almost every drug that has a side 
effect, and you can turn it into sensationalism and be 
inflammatory. I think that this Committee has a more important 
and responsible role here, and we should hear the testimony of 
our witnesses and their answers to our questions; and then, 
only after a careful inquiry, can we make informed judgments on 
what occurred and what corrective actions and followup, Mr. 
Chairman, may be called for.
    Make no mistake, I concur with your issues on 
accountability and responsibility and the question of whether 
our veterans are being well served.
    With that, I will yield back to the Chairman.
    [The prepared statement of Congressman Buyer appears on
p. 83.]
    The Chairman. Thank you, Mr. Buyer.
    I would just note that while most of us here do lack so-
called expertise on the efficacy of drugs, we are experts in 
being parents, we are experts in being family members and we 
should be experts in being guardians of the veterans under our 
care. And there is no more important role than safeguarding 
those veterans.
    And I will tell you, as a father, that if I read that 
Pfizer advisory and my child was on Chantix', I 
would immediately tell them to stop taking the drug. I don't 
need any more expertise than that.
    I want to, once more, thank The Washington Times for the 
articles and the continuing story. Many of our most important 
work on this Committee for the last year and a half has been 
sparked by the media doing its job; whether it was The 
Washington Post dealing with Walter Reed, whether it was ABC 
News dealing with traumatic brain injury, whether it was CBS 
News dealing with suicides, and all the other media out there 
that have looked at these issues and done the work that many of 
us see as our work for oversight on this Committee.
    We thank The Washington Times in this case, but the media 
in general for watching out for our veterans.
    Mr. Stearns. Mr. Chairman, point of order, just a question, 
if I may.
    Normally, in hearings of this magnitude, certainly all 
Members should generally have an opportunity for an opening 
statement. I was wondering, are we going to proceed in regular 
order in which each Member, both the Republicans and the 
Democrats, have an opportunity for a 3-minute, 2-minute opening 
statement? Is that possible? Many of us would like that 
opportunity.
    The Chairman. We have four panels. But at your request, I 
will be happy to do that.
    Mr. Stearns. Sir, I'm not just asking for myself. I'm----
    The Chairman. I'll ask everybody else.
    Mr. Stearns. Well, I think it is important.
    The Chairman. Going down the rostrum--Mr. Mitchell, if 
there is any opening statement any of you would like to make. 
Mr. Mitchell?
    Mr. Mitchell. I'll submit mine.
    [The prepared statement of Congressman Mitchell appears on 
p. 85.]
    The Chairman. Mr. Hall.

             OPENING STATEMENT OF HON. JOHN J. HALL

    Mr. Hall. Thank you, Mr. Chairman. I'll just briefly say 
that the drug in question, I'm looking forward to hearing the 
testimony on.
    I don't think, with all due respect to my friend, the 
Ranking Member, that aspirin, which is probably one of the most 
studied drugs in history, can be compared in terms of our 
knowledge and experience with it to this one.
    But the underlying problem of undiagnosed and untreated 
PTSD is really the story here, in my opinion. And yet again 
yesterday The New York Times had a story about alcoholism and 
self-medication by veterans who sometimes had to go through 
fatal traffic accidents, bar fights, winding up in jail, 
domestic violence that they were arrested for, et cetera, et 
cetera, before they sought or were given treatment for PTSD, 
because they were taught to be tough and to handle things and 
to deal with it as a man or as a woman. But it happens to be 
mostly men through the proportion in the armed services.
    And we voted out of this Committee a bill, which would 
provide for--a presumed stressor for PTSD. It costs more not to 
treat it. In fact, the RAND study said that $6.2 billion in 2 
years for undiagnosed is the cost to our society, to our 
country of undiagnosed and untreated PTSD--$6.2 billion in 2 
years.
    The Congressional Budget Office score for that section of 
the bill was $5 billion over 10 years. So it costs a fifth as 
much for us to treat it as it does not to treat it.
    And I think that I will get back to the topic and allow the 
hearing to resume. But I hope that we'll all look at this in 
the big picture of medications that are being used to try to, 
in this case, stop smoking but are being used on people who--a 
large percentage of whom have undiagnosed and untreated PTSD. 
And that itself is a larger problem.
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Mr. Hall. Thank you for your 
leadership on this.
    Mr. Stearns.

            OPENING STATEMENT OF HON. CLIFF STEARNS

    Mr. Stearns. Thank you, Mr. Chairman.
    Mr. Hall, I have a list here from the Physician's Desk 
Reference which, as you know, is a physician's manual. There 
are over 200 drugs that are listed as suicide-related, and 
people who take these drugs will indeed have the feeling they 
should commit suicide.
    So the Ranking Member, Mr. Buyer, mentioned aspirin. He 
could just as well have mentioned Albutirol, which people take 
for asthma. He could mention Paxil. I mean, they just go on and 
on and on. So Mr. Buyer is mentioning aspirin just to make a 
point, because I think his point is well taken. The title of 
this hearing is inflammatory, is not responsible; and here we 
are together as Republicans and Democrats and Independents 
looking to provide substantive credibility to this hearing. We 
don't want to start the hearing off with something that is so 
inflammatory it sounds like a campaign, a political campaign. 
This is not a political campaign. These are the lives of the 
men and women who are protecting us.
    And to single out this drug is fine. I don't think there is 
anything wrong with having a hearing. But, Mr. Hall, if you 
want to read this list from the PDR, on almost every 
physician's table there are 200 at minimum that could cause 
suicidal thoughts, and they're listed right here. And I would 
venture to guess--and you and I are both adults--in our lives 
we've taken some of these drugs here and didn't even realize 
that they have a possibility of suicidal inclination.
    The second point I would like to make is, the Department of 
Defense prescribes this same medicine to 67,000 military 
personnel. So this is not just something that the VA is doing. 
They are prescribing it to 32,000. So if we are really going to 
look at this, why don't we bring in some people from the 
Department of Defense and ask them, with 67,000 people, more 
than twice what the veterans are using, why don't we look at 
this drug in terms of their history and how it has functioned?
    Now, if you look worldwide, there are 1.3 billion people 
that smoke. Out of that, 7.5 million use this drug today 
worldwide. Now, the problem is we have about--just under 
500,000 people that die from smoking every year in this 
country, and this is a leading cause of a preventable death. So 
anything we can do as Americans to get people to stop smoking, 
so that roughly 500,000 Americans will live is important.
    So I think we have to put in perspective what we're trying 
to do here. Sure, we've got to ask the question, why would the 
VA prescribe a drug that could worsen or magnify the symptoms 
of depression and anxiety to patients suffering from post 
traumatic stress disorder? I think that is worthwhile. But 
let's put it in perspective--perspective in dealing with the 
Department of Defense, worldwide; and what we're trying to do 
in this country is get veterans off smoking because it is a 
preventable death.
    Thank you, Mr. Chairman.
    The Chairman. Mr. Hare.

              OPENING STATEMENT OF HON. PHIL HARE

    Mr. Hare. Thank you, Mr. Chairman. I'm going to be very 
brief.
    You're right, I think we are all parents and want the very 
best not only for our children, but for our veterans. This 
Committee, as I understand, has oversight over the VA and I'm 
not as concerned about the title of the hearing as I am with 
what has happened here. I'm committed to working with my 
colleagues on this Committee to get to the bottom so we can 
ensure that our veterans are treated humanely.
    As is mentioned, we have a report out that approximately 
1,000 veterans per month are attempting suicide. Is this part 
of it? I don't know. I'm not a doctor; I don't claim to be. I 
just want to get to the bottom of what we're doing so we can 
try to put an end to this.
    Every person on this Committee, Republican and Democrat, I 
think wants to see the very best care given to our veterans; 
and if there are things we need to look at, I think we need to 
do that.
    But I especially hope to find out the policies and 
procedures regarding research in human subjects that we are 
following in designing this CSP No. 519 and what oversight, if 
any, was involved. I also want to know if patients were 
adequately informed of the hazards of Chantix'. Did 
the VA respond in a timely fashion to the early communication, 
the Public Health Advisory for Chantix'? And why was 
consent not revised after the FDA's early communication? 
Finally, given new evidence of the risk associated with this 
drug, should the drug continue to be used to treat veterans of 
post traumatic stress syndrome?
    So the bottom line here for me today is to find out what 
happened and what can we do, Republicans and Democrat alike. 
And when the Ranking Member mentioned aspirin and my friend, 
Mr. Stearns, mentioned all these other 200 drugs that are 
available, they could all have side effects, some very, very, 
destructive side effects; the fact of the matter is, to what 
degree, and particularly dealing with veterans with post 
traumatic stress syndrome, does this make this situation worse? 
That is what I really want to find out.
    So what can we do to prevent the suicides that continue at 
record-breaking paces? My fear is, with more veterans coming 
back with post traumatic stress syndrome, this situation is 
going to get worse before it ever gets better.
    Thank you, Mr. Chairman.
    The Chairman. Mr. Boozman, any opening statement?
    Ms. Berkley.
    Ms. Berkley. Mr. Chairman, I'd like to associate myself 
with Mr. Hare's thoughtful remarks. I'm going to reserve my 
time for an opening statement and perhaps submit it in writing 
later, and I would like to get to the witnesses.
    The Chairman. Thank you.
    Mr. Lamborn. That's--okay, somebody next to you.
    Mr. Rodriguez, I didn't see you. Mr. Salazar declined.
    Mr. Rodriguez. Just I'm ready to listen to testimony and 
look forward to it. My main concern would be to see how we can 
begin to hold the system accountable in terms of making things 
happen for our veterans and get to the witnesses.
    The Chairman. Thank you.
    Mr. Scalise.

            OPENING STATEMENT OF HON. STEVE SCALISE

    Mr. Scalise. Thank you, Mr. Chairman. And the Ranking 
Member has a lot of concerns about the report. I definitely 
want to hear from the witnesses.
    But I think our main concern should be about the process 
and if, in fact, accountability is going to show where the 
consent was requested because we have veterans that were being 
subjected to participation and testing, which is not something 
new. But it seems that there is a big gap in the consent 
process from all the reports that have come before us, a real 
concern about the process of making sure that the veterans knew 
what they were doing, those who chose to participate in the 
testing; and if, in fact, medical personnel let them know what 
the side effects were and if consent was garnered, because in a 
number of cases, they haven't been able to produce signed 
consent forms.
    And the fact that veterans may have been participating in 
research studies without proper consent leads to a number of 
major concerns; and I hope that gets addressed in the 
testimony, and I definitely have some questions as we get into 
that section. So I look forward to hearing it.
    [The prepared statement of Congressman Scalise appears on 
p. 85.]
    The Chairman. Thank you, sir.
    Mr. McNerney.

            OPENING STATEMENT OF HON. JERRY McNERNEY

    Mr. McNerney. Thank you, Mr. Chairman. This is an important 
hearing because it appears that established principles in 
patient treatment have been ignored or pushed aside. We want to 
know if this was done because these are veterans or not.
    Any patient who is given a drug is entitled to know what 
the side effects are, especially if the side effects are life 
threatening and especially if the patients are particularly 
susceptible to those side effects.
    Since these subjects are veterans and the drug was 
administered by the Department of Veterans Affairs, it is our 
responsibility to investigate if wrongdoing took place, either 
intentionally or unintentionally. It should be dealt with. And 
we need to make sure that procedures are in place to prevent 
unnecessary sufferings of our veterans.
    Thank you.
    The Chairman. Thank you.
    Mr. Walz.

           OPENING STATEMENT OF HON. TIMOTHY J. WALZ

    Mr. Walz. Thank you, Mr. Chairman, Mr. Ranking Member. 
Thank you to our witnesses.
    Mr. Elliott, thank you for being here. That combat 
infantryman badge (CIB) gives you the right and the privilege 
to sit right where you are at and tell us this, because our 
responsibility is to make sure that what you did to earn that, 
make sure we are doing our responsibility on this end to care 
for you and your family once you return.
    A special thank-you to the VA and to Secretary Peake for 
taking time to be here. No one is more committed to the care of 
our veterans than the Secretary, who is concerned when we have 
lapses in getting them fixed.
    So I look forward to today's testimony because the VA, 
while it provides some of the best care in the world, also has 
a unique responsibility in providing research and especially in 
some of our most vulnerable populations of PTSD and so forth. 
So I'm very concerned on that.
    Now, this incentive to do the research and to get it right, 
especially in preventive medicine, whether it be smoking or 
whether it be diabetes, the VA is a leader and has a real 
unique role in that.
    So this issue of--if corners were cut or protocols were 
skipped, it is tragic in terms of what happens to our veterans 
in their care. But it is also tragic if a very valuable 
treatment is out there and it doesn't get a fair shake to be 
implemented.
    So I do think--and I associate myself with some of the 
remarks that my colleague, Mr. Stearns, made--there is a 
responsibility for us not to hype this or engage in thinking 
that would be gratuitous in terms of what we're talking about 
on this drug.
    But I also think it means we have a responsibility to 
ensure that the VA follows all of the accepted protocols and 
the ethical conduct of these for the very reason as I stated 
earlier, the care of the veterans, as well as protecting the 
research mission that the VA has.
    So I'm very much looking forward to this, and I also thank 
you Mr. Elliott for showing the courage to be here today to try 
to help us understand this.
    So I yield back.
    The Chairman. Thank you.
    Mr. Cazayoux.
    Okay, our first panel has two witnesses, James Elliott and 
Lieutenant Colonel Roger Charles. Mr. Elliott is a veteran from 
the Iraq War, who was given Chantix' by the VA and 
suffered severe side effects while taking the drug. He is 
accompanied by a friend, Tammy Hilburn, who has helped him and 
done a lot of research on the issue.
    Lieutenant Colonel Charles, is the Editor of DefenseWatch, 
and helped Mr. Elliott after his experience. So we look forward 
to your testimony.
    I know again, Mr. Elliott, this is not easy. But I think 
you're taking a position that you want to help other veterans, 
and we appreciate your courage in doing that.
    Mr. Buyer. Mr. Chairman, may the witnesses be sworn in 
today?
    The Chairman. We haven't done that in the past, but I don't 
mind and I don't think the witnesses mind.
    If you'll stand up, the two witnesses, and raise your right 
hand.
    [Witnesses sworn.]
    The Chairman. Thank you all.
    Mr. Elliott, please.

  STATEMENTS OF JAMES G. ELLIOTT, SILVER SPRING, MD (IRAQ WAR 
 VETERAN); ACCOMPANIED BY TAMMY R. HILBURN, SILVER SPRING, MD; 
  AND LIEUTENANT COLONEL ROGER G. CHARLES, USMC (RET.), VICE-
CHAIRMAN, BOARD OF TRUSTEES, SOLDIERS FOR THE TRUTH FOUNDATION, 
     AND EDITOR, DEFENSEWATCH, ON BEHALF OF EILHYS ENGLAND 
  HACKWORTH, CHAIRPERSON, BOARD OF TRUSTEES, SOLDIERS FOR THE 
                        TRUTH FOUNDATION

                 STATEMENT OF JAMES G. ELLIOTT

    Mr. Elliott. Thank you, Mr. Chairman. I have submitted my 
executive summary, and the diagram clearly illustrates that 
there was a vicious web that I was caught up in. That diagram 
is not part of my official testimony, meaning that it is--I 
haven't been allowed to use it as a PowerPoint presentation. I 
know that some of the other witnesses will be having those type 
of presentations.
    And that is really all I have to say. Thank you.
    The Chairman. I'm sorry. You have no further testimony 
today?
    [The prepared statement of Mr. Elliott appears on p. 86.]
    The Chairman. Colonel Charles.

                STATEMENT OF LIEUTENANT COLONEL

                 ROGER G. CHARLES, USMC (RET.)

    Colonel Charles. Chairman Filner, Honorable Members of the 
House Veterans' Affairs Committee, on behalf of Eilhys England 
Hackworth, the Chairperson of the Board of trustees of Soldiers 
for the Truth Foundation, I am humbled to appear before your 
Committee.
    Recent events show that this oversight function of your 
Committee is critical to ensure that the well-being of our 
veterans is, in fact, the highest priority of the VA. These 
events demonstrate that without Congressional oversight, true 
concern for the well-being of our veterans can deteriorate into 
mere lip service of an indifferent and self-serving 
bureaucracy.
    I note that you have scheduled a most impressive group of 
experts on various medical and ethical issues related to human 
subject experiments as conducted by the VA. I do not bring 
their expertise to this hearing. What I do bring is the 
experience of a career Marine Corps officer who believes our 
Nation has a sacred responsibility to care for those who have 
manned the ramparts of freedom on our behalf. I also bring the 
skepticism of a journalist who, for 18 years, has investigated 
misconduct by various Federal agencies in the areas of defense 
and national security.
    Let me now turn to today's hearing. While studying the 
experience of Army combat veteran James Elliott, I was struck 
by three major questions. My first question relates to the 
Hippocratic Oath and a physician's first responsibility to do 
no harm. How then did the VA physicians involved in planning 
and conducting this drug study fulfill their duties under this 
pledge?
    Here are some related follow-up questions to consider: 
Would these physicians have subjected their own sons or 
daughters to such a high-risk drug study? And would they have 
failed to have informed their own children of the substantial 
risks this study entailed?
    My second question relates to the Nuremberg Code and the 
fact that informed consent of all human subjects in medical 
experiments is an absolute requirement under this code. As you 
may recall, it was the exposure of the most heinous and 
gruesome medical experts by Nazi doctors that led to enacting 
the Nuremberg Code.
    Our country's own history has, unfortunately, too many 
examples of medical experiments on unwitting subjects. The 
infamous Tuskegee syphilis experiment is perhaps the best known 
of such shocking violations by physicians of their own 
Hippocratic Oath. I have attached to this statement a Knight 
Ridder press report, dated July 7th, regarding the Federal 
criminal prosecution of a former VA staff physician at the 
Stratton VA Medical Center in Albany, New York. The Federal 
prosecutor asked the court to sentence this former VA 
physician--and I quote--``to spend a year in prison for his 
role in a drug research scandal that killed at least one 
veteran and victimized dozens more,'' end quote. I have 
subsequently learned that this Committee had a major role in 
that investigation. If it pleases the Chairman, I respectfully 
request this article be included in the record.
    The Chairman. So ordered.
    Colonel Charles. My last question for your consideration 
involves the participants themselves, the veterans with PTSD 
who were recruited by VA staff to become the subjects of this 
drug study.
    Why were members of a group who by the VA's own diagnosis 
were struggling to return to mental health normality selected 
for this study? The mental health of these veterans was known 
to have been what a layman would term ``fragile.'' Special 
caution and prudence should have been invoked before exposing 
them to a drug study where, by definition, unknown factors 
risked further damage to their mental health. Instead, the very 
VA physicians trusted to help these vets regain a more normal 
mental condition enticed the vets to join a game of mental 
health roulette while withholding critical information that 
would have permitted true informed consent to have been given.
    Sir, this concludes my prepared statement. I stand ready to 
respond to any questions that the Committee Members may offer.
    The Chairman. Thank you.
    [The prepared statement of Lieutenant Colonel Roger G. 
Charles and the attached article, appears on p. 90.]
    And if I may ask, Mr. Elliott, you have been diagnosed with 
PTSD?
    Mr. Elliott. Yes, Mr. Chairman.
    The Chairman. And you're a heavy smoker?
    Mr. Elliott. Yes.
    The Chairman. And how long were you taking 
Chantix'?
    Mr. Elliott. Less than 3 months.
    The Chairman. And given the kind of advisories that have 
come out, that we have commented on, do you feel you were 
adequately informed of the side effects?
    Mr. Elliott. No, Mr. Chairman, not at all.
    The Chairman. Would you mind describing the event that gave 
you so much publicity--probably unwanted--in terms of what 
happened to you?
    Mr. Elliott. The events of February 5th are very well 
documented, and that issue has been completely resolved in the 
courts.
    The Chairman. In the what?
    Mr. Elliott. In the courts.
    The Chairman. I mean, do you feel that the drug that you 
were taking helped provoke that or not?
    Mr. Elliott. I strongly feel that way.
    The Chairman. And you believe that the drug led to this 
episode with the police?
    Mr. Elliott. That's correct, Mr. Chairman.
    The Chairman. What would be your advice for other people 
taking the drug?
    Mr. Elliott. Anyone who is on an antidepressant should not 
take that drug. That would be my advice. Ask more direct 
questions to your doctor, demand direct answers, demand that 
this Committee help answer some of the questions that are going 
to arise.
    The Chairman. Okay. Thank you so much.
    Mr. Buyer.
    Mr. Buyer. First by way of opening, let me thank both of 
you for your service.
    Mr. Elliott, before starting Chantix', had you 
tried any other smoking cessation aids or drugs?
    Mr. Elliott. Yes, Mr. Buyer, I did.
    Mr. Buyer. Which ones?
    Mr. Elliott. Phase one of Smoking Cessation Program 519, 
it--the program that I signed up for, I began with the nicotine 
patch, 21 milligrams, and that did not work very well. It 
helped to a point, but it did not completely eliminate my 
smoking habit. And then from there, I went to nicotine gum and 
at one point, because my nicotine habit was extremely strong, I 
was given both in conjunction with one another.
    Mr. Buyer. Can you define the word ``strong?'' How many 
cigarettes or packs a day did you smoke?
    Mr. Elliott. Two packs, pretty much two packs a day, 40 
cigarettes.
    Mr. Buyer. What type? What kind?
    Mr. Elliott. Marlboro Medium.
    Mr. Buyer. Filtered or unfiltered?
    Mr. Elliott. Filtered.
    Mr. Buyer. Are you still currently enrolled in a smoking 
cessation program?
    Mr. Elliott. Negative.
    Mr. Buyer. Are you currently using any smoking cessation 
drug or aid at this time?
    Mr. Elliott. No.
    Mr. Buyer. When you entered the study, do you remember 
signing an informed consent form?
    Mr. Elliott. I do remember that very well.
    Mr. Buyer. At any time, did you sign an addendum to the 
informed consent form?
    Mr. Elliott. Absolutely not. That addendum was not sent 
until after this whole affair of February 5th. It was not 
actually sent until we had confronted them about the FDA 
warnings.
    Mr. Buyer. Did your doctor at any time talk to you about 
the advisory that the VA had received from the FDA?
    Mr. Elliott. No, not one single time.
    Mr. Buyer. Did your doctor at any time discuss with you a 
medical belief that your continuing use of cigarette nicotine--
your continuing smoking would have an adverse impact upon their 
treatment for post traumatic stress syndrome?
    Mr. Elliott. No, they never said that by me stopping 
smoking it would help my PTSD diagnosis and symptoms.
    Mr. Buyer. Let me ask, as a patient--you are in a program 
that will help you get better with your PTSD and cessation of 
smoking, and the purpose of the study is the medical belief 
that your smoking does not--that actually works against your 
PTSD treatment. Or didn't your doctor--so when you signed your 
original informed consent, wasn't that the purpose of your 
entering this program?
    Mr. Elliott. I entered the program, 100 percent, because I 
wanted to stop smoking. That was the one and only reason I 
entered that program.
    Mr. Buyer. All right. But at this point, you don't recall 
conversations with your doctor with regard to how important it 
would be to do the cessation of smoking because they could 
better treat mental challenges?
    You don't recall any of those discussions?
    Mr. Elliott. No. Those discussions never took place.
    Mr. Buyer. Prior to the episode in which there was an 
arrest, did you have any success with Chantix'?
    Mr. Elliott. No, not at all. As a matter of fact, I had had 
a terrible reaction to it in the first week.
    Well, Mr. Buyer, as far as stopping--you know, smoking 
cessation goes--yes, I had cut my habit in half overnight. It 
was miraculous, I will say this, Chantix' as far as 
more or less convincing your brain that you do not want to 
smoke anymore, that you get no pleasure from it, it works well.
    I--overnight my smoking habits were cut in half.
    Mr. Buyer. Thank you, Mr. Chairman.
    The Chairman. Thank you, Mr. Buyer. Just as a reminder, I'm 
going in the order of Members who were here when we started the 
hearing, in order of seniority, then those who appeared later.
    Mr. Hare.
    Mr. Hare. Thank you. How are you doing now, Mr. Elliott?
    Mr. Elliott. I have been better. I've been worse. Be more 
specific, please?
    Mr. Hare. Pardon me?
    Mr. Elliott. Be more specific about how am I doing right 
now?
    Mr. Hare. You're no longer taking the drug?
    Mr. Elliott. No, I have not taken Chantix' since 
February 5th.
    Mr. Hare. So, since February 5th, how have you been doing?
    Mr. Elliott. Well, I now know that many of the side effects 
do not occur until after you stop smoking Chantix'. 
I believe they are known as ``withdrawal symptoms.'' And I have 
vomited blood on occasion, had massive testicular swelling; I 
continue to have skin problems.
    Mr. Hare. When you stopped taking Chantix', I'm 
assuming you were still under a physician's care?
    Mr. Elliott. No, not really.
    Mr. Hare. So you didn't go to a doctor and say, I now have 
all of these post----
    Mr. Elliott. I have, absolutely, yes. It should be--in my 
VA medical files.
    Mr. Hare. What did the physicians say to you when you told 
them you were having all these problems after you stopped 
taking the drug? What was their response to you?
    Did they give you----
    Mr. Elliott. ``Thank you, have a great day,'' that was 
pretty much their response.
    You know, in fact, their response was so--I feel it was so 
inadequate that, you know, I will be going for outside medical 
care.
    Mr. Hare. You will or you have?
    Mr. Elliott. I will.
    Mr. Hare. So, in your opinion, all these problems that you 
encountered after you stopped taking the drug, you relayed 
those to a physician, and they basically said, you're on your 
own, there is nothing we can do about this?
    Or did they advise you to start taking the drug again? I am 
confused because the drug causes the problems, you have more 
problems after you stop taking the drug, you see a physician; 
if I'm correct, the physician basically tells you, go have a 
nice day?
    Mr. Elliott. As far as psychiatric help goes, no, my 
original prescribing doctor, who prescribed me the 
Chantix', we have no relationship at all now.
    The doctor who was assigned in her absence, he has never 
really given me any advice as far as any of this goes. Off the 
record, he has told me just to be strong, bear through it.
    You know, we discussed the fact that, you know, my PTSD has 
actually gotten much worse--you know, a lot of the paranoia, 
the things that the Chantix' increased, the PTSD 
symptoms that Chantix' increased, they have not, you 
know, decreased since I quit taking it, and in some cases, they 
may even be worse.
    My primary care physician, him and I, we do not address 
psychological issues. That is not his place. But he has, you 
know--I have had good medical care at the VA since this 
happened, but none of it is related to psychiatric issues.
    Mr. Hare. I don't want to get personal here, but you've 
been diagnosed with PTSD. Are you seeing a psychologist to help 
you with the PTSD? We spoke about the physical effects, but are 
you getting any help from the VA in terms of other treatments?
    Mr. Elliott. I have received no substantive PTSD treatment 
other than the fact that I was prescribed Citalopram years ago, 
and I continue to take Citalopram.
    Mr. Hare. I know I'm out of time, but I hope you are given 
the opportunity to seek additional help, if need be. I 
appreciate and honor your service to this country; and I would 
hope that you would be able to find somebody that would be able 
to help you not only with the physical symptoms and the other 
things that you have, but also with your PTSD. Clearly that is 
something that you will be dealing with, I assume, for quite 
some time. I hope that you can find somebody that you have 
confidence in and that can help you as you move down the line.
    Thank you, Mr. Chairman.
    The Chairman. Thank you.
    Mr. Scalise.
    Mr. Scalise. Thank you, Mr. Chairman.
    Mr. Elliott, if you could describe the process that got you 
involved in the Chantix' study in the first place, 
the conversations with the VA, how did you come to participate 
in the study?
    Mr. Elliott. Well, it has been an ongoing study. I can't 
say how long it has been in place; but as far as I remember, 
while I have been at the Washington, DC, VA Medical Center, I 
have seen posters everywhere, you know, advertising this 
smoking cessation program in one form or another. There's 
different forms of this study going on. I was initially--well, 
let me step back a minute, sir.
    The very first time that I met with a Veterans Affairs 
psychiatrist in Little Rock, Arkansas, his main issue of his 
and--his dialog and my dialog, what he was most concerned with 
was the fact that I smoked and I needed to stop smoking.
    Mr. Scalise. In relation to PTSD or just separately?
    Mr. Elliott. Just in relation to my life, my existence, I 
needed to stop smoking. That is all he wanted to talk about.
    But as far as the DC-VA goes, like I said, I had seen the 
posters; I was well aware of this, but I really had no interest 
in it. At the time, though, my veteran counselor--he is not a 
doctor, he was just a counselor--he assured me that he himself 
was--had, is--was a long-time smoker and a lot of things they 
had to offer were truly beneficial to me and that maybe, just 
maybe, I should think about going into this program. We 
discussed those options for 6 months probably before I actually 
considered, you know, the reality of me entering into this 
program.
    The only deal I was willing to make--you know, if that 
sounds appropriate, I was willing to make a deal. But I said, 
you know, okay, I will go ahead, I will do this, you know, I 
trust you, but you and the hospital administrators that are in 
charge of this program, you have to guarantee me that you will 
be my assigned counselor rather than just they randomly assign 
me to someone, which is how it was described to me.
    I wanted it--I wanted to hear it and see it in writing, if 
possible, that he would be my counselor.
    Mr. Scalise. Did you get that assurance?
    Mr. Elliott. That happened, and that's when I unofficially 
became part of the program.
    Mr. Scalise. To get to the--I guess the official part where 
you actually signed the consent form, you said you did sign a 
consent form. What were those conversations like in terms of 
side effects, in terms of how detailed did that conversation go 
before you signed the consent form to make you aware of what 
the potential side effects would be if you did start this 
process?
    Mr. Elliott. That consent form that I signed, it was 
strictly limited to nicotine patches and nicotine gum. That 
meeting lasted close to 3 hours, just as the consent form 
states.
    It really did take 3 hours. They did most of the speaking 
until the very end. They took a lot of time explaining to me 
that this was a three-year program, they were more interested 
in long-term results rather than short-term results. They were 
well aware of the fact that most of the participants would take 
that $30 and immediately go out and buy cigarettes. They did 
not care about that whatsoever because they were interested in 
long-term results rather than short-term results and----
    Mr. Scalise. But did you sign a consent form for 
Chantix'?
    Mr. Elliott. No, never. Never. Never.
    Mr. Scalise. So when did you start taking 
Chantix'?
    Mr. Elliott. October 30, 2007, my prescribing psychiatrist, 
she, sort of on a spur of the moment, informed me that there 
was a new drug, and it was called Varenicline. I had never 
heard the word Chantix' until after February 25. She 
told me that Varenicline was a new drug; she didn't know very 
much about it, but it had some great results in getting people 
to stop smoking quickly and that it might possibly cause me 
stomach ailments and which, in fact, it did. It got me to puke 
blood.
    Mr. Scalise. But no talk about the other side effects?
    Mr. Elliott. There was no talk whatsoever, and I asked a 
lot of questions.
    Mr. Scalise. The final question would be regarding the FDA 
health advisories that came about periodically about the drug 
while you were taking it. Did you get any conversations, were 
there any conversations with your medical advisers at the VA 
about health advisories that came out from the FDA on Chantix?
    Mr. Elliott. No, but I did receive monthly appointment 
reminders to go in and fill out the questionnaire, of which I 
was given $30 for. I, a lot of times, didn't even cash those 
$30 vouchers.
    Mr. Scalise. Were there health advisories that came out 
during the time when you were taking the drug?
    Mr. Elliott. Say it again.
    Mr. Scalise. Were there health advisories that came out 
from the FDA during the time when you were taking the drug?
    Mr. Elliott. There were three, and I was not told about any 
of those until I requested that those FDA health advisories be 
sent to me.
    Mr. Scalise. After you stopped taking it.
    Mr. Elliott. After I stopped taking it.
    Mr. Scalise. But not during?
    Mr. Elliott. But not during.
    Mr. Scalise. That's all I have. Thank you.
    The Chairman. Ms. Berkley.
    Ms. Berkley. Thank you, Mr. Chairman.
    Mr. Elliott, thank you very much for being here, and thank 
you for your service to our Nation.
    You will forgive me, but I am having a hard time tracking 
this, so perhaps you will help me understand it.
    You were being treated for PTSD by the VA?
    Mr. Elliott. Yes, ma'am.
    Ms. Berkley. And how long had you been in the PTSD program?
    Mr. Elliott. Since spring, 2005.
    Ms. Berkley. And you were a two-pack a day smoker and 
wanted to kick the habit, and in speaking with your 
psychiatrist, she suggested Varenicline? First you were on the 
patch, and then you were on the gum, and then the woman doctor 
suggested--and I am sorry, I didn't catch that, Varenicline?
    Mr. Elliott. Varenicline, Va-ren-i-cline.
    Ms. Berkley. Okay, Varenicline, and you agreed to take the 
Varenicline?
    Mr. Elliott. Yes, ma'am.
    Ms. Berkley. But they never gave you that; they gave you 
the Chantix' instead?
    Mr. Elliott. Chantix' and Varenicline are the 
same product. Varenicline tartrate is the active ingredient of 
what is commonly known as Chantix'.
    Ms. Berkley. So the doctor said you didn't really know 
anything about it; you could suffer some stomach ailments; but 
that she had heard or read that this was a new drug that may 
very well help you kick the habit?
    Mr. Elliott. She did state to me that it was a new drug 
and--hold on. Yes, she stated that it was a new drug, and there 
were little--it was known to work very well, as far as smoking 
cessation goes.
    Ms. Berkley. Okay, and then she prescribed it for you. You 
started taking it. Do you take it on a daily basis? A weekly 
basis? Several times a day? How does it work?
    Mr. Elliott. I received the medication, the Varenicline, in 
the mail approximately November 5th or 6th, 2007. And per the 
instructions, you know, I followed the instructions to a T. You 
know, I always do that. I am very interested in my own personal 
healthcare.
    Ms. Berkley. Did you have periodic checkups with her, or 
did you go back with her and say--you know, did she say, how is 
this working? How are you doing? What's the effect of the 
medication on you? Did you have contact with this doctor again 
after she prescribed it?
    Mr. Elliott. I had a lot of contact with her, and the 
people in the actual clinic who I filled out the paperwork 
with.
    To go back to your first question, I began taking 
Chantix', very small doses, because it is a rather 
hard-core drug. I was told that much, that this is going to be 
a wallop to your neurological process, and I took half a pill 
for 3 days in the morning. I took half a pill for 3 days in the 
morning and the nighttime. And then I took one entire pill one 
time. And then the next day I took two entire--I took one full 
dose of the Varenicline.
    The next morning, I, my whole body broke out in a rash, 
itching, scratching sensation.
    Ms. Berkley. Did you report that?
    Mr. Elliott. Yes, I did. But, first, you know, I am not a 
doctor, but I knew that the only thing new that I had 
introduced into my system was the full dose of 
Chantix', and it was such a miserable experience 
that I immediately said, you know, cease, cease fire. I stopped 
taking it.
    And then, by chance, I had an appointment with my primary 
care physician three days later. He advised me--and I still 
remember his exact words to this day--he said, ``well, Mr. 
Elliott, it looks like we finally found something you are 
allergic to. You should stop taking that.''
    Ms. Berkley. And you did.
    Mr. Elliott. And I stopped taking it for a month, until I 
saw my prescribing psychiatrist again. And she--you know, I 
almost told her verbatim the same exact story I just told you. 
She said, ``well, that's not a long-term problem. If you were 
only--if you were not having any problems while you were taking 
half a dose, then go back to taking half a dose, because it----
    Ms. Berkley. And that----
    Mr. Elliott. And that is rare, so just go back to taking 
half a dose and everything will be fine.'' And I did go back to 
taking that half dose for approximately two and a half months. 
And I suppose I am lucky that I wasn't taking a full dose; 
maybe, perhaps, I would be dead right now.
    But in mid-January, I went in, I was having--I don't--it's 
hard to explain exactly what I was going through, but all my 
PTSD symptoms, you know, increased tenfold, and I tried to go 
in and make an emergency appointment with that doctor.
    Her receptionist and I, you know, we knew each other on a 
name-by-name, face-to-face basis. And initially, she said, 
``all right, Mr. Elliott, I will let her know that you need to 
see her.''
    And so then I got a little bit more frantic, like, ``man, 
you need to understand, this is a severe emergency. I need to 
see her or another doctor right now immediately.''
    At that point, she got out a pen and paper. She took notes 
and said, I will relay this immediately.
    And, unfortunately, I never heard back from that 
psychiatric clinic at the VA hospital until February 5, after 
it was too late.
    Ms. Berkley. All right.
    Thank you very much.
    The Chairman. Thank you, Ms. Berkley.
    Mr. Stearns.
    Mr. Stearns. Thank you, Mr. Chairman.
    Mr. Elliott, let me just thank you for your testimony.
    We are all operating, as the gentlelady from Las Vegas has 
pointed out, she was trying to understand what drugs you were 
taking in addition to Chantix'. The Ranking Member, 
Mr. Buyer, had requested, under the Rules of the House and the 
constitutional oversight authority given to Congress, on behalf 
of both Democrats and Republicans, that staff be granted access 
to medical- and research-related records relating to Mr. James 
Elliott, and we were denied.
    So that some of the questions the gentlelady from Las Vegas 
is asking and Mr. Scalise asked and I am going to ask are 
necessary because we have no medical record. We don't know 
about the interaction of other drugs, perhaps, at the time you 
were taking Chantix'.
    But I do want to point out to my colleagues that Mr. 
Elliott is wearing a combat infantry badge. It's prominent on 
his lapel, so he is a war hero.
    Mr. Elliott, can you just tell me where you served in Iraq 
and your rank, if you would, and then I have some questions. 
Just briefly tell that, because I do want to give you that 
opportunity. If you don't want to----
    Mr. Elliott. I was part of Task Force Bandit. I served 
mainly in central Iraq, and I was a specialist.
    Mr. Stearns. Okay. Some of the questions have been asked, 
and you seem to indicate that, while you were taking 
Chantix', you perhaps had taken some other 
medication, and I think you mentioned something called 
Citalopram, is that right?
    Mr. Elliott. Citalopram.
    Mr. Stearns. Is that the generic name for C-e-l-e-x-a, 
Celexa?
    Mr. Elliott. Yes, that is true.
    Mr. Stearns. Did you know that that's part of the Prozac 
family, which is an antidepressant drug? Did you know that?
    Mr. Elliott. I knew that it was a serotonin reuptake 
inhibitor, yes.
    Mr. Stearns. So, at the same time you were taking 
Chantix', you were also taking a drug, a Prozac 
family-related drug?
    Mr. Elliott. That's correct. And that was one of my primary 
questions to my attending physician was, how is this going to 
react with Citalopram and the other medications that I have 
been prescribed?
    [The following was subsequently received from Mr. Elliott:]

          Mr. Elliott has never taken Prozac. He is on Citalopram.

    Mr. Stearns. Mr. Elliott, I had an opening statement in 
which I mentioned the physicians' manual in which all the drugs 
that are listed can cause suicidal thoughts. And some of these, 
Prozac and Paxil and some of the drugs that you were taking are 
on this list that cause suicide.
    I don't know if you knew that, the side effects, one of the 
side effects is suicide. Did the people who gave you this 
Prozac-related drug tell you that some of the side effects 
would be suicide--could be, could be, possibly?
    Mr. Elliott. The--the psychiatrist who prescribed me the 
Citalopram initially, in spring 2005, he was not concerned that 
I was a suicidal individual. We did speak about----
    Mr. Stearns. But you were taking that at the same time you 
were taking Chantix'?
    Mr. Elliott. That's correct.
    Mr. Stearns. Okay.
    Also, I saw from the record that you started taking 
Chantix' in November of 2007, and it indicated you 
had some hives and some itching, and I think that was brought 
out earlier, that you did have some immediate side effects. Is 
that true?
    Mr. Elliott. That's true.
    Mr. Stearns. And did you tell the doctor about these side 
effects?
    Mr. Elliott. I did.
    Mr. Stearns. In February 2008, The Washington Times 
reported an incident. At that moment you were taking 
Chantix', were you taking any other medication 
besides this Prozac-related drug? Were you, for example, 
drinking alcohol?
    Mr. Elliott. No.
    Mr. Stearns. Just yes or no.
    Mr. Elliott. Alcohol was not an issue.
    Mr. Stearns. No, it's not--the question isn't whether it's 
an issue. The question is, were you drinking alcohol at the 
time this incident was reported in The Washington Times. Just 
yes or no, and I remind you, you are under oath.
    Mr. Elliott. Yes.
    Mr. Stearns. You were drinking alcohol?
    Mr. Elliott. Yes.
    Mr. Stearns. Were you consuming a sufficient amount of 
alcohol that it might have, in your honest opinion, affected 
your judgment at all?
    Mr. Elliott. No.
    Mr. Stearns. Were you consuming alcohol that it would--
well, maybe, let's just be frank. Had you had a lot to drink?
    Mr. Elliott. No. I had such a little amount to drink that 
the police--they didn't give me a breathalyzer. I was never 
charged with public drunkenness.
    Mr. Stearns. I understand, but the point is you were 
drinking alcohol at the time this incident was reported in the 
The Washington Times. You were taking Chantix', and 
also you were taking a family-related drug, Prozac, at the same 
time, too. I mean, those are correct statements, aren't they?
    Mr. Elliott. They are.
    Mr. Stearns. Notwithstanding that fact, the Veterans 
Administration clearly had a responsibility to get your--a 
written approval, and I have here documents that you have 
signed showing that you have given extensive approval for the 
use of the patch. It's page after page where you have agreed to 
take these smoking-cessation drugs. If they had given you this 
form, would you have signed it? Because it seems like you 
signed all these other forms for the smoking-cessation drugs.
    Mr. Elliott. I did sign this form. I did agree to take the 
patch, and I don't believe the patch is considered----
    Mr. Stearns. No, but I am just saying that it appears that 
you were willing to sign forms because you wanted to stop 
smoking.
    Mr. Elliott. That's correct. I was willing to sign forms. 
Had they came with me with a part two form, which I--one can 
conjecture that that part two form would be the consent to take 
Chantix'.
    Mr. Stearns. Yes.
    Mr. Elliott. Maybe I would have. Maybe I wouldn't have. It 
would depend on how honest they were.
    Mr. Stearns. That's a very important point, that you were 
not given the opportunity to sign these forms; and, two, you 
weren't told sufficiently about the side effects. And I think 
that's the point.
    I just want to conclude, Mr. Chairman, to ask Colonel 
Charles, are you aware that the study did not include 
Chantix' in the protocol until January of 2007? Yes 
or no?
    Colonel Charles. No.
    Mr. Stearns. Thank you, Mr. Chairman.
    The Chairman. Thank you, Mr. Stearns.
    Ms. Brown.
    Ms. Brown of Florida. Thank you.
    Mr. Elliott, first of all let me tell you that I want to 
thank you for your service to this country, and I want to thank 
you for coming today to share your story with us. And I hope 
you don't feel that you are in any way under the gun, because 
this--what you are doing will help us as we move forward with 
our responsibility as far as oversight is concerned.
    I have one question I want to ask you, and then I want you 
to share something with us, but I want to know how you are 
doing. Someone else asked you this question, and what I mean by 
how you are doing, are you able to hold a job now? Are you--you 
know, how are you functioning?
    Mr. Elliott. I had to drop out of the university.
    Ms. Brown of Florida. Okay. So you were a student?
    Mr. Elliott. Yes, ma'am, I was a straight-A student.
    Ms. Brown of Florida. A straight-A student.
    Right now, you are just in limbo?
    Mr. Elliott. That's one way to describe it.
    Ms. Brown of Florida. Yes, sir.
    You mentioned that you were involved in a study, and it 
seems that it was a very controlled study. How long was this 
study going on? I mean, it was for years?
    Mr. Elliott. I don't exactly know, but I began going to the 
Washington, DC, VA Medical Center in February or March of 2006, 
and, you know, even from that time I remember seeing the 
posters all over the walls, but it was October 31 of 2006 that 
I became part of the program.
    Ms. Brown of Florida. Okay.
    I have a real concern when you indicated that you contacted 
the office. You told them that you had an emergency situation, 
and it--there was no follow up, no contact, until you had a 
complete breakdown.
    Can you explain why someone did not get back in touch with 
you right away? Did you go into the office?
    Mr. Elliott. Yes, ma'am. I physically went into the office.
    Ms. Brown of Florida. And no one followed up?
    Mr. Elliott. No.
    Ms. Brown of Florida. The Secretary is here. He is sitting 
behind you. What would you share with him as to how we could 
improve the system?
    Mr. Elliott. Well, it's a well known fact that the doctors 
are, you know, under a heavy burden. They have a large case 
load.
    Ms. Brown of Florida. You were in a controlled study. I 
mean, you know, you were limited. It wasn't a large case load. 
You were visiting with----
    Mr. Elliott. Good point.
    Ms. Brown of Florida. Yes, sir. You were visiting with the 
counselor. The list that my colleague gave of drugs that could 
cause certain problems, but that is, when you are just taking 
these drugs. But you were in a controlled state, you were 
seeing a counselor. This should not have happened to you.
    Mr. Elliott. I agree, ma'am.
    I think that, you know, in the future, if a patient who is 
known to be 100 percent PTSD diagnosed, if he comes in in an 
extremely agitated state, he should be seen by someone, you 
know, on the spot.
    Ms. Brown of Florida. Absolutely.
    Mr. Elliott. Another comment I would like to make, ma'am, 
is that you cannot compare aspirin, the common drug aspirin, 
which is, I guess, it is part of the list of 200 drugs that can 
induce suicide. But aspirin is also 100 percent natural 
product. It comes from the bark of a tree. Whereas Varenicline 
tartrate is actually derived from one of the more venomous 
snakes on the Earth, and that is very well known throughout the 
research of alpha-bungaro toxins. Aspirin and Varenicline 
tartrate are not even in the same universe.
    Ms. Brown of Florida. I do understand that. But in addition 
to that, you were in a controlled study.
    Mr. Elliott. Yes, ma'am.
    Ms. Brown of Florida. In other words, you were constantly 
seeing doctors, and you were involved with the VA, as opposed 
to just taking a list of drugs and, you know, not knowing what 
reaction. Clearly, you were having reactions, and there should 
have been follow up.
    Mr. Elliott. That's 100 percent correct, ma'am. I was in a 
controlled study. They knew very well what risk I could be 
facing. They saw me quite often. We had contact both on the 
telephone, in the hallways, in official appointments, at all 
capacities. We were in pretty good contact with one another.
    But when I reached out that one time, and that one time was 
the most important time, I was more--I had the door slammed in 
my face.
    Ms. Brown of Florida. And that is where the system broke 
down?
    Mr. Elliott. And that is where the system broke down.
    Ms. Brown of Florida. I apologize for that. We are going to 
talk with the Secretary about that.
    Do you want to say anything to us about trying to imply 
that taking alcohol or having a drink or having a glass of wine 
could have contributed to this problem?
    Mr. Elliott. I believe that, you know, the two beers that I 
had earlier in that day, they may very well have saved my life. 
I was at such a point of confusion that, you know, due to lack 
of sleep, due to a chemical war going on inside of my head, 
that I just needed to relax so desperately badly that those two 
beers that I drank earlier in the day, you know, they did 
enable me to go to sleep, and they possibly defused the 
situation in a much needed way.
    Ms. Brown of Florida. Once again, thank you for your 
service.
    Mr. Chairman, I yield back the balance of my time.
    The Chairman. Thank you.
    Mr. Boozman.
    Mr. Boozman. Thank you, Mr. Chairman.
    Again, I want to tell you how much we appreciate your 
service to our country. My dad did 20 years in the Air Force. 
And I know the sacrifice on your part and your family's.
    I think we have really got two things going on. We've got 
the study issue, whether this was appropriate and things. And 
then the other thing is it's one thing to initiate a study in 
good faith. It's another thing, perhaps, to have problems like 
you had as far as follow up. In other words, again, it doesn't 
matter what medicine you take or this or that. Sometimes there 
are problems with it. On the other hand, your other contention 
is that you didn't get good care once you started having 
reactions.
    As far as the medication, this is an oversight Committee in 
the sense of looking into this. It's difficult in not knowing 
what medications you were taking. It appears that you were 
drinking some, taking the anti-anxiety medicine along with 
that.
    We didn't get the opportunity to look at your medical 
records in that regard.
    Did anyone else get to look at those? Did you share those 
with anybody else prior to the hearing?
    Mr. Elliott. No.
    Mr. Boozman. Okay. Very good.
    Like I said, I appreciate your service, and, again, I think 
we really do have two things to look at the appropriateness of 
the study and then, again, whether or not you were adequately 
taken care of in the sense that, once you started having 
problems, were people there to follow up with?
    Tell me about, very quickly, you being in and out of the VA 
system, how would you rate it? How would you, besides this 
instance, how would you rate the care that you have had through 
the years?
    Mr. Elliott. Excellent.
    Mr. Boozman. Very good.
    Okay. I yield back--I yield to Mr. Stearns if he has got 
another question.
    Thank you very much.
    Mr. Stearns. Thank you, Mr. Boozman.
    I don't have another thing. I just have a question, if I 
could, for the Chairman and his staff. In light of Dr. 
Boozman's comment about the interaction of these drugs and that 
we really don't know anything and that, as Mr. Elliott has 
pointed out, he did not make his medical records public, the 
question is for the Chairman. Did you or your staff have any 
review, personally, on the records of Mr. Elliott?
    Did you request them? Did you look at them to be sure that 
we had the full picture here, the interaction of all the drugs 
that he has admitted taking at the same time he took 
Chantix'?
    The Chairman. No, I didn't. I did not think that I had 
access to those records or should have access to those records.
    Mr. Stearns. Well, as you know, as we pointed out in our 
letter to you, that you have the constitutional right to have 
access to them. And, in fact, the VA administration would have 
provided them to you, and you and your staff could have 
reviewed this so it wasn't necessary for us to be asking all 
these questions, which are very difficult for Mr. Elliott to be 
asked under oath. And I would just advise in the future that if 
we are going to have this type of hearing that the 
constitutional oversight responsibility is for you to review 
those records before we have the hearing.
    The Chairman. Thank you, Mr. Stearns.
    Mr. Rodriguez.
    Mr. Rodriguez. Thank you, Mr. Chairman.
    And Mr. Elliott, let me thank you also for your service.
    How long did you serve our country?
    Mr. Elliott. Three years and a few days, 3 years and 5 
days. I didn't enlist, sir, until November 11, 2001.
    Mr. Rodriguez. Thank you for your service.
    Let me ask you, Colonel, on, I guess, you know, as 
DefenseWatch, I guess you are an advocate, you know, on behalf 
of soldiers?
    Colonel Charles. Yes, sir, that's one of our functions, 
yes, sir.
    Mr. Rodriguez. One of your functions. Let me ask you, in 
terms of this study, do you have any other information on the 
study in terms of any other problems that have come up with 
anyone else?
    Colonel Charles. I have just seen in the general media 
reports of other incidents, episodes with that same drug. They 
have been covered in the general media, but I have not had any 
contact with other veterans that have expressed any concern.
    Mr. Rodriguez. Yes, apparently, this is something that has, 
you know, serious concerns, and I know that, in any system, you 
know, we have some difficulties that we have to--have you all 
come up with any recommendations as to what needs to occur, 
what needs to happen in terms of making it more transparent?
    Colonel Charles. No, sir, I think the regulations are in 
place. My understanding, if they are appropriately implemented, 
there's usually not a problem. It's when people are not fully 
following their own protocols that we get these episodes, these 
events.
    Mr. Rodriguez. Let me just indicate that I think I have 
gone to a lot of hearings. This is one of the first hearings, 
and I think this is the second time that the Secretary has 
actually been here before they come up. So I do want to thank 
you for being here and listening to some of these comments, 
because the main thing we want to do is see how we improve on 
access to healthcare for our veterans and making sure we close 
some of those loopholes and some of the problems that might 
exist out there.
    And we want to make sure, and we are fully aware of the 
fact that, as a Congress, that we have not in the past provided 
the appropriate resources that are needed in order to make that 
happen. We are hoping that we can close the gaps there and do 
the right things.
    Do we have anything else on the study as to why it came 
about or, you know, on the actual study that has taken place 
and how long it's been in effect or anything?
    Colonel Charles. Are you addressing that to me, sir?
    Mr. Rodriguez. Yes, sir.
    Colonel Charles. I did not really follow this study in 
detail. I did the initial review of the material that Mr. 
Elliott and Ms. Hilburn provided, validated the authenticity, I 
thought, and then in passing the information to The Washington 
Times for further work.
    Mr. Rodriguez. Let me just ask you, I guess, one other 
question, as an advocate of our soldiers, what, if anything, 
you would have to recommend to us, things we can do to help 
improve healthcare to veterans?
    Colonel Charles. Sir, I will just say that, from what I am 
hearing, that if we can get more people like Dr. Peake involved 
in taking these difficult jobs on at the highest level, I think 
veterans would be well served.
    Mr. Rodriguez. Thank you very much.
    The Chairman. If you would yield for a second, and I think 
Secretary Peake will talk about this, there was an internal 
review provided, and I don't know exactly how many people there 
were, but of the people admitted to the VA, they found, who 
were taking Chantix', 11 attempted suicides, 1 
attempted homicide, 9 had suicidal thoughts, 6 suffered from 
hallucinations. But I think Secretary Peake will talk about 
that.
    Mr. McNerney is next.
    Mr. McNerney. Thank you, Mr. Chairman.
    I want to thank you, Mr. Elliott, for coming and testifying 
today. I can imagine how difficult this must be for you.
    Did you start smoking while you were on active duty in the 
Armed Forces?
    Mr. Elliott. No, I smoked before that.
    Mr. McNerney. Do you remember the events of February 5th 
which led to your arrest?
    Mr. Elliott. Vaguely.
    Mr. McNerney. Vaguely.
    Ms. Hilburn, were you with Mr. Elliott during the episode 
which led to his arrest?
    Ms. Hilburn. Yes, sir, I was.
    Mr. McNerney. Did you feel when you were in that situation 
that your life was in danger or anyone else's life was in 
danger?
    Ms. Hillburn. I felt that James was so disoriented and so 
in instinctual combat mode, he had reverted almost to a mode in 
which he was in a combat scenario, that I felt that the car 
keys needed to be secured, and I asked him for the car keys. He 
was highly agitated, and I felt that, indeed, police assistance 
was necessary for his own safety and that of others.
    Mr. McNerney. Mr. Elliott, do you believe or have you been 
told that the memory or the lack of clear memory was due to the 
drug Chantix'?
    Mr. Elliott. No, I have never, no doctors or anyone have 
ever come forward and said that to me, but it's pretty well 
known that Chantix' can cause memory lapses, 
distorted time, the lack of memory, I guess, you can say.
    Mr. McNerney. Thank you.
    The psychologist who prescribed the Chantix' to 
you was Dr. Hallie Lightdale. Is that correct?
    Mr. Elliott. Yes, sir, that's correct.
    Mr. McNerney. Was Dr. Lightdale a VA doctor or assigned in 
any way by the VA?
    Mr. Elliott. As far as I know, she was, you know, a VA 
employee. I mean, she was always presented to me that way. You 
know, but now that you mention it, you know, throughout my 
whole experience with this program, I met lots of people that I 
had never seen before; I had met them on a one-time-only basis. 
They were extremely interested in what was going on in my life 
on a day-to-day basis, my psychological state, et cetera. You 
know, this is especially in the end. This was a very 
degenerative type situation.
    You know, there's a witness on this consent form that I 
signed who I never met. That person was not there, you know, 
which, you know, I didn't really become alarmed at that fact 
until afterwards, but, you know, who are some of these people 
that are in and out of my day-to-day medical care?
    Mr. McNerney. Good question.
    Mr. Elliott. Are they VA employees? Are they Pfizer 
employees? I have no idea. But to answer your question, I have 
always been under the impression that Dr. Lightdale was, 
indeed, a Veterans Affairs sanctioned doctor.
    Mr. McNerney. Did Dr. Lightdale ever recommend that you 
stop taking Chantix'?
    Mr. Elliott. No. She more or less seemed adamant to get it 
down my throat at any cost.
    Mr. McNerney. Since you have stopped taking that drug, have 
you noticed substantial change in your behavior?
    Mr. Elliott. Quite a bit, yes, yes, sir.
    Mr. McNerney. Well, one last question. Were the possible 
mental side effects explained to you before you started taking 
the drug Chantix'?
    Mr. Elliott. No, sir, not at all.
    Mr. McNerney. Thank you.
    I yield back.
    The Chairman. Thank you, Mr. McNerney.
    Mr. Walz.
    Mr. Walz. Thank you, Mr. Chairman.
    And thank you, again, Mr. Elliott.
    I do think that it has been conveyed that some of the 
difficulties in these questions aren't about trying to sterily 
deconstruct your life, that concern for you as an individual is 
definitely amongst everyone in here, amongst those sitting 
behind you. And I applaud you for, again, as I said, the 
courage to come here. Because it's not just about you; it's 
about future veterans who may be put in the same position.
    The goal of this Committee and those here is to try and 
provide that oversight to make sure it happens. When I hear you 
say you received excellent care, I am glad to hear that because 
I, too, believe that the VA provides excellent care. As I have 
told them often, I am their biggest champion and harshest 
critic to make sure we get it right every single time.
    In just a minute, you are going to have the Secretary of 
the VA who is going to come exactly where you are sitting, and 
he is going to raise his hand in exactly the same way, and he 
is going to talk about ways that we can improve this. And I 
think you heard Members talk about this. That's a very good 
thing. It's moving in the right direction.
    So I don't want you to think this is about individual care 
and the deconstruction and the timeline of some of the things 
that we are asking. We are trying to gather the best 
information.
    From my perspective, I think Mr. Boozman was summing this 
up right. I have grave concerns about the study itself, about 
some of the protocols that were in place, the common rule and 
some of those. Those will be dealt with, with the witnesses 
afterward.
    The other thing that comes to my attention and one thing 
that I am equally or more concerned about is, what happened to 
your trust in the VA as it eroded and what led to a situation? 
And I can guarantee you, on the comments that you went there in 
what you considered to be an emergency situation, and not 
receiving immediate care; every time one of those situations is 
brought up, we will find every single minute of what transpired 
in that. You can be sure that we will go to that, and the VA 
will do that.
    We had an episode in Minnesota that we were able to 
backtrack and put all the information together. Because there 
are two very important things that happen when something like 
that happens. If it turns out that the veteran is truly 
misserved like that, it's absolutely tragic. If something 
happens that the information that's conveyed to the public is 
not exactly the way it turned out, it ruins the trust in the VA 
system.
    And I would tell you, I sit here as a 24-year veteran. I am 
a retired Command Sergeant Major in the Army. My concern for 
you and the troops is the paramount issue, and building trust 
is the single biggest factor in a successful unit, as you well 
know.
    You trusted those people to watch your back as you were 
patrolling the streets and kicking doors and everything else 
that happened. We need to make sure that that same trust is 
felt for the VA.
    So my concern--and what I would like to try to figure out 
here is--I am pleased that you entered the system. You went, 
and as you know, PTSD is the normal human reaction to an 
abnormal situation. So to be in that position is absolutely 
normal at what you went through.
    How did you first go to the VA? I mean, why did you first 
enter the VA? You said you were there in the spring of 2005, 
and you were in Iraq in 2003 and 2004. Is that correct?
    Mr. Elliott. That's correct, sir.
    Mr. Walz. Okay, could you just explain to me how you got 
there and how that interaction went, with your first initial 
visits to the VA and how they started diagnosing PTSD and how 
they were treating that? Could you just briefly summarize, if 
that went the way you would like to think the system should 
work?
    Mr. Elliott. Well, my family immediately noted the changes 
in me from before I went into combat and the changes that were 
very evident to them when I came back home to America, you 
know, after my Expiration of Time and Service (ETS) date. They 
strongly urged me to go and seek psychiatric help, and that is 
how I got into the system.
    As I stated earlier on the record, my very, very first 
visit with a VA psychiatrist was unsatisfactory, to say the 
least. I mean, he wasn't concerned about my day-to-day life. He 
was only concerned with the fact--he wasn't concerned with my 
war-time experiences. He wasn't concerned about if I was going 
to make it home safely after the appointment.
    His only concern was the fact that I had a very strong 
nicotine habit.
    Mr. Walz. The first consultation you had when you were 
going in and your family was concerned about PTSD----
    Mr. Elliott. Very, very, very first consultation.
    Mr. Walz. The conversation went right to smoking?
    Mr. Elliott. Yes, sir.
    Mr. Walz. Did it improve any after that? I mean, the 
subsequent consultations and things. Was there more of what you 
were hoping they would talk to you about, about the things you 
had seen or the ways you were feeling different or the reaction 
your family was having toward you? Did any of that start to 
come up then?
    Mr. Elliott. It didn't come up on that day, but I only saw 
that doctor one time. After that, I was--I spoke with the chief 
of psychiatry there at North Little Rock Veterans Hospital, and 
he immediately had me assigned to a new doctor, and everything 
went very well after that.
    Mr. Walz. Okay.
    Well, again, I thank you for coming here. I appreciate your 
understanding of why these questions--they will benefit those 
that follow with the same situation that you are in, and that's 
what we are trying to get at.
    So thank you.
    And I yield back.
    The Chairman. Thank you.
    Mr. Mitchell.
    Mr. Mitchell. Thank you.
    Mr. Elliott, it concerns me that the VA would participate 
in this kind of a study with participants who are suffering 
from PTSD and are on the narcotic morphine, both of which 
impair mental stability.
    Do you now consider yourself to have been in the proper 
state of mind to participate in a medical study?
    Mr. Elliott. Say again, sir?
    Mr. Mitchell. Do you now consider yourself, after--do you 
now consider yourself to have been in the proper state of mind 
to participate in a medical study?
    Mr. Elliott. No, not at all.
    Mr. Mitchell. Again, I would like to, as everyone here has, 
thank you for your service and thank you for coming today.
    I yield back.
    The Chairman. Thank you, Mr. Mitchell.
    Mr. Hall.
    Mr. Hall. Thank you, Mr. Chairman.
    I, too, would like to thank you, Mr. Elliott, for your 
service to our country and offering you my best wishes and 
blessings as you go forward, and hopefully things will get 
better from here, and thanks for sharing your experience with 
us.
    I actually wanted to ask Colonel Charles just one question. 
Should, in your opinion, the VA be putting soldiers or veterans 
who have been diagnosed with PTSD into test studies of new 
drugs of which one of the side effects is predicted to be 
possible suicidal tendencies?
    Colonel Charles. Congressman, that's a very difficult 
question to make just a broad general answer to. I think you 
have to look at the specifics of each individual, but I will 
say that it raises the bar, in my mind, to a very high level 
before you can justify putting someone, who is already 
struggling for mental normality, into a drug study where one of 
the known side effects is a threat, a risk to that very mental 
normality.
    So I wouldn't make a blanket statement, because there are 
many pressing medical needs out there and so on, but I would 
say the burden is on somebody to show why the risk is justified 
in this case.
    Mr. Hall. All right, and I would acknowledge the validity 
of my colleague, Mr. Stearns, and Mr. Boozman's point about the 
different drugs that we take for different things, and 
sometimes it's a risk-benefit analysis. There may be another 
condition, physical or mental or psychological, that's being 
dealt with, and the doctor or psychiatrist needs to make these 
judgments.
    But since one of the symptoms of PTSD is an increased 
likelihood of suicide attempts, it seems that that bar, as you 
say, should be raised for a drug study where the side effect of 
that drug may include the same thing. It could be a multiplier.
    Thank you very much.
    Mr. Elliott. Yes, sir.
    Mr. Buyer. Will the gentleman yield?
    Mr. Hall. Yes, I would.
    Mr. Buyer. You kept referring to this as a drug study. This 
was not a drug study.
    I yield back to the gentleman.
    It's a smoking cessation study. It's not a FDA drug study.
    The Chairman. But the VA was trying to decide which patient 
was the best for the drugs.
    Mr. Hall. Reclaiming my time, I would just say that I 
accept the point but would just say that a smoking cessation 
study, which is employing certain drugs----
    Mr. Buyer. That's correct.
    Mr. Hall. Nonetheless gives the medical people, the VA, the 
option to determine which drugs to use, but, more importantly, 
which veterans to put in the study, and I think that's my 
point.
    Mr. Hare. Would the gentleman yield?
    Mr. Hall. I would yield whatever time is left.
    Mr. Hare. Thank you. I am confused here.
    Mr. Elliott, if I understand you correctly, you went to the 
VA initially for PTSD.
    Mr. Elliott. Yes, sir.
    Mr. Hare. And, the answer to PTSD was smoking cessation?
    Mr. Elliott. From the very first day it seems apparent to 
me that they were very interested in my smoking habits.
    Mr. Hare. So you go to the VA, and you say, I think I have 
this problem; I need to see somebody. You are diagnosed with 
PTSD, and you're prescribed smoking cessation. But instead of 
beginning something that would treat the PTSD, they want to 
stop your smoking; is that what you are saying?
    Mr. Elliott. That's what I was saying.
    Mr. Hare. I find that very confusing.
    Mr. Elliott. It's confusing. It's incredible. It's scary. 
It's sad.
    Mr. Hare. Thank you, Mr. Chairman.
    Mr. Hall. If I could, in just the couple of seconds that 
remain of my time, reclaim it and say that this was officially, 
PTSD and Smoking Cessation Study Number 519, just for the 
record.
    I yield back.
    The Chairman. Thank you, Mr. Hall.
    Mr. Snyder.
    Mr. Snyder. I just want to thank you all for testifying 
today.
    I don't have any questions, Mr. Chairman.
    The Chairman. Thank you.
    Mr. Elliott, you have heard all of our questions. Is there 
any last statement you would like to make, any observations, or 
any advice for us as we proceed to hearing from the VA and 
other witnesses?
    Mr. Elliott. Well, I agree with Lieutenant Colonel Charles 
that human testing at the VA hospital should be eliminated. And 
I would like to point out that the graph that is part of my 
executive summary, you know, it clearly shows a criminal 
network and motive, and, you know, that motive is money. And 
that's all I would say.
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Mr. Elliott.
    Mr. Charles, any last statement?
    Colonel Charles. Mr. Chairman, I would just like to thank 
the Committee for their attention, and I hope, on a bipartisan 
basis, working with General Peake, you all will be able to 
solve what seems to have been a serious problem, and we hope 
it's not a big problem.
    The Chairman. Thank you.
    We thank you for your help in leading Mr. Elliott to ask 
the right questions.
    And as everybody has said, we thank you, Mr. Elliott. We 
know it took a lot of courage, and it's not the easiest thing 
to share your personal story. We appreciate it very much.
    We will adjourn this panel and move on to panel two.
    Mr. Elliott. Thank you.
    The Chairman. Secretary Peake, thank you.
    To be consistent with Mr. Buyer's request, if all the 
witnesses will please stand and raise your right hand.
    [Witnesses sworn.]

   STATEMENTS OF HON. JAMES B. PEAKE, M.D., SECRETARY, U.S. 
DEPARTMENT OF VETERANS AFFAIRS; ACCOMPANIED BY JOEL KUPERSMITH, 
 M.D., CHIEF RESEARCH AND DEVELOPMENT OFFICER, VETERANS HEALTH 
 ADMINISTRATION; J. THOMAS PUGLISI, PH.D., CIP, CHIEF OFFICER, 
 OFFICE OF RESEARCH OVERSIGHT, VETERANS HEALTH ADMINISTRATION; 
 MILES McFALL, PH.D., DIRECTOR, POST-TRAUMATIC STRESS DISORDER 
 TREATMENT PROGRAMS, VETERANS AFFAIRS PUGET SOUND HEALTH CARE 
  SYSTEM, VETERANS HEALTH ADMINISTRATION, U.S. DEPARTMENT OF 
  VETERANS AFFAIRS; AND PAUL SELIGMAN, M.D., M.P.H, ASSOCIATE 
 DIRECTOR OF SAFETY POLICY AND COMMUNICATION, CENTER FOR DRUG 
  EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION, U.S. 
DEPARTMENT OF HEALTH AND HUMAN SERVICES; ACCOMPANIED BY ROBERT 
 TEMPLE, M.D., DIRECTOR, OFFICE OF MEDICAL POLICY, CENTER FOR 
  DRUG EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION, 
          U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

    The Chairman. Secretary Peake, we thank you, and appreciate 
knowing that you were paying very close attention to the 
testimony.
    Joining you today is Dr. Joel Kupersmith, the Chief of 
Research and Development; Dr. Thomas Puglisi, the Chief Officer 
of Oversight Research; Dr. Miles McFall, the Director of the 
PTSD Patient Care Line at VA Puget Sound Health Care System. 
Also joining you is Dr. Seligman who is the Associate Director 
of Safety Policy and Communication, Center for Drug Evaluation 
and Research for the Food and Drug Administration.
    I am sorry--that was Dr. Seligman, and he is accompanied by 
the Director of the Office of Medical Policy, Dr. Robert 
Temple.
    We thank each of you for being here. It's a very important 
issue, and we thank you for your testimony.
    Secretary Peake, you are recognized.

             STATEMENT OF HON. JAMES B. PEAKE, M.D.

    Secretary Peake. Mr. Chairman, I have a statement to submit 
for the record with your approval.
    The Chairman. So ordered.
    Secretary Peake. Mr. Chairman, Congressman Buyer, Members 
of the Committee, thank you for holding this hearing and for 
the opportunity to discuss the important issues on our use of 
FDA-approved medicine, of our Cooperative Study Research 
Protocol No. 519 and of the integrity of our research programs.
    The issues raised are integral to the care of our veterans 
today, to their best care in the future, and to our absolute 
obligation to them for the quality of that care and maintaining 
a research system that keeps their well-being and safety as an 
unequivocal priority.
    That makes it particularly painful to hear Mr. Elliott's 
experience with PTSD and some of his perceptions about VA care.
    I was appreciative to read in the paper 2 weeks ago the 
accolades he gave for those who provided care at the VA and to 
hear him today, again, talk about, today, the excellent care.
    While I was appalled to hear about his experience in 
seeking emergency care--and I can guarantee you, I am going to 
look into that--regarding the medication Varenicline and its 
use in helping veterans stop the dangerous and addictive 
behavior of smoking.
    First, Varenicline, also known under the brand name of 
Chantix', the same thing, has been FDA-approved 
since May of 2006. It has been widely prescribed in the United 
States and overseas since that time.
    The VA, after usual consideration, which is significant, 
and review, 8 months later placed it on the national formulary, 
January 2007. This is a prescribed medicine, which means that 
the decision for its use is an individual decision between the 
patient and his or her healthcare provider.
    Just as with any prescribed medicine, the provider, with 
the patient, weighs the potential benefits of a medicine 
against any potential side effects.
    In the case of Varenicline, it has been considered a 
medicine primarily, as you heard, for those who have failed 
other forms of smoking addiction assistance. Tobacco use 
remains the single most preventable cause of morbidity and 
mortality in the United States. Stopping smoking before the age 
of 50 reduces the risk of death by 50 percent over the next 15 
years.
    The Chairman. Secretary Peake, I shouldn't interrupt you, 
but you had the benefit of listening to the earlier testimony.
    Secretary Peake. Yes.
    The Chairman. When something is directly dealing with 
something that you are saying, I would ask you to address it, 
because you said that there has to be close consultation with a 
doctor and a patient about the side effects. The testimony was 
that there was no such thing.
    I think you need to address those issues as you bring them 
up and not just wait for us to say----
    Secretary Peake. I can address that now, or I can complete 
my statement.
    In fact, I did listen to, very carefully, Mr. Elliott, who 
talked about being, in consultation, in November, with his 
physician, told about the side effects of nausea, stomach 
upset----
    The Chairman. He testified he was not told of the side 
effects of Chantix'----
    Mr. Buyer. I would ask for regular order----
    The Chairman [continuing]. And he was given no consent form 
to sign.
    Mr. Buyer. I ask for regular order and permit the Secretary 
to testify, Mr. Chairman.
    The Chairman. I am the Chairman, and I am following the 
regular order.
    The testimony was that there was----
    Mr. Buyer. The rules decide the regular order of the 
Committee, Mr. Chairman.
    Allow the Secretary to testify.
    The Chairman. The rules do not allow you to interrupt.
    Mr. Buyer. Allow the Secretary to testify, I think is what 
the Committee would like.
    The Chairman. Secretary Peake, the testimony stated that 
there was no such explanation of the side effects, and there 
was no consent form. You stated that the process is that there 
should be such consultation. So, please address that, sir.
    Secretary Peake. Sir, this was, as the Ranking Member 
pointed out before, not a drug study. There is, there was not a 
separate consent form for Chantix', which was an 
FDA-approved drug that 32,000 people--70,000 people, actually, 
across the VA, 32,000 currently, are getting in consultation 
with their individual physicians.
    The Chairman. How many of those have PTSD?
    Secretary Peake. About 6,000, sir.
    And what I would--as I listened to the testimony, the side 
effects that were described, when Mr. Elliott started, was 
started on Chantix', were the side effects that were 
known at the time, and that was specifically as he talked 
about, nausea and so forth. I mean, that's----
    The Chairman. Yes, but other side effects became known 
later, and he said he wasn't informed about them. So address 
the issues here, not just what was----
    Mr. Buyer. Regular order, please.
    The Chairman. Stop interrupting me, Mr. Buyer.
    Mr. Buyer. Regular order. I ask for regular order.
    The Chairman. Secretary Peake, you said he----
    Mr. Buyer. I ask for regular order for Mr. Secretary to 
testify.
    The Chairman. I heard you, Mr. Buyer.
    He is at the Committee. I am asking a question about his 
testimony.
    Mr. Buyer. I asked the Secretary to testify. Please do not 
be rude. There are three equal branches of government. This is 
a Secretary of a department of the government.
    Please do not be rude to the Secretary.
    The Chairman. I am not being rude to the Secretary. I am 
asking him to explain why he keeps saying that there was this 
process. We heard testimony that the process was not followed. 
Please address that point, sir.
    Secretary Peake. Sir, if I could explain the nature of this 
study, it might be helpful.
    The nature of the study was, had nothing to do with the 
drug. It could take any medicine that the doctor, that his 
doctor would prescribe to help him to stop smoking. I believe 
Mr. Elliott explained that.
    The issue of the study was solely about whether you 
received that smoking cessation medicine or counseling or 
therapy from your PTSD provider or in a venue other than your 
PTSD provider.
    The medicine, sir, was prescribed based on what you and 
your doctor decided was best.
    The Chairman. But new warnings had come up?
    Secretary Peake. Sir, I can address--I would like to talk 
about the sequence of the warnings, if you would like.
    The Chairman. Okay.
    Secretary Peake. And on 19--but I should tell you that on 
19 November, the Medical Letter on Drugs and Therapeutics, one 
of the most widely read and authoritative sources used by 
clinicians for current information on medications, updated 
their previous comments on smoking cessation, stating: More 
recent publications and the clinical experience of the Medical 
Letter consultants now suggests that Varenicline is the most 
effective drug available for this indication, more effective 
than nicotine replacement therapy or Bupropion, which is Zyban.
    In that same report, the Medical Letter did add, and I 
quote, ``a word of caution: Exacerbations of psychiatric 
illness have been reported in patients who took higher than 
recommended starting doses of Varenicline.''
    Related to this word of caution, they refer to two case 
reports, one of an exacerbation of schizophrenia and another of 
a manic episode in a patient with bipolar disorder.
    There's no recommendation to not use the medicine. On 21 
November, 1 day later, the FDA did issue an early communication 
on Varenicline.
    This is a source of information to clinicians to help 
inform their individual prescribing practices. Unlike a 
provider in private practice, who must keep up with this kind 
of information on their own, the VA provides this kind of 
information retransmitted through our pharmacy program, just as 
they did in this case, one day later on the 21st of November. 
This early communication is not a drug alert, not a warning.
    It suggested that healthcare professionals monitor patients 
for behavior and mood changes; that patients contact their 
doctors if they experience behavior or mood changes; and that 
patients use caution when driving or operating machinery.
    On 18 January of 2008, further information was similarly 
distributed to VA healthcare providers reporting on Pfizer's 
labeling changes and the European Medicine Agency's preliminary 
warning noting that Varenicline should be reserved for--as we 
told them--for veterans who have not been successful with or 
for whom nicotine replacement therapy are contraindicated; also 
that the healthcare provider should educate veterans about the 
changes in behavior or mood and instruct them to report such 
changes to the provider.
    Again, this information was provided to our clinicians to 
have them better informed so that they, in conjunction with 
their patient, can make the best clinical decision.
    On 1 February, the FDA issued a public health advisory for 
healthcare professionals to highlight revisions to the warnings 
and precautions section of the full prescribing information for 
Chantix' regarding serious neuropsychiatric 
symptoms. These symptoms included changes in behavior, 
agitation, depression, mood, suicidal ideation, and attempted 
and completed suicides.
    Specifically noted on the Web site was that the FDA is not 
advising practitioners to discontinue prescribing the product.
    There was not then, nor is there now, a black box warning 
or a product recall on Chantix'.
    On 5 February, based on this updated information, the VA's 
pharmacy benefit management--that's 4 days later--our Benefits 
Management Service issued an alert through the pharmacy 
channels to all of our clinicians so that all who might be 
prescribing Varenicline were aware of the updated information 
and specifically the recommendations that patients tell their 
doctor about any history of psychiatric illnesses prior to 
using Varenicline, that healthcare professionals, patients, 
patients' families, caregivers be alert to and monitor changes 
in mood and behavior in Varenicline and that Varenicline 
patients immediately report changes in mood and behavior to the 
doctor. This information went to clinical staff, VA smoking 
cessation lead clinicians, Smoking and Tobacco Use Cessation 
Technical Advisory Group, the Medical Advisory Panel, pharmacy 
chiefs, chief medical officers and clinical pharmacists. You 
know, this drug was officially added to the VA national 
formulary, as I said, in January of 2007. Concurrently, VA 
reviews of Varenicline were begun in the VA focusing on 
dehydration and a Atrial fibrillation that were the things that 
we knew at that time were associated with Varenicline.
    In October of 2007, we were seeing some reports of 
psychiatric issues in patients on Chantix'. Data at 
that time suggested just under one-half of 1 percent had such 
symptoms reported. These are through the adverse drug event 
reporting system that we had. In December of 2007, our VA Med 
Safe Group instituted a rapid cycle analysis as we watch lots 
of different medications to look at adverse events, laboratory 
findings, International Classification of Diseases (ICD)-9 
codes, Current Procedural Terminology (CPT) codes, mortality 
data from administrative databases. From December of 2007 
through March, that data was analyzed. From March to May, VA 
developed and vetted and published Varenicline formulary 
prescribing and guidance. In the meantime, the medication 
label, which goes on each container, was updated in December of 
2007 and again following--and I think we have a copy of that 
there up on the screen--was updated again in February. So that 
every bottle that came had that warning appropriately on it.
    The point, Mr. Chairman, is that there has been a lot of 
due diligence about this medication. Medical professionals 
engaged in each step along the way to assist providers to 
appropriately use this medicine for their patient, making that 
individual decision with the best information available. And 
again, it is for not just those in the study, but for the 
32,000 folks, 6,000 of which have PTSD that are out there 
trying to stop smoking.
    This is very important as I turn now to the issue of the 
cooperative studies program, Protocol No. 519. It is a study 
designed to find the best venue to provide smoking cessation 
assistance in patients with stable PTSD. Can I have that next 
slide? This is not a study of this drug or any other drug. It 
can be just counseling for that matter if that is what your 
doctor thinks you need. All therapy is between the healthcare 
provider and the patient using only FDA approved medicines in 
association with counseling. There was no investigational drug 
involved. The smoking cessation complement can be provided 
either in the PTSD treatment venue or in another smoking 
cessation venue.
    At the beginning of this study, Chantix' was not 
even on the market and that was back in 2004. When it became 
FDA approved and available as part of the armamentarium for 
providers in general to use in smoking cessation, it became one 
more tool for the individual provider and the patient to use to 
help stop smoking. All of the information on this medicine and 
the updates, so that information from the post marketing 
experience was available to the clinicians caring for our 
veterans in this study. In addition, because of this study, 
additional consideration--really because of the study--I want 
to emphasize that--additional consideration was given to first 
the early communication with discussions by medical 
professionals, seriously considering this issue, aware and 
experienced with dealing with veterans in this study and 
patients with PTSD in general.
    On 26 November, again on 4 December, they had conference 
calls of the Cooperative Study Group. And it was their 
considered opinion that there should be no recommendation to 
alter the study at that time. Following the February alert, the 
Cooperative Studies Group in addition to immediately forwarding 
the alert through research channels again had discussions to 
further consider this new information consistent with the 
promise to update veterans in the study on new information on 
smoking cessation, an addendum to the consent form was produced 
and a draft letter, the wording of which was carefully 
considered, encouraging patients to follow up at the next study 
visit to discuss and to report immediately any changes in mood 
or behavior or a desire to discontinue Chantix'.
    This letter itself did not contain the word ``suicide.'' I 
acknowledge that. However, the addendum to be attached did have 
the full description of the alert to include the word 
``suicide.''
    Each study location has an institutional review board (IRB) 
responsible for ensuring that the research done at that 
institution is ethical and meets the scientific standards 
required. The IRB has the final say in the conduct of such 
research to include materials sent to patients, the content of 
the consent and other informational materials, and consider the 
guidance that comes from the Cooperative Study Group in such a 
multi-institutional research study as this.
    Ultimately, each IRB, as was done at the Washington VA, 
approved the letter and addendum with the appropriate local 
information added and points of contact to be sent to the 
patients in the study.
    Turning back to the title of this hearing. As we have 
reviewed this study, including those study subjects who had 
obtained Chantix' from any VA source, we found 241 
who had been on Chantix' at some time during this 
study. The only two deaths in this group was one from liver 
cancer and one from coronary artery disease, neither in any way 
potentially related to Chantix'. There were no 
deaths from suicide in this group. Of the 241, there were 19 
veterans who had sometime during the study, reported one or 
more psychological adverse events, to include 11 who reported 
some level of suicide ideation. I would point out that in any 
study reporting of adverse events includes any event that 
happens to the person in the study and is not necessarily 
causally related to the study at all or to any particular 
medicine in the study.
    And if I can have the next slide. We watched these serious 
adverse events from the very beginning of the study out to May. 
You can see that it is relatively constant and you can see when 
Chantix' was started and you can see there wasn't 
any big--or statistical bump to make us think that there were 
some real worrisome thing. The next piece is--you know, the 
ordinate is--the Y axis there is important. This is .01 
percent, is that first grid line, and this is the psychological 
issues that were reported in terms of serious adverse events 
(SAEs) in this study. You see a little bump there at the right-
hand side of the graph? It is right after the FDA warning came 
out. I think people are more alert to those kinds of things. 
But, again, that is at the .01 percent level. Next line. 
Currently there are only 40 who are prescribed 
Chantix' that are under the care of a provider in 
this study. Over the same period of the study in this 
population of patients with PTSD, of the 704 veterans not on 
Chantix', 28 experienced psychological adverse 
events, one completed suicide and one died of an intentional 
overdose yet to be characterized as a suicide. And that was 
among over the course of the study 25 total deaths.
    All of this information has been reviewed by the Data 
Monitoring Committee who fully aware of the concerns, concluded 
that the actions that we have taken and that have been taken 
have been the right ones.
    I have spent a fair amount of time to lay out the 
particulars in this case, sir, and I appreciate your 
indulgence. I do fully appreciate the unique population that we 
serve and the importance of the research to ensure that their 
unique needs are appropriately studied and that we apply the 
best evidence-based medicine on their behalf. Far from 
considering our veterans as Guinea pigs or disposable heroes, 
as has been suggested in some of the headlines, they are a 
precious national resource and they deserve the best of science 
and medicine by people who care about them and people who 
understand their sometimes unique characteristics and needs.
    I know you share this concern and our Ranking Member 
particularly pushed to reform our research institutions 
establishing Dr. Puglisi's organization, the Office of Research 
and Oversight (ORO). Over time, we have put in place a 
structure with this ORO oversight and the Office of Research 
Development, institution review boards and cooperative studies 
human rights Committees that absolutely can support the finest 
scientific inquiry and the proper considerations and safeguard 
of our veterans while meeting their needs.
    However, I will tell you, excellent structure must be 
matched with excellent execution. And while I believe the 
appropriate decisions and considerations were ultimately made 
in the course of this study, I have directed a detailed review, 
not only of this study, but of all ongoing studies involving 
our veterans with PTSD.
    Our Office of the Inspector General has reviewed the 
execution at the Washington VA around this study, specific 
concerns have been raised about the thoroughness of the patient 
contact, ready availability of information on and about study 
subjects and of the quality of the study audits. In one 
instance, a research misconduct inquiry has already been 
directed to investigate an allegation of improper data 
collection. Each of the OIG findings and each of their 
recommendations will be examined and acted upon. Their work 
will inform the ongoing review that I have already directed and 
their additional investigation will be complementary and a 
complete review for me to understand what additional safeguards 
in our research programs should be implemented.
    Further, where we find inadequacies, I will demand 
institutional and personal accountability. That is what we owe 
to our veterans and that is what we owe to the American people.
    I listened carefully to Mr. Elliott. It hurts me when any 
of our veterans suffer like that. And while I do not agree at 
all with his feeling that the VA should not be engaged in 
research, I do believe that in the research we do have a 
special responsibility and we must go that extra mile.
    Mr. Chairman, I thank you and I look forward to your 
questions.
    [The prepared statement of Secretary Peake and slides 
appear on p. 92.]
    The Chairman. Thank you. Dr. Seligman?

            STATEMENT OF PAUL SELIGMAN, M.D., M.P.H.

    Dr. Seligman. Mr. Chairman, I do have a very brief 
statement to make. As you know, I am here today on behalf of 
the Food and Drug Administration Center for Drug Evaluation and 
Research, and I am joined by Dr. Robert Temple, who is the 
Director of Medical Policy.
    As you know, FDA is responsible for the regulation of 
prescription and over-the-counter drugs that play an 
increasingly important role in improving and maintaining our 
health. FDA's oversight responsibilities for drugs include pre-
market testing, evaluation of drug applications and, where 
appropriate, approval of drugs for marketing. It also includes 
post-marketing monitoring of drug safety and communicating 
information to healthcare professionals and patients to help 
guide their decisions in the safe and appropriate use of drugs.
    FDA's drug review process is considered and recognized to 
be the worldwide gold standard. We incorporate the latest 
advances in medical science in our reviews, which include a 
complete assessment of the drug's metabolism, its interactions 
with other drugs, and potential differences and effectiveness 
and safety in people of different genders, ages and races.
    All drugs, as you know, carry risks and can cause side 
effects. A critical aspect of evaluating the safety of drugs 
and assuring their most appropriate use is the effort to assess 
drugs after they are approved. No amount of pre-market study 
can discover all we need to know about a drug's effectiveness 
or its risks. New safety problems are regularly identified when 
a new drug is used by the general population in larger numbers 
than studied in pre-market.
    FDA's post-marketing monitoring program plays an essential 
role by collecting and assessing information about adverse 
events and medication errors identified after approval. We 
learn about these effects in various ways, but mostly from 
reports from physicians, nurses, pharmacists, healthcare 
institutions and other providers sent directly to the FDA or 
via the drug company. We now receive almost a half a million 
reports a year for all drugs nationwide. We evaluate these 
reports together with information from other sources as 
available, as part of our continuous assessment and 
reassessment of the balance between the benefits and risks of 
the product. Our response to information from this ongoing 
surveillance depends on our evaluation of the aggregate public 
health benefits of the product compared to its evolving risk 
profile.
    FDA also uses a broad range of methods to communicate drug 
safety information to the public. Certain forms of 
communication are targeted to specific audiences such as 
physicians or patients. Others are directed to more than one 
group to ensure their widespread dissemination.
    The FDA approved drug product label is the primary source 
of information about a drug's safety and effectiveness. It 
summarizes the essential scientific information needed for the 
safe and effective prescribing and use of the drug. Labeling 
for prescription drug products is directed primarily to the 
healthcare professional but often includes patient counseling 
information as well. As we learn new information about the 
safety of the drug, we update the section of the label that 
lists the adverse events and that describes the warnings and 
precautions for its use.
    More information going directly to the patient is 
considered important. It can be provided in the form of a 
medication guide or a patient package insert that accompanies 
the dispensed drug. In addition to the professional label, FDA 
uses a variety of means to communicate important often emerging 
safety information.
    As Mr. Secretary pointed out, we use public health 
advisories, which are directed to help patients and healthcare 
professionals and the general public and are used to highlight 
important safety information. We also use healthcare 
professional information sheets again to communicate important 
information and to provide recommendations to mitigate 
potential risks.
    Since August of 2007, FDA has issued early communications 
about ongoing safety reviews to keep healthcare professionals 
and the general public informed of post-market safety issues 
that are currently being evaluated by the FDA. Early 
communications are issued at the beginning of FDA's assessment 
prior to conclusive determination of the clinical or public 
health significance of the information under evaluation and 
before a decision has been made about what regulatory actions, 
if any, should be taken. All of our communications are 
available on our Web site, disseminated through our MedWatch 
Partners Program and our LISTSERV that includes 92,000 
subscribers.
    FDA plays a critical role not only in the detection and 
management of safety issues, but a critical role in 
communicating this information to the public. Our goal, 
regardless of the tool that we use, is to make the most up-to-
date drug safety information available to the public in a 
timely manner so that healthcare professionals and patients can 
consider the information when making decisions about medical 
treatment. We are committed to providing accurate, clear, 
reliable and useful drug safety information to the American 
public.
    Thank you for the opportunity to testify and for being 
before the Committee today. And again, we are happy to respond 
to any questions.
    [The prepared statement of Dr. Seligman appears on p. 101.]
    The Chairman. Thank you for your testimony. You know, the 
reason why we put you on panel two instead of panel one is so 
you could hear the testimony of panel one. It looked like you 
were listening attentively, but your testimony made no 
reference to it. I understand the process and on paper it looks 
fine. We had testimony--I agree it is one individual--that said 
this process didn't work. You both spent your whole time saying 
it depends on informing the health professional. Well, you 
don't know that the health professional is informed. You send 
out something. We had testimony that it didn't work. The health 
provider didn't pass on those warnings. There was no consent 
form that was ever offered. He came and reported emergency 
problems, which were dismissed. So all that data that you have 
depends on someone reporting it. What if we have every health 
professional treating their patient like Mr. Elliott? If that 
happened, your data is useless.
    So we have a reality. That is why we had panel one. The 
process that you laid out did not work. I mean, is that what 
you heard or not?
    Secretary Peake. Mr. Chairman, I did hear that and I truly 
had some difficulty following totally kind of the sequence of 
events there. But as you all asked your questions, I thought I 
understood where Mr. Elliott was in his experience. It sounded 
to me that he was treated for his PTSD, it was begun some time 
ago. He clearly had a problem with tobacco that was in fact 
considered by his healthcare professionals to be a problem and 
he wanted to stop smoking. And that was the criteria for being 
in this. It was also that you had relatively stable PTSD, not 
with other psychoses or serious mental illnesses or so forth. 
When he started on the medicine by his private physician, by 
his personal physician, what was known and before any warnings 
came out from FDA, the early communique--even before the early 
communication what was known was some of these dehydration----
    The Chairman. Before the FDA warning, the doctors in the VA 
knew that there was something going on because they started 
their own internal review before that.
    Secretary Peake. You are right. We start following----
    The Chairman. You knew something----
    Secretary Peake [continuing]. The post-marketing survey in 
conjunction with working with the FDA.
    The Chairman. So people knew something before the November 
incident. Why was it never communicated to Mr. Elliott's 
physician?
    Secretary Peake. Sir, there was very little information to 
make any qualified judgment about this medication. As I 
indicated, it was like half of 1 percent that we were getting 
some reports on.
    The Chairman. Based on the information----
    Secretary Peake. That information was shared with the FDA 
to say ``what--are you seeing anything?'' I mean, it was one of 
the things that was discussed with the FDA. I agree that--with 
Dr. Seligman, that they really are the gold standard and we----
    The Chairman. But you heard testimony that the process 
broke down. Neither the information that the health provider 
should have passed on nor the symptoms that the patient had 
were included in your data. Doesn't that give you some pause 
about your incredible confidence in this gold standard system? 
It depends on these individuals having that same----
    Secretary Peake. Sir, you are right.
    The Chairman. Is this doctor going to be asked about this 
testimony, for example?
    Secretary Peake. I beg your pardon, sir?
    The Chairman. Is the doctor who Mr. Elliott said did not 
inform him of the side effects going to be questioned about 
that?
    Secretary Peake. Yes, sir.
    The Chairman. Thank you.
    Secretary Peake. I would like to also make it clear that--
--
    The Chairman. Is the process we are going to be looking at 
in other VA facilities where people did not take seriously the 
emergency status of the individual leading to suicides in other 
cases--almost suicide in this case--is that going to be looked 
at in the detail that Mr. Walz talked about?
    Secretary Peake. It absolutely will, sir. In this 
particular case as well. And I will tell you I totally agree 
with your concern about suicide as an issue. As we talked last 
night, we are continuing to address that as a significant 
issue, one that we need to be very concerned about. I will tell 
you that there is great literature to support the notion that 
smoking itself, ongoing current smoking itself is associated 
with suicidal behavior. So, you know, this is a very 
complicated subject.
    The Chairman. Of course it is.
    Secretary Peake. Smoking is a bad problem and it kills 
people.
    The Chairman. So does suicide.
    Secretary Peake. I agree.
    The Chairman. What disturbed me in the press accounts 
leading up to this hearing was Dr. McFall was quoted as saying 
there is no causation here, we'll wait until the study is over. 
Well, if there was causation, we would know because some would 
be dead.
    But it seemed to me that you had a limited number of 
people, something like 144, that were particularly fragile 
because of PTSD. It was a small group of people. You could have 
called them all. I mean, if it was my child involved, I would 
have wished that you would have called them all. They had 144. 
Call them, tell them what is going on, tell them to come and 
visit the physician. Deal with these people in a very personal 
way. You are dealing with everything bureaucratically. You 
issue a letter to 225,000 people, you think it is going to be 
read by everybody, you think everybody is going to follow it, 
you think the patient is going to be heard. Call the patients. 
You have their phone numbers. Call them up. Tell them they have 
PTSD, they are taking Chantix', they need to see 
their physician immediately.
    As Colonel Charles said, there is a higher bar in this kind 
of study. There is a higher bar and I don't believe you met it 
and you could have. I mean if you had asked me, as soon as I 
read it, I would have called 144 of them and gotten them in to 
the doctor. But now, we are going to wait until the study 
proceeds because it is only .1 percent; we will take 4 months 
to study this and on and on and on. This is life and death. And 
you are operating as a bureaucracy, which takes months and 
months and months, and we saw possibly only one of the 
outcomes.
    You found others that bother me particularly. I don't care 
if it is 1 percent or 50 percent. From the testimony I will bet 
that you don't know all the data.
    Secretary Peake. Sir, I will tell you that I would have--I 
was--we had about 240--there were 945 people in the study, on 
both arms of the study, and only about 241 of them were taking 
Chantix' any time during that study. One of the 
reasons I have asked for a detailed review of this study, in 
particular, is to understand where we might have fallen down in 
terms of the notification. We have only about half of the folks 
that have signed----
    The Chairman. But you are still studying it and there are 
still people in it. I would have suspended the study until you 
found out if there is causation. You have 40 people left. Get 
them off of the drugs. Don't take any chances.
    Secretary Peake. Forty people smoke and are trying not to 
kill themselves with smoking. And I think it is up to the 
doctor and not an editor or not perhaps a Committee that ought 
to withhold a medicine from a doctor.
    The Chairman. If the doctor didn't do his job, we are in 
trouble.
    Mr. Buyer. Mr. Secretary, you have had over 40 years in the 
United States Army in many capacities, but most of which as a 
medical doctor, sir. I almost had a flashback here that I was 
back at Fort Eustis as an Army Judge Advocate General captain 
sitting in to give legal counsel to the Quality Assurance Risk 
Management Committee that was examining whether a particular 
doctor exercised good judgment in the interest of their patient 
on whether or not it gave them the proper consent about the 
advisory of a drug. And in this particular case, I look at this 
one as a layperson and we have an individual who was taking a 
particular drug that Mr. Stearns had had an interaction with 
this individual and the drug had a neuropsychotic side effect; 
i.e., suicide ideation. So he is already taking that drug and 
now all of a sudden he is prescribed Chantix' and 
then when the doctor learns that there is an advisory opinion 
on Chantix' that also could have a side effect; 
i.e., suicide ideation, now I have a patient that is taking two 
drugs that have a possible side effect of ideation. What are 
the propensities or the multiplier effect of that, of the 
interaction of both of these drugs, on top of that taking 
alcohol?
    I mean, that is pretty volatile, I would think. And so I 
kind of look at this and say, okay, we have a large VA study 
and you have many institutional review boards. About how many 
do you have?
    Secretary Peake. Sir, in this study there were 10. There 
were 11. One was the oversight where they weren't treating 
patients. So really 10 study sites.
    Mr. Buyer. And are the 10--but outside of this study, you 
have about 100--are there about 120 institutional review 
boards?
    Secretary Peake. One-hundred seventeen, sir.
    Mr. Buyer. There are 117. But 10 of those participated in 
this study?
    Secretary Peake. That is correct.
    Mr. Buyer. And do each of these institutional review boards 
sort of act independently of each other?
    Secretary Peake. In fact they do. That is their charter, to 
ensure that at that institution, that the medicine and the 
science and the protection of the human subject is paramount.
    Mr. Buyer. So we boil this down quickly; when the Chairman 
sort of gave us a charge in his opening about how are the 
execution of procedures, I look at this and say, well, first 
what is so important is the doctor/patient relationship, the 
doctor having the best of the interest of his patient at heart. 
And that there are many drugs out there, there are many 
advisory opinions that come down and they are to keep their 
patient's best interest at heart.
    Now, we have a case whereby--the testimony of Mr. Elliott, 
whereby he said he didn't sign an addendum to an informed 
consent. My question is, just because there is an advisory 
opinion by the FDA, does that mean that there is required to be 
a signed addendum to an informed consent?
    Secretary Peake. There is not, sir. The reason that we 
provided the addendum was in the very first consultation where 
he said he had 3 hours of counseling to understand this study 
and seemed to understand it pretty well. In that environment, 
he was told that we would inform him if there was any changes 
in the treatment for smoking cessation. And so that was our 
obligation, to make sure that we informed all of the folks in 
this study about the change.
    Mr. Buyer. So we have 10 institutional review boards, each 
acting a little bit different with regard to the advisory 
opinions. As of now, no black box advisory from 
Chantix'. Chantix' is still a legally 
prescribed drug, correct?
    Dr. Seligman. That is correct.
    Mr. Buyer. And, Dr. Seligman, is it accurate or fair at all 
for me to describe Chantix' as a suicide inducing 
drug?
    Dr. Temple. No, I don't think we know that. What we have is 
evidence, but it is not really complete. It comes from 
spontaneous reports that there are people who became suicidal 
on the drug.
    Mr. Buyer. I don't need the clinical. It is not accurate to 
call it a suicide inducing drug?
    Dr. Temple. Not that we----
    Mr. Buyer. The last comment--thank you, Mr. Chairman--is, 
Mr. Secretary, with regard to your interest on the 
pharmacological protections and surveillance, you have some 
findings from the Data Safety Board. Could you advise us to 
that? Was there any review from a Data Safety Board?
    Secretary Peake. Yes, sir. Our Data Monitoring Committee. 
Sorry, we changed the name and I am catching up with the name. 
In fact, they reviewed all of the data, all of the SAEs, and 
basically said that they found no reason to alter the study, 
that they found no reason to withdraw the use of any medicine 
in the study and that they concurred with all of the steps that 
had been taken and in the way that they had been done.
    Mr. Buyer. Could you provide that to the Committee?
    Secretary Peake. I can, sir.
    [The following information from the VA was subsequently 
received:]

          Question: Can you please provide the Data Monitoring 
        Committee's review of adverse events and serious adverse 
        events?
          Response: The Data Safety Monitoring Board (later renamed the 
        Data Monitoring Committee) met in both open and closed sessions 
        on February 27, 2008, to discuss several issues related to 
        Cooperative Studies Program (CSP) study #519 on smoking 
        cessation. During the open session, one of the principal 
        investigators raised questions about the high number of serious 
        adverse events and the Committee agreed to collect adverse 
        events and serious adverse events, which would be reported to 
        the Food and Drug Administration together. The Committee 
        further analyzed data on serious adverse events while in closed 
        session.
          The Data Monitoring Committee reconvened on July 3, 2008, 
        where the members discussed the incidence of serious adverse 
        events in both closed and open session.
          The attached minutes from the Data Monitoring Committee 
        meetings held on February 27 and July 3, 2008, included 
        portions which were closed sessions. This information must be 
        withheld from the investigators so as to avoid biasing their 
        research and will not become part of the public record. The 
        minutes are being retained in the Committee files.

    Mr. Buyer. All right. Thank you, sir.
    The Chairman. Thank you.
    Mr. Hare.
    Mr. Hare. Thank you, Mr. Chairman. Mr. Secretary, welcome 
to the hearing. I did not read The Washington Times article, 
but coming out it said that it took the VA 3 months to notify 
veterans of the side effects of the Chantix' and 
that the warning letter was tied up in ``bureaucracy,'' 
according to the article.
    Would you care to respond to that? And then if so, why did 
it take so long and do you think that is an appropriate time 
frame?
    And then lastly, what do you think we need to do to make 
the bureaucracy more efficient so our veterans are timely and 
appropriately notified?
    Secretary Peake. Sir, first on the timing. The 3 months I 
think came from the idea that on the 20th of November the early 
communication came out. In fact, the very next day we notified 
the clinicians through our pharmacy benefits channel. There was 
not felt to be, and I think appropriately so on the basis of 
that very early communication, a reason to go out and contact 
every patient that was on Varenicline. I don't think that was--
I think that was an appropriate judgment at the time.
    The other aspect of it, sir, is on February 1st, when the 
public health advisory came out from the FDA, that was a more--
we took that more seriously in terms of as a call to action, if 
you will. Again, immediately that was passed both through 
research channels and through our clinical channels to those 
that prescribed Chantix' and had patients on 
Chantix'. In the mid month, the research community 
that was responsible for the study got together and had a 
discussion about it and decided we should notify our patients, 
and that is when that letter that I described was put together, 
along with the addendum that was put together for the consent, 
and that was sent to each of those review boards that I talked 
about, the 10 review boards that the Ranking Member mentioned. 
Each of them then had to decide what is the best way to notify 
the patients locally and should they do it and did they want to 
change? One review board rewrote the letter, kept the same tone 
and everything, but went through that deliberation because they 
felt that is their responsibility. And so there was a lapse. 
Some, Washington Hospital Center as an example, sent that 
letter out by the end of February. So that would have been a 
one-month delay, if you will, or perhaps an appropriate 
deliberation period. Others didn't send it out until June. That 
to me, I am not sure I understand why, that is why I have asked 
Dr. Puglisi to take a good look at all these and understand 
why.
    I think we have--going to your next question, sir, the 
problem is that we do have all of these independent review 
boards when we are doing cooperative studies and I think--and 
we are already starting a central IRB, Institutional Review 
Board, so that we can have better and tighter discipline in 
terms of the execution in a study like this so they have a 
common standard, so everybody is--you have a way to hold people 
accountable, to be able to get the word out.
    The other piece is we will be looking, as part of our deep 
dive into this particular environment, to understand what kind 
of--going back to the Chairman's point, what should we be doing 
if we want to notify a patient? Do we need to call them? Do we 
need to send by return mail? So that we have a standard as 
opposed to do-it-however-you-feel sort of best at the local 
level.
    So we will be instilling that kind of discipline as we move 
through our system and move through our review of this 
particular case and apply it across the VA.
    Mr. Hare. I would appreciate that, Mr. Secretary. I 
appreciate your willingness to look into the situation with Mr. 
Elliott, and I also appreciate you being here today. And with 
that, Mr. Chairman, I yield back.
    The Chairman. Thank you, Mr. Hare.
    Mr. Stearns.
    Mr. Stearns. Thank you, Mr. Chairman. Let me welcome the 
Secretary of Veterans Affairs. How long, Mr. Secretary, have 
you been in this position?
    Secretary Peake. About six and one half months, sir.
    Mr. Stearns. Six and a half months. Okay. And I was just 
reading your distinguished biographical data on you, that you 
are a retired lieutenant general, you went to West Point and 
that you also served with distinction in Vietnam and you got 
the Bronze Star with a V, the Silver Star, Purple Heart, Oak 
Leaf Cluster. So you have served your country admirably and we 
appreciate your service and we also appreciate you willing to 
take on this very difficult job of being Secretary of Veterans 
Affairs.
    I think I will just get to maybe a very important point 
that we should all establish here. Do you have the numbers that 
we could know today for veterans who have participated in the 
smoking cessation program who have actually stopped smoking; 
for example, using the nicotine patch, how many have actually 
stopped, using the nicotine gum, and then Chantix'? 
Has there been any data that we know of that you could give us 
today?
    Secretary Peake. Sir, this has--this is a long-term study. 
It is not over yet. We don't have it all closed. But the 
principal investigator is here and perhaps has some insights 
into that.
    Mr. McFall. Thank you for the question. The study is due to 
be completed in July of 2009, meaning all of the enrollees, the 
participants, will have had their follow-up data then. At that 
point would be the appropriate time for us to be able to give 
the analysis to you and then the study will essentially----
    Mr. Stearns. Give me a premature blush; that is, is the 
smoking cessation program working?
    Mr. McFall. The biostatistician has that data. I do not. I 
am a principal investigator and I am deliberately kept blind to 
that data so as not to bias----
    Mr. Stearns. So you can't tell me if the nicotine patch or 
the nicotine gum is working at all?
    Mr. McFall. I am not personally able to do that because I 
do not have access to the data. I am kept blind. They don't 
want me to see the data for fear of biasing the outcome. The 
only persons who really know that are the study 
biostatisticians.
    [The following information was subsequently provided by the 
VA:]
                    Preliminary Results of the Study
          Question: Do we have any indication of the results of the 
        study? Can the study's biostatisticians provide any data to the 
        Committee?
          Response: The Department of Veterans Affairs cannot release 
        any results of the study until its completion in July 2009 so 
        that we can preserve the data's integrity and the study's 
        validity. However, information about adverse events is 
        submitted for review to local Institutional Review Boards, 
        Human Rights Committees and the Data Monitoring Committees to 
        evaluate whether there is a clear harm or benefits for 
        participants while a clinical trial is still ongoing. VA shared 
        this preliminary information in testimony before the Committee 
        on July 9.
          The study in question is not a drug trial of varenicline, and 
        is not designed to provide information on the safety and 
        effectiveness of varenicline, bupropion or nicotine replacement 
        therapy. The study is seeking to determine if it is easier to 
        stop smoking when smoking cessation treatment is combined with 
        PTSD therapy, or whether the two therapies are more effective 
        if they are provided separately. In this study, patients may be 
        receiving one of several proven smoking cessation treatment 
        options, including counseling, behavioral modification and/or 
        drugs prescribed by their own physicians. Drugs include 
        varenicline, bupropion, transdermal nicotine patches and 
        nicotine gum, all of which are on the VA Formulary and are Food 
        and Drug Administration (FDA) approved treatments which have 
        undergone substantial evaluation to receive FDA approval. ``The 
        Medical Letter on Drugs and Therapeutics'' has found, based on 
        their evaluation, that ``. . . varenicline is the most 
        effective drug available for this indication (smoking 
        cessation), more effective than nicotine replacement therapy or 
        buproprion SR (Zyban).''
          The study chair is kept ``blind'' (unaware) of the results 
        until all data have been collected and analyzed. ``Blinding'' 
        is an important means for reducing or minimizing the risk of 
        biased study outcomes. This commonly used mechanism in clinical 
        trials research helps to prevent preliminary results from 
        influencing how the study is conducted or other key study 
        decisions. However, results of the study (``unblinded data''), 
        including adverse events and serious adverse events, are 
        continuously monitored by other members of the study team, 
        including the study biostatistician and study pharmacist.

    Mr. Stearns. There is no feedback then? I mean, this 
program has been going on since 2006, right? 2004. Almost 4 
years and we have no data to indicate whether any of these 
programs are working?
    Mr. McFall. The data is available. It is reviewed by the 
Data Safety Monitoring----
    Mr. Stearns. Oh, I know bureaucratically. I understand 
that. But you are here today to tell us these programs are 
important and you want to continue them. I am asking you, does 
nicotine gum work?
    Mr. McFall. Well, the intervention is again, sir, not just 
about gum or patch or any other medication. It is a 
comprehensive program that includes counseling and medicines as 
optional.
    Mr. Stearns. Mr. Secretary, could you say as lieutenant 
general, if your superior said to you, gee whiz, General, we've 
had this program for almost 4 years, is it working, I want to 
know whether to continue it. What would be your answer?
    Secretary Peake. Sir, what I would tell you is that the 
modalities that we are using are proven modalities for stopping 
smoking. The question to be answered that you can't answer in 
the short term is, is it better to do it with PTSD treatment or 
is it better to do your PTSD treatment separately from the 
smoking cessation environment. And that is why we are trying to 
answer this question. The modalities are proven modalities.
    Mr. Stearns. Let me ask you this, Mr. Secretary. I need you 
to elaborate. Of the 945 veterans who enrolled in this study, 
and I guess there are 245 on Chantix'. Were they 
counseled on the complications of this drug? Let me just 
establish that. Yes or no, were they counseled on the FDA 
clinical advisory of February 2008? Were they, yes or no? And I 
think the answer for you is you don't know.
    Secretary Peake. Well, I will tell you that each of them--
--
    Mr. Stearns. Because it is on your watch. February 2008, 
FDA made this advisory----
    Secretary Peake. If your question is were they counseled 
specifically about the FDA warning, I cannot definitively tell 
you that at this point.
    Mr. Stearns. So the answer would be no. Now, when I go 
through and I go to Hampton, Virginia, and I see the number of 
people who are taking Chantix' and the people who 
had a consent agreement--and I saw the consent agreement--what 
it looks like. Out of the 28, 15 had no consent agreement. Then 
I go to Houston, Texas. Of the 35 there, 19 there was no proof 
of consent agreement. When I go to Minneapolis, there is 14 out 
of----
    Secretary Peake. About 50 percent of them don't have----
    Mr. Stearns. What I am saying, Mr. Secretary, in all 
deference to you, here is a program in which you are not 
getting consent agreement from the patients. And that seems to 
me a bad procedure and that somebody should have taken care of 
it because you should get consent agreements--in the 3 hours of 
counseling that was done for these folks in the beginning, 
there wasn't any kind of counseling done for 
Chantix' or any kind of advisory after the FDA 
issued this in February of 2008; is that correct?
    Secretary Peake. Sort of. Let me explain it if I may. 
Chantix' was not added to the study at all until it 
became FDA approved and then put onto the addendum that was 
created at that time based on what we knew about 
Chantix' at that time. As the FDA has testified, 
there is emerging information that goes along with it.
    Mr. Stearns. I will grant you that point. But I gave you 
Houston, Minneapolis, Hampton, Virginia? I mean, 50 percent of 
these people are not getting any consent agreement. Don't you 
admit that is wrong?
    Secretary Peake. First of all you need--the consent 
agreement is really an addendum to the consent form. They 
already agreed to the study.
    Mr. Stearns. Shouldn't they get an addendum to the consent 
form?
    Secretary Peake. The addendum to the consent form is to 
ensure that they have been informed about the change. The 
answer is yes.
    Mr. Stearns. No. The question is should they have an 
addendum to the consent form? Yes or no.
    Secretary Peake. Yes.
    Mr. Stearns. They were not done here.
    Secretary Peake. They were sent the addendum in the mail.
    Mr. Stearns. Why were 50 percent of these not signed and 
you couldn't produce them?
    Secretary Peake. Part of the reason is because they were--
said if you are doing fine, come in at your next visit, which 
could be 6 months later, and we will sit down and go over it. 
But you have the information in hand. So that is part of it. 
Part of it is--I am concerned--some people moved out of the 
area----
    Mr. Stearns. Have you taken procedures to correct this so 
that if I come back in 6 months and I pull the same data, it 
won't be that 50 percent have not signed the addendum to the 
consent agreement? Have you taken procedures to do something 
about that?
    Secretary Peake. That is exactly what this in-depth study 
of this particular----
    Mr. Stearns. Do you need a study to get conformance on a 
consent agreement addendum?
    Secretary Peake. What I want to do is make sure we have the 
right processes and we can be able to hold the accountability 
right down to the grassroots level to ensure that these kinds 
of things, to include this consent agreement, get done.
    Mr. Stearns. In all fairness, if you were chief executive 
officer of a company and I saw this data, I would call up 
Houston, I would call Minneapolis, I would call Hampton and I 
would get together on the phone and say get the addendum 
consent agreement right now.
    Secretary Peake. That has been done.
    Mr. Stearns. You have done that?
    Secretary Peake. That has been done.
    Mr. Stearns. Okay. Okay. All right. Thank you, Mr. 
Chairman.
    The Chairman. Thank you, Mr. Stearns.
    Ms. Berkley.
    Ms. Berkley. I thank you, Mr. Chairman. This has been 
perplexing to me. Could you, Mr. Secretary, explain to me, was 
this gentleman, Mr. Elliott, part of the study, not part of the 
study, and if he was part of a study, what were we studying?
    Secretary Peake. Yes, ma'am. He was part of the study. The 
study was to see if it is better to get smoking cessation 
treatment, whatever that may be between you and your doctor, 
whether it is counseling alone, whether it is nicotine patches, 
whether it is Chantix'--whatever you and your doctor 
decide is the best smoking treatment for you; if it is better 
to get that treatment from the guy or gal that is giving you 
your PTSD treatment, or get your PTSD treatment separately and 
smoking in a different environment, smoking cessation clinic or 
your primary care doctor or whatever.
    Ms. Berkley. How long has that study been going on?
    Secretary Peake. It has been since 2004 and it should be 
concluded here in 2009. And the idea was not just can you stop 
smoking this week, but what is your long-term ability to stop 
smoking? Because that is really ultimately what makes a 
difference for people's health and life and complications of 
smoking.
    Ms. Berkley. So it is essentially if you have PTSD and you 
are a chronic smoker how do we best treat both of these 
symptoms, or both of these problems I should say?
    Secretary Peake. What is the best place to do that 
treatment, is it better to get it from your PTSD doctor. PTSD 
people smoke more than twice the rate of other people. So it is 
a big problem for them.
    Ms. Berkley. Let me ask you something and I hate to call 
this woman the lady doctor, but I don't have her name in front 
of me. My stepdaughter is a lady doctor. I think she would be 
very offended if I called her that. Was she part of our VA? Was 
she a VA doctor?
    Secretary Peake. Yes, ma'am. In fact, yes.
    Ms. Berkley. So she was treating Mr. Elliott for his PTSD 
symptoms--problems and his smoking?
    Secretary Peake. Yes, ma'am. You know, he has not released 
his medical records, so I really can't get into the discussion 
about his--the details of his healthcare.
    Ms. Berkley. I am kind of gleaning from his testimony that 
she was his psychiatrist and she had recommended to him that he 
take this anti-smoking medication, that----
    Secretary Peake. From his testimony, that is what I gather. 
In fact, it sounds like others have talked to him about the 
smoking problem before.
    Ms. Berkley. So he signed his consent form that had patch 
and had gum but did not mention this other drug but he 
consented to it, obviously he started taking it on the 
recommendation or suggestion of his doctor. Did the information 
on the adverse effects of the drug get to his healthcare 
provider, his psychiatrist? Was she aware of it?
    Secretary Peake. She--the procedure was in place that she 
should have been aware of it. I do not know.
    Ms. Berkley. Is the breakdown--I am sorry. I don't mean to 
step on your answer.
    Secretary Peake. No. I actually think that she would have 
been aware of this. And through all of the things that we have 
already talked about in the manner in which we communicate down 
to the physician.
    Ms. Berkley. Okay. So we are going to assume that she had 
the alert but we do not know and, according to Mr. Elliott's 
testimony, she did not communicate the potential adverse 
effects to her patient, to the VA patient?
    Secretary Peake. That is--I agree with you, that is what he 
said.
    Ms. Berkley. Now, are you developing protocols to ensure 
that this information gets to the patient? Now he may have 
decided on his own not to take it, he was beginning to have a 
lot of adverse symptoms, but he was not informed, I guess, 
officially, according to his testimony, that there were 
possible psychotic problems.
    Secretary Peake. Right. We should make it clear about the 
timing of this. The FDA alert came out on the 1st.
    Ms. Berkley. Right.
    Ms. Berkley. And he was also breaking out in rashes and 
other things.
    Secretary Peake. As I believe he testified, he did see his 
doctor and talked about the rashes, and so forth. So they were 
aware of that. I think the real question is was he counseled 
about what we knew at the time about potential psychological 
issues.
    Ms. Berkley. How do we find that answer out?
    Secretary Peake. It would have to be with inspecting the 
medical record.
    Ms. Berkley. All right. When he came in for emergency 
help--and I think this is something that concerns us all, where 
was--why----
    Secretary Peake. It concerns me and I actually don't know. 
I will find out.
    Ms. Berkley. Has anyone been in communication with the lady 
doctor?
    Secretary Peake. Ma'am, I have not heard that--his 
emergency problem and not having care until he testified here 
today.
    Ms. Berkley. Because it sounded as if he knew he was having 
a meltdown, he did what appeared to be the appropriate thing; 
he went back to his psychiatrist and was asking for immediate 
intervention and did not get it?
    Secretary Peake. That is what he testified to. As I say, 
that is something we need to drive down and make sure what 
really happened and ensure that it would never happen again.
    Ms. Berkley. Let me ask you another question. How does the 
VA monitor the number of medications that are being taken by 
our patients? And as you know, I had the Justin Bailey 
situation in my district where he was taking multiple 
medications and was prescribed yet another and died of an 
overdose. And the combinations--it would seem to me knowing 
what Prozac can do, exacerbated by this anti-smoking drug that 
seems to have the same issues, plus a couple of glasses of 
beer, I mean, that seems like a real problem. Is anybody--
forget the beer--how do we monitor, if you are taking Prozac 
and now you are being prescribed this, this should be a red 
flag.
    Secretary Peake. It should be something that your provider 
really understands and is making a conscious decision based on 
you and your care. In this particular case, my understanding is 
that it would have been the same provider making both the 
prescriptions from what I heard him say. Now, I would also tell 
you that with our computerized patient record, it gives us an 
advantage over other places because there is an opportunity for 
medicines reconciliation where you see all the medicines that 
that person is on unless they get them from outside the VA or 
something. But all the medicines that are prescribed so that 
the provider can have that information readily at hand to try 
to make those decisions.
    I will tell you also that I do agree that we are concerned 
about this issue of polypharmacy and we have asked 
specifically, our Pharmacy Benefits Management Group to take a 
look using our computerized system--to see how many people 
really are on multiple--the same kinds of multiple classes of 
drugs and so forth. So I am looking forward to getting the 
information back from them so we can do a better analysis of 
just that problem, not necessarily related to this study, but 
it would include looking at these same medications, though.
    Ms. Berkley. And also is there a way that we monitor--and I 
don't want to accuse--my husband is a doctor. I am not accusing 
anybody. But do we know the quality of our doctors? Perhaps 
there was an individual doctor that was at fault here? Is this 
a problem systemwide with the VA? I mean, how do we get to--how 
do we solve this problem and what can we do in the future? And 
when will you be reporting back to us the information that you 
are going to gather?
    Secretary Peake. I would be delighted to report back to you 
the information we find out about this case. Very quickly 
because we will get to it quickly. However, I will tell you 
that we have the same kind of credentialing process, the same 
kind of peer review, the same--many of our doctors are 
affiliated with medical schools and universities, and so I 
think we have quite a high caliber of medical professionals 
throughout the VA and I think it is--so you have to rely on 
some level on their professional qualifications and judgments.
    Ms. Berkley. I don't doubt the level of expertise of our VA 
doctors. I am just concerned that we had a breakdown here and 
how do we prevent this from happening again?
    Secretary Peake. And I am concerned about the same thing, 
ma'am.
    Ms. Berkley. And when do you think you will be getting back 
to us with a report on what transpired in this particular case 
and how we are going to be able to prevent this in the future?
    Secretary Peake. I will shoot for the end of next week. How 
about that?
    Ms. Berkley. That is impressive. All right. Thank you very 
much.
    [The letter from VA appears on p. 129. The attached report 
will be retained in the Committee files due to confidential 
personal information included in the report.]
    The Chairman. Don't shoot anybody.
    Mr. McNerney?
    Mr. McNerney. Thank you, Mr. Chairman. Secretary Peake, 
thank you for coming and testifying today. Like I said to Mr. 
Elliott, I am sure this isn't an easy hearing for you. I 
believe there are two important issues here. The first is 
should risky treatments be administered to vets, especially 
vets suffering from PTSD, and second, if so, are they being 
administered under sufficiently careful conditions that 
includes letting the vets know that there is a risk involved? 
Especially this kind of risk. And is that information being 
disclosed as soon as possible?
    As Mr. Buyer pointed out, a professional should probably 
decide the first question, but the second question in my 
opinion is clearly under our jurisdiction. It appears that 
warnings were not being passed along and we want to make sure 
that appropriate procedures and responsibilities are in place 
to prevent this from happening again.
    Let's recap what happened here. On November 20th, the FDA 
notified the VA of serious side effects. On February 29th, 
participants using Chantix' were notified. Why did 
it take so long? That is the basic question.
    Secretary Peake. Well, sir, I would tell you that that 
early warning was absolutely considered by healthcare 
professionals and even by, I think, the discussion by the FDA 
here, it does not rise to the level where alarming or reaching 
out to try to touch everybody on the medication. We did not do 
that. I don't think anybody did that because I don't think it 
was the appropriate standard of medical practice to do it.
    Mr. McNerney. That is a matter of judgment, then.
    Secretary Peake. It is a matter of judgment, sir. That is 
my point. It is a matter of judgment that healthcare 
professionals considered seriously and felt it was not--you 
know, not warranted. So I agree with you, it is a matter of 
judgment.
    And I guess I would say, going back to Ms. Berkley's point, 
we really have some very high quality people who are used to 
taking care of patients with PTSD, who are used to using these 
medications that were part of that consideration.
    Mr. McNerney. Well, in conjunction with that, VA doctors, 
according to the Times article, The Washington Times, the VA 
doctors were reporting concerns about Chantix' 
causing serious events throughout 2007. Was this information 
acted upon in any way?
    Secretary Peake. Yes, sir, it was. In fact in--I think it 
was about October of 2007, as I say, we had seen half of 1 
percent of folks on Chantix' have something. Whether 
it is related to Chantix' or not, you can't really 
tell. We are still not clear. And I don't think FDA has made a 
causal connection with these issues and Chantix' 
either at this point. But that information, along with some 
anecdotal stuff, hey, Joe, I am seeing this, are you? And that 
information was passed to FDA because we have a member on the 
Safety Board there to say let's take a look at this and because 
we don't have--and there was, I think, already mentioned about 
7 million patients on Chantix'--the VA has had about 
70,000 and we haven't seen a big blip in, you know, over the 
course of treatment. It is about a 12-week treatment that can 
be extended to 24 weeks. So it has a longtime exposure. And so 
I guess I would tell you there was action taken. We were 
looking at it all along, starting in--I guess it was October we 
started adding the things we were watching more carefully to 
try to understand if there were more serious--or psychological 
side effects, adding to the data.
    That is what led to that discussion in December, that 
review in December that I discussed in my opening statement. So 
that we started looking at really in more detail to try to 
understand is there really something here that we ought to be 
more worried about. So, the notion that we weren't doing 
anything I think is not correct.
    I appreciate the Chairman's point, that if you were a dad, 
would you want--but, as we talked last night, I said if I were 
you sitting down with your doctor, do you want them not to have 
what is said to be the best medicine to help you stop smoking 
if you are a two and three pack a day smoker?
    Mr. McNerney. Right. But you also want to tell them that 
there is a risk involved.
    Secretary Peake. Yes, sir. On the 20th of November, that 
first notice came out. On the 21st of November, we passed that 
through the clinical channels so all the clinical people would 
have that information available to them.
    Mr. McNerney. Well, in my experience, this Committee has 
been finding out about serious issues from the media rather 
than from the Veterans Administration itself. The Washington 
Times report is an example. Do we have a lack of accountability 
here? Is that why we are not hearing--why aren't we hearing it 
here in the Committee before the newspaper tells us?
    Secretary Peake. You know, sir, with all due respect to the 
newspaper, as I have testified, I think in this case, except 
for the issue of the execution in the particular study of the 
signing of the consent addendums and doing that promptly and so 
forth, I think the clinical decisions have been appropriate 
and, you know, it is always tragic and I tell you I have 
absolute sympathy for a fellow CIB wearer that has had those 
kinds of problems and had the trials and tribulations of PTSD 
and so forth. I mean there is no--absolutely I am sympathetic 
to a fellow soldier. But, to say, well, should we act on that 
single case and deprive the 32,000 people out there who want to 
stop smoking from being able to work with their doctor, to 
decide is this the right therapy for me with that doctor 
knowing--having the information--and as I say, we keep updating 
the information as we get it. If the FDA in conjunction with us 
or we see something that suggests that this ought to have a 
black box warning or be a recall, I mean, we can do that very 
quickly and we would. And without hesitation I would restrict 
it within the VA if the evidence started to show that this was 
something that was truly putting our veterans at risk.
    Mr. McNerney. Well, I think the VA has some excellent 
policies in place to safeguard the veterans. My concern is, are 
those safeguards being followed? Are the policies of the 
Veterans Administration being administered properly in the VA?
    Secretary Peake. Sure, that's exactly why I have asked for 
these particular internal reviews of not only this study, but 
other studies as well, to also look specifically at our 
pharmacy program and how we cascade information and how quickly 
we do it and the standards to which we hold people.
    I agree with you.
    Mr. McNerney. Again, thank you for testifying; and I do 
look forward to working with you to resolving these problems 
that have come to light today.
    Secretary Peake. Thank you.
    Mr. McNerney. I yield back.
    The Chairman. Thank you.
    Mr. Walz.
    Mr. Walz. Thank you, Mr. Chairman.
    And, Mr. Secretary, thank you again for spending your 
morning down here. You have been very open since your tenure 
started just a short time ago in addressing these issues. I 
really appreciate that.
    I also want to make notice of the focus on the quality of 
care and especially on the research and the preventive side 
that the VA is taking--what I think is almost a unique position 
in American healthcare in dealing with that. And you have been 
dealt some pretty heavy ones, especially smoking.
    I know it's several decades ago, but when I ended up at 
Fort Benning, the 60 in my platoon, 5 of us didn't smoke. So, 
very common amongst members who have been there, so--and, 
rightfully, the causation between that and everything else that 
comes out of smoking is a focus.
    Now, we also agree that PTSD falls into a psychological 
disorder that can cause problems, too, down the road. It's on a 
spectrum, I am assuming, from mild to severe. So the VA is 
dealing with two issues at the same time amongst veterans. And 
I understand that that's where the physicians and the medical 
professionals make a diagnosis on this.
    And I am glad to hear--one of my questions was, how were 
you dealing with this or why are you dealing with that? You 
gave me data to say that these people smoke almost twice as 
much, on a much higher frequency, and things like that. So I am 
sure you are assuming and realizing that getting them off 
smoking--that you are trying to find out, does that help their 
PTSD recovery; is that correct?
    Secretary Peake. Sure.
    It's not just that it helps their PTSD recovery. We--
smoking alone is a reason to stop. I mean, it has----
    Mr. Walz. Do we know that smoking is not a release from the 
tensions of PTSD? I mean, I don't like to think that's a 
positive thing. I mean, it's a lesser of two evils, but that 
has to be a consideration, correct?
    Secretary Peake. It is. And actually one of the secondary 
objectives of the study----
    Mr. Walz. That's why you picked stable PTSD?
    Secretary Peake. Yes.
    Mr. Walz. Now my question comes up now--and this is where 
perception becomes a problem. When I heard the testimony of Mr. 
Elliott, it seemed that at first there was more of an emphasis 
on getting him in a smoking program than dealing with the PTSD 
on the first, initial consultation.
    And, again, perception is a problem. This is where we have 
to talk to the public. It is the gorilla in this room, as we 
speak about your predecessor's relationship with Pfizer, the 
maker of this drug, which brings up concerns.
    Now, whether those are founded or not is something we have 
to ask. So now we are in a situation where a soldier comes in 
with PTSD, his first consultation is to get into a smoking 
cessation program, which I applaud grandly. This is a great 
initiative, it's one that nobody is probably doing better. And 
I agree that if this drug can be proven to be safe, and take 
out the drug interactions and all of that, I want to see it 
work for people and get them off of this.
    My concern is this part of it that appears--that's where I 
think the questions come up. So I think the things that are in 
place from the procedures that Mr. Buyer initiated with some of 
the oversight to the IG--I would ask you, Mr. Secretary, what 
was the most troubling about the IG report to you? I mean, what 
did you find most troubling about this whole situation?
    Secretary Peake. What really troubled me about the IG 
report was, when they went in--and they went in quickly, and I 
thought they did a good job, but they seemed to have difficulty 
at the Washington VA of getting the information that was, how 
many people do you really have on this? Okay.
    Well, that was a question that was raised in the IG report, 
and why that couldn't be answered right away concerned me. The 
idea that they couldn't find the consent forms easily, the fact 
that the second--the consent addendums had not been signed.
    Mr. Walz. That was exactly the part that I picked out, too, 
for two reasons. One is--and it's not a cover-your-butt 
situation, I know that; I know you better than that--that you 
want to get these to make sure that the veteran knows what 
they're doing, not after the fact to cover that.
    My concern is the validity of the research then, the 
validity of the research--who is on it, when they have been 
taking it. And in some cases, they couldn't provide that. They 
couldn't say who was getting it.
    So now, as Mr. Stearns pointed out, we are 4 years into 
this study. And if we have an issue of validity and 
reliability, that's a concern.
    Secretary Peake. Sir, I would like to clarify that. Because 
it really doesn't matter from the research perspective, because 
of the question that's been asked in this research, what drug 
they're on, or if the issue is, did they get their--at the end 
of the day, did more of them stop smoking if whatever they got 
was from their PTSD provider; or whatever they got was--from a 
smoking cessation perspective, was provided by a smoking clinic 
or their primary care doctor, it doesn't really matter which 
medicine that they are on.
    That's sort of a byproduct of the fact that you are in a 
study, so you keep looking at those things.
    One of the things, probably--we didn't--the other thing 
that concerned me, on the 18th of June, we had 143 people, I 
was told, had been on Chantix'. When I started 
rolling it back and seeing there were other people--had been on 
Chantix', so we came up with a total of 241. That is 
because we were able to go and search our database that nobody 
else really has like that, and be able to say, okay, who got a 
prescription someplace else that was still in the study?
    So, you know, to answer the research--from a research 
perspective it's not so important.
    Mr. Walz. Okay.
    My last question--and I know my time is up, and I know this 
is much broader to ask you to deal with these issues in a 
green, yellow and red time zone here, it's tough--my concern 
is, and I hear this time and time again, is the mental health 
providers and the lack thereof in the system in general. That 
might be the bigger framework that we are dealing with.
    Secretary Peake. Yes.
    Mr. Walz. My question to you is in the spirit of being 
proactive to solve this, what do we need to do there? How do we 
entice this? How do we make sure, like, these gentlemen sitting 
with you choose to go to the VA and not the private sector, 
especially mental health-wise?
    After that, I will yield back.
    Secretary Peake. Couple of points, sir.
    First of all, we have really been on a hiring push. We are 
up to like 3,900 new mental health providers. Today, we have 
announced an increase in our Vet Centers, 39 new Vet Centers, 
because that gets people in, because it's a nonstigma 
environment and, you know, it's very receptive and they do a 
lot of outreach.
    So, you know, there's pieces there. As I mentioned, we are 
going to hire another 145 suicide prevention coordinators, more 
mental health people to put out there to be able to manage 
folks. And so, I think--I don't know, specifically, at 
Washington Hospital Center what the workload for this 
particular doctor was. That's part of the thing we will look 
into. I mean, there's no reason for somebody not to be able to 
access emergency care when they need it.
    Mr. Walz. If I could, Mr. Chairman, just on the record 
here, I would like to point out, the followup that was done on 
the incident in Minnesota was highly professional, was very 
detailed and got to the heart of what the situation there was. 
And that entire process through this step of the way, I was 
kept very well informed by them.
    So I know Ms. Berkley is no longer here, but when the 
Secretary says he will follow up on these situations, I trust 
that will happen, because I have seen it in action. So I thank 
you for that.
    Secretary Peake. Thank you, sir.
    [The following information was subsequently received from 
the VA:]
      Mental Health Caseloads at Washington, DC, VA Medical Center
          Question: Is there any indication that mental health 
        providers at the Washington, DC, VA Medical Center are carrying 
        too great of caseloads to provide quality care to patients?
          Response: At the request of Representative Walz and the 
        Committee, the Department of Veterans Affairs has reviewed 
        average caseloads for mental health providers at the 
        Washington, DC, VA Medical Center (VAMC). Overall, 90 percent 
        of veterans are seen within 14 days of their requested 
        appointment, and emergency care is available to those in need.
          For general mental healthcare (including psychiatry, 
        psychology, mental health consultation, post-traumatic stress 
        disorder [PTSD], substance use disorder, and other conditions), 
        between October 1, 2007, and July 15, 2008, the Washington, DC, 
        VAMC provided 142,459 encounters and scheduled 93,780 visits 
        for 8,569 unique patients. This information is included in a 
        table below for ease of reference.
          In regard to mental health staffing, the Washington, DC, VAMC 
        has 106.5 FTEE:

            22 psychiatrists,
            1 psychiatrist,
            19 psychologists,
            1 psychologist,
            17 Addiction Therapists,
            5 Psychology Technicians,
            10 Vocational Rehabilitation Specialists,
            27 Social Workers,
            34 Registered Nurses,
            4 Licensed Practical Nurses,
            5 Nursing Assistants, and
            3 Nurse Practitioners.

          In regard to mental health staffing within Trauma Services, 
        which includes PTSD treatment, the Washington, DC, VAMC has 26 
        FTEE, including:
            2 psychiatrists,
            6 psychologists,
            1 Addiction Therapist,
            2 Psychology Technicians,
            1 Administrative Assistant,
            3 Vocational Rehabilitation Specialists,
            7 Social Workers,
            2 Registered Nurses, and
            2 Clinical Nurse Specialists.

          The Washington, DC, VAMC is actively recruiting to fill four 
        vacancies of the 26 FTEE listed above, and they expect to fill 
        two of these positions by the end of September. Between the 
        PTSD Clinical Team's individual appointments and the PTSD 
        Clinical Team's group meetings, the Washington, DC, VAMC had 
        19,607 encounters and 18,384 visits from 2,705 unique patients 
        between October 1, 2007, and July 15, 2008. This information is 
        included in a table below for ease of reference.
     Washington, DC, VA Medical Center Mental Health Workload Data
                (October 1, 2007, through July 15, 2008)

          Source: Washington, DC, VA Medical Center, Office of the 
        Director

 
----------------------------------------------------------------------------------------------------------------
             Washington, DC, VAMC                  # of FTEE        Encounters      Visits     Unique Patients
----------------------------------------------------------------------------------------------------------------
General Mental Healthcare                                106.5          142,459     93,780                8,569
----------------------------------------------------------------------------------------------------------------
PTSD Clinical Team*                                         26           19,607     18,384                2,705
----------------------------------------------------------------------------------------------------------------

          * = Figures include both individual and group appointments.

          Washington, DC, VA Medical Center's caseload figures are 
        comparable with other facilities across the Nation. The data 
        below compare the Washington, DC, VA Medical Center's caseload 
        figures to the most recently available national data, from 
        fiscal year (FY) 2007. The Washington, DC, PTSD Clinical Team 
        had an average caseload for the PTSD Clinical Team of 122 
        veterans per FTEE, versus a national average of 118 veterans 
        per FTEE.
            Comparison of Washington, DC, VA Medical Center
           Mental Health Workload Data with National Averages
    (Fiscal Year 2007: October 1, 2006, through September 30, 2007)

          Sources: Northeast Program Evaluation Center, VA Connecticut 
        Healthcare System, West Haven, CT; National Mental Health 
        Program Performance Monitoring System: Fiscal Year 2007 Report; 
        The Long Journey Home XVI: Treatment of Post Traumatic Stress 
        Disorder in the Department of Veterans Affairs: Fiscal Year 
        2007 Service Delivery and Performance; Washington, DC VA 
        Medical Center, Office of the Director.

 
----------------------------------------------------------------------------------------------------------------
                                                                                      Patients per   Visits per
                                       # of FTEE      Visits       Unique Patients        FTEE         Patient
----------------------------------------------------------------------------------------------------------------
Washington, DC, VAMC
----------------------------------------------------------------------------------------------------------------
General Mental Healthcare                  145.3        80,358                8,117          55.9           9.9
----------------------------------------------------------------------------------------------------------------
PTSD Clinical Team*                         13.7        20,732                2,705         122.0           7.7
----------------------------------------------------------------------------------------------------------------
VHA National-All VAMCs
----------------------------------------------------------------------------------------------------------------
General Mental Healthcare               26,324.9    10,665,839              984,842          37.4          10.8
----------------------------------------------------------------------------------------------------------------
Providers who deliver PTSD                 684.5       828,245              137,822         118.0           9.9
 Specialty Care*
----------------------------------------------------------------------------------------------------------------

          * = Figures include both individual and group appointments.

    The Chairman. Thank you, Mr. Walz.
    Brief questions from Mr. Buyer, and then I will conclude.
    Mr. Buyer. Thank you.
    The Chairman. I am sorry.
    Mr. Buyer. Dr. Snyder.
    The Chairman. He just walked in. Do you want to ask 
questions of the Secretary? You are next.
    Mr. Snyder. Thank you, Mr. Chairman.
    Mr. Secretary, thank you and your team for being here 
today.
    One of the unfortunate things that was said today, I think, 
was that somehow implying that research at the VA is a bad 
thing or should be eliminated. That would be absolutely tragic. 
I mean, never in my history have I heard that view expressed 
before, and it would just be heartbreaking if somehow the take-
home was, we should not be doing research at the VA system.
    A lot of us have been advocating for more funds for 
research, and I think that this Committee in a bipartisan 
manner, and the leadership--Mr. Buyer, Mr. Filner and Mr. Smith 
before that--have been really strong advocates of trying to get 
you all additional money.
    Also the nature of the study: This is the kind of study 
that doesn't get funded over this long term very much. Now, why 
is that? Because there's not money to be made in this study. 
This is about delivery of products that are already on the 
market. And I am a family doctor; we talk about that. We need 
more primary care research, because you are talking about where 
is the best place to do the treatment?
    Now, the treatment may be exactly the same, but is it best 
to incorporate it as part of a PTSD clinic--I think the idea 
probably is, maybe they are more likely to come back on a 
regular basis to their PTSD clinic; maybe they are more 
accepting of a PTSD network--or should it be part of their 
primary care operation?
    This kind of research--this country needs more of this kind 
of research, because there's no--at the end of the game, it 
turns out that it's best that it's in the PTSD clinic, and now 
somebody can go out and patent that and make a lot of money. 
It's not that there's not that kind of incentive here.
    This is about delivery of healthcare. And, in fact, the VA 
system may be one of the few systems that is going to be able 
to do that because nobody will have that kind of money to 
support the research. So I commend you for doing that kind of 
research.
    The issue of how many--I think I was trying to watch this, 
and I was like most people running around here--how many 
Americans do we think have used this drug so far--not veterans, 
Americans?
    Secretary Peake. It's about five million Americans, I 
think. Internationally, it's about seven million, as I 
understand, sir.
    Mr. Snyder. Now, how long is the average length that people 
take the medicine?
    Secretary Peake. Twelve weeks is the standard, and then 
they can up it to 24 weeks if they're doing well and still need 
some help, is what I understand.
    Mr. Snyder. What would be your guess, Mr. Secretary, this 
is out of your area of knowledge of those, you say, five 
million Americans?
    Secretary Peake. Uh-huh.
    Mr. Snyder. When this additional information started coming 
out, how many of the ones not in the VA system, do you think, 
were notified by their physicians or practitioners about these 
changes in the warnings?
    Secretary Peake. I would think none were outreached to 
specifically. I would think that because of the FDA's work in 
being able to get to the primary care doctors--as a matter of 
fact, if they read the warning, they may well, in the interface 
with their patient, have that discussion.
    Mr. Snyder. And they come back the next time?
    Secretary Peake. Yes, sir.
    Mr. Snyder. I also like--I mean, we all rely on pharmacists 
so much. I mean, I do that with my kids and wife. When you get 
the little medicine bottle, and it has what to watch for, that 
may--if these prescriptions are renewed on a monthly basis or 
something, that may have been the time when people got the new 
information what to watch for, and I think a good pharmacist 
would have called attention to that.
    But I think the reality of the healthcare out there, was--I 
suspect, almost none of the folks in the other system would 
have gotten the kind of somebody picking up the phone. But most 
private clinics don't have electronic medical records; they 
would not have been able to find the patients that had been 
prescribed that.
    I think there's a lot of issues there that are part of the 
gaps in our healthcare system. I'm not saying that shouldn't be 
the goal. It should be the goal, but it's not there now.
    In the outpatient clinics that the VA contracts out, of the 
patients that are on a medicine which gets some kind of 
warning--not just this medicine--what kind of a system do we 
think we have now in those clinics for notifying patients of a 
change? Or, again, are you just dependent on the practitioner?
    Secretary Peake. You are talking about our community-based 
outpatient clinic (CBOC) contracts?
    Mr. Snyder. Yes, sir.
    Secretary Peake. They're on the Computerized Patient Record 
System (CPRS), so they get the same information as the VA 
practitioners.
    Mr. Snyder. But they don't have electronic medical records?
    Secretary Peake. No, they do.
    Mr. Snyder. They all have electronic outpatient records, so 
they can hit a button with a drug and pull up a list of all of 
the names of people who are getting that medication, do you 
think?
    Secretary Peake. Yes. And when the November warning came--
early communication came through, my recollection is that at 
Washington VA they actually ran the list and ran around and 
shared them.
    And it just comes right out of the----
    Mr. Snyder. Because that clearly is the standard for the 
healthcare system in America.
    Well, I am out of time. The final note, I would say--as you 
usually do, Dr. Peake--you learn from these things. The most 
unfortunate thing is, we have somebody there who is not doing a 
good job of recording the data of the study, and it can call 
into question the whole study. And then it calls into the 
question what's going on in other studies, because the 
independent asking a question to the patient and not just 
copying off what somebody else asked them is a way of 
corroborating the information.
    As you know, I am not telling you anything you don't know. 
I think that's the biggest glitch I see here today.
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Dr. Snyder. Thank you.
    Mr. Buyer.
    Mr. Buyer. Mr. Chairman, I want to thank Dr. Snyder.
    You went right to the question that I wanted to ask here on 
the standards of care, not just within the VA, but across the 
country.
    Many States up there and the community health clinics are 
promoting utilization of Chantix'. Some States are 
paying for using it as a smoke cessation aid or drug.
    And, you know, you have States out there, I will pick on 
the Chairman here for a second--California's State Department 
of Health recommends the use of Chantix'. However, a 
list of Chantix''s side effects on the Health 
Department Web site has not been updated for 2 years. It does 
not reflect the FDA's latest findings, nor does it list the 
serious psychological side effects associated with 
Chantix' use, such as suicidal contemplations.
    So you are probably right. All across the country, this is 
a medication that is being used.
    You have the FDA, and your advisory here to the doctors, I 
think is pretty strong. I mean, you are telling them, you know, 
you need to let your patients know this.
    I thought it was interesting that you also let the health 
providers know, Dr. Snyder, in the clinical trial that patients 
that may have had a psychiatric illness were not included in 
the clinical trial. I think that's sort of an interesting sort 
of note that the FDA has put in here, and maybe it even is 
intriguing on whether we should do a second look or not. I 
don't know. I'll leave that in the experts' hands.
    But in their own advisory, when we had our witness testify, 
you come right out and say, patients should tell their 
healthcare provider about any history of psychiatric illness 
prior to starting Chantix'.
    Mr. Elliott, even though he was taking this generic form of 
Prozac that had side effects--for instance, suicidal ideation--
said that he was okay, he didn't have any of that at all. So I 
guess he didn't feel the need to inform, because he didn't have 
that thought.
    But I find it interesting that you say that 
Chantix' may cause worsening of current psychiatric 
illnesses, even if it is currently under control. That's pretty 
doggone important. That's the advisory, I think, that goes 
right, Mr. Secretary, to the heart of this matter. I look at 
this one, and I made these comments about I feel like I am at a 
risk management hearing at a local hospital about a particular 
doctor. But then it can be, is it systematic?
    Now when we talk about the standards of care--so when Dr. 
Snyder pointed out, I think aptly so, that perhaps doctors 
around the country might get a patient on Chantix', 
or they're really going that far, as even noting a counseling 
on a medical record, well, that may be different. We can't 
control the standards of communities of care out there.
    What we can control is our own community standard of care, 
for instance, the VA healthcare system. Would you not concur?
    Secretary Peake. I would, sir.
    Mr. Buyer. So, even though you can say, correctly so, that 
doctors are not required to have an addendum of the informed 
consent, would you not concur that if you want to establish the 
highest quality of care, that is something that we should have 
done and now should do in the future?
    Secretary Peake. Within the study, I agree, it is something 
we should have done, because we said we should do it. And I 
think it--and it concerns me that--because, to my knowledge, we 
have about 50 percent of them done, only. I want to get to the 
bottom of why that is.
    We have about, as you point out, sir, 32-, 33,000 people on 
Chantix' across the VA. I think it is the--the 
standard of care is appropriate that their physicians have been 
notified through their personal responsibility to keep up with 
the medical issue, but also through the additional push of 
information to the VA so that they are aware of what they need 
to do to best take care of their patient.
    I would tell you, sir, that because of the headlines and so 
forth, I did send out a letter to 32-, 33,000, everybody that 
we have a record of being on Chantix', encouraging 
them, first of all, to, if they have any of these side effects 
to include suicidal tendencies, thoughts, so forth.
    So I sent them a personal letter saying, go see your 
doctor. If you have any concerns from what you've read about 
Chantix', go see your doctor. We will find some 
other way to help you. If you are having any other kind of 
acute problems, here is our suicide hotline, here is how to get 
care.
    So I think, as you say, sir, the standard of care issue is 
such that we should step beyond that, and I think we should.
    Mr. Buyer. The last thing, Mr. Chairman, with your 
indulgence--it really kind of bothers me.
    Dr. Puglisi, you have a position whereby this Committee 
created that position, and we didn't want these types of things 
to happen again.
    We have a Washington hospital, call it Washington VA, which 
did not receive an accreditation. One of the failures was in 
the area of informed consent. So I look at this and go, we 
created your position to help the VA--and, in particular, the 
Secretary--and we have a particular hospital that's 
participating in a study that can't even get an accreditation 
on the human research issues.
    Does this bubble to your attention? Have you got some 
concerns here? I don't get it.
    Dr. Puglisi. I have several concerns. I have concerns on 
the level of this particular study, and I have concerns system-
wide.
    In terms of this particular study, I'm concerned that it 
appears that at least some veterans who were prescribed 
Chantix' had never received written information 
about Chantix'. I'm concerned that at some of the 
study sites there appeared to be an undue delay in getting 
information to study participants.
    I'm concerned on a systemic level that we apparently don't 
have the required mechanisms to make sure that these things are 
done in a timely fashion. I'm concerned any time informed 
consent appears not to have been adequate, because that's one 
of the keystones of human subject protections.
    So to answer your questions, I am very concerned.
    The Secretary has asked my office to look at these--this 
study in great detail, as well as all of the studies involving 
PTSD patients. And we will make very specific recommendations 
about how the system needs to be changed to make sure this 
doesn't happen again, and we will make specific recommendations 
relative to accountability of individuals who appear not to 
have fulfilled their responsibilities.
    Mr. Buyer. Thank you, Mr. Chairman.
    The Chairman. Thank you for that last statement. I am glad 
we are finally concerned.
    Let me just conclude this panel. Several things bother me, 
as they bother Dr. Puglisi here.
    First, Secretary Peake, you have incredible faith in this 
bureaucracy. I mean, there are almost 250,000 people at the VA. 
I don't know how this advisory went out, e-mail or circular. 
How did it go out?
    Secretary Peake. Electronic, sir.
    The Chairman. I mean, I go into my e-mail all the time. 
These guys have stuff in their in-box. Their e-mails are loaded 
up and I don't know who reads what. If it says FDA advisory, 
maybe they think its another one of 50 or 100 advisories. I 
don't know.
    Secretary Peake. There are 50 a month.
    The Chairman. Afraid so. That's why we are sending out----
    Secretary Peake. That's why we have this system that says, 
which of these are really important. You've got 12 of them; you 
pop them and send them out.
    The Chairman. Yes, but you don't know; you have no proof. 
In fact, we have the opposite proof the system is not working: 
50 percent of the consent forms, in your knowledge. By the way, 
you said you are going to get to the bottom of that.
    I mean, if I was sitting there, Secretary Peake, we are 
dealing with a very limited number of people in this study, 900 
and something. Fifty percent haven't signed it, I would call up 
the 450 and say, get yourself to the doctor; and we'll get to 
the bottom of it. We will have a report, and there will be 
months and months that go by, and who knows what will happen in 
the interval.
    I don't understand how you are going to get to the bottom 
of this? We have no proof of counseling. You said yourself that 
someone might come in six months later for their next 
appointment. They could commit suicide by then. We don't have 
any results, apparently, after 5 years of study. Your faith in 
the bureaucracy is overwhelming to me.
    Second, the fact that everybody said--every quote I have 
ever read in any of the papers on this subject from Dr. McFall, 
to yourself, to anybody, this study is going to continue. It's 
as if the train started and nobody wants to stop it--it's going 
to continue at all costs. No causal connections have been made.
    You said--and I just can't believe, Secretary Peake, that 
you said it doesn't matter which medicine, in terms of this 
study, to a very fragile group of people who have PTSD, were 
given something that was said to be possible suicide inducing.
    Two hundred forty-five people are on that. Stop it, is what 
I would advise you.
    You are going to go through another year of this study. You 
are going to get to the bottom of this. You have 245 people--
although now, because of all the publicity, it may be down to 
40.
    I don't understand that, Dr. McFall or Dr. Puglisi.
    Do you have the confidence to continue this study knowing 
what we know now?
    Do you have the confidence, Mr. Puglisi? You said you had 
concerns. Would you consider this at all costs?
    Dr. Puglisi. I wouldn't continue the study at all costs. My 
review is going to be done on July 18, which is about 10 days 
from now, and at that time I will give----
    The Chairman. When did you start that?
    Dr. Puglisi. June 18.
    The Chairman. Well, I mean, wouldn't you just say, stop 
giving Chantix' for a month? I don't understand it.
    Dr. Puglisi. There are risks----
    The Chairman. You are going by procedures, you are going by 
risks.
    These people have PTSD. You are giving them something you 
know can lead to further thoughts of suicide--stop it.
    Dr. Puglisi. I would say that every person who has taken 
Chantix' or is now taking Chantix' needs 
to be notified immediately to consult with their physician.
    The Chairman. Well, thank you.
    Mr. Buyer. You haven't. The VA has not done that. You sent 
a letter out to 32,000 people.
    Secretary Peake. Sir, we have 40 people on 
Chantix' now. Every one of them has been notified.
    The Chairman. How?
    Secretary Peake. Do you want to discuss that?
    Mr. McFall. Yes, sir.
    The Chairman. I would personally call all 40 and tell them 
to get to their doctor.
    Did you call them? Did Secretary Peake call them?
    If I were you, I would call them, Dr. Peake.
    Mr. McFall. Mr. Chairman, what we can tell you is, all 
individuals who were on Chantix' as of February 1, 
2008, which is when the FDA alert came out, have either been 
notified through the study staff or their provider.
    The Chairman. You don't know that. You have asked the study 
staff to consult with them. You don't know that they have been 
consulted, right?
    Mr. McFall. Through chart review.
    The Chairman. Have you asked for a return saying, yes, you 
have notified them?
    Mr. McFall. Let me check it out and let you know what we 
have. Maybe that will help.
    The number of individuals, of those 120, who have a consent 
addendum signed is 56, and that leaves 64 that do not have a 
consent addendum signed. That's because the study visits 
haven't come up yet.
    However, of those 64, they were notified by the provider 
who takes care of them or by the study staff.
    The Chairman. I mean, how were they notified?
    Mr. McFall. Through chart review.
    The Chairman. I don't understand what that means. Does 
somebody call them----
    Mr. McFall. Phone.
    The Chairman. Did somebody call them and say, come in and 
see your doctor right away?
    Dr. Kuppersmith. Uh-huh.
    Mr. McFall. Well, the provider may have spoken.
    The Chairman. Shouldn't they all have been called and told, 
come in and see the doctor right away?
    Mr. McFall. What we can say is that the 120 people who had 
been on Chantix', all have been contacted about the 
FDA safety risks published in February.
    The Chairman. How have they been contacted? You said, 
either through their provider----
    Mr. McFall. Either through the provider or the study staff, 
sir.
    The Chairman. Do you know that they contacted them?
    Mr. McFall. Yes, that's what we know.
    The Chairman. How do you know? Is it on the chart or what?
    Mr. McFall. Well, we asked them to have this data 
extracted.
    The Chairman. You asked them to do it. How do you know that 
they did it?
    Mr. McFall. Well, how do we know? Well, either we got the 
consent addendum back, it's in the records, that's been signed 
by the patient. So that accounts for----
    The Chairman. How many of those have been?
    Mr. McFall. Pardon me?
    The Chairman. How many are those?
    Mr. McFall. The number of people who signed the consent 
addendum was 56. So we have that many individuals.
    The Chairman. You said that was the original process, and 
there were 64 that didn't.
    Mr. McFall. Sixty-four didn't.
    The Chairman. So how many of the 64 have now signed it, 
because they have all been notified, according to you?
    Mr. McFall. What I can tell you, of the remaining 64 who 
had not yet signed a consent addendum, information about the 
risk from the FDA alert has been conveyed to all, either 
directly by the provider verbally or through a medical record 
documentation. That's 42----
    The Chairman. Medical record documentation, that means they 
write it in a record?
    Mr. McFall. They would write down in a record if they spoke 
to the patient about----
    The Chairman. You said three times the same thing. I keep 
asking you, how do you know they actually did it?
    Secretary Peake. What we have, sir, is a consent addendum 
signed, 56.
    Of the 64 that we do not have a consent addendum signed, of 
those 64, it is documented in the medical record that they have 
been notified and discussed with their provider, or with 
somebody, some member of the staff.
    The Chairman. I would like to see those 64. I bet that 
hasn't happened.
    So those 64 still haven't signed the addendum?
    Mr. McFall. They have not signed the consent----
    The Chairman. Then why do you let them continue in the 
program? Wouldn't you ask that, Dr. Puglisi? I mean, why are 
they in the program?
    Dr. Puglisi. The standard that the medical professionals 
determined was appropriate was to have individuals sign the 
consent addendum at their next visit to the study clinic.
    In some cases, they have not had a study visit. However, I 
am not going to sit here and tell you that every person who is 
in this study had the opportunity to have a discussion at their 
next study visit or to sign the consent addendum. That's one of 
the things I am trying to find out.
    The Chairman. That's the problem here.
    Mr. Buyer. Dr. Puglisi, were these judgments by each of the 
individual institutional review boards? Is that why everything 
is so different?
    It's hard for him to answer a specific question to the 
Chairman.
    If you have different directives coming out from different 
institutional review boards about what docs are supposed to do, 
isn't that part of what the problem is, Mr. Secretary? Isn't 
that part of the challenge here?
    Secretary Peake. It's why we want to go to a central--it's 
why we want to go to a central IRB. But I want to go back, so 
we can have consistency across this, and accountability, as I 
mentioned before.
    But from the 1 February--as I say, across the course of the 
study, there are 241 who have been on Chantix'. 
Since 1 February, since this alert came out, there have been 
120. That's the 120 that Dr. McFall is talking about.
    All of them have been--we have documentation that each of 
them have been notified about the side effects.
    Mr. Buyer. The Chairman--if I may be responsive here to the 
Chairman, because he--his point, I think, is probably pretty 
accurate.
    You have 10 institutional review boards out there that now 
set all different kinds of standards on when an individual 
should receive their notice.
    The Chairman's position is ``now.''
    Secretary Peake. That's right.
    Mr. Buyer. You would concur with that, Mr. Secretary, 
right?
    Secretary Peake. That's right.
    Mr. Buyer. And that's why you want to do these independent 
institutional review boards so they can feel your power and 
authority with regard to communication and oversight of this 
particular office; is that correct?
    Secretary Peake. That's correct.
    Mr. Buyer. I yield back.
    The Chairman. I know you have nothing better to do, but I 
would call those 60 personally, Secretary Peake.
    Let me just finally say the bureaucratic process goes on, 
there are still studies. I would have thrown some doubt on the 
fact of your in-depth study. It's internally by the very people 
you are trying to study. I have more confidence, having heard 
Dr. Puglisi's statement, so I will leave you alone on that one 
for now.
    But, a bureaucracy study in itself is not what gives 
confidence to the public that it's been done.
    I mean, if you want an independent study, you give me the 
120 charts and I will read them. I will tell you, because I 
don't believe it, that all 64 were personally notified in a way 
that makes sense. That's how I would get accountability, not by 
asking the same doctor who is responsible for the study to tell 
me.
    Ask me to look at it. Ask the Inspector General. Ask any of 
the staff here. Then I might believe you.
    Secretary Peake. I was pleased that the Inspector General 
took on the task of taking a look.
    The Chairman. If you want, give me the 120 charts, and I 
will tell you whether you have done the job or not.
    Again, we are dealing with our children here.
    I don't comprehend how all of you are sitting there, with 
all of your statements about clinical channels and how the 
clinical system is appropriate and that you have faith in the 
next study and that no one taking Chantix' is going 
to die from suicide.
    I just can't imagine that you have so much faith in all 
these processes and all this bureaucracy--and if somebody does 
die, I will be at the trial to talk about your criminal 
negligence here--because the facts are with us, Mr. Secretary. 
Prudence says--if we talked about a bar being high enough and 
all of that, prudence says for these individuals who have PTSD, 
they have enough problems. Don't exaggerate it. Don't aggravate 
it.
    You said, there will be millions of other things to stop 
the smoking, but that's not something we give to them. We are 
giving them the Chantix', and that's our 
responsibility.
    I can't believe that you all have 100 percent confidence 
that we are not causing a suicide.
    You have the last word, Mr. Secretary.
    Secretary Peake. Sir, I appreciate the chance to come here 
and talk about this issue. We actually don't agree, I think, on 
the issue of this medicine. I think you can find similar kinds 
of concerns about, really, any of the other smoking cessation 
therapy.
    What we do agree on, sir, is an absolute commitment to our 
veterans and trying to do the absolute right thing by them. We 
absolutely do agree on ensuring that the integrity of the 
research that we do in the VA meets and exceeds the highest 
standards in this Nation, and I am absolutely committed to 
making sure that that happens.
    The Chairman. You don't believe that 11 suicide attempts, 
attempted homicide, nine suicidal thoughts, six suffering from 
hallucinations doesn't give you pause? This is from your own 
study.
    I don't know if you have studied the whole 32,000 or not.
    Secretary Peake. It's about 70,000 that have been on 
Chantix'.
    The Chairman. You studied all 70,000 for those symptoms?
    Secretary Peake. Sir, those are the--this was not a 
scientific drug--that's the observations that we have about it.
    The Chairman. That's my point.
    Secretary Peake. That's why we are working with the FDA.
    The Chairman. I thought you were going to say, it was only 
0.05 percent of people attempting suicide, so it's nothing to 
worry about.
    But what you are saying does not constitute a scientific 
study, you have this anecdotal data and you don't have pause 
about giving this stuff to these people?
    Secretary Peake. That is exactly why we are working with 
the FDA to try to understand what is the best route.
    The Chairman. Yes, but don't give it to them while you are 
working with the FDA. Have some prudence here. That's what I 
would advise.
    Okay. We are on the next panel.
    Dr. Subbiah, thank you for joining us. We had a two-person 
panel, but Dr. Koocher from the School of Health Sciences at 
Simmons College in Boston had to get to another appointment.
    [The prepared statement of Dr. Koocher appears on p. 117.]
    Dr. Subbiah is from Pfizer--I just want to get your exact 
title here--Vice President for Medical Affairs at Pfizer.
    We would be interested to hear your thoughts on the process 
for human research subjects and relationship between 
pharmaceutical companies and researchers. Since it is your 
drug, what would you advise in this situation?
    Mr. Buyer. Mr. Chairman, may I have a question?
    The Chairman. Please.
    Mr. Buyer. I have no objection if you want to combine 
panels three and four.
    The Chairman. Okay. If panel four would join us also from 
the Inspector General's Office?
    Mr. Buyer. Thank you.
    The Chairman. We will save some time. Thank you.
    Dr. Subbiah, you can begin, and then we will call on the 
others.

  STATEMENTS OF PONNI SUBBIAH, M.D., M.P.H., VICE PRESIDENT, 
MEDICAL AFFAIRS, PFIZER INC., NEW YORK, NY; AND JOHN D. DAIGH, 
  JR., M.D., CPA, ASSISTANT INSPECTOR GENERAL FOR HEALTHCARE 
 INSPECTIONS, OFFICE OF INSPECTOR GENERAL, U.S. DEPARTMENT OF 
VETERANS AFFAIRS; ACCOMPANIED BY ANDREA BUCK, M.D., JD, SENIOR 
PHYSICIAN, MEDICAL CONSULTATION AND REVIEW DIVISION, OFFICE OF 
   HEALTHCARE INSPECTIONS, OFFICE OF INSPECTOR GENERAL, U.S. 
  DEPARTMENT OF VETERANS AFFAIRS; AND RANDALL SNOW, ASSOCIATE 
DIRECTOR, WASHINGTON, DC, REGIONAL OFFICE, OFFICE OF HEALTHCARE 
 INSPECTIONS, OFFICE OF INSPECTOR GENERAL, U.S. DEPARTMENT OF 
                        VETERANS AFFAIRS

            STATEMENT OF PONNI SUBBIAH, M.D., M.P.H.

    Dr. Subbiah. Good afternoon, Mr. Chairman, Mr. Buyer, 
Members of the Committee. My name is Ponni Subbiah. I am a 
medical doctor and Vice President of Medical Affairs at Pfizer. 
I am responsible for the medical and scientific activities for 
products in the urology/respiratory area, which includes 
Chantix'. On behalf of Pfizer, again thank you for 
the opportunity to speak with you today.
    I would like to briefly address the following areas: the 
epidemic of tobacco addiction, the role of Chantix' 
in helping patients stop smoking, clinical trials and drug 
safety monitoring, and the recent updates of the 
Chantix' label.
    As already mentioned, the World Health Organization has 
described tobacco as a leading, preventable cause of death. 
Worldwide, approximately 1.3 billion people currently smoke 
cigarettes. In the U.S. alone, more than 400,000 deaths are 
related to smoking each year. In fact, cigarette smoking is a 
risk factor for six of the eight leading causes of death in the 
world. Healthcare costs from smoking-related diseases are $75.5 
billion annually.
    It is important to understand that for most people smoking 
is not a lifestyle choice or habit, but rather an addiction to 
nicotine. Nicotine is a highly addictive drug, as addictive as 
heroin or cocaine.
    Smokers become physically and psychologically dependent on 
nicotine. Quitting smoking, with or without treatment, is 
associated with nicotine withdrawal symptoms, and this may 
include irritability, anger, depressed mood and weight gain.
    Quitting smoking has also been associated with exacerbation 
of underlying psychiatric illnesses, so it is very important to 
assess the benefits and risks of smoking cessation treatments 
in the context of this setting.
    In the U.S., currently 21 percent of the population, in 
general, smoke cigarettes. By comparison, the smoking rate in 
the VA is 33 percent. The smoking rate in the PTSD patients 
ranges from 45 to 60 percent.
    So Chantix' is the first non-nicotine-based 
medicine approved by the FDA in nearly a decade. It has been 
demonstrated to be more efficacious than a placebo as well as 
Zyban, which is another smoking cessation treatment that's 
available in the market.
    Chantix' is not intended to be a long-term drug. 
It is indicated for use over 12 weeks and then an additional 12 
weeks if the patient successfully quits. Today, 
Chantix' has been prescribed in approximately 7.5 
million patients worldwide, 5.6 million of those in the U.S.
    Consideration of benefits and risks of a medicine is a 
critical component of the dialog that needs to occur between 
the patients and their doctors. Gathering data to continuously 
inform that benefit/risk assessment is accomplished through 
various means, including the conduct of clinical trials and 
epidemiological studies. There are also clinical trials of 
Pfizer medicines, such as the trial that is the subject of this 
hearing, that are conducted independently of Pfizer.
    Once the medicine is available in the market, any 
researcher can obtain the medicine and conduct studies without 
of the involvement of Pfizer. These studies may be funded from 
other non-Pfizer sources, such as academic institutions or the 
National Institutes of Health.
    The Pfizer drug safety surveillance system is designed to 
continuously gather and analyze reports received about patient 
experiences with our products. These adverse-event reports are 
routinely shared with the FDA, as well as other regulators 
around the world. The primary mechanism of communicating 
changes in a medicine's benefit/risk profile is the product 
label. It is common for the label to be revised numerous times 
in a product's life cycle.
    With regard to Chantix', there have been 
adverse-event reports of certain neuropsychiatric symptoms, 
including depressed mood, agitation, changes in behavior, 
thoughts of suicide and suicidal behaviors in patients 
attempting to quit smoking with Chantix'.
    Reports of an adverse event does not necessarily mean 
there's a causal association between the product and the event. 
In the case of Chantix', a causal relationship 
between these reports and the use of Chantix' has 
not been established. However, in some reports related to 
Chantix', a causal relationship could not be 
excluded.
    In November 2007, Pfizer worked with the FDA to update the 
Chantix' label to reflect these reports. Additional 
label updates were made in January and May 2008, respectively, 
to put this information on the warning section of the label to 
heighten awareness and to provide further guidance to 
physicians and patients about these symptoms.
    The current label advises that a patient should stop taking 
Chantix' and contact their healthcare provider 
immediately if these neuropsychiatric symptoms are observed. 
Pfizer communicated these label updates to physicians, study 
investigators and other healthcare professionals through 
various routes, including updates to the product label, written 
communications, Web site updates and communications directly 
from Pfizer employees.
    Patients also have access to this information through their 
healthcare provider, as well as through the Chantix' 
Web site. Based on our review of available safety information, 
including the adverse-event reports received to date, we 
believe the Chantix' label accurately reflects the 
product's efficacy and safety profile.
    There are few things that provide greater health benefits 
than quitting smoking. It has been reported that nearly 70 
percent of smokers want to quit. However, fewer than 7 percent 
of those who try are able to quit on their own. So given the 
devastating health effects of smoking, it is essential to have 
treatment options available to help smokers break free of 
nicotine addiction and stop smoking.
    Thank you, and I would be happy to answer any questions you 
may have.
    [The prepared statement of Dr. Subbiah appears on p. 105.]
    The Chairman. Thank you.
    Also with us is Dr. John Daigh, the Assistant Inspector 
General for Healthcare Inspections of the Department of 
Veterans Affairs, accompanied by Dr. Andrea Buck, who is a 
Senior Physician in the Medical Consultation and Review 
Division of the Office of Healthcare Inspections; and Mr. 
Randall Snow, who is the Associate Director of the DC Regional 
Office of Healthcare Inspections.
    Thank you, Dr. Daigh, for being here. Is that how you 
pronounce it, ``day?''
    Dr. Daigh. Yes, that's right.
    The Chairman. Why don't you spell it D-A-Y like everybody 
else?
    Dr. Daigh. Yes, sir.
    If I may ask, sir, that my written testimony be entered 
into the record.
    The Chairman. Of course. Thank you. So ordered.

           STATEMENT OF JOHN D. DAIGH, JR., M.D., CPA

    Dr. Daigh. I would just like to make a couple of comments.
    One, we limited our review of this study to what happened 
at the Washington, DC, VAMC primarily. So that was the focus of 
the report.
    The first thing I would like to say is that we do not 
interpret at all that there are dramatic deviations from human 
subject protections in this study, in that you had to sign 
consent in order to be--to determine whether or not you were a 
reasonable candidate for the study. You had to sign a second 
consent in order to be part of the study.
    The problem from our point of view is that the study began 
and, over time, knowledge changed about the therapies for 
Chantix'. So where we have difficulty is, when it 
became clear, with the February warning, that there was a 
significant risk, and the DC VAMC IRB made the judgment that 
the patient should be notified, but the execution of that plan 
failed. And so that's the difficulty we have with the execution 
of this study as it stands right now.
    I would have to say that the pharmaceutical staff reacted 
aggressively in taking the names of individual patients to the 
clinical leaders in the hospital so that they were aware of the 
patients under their charge who were on this drug. So we found 
that that effort on the clinical side, again separating out the 
world of research, was effective.
    In a prior review, my office looked at VA's response to an 
FDA alert regarding tissue that was contaminated and should be 
pulled from the shelves. We published that in the last 6 or 8 
months, and we found that there they also had responded very 
well. We had no significant issues derived from that review.
    I do, however, have, in the work that we have done, we do 
believe that there are problems in the research community; and 
I think characterizing them as execution of the standard 
protocols and of performing the job that they are supposed to 
perform is an issue sporadically in our work that we have seen.
    And I think that among the things that one needs to 
consider, in adjusting current business, is sunlight; that is, 
there are individuals at facilities and ORO who are charged 
with auditing protocols, looking at the research community, and 
ensuring that their reports do, in fact, make it to people who 
will take action, based on the findings of those reviews.
    And so the problems that we have had and seen sporadically, 
in addition to the DC/VA are, are the protocols done in a 
manner that lends--is a protocol review done in a manner that 
lends credence to the fact that the audit is successful in 
determining or demonstrating how the performance of that 
protocol is, and then ensuring that the protocol--that those 
audit results, when shown to the proper authorities, that they 
take the appropriate action on that.
    That would be the end of the statement I would have, sir.
    The Chairman. Thank you.
    [The prepared statement of Dr. Daigh, appears on p. 108.]
    The Chairman. When you said the execution failed, did that 
include the notification from the doctor to the patient of the 
risk? Did that include the lack of an addendum to the consent 
form, the fact that when he came in for emergency care, he 
didn't get it?
    Did you look at those issues?
    Dr. Daigh. What we did was, we picked the arbitrary 
timeframe of prior to the news media making a big announcement 
about this, and looked at the medical record to see whether the 
doctor noted in the medical record that there had been a 
discussion with patients regarding notification of problems 
with Chantix' for the study patients.
    So you find, in my view, a failure that the IRB in DC 
decided that patients on Chantix' should have the 
amended review signed. And that did not get accomplished 
quickly, as you have already discussed.
    But you do find in some of those charts, again, prior to 
June 20, that there was a discussion between their provider and 
that patient about risk of Chantix'.
    The Chairman. In the case we heard today?
    Dr. Daigh. No, sir, I am not going to comment on any one 
particular case.
    So it is a complex issue in responding to your question, 
given the time of cutoff that you look at when notification 
occurred.
    So we believe that the IRB's plan to notify patients, whom 
they had a special relationship for because they were in the 
study, was not executed correctly.
    The Chairman. Thank you. I hope we get some accountability 
for that.
    Dr. Subbiah, I probably agree with everything you said in 
your statement, how important it would be to have such a drug.
    The only thing that I would ask you about, or to qualify--
and that's the root of this problem here--is that we were 
giving this drug to PTSD sufferers; and that's the real 
problem. That's why I think all of the witnesses who were up 
before you should have had some pause.
    We are not talking about the average smoker, we are talking 
about people suffering from combat stress injury. Doesn't that 
alter some of the things you would say about how important the 
drug is, or doesn't the risk get heightened with those kinds of 
patients?
    You made a general statement, that there are seven 
million--although we don't know how many of those have PTSD, 
but wouldn't that be a high risk?
    Dr. Subbiah. Well, first, I think it is really important to 
step back and understand that patients with mental illness also 
have other illnesses that they can die from. So we know that 
patients who smoke--and specifically it has been shown that 
PTSD patients, not only 45, 60 percent of them, smoke, but 
actually many of them are heavy smokers.
    And so, yes, they do have PTSD, but they can just as well 
have other comorbidities and actually die from sudden cardiac 
events and lung cancers and other illnesses.
    So it is important that we continue to improve the standard 
of care, and options that are available to treat their other 
comorbidities, and so that is why I think research, in general, 
should be continued not only in the general population, but 
also in subpopulations.
    The Chairman. So you don't have any problem now of advising 
anybody who has PTSD and who is a heavy smoker to take it? You 
have no problem with that?
    Dr. Subbiah. Well, I think, as indicated and as indicated 
on our label and with the changes, that any time that a patient 
who wants to quit goes to see his doctor, there has to be a 
communication and a discussion of the benefits and risks.
    It's not just for Chantix'. It's with any 
prescription product.
    The Chairman. I agree, but, apparently that didn't occur in 
all cases.
    Has Pfizer done a study particularly with mental illness 
and Chantix', or not?
    Dr. Subbiah. We have a study currently ongoing in patients 
with schizophrenia, who--you know, that population, over 80 
percent of them smoke. So that's currently ongoing.
    The Chairman. Have you found anything worrisome about that 
one?
    Dr. Subbiah. Well, as the research is ongoing, it's 
difficult to make conclusions on the results. So we are going 
to have to wait to get the results.
    The Chairman. Does Pfizer have any consultant relationships 
with VA doctors?
    Dr. Subbiah. So, as--you know, in general, Pfizer as a 
pharmaceutical company does have interactions with the VA. For 
example, so with all of our customers, if they want to use any 
of our products, we often interact with them to communicate the 
benefits, risks and efficacy and safety data of our products.
    So, for example, we could have people such as our sales 
representatives, as well as people that interact with 
formularies, that could have have interactions with the VA.
    The Chairman. That is not what I asked.
    Do you have any paid consultants who work for the VA who 
are paid by Pfizer to consult on the use of drugs?
    Dr. Subbiah. We do have--I am not aware specifically of 
paid consultants for the VA. But let me just comment generally 
on how we work with external experts and physicians.
    The Chairman. I know how you work. That's what I am afraid 
of.
    Dr. Subbiah. Can I answer the question?
    The Chairman. Well, I would like you to get back to me. Do 
you have any paid people who work for the VA? You said you 
don't know. Can you get back to me with that answer?
    Dr. Subbiah. Yes. So we can get an answer back to you.
    The Chairman. How many and who?
    Dr. Subbiah. Sure.
    The Chairman. And, how much they are paid?
    [The response is included in the answer to Question 5 of 
the Post-Hearing Questions and Responses for the Record, which 
appears on p. 134.]
    Mr. Buyer.
    Mr. Buyer. When did Pfizer become aware of the 
independently run smoking cessation research project being done 
by the Department of Veterans Affairs?
    Dr. Subbiah. Are you referring to this particular study 
under discussion?
    Mr. Buyer. Yes.
    Dr. Subbiah. As far as I am aware, I personally became 
aware of this when we heard about the hearing from the--in The 
Washington Times article.
    Mr. Buyer. You said ``I personally.''
    Dr. Subbiah. Yes.
    Mr. Buyer. You are here speaking on behalf of Pfizer, so I 
now know your personal opinion.
    Were you aware of whether the VA ever gave any notification 
to Pfizer?
    Dr. Subbiah. So there are two things. One is awareness and 
one is involvement.
    Mr. Buyer. No. There is one specific question I have asked.
    Dr. Subbiah. Okay. With regards to----
    Mr. Buyer. Notification.
    Dr. Subbiah. With regards to awareness of the study.
    Mr. Buyer. No, Doc.
    Dr. Subbiah. I am sorry. I don't understand.
    Mr. Buyer. Notification.
    Dr. Subbiah. Notification?
    Mr. Buyer. Did the VA, anyone at the VA, ever tell Pfizer, 
we have an ongoing study on smoking cessation, and we are using 
your product? Do you know whether that notification, 
officially, ever happened?
    Dr. Subbiah. I am not aware of any official communication. 
However, it is important to understand that there are Pfizer 
employees that do interact with staff at different VA centers, 
so there could have been some communication on the study. But 
there was no official communication, and there was no 
involvement by Pfizer in either the design, the conduct or the 
implementation of the study.
    Mr. Buyer. Okay.
    Now, let me ask the question of, had you known--okay, had 
you known, as a manufacturer of a product, that now that you 
are working in concert with the FDA to make sure that advisory 
opinions go out to medical providers, had you known that the VA 
was conducting this type of a study with individuals that have 
PTSD or other forms of neuropsychiatric disorders, what would 
your counsel have been to the VA?
    Dr. Subbiah. Well, I can't comment on that particular 
study.
    Mr. Buyer. All right.
    Wait, wait, wait, Doc.
    Dr. Subbiah. Okay.
    Mr. Buyer. I will rephrase the question.
    Now you know there's a study----
    Dr. Subbiah. Yes.
    Mr. Buyer [continuing]. Out there. What is your counsel to 
the VA with regard to the use of your product?
    Dr. Subbiah. In PTSD or in general?
    Mr. Buyer. With the use of your product in this VA research 
study, what is your counsel to VA?
    Dr. Subbiah. That the benefits and risks of 
Chantix' should be discussed with individuals where 
Chantix' is being considered, whether it's in the 
clinical setting between the patient and the doctor, or if it's 
in the research setting.
    The patient should be fully informed.
    Mr. Buyer. Now that we know, though, that in your clinical 
trial--did not include individuals who have psychiatric 
illnesses or disorders, does that raise any concerns to you? Is 
this something that you as a manufacturer should take a relook, 
or the FDA should--in other words, if you don't do it 
voluntarily, obviously, it always could be directed.
    Dr. Subbiah. So I think it's important to understand, then, 
the research during the development process. Because when we 
have a new molecule that we want to bring to the market, a 
specific disease area, we want to study it in a core group with 
people that have less comorbidities and less concomitant 
medications.
    Because we need to figure out what--if there's benefits or 
risks, we need to figure out, is it from the drugs or is it 
from other things. So we try to minimize comorbidities.
    Mr. Buyer. All right. I got you. I got you.
    Dr. Subbiah. All right.
    Mr. Buyer. Maybe it's me. Maybe we are two different 
pistons; you go up, I go down. We're not communicating very 
well here.
    We now know that Chantix' as a cessation drug is 
being utilized in a study, right, that also incorporates PTSD. 
Now, let me just hold that because, Dr. Daigh, you had 
mentioned, quote, subjects could not be enrolled if they had a 
psychiatric disorder not in remission, were at imminent risk 
for suicide or violence or had severe psychiatric symptoms. So 
we wanted to make sure that--we are going to have a study, but 
we don't want to have any individuals that may have any of 
these particular symptoms that is not in remission. That is 
correct, right?
    Dr. Daigh. Yes, sir.
    Mr. Buyer. Now we end up in a study whereby in the middle 
of that study we bring in Chantix'. So the original 
informed consent that were all signed by everyone, now we bring 
in a new drug. Now FDA says that drug has a side effect. We 
have this question about community standard, should there be an 
addendum with regard to informed consent. I look at this one 
now and go, all right, when you establish the protocols for the 
study, one of those protocols--one of those very important 
things that you are looking at is we didn't want individuals 
that may have a psychotic disorder not in remission. But if, in 
fact, we have now introduced a drug that could have a side 
effect of suicide ideation, I look at that and go we have a 
problem, we have a problem with the results of our study. Would 
we not here, Dr. Daigh, Dr. Subbiah.
    Dr. Subbiah. I think what you had mentioned was that the 
patients that were not stable were not to be included in the 
study. That is two different things. So often, in general, when 
you do studies in mental illness, often you don't include 
unstable patients. But we need to continue to see how to 
improve care in these patients so you do continue to do studies 
as we are currently doing a study in schizophrenia. But we make 
sure they are stable clinically before they are enrolled in the 
trial.
    Mr. Buyer. Right. Then in the middle of your trial they end 
up taking a drug that causes them to be unstable. Do you 
continue having them in the study or do you move them out of 
the study?
    Dr. Subbiah. Well, I think, first of all, it has not been 
shown based on data that Chantix' definitively 
causes all these symptoms. That is what we are continuing to 
study right now. The smoking cessation process is a very 
complex process. Smokers themselves are at a higher risk of 
suicide. The withdrawal process, regardless of having any 
treatment, has similar symptoms like depressed mood, 
irritability, anger, frustration. And then you have drug 
treatment. So it is important to remember these complexities 
when trying to make interpretations. And that is why it is 
important to continue to do research to be able to delineate 
this.
    Mr. Buyer. When you do your clinical trials--I know I am 
over my time. When you do your clinical trials, it is also 
important that you understand the interaction of your drug with 
other drugs, correct?
    Dr. Subbiah. Yep.
    Mr. Buyer. So we had some testimony today by an individual 
who was taking this generic version of a Prozac that has a side 
effect of suicide ideation. And now--do you know whether or not 
in the clinical trial, were there other drugs that you studied 
in the clinical trial that it could have exacerbated these 
ideations?
    Dr. Subbiah. Yes. So when you do a clinical trial--and in 
the Chantix' clinical trials what we do is we do 
continuously monitor for drug interactions and adverse events. 
So, yes, that is something we look for and then try to 
identify. But we can't base it just on one case. We have to 
look for what is going on between the treated group versus the 
placebo group and make comparisons.
    Mr. Buyer. The last thing. I apologize, Dr. Snyder. I will 
get to you real quick. I know that the Chairman had the 
Secretary comment on that they are looking at 
Chantix', you are looking at yourself, the FDA is 
looking at you and--because we have got a drug here that we 
know is helping people with regard to trying to stop smoking, 
otherwise it is going to kill them. Right? Do you have an 
ongoing study right now with regard to examination of the side 
effect for suicide ideation?
    Dr. Subbiah. Yes. So in the studies--like, for example, in 
the schizophrenia study, we do have measures to look at 
suicide--there is a scale called the Columbia suicide scale. We 
have a scale that is looking at depression as well as anxiety, 
these are some of the other symptoms that we want to monitor 
for.
    Mr. Buyer. All right. Thank you.
    The Chairman. Did you tell the VA that you have that study?
    Dr. Subbiah. No, I didn't.
    The Chairman. If I were you, Mr. Secretary, I would just 
wait until their study is complete. Prudence. When will you 
have your study complete?
    Dr. Subbiah. This will be done--the schizophrenia study 
will be done in 2010.
    The Chairman. You'll still be around, Dr. Peake. Just wait.
    Dr. Snyder.
    Mr. Snyder. I'd like to pursue that a little bit, Mr. 
Chairman, because it can be very easy for Secretary Peake and 
his folks to decide not to put a drug on the formulary. I mean, 
that could be a decision to say we are not going to include 
this drug. And what it would mean is that veterans who might 
benefit from it safely won't have the benefit of it. We used to 
say--I don't know--maybe General Peake didn't ever say this. 
But we always said never be the first one to start prescribing 
a drug and never be the last one to start prescribing a drug 
because--let the first guys be the ones that discover the side 
effects, but don't be the last guy in town that actually 
discovered a new treatment.
    Well, I think we want the VA to have mainstream care. And 
if the medical letter which was referred to earlier--Secretary 
Peake referred to it--I used to subscribe to it back when I was 
practicing medicine. It was very helpful. It cut right to the 
chase and it gave you the big warnings. And when it says this 
is the best drug out there right now, you pay attention to 
that. And that is the kind of information--you are probably 
going to change your prescribing patterns. You are probably 
going to--not everybody liked the nicotine patches.
    The Chairman. But the PTSD patient, that is the key here.
    Mr. Snyder. I think this is my time, Mr. Chairman. I have 
listened to you. Here is the issue. Let's talk about PTSD. I 
think we do a disservice to anyone with PTSD if we somehow say 
you have lost all your mental faculties and judgment to sit 
down with your doctor and make a decision about what is the 
best treatment for you. My dad had PTSD. He was a World War II 
guy. He was one of Patton's folks. And he got involved in 
burial details of guys who got burned and killed in tanks. It 
was terrible. And to the day he died he did not watch anything 
on TV but variety shows and game shows, no cowboys and Indian, 
no war, no crime. He didn't want anything that smacked of 
violence. Now, he didn't know he had PTSD, he didn't talk about 
PTSD. He died of his smoking. He went in to have a surgery and 
couldn't get off the ventilator and he died. Now, I don't think 
he was suicidal. I think if he had any inclination at all of 
what smoke would have done to him, and we have a better 
understanding now, he would gladly have sat down with a 
practitioner and said do you mean if I take that little pill I 
can get rid of this habit that is trying to kill me. But I 
don't have any reason to think that--well, anyway, I made my 
point.
    I think we do a disservice to PTSD folks by somehow saying 
that they are not capable of making a decision with their 
doctor. There clearly are PTSD folks that have big time 
problems, but that is, I think, part of our job here is we want 
to convince the American public that just because someone has 
PTSD, it is a step toward doing better. It is not some kind of 
diagnosis that you are impaired forever. That is not what we 
are about. That is not what the VA is about.
    So the only point I was going to make is I hope that what 
comes out of this today--I think this has been a pretty healthy 
discussion. I mean, research in big systems is always 
difficult, as General Peake can't pull strings on the hundreds 
and thousands of people that are out there. But I'd hate a 
signal to be going out there that for folks that have anxiety 
or bipolar disease or depression or PTSD, that somehow the 
studies aren't out there yet, keep smoking, wait a few years, 
keep smoking, put those two or three packs away or keep 
puffing. I think that would be a terrible, terrible disservice, 
and I think what our goal is, is to have our veterans 
population get the same quality of care, if not better--I think 
it is better in a lot of cases--as they would out in the 
private world.
    Right now that means a drug that seems to be proving most 
effective. That doesn't mean there is problems with how this 
study was conducted. And I think Dr. Daigh is getting at that 
and all, but I think we need to be sure what our ultimate 
message is. Our ultimate message is healthy people; even if you 
have PTSD, you can still get off cigarettes. If you have PTSD, 
you may want to discuss--I would encourage you to discuss in 
more detail what the side effects are of any medications just 
like you would if you had depression or anxiety or anything 
else. But it does not mean that you should wait a few years and 
be the last person in town to try getting off cigarettes. I 
think that would be a great disservice.
    Thank you.
    The Chairman. Thank you, Mr. Snyder. If I was unclear, no 
one is suggesting that such people are not capable of making 
those decisions. The issue is informed consent. And when you 
are offering that drug in a study and, one, you haven't given 
informed consent or signed anything, you are making it 
available at a time when you know there are problems. The 
doctor hasn't had the informed consent yet because we don't 
know what is going on with this thing.
    Mr. Snyder. I am just responding to your comment, Mr. 
Chairman, that you said prudence, Mr. Secretary, don't give the 
drug to anyone----
    The Chairman. No. What I meant was that I wouldn't give the 
drug in this controlled study to those with PTSD. Don't give 
that drug in this controlled study.
    Mr. Snyder. Let me make sure I understand. So if a person 
with PTSD, a veteran, is going to a CBOC or going to their 
primary care doctor--and all people with PTSD, as you know, in 
the VA system don't go to PTSD clinics. They get their care 
through primary care. You are okay with them getting this 
medication as long as they are not in this study?
    The Chairman. I am okay if they have completely discussed 
this with the doctor.
    Mr. Snyder. Oh, that's different than what----
    The Chairman. That they are informed. We are talking about 
the study.
    Mr. Snyder. Then I misunderstood you. I thought all you 
said is prudence, pull the drug, don't give it to anyone with 
PTSD.
    The Chairman. That's not what I said. I said pull it from 
this study. I am glad you clarified that because I agree with 
you. By the way, when you said you were appalled by the 
suggestion that we should stop research, I join you in that. 
That is not a message we want to give. The message I want to 
give is that in this controlled study where you have 
questions--as Mr. Buyer said--these people were supposed to be 
excluded and the warning from FDA said this could cause a 
recurrence of a past psychotic problem. So you are giving 
someone a drug that might--as he said, make the study invalid 
to begin with. That person should never have been in it if that 
is what could occur. You subjected them to the condition to 
which you were trying to exclude, and I think there was a 
change in the middle of the study that created new problems 
that the veteran was not informed about. That is when I would 
have stopped it because a change had occurred and we should 
have used prudence until we knew more. I am not saying this to 
all 32,000 that we are giving this drug to--it was in this 
particular context.
    But I thank you for your clarification. Last statement, Mr. 
Buyer?
    Mr. Buyer. I have one in particular. Our colleague, Ginny 
Brown-Waite, wanted to be here. She is the Ranking Member on 
the Oversight and Investigations Subcommittee of the VA 
Committee. Her husband has Stage 4 cancer and obviously there 
is a medical emergency at the moment. So she is not with us 
here today.
    Final two questions that I would have, Mr. Chairman, to Dr. 
Daigh. Do you have an opinion right now on whether these 
patients included in the study should continue to take 
Chantix'?
    Dr. Daigh. No. I answer it because----
    Mr. Buyer. No, you do not have an opinion?
    Dr. Daigh. No, I do not have an opinion.
    Mr. Buyer. Thank you. Is this--I am going to take the next 
step. Because I made comments earlier in the hearing about the 
importance of the doctor/patient relationship; it is the doctor 
that has the best interest of the patient at heart and is 
supposed to know and understand their human physiology and--
which also includes mental. And they also want to be able to 
save their life through the smoking cessation, treat the mental 
disorder, and I don't want to interfere with that. We have an 
FDA approved drug that has specific side effects.
    In your study that is going on, Dr. Subbiah, either now or 
maybe in previous studies, do we know the impact of alcohol on 
Chantix'?
    Dr. Subbiah. So in the development program, patients were 
allowed to consume alcohol; however, patients who had history 
or diagnosis of alcohol dependence and abuse were excluded from 
the trials. In the registration trials, average patients 
reported consuming about one drink a day. So specifically that 
was what the patients had--we were studying it with regards 
to--as a concomitant medication. So we don't have any specific 
data on alcohol abuse but as, like Mr. Elliott, the normal use 
of alcohol was allowed.
    Mr. Buyer. All right. So sometimes the doc gives you a 
drug, you say all right, don't take alcohol. That is not with 
Chantix'? You can take Chantix' and it is 
permissible to take alcohol?
    Dr. Subbiah. Yes. Our current label does not indicate a 
contraindication in the use of alcohol.
    Mr. Buyer. All right. Thank you. I yield back.
    The Chairman. Thank you again. In the fifth century B.C., 
Hippocrates said--I am sorry. Mr. Scalise, I apologize. Do you 
have any questions?
    Mr. Scalise. No.
    The Chairman. Okay. I am sorry. In the fifth century B.C., 
Hippocrates said, ``first, do no harm.'' And I think that 
should be your credo here, Secretary Peake. We don't know if we 
are going to do harm. I think the prudent thing is not to do 
harm.
    I thank you all for being here. Secretary Peake, I thank 
you for staying for the entire hearing and listening carefully 
to what everybody has said. We hope that we can continue to do 
research and do no harm.
    This hearing is adjourned.
    [Whereupon, at 2:20 p.m., the Committee was adjourned.]



                            A P P E N D I X

                              ----------                              

            Prepared Statement of Hon. Bob Filner, Chairman,
                  Full Committee on Veterans' Affairs
    I would like to thank the Members of the Committee, our witnesses, 
and all those in the audience for being here today.
    I was appalled when The Washington Times published an article 
revealing that the VA was and continues to use Chantix' in 
Cooperative Studies Program #519--``Smoking Cessation Treatment for 
Veterans with PTSD.'' Some Veterans with Post-Traumatic Stress Disorder 
(PTSD) enrolled in a VA smoking cessation study were being, and 
continue to be, administered Chantix'.
    Chantix' received FDA approval on May 11, 2006. However, 
on November 20, 2007, the FDA issued an early communication about an 
ongoing safety review of Chantix'. It revealed that FDA had 
received reports of ``suicidal thoughts and aggressive and erratic 
behavior in patients who have taken Chantix'.'' At this 
point, the VA should have suspended the study and immediately notified 
all patients of the possible dangers.
    The loss of a single veteran to suicide is a tragedy. Since 
December 2007, this Committee has held two hearings regarding the issue 
of veterans' suicide. This is why I fail to understand why the VA did 
not react when the FDA issued the early communication concerning the 
dangerous side effects of Chantix'.
    On February 1, 2008, the FDA issued a Public Health Advisory 
stating: ``Chantix' may cause worsening of current 
psychiatric illness even if it is currently under control and may cause 
an old psychiatric illness to occur . . . symptoms may include anxiety, 
nervousness, tension, depressed mood, unusual behaviors and thinking 
about or attempted suicide.''
    The VA waited until February 29, 2008, to send a letter and new 
consent form to study participants to notify them of the dangers 
associated with Chantix'. The letter informed patients that 
they may experience ``an increase in psychiatric symptoms such as 
anxiety, nervousness, tension, depression as well as untoward changes 
in behavior.''
    But it failed to mention the fact that Chantix' may lead 
to suicidal ideation or attempted suicide. This fact was buried in the 
consent form.
    Regardless, the warning was too late for Mr. Elliott, an Army 
veteran of OIF. In February, he suffered a psychotic episode that led 
to a confrontation with the police. Mr. Elliott, I appreciate your 
appearance before the Committee today and look forward to your 
testimony.
    This is merely the latest incident in a series of events, from the 
suicides in Dallas to the e-mail suggesting VA providers downgrade the 
diagnosis of PTSD to ``adjustment disorders'' to the e-mail downplaying 
the epidemic of suicides in the VA, that have caused me and the other 
Members of this Committee to question the VA's accountability measures 
and also the Department's dedication to addressing the mental health 
needs of our returning servicemembers.
    Today we will look at VA's procedures for handling human research 
subjects, determine whether they were followed in the design and 
execution of the smoking cessation study and explore whether there was 
adequate oversight of the study. Furthermore, I want to investigate 
VA's responsibility to respond to FDA advisories and VA's decision to 
continue to use Chantix', a suicide-inducing drug, on 
veterans with PTSD.
    But in a much larger sense, we use this hearing today to ask the VA 
when are you going to take responsibility, when will you hold people 
responsible for the numerous issues that have been identified over the 
last few months.
    We see this in an email sent from Temple, Texas, stating that 
``given that we are having more and more compensation seeking veterans, 
I'd like to suggest that you refrain from giving a diagnosis of PTSD 
straight out. Consider a diagnosis of Adjustment Disorder.''
    We see this in Dallas, where, after four patients committed suicide 
this year, the psychiatric ward was forced to close. We see this time 
and time again, where we hear soothing words like ``responsibility'' 
and ``accountability,'' but we do not see action. Talk is indeed cheap, 
especially when it comes to the safety and well-being of our veterans.
    It seems to me, and to other Members of this Committee, that the VA 
continues to follow the same old pattern . . . deny, deny, deny. And 
then when caught and confronted . . . cover up, cover up, cover up . . 
. or tend to try and minimize the importance of the issue, or show the 
veteran as an anomaly. But no one is held accountable and the system 
goes on.
    When questioned, the VA immediately wants to defend ``the 
process.'' When is the VA going to understand that it is not about the 
process, but about the veteran? When will the VA stop being the 
veteran's adversary and start being the veteran's advocate?
    We are talking about people . . . we are talking about our 
veterans. Don't defend your process . . . defend our veterans . . . our 
heroes.

                                 
   Prepared Statement of Hon. Steve Buyer, Ranking Repubican Member,
                  Full Committee on Veterans' Affairs
    Mr. Chairman, Thank you for yielding. I appreciate you calling this 
hearing so quickly.
    The title of this hearing, ``Why Does VA Continue to Give a 
Suicide-Inducing Drug to Veterans with PTSD,'' is certainly an 
attention getter; however, Mr. Chairman, I think it misses the mark.
    With the possible exception of the physicians on our Committee, 
doctors Boozman and Snyder, I doubt that anyone on this Committee, 
including myself, have the expertise to determine which drugs should be 
used by VA.
    I'll defer to the experts on that matter, and Chantix' 
has been an FDA approved drug since May 2006 and is used by over 7 
million people world-wide to help them stop smoking. What I think this 
Committee should investigate, is whether VA failed to protect veterans 
who volunteered to be research subjects.
    The VA Office of the Inspector General briefed our Committee staff 
prior to this hearing, and we know what their preliminary findings 
were. I am very disappointed that longstanding problems with the VA 
research program have apparently not been corrected.
    Those problems relate to strict human research subject protections 
that require fully informed consent of patients before they participate 
in any research studies. It appears VA may have failed to disclose 
important facts veterans need to make informed decisions before 
participating in the study.
    If they were not provided full information about the possible risks 
of their involvement in the VA smoking cessation study, this is a major 
problem, one that is made worse because it is not the first time there 
has been an informed consent problem in VA research.
    During the 108th Congress, while serving here as the Chairman of 
the Oversight and Investigations Subcommittee, I introduced H.R. 1585, 
to establish the Office of Research Oversight within the Department of 
Veterans Affairs.
    The language of this bill became Public Law 108-170. These 
provisions of this law established within the Veterans Health 
Administration (VHA) an Office of Research Oversight to monitor, review 
and investigate matters of medical research compliance and assurance in 
the VA, including matters relating to the protection and safety of 
human subjects and VA employees participating in VA medical research 
programs.
    What gave rise to the legislation was an OIG report entitled 
``Alleged Research Improprieties and Informed Consent Issues, Jerry L. 
Pettis Memorial Veterans Hospital, Loma Linda, California'' issued on 
October 7, 1999, along with several hearings that followed on VA 
research and informed consent issues.
    The purpose of the legislation was to avoid the occurrence of 
situations like the unfortunate one we are here to discuss today.
    The Committee was briefed on potential research misconduct at the 
Albany VA in January 2003. We were informed that the VA Inspector 
General and VHA were conducting an inquiry into the matter.
    The clinical trial drug company sponsor detected clinical results 
inconsistent clinical trial data being submitted by the VA's principal 
investigator and brought that to his attention. This notification to 
the principal investigator turned out to be a flawed process, as senior 
managers were not apprised of this situation till much later and 
launched an internal investigation.
    We closely monitored the progress of this investigation, but were 
informed that further updates would be limited as this had become a 
Federal criminal investigation.
    This situation and many more incidents revealing weak departmental 
oversight in the protections of veterans in human and animal subjects 
research led me to create and legislate an independent oversight board 
to insure greater protections to vulnerable veterans that have 
volunteered to serve their country and volunteered to be subjects in 
clinical research.
    Mr. Chairman, in August 2003, VA initiated a cooperative studies 
program, ``Integrating Practice Guidelines for Smoking Cessation into 
Mental Health Care for Posttraumatic Stress Disorder (PTSD).''
    This research project was to compare effectiveness of integrating 
smoking cessation with mental health treatment versus keeping them as 
separate treatment programs. The protocol medications for this research 
project included the nicotine patch and nicotine gum.
    In January 2007, VA modified the protocol by adding 
Chantix' after FDA's approval of the drug for public use.
    As of today, VA has approximately 32,000 patients on 
Chantix', and the Department of Defense has approximately 
67,000 patients on Chantix'.
    On June 17, 2008, an article appeared on the front page of The 
Washington Times detailing the use of the drug Chantix' in 
the VA study, and the subsequent effects that may have been caused by 
this drug in one veteran in particular. That same day, I wrote a letter 
to the VA as well as to the VA Inspector General's office requesting an 
investigation and an immediate briefing on the allegations detailed in 
the Washington Times' article.
    On June 18, 2008, I, along with Committee staff, and a 
representative from Congresswoman Brown-Waite's office attended the 
briefing with the Principal Deputy Under Secretary for Health; the 
Chief of Research and Development; the Chief Officer of the Office of 
Research Oversight; and the Acting Deputy, Chief Research and 
Development Officer. At this briefing, we were provided a chronology of 
events leading up to the Washington Times' article.
    Committee staff again met with the Chief of Research and 
Development and the Acting Deputy, Chief Research and Development 
Officer on June 19, 2008, and requested all documentation of all 
amended informed consent forms for all study subjects, as well as all 
Adverse Drug Reactions (ADRs) and Serious Adverse Events (SAEs) related 
to this study that have been reported to VA's Cooperative Studies 
Center in Albuquerque, New Mexico.
    To date, neither the Committee staff nor I have seen the amended 
consent forms. I asked the Secretary to be prepared to explain the 
absence of these forms during the question/answer period following his 
testimony.
    Because of the preliminary findings, on July 3, 2008, I further 
requested a nationwide investigation by the Office of the Inspector 
General on human research subject protections. I'll have much more to 
say about this when Dr. Daigh of the Inspector General's office 
testifies.
    The FDA and Pfizer are going to be testifying to inform the 
Committee about Chantix'. They are the only witnesses here 
today who can be considered experts or authorities on drug safety and 
Chantix'.
    I caution my colleagues that this Committee lacks the expertise as 
well as the jurisdiction over the FDA and drug safety, for a topic more 
appropriately addressed by the Committee on Energy and Commerce.
    To attack a drug as being unsafe and to characterize it as suicide-
inducing is at best premature. We should be very careful in making 
sensational public statements about the safety of an FDA regulated drug 
without full information about it, when it could be of enormous benefit 
in saving lives.
    Let us not jump to conclusions that we are poorly qualified to 
make. We should hear the testimony of the witnesses and their answers 
to our questions, and then only after careful inquiry make informed 
judgments on what occurred and what corrective actions and followup may 
be called for.
    Make no mistake, we are all about accountability and if veterans 
have not been well served, I for one will not hesitate to aggressively 
seek appropriate corrective measures, including actions against VA 
officials.
    Mr. Chairman, as you are well aware, the safety of patients at the 
Department of Veterans Affairs is of primary importance to those of us 
here on this Committee.
    Thank you again, Mr. Chairman, and I yield back my time.

                                 
              Prepared Statement of Hon. Harry E. Mitchell
    Thank you, Mr. Chairman.
    I appreciate you holding this hearing today to discuss the 
Department of Veterans' Affairs protocols and procedures following 
patient claims of mental health effects while participating in the VA 
Cooperative Studies Program #519, ``Smoking Cessation Treatment for 
Veterans with PTSD.''
    While the goal of CSP #519, smoking cessation, is critical to the 
overall health of our veterans, there are several aspects of concern. 
Among these concerns are that accurate informed consent was not 
obtained from all participants, and those already enrolled in CSP #519 
were not informed of possible serious side effects as new information 
from the FDA became available.
    It is important to provide all information necessary regarding 
participation in such studies, and not doing so is simply unacceptable. 
While studies and tests are necessary for improving care, our veterans 
should never be subjects unwittingly.
    Under your leadership, this Committee has made caring for the 
mental health of our veterans a top priority. We have repeatedly 
witnessed the serious needs of veterans at risk for suicide, and we 
must remain vigilant to treat these veterans with the highest quality 
of care available.
    Our Nation's veterans have served honorably to protect us and our 
country. The least we can do is fight for them when they come home.
    I yield back the balance of my time.

                                 
               Prepared Statement of Hon. John T. Salazar
    Good morning, Mr. Chairman.
    I have been following the Chantix' story over the last 
few weeks and share your concerns over this incident.
    Recent reports of the damage and mental breakdown experienced by 
veterans as a result of Chantix' are very disturbing.
    Like my colleagues on this Committee, I question why this happened 
and if this is happening in other studies.
    More importantly, I am interested in hearing the steps the VA is 
taking to ensure that this incident is not repeated.
    For a veteran in a rural district like mine, seeking help can mean 
traveling over dangerous terrain and mountain passes in unpredictable 
weather.
    Should one of them experience a mental breakdown the damage can be 
even more severe than if it took place in a big city.
    I know that the almost 70,000 veterans that I have in my district 
go to VA centers expecting a system that is looking out for their well-
being.
    Many of the Veterans in Colorado's Third District are low income 
and live in rural communities.
    Most have to travel long distances to get to their nearest VA 
facility.
    However, they go through a great deal of hardship because they know 
that they will be receiving the best care available in gratitude for 
their service to our Nation.
    It is this confidence that leads many veterans to take part in 
studies to better their lives and the lives of their fellow veterans.
    We cannot dishonor their desire to continue to serve their fellow 
servicemen and women by not informing them of all the risks involved.
    Our veterans need to be confident that they are safe when they go 
to a VA hospital, take their medications or take part in a VA study.
    Incidents like this one shake their confidence in the system that 
is in place to care for them.
    Veterans have given enough for this Nation and we must ensure that 
they have healthcare that takes care of their needs safely and 
effectively.
    Mr. Chairman, I thank you and the Members of this Committee for the 
opportunity to review this incident to ensure that this does not happen 
again.

                                 
                Prepared Statement of Hon. Steve Scalise
    Mr. Chairman, thank you and Ranking Member Buyer for holding this 
important hearing on the VA smoking cessation program for patients with 
Post-Traumatic Stress Disorder (PTSD) and the alleged failure of the VA 
to promptly notify program participants of FDA health advisories, as 
well as documentation that informed consent procedures were properly 
followed.
    It is important that we examine the process of how veterans in this 
study were informed of the side effects of prescribed drugs and whether 
they gave proper consent. More importantly, while we will hear 
testimony about drug safety, consent procedures, and bureaucratic 
oversight, we must remember that today's hearing is about the 
patients--the veterans who bravely served our country and now rely on 
the VA for proper healthcare.
    Many of our veterans are suffering from PTSD as a result of their 
service to our Nation, including thousands returning from the conflicts 
in Iraq and Afghanistan. We must honor their service by ensuring they 
receive proper treatment, and we must make certain they are not taken 
advantage of for the purpose of clinical study.
    I find it alarming when I read claims that veterans were not given 
adequate and prompt notification of the FDA advisories, as required by 
human research subject protections on informed consent. Furthermore, I 
am disturbed by the lack of informed consent documents in cases 
involving the Cooperative Study Program No. 519.
    Veterans should be allowed to have a face to face conversation with 
their doctor about the treatment they are receiving, along with 
potential side effects, and the drugs they are taking so they can make 
informed decisions about their care. Discussing possible side effects 
and obtaining proper consent are vital to the doctor-patient 
relationship and the cornerstone of the human subject research. If 
veterans in this study did not receive adequate information about their 
treatment and did not consent, this threatens the validity and 
integrity of all VA research.
    Mr. Chairman, I hope that our witnesses will address the 
notification and consent procedures involved in this study. And I hope 
that we gain a greater understanding of the procedures required to 
conduct medical research studies and what steps will be taken to hold 
anyone accountable if they did not follow the procedures.

                                 
       Prepared Statement of James G. Elliott, Silver Spring, MD
                           (Iraq War Veteran)
                           Disposable Heroes
The Use of Veterans and Military Personnel as Research Lab Rats by the 
                  U.S. Veterans Health Administration
     I.  Timeline
     II.  Diagram
    III.  Select bibliography
     IV.  Binder with supporting research documentation

I. TIMELINE:
November 11, 2001, James G. Elliott enlist date--U.S. Army
 James Elliott's experience while under the care of Washington VA 
        Psychiatric Staff
    October 30, 2007
         A prescription for Varenicline was issued for James G. Elliott 
        by the Washington VA Psychiatric Department after he was talked 
        into enrolling into a study entitled ``PTSD and Smoking 
        Cessation Study #519''. His prescribing physician, Hallie 
        Lightdale, informed James that he was a ``good candidate for 
        the study'' because he ``gives her good feedback.''
    November 5-6, 2007
         James received the prescription and began taking as 
        prescribed.
    Nov 12-13 (approx.), 2007
         James began experiencing dermatological side effects (i.e. 
        hives, uncontrolled itching) on the first day he took the full 
        dose. The dosage instructions were to take \1/2\ tablet by 
        mouth every morning for 3 days, then take \1/2\ tablet twice a 
        day for 4 days, then take 1 tablet twice a day. James was 
        experiencing serious dermatological side effects by the time he 
        achieved the full dosage regimen as prescribed. As a result, he 
        quit taking the medicine briefly until an appointment with his 
        primary care physician, Dr. M. Villaroman, who advised James to 
        cease taking Varenicline.

           Nov. 20, 2007, First FDA warning on Varenicline regarding 
        serious neuropsychiatric symptoms experienced in patients 
        taking Varenicline.

           VA does not notify study participants. James receives no 
        warning but continues to receive mailed appointment reminders 
        from the Washington VA to come in personally in order to 
        complete the monthly study questionnaire.

    Mid-December 2007
         James attends his regularly scheduled appointment with Dr. 
        Hallie Lightdale, his prescribing psychiatrist for Varenicline. 
        She advised him to resume Varenicline at a reduced dose and 
        dismissed side effects as temporary. James resumes taking 
        Varenicline.
    Early January 2008
         James attends couples counseling with his fiancee due to his 
        erratic behavior. The appointment is at the Silver Spring Vet 
        Center with Gil Becker. Counseling was not successful because 
        James' behavior during the session was not conducive to 
        therapeutic interaction. His erratic behavior and emotional 
        crisis continues to spiral downward.
    Mid-January 2008
         James attempts, in person and in an extremely agitated state, 
        to see his psychiatrist Dr. Hallie Lightdale. He speaks with 
        the receptionist, Evelyn Littlejohn, who says she will relay 
        the message. He tells Ms. Littlejohn that it is an extreme 
        emergency and that he must see a doctor. Ms. Littlejohn takes 
        notes and James leaves without emergency treatment.

           February 1st 2008, second FDA safety advisory on 
        Varenicline/Chantix' regarding serious 
        neuropsychiatric symptoms experienced in patients taking 
        Varenicline. VA does not notify study participants. James 
        receives no warning, but continues to receive mailed 
        appointment reminders from the Washington VA to come in 
        personally in order to complete the monthly study 
        questionnaire.

    February 5, 2008
         James' behavior has become so erratic that his fiancee feels 
        that the car keys need to be secured. He will not comply with 
        her requests for the car keys, so she calls Montgomery County 
        Police Department for assistance. James is then involved in a 
        near-death situation/standoff with the police. He is tased for 
        his own safety and secured by the police. He is hallucinating 
        and reverts to combat-oriented behavior out of survival 
        instinct. He does not recognize his own fiancee. His concept of 
        time is so skewed that he perceives a 20-minute standoff with 
        police as happening in a matter of minutes. He does not 
        remember the entire event to this day. A straight-A, PTSD 
        success story, Mr. Elliott is days away from a gala event for 
        which he has been chosen to meet Colin Powell as a 
        representative of successful, recovering veterans returning 
        from theatre. Now, he is on the ground, tased and lucky to be 
        alive.
    February 8, 2008
         Gil Becker, Silver Spring Vet Center Counselor, takes James 
        Elliott from Montgomery County Jail to Washington VA. In a 
        meeting with Dr. Stacey Pollack, Dr. Hallie Lightdale, and Gil 
        Becker, he is told by Dr. Lightdale that the 
        Chantix'/Varenicline is the likely cause of the 
        episode. She stated, ``There had been problems with other 
        people, but I never thought it would happen to you. I am so 
        sorry, Mr. Elliott (para.)''. This is the only time to date 
        that the Washington VA psychiatric department has admitted that 
        Varenicline caused Mr. Elliott's February 5th psychotic 
        episode.
    February 9, 2008
         James' fiancee, after close review of his medical files, 
        realizes that he has been participating in a dubious research 
        study. She meets with VA doctors, including Dr. Stacey Pollack 
        and Dr. Hallie Lightdale. They offer no explanation for James' 
        psychotic break. They accuse Ms. Hilburn of being controlling 
        and overbearing. James is still suffering from Varenicline 
        withdrawal. He is also overdosed on extended-release morphine 
        that he is usually allowed to take as needed at home. He is 
        forced to take 150 mg of extended-release morphine per day 
        while hospitalized at Washington VA.

         During the meeting, Ms. Hilburn holds up the booklet for study 
        #519 and states that this is the ``most heinous s*** I have 
        ever seen.'' She also states, ``My lawyer will kill me for 
        saying this, but if it keeps you from prescribing 
        Chantix' to even one more veteran, it will be worth 
        any trouble we go through.'' The doctors rise and state that 
        the meeting is over. They refuse to talk with Ms. Hilburn and 
        shuffle James down the hallway. James is confused and unaware 
        of the situation.

    February 15, 2008
         While hospitalized, James is forced to daily take 150 mg 
        extended-release morphine at full dosage, even after VA doctors 
        and staff were informed that he was allowed after a pain 
        management class to take morphine as needed. James usually 
        takes 50 mg extended release morphine every two days for 
        severe, demobilizing back pain related to an inoperable combat-
        related injury (fall from roof through third floor of mortar-
        damaged house while on night raid). By February 14, James has 
        ceased passing stool and has begun to have problems urinating, 
        signaling potential kidney failure. Ms. Hilburn is advised by 
        outside medical counsel to have James signed out and examined 
        by private medical facility. Washington VA doctors force James 
        to sign out AMA. Upon examination at a private medical 
        facility, James is found to have a possible bowel obstruction 
        and enlarged spleen. James is forced, due to legal constraints, 
        to stay in a hotel, with no contact verbally or physically from 
        his fiancee, for over a month. He cannot return home. He is 
        alone, scared, wounded and betrayed by the VA. The Washington 
        VA psychiatric staff is, by this time, only concerned with 
        appearances and covering any indication that they were at 
        fault. James is highly unstable, alone, and suffering 
        withdrawals from a myriad of substances administered by the 
        Washington VA.
                               __________

    James is lucky to be alive. There are likely many veterans who are 
not, due to this type of abuse at the hands of VA researchers.
    We submit to the U.S. House of Representatives Committee on 
Veterans' Affairs this documentation in the hope that it will receive 
the deep investigation that it warrants. The actions taken by U.S. 
House of Representatives Committee on Veterans Affairs in relation to 
this submitted evidence will be judged by the American public and the 
international community and will determine, it is hoped, a new standard 
by which we care for our veterans and military staff in the United 
States.
    The Hippocratic Oath is not alive and well in the Washington VA 
Psychiatric Department. We hereby ask for a criminal investigation in 
any death, suicide, attempted suicide, violent act or act suffered at 
the hands of any veteran or military personnel, civilian dependents or 
spouses that were enrolled in research programs conducted by the 
Veterans Administration to ensure that these situations were not caused 
by the same lapses in ethical medical conduct that were experienced by 
Mr. James Elliott. James Elliott was asked twice in closed offices 
``what it would take to make him happy''. Each time, he told those that 
were asking this question that he wanted the testing to stop. He said 
that he wanted them to quit killing his friends.
    Please see the attached diagram for additional details regarding 
what Mr. Elliott and Ms. Hilburn learned after conducting research on 
Mr. Elliott's participation in the study, past VA studies and the ruse 
of smoking cessation as a benign and benevolent goal of VA medical 
staff. The information learned indicates unethical relationships 
between the U.S. Veterans Administration, Pfizer, its endowed 
universities and subsidiaries. The diagram details the research food 
chain in which Mr. Elliott found himself suspended without any recourse 
to due process.
    Sadly, Mr. Elliott and other veterans were unwittingly used in this 
Nazi-like human medical research nightmare.
    We maintain that the Veterans Health Administration should not be 
participating in medical testing on human subjects that have served our 
country. The Veterans Health Administration should be a place for 
veterans to heal, not heel.
    James Elliott officially submits this evidence and information to 
the U.S. House of Representatives Committee on Veterans' Affairs for 
action as deemed necessary.
II. DIAGRAM:




III. BIBLIOGRAPHY:
    Y. Tizabi \1\, John Mastropaolo \2\, Chan H. Park 2, 
Raine L. Riggs 2, D. Powell 2, Richard B. Rosse 
2, and Stephen I. Deutsch 2
---------------------------------------------------------------------------
    \1\ Department of Pharmacology, College of Medicine, 520 W Street 
N.W., Howard University, Washington, DC 20059, U.S.A. Fax: +1-202-806-
4453, U.S.
    \2\ Psychiatry Service, Department of Veterans Affairs Medical 
Center, 50 Irving Street N.W., Washington, DC 20422, U.S.A, U.S.
---------------------------------------------------------------------------
    Abstract Dizocilpine (MK-801) administration to an outbred strain 
of NIH Swiss mice elicits discrete episodes of explosive jumping 
behavior designated as ``popping.'' This behavior may serve as a useful 
preclinical paradigm for the screening of potentially novel 
antipsychotic medications. Both nicotine and mecamylamine, a nicotinic 
antagonist, dose-dependently blocked dizocilpine-induced popping. The 
data suggest that nicotine may be of therapeutic benefit in the 
treatment of schizophrenia and that some of its effects may be mediated 
by non-nicotinic receptors.
        Key words Dizocilpine--MK-801--Nicotine--Mecamylamine--Mice--
        Schizophrenia
        Received: 17 December 1997/Final version: 10 March 1998
    Select Bibliography
    This bibliography is ordered in a timeline per category to show 
agency interest in psychosis and nicotinic receptors, historical 
perspective, and also corporate interest. Therefore, it is not 
formatted in the typical, academic fashion, but rather to show 
collective interest and connections. The research publications from a 
wider body of institutions and companies are submitted separately to 
the Committee in a binder prepared by Elliott and Hilburn.

    Categories of research abstracts

     I.  Historical Interest in the treatment of Schizophrenia in 
conjunction with nicotine--1 abstract
     II.  Pfizer research on nicotinic receptors and Schizophrenia--1 
abstract
    III.  Research publications focusing on nicotinic receptors and the 
treatment of Schizophrenia published through Mental Health Service 
Line, Department of Veterans Affairs Medical Center, Washington, D.C. 
and Linthicum, MD in conjunction with Georgetown University and 
University of Maryland.--7 abstracts
     IV.  Research publications from the Department of Psychiatry, 
Veterans Affairs Medical Center, Denver, CO. with focus on the link 
between nicotinic receptors and Schizophrenia.--7 abstracts--not cited 
below but included in submitted binder.
      I.  Historical Perspective
        1.  Treatment of schizophrenia with nicotinic acid and 
nicotinamide. Hoffer A, Osmond H, et al. J Clin Exp Psycohopathol. 1957 
Apr-Jun; 18(2): 131-58.
     II.  Pfizer Research
        1.  Discovery of N-[(3R)-1-azabicyclo [2.2.2] oct-3-
yl]furo[2,3-c] pyridine-5-carboxamide, an agonist of the alpha7 
nicotinic acetylcholine receptor, for the potential treatment of 
cognitive defects in schizophrenia: synthesis and structure-activity 
relationship. Wishka GD, Walker DP, et al. J. Med Chem. 2006 Jul 13; 49 
(14): 4425-36.
    III.  Washington VA Psychiatric/Mental Health Service Line, 
Department of Veterans Affairs research publications related to 
Schizophrenia and other neurodegenerative diseases in conjunction with 
interest in nicotinic and acetylcholine receptors.
        1.  Both nicotine and mecamylamine block dizocilpine-induced 
explosive jumping behavior in mice: psychiatric implications. Tizabi, 
Mastropaolo, Park, Riggs, Powell, Rosse and Deutsch. 
Psychopharmacology, Vol. 140, No. 2, November 1998.
        2.  Progressive worsening of adaptive functions in Down 
syndrome may be medicated by the complexing of soluble Abeta peptides 
with the alpha 7 nicotinic acetylcholine receptor: therapeutic 
implications. Deutsch, Rosse, Mastropaolo and Chilton. Clin 
Neuropharmacology. 2003 Sep-Oct; 26 (5): 277-83.
        3.  Anabasine, a selective nicotinic acetylcholine receptor 
agonist, antagonizes MK-801-elicited mouse popping behavior, an animal 
model of schizophrenia. Mastropaolo, Rosse, Deutsch. Behav Brain Res. 
2004 Aug 31; 153 (2): 419-22.
        4.  Behavioral consequences of methyllycaconitine in mice: a 
mode of alpha7 nicotinic acetylcholine receptor deficiency. Chilton, 
Mastropaolo, Rosse, Bellack, and Deutsch. Life Sciences. Vol. 74, issue 
25, 7 May 2004, pp. 3133-3139.
        5.  Therapeutic implications of a selective alpha7 nicotinic 
receptor abnormality in schizophrenia. Deutsch, Rosse, Schwartz, 
Weizman, Chilton, Arnold and Mastropaolo. Isr. J. Psychiatry Relat Sci. 
2005; 42 (1): 33-44.
        6.  Effects of CDP-choline and the combination of CDP-choline 
and galantamine differ in an animal model of schizophrenia: development 
of a selective alpha7 nicotinic acetylcholine receptor agonist 
strategy. Deutsch, Rosse, Schwartz, Schooler, Gaskins, Long and 
Mastropaolo. Eur Neuropsychopharmacol. 2008 Feb, 18 (2): 147-51. Epub 
2007 Jul 26.
        7.  First administration of cytidine diphosphocholine and 
galantamine in schizophrenia: a sustained alpha7 nicotinic agonist 
strategy. Deutsch, Schwartz, Schooler, Rosse, Mastropaolo and Gaskins. 
Clin Neuropharmacol. 2008 Jan-Feb; 31 (1): 34-9.
     IV.  Research publications from the Department of Psychiatry, 
Veterans Affairs Medical Center, Denver, CO. with focus on the link 
between nicotinic receptors and Schizophrenia.--7 abstracts.
IV. BINDER:
    Please see submitted binder for these abstracts and a selection of 
other related research abstracts. [The binder is being retained in the 
Committee files.]
    Prepared by James G. Elliott and Tammy R. Hilburn

                                 
Prepared Statement of Lieutenant Colonel Roger G. Charles, USMC (Ret.),
  Vice-Chairman, Board of Trustees, Soldiers for the Truth Foundation,
    and Editor, DefenseWatch, on behalf of Eilhys England Hackworth,
   Chairperson, Board of Trustees, Soldiers for the Truth Foundation
    Chairman Filner, and honorable members of the House Veterans' 
Affairs Committee, on behalf of Eilhys England Hackworth, Chairperson 
of the Board of trustees of Soldiers For The Truth Foundation, I am 
humbled to appear before your Committee as you carry out your 
responsibilities under the Constitution to exercise congressional 
oversight of the Department of Veterans' Affairs.
    Recent events show that this oversight is critical to ensure that 
the well-being of our veterans is in fact the highest priority of the 
VA. These events demonstrate very clearly that without congressional 
oversight, true concern for the well-being of our veterans can 
deteriorate into mere lip service of an indifferent and self-serving 
bureaucracy.
    I note that you have scheduled a most impressive group of experts 
on various medical and ethical issues related to human subject 
experiments as conducted by the VA.
    I do not bring their expertise to this hearing.
    What I do bring is the experience of a career Marine Corps officer 
who believes that our Nation has a sacred responsibility to care for 
those who have manned the ramparts of freedom on our behalf.
    I also bring the skepticism of a journalist who for 18 years has 
investigated misconduct by various Federal agencies in the areas of 
defense and national security.
    Let me now turn to the question that serves as the title for 
today's hearing. ``Why Does the VA Continue to Give a Suicide-Inducing 
Drug to Veterans with PTSD?''
    While studying the experience of Army combat veteran James Elliott, 
I was struck by three major questions which I believe this Committee's 
investigation should consider.
    My first question relates to the Hippocratic Oath and a physician's 
first responsibility, ``to do no harm.''
    How then did the VA physicians involved in planning and conducting 
this drug study fulfill their duties under this pledge?
    Here are some ``followup'' questions I suggest you and your 
Committee staff might also consider:
          Would these physicians have subjected their own sons 
        or daughters to such a high-risk drug study?
          And, would they have failed to inform their own 
        children of the substantial risks this study entailed?
    My second question relates to the Nuremberg Code, and the fact that 
informed consent of all human subject medical experiments is an 
absolute requirement under this code.
    As you may recall, it was the exposure of the most heinous and 
gruesome medical experiments by Nazi doctors that led to enacting the 
Nuremberg Code.
    Our country's own history has, unfortunately, too many examples of 
medical experiments on unwitting subjects. The infamous Tuskegee 
syphilis experiment is perhaps the best known of such shocking 
violations by physicians of their Hippocratic Oath.
    I have attached to this statement a Knight Ridder press report 
dated July 7 that describes the latest legal action in a Federal 
criminal prosecution of a former VA staff physician at the Stratton VA 
Medical Center in Albany, New York. The Federal prosecutor asked the 
court to sentence this former VA physician, and I now quote from the 
press report, ``to spend a year in prison for his role in a drug-
research scandal that killed at least one veteran and victimized dozens 
more.''
    If it pleases the Chairman, I respectfully request that this 
article be included in the record.
    My last question for your consideration involves the participants 
themselves, the veterans with PTSD, who were recruited by VA staff to 
become the subjects of this drug study.
    Why were members of a group, who by the VA's own diagnoses were 
struggling to return to mental health normality, selected for this 
study?
    The mental health of these veterans was known to have been, in 
various degrees, what a layman would term ``fragile.'' Special caution 
and prudence should have been invoked before exposing them to a drug 
study where by definition ``unknown'' factors might further damage 
their mental health.
    Instead, the very VA physicians trusted to help the vets regain a 
more normal mental condition enticed the vets to join a game of mental-
health roulette, while withholding critical information that would have 
permitted true ``informed consent'' to have been given.
    Sir, this concludes my prepared statement. I stand ready to respond 
to any questions the committee members may offer.
                               __________

                 Doc in VA Drug Study Scam May Get Jail
                             July 07, 2008
                             Knight Ridder
    ALBANY--Federal prosecutors want a former Stratton VA Medical 
Center oncologist to spend a year in prison for his role in a drug-
research scandal that killed at least one veteran and victimized dozens 
more.
    A year in jail is the maximum punishment that Dr. James A. Holland, 
50, faces under his guilty plea last year to a misdemeanor charge in 
which he admitted failing to protect his patients from a rogue 
researcher who falsified medical records to enroll them in drug 
studies.
    Holland's sentencing had been scheduled to take place in May, but 
was delayed as federal prosecutors and his attorney have made formal 
arguments about what punishment he should face. A new sentencing date 
has not been set.
    ``This crime was committed over a 3-year period, with many 
obviously altered documents involving a large number of cancer patients 
needing careful attention because of the gravity of their conditions,'' 
assistant U.S. Attorney Grant C. Jaquith wrote in a memorandum to U.S. 
District Senior Judge Frederick J. Scullin, Jr.
    Jaquith argues in court papers that the high number of victims and 
significant financial losses to the drug companies and Department of 
Veterans Affairs warrants a maximum prison term.
    Holland has placed blame for the scandal on Paul H. Kornak, 56, a 
former research coordinator at Stratton who posed as a doctor while 
advising patients and their families on life-or-death medical 
decisions. Kornak had a felony criminal record for lying on a medical 
license application when he was hired at Stratton. He never finished 
medical school and falsified his college transcripts to get there, 
records show.
    Kornak was sentenced in November 2005 to a 6-year prison term for 
his guilty plea to felony counts of mail fraud and negligent homicide 
in connection with the death of James J. DiGeorgio, a 71-year-old Air 
Force veteran from Brunswick.
    Another 64 veterans were harmed by the forgeries, which involved 
manipulating their medical backgrounds so they would qualify for drug 
studies that were lucrative for the hospital and had furthered the 
researchers' careers.
    Federal authorities claim the research violations took place over 
about 3 years, beginning in May 1999. But VA workers have said the 
cancer program's problems, including the endangering of patients, 
stretched back years and involved other researchers.
    Kornak blamed his actions on hospital officials, including Holland, 
claiming they urged him to enroll as many patients as possible in drug 
studies.
    Gaspar M. Castillo, Holland's attorney, has cast Holland as a 
victim of Kornak and blames hospital administrators who allowed Kornak 
to masquerade as a physician.
    ``The defendant assumed, and it was reasonable for him to have 
assumed, that the VA had conducted appropriate background checks of Mr. 
Kornak,'' Castillo wrote last month in a letter to Scullin. Holland's 
guilty plea in April 2007 has not derailed his medical career. He works 
for a cancer program at Archbold Medical Center in Thomasville, Ga.
    Holland and Kornak were fired by the hospital in 2002 after a 
private drug company investigator noticed problems with the medical 
records of patients. Authorities have never offered a clear motive for 
the forgeries.
    A Times Union investigation found that Stratton's cancer research 
program was the target of internal complaints dating to the mid-1990s. 
Hospital staffers said they were harshly retaliated against for warning 
hospital administrators as early as 1994 that cancer patients were 
being placed at risk and being enrolled in drug studies without signing 
consent forms indicating they knew the risks.
    Copyright 2008 Knight Ridder. All rights reserved. This material 
may not be published, broadcast, rewritten or redistributed.

                                 
      Prepared Statement of Hon. James B. Peake, M.D., Secretary,
                  U.S. Department of Veterans Affairs
    Chairman Filner, Congressman Buyer, members of the House Committee 
on Veterans' Affairs, good morning. Thank you for the opportunity to 
appear here today to discuss VA Cooperative Study Program No. 519, our 
pharmacy benefits management program, and our work in protecting the 
health and well-being of veterans who volunteer to participate in our 
research studies. We share a common goal; to provide the best 
healthcare available anywhere for our Nation's veterans; and all of 
VA's employees and volunteers work hard every day to ensure that this 
goal is met.
The Purpose of CSP-519
    For more than 60 years, VA's research program has improved lives 
through innovation and discovery. VA researchers played key roles in 
developing the cardiac pacemaker, the CT scanner, radioimmunoassays, 
and improvements to artificial limbs. The first liver transplant in the 
world was performed by a VA clinician investigator. Clinical trials 
established the effectiveness of new treatments for tuberculosis, 
schizophrenia and high blood pressure. The Seattle Foot allows people 
with amputations to run and jump.
    Recently, there have been questions and concerns with regard to VA 
research programs; in particular, with the VA Cooperative Study 
entitled ``Integrating Clinical Practice Guidelines for Smoking 
Cessation into Mental Health Care for Veterans with Post-traumatic 
Stress Disorder (PTSD)'' (CSP-519). This study is designed to determine 
whether integrating smoking cessation and PTSD therapies is more 
effective in stopping smoking than smoking cessation therapies 
delivered separately through a smoking cessation clinic, the usual way 
care is provided at VA.
    Entering patients into the study began in November 2004, and ended 
in December 2007. The patients who entered the study all had PTSD, and 
all wanted to quit smoking. Patients in the study were allowed to 
receive medications from their healthcare providers to help them quit 
smoking. This is not a drug study. In many cases, the drugs patients 
are taking are prescribed by healthcare providers who are not at all 
associated with the study. Whether or not patients were enrolled in 
this study, all prescribing decisions were made by healthcare providers 
in one-on-one consultations with their patients, with those providers 
deciding which approach was most likely to work for those patients.
    The study is being conducted at 10 medical centers, and 945 
patients have been enrolled in the study. Patients participating in the 
study were randomly assigned into one of two study arms, and they were 
equally divided between those receiving integrated smoking cessation 
and PTSD therapies and those receiving smoking cessation therapies 
delivered separately through a smoking cessation clinic. All smoking 
cessation medications that were FDA-approved and on the VA formulary 
were made available to providers in both arms. Every patient enrolled 
in the study signed an informed consent form.
    On June 20, 2008, VA's Chief Ethics in Health Care Officer provided 
me with her review of CSP-519. She concluded that the study aim is 
consistent with VA's mission to improve the health and well-being of 
veterans; the scientific design of the study was appropriate to address 
the research question and to yield useful data; the study does not 
expose patients to undue risk; the information about varenicline 
provided in the informed consent document was appropriate; the study's 
subject selection is appropriate; the study protocol adheres to ethical 
standards for privacy and confidentiality; the plan for monitoring the 
research is appropriate in terms of timeliness and thoroughness; the 
protocol reflects consideration and implementation of special 
safeguards to protect the rights and welfare of research subjects who 
may be vulnerable to coercion; and the remuneration offered for 
participation is modest, appropriate, and not coercive.
    On June 25, 2008, I asked for a comprehensive review of the study--
looking at whether protocols and safeguards were followed and met to 
ensure that our patients were receiving proper notice and quality care. 
I will discuss this in additional detail later in my remarks.
Importance of the Study
    Every year in the United States, smoking accounts for approximately 
440,000 deaths. Premature deaths from smoking rob more than 5 million 
years from the potential lifespan of those who have died. Forty years 
after the first Surgeon General Report outlined the health effects of 
smoking, smoking remains the leading cause of preventable death and 
disease in the United States. Smoking is a chronic, relapsing disorder, 
and even smokers who are highly motivated to quit may attempt to quit 
multiple times before they are finally successful.
    Between 33 percent and 45 percent of smokers will die of smoking-
related illnesses. The risk of dying from lung cancer is more than 23 
times higher among men who smoke cigarettes. Smoking is associated with 
at least 14 other types of cancers, including cancer of the stomach, 
oral cavity, pharynx, larynx, esophagus, pancreas, and nasal cavity.
    Cigarette smokers are 2-4 times more likely to develop coronary 
heart disease than nonsmokers. Smoking is also a major cause of 
cerebrovascular disease, chronic bronchitis, and emphysema, and is 
associated with gastric ulcers.
    Smokers who quit before the age of 50 cut their risk of dying in 
the next 15 years in half. Smokers who quit have a slower rate of 
decline in lung function and a lower incidence of bronchitis, emphysema 
and other respiratory conditions than persons who continue to smoke. 
Quitting smoking reduces the risk for further congestive heart disease 
morbidity and mortality. Smokers with cancer who continue smoking 
during treatment decrease treatment effectiveness, overall survival 
prognosis and quality of life, and increase the risk for new 
morbidities. Smoking itself has psychiatric consequences. A recent 
study on smoking and suicide (Bronsich, et. al., Smoking predicts 
suicidality: Findings from a prospective community study, in the 
Journal of Affective Disorders 108 (2008)) found that suicide ideation 
and suicide attempts were strongly associated with occasional and 
regular smoking and nicotine dependence, with odds ratios from 1.4 
suicides to 5.8 suicides among smokers to one among non-smokers.
    Studies have shown that individuals with PTSD are more than twice 
as likely to smoke as the general population. While the rate of smoking 
among VA enrollees in general is approximately 30 percent, (Miller, 
D.R., et al., Health Behaviors of veterans in the VHA: Tobacco use: 
1999 large health survey of VHA enrollees, VHA Office of Quality and 
Performance, 2001.) the rate of smoking among veterans with PTSD under 
VA care is 53 percent to 60 percent. (Beckham, JC et al, Prevalence and 
correlates of heavy smoking in Vietnam veterans with chronic 
posttraumatic stress disorder, Addictive Behaviors, September-October 
1997.; Beckham, JC et al, Smoking in Vietnam combat veterans with post-
traumatic stress disorder, Addictive Behaviors, September-October 
1997.) Veterans with PTSD are more likely to be heavy smokers and are 
only half as likely to quit as are smokers without PTSD in the general 
population. VA believes it is our responsibility to help this 
population and all veterans to quit smoking, and we are continually 
working to find ways to do so.
The Use of Medications in CSP-519
    CSP-519 is not a drug study. It is not a test of 
Chantix' or any other medication. The study was proposed, 
funded, and initiated before Chantix' ever came into 
existence. Instead, CSP-519 is a study comparing the effectiveness of 
two different methods for delivering standard, evidence-based 
treatments for tobacco use for veterans with PTSD. These treatments 
consist of behavioral counseling to stop smoking, which is required for 
study participation, plus recommended but optional medications for 
smoking cessation. Subjects could participate in the study without ever 
taking any medications for smoking cessation.
    It is important to note that all medications have possible side 
effects. Attempting to regulate body chemistry by using medicines can 
have both beneficial and harmful effects. Two people who take the same 
medicine can have very different experiences. Physicians must always 
assess the risk of side effects against the expected benefits of any 
medication.
    The side effects for any smoking cessation medication can be 
significant. Nicotine patches may cause headache, dizziness, 
lightheadedness, drowsiness, stomach upset, nausea or facial flushing. 
Patients wearing nicotine patches can experience more serious effects 
including breathing difficulties, chest pain, irregular heartbeat, 
nervousness, anxiety, tremors.
    Buproprion, marketed as Wellbutrin' or 
Zyban', can cause abdominal pain, constipation, decrease in 
appetite, dizziness, dry mouth, increased sweating, nausea or vomiting, 
trembling or shaking, trouble sleeping, weight loss, blurred vision, 
change in sense of taste, drowsiness, feeling of fast or irregular 
heartbeat, frequent need to urinate, unusual feeling of well-being, 
agitation, anxiety, tinnitus, skin rash, hives, itching, confusion, 
extreme distrust, hallucinations, seizure, and trouble concentrating. 
Overdoses can result in fast heartbeat, hallucinations, loss of 
consciousness, nausea, seizures, and vomiting. The FDA has required a 
``black box warning'' for Buproprion stating that the medication, like 
all antidepressants, may increase the risk of suicide in persons 
younger than 25.
    Varenicline, marketed as Chantix', has been described by 
``The Medical Letter'' publication as the most effective FDA approved 
smoking cessation medication available. During premarketing development 
of Chantix', more than 4500 individuals were treated with 
the drug. Side effects of varenicline based on this clinical trial 
include nausea, which is fairly common; headache, difficulty sleeping, 
and abnormal dreams. Rarer side effects include a change in taste, 
vomiting, abdominal pain, flatulence, and constipation.
    On November 20, 2007, the FDA issued an ``Early Communication'' 
based on post-marketing reports from users of the drug. In that 
message, they wrote that Pfizer, Inc., the manufacturers of 
Chantix', had recently submitted to FDA postmarketing cases 
describing suicidal ideation and occasional suicidal behavior among 
Chantix' users. They also wrote that ``Chantix'' 
role is not clear,'' and made several recommendations on more closely 
monitoring patients for behavior and mood changes.
    On February 1, 2008, FDA issued a ``Public Health Advisory'' 
notifying healthcare providers that there may be an association between 
Chantix' and serious neuropsychiatric symptoms. It asked 
that patients and providers be made aware of this finding and stated 
that it appeared ``increasingly likely'' there may be an association 
between Chantix' and serious neuropsychiatric symptoms. To 
date, FDA has not asked that varenicline be removed from the market; 
has not issued a ``black box warning'' for the medication; and the drug 
continues to be FDA-approved.
    Varenicline is one of approximately 62 FDA-approved drugs which, in 
their labeling, have been associated with or have concerns related to 
adverse effects that include suicidal ideation or suicidal behavior. 
These include a number of drugs with well-known brand names, including 
Neurontin', Topamax', Depakote', 
Sustiva', Cipro', Accutane', 
Lariam', Reglan', Provigil', 
Abilify', Clozaril', Zyprexa' and 
Risperdon'. If VA were to withhold these medications from 
our patients with mental health issues, we would have great 
difficulties in treating them at all.
    Approximately 6 million Americans have received prescriptions for 
varenicline. This figure includes 70,000 VA patients who have received 
prescriptions for varenicline since VA approved the drug in January 
2007 for its formulary. Nearly 33,000 VA patients are currently taking 
the medication. Approximately 6,500 patients now taking varenicline 
have been diagnosed with PTSD. 2,012 of the 70,000 patients who have 
taken varenicline, including 400 of those with PTSD, are veterans of 
Operation Enduring Freedom or Operation Iraqi Freedom.
    Two-hundred forty-one patients have been prescribed varenicline at 
some time during the course of the study, either by VA physicians or by 
physicians not associated with VA. As of June 25, 2008, VA is aware of 
40 study subjects who are currently taking this medication.
    A review of Serious Adverse Effect data among CSP-519 participants 
indicates that, from January 1, 2007 through June 25, 2008, of the 241 
patients prescribed varenicline, 75 had a total of 114 significant 
adverse effects. Nineteen of those seventy-five had 22 psychiatric 
significant adverse effects, including 11 patients who had 12 episodes 
of suicidal ideation. There was one suicide attempt in that group, and 
no suicide completions.
    Of the 704 patients who were not prescribed varenicline, between 
January 1, 2007 and June 25, 2008, 124 unique patients had 171 
significant adverse effects during the study. Twenty-eight of those 
patients had 36 psychiatric significant adverse effects, including 11 
patients who had 14 episodes of suicidal ideation. Four patients who 
were not prescribed varenicline attempted suicide, and one committed 
suicide. There was one intentional drug overdose, not yet classified as 
suicide. It is important to note that adverse effects occur during 
studies which are unrelated to the study itself. Throughout the entire 
course of the study, there were two deaths, unrelated to the study, in 
the group of patients taking varenicline. There were also 25 deaths in 
the group that did not take varenicline, which have not been analyzed.
    The patients participating in this particular study, or any VA 
study, are under the care of physicians who are closely monitoring and 
evaluating them and changing their treatment if necessary. The care of 
our patients is our number one concern whether the veteran is 
participating in a study or not.
Patient Awareness of Issues Related to Varenicline Use
    On the national level, VA quickly responded to FDA communications 
about varenicline. FDA's November ``Early Communication'' was 
distributed to all VA facilities the day after it was issued. Once VA 
received the preliminary message, we aggressively searched for events 
which might signal a problem among our patient population. This was 
done not only through an evaluation of the voluntary reporting of 
adverse drug events throughout our system, but also through the use of 
VHA's integrated medication databases to search for any potential 
safety issues.
    On January 18, 2008, VA issued guidelines to providers stating that 
varenicline ``should be reserved for veterans who have not been 
successful with nicotine replacement therapy and/or buproprion, or for 
whom buproprion is contraindicated.'' It also stated that before 
starting varenicline treatments, VA healthcare providers should educate 
veterans about the possibility of changes in behavior and mood, and 
they should be carefully monitored, and that veterans using varenicline 
should be warned that it can cause drowsiness and should use caution 
while driving or operating machinery.
    On February 24, 2008, after testing at three medical centers, VA 
provided updates for local medical centers to their prescription 
software. The updates provided additional labeling on prescriptions for 
varenicline. It stated ``Call your doctor immediately if you have 
mental/mood changes like confusion; new/worsening feelings of sadness/
fear; thoughts of suicide, or unusual behavior.'' By April 1, all VA 
facilities except one had completed this update. VA also provides 
patient medication information sheets on all new and renewed 
prescriptions. Information on those sheets was updated in the same way.
    Institutional Review Boards (IRBs) at all CSP-519 study sites were 
notified of the FDA ``Public Health Advisory'' on February 5. On 
February 13, the study coordinators sent all study leaders a new 
patient consent form for patients in the study to sign who were taking 
varenicline. They also sent a draft letter for patients informing them 
of the FDA's warning. The draft letter was written by a team of 
psychiatrists and psychologists who felt the issue of suicide should be 
discussed in a clinical setting, not a mass mailing, when patients 
reported to their study coordinators for regular follow ups. It did 
explicitly advise patients that they should inform their doctor or the 
study staff immediately if they noticed any changes in their mood or 
behavior, or if they would like to stop using the medication.
    The cover letter was never intended to serve as a stand-alone 
document that would duplicate the consent addendum, which was attached. 
Instead, the purpose of the cover letter was to provide a brief and 
concise introduction to the addendum--an addendum that explicitly 
listed all the potential side effects identified by the FDA's warning, 
including suicidal ideation and suicidal behavior.
    The timing of mailings of the letter and the consent form addendum 
were left to the individual IRBs. VA's agreement with study 
participants indicated that if any new specific information became 
available related to the study we would inform them, and study leaders 
felt that the FDA ``Public Health Advisory'' met that standard.
    This plan was formulated by the CSP-519 study team, which included 
a physician; a pharmacist; a psychologist; a social worker; and other 
representatives of the CSP Pharmacy Coordinating Center, the CSP 
Coordinating Center, and the study Chair's office. The plan was 
approved by the CSP Human Rights Office and the CSP-519 Executive 
Committee, and was overseen by the CSP-519 Data Safety Monitoring 
Board.
    Letters to patients were sent or hand-delivered between February 
and June. I am concerned about the time that elapsed at a number of 
study sites between the receipt of the letters and consent addendums by 
IRBs, and when they were received by veterans. I am also concerned 
about the lack of followup by study coordinators to ensure that their 
directions were carried out. There is a clear need for improved follow 
up in this area.
    Since March 2007, the VA Center for Medication Safety has monitored 
varenicline through national pharmacovigilance efforts such as 
collecting and analyzing spontaneous reports of adverse events. As a 
result of their data, FDA's Public Health Advisory, and the Federal 
Aviation Administration's banning of the use of varenicline in airline 
pilots and air traffic controllers, VA issued a National Pharmacy 
Benefits Management Services Bulletin on May 30 to all practitioners 
informing them of the new warnings. They also sent a Patient Letter for 
Formulary Leaders and Pharmacy Chiefs to provide to their patients. 
Following news reports on the issues at this hearing, I sent a letter 
June 20 to all 33,000 patients with a current VA prescription for 
varenicline, offering to find another way to help them quit smoking if 
they were concerned about taking varenicline or had experienced any 
side effects.
    VA has consistently and continually provided FDA with information 
on our experience with varenicline, and is continually looking for 
evidence to indicate whether its use should be continued in our patient 
population. To date, however, we have found no evidence that would 
cause us to discontinue the use of this drug in our patients. No other 
healthcare system approaches the vigilance VA has demonstrated in 
educating its providers and patients on the possible newly reported 
risks of varenicline. The care, treatment, and health of our patients 
is our number one concern. The research we do benefits them as well as 
patients throughout the world.
Safeguards and Protections in VA's Human Research Program
    VA research, done with patient consent, benefits veterans; all 
Americans; and all citizens of the world. VA gratefully acknowledges 
the contributions of veterans who volunteer to participate in our 
research and we take our responsibilities for their care very 
seriously. In the past 7 years alone, VA employees have authored or co-
authored more than 46,000 scientific articles. Nearly 900 were 
published in the most eminent of the Nation's scientific journals, 
including Science; the New England Journal of Medicine; and the Journal 
of the American Medical Association.
    VA's Cooperative Study Program (CSP) specializes in designing, 
conducting, and managing multi-site clinical trials and epidemiological 
research. These include studies establishing the cornerstone for 
hypertension treatment; the long term effects of coronary artery bypass 
surgery; a study showing that aspirin reduces deaths and heart attacks 
in patients with unstable chest pain; and a study demonstrating the 
efficacy of a shingles vaccine. Just last week, the New England Journal 
of Medicine published the latest CSP contribution, which compared 
intensive versus standard therapy in patients with acute renal failure. 
The VA Cooperative Studies Pharmacy Coordinating Center is ISO 9000 
compliant, and has received many awards for its effective management of 
clinical trials.
    VA policies and procedures in this area are among the best in the 
Nation. Every VA research facility must have an IRB, the local 
Committee charged with the oversight of all research activities 
involving the use of human subjects. IRBs must have at least five 
members with varied backgrounds to promote complete and adequate review 
of research activities; at least one member whose primary expertise is 
scientific and one whose primary expertise is non-scientific; and at 
least one member not otherwise affiliated with the VA medical center. 
No IRB may consist entirely of members of one profession.
    IRBs must approve, require modifications to, or disapprove all 
research activities. Before approval, they must determine that the 
following requirements are satisfied: risk must be minimized; there 
must be a reasonable risk to benefit ratio; subjects must be equitably 
selected; informed consent forms must be valid; the informed consent 
process for patients must be documented; safety must be monitored; 
privacy and confidentiality must be maintained; vulnerable subjects 
must be protected; conflicts of interest must be managed, reduced or 
eliminated; and investigators must meet education requirements for the 
protection of human subjects in research. All IRBs are required to 
fully document their activities.
    VA's CSP goes above and beyond what other organizations do in the 
area of human subjects protection through our Human Rights Committees, 
which determine whether protections of patients' rights and welfare in 
VA research studies are adequate. These Committees are composed of 
individuals from the community and VHA with the interest and background 
required to consider the ethical and legal issues involved in the 
participants of human subjects in research. They are also responsible 
for ensuring that patients' rights and welfare are protected during 
studies, and for talking directly to patients to ensure that human 
rights aspects of cooperative studies are receiving proper attention.
    VA has established numerous other safeguards for our patients in VA 
research studies. We are one of sixteen federal agencies who have 
adopted the Common Rule for the protection of human subjects in 
research. In 1999, we established an independent office of research 
compliance and assurance. This office was succeeded, in 2003, by the 
Office of Research Oversight (ORO), VA's primary office responsible for 
overseeing the responsible conduct of research throughout our system. 
In 2003, its first year of operations, ORO made 19 site visits to 
facilities. In 2004, that number increased to 22 visits; by 2007, it 
had tripled, to 67.
    In 2001, VA published a brochure to help veterans understand their 
rights as research volunteers and to decide whether they want to be 
research participants. This was followed, in 2003, by the publication 
of a handbook describing the procedures all our research facilities 
must use to implement our agreement to follow the Federal Policy for 
the Protection of Human Subjects.
    In addition, VA has developed a program to accredit all VA research 
programs by the Association for the Accreditation of Human Research 
Programs. In 2003, we required all VA employees involved in human 
research support programs (except secretaries) to undergo annual 
training in good clinical practice and the ethical principles of human 
research protection. More than 15,000 employees completed the training 
within 90 days of its establishment. Since 2003, we have created more 
than 15 different training programs in human research protection for 
our employees.
    Also, we have established a Central Institutional Review Board to 
preclude some of the variability we have seen in execution of multi-
site projects such as CSP-519.
Actions Underway
    Though VA research is regularly reviewed by many organizations, we 
have directed that each VA human subject protection program must seek 
accreditation through the Association for the Accreditation of Human 
Research Protection Programs. At present, 112 of 115 VA facilities 
conducting human subject research have submitted applications for 
accreditation to this organization; all will be reviewed by the end of 
Calendar Year 2008. Of these 112 facilities, 57 have already received 
full accreditation. In some cases, this supplants previous 
accreditations received from the National Committee for Quality 
Assurance (NCQA). VA leads all federal agencies in accreditation of 
human research protection programs.
    VA's National Research Advisory Council, which is composed of 
internationally recognized medical scientists, has consistently 
recognized VA's research program for its success in meeting its 
obligations to taxpayers and to veterans.
    While we have procedures and safeguards in place for the protection 
of our patients, I am committed to making sure we are doing everything 
we can on behalf of our Nation's veterans. On June 25 I directed the 
Under Secretary for Health to conduct four evaluations:
    First, I requested a comprehensive review of CSP-519, through VA's 
Office of Research Oversight, with results to be reported to me within 
30 days and with an action plan to address recommendations to be 
completed not more than 10 days later.
    Second, despite the fact that CSP-519 is not a drug study, I 
directed that there be Institutional Review Board reviews of all PTSD 
drug protocols in our system to ensure that there is appropriate 
sensitivity to the study population in the context of FDA alerts and 
warning. I also directed a review of the risks of medications that are 
likely to be used in the study population, and that there has been 
proper subject notification of associated risks. The Office of Research 
Oversight is to report results to me within 45 days, and the Under 
Secretary for Health will provide me with an action plan 10 days later.
    Third, I tasked the Office of Research and Development and the 
Office of Pharmacy Benefits Management to conduct a review of our 
adverse event reporting system to ensure that there is, in fact, timely 
reporting and analysis of data, and that the system supports the 
appropriate escalation of reporting and sensitive issues for subject 
safety. I expect their results within 20 days, with action plans 
provided 10 days later.
    And fourth, I required the Office of Pharmacy Benefits Management 
to review VHA's medication notification system to ensure the system's 
policies support timely communications to patients and providers, 
including those in research programs. Results here are to be reported 
within 20 days and action plans provided 10 days later.
    In addition, the Inspector General is investigating human subject 
protections in CSP-519 at the Washington VA Medical Center. He will 
testify on what he has learned later in this hearing. He and his staff 
have discussed his findings with me. I appreciate the speed with which 
he prepared his report, and have appreciated his consideration on 
clarification of some factual matters.
    I have tremendous sympathy for any veteran who has been distressed 
by reports about this study. At the same time, VA has an outstanding 
research program, and has been innovative in its ability to protect its 
research subjects. I commit to veterans, and to you, that I will be 
comprehensive and thorough in my investigations of how this study has 
been, and is being, conducted. I am determined that VA will remain a 
leader in the protection of human subjects and in veteran-centric 
research. Thank you again for the opportunity to discuss the important 
work we were doing for and with the help of veterans.






Department of Veterans Affairs
Memorandum
Date: June 23, 2008
From: Secretary (00)
Subj: Evaluation of Research
To:  Under Secretary for Health (10)
      1. In response to recent allegations I direct you to conduct 
evaluations of VHA Research and related support functions as outlined 
below:

          a. Part I: The Office of Research Oversight (ORO) will 
continue a comprehensive review of Cooperative Studies Protocol #519 
(Integrating Practice Guidelines for Smoking Cessation into Mental 
Health Care for Posttraumatic Stress Disorder [PTSD]) consistent with 
the plan outlined by the Chief Research Oversight Officer (see 
attachment). ORO should report results to me within 30 days. I expect 
an action plan to address ORO's recommendations within 10 days after 
the report has been completed;
          b. Part II: ORO will oversee Institutional Review Board 
reviews of all PTSD protocols to ensure there is: appropriate 
sensitivity to the study population in the context of FDA alerts and 
warnings; a review of the risks of medications likely to be used in the 
study population; and proper subject notification of associated risks. 
ORO should report results to me within 100 days. I expect an action 
plan to address those recommendations within 10 days of the report's 
completion;
          c. Part III: The Office of Research and Development (ORD) and 
the Pharmacy Benefits Management (PBM) Strategic Healthcare Group will 
conduct a review of the adverse event reporting system in 
investigational and clinical settings to ensure there is timely 
reporting and analysis of data and that the system supports the 
appropriate escalation of reporting and sensitivity issues for subject 
safety. The review should also address triggers for reporting or 
escalation of reporting. ORD should report results to me within 20 
days. I expect action plans to address the recommendations within 10 
days afterward; and
          d. Part IV: The PBM will conduct a review of the Veterans 
Health Administration medication notification system to ensure that the 
system's policies support timely communication to patients and 
providers, including those in research programs. Recommendations from 
the review will be coordinated with Operations, ORO and ORD to ensure 
policy coordination. PBM should report results to me within 20 days. I 
expect an action plan and revised policy to be completed within 10 days 
of the report.

      2. If you have any questions about these tasks, please let me 
know.
                                               James B. Peake, M.D.
    Attachment

                                 
            Prepared Statement Paul Seligman, M.D., M.P.H.,
         Associate Director of Safety Policy and Communication,
         Center for Drug Evaluation and Research, Food and Drug
      Administration, U.S. Department of Health and Human Services
INTRODUCTION
    Mr. Chairman and Members of the Committee, I am Dr. Paul Seligman, 
Associate Director of Safety Policy and Communication in the Center for 
Drug Evaluation and Research (CDER) at the Food and Drug Administration 
(FDA or the Agency), which is part of the Department of Health and 
Human Services (HHS). I am accompanied today by Dr. Robert Temple, 
Director of the Office of Medical Policy in CDER. We are pleased to be 
here today to discuss FDA's role in identifying and communicating about 
drug safety issues, as well as our role in the protection of human 
subjects. In my testimony, I will first discuss the importance of FDA 
drug regulation, including several new initiatives to improve the drug 
safety system. I will then discuss how the Agency manages drug safety 
issues and informs the public when drug safety concerns arise. Lastly, 
I will discuss FDA's role with respect to protection of human subjects.
THE VALUE OF DRUG REGULATION
    FDA promotes public health through the regulation of prescription 
and over-the-counter drugs, which are an increasingly critical 
component in improving the health of many Americans.
    FDA's responsibilities for oversight of the entire life cycle of 
drugs--from premarket drug testing and development through drug 
approval, postmarket surveillance, and risk management--have never been 
more important. FDA continuously seeks to provide the means for 
translating new scientific advances into benefits for patients (for 
example, biomarkers and pharmacogenomics), take advantage of new ways 
to monitor the performance of marketed drugs, and communicate this 
information to healthcare professionals and patients to help ensure the 
safe use of drugs.
    One aspect of assuring the most appropriate use of marketed drugs 
is to study them carefully before approval. FDA's drug review process 
is recognized worldwide as the gold standard, and we actively monitor 
the scientific bases for our processes to ensure that they reflect 
advances in medical science. FDA approves drugs after they undergo 
comprehensive safety evaluations. It is not always recognized, but at 
least half of the effort by FDA's premarket reviewers is dedicated to 
the assessment of safety. Major changes have taken place in how drugs 
are evaluated, including a complete evaluation of their metabolism, 
their interactions with other drugs, and potential differences of 
effectiveness or safety in people of different genders, ages, and 
races. In addition, FDA staff perform systematic assessments of safety 
that yield comprehensive reviews, focusing on the potential problems 
with the greatest clinical importance.
    The other critical aspect to assuring the most appropriate use of 
marketed drugs is the process FDA has in place to assess drugs after 
they are approved. FDA grants approval to drugs after sponsors 
demonstrate that the drugs meet the Federal Food, Drug, and Cosmetic 
(FD&C) Act's standard for safety and efficacy. However, no amount of 
premarket study can provide all of the information about effectiveness 
or all the risks of a new drug when it is used by the general 
population in the myriad ways not studied during clinical trials. As a 
result, FDA's postmarket drug safety program plays an essential role by 
collecting and assessing information about adverse events and 
medication errors identified after approval. A key role of our 
postmarket safety system is to detect serious unexpected adverse events 
and take definitive action when needed.
NEW INITIATIVES TO IMPROVE DRUG SAFETY
    Within the last year, FDA has launched several new initiatives to 
ensure drug safety. Outlined below are some examples.
Food and Drug Administration Amendments Act of 2007 (FDAAA)
    As you know, in September 2007, Congress passed FDAAA, which 
included new resources for medical product safety and new regulatory 
tools and authorities to ensure the safe and appropriate use of drugs. 
For example, under Title IX--Enhanced Authorities Regarding Postmarket 
Safety of Drugs, FDA can require drug sponsors to make certain safety-
related labeling changes and conduct postmarketing studies and clinical 
trials instead of relying on voluntary actions. In addition, under 
FDAAA, if FDA determines that a risk evaluation and mitigation strategy 
(REMS) is necessary to ensure that the benefits of a drug outweigh the 
risks of the drug, FDA can require manufacturers to submit a REMS when 
a drug comes on the market, or later if FDA becomes aware of new safety 
data.
Sentinel Initiative
    FDAAA requires the HHS Secretary to develop methods to obtain 
access to disparate data sources and to establish a postmarket risk 
identification and analysis system to link and analyze healthcare data 
from multiple sources. On May 22, 2008, FDA launched the Sentinel 
Initiative with the ultimate goal of creating and implanting the 
Sentinel System--a national, integrated, electronic system for 
monitoring medical product safety. The Sentinel System will strengthen 
FDA's ability to ensure that safe and effective new drugs are available 
as quickly as possible and that marketed drugs remain safe and of the 
highest quality.
Action Plan for Import Safety
    Another critical aspect to drug regulation is the safety of 
products imported into the United States. On November 6, 2007, 
Secretary Leavitt presented to President Bush the ``Action Plan for 
Import Safety'' completed by the Interagency Working Group on Import 
Safety. The Import Action Plan presents broad recommendations and 
specific short- and long-term action steps, categorized under the 
organizing principles of prevention, intervention, and response. On 
July 1, 2008, FDA issued the ``Import Safety--Action Plan Update.'' The 
update outlines the significant progress FDA has made and the key steps 
that are planned for the future to enhance the safety of imported 
goods. Thus far, FDA has taken strong enforcement actions, signed 
agreements with key trading partners, hosted bilateral and multilateral 
discussions, shared critical information on safety and best practices, 
and began a process to improve safety practices, both inside and 
outside of government.
    Prevention. FDA is seeking to ensure that imported drug products 
are safe and effective prior to reaching U.S. ports of entry. FDA is 
pursuing this goal by maximizing foreign product pre-approval 
inspections, increasing FDA presence in China, increasing FDA 
inspections, increasing the sharing and use of foreign competent 
authority inspection reports and other information, developing plans to 
use third-party certification, and increasing capacity building with 
countries that have less developed regulatory systems to ensure product 
safety.
    Intervention. FDA recognizes the importance of a strong and 
effective intervention capacity to identify problems as they occur. FDA 
has several plans to enhance its Information Technology systems in ways 
that will enable the Agency to better utilize risk-based information 
from the entire life cycle of imported products. FDA is expanding 
laboratory capacity and developing rapid test methods for detection of 
pathogens and other contaminants in drugs, and ensuring that these test 
methods are available at ports of entry to assist in determining 
whether a product should be admitted into the United States. In 
addition to increasing pre-approval inspections, FDA is increasing 
surveillance inspections, as well as determining which manufacturing 
facilities may pose a risk to the American consumer. The Import Action 
Plan also outlines several action steps intended to help ensure that 
domestic companies importing foreign source material meet their 
responsibility to import safe and effective medical products. FDA 
inspects all facilities listed in a drug application, both foreign and 
domestic, to determine if they meet the Agency's quality standards. 
During these inspections, FDA routinely evaluates the domestic drug 
manufacturer's testing and controls of ingredients (domestic and 
foreign-sourced) and supplies. If deficiencies are discovered, FDA may 
take enforcement action.
    Response. FDA must be ready to take immediate action when a health 
threat emerges with any FDA-regulated product. The Import Action Plan 
calls for increased FDA and U.S. Customs and Border Protection (CBP) 
cooperation, including developing interdepartmental procedures for 
clearing and controlling shipments at ports of entry, co-locating FDA 
and CBP at locations to improve coordination and efficient use of 
resources, and increasing import information sharing between FDA and 
CBP through new technology applications. FDA is also working to 
facilitate the adoption of track-and-trace technologies to identify and 
track a product along the product life cycle. These technologies will 
facilitate the timely recovery of the violative product and reduce the 
opportunity for harm, as well as secure the integrity of the supply 
chain by providing an ``e-pedigree''--an electronic record documenting 
that the drug was manufactured and distributed under secure conditions.
HOW FDA MANAGES DRUG SAFETY ISSUES
    Once FDA approves a drug, the postmarket monitoring stage begins. A 
drug manufacturer is required to submit regular postmarketing reports 
to FDA on its drug. These reports include critical information about 
adverse events associated with the use of one or more drugs. Reports 
are submitted in an expedited fashion for serious and unexpected risks, 
and periodically for less urgent safety issues. Manufacturers submit 
several other types of postmarketing reports, including new clinical 
trial results. Also during this period, we continuously receive adverse 
event reports directly from sources, such as healthcare professionals 
and patients, through our MedWatch program. Stored in a computerized 
database, these reports are reviewed and analyzed by FDA 
epidemiologists and safety evaluators to assess the frequency and 
seriousness of the adverse events and to determine their causes. An 
adverse event may occur because of simple or complex reasons, including 
drug exposure, an interaction between one or more drugs, other 
therapies, environmental factors, an individual's characteristics, and 
underlying diseases. Our response to information from this ongoing 
surveillance depends on an evaluation of the aggregate public health 
benefits of the product compared to its evolving risk profile.
    Decisions about regulatory action in response to evidence of a drug 
safety risk are complex, taking into account many factors. As more 
becomes known about the potential risks or benefits of a drug, often 
its FDA-approved labeling will be revised so that it better reflects 
information on appropriate use. For example, FDA may seek revisions to 
a drug's labeling to add information on adverse reactions not 
previously listed, to add new warnings describing conditions under 
which the drug should not be used, or to add new precautions advising 
doctors of measures to minimize risk. If labeling alone is inadequate 
to manage risks, additional actions may include revising drug names or 
packaging, issuing ``Dear Healthcare Professional'' letters (sometimes 
referred to as ``Dear Doctor'' letters), educational/special risk 
communications, requiring restricted distribution programs, or 
withdrawing a drug's approval.
HOW FDA COMMUNICATES ABOUT DRUG SAFETY ISSUES
    FDA uses a broad range of methods to communicate drug safety 
information to the public. Certain forms of communication are targeted 
to specific audiences (e.g., healthcare professionals or patients). 
Others are directed at more than one group to ensure widespread 
dissemination of information about important drug safety issues, 
including emerging drug safety issues. FDA continuously evaluates its 
communication efforts and modifies them to enhance their accessibility 
and effectiveness. We welcome public comment at any time suggesting 
ways to improve our safety communications. The different types of drug 
safety communications are described in more detail below.
    Labeling. FDA-approved drug product labeling is the primary source 
of information about a drug's safety and effectiveness, and it 
summarizes the essential scientific information needed for the safe and 
effective use of the drug. Compliance with the recently issued 
physician labeling rule for prescription drugs is expected to further 
enhance the usefulness of product labeling and further facilitate the 
safe and optimal use of prescription drugs.
    Labeling for prescription drug products is directed to healthcare 
professionals but may include patient counseling information as well. 
For some prescription drugs, such as oral contraceptives and estrogens, 
FDA determined several years ago that the safe and effective use of 
these drugs required additional labeling in nontechnical language be 
distributed directly to patients by their healthcare professional or 
pharmacist (Title 21 of the Code of Federal Regulations (CFR) 310.501 
and 310.515). FDA-approved patient labeling also may be provided by 
manufacturers for other drugs.
    Early Communications about Ongoing Safety Reviews. Since August 
2007, FDA has issued Early Communications about Ongoing Safety Reviews 
(ECs) to keep healthcare professionals and the general public informed 
of postmarket safety issues that are currently being evaluated by FDA. 
ECs are issued at the beginning of FDA's assessment, prior to 
conclusive determination of the clinical or public health significance 
of the information under evaluation and before a decision has been made 
about what regulatory actions, if any, should be taken. Rather, they 
reflect FDA's current analysis of available data concerning these 
drugs, but posting the information as an EC does not mean that FDA has 
concluded there is a causal relationship between the drug and the 
emerging safety issue. It also does not mean that FDA is advising 
healthcare professionals to discontinue prescribing these products. In 
general, ECs have included a timeframe for when FDA anticipates 
completing the safety review and providing followup.
    Public Health Advisories. FDA issues Public Health Advisories 
(PHAs) to provide information regarding important public health issues 
to the general public, including patients and healthcare professionals. 
For example, PHAs may highlight important safety information, inform 
the public about the completion of FDA's evaluation of an emerging drug 
safety issue, announce the implementation of methods to manage the 
risks identified for a marketed drug, or provide other important public 
health information.
    PHAs regularly include recommendations to mitigate a potential risk 
and often are issued in conjunction with other drug safety 
communications, such as Healthcare Professional Sheets. PHAs related to 
drugs are available through the CDER Web site and disseminated via the 
MedWatch Partners Program.
    Healthcare Professional Sheets. FDA issues Healthcare Professional 
Sheets, which provide a summary of important and often emerging drug 
safety information for a particular drug or drug class. Healthcare 
Professional Sheets begin with a summary ``Alert'' paragraph, followed 
by more detailed sections explaining the ``Alert,'' including clinical 
considerations or recommendations for the healthcare professional, 
information that patients should be made aware of and discuss with 
their healthcare professional, a summary of the data that were the 
basis for the recommendations, and, when applicable, implications of 
the ``Alert.''
    Healthcare Professional Sheets are intended to provide adequate 
factual information to address potential questions from patients and 
facilitate a healthcare professional's consideration of the drug safety 
issue. As with the PHAs, FDA continues to collect input on the 
usefulness of these communications through a variety of feedback 
mechanisms, and anticipates that healthcare professional communications 
will continue to evolve.
    Other Methods of Communication. FDA continues to explore other 
methods of making its written communications more effective, as well as 
the use of other media such as podcasts, video broadcasts and 
conference calls, to disseminate drug safety information.
    Sponsors also use various methods to communicate drug safety 
information. For example, a sponsor may distribute a ``Dear Healthcare 
Professional'' letter to convey important information regarding a 
marketed drug. ``Dear Healthcare Professional'' letters may be used to 
disseminate information regarding a significant hazard to health, 
announce important changes in product labeling, or emphasize 
corrections to prescription drug advertising or labeling.
    To summarize, FDA has a critical role in the detection and 
management of safety issues that are identified after a drug is 
approved, including a critical role in communicating information to the 
public. The actions taken depend on the characteristics of the adverse 
events, the frequency of the reports, the seriousness of the diseases 
or conditions for which the drug provides a benefit, the availability 
of alternative therapies, and the consequences of not treating the 
disease. Our goal, regardless of the communication tool employed, is to 
make the most up-to-date drug safety information available to the 
public in a timely manner so that healthcare professionals and patients 
can consider the information when making decisions about medical 
treatment and be aware of uncertainties in the data. The Agency is 
committed to providing accurate, clear, reliable, and useful drug 
safety information.
FDA'S ROLE WITH RESPECT TO PROTECTING HUMAN SUBJECTS
    The FD&C Act and its implementing regulations are one part of a 
complex system of safeguards designed to protect human subjects. 
Several groups play key roles in the clinical research of products 
subject to FDA regulation--the company that sponsors the research, the 
clinical investigator who conducts the research, the Office of Human 
Research Protection within HHS, when the clinical investigation is 
federally funded, and the Institutional Review Board (IRB) that has a 
role in protecting the rights and welfare of the patients who are 
taking part in clinical investigations. For example, investigators must 
sign an FDA-Form 1572, committing to comply with their regulatory 
obligations, and IRBs are subject to detailed rules in 21 CFR part 56. 
FDA is responsible for regulating the activities of sponsors, 
investigators, IRBs and others involved in a clinical trial. We take 
very seriously our role to protect patients enrolled in clinical 
trials. It should be appreciated, however, that, while a broad set of 
protections are built into the law and regulations, the professional 
and ethical conduct of the parties involved in clinical research is 
crucial to the protection of human subjects.
CONCLUSION
    At FDA, assuring the safety and effectiveness of medical products 
for the American people is one of our core responsibilities. Working 
with patients, physicians, pharmacists, industry, and State regulators, 
FDA plays a critical role in the detection and management of drug 
safety issues, by helping to ensure the safe use of marketed drugs by 
providing the best possible information to the American public. We also 
take our role in the protection of human subjects very seriously; 
working with many other partners to assure that clinical trials are 
conducted appropriately.
    Once again, thank you for the opportunity to testify before the 
Committee today. We are happy to respond to questions.

                                 
            Prepared Statement Ponni Subbiah, M.D., M.P.H.,
       Vice President, Medical Affairs, Pfizer Inc., New York, NY
    Good morning Mr. Chairman, Ranking Member Buyer and Members of the 
Committee.
    My name is Ponni Subbiah. I am a medical doctor and a Vice 
President in Medical Affairs at Pfizer. I am responsible for the 
medical and scientific activities for products in the Urology/
Respiratory area, which includes Chantix. On behalf of Pfizer, thank 
you for the opportunity to speak with you today. I would like to 
briefly address the following areas: the global epidemic of tobacco 
addiction and its impact on public health; the role of Chantix in 
helping patients stop smoking; the clinical trial process at Pfizer; 
how Pfizer monitors drug safety; and, finally, the recent updates to 
the Chantix label.
    The World Health Organization has described tobacco use as the 
leading preventable cause of death. Worldwide, approximately 1.3 
billion people currently smoke cigarettes.\1\ In the U.S. alone, more 
than 438,000 deaths are attributable to smoking each year.\2\ More 
people die from smoking annually than inhabit the city of Miami, 
Florida.\3\ In fact, cigarette smoking is a risk factor for six of the 
eight leading causes of death in the world--including heart disease, 
stroke, lung disease such as emphysema, tuberculosis, and lung 
cancers.\1\ Health care costs from smoking-attributable diseases are 
$75.5 billion annually as per the 2004 Surgeon General's report.\4\
    It is important to understand that, for most people, smoking is not 
a lifestyle choice or habit, but rather an addiction to nicotine. 
Nicotine is a highly addictive drug--as addictive as heroin or cocaine. 
Smokers become physically and psychologically dependent on nicotine. 
Less than 7 percent of smokers are able to quit on their own.\5\ 
Therefore, medications and other therapeutic options are needed to 
assist smokers who are motivated to quit. Quitting smoking, with or 
without treatment, is associated with nicotine withdrawal symptoms, 
which are both physical and mental and may include irritability, anger, 
depressed mood and weight gain. Quitting smoking has also been 
associated with the exacerbation of underlying psychiatric 
illnesses.\6\ It is important to assess the benefits and risks of 
smoking cessation treatments in the context of this setting.
    In the United States, currently 20.8 percent of the population in 
general smoke cigarettes.\7\ By comparison the smoking rate in the VA 
population is 33 percent.\8\ Of interest to this hearing, there is a 
strong link between smoking and a range of psychiatric disorders. A 
study by Harvard Medical School showed that 35-41 percent of people 
with mental illness smoke.\9\ Smoking prevalence rates are 50-70 
percent \10,11\ in patients with major depression and over 80 percent 
in patients with schizophrenia.\11\ The smoking rate in post traumatic 
stress disorder (PTSD) patients ranges from 45-60 percent.\12,13\
    Chantix' is the first non-nicotine based medicine 
developed specifically for smoking cessation and the first prescription 
aid to smoking cessation approved by the FDA in nearly a decade. It is 
currently approved in 74 countries and is designed to bind at the same 
receptor in the brain as nicotine, which allows it to reduce the urge 
to smoke, while at the same time blocking the effects of nicotine.\14\ 
Chantix' has been demonstrated to be more efficacious than 
placebo and Zyban (another popular smoking cessation treatment) in two 
clinical trials. To date, Chantix' has been prescribed to 
approximately 7.5 million patients worldwide, 5.6 million of those in 
the U.S.
    Chantix' is not a treatment that is used over a 
prolonged period of time. Rather, physicians should prescribe 
Chantix' for 3 months for their patients who wish to quit 
smoking. For those patients who successfully quit with 
Chantix' by the end of the 3 months, an additional 3 months 
of Chantix' is recommended to help them remain smoke 
free.14
    Chantix' was studied in a comprehensive clinical trial 
program involving more than 5,000 patients over a span of 10 years. The 
studies conducted during development of a drug for approval are done in 
order to fully characterize the unique properties of a medicine. The 
FDA will approve a medicine for use only when its benefits outweigh the 
risks. Even after a medicine enters the market, and throughout the 
lifecycle of the product, Pfizer strives to enhance its knowledge 
regarding the safety and efficacy of its products through ongoing 
research in order to continually assess the benefit/risk profile. This 
includes information not only on risks but also on the important 
benefits that these medicines may have, especially in specific 
subpopulations. The benefits and risks that need to be considered will 
vary between different disease areas as well as between individual 
patients. Thus, consideration of benefits and risks of medicines is a 
critical component of the dialog that needs to occur between patients 
and their doctors.
    Gathering data to continuously inform the benefit/risk assessment 
is accomplished through various means, including conducting clinical 
trials and epidemiological studies. Gathering this information requires 
Pfizer to work with outside researchers in a variety of ways such as 
getting scientific input and involving external experts in Pfizer's 
clinical study program for a medicine. When clinical trials are 
conducted, there are various mechanisms in place designed to protect 
patients from harm. These include independent Institutional Review 
Boards (IRBs), which are designed to assure that appropriate steps are 
taken to protect the rights and welfare of patients. Patients must also 
give their informed consent prior to participating in a study.
    Prior to a medicine's approval, Pfizer is the sponsor of, and 
responsible for, the clinical trials involving the medicine. The 
company contracts with independent researchers to conduct studies 
according to international standards and FDA's good clinical trial 
practice (GCP) regulations. After the medicine is approved, there may 
be studies done that are not sponsored by Pfizer, but may be supported 
by the company through the provision of grant funding or free supplies 
of Pfizer medicines for independent investigator research (IIR) to 
advance scientific knowledge and understanding. However, Pfizer is not 
involved in the design, conduct or publication of an IIR study.
    There are also clinical trials of Pfizer medicines, such as the 
trial that is the subject of this hearing, that are conducted 
independently of Pfizer. Once a medicine is available on the market, 
any researcher can obtain the medicine and conduct studies without the 
involvement of Pfizer. These studies may be funded from non-Pfizer 
sources such as academic institutions or the NIH.
    The Pfizer drug safety surveillance system is designed to 
continuously gather and analyze reports received about patient 
experiences with our products after they have become available in the 
market. These adverse event reports are routinely shared with the FDA 
and other regulators as required. Based on clinical study data and 
post-marketing reports, we work with regulators on a continuing basis 
to effectively communicate to patients and healthcare professionals any 
change in the benefit/risk profiles of our medicines. The primary 
mechanism of communicating changes in a medicine's benefit/risk profile 
is the product labeling. It is common for the label to be revised 
numerous times in a product's lifecycle. In fact, in 2007 there have 
been over 500 FDA approved safety related labeling changes across 
various prescription medicines in the U.S. Pfizer's primary goal is to 
communicate to both physicians and patients what is known about the 
benefits and risks so that doctors and patients can decide together 
whether a particular medicine is the best treatment option.
    With regard to Chantix', there have been adverse event 
reports of certain neuropsychiatric symptoms, including depressed mood, 
agitation, changes in behavior, thoughts of suicide and suicidal 
behaviors, in patients attempting to quit smoking with 
Chantix'. The report of an adverse event does not 
necessarily mean there is a causal relationship between the product and 
the event and, in the case of Chantix', a causal 
relationship between these reports and the use of Chantix' 
has not been established. However, in some reports related to 
Chantix', a causal relationship could not be excluded. In 
November 2007 Pfizer worked with the FDA to update the 
Chantix' label to reflect these reports. Additional label 
updates were made in January and May 2008, respectively, to put this 
information in the Warnings section of the label to heighten awareness 
and to provide further guidance to physicians and patients about these 
symptoms. The current label advises that a patient should stop taking 
Chantix' and contact their healthcare provider immediately 
if agitation, depressed mood, or changes in behavior that are not 
typical for them are observed or if the patient develops suicidal 
ideation or behavior.
    Pfizer communicated these label updates to physicians, study 
investigators and other healthcare professionals through various routes 
including product labeling, written communications, Web site updates 
(e.g. PfizerPro.com, Chantix.com) and communications from our sales 
representatives. Patients have access to this information through their 
healthcare provider as well as through the Chantix' Web site 
(Chantix.com).
    Pfizer reviews the benefit/risk profile of all our products, 
including Chantix', on a continuing basis. Based on our 
review of the available safety information, including the adverse event 
reports received to date, we believe the Chantix' label 
accurately reflects the product's efficacy and safety profile, thereby 
facilitating appropriate use by physicians and patients. In particular, 
full awareness and understanding by both physicians and patients of the 
neuropsychiatric symptom related labeling, highlights the key role that 
doctors and patients can play in managing and mitigating the potential 
risks, so that the important benefits of Chantix' as an aid 
to smoking cessation can be realized when appropriate.
    There are few things that provide greater health benefits than 
quitting smoking. Patients who smoke cigarettes should be encouraged to 
seek support from a healthcare professional and counseled to quit. 
Health care providers should discuss the risks of smoking, the health 
benefits of quitting smoking, and the benefits and risks of available 
treatment options including Chantix'. It has been reported 
that nearly 70 percent of smokers want to quit, although as indicated 
earlier, fewer than 7 percent of those who try are able to quit on 
their own.\5\ Given the devastating health effects of smoking, it is 
essential to have treatment options available to help smokers break 
free of nicotine addiction and stop smoking.
    Thank you. I look forward to answering any questions you may have.
References
    1. World Health Organization. WHO Report on the Global Tobacco 
Epidemic, 2008: The MPOWER package. Geneva: WHO; 2008.
    2. Centers for Disease Control and Prevention. Annual Smoking-
Attributable Mortality, Years of Potential Life Lost, and Productivity 
Losses--United States, 1997-2001. MMWR. 2005;54(25):625-628.
    3. U.S. Census Bureau. Annual Population Estimates 2000 to 2007. 
2007.
    4. Centers for Disease Control and Prevention. Smoking-attributable 
mortality, morbidity, and economic costs (SAMMEC): adult and maternal 
and child health software. Atlanta, GA: U.S. Department of Health and 
Human Services, CDC; 2004.
    5. National Institute on Drug Abuse. Nicotine Addiction. NIH 
Publication 01-4342. Bethesda, MD: National Institute on Drug Abuse; 
2001.
    6. American Psychiatric Association. Diagnostic and Statistical 
Manual of Mental Disorders, 4th Ed, Text Revision (DSM-IV-TR). 
Washington, DC; 2000.
    7. Centers for Disease Control and Prevention. Cigarette smoking 
among adults--United States, 2006. MMWR. Nov 9 2007;56(44):1157-1161.
    8. McKinney WP, McIntire DD, Carmody TJ, Joseph A. Comparing the 
smoking behavior of veterans and nonveterans. Public Health Rep. May-
Jun 1997;112(3):212-217; discussion 218.
    9. Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, 
Bor DH. Smoking and mental illness: A population-based prevalence 
study. JAMA. Nov 22-29 2000;284(20):2606-2610.
    10. George TP, Krystal JH. Comorbidity of psychiatric and substance 
abuse disorders. Current Opinion in Psychiatry. 2000;13(3):327-331.
    11. Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA. Prevalence 
of smoking among psychiatric outpatients. Am J Psychiatry. Aug 
1986;143(8):993-997.
    12. Beckham JC, Kirby AC, Feldman ME, et al. Prevalence and 
correlates of heavy smoking in Vietnam veterans with chronic 
posttraumatic stress disorder. Addict Behav. Sep-Oct 1997;22(5):637-
647.
    13. Fu SS, McFall M, Saxon AJ, et al. Post-traumatic stress 
disorder and smoking: a systematic review. Nicotine Tob Res. Nov 
2007;9(11):1071-1084.
    14. Chantix' (varenicline) [U.S. prescribing 
information]. New York, NY: Pfizer, Inc.; May 2008.

                                 
           Prepared Statement John D. Daigh, Jr., M.D., CPA,
        Assistant Inspector General for Healthcare Inspections,
    Office of Inspector General, U.S. Department of Veterans Affairs
    Mr. Chairman and Members of the Committee, thank you for the 
opportunity to testify today on whether the Veterans Health 
Administration (VHA), Department of Veterans Affairs (VA), protected 
human research subjects appropriately following notification from the 
Food and Drug Administration (FDA) of potentially harmful effects 
associated with the drug varenicline (Chantix'). 
Accompanying me today is Dr. Andrea Buck and Mr. Randall Snow.
    Chantix' is a medication approved by FDA for use in 
helping patients to quit smoking. Concerns involving the use of 
Chantix' escalated following an incident reported in the 
media in which a veteran taking Chantix' while enrolled in a 
VHA research study at the Veterans Affairs Medical Center, Washington, 
DC (VAMCDC) allegedly experienced an episode of agitated and/or 
aggressive behavior.
    To address concerns regarding the use of Chantix', we 
focused our review on issues of informed consent, patient notification 
of potential adverse effects associated with Chantix', and 
the tracking and reporting of adverse events occurring during the 
course of the research study. The scope of our review was limited to 
the VAMCDC. Our first site visit to VAMCDC was on June 19, 2008. While 
conducting our inspection, we received allegations of potential 
inappropriate documentation, which we also reviewed.
    The Office of Inspector General initiated this review in response 
to requests from this Committee and other Members of Congress. My 
statement today is based on the results of our review, which have been 
provided to VHA in a draft report for comment. Until we receive VHA's 
official response and issue the final report, our findings are subject 
to further clarification.
BACKGROUND
    The VHA research study enrolling the veteran compared the 
effectiveness of smoking cessation treatment administered by mental 
health providers to that administered by primary care providers in 
patients with post-traumatic stress disorder (PTSD); it will hereafter 
be referred to as ``the smoking cessation study'' or ``the study.''
    The protocol, a written document describing the method for 
conducting the smoking cessation study, stated that patients assigned 
to mental health providers for their smoking cessation therapy would 
receive medications for smoking cessation unless contraindications 
existed. While Chantix' was not available when this research 
study began in 2004, the protocol was modified on January 17, 2007, to 
include circumstances under which Chantix' could be used. 
Specifically, the protocol indicated that Chantix' would be 
provided, ``at the discretion of prescribing clinicians for subjects 
who cannot tolerate or who have failed adequate trials of other smoking 
cessation medications.'' Subjects enrolled were required to have the 
diagnosis of PTSD and to be actively receiving treatment for that 
disorder. Subjects could not be enrolled if they had a psychotic 
disorder not in remission, were at imminent risk for suicide or 
violence, or had severe psychiatric symptoms.
    The Cooperative Studies Program (CSP) provided us with a list of 10 
\1\ different VA medical centers which enrolled patients receiving 
Chantix' in this smoking cessation study. The various sites 
were overseen by the Cooperative Studies Program (CSP), a VHA program 
designed to coordinate research occurring at multiple facilities. CSP 
maintains five coordinating centers, a clinical research pharmacy, four 
epidemiological research and information centers, and a health 
economics resource center. The coordinating centers provide statistical 
and methodological guidance to VA researchers involved in clinical 
trials. CSP trials have resulted in numerous important contributions to 
research, including demonstrating the efficacy of a vaccine for 
shingles and coordinating multiple trials involving cardiovascular 
treatments that resulted in major innovations in the treatment of 
hypertension and coronary artery disease.
---------------------------------------------------------------------------
    \1\ Houston, Hampton, Minneapolis, New Orleans, Philadelphia, 
Portland, Providence, San Diego, Tuscaloosa, and Washington, DC.
---------------------------------------------------------------------------
    The research protocol in question utilized the Palo Alto CSP 
Coordinating Center (the Coordinating Center). The Coordinating Center 
received all study data from the sites. It forwarded information 
pertaining to serious adverse events (SAEs) to the Albuquerque Pharmacy 
Coordinating Center. In an e-mail of June 20, 2008, CSP reported that 
as of June 18, 2008, there were 158 subjects nationwide who had 
received Chantix' while enrolled in the research study. This 
CSP data was based on self-reporting by research subjects during the 
course of the study. VHA indicated that there is no single data source 
that can completely and accurately portray actual Chantix' 
use by those in this study. In addition, VHA reported to us that there 
was a total of 945 subjects in the study nationwide.
    CSP had also reported in the June 20, 2008, e-mail that 11 of the 
VAMCDC subjects received Chantix'. However, the senior 
researcher (also known as the senior investigator (SI)) conducting the 
smoking cessation study at VAMCDC informed us on June 19 (the date of 
our first onsite visit), that there were a total of 109 subjects in the 
study at VAMCDC and that 12 of those 109 subjects received 
Chantix'. Following chart review for these 12 subjects, we 
found that 1 patient had never actually taken Chantix'. 
Later, on June 27, 2008, the SI informed us of an additional 4 patients 
at VAMCDC who received Chantix' at some time during the 
course of the study; this made a total of 15 patients who received 
Chantix' as part of this study at VAMCDC. It is these 15 
patients whom we discuss throughout this report.
    VAMCDC is part of the VA Capitol Health Care Network (Veterans 
Integrated Service Network (VISN) 5). In addition to acute care 
services, it maintains a 120 bed long-term care unit and four Community 
Based Outpatient Clinics. It is affiliated with three medical schools 
and is a medical readiness partner with three Department of Defense 
facilities. The VAMCDC also has an active research program, with 70 
researchers and 185 active protocols as of June 27, 2008. It also 
maintains one of two VA War Related Illness and Injury Study Centers.
FDA Notifications Pertaining to Chantix
    The FDA approved Chantix' on May 10, 2006, as an aid for 
smoking cessation. During pre-marketing studies, more than 4,500 people 
received Chantix'. Recorded adverse psychiatric reactions 
included frequent anxiety, depression, emotional disorders, 
irritability, and restlessness. Initial product labeling did not 
include any warning regarding any suicidal ideation. VHA added the 
product to its National Formulary as a third line agent, following 
failure of nicotine replacement strategies and buproprion, another 
medication for smoking cessation.
    As additional information became available during post-marketing 
studies, the sponsor modified the patient package insert on November 
20, 2007, to include possible adverse reactions such as depression, 
suicidal thoughts, and agitation. At this time, the FDA issued an 
``Early Communication About an Ongoing Safety Review'' because of post-
marketing cases involving suicidal ideation and behavior. This 
communication specifies that the FDA had not concluded that a causal 
relationship existed, nor did they advise healthcare professionals to 
discontinue the product. On January 31, 2008, in response to additional 
reported adverse events, the FDA requested that all advertising 
materials be modified to reflect the additional risks. On February 1, 
2008, the FDA issued a public health advisory stating that ``. . . it 
appears increasingly likely that there may be an association between 
Chantix' and serious neuropsychiatric symptoms.''
Human Subjects Protections in Research
    Determining if and to what extent this public health advisory 
altered the relative risks and benefits of the smoking cessation study 
was the responsibility of the facility's Institutional Review Board 
(IRB). Each facility in VHA conducting research involving human 
subjects must have an IRB, which is a Committee vested with the 
responsibility of protecting human research subjects. The IRB is 
composed of scientists, physicians, and community members. In the VA, 
the IRB is a Subcommittee of the Research and Development (R&D) 
Committee. Any research project must have both IRB and R&D Committee 
approval.
    In research protocols conducted at multiple sites, each site's IRB 
must approve the protocol, as well as any substantive modifications. In 
approving the protocol, the IRB must determine that the potential 
benefits outweigh any risks to subjects involved in the research. 
Further, the IRB must approve any modifications to informed consent and 
ensure that each protocol has an adequate plan for monitoring the 
safety of subjects enrolled in the protocol.
    IRBs are required to meet regularly and to maintain minutes of 
those meetings. They must review all protocols at least annually. IRB 
Chairpersons may unilaterally approve minor changes to previously 
approved research using expedited review procedures, providing that the 
IRB reviews these actions at the next regularly convened meeting.
    In addition, IRBs review adverse events (AEs) and serious adverse 
events (SAEs) occurring during the course of research studies. AEs are 
defined as ``any untoward occurrence (physical, psychological, social, 
or economic) in a human subject participating in research.'' SAEs 
include ``death; a life threatening experience; hospitalization (for a 
person not already hospitalized); prolongation of hospitalization (for 
a patient already hospitalized); persistent or significant disability 
or incapacity; congenital anomaly and/or birth defects; or an event 
that jeopardizes the subject and may require medical or surgical 
treatment to prevent one.''
    IRBs do not, however, routinely review files maintained by the 
researchers, including whether there is a signed informed consent for 
each research subject. This type of information would be gathered 
through protocol audits, a process of reviewing the actual 
implementation of the protocol in accordance with human subjects 
protections. VHA Directive 2008-014, dated March 12, 2008, mandated 
that facilities perform such audits. Audit requirements included an 
evaluation of informed consent. Prior to this Directive, facilities 
were not required to fully audit research protocols. Rather, IRBs were 
only required to have a procedure for conducting such audits.
    IRBs in VHA are evaluated as part of an accreditation process in 
VHA. VHA contracted with the Association for the Accreditation of Human 
Research Protection Programs, Inc. (AAHRPP) to accredit its human 
subjects protection programs. Accreditation Standards used by AAHRPP 
include multiple measures of IRB compliance with Federal regulations 
and VHA policy. They conducted a site visit at the VAMCDC from October 
30, 2007-October 31, 2007. Accreditation was not granted. The facility 
received a status of Accreditation-Pending and was given the 
opportunity to submit an Improvement Plan.
Scope and Methodology
    To address the concerns regarding the use of Chantix' in 
this research study, we chose to focus our review on issues of informed 
consent, patient notification of potential adverse effects associated 
with Chantix', and the tracking and reporting of adverse 
events occurring during the course of this research study. The scope of 
this review is limited to the VAMCDC. Our first site visit to VAMCDC 
was on June 19, 2008. While conducting our inspection, we received 
allegations of potential inappropriate documentation, which we also 
reviewed.
    We addressed issues of informed consent by obtaining study records 
for the research subjects who we were told received Chantix' 
during the course of the study at VAMCDC. We compared these records to 
the patients' electronic medical records. As discussed on page 2 of 
this report, we had identified 15 patients who had received 
Chantix' at some time during the research. We then attempted 
to contact 14 of the 15 patients by telephone to determine when and if 
they had consented to enrollment in a smoking cessation study. As of 
June 30, 2008, we have been able to speak with 10 of 15 patients; 1 of 
the 10 was hospitalized and could not be interviewed. An 11th patient 
was deceased as the result of an unrelated illness. We have called 3 
patients whom we have been unable to contact. Therefore, we interviewed 
9 of 15, spoke to 1 we could not interview, and were unable to reach 3 
of 15; 1 of 15 was deceased as a result of unrelated causes, and 1 we 
did not attempt to contact.
    In addition, we reviewed IRB files, files maintained by the SI at 
the VAMCDC, e-mail, and pharmacy correspondence pertaining to this 
protocol. We interviewed the SI, Associate Chief of Staff (ACOS) for 
Research and Development, the IRB Administrator, study personnel, the 
research compliance officer, and the Acting Chief of Staff. We obtained 
and reviewed records from the CSP Coordinating Center in Palo Alto, 
California, and interviewed staff located at that facility. We reviewed 
CSP policies and procedures, adverse event reports, and numerous 
documents from VHA's Office of Research and Development pertaining to 
the smoking cessation study as conducted by VAMCDC. We also asked the 
FDA for an opinion regarding whether the November 20, 2007, early 
communication should have prompted a modification to the protocol. As 
of the date of this draft, we have not yet received this opinion.
    In this report we did not review or comment upon the medical care 
provided to individual veterans. We reported our findings only in the 
aggregate form. We performed the inspection in accordance with the 
Quality Standards for Inspections published by the President's Council 
on Integrity and Efficiency.
RESULTS
Issue 1: Patient Notification of FDA Communications Concerning Chantix
    The CSP Coordinating Center and the facility's Pharmacy Service 
appropriately notified providers following the FDA's Early 
Communication of November 20, 2008. However, following the February 1, 
2008, Public Health Advisory, we found that the facility's research 
service did not ensure that patients involved in the smoking cessation 
study were notified of the risk of suicidal thoughts or behavior in a 
timely manner.
The November 20, 2007, Early Communication from FDA
    The VAMCDC IRB approved the smoking cessation study on August 16, 
2004. The R&D Committee there initially approved the smoking cessation 
study on August 27, 2004. R&D Committee minutes describe the study as a 
greater than minimal risk study involving patients with PTSD. The study 
further required monitoring of PTSD and depression symptoms to 
determine whether smoking cessation would worsen these conditions.
    The IRB re-approved the study under continuing review procedures on 
July 11, 2005; on May 15, 2006; and on April 9, 2007. The R&D Committee 
also re-approved the study annually, with the last such approval 
occurring on April 24, 2008. On April 30, 2007, the IRB approved an 
amendment to the study, adding Chantix' as a study 
medication. Further, the consent form was amended to reflect the risks 
of Chantix' which were known at that time; these included 
insomnia, unusual dreams, headache, and constipation.
    On November 20, 2007, the FDA issued its early communication 
notifying healthcare professionals of post-marketing cases involving 
suicidal ideation and occasional suicidal behavior. The Associate Chief 
of Pharmacy at the facility received this alert the same day via e-mail 
through a subscription to a service informing healthcare professionals 
of medication alerts. E-mails describing the risks were sent to 
providers at the facility on November 21, 2007. The Associate Chief of 
Pharmacy generated lists of patients by prescriber between November 23, 
2007, and November 26, 2007, and indicated that these lists were 
distributed. They were paper rather than electronic, because all the 
providers at the facility do not have encrypted e-mail to ensure the 
privacy and security of the patients' personal information. The Chief 
of Primary Care confirmed that these lists were distributed.
    CSP conducted three conference calls with site researchers between 
November 20, 2007, and December 31, 2007. The first of these conference 
calls occurred on November 26, 2007. These minutes record the following 
statement: ``. . . because this is not a drug study, it is not 
necessary to take action on this [the FDA communication] unless your 
local IRB requires that you report it to them.'' On December 3, 2007, 
minutes reiterate that it was considered the decision of the local IRB 
as to what actions should be taken following an FDA warning. On 
December 4, 2007, minutes state the following:

         Given that this is not a drug study and use of varenicline is 
        optional, the Chairs don't feel that sites need to inform their 
        IRBs of this issue unless particular subjects report adverse 
        events related to the medication.

    On January 18, 2008, a communication from the VHA Pharmacy Benefits 
Management Service to healthcare providers stated the following: 
``FDA's preliminary assessment indicates that many cases presented with 
new-onset of depressed mood, suicidal ideation, and behavior and 
emotional changes within days to weeks of starting varenicline 
[Chantix'].'' Further, the communication described a warning 
from the European Medicines Agency of suicidal ideation and suicidal 
attempt in some patients taking Chantix'. The communication 
recommended that providers ``monitor patients taking varenicline for 
changes in mood and behavior.'' We could find no documentation that the 
SI formally reported this to the IRB, or that the IRB addressed any of 
the events related to the November 20, 2007, communication. 
Documentation supplied regarding CSP conference calls between November 
20, 2007, and December 31, 2007, make it clear that the CSP believed 
that local IRBs should decide whether this communication warranted 
action.
    This lack of action is concerning, because it is evident that the 
pharmacy service considered the November 20, 2007, communication 
important information requiring dissemination to providers and the 
creation of lists of patients on this medication. This was particularly 
important in the smoking cessation study, as it by definition enrolled 
only those veterans who had PTSD. Because not all the research subjects 
in the smoking cessation study received their medications from VA 
providers, and because all providers prescribing Chantix' 
for patients involved in the study were not listed on the protocol, we 
were unable to determine by the date of this draft report whether all 
providers notified patients of these events.
The February 1, 2008, Public Health Advisory
    The CSP Coordinating Center and the IRB reacted following FDA's 
Public Health Advisory of February 1, 2008. Minutes from a February 5, 
2008, conference call between study coordinators and assessment 
technicians and Coordinating Center staff indicated that the new safety 
information should be passed along to site clinicians to ensure patient 
notification. The Human Rights Committee at Palo Alto sent a memorandum 
to the Director of the Coordinating Center on February 8, 2008. This 
memorandum stated that, ``it is appropriate that veterans who are or 
who might be prescribed this medication while participating in the 
study be informed, and given the opportunity to discuss alternative 
treatments with their provider.'' This memorandum also contained the 
following statement:

         The proposed procedure is that all participants be given the 
        information at their next follow up visit; this will be 
        documented by their signature on the addendum. While this is 
        acceptable for participants who are not receiving the 
        medication, those who are taking varenicline should be notified 
        more urgently.

    The CSP Coordinating Center sent a memorandum dated February 13, 
2008, to researchers at the VAMCDC stating that patients currently on 
Chantix' ``will receive a copy of the consent addendum in 
the mail, along with a cover letter explaining the reason for the 
addendum.'' The Center provided a draft of the letter. The letter 
described risks of ``anxiety, nervousness, tension, and depression as 
well as untoward changes in behavior.'' It did not contain any 
information regarding increased risks of suicidal thoughts or behavior. 
While the letter did not describe these risks, the informed consent 
addendum did state that side effects included ``thoughts of suicide, 
and attempted and completed suicide''. However, CSP indicated that 
patients could sign the addendum at their next study visit. The SI at 
each site was responsible for ensuring that the letters were sent 
following IRB approval.
    The IRB at VAMCDC subsequently met on March 3, 2008. Minutes from 
that meeting document that the IRB Chair and Administrator met with the 
SI on February 29, 2008, to discuss patient notification issues 
following that advisory. The IRB Chair approved the addendum to the 
consent form addressing these risks by expedited review on the same 
day. The SI was to notify all study participants by mail with the 
letter in addition to the informed consent addendum. The SI planned to 
notify all study participants, whether or not they were on 
Chantix'. The minutes include the following sentence: ``The 
FDA states that some patients on varenicline [Chantix'] have 
an increased risk of depression and suicidality.'' Minutes also state 
that patient notification issues were reported to the research 
compliance officer for followup.
    We interviewed the SI, IRB Administrator, IRB Chair, and study 
coordinator for the smoking cessation trial at VAMCDC. The IRB 
Administrator and Chair indicated that it was the SI's responsibility 
to actually send the letters. The SI stated the letters were sent to 
all 109 participants. The study coordinator reported assisting in this 
task. The letters were not sent with any return receipt requested, or 
with any other means of verifying delivery to the appropriate 
individuals. There was no consistent documentation in the electronic 
medical record that such letters were sent. We interviewed nine of the 
patients by phone. Three of these patients recalled receiving a letter. 
The study coordinator indicated that a few letters came back, but we 
were unable to locate documentation of any follow-up actions to address 
these returned letters, or exact numbers of how many were returned.
    While we believe these letters were sent, we have no reliable way 
of determining how many of the veterans actually received notification. 
Further, we concluded that the letter did not adequately explain the 
risks associated with Chantix' at that time. We were told 
that the informed consent addendum was included with the letter when 
the letters were mailed, but we were unable to find any documentation 
of sending these items to all affected veterans. Therefore, we found 
that the notification procedures for patients in the smoking cessation 
study at the VAMCDC following the February 1, 2008, Public Health 
Advisory did not adequately ensure that all patients were notified of 
this risk in a timely manner.
    On May 30, 2008, VHA's Pharmacy Benefits Management Service sent an 
e-mail to VISN formulary leaders and pharmacy chiefs asking them to 
distribute a letter to veterans taking Chantix' that 
informed them of the risk of suicide associated with the medication. 
Two of the six veterans who did not recall receiving the initial letter 
from the SI recalled getting this letter recently.
    While the facility's Pharmacy Service appropriately notified 
providers of the risks associated with Chantix', we do not 
find that the research service ensured that subjects enrolled in the 
smoking cessation study were notified of these risks. We therefore 
concluded that the facility notified providers of the adverse effects 
of Chantix' in an appropriate and timely manner but did not 
ensure that patients enrolled in the smoking cessation study received 
this information.
Issue 2: Adequacy of Informed Consent
    Federal informed consent regulations govern the use and 
participation of human subjects in research. The purpose of the 
regulations is to safeguard the welfare of humans and to assure that 
the subjects are given enough information about the research so that 
they may make informed decisions about whether or not to participate.
    Patients enrolling in the smoking cessation study were initially 
required to sign two consent forms. The first indicated the patient's 
consent to be screened for the study to determine whether they were 
eligible. If a patient was found eligible for the study, the patient 
would then sign a second consent form to participate in the research 
and be informed of any medications which might be used in the study. 
Over time there were three versions of this second consent form. The 
first version, we call ``the original second consent form.'' The second 
version of this form we refer to as the ``revised consent form''; it 
introduced Chantix' to the study and informed the patients 
of the earliest known risks. The third version of this form we refer to 
as ``the addendum''; it disclosed the greater risks of 
Chantix' as of February 2008.
    Thus, the ``original second consent form'' to participate in the 
study contained information pertaining to the risks of nicotine 
patches, nicotine gum, and buproprion, another medication used for 
smoking cessation. The original second consent did not contain a 
mention of Chantix', which at that time had not yet received 
FDA approval and was not a part of the research study.
    On April 9, 2007, the IRB approved a new second consent form to 
participate in the study, which is referred to here as the ``revised 
consent'' form; it replaced the original second consent. This revised 
consent form included information on the risks of Chantix' 
that were known at that time, to include changes in dreams and nausea. 
We reviewed all the consent forms for all 15 patients identified by the 
SI as being on Chantix' at some time during the course of 
the study. We could locate the revised consent form for only 5 of the 
15 patients on Chantix'. The SI indicated that patients 
entering the study after April 9, 2007, were to sign that revised 
consent form, but that individuals who had already signed the original 
second consent form were not re-consented during the research study.
    Following the February 1, 2008, FDA Advisory, an addendum was 
created and added to the revised consent form to include information 
about the risks of suicidal thoughts or behavior for patients taking 
Chantix'. In this report, we refer to the addendum to the 
informed consent, which is essentially the third version of the second 
consent form, as ``the addendum.'' The addendum was initially approved 
through expedited review on February 29, 2008, and disclosed that 
Chantix' could cause ``changes in behavior, anxiety, 
nervousness, tension, depression, thoughts of suicide, and attempted or 
completed suicide.'' The SI stated that she mailed the addendum to all 
patients within the study, not just to those on Chantix'. On 
April 1, 2008, minutes from a CSP conference call between study 
personnel and the Coordinating Center indicated that the study 
coordinator and assessment technician from the VAMCDC site reported 
that ``a number of patients have signed the consent addendum.''
    Chantix' next appears in the VAMCDC IRB minutes of May 
5, 2008. These minutes document a discussion between a patient who 
experienced an episode of aberrant behavior while on 
Chantix' and the SI and the Chief of Psychiatry. The patient 
wanted to withdraw from the study and a letter to that effect was 
signed by these parties and witnessed by the IRB Chair. On May 6, 2008, 
another CSP conference call occurred in which VAMCDC study personnel 
stated that they were ``actively approaching subjects about the 
varenicline (Chantix') addendum and obtaining signatures.''
    We reviewed only those charts of the 15 patients identified as 
having taking Chantix' at some time during the course of the 
review. We could locate signed addendums including information about 
the risks of suicidal thoughts or behavior for only 6 of these 15 
patients as of June 23, 2008. Of these 6, only 2 were signed prior to 
June 20, 2008. We do note that, of the patients without a signed 
addendum in their chart, one had died as the result of an unrelated 
illness and another had moved out of the area. Medical records 
demonstrate that 11 of the 15 patients had visited the medical center 
between March 3, 2008, and June 20, 2008.
    Despite evidence that study personnel at the VAMCDC reported that 
the consent process was going well on numerous occasions, we found that 
the facility failed to obtain patient signatures on the addendum to the 
informed consent describing the risk of suicidal thoughts in patients 
taking Chantix'. Patients also were not re-consented with 
the April 9, 2007, consent form, which added Chantix' to the 
list of medications already utilized by study prescribers and disclosed 
risks known to be associated with the drug at that time. Minutes from a 
June 2, 2008, conference call between CSP and research personnel at the 
VAMCDC once again record that VAMCDC told the CSP that ``[T]he 
varenicline [Chantix'] consent process is going well.''
    Further, we found that the facility's research compliance program 
failed to appropriately monitor the adequacy of the informed consent 
process at the facility. The research compliance officer obtained her 
current position in October of 2007. Since that time, she told us she 
has ``been in training mode.'' She reviewed the consent forms for this 
study but did so only from the perspective of whether the informed 
consent process was documented appropriately. She did not verify that 
there were consents for all patients enrolled in this study. AAHRPP 
noted several deficiencies relating to the informed consent process in 
its October 2007 visit. Standards described as ``NOT MET'' by AAHRPP 
included:

    1.  Researchers ``develop an informed consent process and method of 
documentation appropriate to the type of research and the study 
population, emphasizing the importance of participant comprehension and 
voluntary participation.''
    2.  The Research Review Unit has and follows ``written policies and 
procedures requiring that the investigator has and follows a procedure 
for properly documenting informed consent.''
    3.  The Research Review Unit ``reviews the content of the consent 
process including the consent document, and the process through which 
informed consent is obtained from each participant, focusing on 
measures to improve patient understanding and voluntary 
decisionmaking.''

    We do note, however, that the facility did not receive a copy of 
the Final Site Visit Report from AAHRPP until March 19, 2008. AAHRPP 
did not accredit the VAMCDC; rather, they gave it a status of 
Accreditation Pending. An Improvement Plan is due to AAHRPP on July 14, 
2008.

Issue 3: Psychiatric AEs and SAEs in Patients Enrolled in the Smoking 
        Cessation Study Receiving Chantix
    We also reviewed whether the VAMCDC appropriately monitored AEs and 
SAEs occurring during the course of the smoking cessation study. Our 
review of SAEs was limited to psychiatric events occurring at the 
VAMCDC in patients who had taken Chantix' at some time 
during the course of the study. We did not evaluate all adverse events 
from the VAMCDC or SAEs from any of the other sites.
    At the VAMCDC, we found reports for 4 SAEs relating to psychiatric 
hospitalizations for 3 of the 15 patients; 1 of those patients was on 
Chantix' at the time. Three SAEs were dated in early 2007; 
the fourth was in early 2008.
    We then sought to determine whether the Coordinating Center had 
evaluated the communications from FDA in terms of the study results 
nationwide. We did find that they considered this problem. They 
initially decided not to change reporting requirements of AEs following 
the November 20, 2007, communication. Prior to the February 1, 2008, 
warning, sites were required to report SAEs but not all AEs. However, 
following the February 1 warning, sites were required to report AEs and 
SAEs. The Data and Safety Monitoring Board for the nationwide 
Chantix' study met on February 27, 2008. Minutes from this 
meeting contain the following statements:

         [A Board member] reported that the number of SAEs [includes 
        all SAEs, not just psychiatric SAEs] continues to be high. 
        Often one or two life-threatening events are reported in a day, 
        but most are not study related... The study chose to include 
        varenicline [Chantix'] when it became available. 
        [The Board member] noted that the original [market-related] 
        studies [on Chantix'] did not include people with 
        active mental disorders, so we are starting to see the affect 
        [sic] now in our population. We are asking sites to report 
        these side effects on the SAE forms even if they are only AEs 
        [adverse events].

    Also on February 27, 2008, the human rights Committee at the CSP 
Coordinating Center in Palo Alto met and discussed Chantix'. 
Minutes reflect a discussion of the fact that the initial 
Chantix' studies evaluating its safety did not include 
subjects with comorbid mental health diagnoses. Minutes state that the 
``study Co-Chairs agreed to check with sites and review how those 
participants who are taking varenicline, but are not in therapy, are 
being monitored.'' We were not provided with any written documentation 
regarding if or when this occurred.
    Study results provided to us described 25 serious adverse events of 
a psychiatric nature which occurred while patients were enrolled in the 
study nationwide. This did not mean that these events were related to 
the study or that they occurred while the patient was actually taking 
Chantix'. By definition, all patients in the study had pre-
existing mental illness. The 25 events disclosed included 16 patients 
with suicidal ideation; 1 who attempted suicide; and 1 who had 
homicidal thoughts.
    We are concerned, however, by the comment in the Data Safety and 
Monitoring Board minutes stating that we are seeing the effects now 
``in our population.'' This made the human rights Committee decision to 
review how patients taking Chantix' were to be monitored all 
the more important. However, we do note that data provided reflected 
that only a single possible Chantix'-related event occurred 
during the course of this study nationwide. Interpreting nationwide 
data for this study, however, is expressly beyond the scope of this 
review.
Issue 4: Alleged Documentation Irregularities in the Smoking Cessation 
        Study at VAMCDC
    During the course of our review, we received allegations that study 
personnel had falsified certain study records at VAMCDC. The smoking 
cessation study required study personnel to fill out a number of 
written documents based upon direct patient interviews. One such 
document was the Clinician Administered PTSD Scale (CAPS) form. This is 
a structured interview used in part to assess the severity of PTSD 
symptoms in study participants. At VAMCDC the study coordinator could 
not complete this form because he was not a clinician. The assessment 
technician typically completed these forms at the VAMCDC.
    On June 24, 2008, the ACOS for R&D notified ORO of allegations he 
received regarding inappropriate documentation of information contained 
on the CAPS form for two patients associated with the smoking cessation 
study. It was reported that the study coordinator completed these forms 
based on information contained in other documents, rather than from a 
direct patient interview.
    We reviewed the CAPS forms, and interviewed the study coordinator. 
We were unable to interview the assessment technician because of 
reported health problems. The study coordinator admitted that in two 
instances, he completed these forms from information obtained from 
other forms. He further stated that he had the assessment technician on 
the telephone who offered advice as to how to complete these forms. We 
verified that in at least one of these instances, the assessment 
technician was on leave without pay on the day of the patient's visit.
    Based upon this information, we conclude that the CAPS form in at 
least one instance was not completed by a clinician during a direct 
patient interview as required by the protocol. Further, we were told 
that this particular record was faxed to the Coordinating Center along 
with the other data collected at this site. We therefore found that 
this employee did not complete the form in accordance with the 
protocol, and we question the accuracy of the data contained on that 
form.
    In addition, we reviewed quality control reports sent from the 
Coordinating Center concerning their evaluation of study data submitted 
from the VAMCDC. These reports were provided on a weekly basis. The 
Coordinating Center reports contain numerous entries concerning 
VAMCDC's missing pages, missing data, and inconsistent data. While data 
entry errors are exceedingly common, we are concerned about these 
reports in light of the information described above.
CONCLUSION
    The actions of study personnel regarding the completion of the 
smoking cessation study records suggest that the accuracy of such 
records may be in dispute. Data used in the type of important trials 
described in this report may be used to define the standard of care for 
PTSD patients who want to stop smoking. The quality control reports 
reflect that CSP monitored data submissions regularly. However, the 
Coordinating Center could not be expected to detect whether the CAPS 
form was appropriately completed from a direct patient interview or 
extrapolated from other study data. These kinds of documentation 
irregularities may affect the credibility of study results. While in 
this case we have no reason to believe that the problem is not 
remediable, it reinforces the need for monitoring of data collection 
and researcher records at a local level.
    The human rights Committee at the Coordinating Center suggested 
special monitoring for study subjects taking Chantix' and 
not receiving therapy. We were not able to locate documentary evidence 
that this recommendation was ever implemented at VAMCDC. Further, the 
VAMCDC did not initially supply us with an accurate number of patients 
having ever taken Chantix' during the course of the study, 
suggesting that local sites may not have been tracking which patients 
were and were not taking Chantix'. This makes it unlikely 
that they ever identified the subgroup of those patients who were not 
actively receiving therapy while taking Chantix'.
    In addition, the absence of signed informed consent addendums 
describing the effects of Chantix' after they were known to 
researchers at the VAMCDC is also of concern. While the SI at the 
VAMCDC did send out a letter in late February or early March 2008 to at 
least some participants in the study, we have no documentary evidence 
of who received it or when. This prevents us from ensuring that 
patients were notified in a timely fashion once side effects of 
Chantix' were known. We also did not find that the letter 
contained sufficient warning regarding the possible risk of suicidal 
thoughts or actions, but note that this information was in the enclosed 
addendum to the consent form.
    We also found that the pharmacy service provided timely 
notification to clinical care providers, including lists of patients on 
the medication. The VA sent letters dated May 30, 2008, to identified 
patients on Chantix' to alert them to medication side 
effects. We believe that this was sufficient for the general population 
of patients in the facility taking Chantix'. However, 
research subjects, who by definition had active PTSD, represented a 
group uniquely susceptible to neuropsychiatric side effects. We believe 
that the Coordinating Center recognized this in deciding to modify the 
informed consent and mail letters to patients. The local implementation 
of this directive, however, is at issue in that the VAMCDC did not 
ensure that these patients signed informed consent addendums or 
received letters notifying them of the additional risks.
    Finally, the deficiencies involving informed consent identified in 
the AAHRPP review suggest that the VAMCDC may not be adequately 
monitoring the informed consent process on a systemic scale. The scope 
of this review prevents us from making a definitive statement with 
regard to the VAMCDC's research program overall, but deficiencies 
identified in the AAHRPP report suggest that some issues may be 
systemic in nature. Therefore, we make the following recommendations:
RECOMMENDATIONS
    1.  The Under Secretary for Health will ensure that all patients 
who currently take Chantix' have been informed of the 
possible association between Chantix' and suicidal thoughts.
    2.  The Under Secretary for Health will develop a formal mechanism 
for ensuring that Institutional Review Boards are directly notified of 
FDA communications concerning medications when they are responsible for 
protocols involving those medications.
    3.  The Under Secretary for Health will ensure that all patients 
involved in the smoking cessation study are informed of the risks 
associated with Chantix' by VHA study personnel and given 
the opportunity to sign the addendum to the informed consent disclosing 
those risks.
    4.  The Under Secretary for Health will take appropriate 
administrative action, to include a research misconduct inquiry, based 
upon the findings contained within this report.
    5.  The VISN 5 Director will require that the smoking cessation 
study data collected at VAMC Washington, DC, be validated to ensure its 
accuracy.
    6.  The VISN 5 Director will require the medical center director to 
audit a representative sample of all active protocols involving human 
subjects for compliance with VHA informed consent requirements, 
including whether an informed consent can be located for each study 
participant.
    7.  The VISN 5 Director will require the medical center director to 
ensure that protocols are being audited in accordance with VHA 
Directive 2008-014.
    Mr. Chairman, in closing, I would like to once again thank you and 
the other Members of the Committee for the opportunity to testify on 
this important matter. Dr. Buck, Mr. Snow, and I would be pleased to 
answer any questions.

                                 
 Statement of Gerald P. Koocher, Ph.D., Professor and Dean, School of 
              Health Sciences, Simmons College, Boston, MA
    Mr. Chairman,
    I welcome the opportunity to appear before the Committee today in 
an effort to provide information that may prove useful to the Members 
and staff as you seek answers to questions about ethical standards in 
the design and execution of behavioral and bio-medical research with 
vulnerable human participants.
    The central ethical concerns in any research involving people 
should focus on their informed participation and safety. The first 
ethical cornerstone involves an individual's consent to participate. 
Often called ``informed consent,'' the concept involves providing 
information by its very definition. The key elements to consent 
include:
      Access to all of the information that might reasonably 
influence one's willingness to participate;
      Adequate knowledge and understanding of that information, 
and
      Voluntariness and freedom from coercion in the decision 
to participate or withdraw from participation.
    Obtaining consent does involve documentation, but is best 
conceptualized as a process by which the investigator makes certain 
that potential participants know what will be asked of them, what risks 
or hazards may be involved, what benefits may result. In addition, the 
consent process must inform participants about their right to withdraw 
at any time, and provide contact information for responsible parties in 
the event of any problems or complaints. Those providing this 
information have the obligation to communicate these details in 
language the participants can understand. If the investigator plans 
changes to a project after obtaining consent, the process must be 
reinitiated with the new details provided and agreed to by 
participants.
    Many research projects involve studying healthy people. However, 
most research populations of interest and available to mental health 
professionals are restricted or vulnerable in ways that may not allow a 
full measure of self-determination. From the standpoint of this 
Committee's concerns, such populations may include people at high risk 
for some possibly preventable outcome, disabled individuals, and those 
who may face social or economic disadvantage. Some potential 
participants may have additional vulnerabilities because of their 
mental or emotional condition, such as anxiety, depression, or symptoms 
of post-traumatic stress. Other vulnerabilities may arise from physical 
illness or issues of confidentiality that bear on social stigma or 
discrimination.
    In addition to adhering to legal regulations, the ethical 
obligation to protect all research participants rests with the 
investigators, who stand accountable to professional codes of ethics 
and a number of regulatory bodies including Institutional Review Boards 
(IRBs), Data Safety Monitoring Boards (DSMBs), and federal agencies 
such as the Food and Drug Administration (FDA). Both IRBs and DSMBs 
include independent content area experts and representatives of the 
public. IRBs and DSMBs typically review research plans, eligibility or 
exclusion criteria, consent forms, data analysis/management protocols, 
and adverse events (generally characterized as AEs, adverse events, or 
SAEs--serious adverse events, as when a death occurs). Any changes in 
research protocols that might bear on the safety of participants 
require advance approval by the institutional IRBs, and DSMBs in the 
case of multi-site trials. All of these processes and safeguards 
generally involve substantial documentation.
    In certain exceptional circumstances an IRB may waive obtaining 
written consent. For example, suppose an investigator seeks anonymous 
survey data via the Internet or unobtrusively observes the public 
behavior of anonymous people in everyday settings (e.g., recording how 
often many people line up at the ``8 items or less'' supermarket 
checkout counter with more than 8 items). In such circumstances an IRB 
would typically waive the requirement of individual consent. Even in 
such instances, however, the investigator would formally request the 
waiver and the IRB would document granting it.
    As a person who has served as a principal investigator, as an IRB 
member, as a current DSMB member for the N.I.M.H., and who has studied 
IRBs and research integrity, I hope that I can provide the Committee 
with information that will assist you in reviewing the research 
projects of concern to you.

                                 

                   MATERIAL SUBMITTED FOR THE RECORD

                             110TH CONGRESS
                                   A
                               RESOLUTION
                         OFFERED BY MR. FILNER
    Be it resolved by the Committee on Veterans' Affairs, that the 
Democratic Membership of the standing subcommittee of the Committee for 
the 110th Congress shall be as follows:
                         Subcommittee on Health
                  Michael H. Michaud, Maine, Chairman
    Corrine Brown, Florida
    Vic Snyder, Arkansas
    Phil Hare, Illinois
    Shelley Berkley, Nevada
    John T. Salazar, Colorado
    Donald J. Cazayoux, Jr., Louisiana

                                 
     ``VA Testing Drugs on War Veterans, Experiments Raise Ethical 
                              Questions''
                          The Washington Times
                            By Audrey Hudson
                             June 17, 2008
    The government is testing drugs with severe side effects like 
psychosis and suicidal behavior on hundreds of military veterans, using 
small cash payments to attract patients into medical experiments that 
often target distressed soldiers returning from Iraq and Afghanistan, a 
Washington Times/ABC News investigation has found.
    In one such experiment involving the controversial anti-smoking 
drug Chantix, the Department of Veterans Affairs (VA) took three months 
to alert its patients about severe mental side effects. The warning did 
not arrive until after one of the veterans taking the drug had suffered 
a psychotic episode that ended in a near lethal confrontation with 
police.
    James Elliott, a decorated Army sharpshooter who suffers from post-
traumatic stress disorder (PTSD) after serving 15 months in Iraq, was 
confused and psychotic when he was Tasered by police in February as he 
reached for a concealed handgun when officers responded to a 911 call 
at his Maryland home.
    Mr. Elliott, a chain smoker, began taking Chantix last fall as part 
of a VA experiment that specifically targeted veterans with PTSD, 
opting to collect $30 a month for enrolling in the clinical trial 
because he needed cash as he returned to school. He soon began 
suffering hallucinations and suicidal thoughts, unaware that the new 
drug he was taking could have caused them.
    Just two weeks after Mr. Elliott began taking Chantix in November, 
the VA learned from the Food and Drug Administration (FDA) that the 
drug was linked to a large number of hallucinations, suicide attempts 
and psychotic behavior. But the VA did not alert Mr. Elliott before his 
own episode in February.
    In failing to do so, Mr. Elliott said, the VA treated him like a 
``disposable hero.''
    ``You're a lab rat for $30 a month,'' Mr. Elliott said.
    One of the Nation's premier medical ethicists said the VA's 
behavior in the anti-smoking study violated basic protections for 
humans in medical experiments.
    ``When you're taking advantage of a very vulnerable population, 
people who have served the country, and the agency that's responsible 
for their welfare isn't putting their welfare first, that's a pretty 
serious breach of ethics,'' said Arthur Caplan, director of the Center 
for Bioethics at the University of Pennsylvania.
    In all, nearly 1,000 veterans with PTSD were enrolled in the study 
to test different methods of ending smoking, with 143 using Chantix. 
Twenty-one veterans reported adverse effects from the drug, including 
one who suffered suicidal thoughts, the three-month investigation by 
The Times and ABC News found.
    Mr. Caplan, who reviewed the consent and notification forms for the 
study at the request of The Times and ABC News, said the VA deserved an 
``F'' and that it has an obligation to end the study, given the 
vulnerability of veterans with PTSD and the known side effects of 
Chantix. ``Continuing it doesn't make any ethical sense,'' he said.
    The VA continues to test Chantix on veterans, even as reported 
problems with the drug increase and have prompted at least one other 
federal agency to take action. On May 21, the Federal Aviation 
Administration banned airline pilots and air traffic control personnel 
from taking Chantix, citing the adverse side effects.
The VA responds
    VA officials defend their use of veterans in medical studies, 
saying that helping PTSD sufferers to stop smoking would prolong their 
lives. As for the three-month delay in notifying its patients about the 
Chantix problems, the VA said bureaucracy slowed down their warning 
because the alert letters had to be issued through an Institutional 
Review Board (IRB) that oversees the experiment at each VA location.
    ``We don't have the authority to just send directly to patients 
material that has not been approved by the IRB sites,'' said Miles 
McFall, director of the VA's programs for PTSD sufferers. ``We did 
sense urgency. And we respond to that urgency doing just what we did 
here, which was, I think, incredibly quick response for a governmental 
institution.
    ``We believe that we took responsible action by informing the 
clinicians who are the people most in touch with the patients to be on 
the lookout for any potential side effects and to respond 
appropriately,'' he said.
    While Mr. Elliott blames Chantix for his mental breakdown and 
confrontation with police, VA officials said they cannot be sure.
    ``We don't know that Chantix was the cause of this, first of all. 
And it's presumed that that's the case. We don't know that to be a 
fact,'' Mr. McFall said.
    Mr. McFall said the veterans with PTSD in the anti-smoking study 
``are at high risk to use tobacco'' and the goal of the experiment is 
to determine how best to deliver treatment--through a mental health 
counselor or a smoking clinic. Chantix was one of several options 
tested on the veterans.
    ``FDA approved, and that drug is available to help individuals stop 
smoking and VA makes that drug available,'' Mr. McFall said. ``It does 
not deny access to them.''
    Asked about adverse reactions now linked to the drug, Mr. McFall 
said: ``We are certainly aware of FDA warnings and we took all 
precautions. . . . so it can be used safely. All drugs have side 
effects or potential side effects.''
Dark history of medical tests
    The government has a controversial history of using military 
personnel as human research subjects.
    Mustard gas was tested on the military during World War II, 
radiation during the early Cold War period, LSD in the sixties, 
herbicide in Vietnam and Panama, and chemical and biological warfare 
drugs during the Gulf War, according to Senate testimony given by the 
Vietnam Veterans of America (VVA) on July 10, 2002.
    In most of those cases, few if any military test subjects were 
informed of the potential health consequences of the exposure.
    ``We have a phrase to describe this phenomenon--the disposable 
soldier syndrome,'' said Richard Weidman, former VVA director of 
government relations.
    The most infamous government experiment is the Tuskegee Syphilis 
Study conducted by the U.S. Public Health Service from 1932 through 
1972, which used 400 poor and uneducated black male sharecroppers who 
carried the sexually transmitted disease.
    The men were purposely undiagnosed and untreated for a disease that 
already had progressed to late stages, and were studied through 
autopsy.
    The government effectively blocked the unwitting participants, who 
also were drafted in 1940 to serve in WWII, from receiving medical 
treatment for symptoms they were told were caused by ``bad blood.'' Of 
the participants, 28 men died of the disease, 100 others died from 
complications brought on by syphilis, and the disease spread to 40 
wives and 19 children.
Ongoing tests with vets
    The VA has extensive screening of veterans who enroll in medical 
experiments and requires detailed consent forms to ensure patients know 
about the potential complications and benefits.
    Currently, the VA and other federal agencies are conducting nearly 
300 clinical studies involving veterans with PTSD. Most studies are 
behavioral, including one that tests the effects of yoga on PTSD 
sufferers.
    Twenty-five, however, are testing drugs on 4,796 veterans, more 
than half (2,488) of whom are just returning from the wars in Iraq and 
Afghanistan, according to clinical trials filed with the National 
Institutes of Health (NIH) and reviewed by The Times.
    One study conducted by the National Institute of Mental Health is 
using virtual-reality exposure--sights, sounds and smells from the Iraq 
battlefield, along with a drug called D-Cycloserine that reduces fear.
    Other studies are testing drugs on veterans with PTSD, including 
the antidepressants paroxetine, mirtazapine and citalopram--all carry 
warnings of suicidal side effects.
    ``Over 150,000 soldiers are currently deployed in Iraq as part of 
Operation Iraqi Freedom (OIF) and 12 percent of returning OIF veterans 
have PTSD,'' said one study that is using the drug paroxetine on 160 
veterans ``who have returned from the Iraq theater within the past six 
months.''
    Warnings about taking paroxetine include ``suicidal thinking about 
harming or killing oneself or planning to trying to do so'' among young 
adults up to 24 years of age, according to NIH.
    Another study on the use of mirtazapine for veterans of Iraq and 
Afghanistan is testing the efficacy and tolerability of the drug on 100 
veterans. Citalopram is being tested on 300 veterans ``exposed to high 
levels of combat stress.''
    The NIH warning for paroxetine also applies to mirtazapine and 
citalopram.
    The VA has not revealed how many veterans are registered in an 
experiment to study the effects of divalproex in the treatment of PTSD, 
but the FDA warned health care professionals on Jan. 31 it had received 
reports of suicide and suicidal thoughts linked to the anticonvulsant 
drug.
Smoking study's fine print
    Mr. Elliott was one of 940 veterans with PTSD who participated in 
the Veterans Affairs Cooperative Studies Program (CSP) # 519, 
``smoking-cessation treatment for veterans with post traumatic stress 
disorder'' ongoing at 10 VA clinics.
    The CSP studies date back to the 1940s, when 10,000 veterans 
suffering from tuberculosis were recruited into VA studies to test 
different drugs to treat the disease.
    The smoking-cessation study uses nicotine replacement products like 
gum and patches as well as Chantix--a drug that is supposed to block 
certain brain receptors that make smoking pleasurable. The $11 million 
taxpayer-funded study was approved in 2004, two years before the FDA 
approved Chantix for prescription use.
    The FDA says that nearly 40 suicides and more than 400 incidents of 
suicidal behavior have since been linked to Chantix.
    Mr. Elliott began taking Chantix on Nov. 6. Two weeks later, on 
Nov. 20, the FDA issued its first alert that it had ``received reports 
of suicidal thoughts and aggressive and erratic behavior in patients 
who have taken Chantix,'' also known as varenicline.
    ``A preliminary assessment reveals that many of the cases reflect 
new-onset of depressed mood, suicidal ideation, and changes in emotion 
and behavior within days to weeks of initiating Chantix treatment,'' 
the November FDA alert said.
    ``The role of Chantix in these cases is not clear because smoking 
cessation, with or without treatment, is associated with nicotine 
withdrawal symptoms and has also been associated with the exacerbation 
of underlying psychiatric illness. However, not all patients described 
in these cases had pre-existing psychiatric illness and not all had 
discontinued smoking,'' the FDA said.
    On Jan. 18, the drug manufacturer Pfizer revised its warning label 
to state ``patients who are attempting to quit smoking with Chantix 
should be observed for serious neuropsychiatric symptoms, including 
changes in behavior, agitation, depressed mood, suicidal ideation and 
suicidal behavior.''
    On Feb. 1, the FDA held a news conference to announce that new 
health risks have been associated with the drug.
    VA officials started addressing the FDA alert on Nov. 26 and Dec. 4 
with conference calls among government officials ``to inform 
prescribers about these potential problems and advise patients 
accordingly,'' according to a timeline agency officials provided The 
Times.
    On Feb. 4, VA officials were told to ``formulate and approve an 
action plan,'' and on Feb. 13, a second consent form and letter was 
submitted for approval by VA officials.
    The letter received by Mr. Elliott and other veterans was dated 
Feb. 29, more than three weeks after he already had suffered his mental 
breakdown and confrontation with police.
VA letter watered down?
    While the alerts from Pfizer and the FDA clearly mentioned suicide 
and suicidal thoughts as possible side effects, the VA's letter to its 
veterans used no such language.
    ``Scientists have recently learned that varenicline can sometimes 
have serious side effects in some people,'' the VA letter said. ``These 
side effects may include an increase in psychiatric symptoms such as 
anxiety, nervousness, tension and depression as well as untoward 
changes in behavior.''
    Asked why the letter omitted the most significant side effect, Mr. 
McFall said ``the more verbiage you use, the more difficult and lengthy 
it becomes, hard to read. It's more likely veterans won't pay attention 
to it if you overdo.''
    However, a secondary research consent form sent with the letter 
that participants are now being asked to sign cites ``changes in 
behavior, anxiety, nervousness, tension, depression, thoughts of 
suicide, and attempted and completed suicide.''
    Mr. McFall said the serious side effects were included in the 
secondary consent form, and not the notification letter, because ``it's 
better to have the letter be brief'' so that it is not a ``burden for 
people who sometimes have problems reading.''
    ``They have eyesight problems,'' Mr. McFall said. ``Many of our 
veterans are getting elderly, so we're trying to keep things simple and 
to the point, while at the same time pointing them to the most 
important document, which is the consent form.''
    Veterans who are participating in the smoking-cessation program are 
carefully screened to ensure they are not suicidal, psychotic or 
homicidal, Mr. McFall said.
    According to the VA research consent form Mr. Elliott initially 
signed, he would be required to fill out questionnaires ``about some 
war zone events that you may have experienced'' and interviews 
``regarding symptoms of other psychiatric disorders and your use of 
drugs and alcohol.''
    ``Has there been a time in the past month when things were so bad 
that you were thinking a lot about death or that you would be better 
off dead?'' is one example question listed on the consent form.
    Mr. Elliott filled out monthly checklists on the extent to which he 
had nightmares about his military experience or flashbacks, became 
``super alert'' or on guard, and whether he had a ``feeling as if your 
future will somehow be cut short.''
Chantix debate
    New York Magazine writer Derek De Koff detailed the nightmares and 
suicidal behavior he suffered while on Chantix in a Feb. 10 article, 
and said that at one point he felt like throwing himself in front of a 
tour bus or crashing his head into a computer screen.
    ``All this seemed logical, but also weirdly funny, even at the 
time: I could see how crazy these impulses were, I could recognize them 
as suicidal cliches. But I couldn't make them go away,'' Mr. De Koff 
wrote.
    In September, musician Jeffrey Carter Albrecht was shot by a 
neighbor who mistook him for a burglar. The guitarist and keyboardist 
who once played with Edie Brickell & New Bohemians went on a rant that 
friends say was fueled by alcohol and the drug Chantix.
    A spokesman for Pfizer could not be reached after three calls 
seeking comment. However, in full-page ads published May 29 in several 
newspapers including U.S.A. Today, Dr. Joseph Feczko, Pfizer chief 
medical officer, said the company is ``committed to patient safety'' 
and ``furthering our knowledge of Chantix.''
    The FDA has declined to pull Chantix from the market, citing the 
health benefits of smoking cessation.
    ``This actually is a very important drug,'' Dr. Celia Winchell, 
team leader for the FDA division of anesthesia, analgesia and 
rheumatology, said during the February teleconference announcing the 
new warning.
    ``Although we are getting these reports, there's also a lot of 
anecdotal reports out there where this drug has worked when no other 
drug would,'' Dr. Winchell said.
    ``Smoking itself has very serious consequences. And so I think it's 
important to try to manage the risk associated with the drug, also 
realizing that it has a lot of benefits for some folks,'' Dr. Winchell 
said.
    More than 5,000 people were treated with the drug in preliminary 
trials before it was approved for prescription use. However, patients 
with serious psychiatric illness such as schizophrenia, bipolar 
disorder and major depressive disorder did not participate in those 
tests.
Ethics of future VA tests
    Mr. Caplan, the bioethicist, said that using veterans with PTSD in 
clinical trials carries a ``high risk'' that must be addressed by the 
VA.
    ``Researchers have a special obligation to vets with PTSD since 
they are a vulnerable population somewhat prone to threats or even 
violence against themselves or others,'' he said. ``They need to keep a 
hawk-like eye on subjects involved in high stress experiments and make 
sure that families and friends are involved and on board any research 
projects to help monitor subjects.''
    ``I am not against research to try and improve the health of those 
with PTSD but only if it is done with the highest levels of consent, 
transparency, supervision and accountability,'' he said.
    Mr. Caplan recommended several steps the government should adopt 
before allowing future testing on vulnerable veterans, including more 
participation by families and veterans on Committees that review and 
approve research proposals.
    Future studies that involve veterans with PTSD also should receive 
special approval from the VA secretary.
    And a clear policy should be established that prohibits drugs 
reported to have serious side effects be tested on populations at risk 
of those side effects, including veterans with PTSD, he said.

                                 
          ``Congress Demands VA Investigation, Obama, Pelosi,
                       Others Hit Drug Testing''
                          The Washington Times
                    By Audrey Hudson and S.A. Miller
                             June 18, 2008
    Democratic presidential candidate Sen. Barack Obama and 
congressional leaders on both sides of the aisle Tuesday called for 
investigations into the Department of Veterans Affairs (VA) failure to 
inform in a timely manner veterans participating in medical tests that 
a drug they were taking has side effects that can lead to psychosis and 
suicide.
    Responding to an investigative report published in The Washington 
Times, Tuesday, Mr. Obama, a member of the Senate Committee on 
Veterans' Affairs, said the VA's actions in sponsoring the drug tests 
were ``outrageous'' and ``unacceptable.''
    ``Our veterans--particularly those suffering from mental health 
injuries--should have the very best healthcare and support in the 
world, they should never be needlessly exposed to drugs without proper 
notification of the dangers involved or effective monitoring of the 
side effects,'' said Mr. Obama, Illinois Democrat.
    Rep. Steve Buyer of Indiana, the ranking Republican on the House 
Committee on Veterans' Affairs, sent a letter to the VA inspector 
general and the VA's chief research and development officer requesting 
an investigation.
    ``I am troubled by allegations that these safeguards may have not 
been in place for this study and I am requesting an immediate 
investigation into this matter and I asked that VA report back to me as 
soon as possible,'' he said.
    A spokesman for House Speaker Nancy Pelosi, California Democrat, 
said Congress also will look into the matter.
    ``This report raises many disturbing questions about the treatment 
of our veterans and the House Veterans' Affairs Committee will get to 
the bottom of this,'' said Pelosi spokesman Nadeam Elshami. ``We expect 
full and immediate cooperation from the VA.''
    The VA took three months to notify its patients about severe mental 
side effects of the anti-smoking drug Chantix, after the Food and Drug 
Administration issued an alert about side effects that could lead to 
psychosis and suicide.
    The VA said notification letters were tied up in bureaucracy, but 
thought the three-month timeframe was not unrealistic. The VA also said 
warnings about suicide were omitted from the letter notification 
because many veterans are elderly or have eyesight problems.
    ``This is the most pathetic excuse that can be dredged up; it's 
insulting,'' retired Marine Lt. Col. Roger Charles, editor of 
DefenseWatch, the Internet newsmagazine of Soldiers for the Truth, said 
Tuesday.
    ``And then to brag you got it done in three months because of a 
cumbersome bureaucracy? What if people's lives were at risk? Oh wait, 
they are,'' Col. Charles said.
    The VA continues to test Chantix on veterans suffering from post-
traumatic stress disorder (PTSD), even as the Federal Aviation 
Administration has banned airline pilots and air traffic control 
personnel from taking the drug, citing the adverse side effects.
    Arthur Caplan, one of the nation's premier medical ethicists, said 
the VA's behavior in the anti-smoking study violated basic protections 
for humans in medical experiments, The Times reported.
    The White House on Tuesday defended the VA, saying the program is 
designed to help soldiers with PTSD.
    ``The VA is doing everything they can to be mindful of the safety 
of these veterans in all their programs and try to help them. This is 
the [VA], under wonderful leadership by [Secretary James B. Peake], who 
is interested in the health and safety of these veterans that are under 
his care, and every other member of that VA system is the same,'' White 
House spokesman Tony Fratto said.
    ``These are people who care for our veterans. They care for the 
troops that have been out there every day, fighting for this country. 
And they're interested in their safety,'' he said. ``Remember, this is 
a program dealing with former soldiers with PTSD. And it's a smoking-
cessation program. And they're interested in helping these veterans. So 
that's my reaction to it.''
    Nearly 1,000 veterans with PTSD were enrolled in the VA study to 
test methods of ending smoking, with 143 using Chantix. Twenty-one 
veterans reported adverse effects from the drug, including one who 
suffered suicidal thoughts, a three-month investigation by The Times 
and ABC News found.
    ``I was very concerned to read this morning's Washington Times and 
learn that the Department of Veterans Affairs (VA) has yet again failed 
to take appropriate steps to safeguard the health and well-being of 
veterans participating in drug trials,'' Mr. Obama said in a letter 
Tuesday to Mr. Peake.
    Mr. Obama cited a Government Accountability Office investigation of 
VA healthcare in Los Angeles that resulted in the suspension of all 
human testing because of numerous problems, including ``failures to 
provide adequate information to subjects before they participated in 
research.''
    ``Accordingly, I call on you to conduct a full and thorough 
investigation of the process by which VA conducts clinical trials and 
to take immediate corrective action to address the problems that were 
first identified by GAO 8 years ago,'' he said in the letter.
    Sen. John Cornyn, Texas Republican and a member of the Senate Armed 
Services Committee, also requested that Mr. Peake review the studies 
and identify everyone involved, as well as provide care ``to any 
veterans who have undergone this testing and ensure that any unethical 
practices are immediately brought to a halt.''
    ``Our wounded troops and veterans deserve the very best in care, 
but unfortunately, recent studies and incidents illustrate that some VA 
services have failed to live up to the standard of excellence that is 
expected,'' Mr. Cornyn said.
    In addition, Senate Veterans' Affairs Committee Chairman Daniel K. 
Akaka said his panel will question the ethics of the clinical trial 
involving the drug Chantix.
    ``The suggestion that VA researchers are not properly informing 
veterans about possible risks is troubling and deserves further 
investigation,'' the Hawaii Democrat said.
    Sen. Richard M. Burr of North Carolina, ranking Republican on the 
Veterans' Affairs Committee, also is questioning the VA clinical 
trial--in particular the timing of notification to study participants.
    ``VA should make every effort to quickly inform participants of any 
new drug information,'' Burr spokesman Mark Williams said.
    Added Kevin Bishop, spokesman for Sen. Lindsay Graham, South 
Carolina Republican: ``Advances in medicine should not come at the 
expense of our troops.''
    Stephen Dinan and Jon Ward contributed to this report.

                                 
                      ``Veterans as `Lab Rats' ''
                     The Washington Times Editorial
                             June 18, 2008
    It's time that the House and Senate Committee chairs investigate 
the Department of Veterans Affairs for medical ethics. As a three-month 
Washington Times/ABC News investigation revealed Tuesday, the VA is 
testing drugs with sometimes-severe side effects on hundreds of 
military veterans, including many post-traumatic stress syndrome 
patients, in trials whose risks the participants may not fully 
recognize. Evidence of troublingly slow risk assessment and predatory-
sounding enticements for Iraq and Afghanistan veterans are the chief 
shortcomings that beg Galen's principle: ``First, do no harm.'' The 
lives of service-member participants are too important, and the 
integrity of government post-traumatic stress disorder research is too 
vital, for the federal government to be taking these manifest risks.
    The scope of the problem is potentially very large, even systemic. 
The federal government has conducted 25 drug tests on veterans with 
post-traumatic stress disorder and carried out 300 studies on the 
disorder itself. (An estimated 300,000 Iran and Afghanistan veterans 
suffer from the disorder or from depression.) There are at least five 
test drugs bearing warnings about suicide or suicidal thoughts. Also, 
4,796 military veterans are enrolled in post-traumatic stress disorder 
studies--including 940 in the smoking cessation study that raised red 
flags. One hundred forty-three veterans in this study take Chantix, 
which is made by Pfizer Inc. and is the drug-cessation drug under 
special scrutiny in The Washington Times/ABC News investigation. The 
potential side effects of Chantix include neuropsychiatric symptoms, 
such as suicidal thoughts and depressed mood. Twenty-one veterans have 
reported adverse side effects because of Chantix--and the drug is still 
being used in VA studies.
    ``Lab rat'' is how one Iraq veteran describes his experience in the 
VA's volunteer medical experiments--and little wonder. Former Army 
sharpshooter James Elliott of Silver Spring was not informed of the 
serious potential side effects of Chantix until after a post-traumatic 
stress disorder recurrence that resulted in a potentially lethal 
encounter with police. The Iraq veteran assumed the study would follow 
safe protocols when he signed up for a chance to quit his habit of 
three packs of cigarettes a day and to receive the $30 monthly 
enticement. But soon, his nightmares and stress reactions returned with 
suicidal thoughts, to the point that his fiance called the police 
fearing Mr. Elliott might hurt himself. In the resulting standoff, 
police Tasered the armed Mr. Elliott, who recollects in an interview: 
``I would have shot me.''
    Why was a distressed veteran, who served 15 months in Iraq, not 
informed of Chantix's serious potential side effects until after this 
potentially lethal encounter?
    Chantix was a moving target, but the federal government was much 
too slow to respond. In November, the Food and Drug Administration 
(FDA) issued its first warning about Chantix. On Jan. 18, Pfizer 
updated its warning label: ``[P]atients who are attempting to quit 
smoking with Chantix should be observed for serious neuropsychiatry 
symptoms, including changes in behavior, agitation, depressed mood, 
suicidal ideation and suicidal behavior.'' Yet it was not until Feb. 29 
that the VA wrote to veterans and issued its own warning about 
``untoward changes in behavior'' and side effects, including ``anxiety, 
nervousness, tension, depression, thoughts of suicide, and attempted 
and completed suicide.''
    According to the FDA, nearly 40 suicides and more than 400 
incidents of suicidal behavior have been linked to Chantix. But it took 
three months for the Chantix warning to make its way through the VA 
system and to the patients, as this week's Washington Times/ABC News 
study showed. It was during that time Mr. Elliott relapsed into post-
traumatic stress.
    Too many lives were put at unnecessary risk--veterans' lives and 
those of neighbors, family and law enforcers--in a pattern that could 
easily recur unless and until the VA is better managed. At the very 
least, the VA should end the trials of Chantix.
    The lax communications regarding the Chantix trials are 
unconscionable. The federal government can do better: It must do 
better.
    The changes coming to bear at institutions like Walter Reed Army 
Medical Center and VA medical facilities are welcome. But human life is 
more important. This is a prime opportunity for those in Congress who 
strive for improved oversight of the executive branch. James Elliott's 
story is not one the government should allow to be repeated.

                                 
                   ``VA Reports More Chantix Effects,
              Study Participants Had 26 `Serious' Events''
                          The Washington Times
                     By Audrey Hudson and Amy Fagan
                             June 19, 2008
    War veterans with post-traumatic stress disorder suffered a total 
of 26 serious adverse events while participating in a Veterans Affairs 
study of the anti-smoking drug Chantix, a VA official said Wednesday 
night.
    ``Based on current data 26 Serious Adverse Events (SAE) occurred in 
patients while on Chantix,'' VA spokesman Matt Smith said in a 
statement e-mailed to The Washington Times, adding that 10 of the 
adverse events ``were of a psychiatric nature.''
    His e-mail also said, under a listing of ``Adverse Events,'' that 
there were two cases of suicidal thoughts.
    The agency previously said that 21 adverse events, only one of them 
serious (a case of suicidal thoughts), were recorded in the study that 
uses a drug now linked to psychotic and suicidal behavior, the details 
of which were reported in an exclusive Washington Times/ABC News 
investigation this week.
    Mr. Smith said officials could not determine whether the drug study 
is linked to the side effects.
    ``Causality can only be determined at the conclusion of a study 
when there are sufficient data available for analysis,'' he said.
    House Veterans' Affairs Committee Chairman Bob Filner, with other 
Democrats on his panel, sent a letter Wednesday to VA Secretary James 
B. Peake requesting immediate response to dozens of questions about his 
agency's treatment of servicemembers in its medical studies. The letter 
was issued before the agency released the new numbers.
    Mr. Smith said the new numbers are based on ``additional data'' 
that has accumulated since the agency spoke to The Times on May 21.
    ``A single patient can have more than one event--a breakdown 
patient by patient is not available,'' Mr. Smith said.
    Citing the investigative report, the congressmen inquired about how 
the VA informs participants involved in drug studies about possible 
side effects and whether the agency terminates studies that use drugs 
after the Food and Drug Administration (FDA) has issued alerts about 
them.
    ``This report raises serious questions about how the VA and FDA 
coordinate their studies, and how the VA responds to FDA post-approval 
alerts, particularly when vulnerable segments of the veteran population 
are involved in the studies,'' Mr. Filner, California Democrat, and 
fellow Democratic Reps. Edward J. Markey of Massachusetts and Paul W. 
Hodes of New Hampshire, said in their letter.
    The Times and ABC News first reported on Tuesday that a VA-
sponsored smoking-cessation experiment on nearly 1,000 veterans 
suffering from post-traumatic stress disorder (PTSD) provided the drug 
Chantix to 143 participants.
    The drug testing began in January 2007, and the FDA issued its 
first alert about dangerous side effects to Chantix in November. The VA 
did not warn its participants taking Chantix until 3 months later.
    Earlier Wednesday, Mr. Filner demanded that the VA immediately 
terminate experiments in which a drug now linked to psychotic and 
suicidal behavior is being administered to soldiers suffering from 
PTSD.
    ``The VA must immediately suspend this study until a comprehensive 
review of the safety of the protocol is conducted,'' he said.
    ``Once the FDA issued the warning that it had received reports 
linking Chantix to suicidal thoughts and aggressive and erratic 
behavior, the VA should have immediately suspended this study and 
notified participants of the possible dangers. Instead, the VA took 
more than 3 months to notify patients and they did so in bureaucratese 
that did not clearly state the side effects of the drug.''
    Mr. Filner also announced that he will hold hearings in early July 
``to figure out why it took so long to notify patients of the side 
effects of the drug that was used in this study.''
    The VA warning was issued too late for James Elliott, a decorated 
Army marksman who suffered a psychotic episode that ended in a nearly 
fatal confrontation with police. Mr. Elliott said the VA treated him as 
a ``disposable hero.''
    According to the FDA, nearly 40 suicides and more than 400 
incidents of suicidal behavior have been linked to Chantix. Yet the VA 
has continued the study and administered Chantix to veterans with PTSD.
    Arthur Caplan, one of the Nation's premier medical ethicists, said 
the VA's behavior in the anti-smoking study violated basic protections 
for humans in medical experiments, The Times reported.
    On Tuesday, presumptive Democratic presidential candidate Sen. 
Barack Obama and congressional leaders on both sides of the aisle 
called for investigations into the VA's failure to inform in a timely 
manner veterans participating in the medical tests.
    Rep. Steve Buyer of Indiana, the ranking Republican on the House 
Veterans' Affairs Committee, sent a letter to the VA inspector general 
and the VA's chief research and development officer requesting an 
investigation. A spokesman for House Speaker Nancy Pelosi, California 
Democrat, also said Congress also will look into the matter.
    The White House on Tuesday said that the VA is doing everything it 
can to be mindful of the safety of these veterans in all its programs 
and try to help them.
    ``These are people who care for our veterans. They care for the 
troops that have been out there every day, fighting for this country. 
And they're interested in their safety,'' White House spokesman Tony 
Fratto said.
    On Wednesday afternoon, Mr. Filner told The Times' ``Inside the 
Story'' radio program that Mr. Elliott's story ``speaks volume.''
    ``This is the bureaucratic dynamic in all its glory,'' Mr. Filner 
said.
    Mr. Elliott praised the medical treatment he has received from his 
doctors at the VA but said human testing belongs in the private sector.
    ``I don't lambaste the VA as a whole,'' he said. ``They have 
treated me well, the prosthetics department, my primary care doctor, a 
lot of people work very, very hard and they themselves are veterans and 
they do care.''
    ``It's just sad the psychiatric department has bought into human 
research. The VA should never conduct human research. They should be 
there to treat veterans' existing problems. Advancing healthcare should 
not be at the cost of men and women in the military,'' Mr. Elliott 
said.

                                 
              ``Doctors Raised Chantix Worries Last Year,
           Quiet Investigation Preceded Warnings by Months''
                          The Washington Times
                     By Audrey Hudson and Amy Fagan
                              July 8, 2008
    Department of Veterans Affairs doctors began raising red flags last 
year about whether the smoking-cessation drug Chantix was causing 
severe psychotic episodes among veterans, prompting a quiet 
investigation last fall but no warning for many months to the 32,000 
retired servicemembers prescribed the medication, according to internal 
agency documents reviewed by The Washington Times.
    ``Early reports'' from doctors at VA medical centers were flowing 
in throughout 2007, well before the U.S. Government and drug maker 
Pfizer Inc. issued public warnings late last year and earlier this year 
that Chantix had been linked to psychotic behavior, hallucinations and 
suicides, VA officials said.
    By late November, VA officials began collecting data showing nearly 
one out of every 1,000 veterans taking the drug had been hospitalized 
for severe psychosis, a rate noticeably higher than for veterans trying 
to stop smoking with alternative treatments like nicotine replacement, 
the documents show.
    VA officials told The Times that they decided to proceed with their 
normal process of studying their data for several months to determine 
whether the trend was ``statistically significant'' and did not issue 
immediate warnings.
    In the interim, more veterans were prescribed the drug, including 
some suffering from post-traumatic stress disorder (PTSD) who were 
enrolled in a medical experiment in which VA officials acknowledged 
Monday that the number of severe side affects averaged nearly one 
problem for every two veterans taking Chantix. VA officials said they 
wished in retrospect that their warnings had been issued sooner and 
they are examining how to improve their communications process.
    The House Veterans' Affairs Committee is set to investigate the 
VA's conduct in prescribing Chantix at hearings Wednesday, and the 
Committee's chairman said Monday that the inaction detailed in the 
documents obtained by The Times raised serious, new questions about 
whether the agency cared enough about the veterans it treats.
    ``When questioned, the VA immediately wants to defend `the 
process,' '' said Rep. Bob Filner, California Democrat. ``When is the 
VA going to understand that it is not about the process, but about the 
veteran? Veterans don't want to hear the VA defend its process. It's 
time for the VA to defend our veterans, our heroes.''
    Doctors treating veterans were reporting last year into a medical 
surveillance database maintained by the VA numerous instances in which 
the patients were taking Chantix when they were hospitalized for 
serious psychotic episodes. By October, the VA changed its tracking of 
Chantix side effects to include psychosis because of the concerns 
raised by doctors. A month later, the VA began a formal review that 
took nearly 4 months to complete, gleaning from the database all 
reports of psychotic behavior that required hospitalization.
    That review found that among 27 patients taking Chantix who were 
admitted to VA hospitals for psychiatric problems since the drug was 
approved for the market in 2006, 11 had attempted suicide, one 
attempted homicide, nine had suicidal thoughts, and six were suffering 
from hallucinations, according to an internal report completed on March 
18.
    Results ``show a greater crude rate of severe psychosis with 
varenicline compared to nicotine or nicotine/bupropion but do not reach 
statistical significance,'' the report concluded. ``These data show a 
signal for potential increased psychosis and warrant further 
examination to determine actual incidence and potential causality 
compared to control.''
    The study was never released to the public, but VA officials agreed 
to let The Times review it.
    The VA internal analysis examined more than 100 hospitalizations 
for psychiatric episodes of VA patients who had just begun trying to 
quit smoking by taking either varenicline (Chantix), nicotine-
replacement therapy, or nicotine-replacement therapy along with 
bupropion. It looked back at the time period between September 2006 and 
September 2007.
    VA officials noted that patients in the other groups also were 
admitted to hospitals for similar episodes, including 73 veterans who 
were trying the nicotine-replacement therapy and seven who were trying 
nicotine-replacement therapy and bupropion.
    But the rates of these events were highest among the Chantix 
group--9.8 hospitalizations per 10,000 patients. For instance, veterans 
taking nicotine replacement were suffering psychotic episodes requiring 
hospitalizations at a lesser of rate 6.8 per 10,000 patients.
    The report also found that nearly all of the patients in each of 
the three groups who were admitted to hospitals with psychiatric 
problems had histories of psychiatric problems, and more than half in 
each group had histories of some sorts of suicidal behaviors.
    By the time the review was completed in March, the Food and Drug 
Administration (FDA) and Pfizer already had issued public warnings 
about Chantix.
    Even then, VA officials conducting the review didn't urge that all 
veterans taking the medicine under the VA's care get warning letters. 
Instead, the review recommended that the FDA conduct a full 
epidemiological study of the drug at a cost of $250,000.
    Virginia Torrise, VA's deputy chief consultant of Pharmacy Benefits 
Management, said agency officials were not able in their informal 
review ``to actually correlate and say there was a causal effect'' 
between any of the drugs or nicotine treatments and the psychiatric 
events and that is why they recommended a formal FDA study.
    The VA began sending warning letters to all 32,000 veterans who 
have taken Chantix in late spring, nearly 3 months after the internal 
review was completed. The first letters were sent on May 30 and told 
veterans that they should be careful operating heavy machinery if they 
are taking Chantix, repeating a warning just days earlier from the 
Federal Aviation Administration when it banned pilots from taking the 
drug.
    Updated guidelines for prescribing Chantix were posted on the VA 
Web site June 18, and the agency then sent out letters to all veterans 
taking the drug to specifically warn them that suicidal tendencies were 
a possible side effect.
    Those actions were prompted by a joint investigative report by The 
Times and ABC News on June 17 that documented how the VA failed to warn 
more than 200 veterans suffering from PTSD who where participating in a 
smoking-cessation study of Chantix's possible side effects. During the 
delay, one of the Iraq War veterans, former Army sharpshooter James 
Elliott, in that study suffered a psychotic episode so severe that it 
led to a near lethal confrontation with police, The Times reported.
    The VA initially reported that 143 veterans had taken Chantix in 
conjunction with the smoking-cessation study, and about two dozen had 
suffered some side effects. But on Monday, VA officials significantly 
raised those numbers, acknowledging that at least 241 veterans in the 
study had taken Chantix as of June 25, and that 114 serious adverse 
events were reported by 75 of those participants. Among the side 
effects, 22 involved psychiatric events.
    The number of veterans now taking Chantix in that study has dropped 
to 40, officials said.
    The description of the study's effort provided to The Times said 
that when the FDA approved Chantix, ``the drug had not been studied in 
VA patients or patients with mental health conditions.''
    ``VA received early reports of . . . adverse drug reactions from 
various medical centers which signaled to VA the need for a 
pharmacovigilance effort that added psychosis to the events being 
tracked and ultimately analyzed and placed into a report,'' the VA 
said.
    Wednesday's congressional hearing will review the VA process for 
handling human research subjects, the agency's responsibility to 
respond to the FDA's advisories, and the relationship between 
pharmaceutical companies and researchers. Witnesses include VA 
Secretary James B. Peake; Dr. John D. Daigh, assistant inspector 
general; Mr. Elliott; and Lt. Col Roger Charles, editor of 
DefenseWatch.
    Lawmakers are concerned because the VA's alerts about Chantix side 
effects lagged those of the drug maker and the FDA.
    For instance, Pfizer updated its Chantix label in January to warn 
of possible ``serious neuropsychiatric symptoms, including changes in 
behavior, agitation, depressed mood, suicidal ideation and suicidal 
behavior.''
    The FDA first issued a notice about possible additional side 
effects of Chantix in November and issued a health alert on Feb. 1, 
warning that Chantix could result in changes in behavior, agitation, 
depressed mood, suicidal thoughts and attempted suicide.

                                 

                                U.S. Department of Veterans Affairs
      Assistant Secretary for Congressional and Legislative Affairs
                                                    Washington, DC.
                                                      July 18, 2008
The Honorable Bob Filner
Chairman
Committee on Veterans' Affairs
U.S. House of Representatives
Washington, DC 20515

    Dear Mr. Chairman:

    As promised by the Secretary of the Department of Veterans Affairs 
during the House Veterans Affair's Committee hearing on July 9, 2008, 
enclosed is the response to Congresswoman Shelley Berkley's inquiry 
about a veteran testifying that he had unsuccessfully sought emergency 
care at the Washington DC Veterans Affairs Medical Center. This 
response is the result of the findings of the Office of Medical 
Inspector.
    Please note that the enclosure contains individually identified 
personal information which is protected by the Privacy Act, 5 U.S.C. 
Sec. 552a, the Veterans Records Confidentiality Statute, 38 U.S.C. 
Sec. 5701 (a), 38 U.S.C. Sec. 7332, and the HIPAA Privacy Rule, 45 
C.F.R. Parts 160 and 164. Each of these authorities limits the 
Department's ability to publicly disclose the information in an 
individually identifiable form. While this information is not protected 
by these authorities once under the Committee's jurisdiction, it is 
considered to be of a sensitive nature. You may wish to consider this 
fact in any decision whether to redisclose this information. In order 
to protect the personal privacy of individuals who may be identified 
from the records provided to the Committee, the Committee may wish to 
delete any identifying personal information before redisclosing these 
records. If the Committee wishes, the Department would be pleased to 
assist by providing a suitably redacted copy for public release.
    As the Secretary has said many times, trust, accuracy and 
transparency are paramount to maintaining the Department of Veterans 
Affairs' relationships with our veteran patients, with you and other 
Members of Congress.
            Sincerely yours,
                                                  Christine O. Hill
                                         Acting Assistant Secretary
    Attachment:
    ``Quality of Care Concern--Veterans Integrated Service Network 5 
Veterans Affairs Medical Center Washington, DC,'' Interim Report 2008--
D-963, Office of the Medical Inspector, Veterans Health Administration, 
U.S. Veterans Administration, July 18, 2008. [The attached report will 
be retained in the Committee files due to confidential personal 
information included in the report.]

                                 

                                     Committee on Veterans' Affairs
                                                    Washington, DC.
                                                      July 14, 2008
James Elliott
407 Thayer Place
Silver Spring, MD 20910

    Dear James:

    In reference to our Full Committee hearing ``Why Does the VA 
Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?'' on 
July 9, 2008, I would appreciate it if you could answer the enclosed 
hearing questions by the close of business on August 20, 2008.
    In an effort to reduce printing costs, the Committee on Veterans' 
Affairs, in cooperation with the Joint Committee on Printing, is 
implementing some formatting changes for materials for all full 
committee and subcommittee hearings. Therefore, it would be appreciated 
if you could provide your answers consecutively and single-spaced. In 
addition, please restate the question in its entirety before the 
answer.
    Due to the delay in receiving mail, please provide your response to 
Debbie Smith by fax at 202-225-2034. If you have any questions, please 
call 202-225-9756.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

                        QUESTIONS FOR THE RECORD
                Questions from the Honorable Bob Filner
                          For James G. Elliott
           Before the Committee on Veterans' Affairs Hearing
                  ``Why Does the VA Continue to Give a
             Suicide-Inducing Drug to Veterans with PTSD?''
                              July 9, 2008
    Question 1: From what I understand, the primary objective of the 
study was to compare the effectiveness of two approaches for delivering 
smoking cessation treatment for veterans with PTSD. The first approach 
was offering smoking cessation treatment in conjunction with mental 
health care for PTSD and the second approach was referral to 
specialized smoking cessation clinics (VA's usual standard of care). 
This study was not a drug trail or investigation into the effectiveness 
of Chantix'. Was this your understanding of the study you 
were enrolled in? If no, please explain what you thought was the 
purpose of the study?
    Response: The use of oral medications was never mentioned to me 
until 30 October, 2007. In the initial 3-hour meeting with Mary Ann 
Rapp and Lloyd Webster, I was told that the study was to last three 
years and that it would in conjunction with my mental health care. I 
was told that Dr. Hallie Lightdale would prescribe me nicotine patches. 
I was told that they were not concerned about short term results.
    Question 2: According to the VA, Chantix' is meant to be 
used as a third option for those who fail to quit smoking by nicotine 
replacement therapy and Zyban (buproprion). Were you given any other 
smoking cessation drugs prior to Chantix'?
    Response: No, I was never offered any other pharmaceutical options 
other than Varenicline Tartrate/Chantix'.''
    Question 3: You mentioned in your written testimony that you began 
to suffer serious dermatological side effects by the time you started 
taking the full dosage regimen for Chantix'. As a result, 
you quit taking the medicine until you were told to resume by your 
prescribing physician. From the time you initially took 
Chantix' to the time you quit, due to the dermatologic side 
effects, did you experience any other side effects, such as anxiety, 
nervousness, tension, depressed mood, unusual behaviors or suicidal 
ideation?
    Response: Yes. I began having extreme nightmares, paranoia and 
began calling in air strikes at night in my sleep.
    Question 3a: When you were told to resume Chantix' by 
your physician, were you informed of the possible side effects listed 
in the FDA Early Communication?
    Response: I was not informed of the possible side effects listed in 
the FDA early communication when Dr. Lightdale told me to resume taking 
Varenicline Tartrate/Chantix'.
    Question 4: In November, the FDA issued an Early Communication 
saying that it had received reports of suicidal thoughts and aggressive 
and erratic behavior in patients who have taken Chantix'. If 
the VA had told you these were possible side effects of 
Chantix', would you have requested to be withdrawn from the 
study or considered using another smoking cessation drug?
    Response: If the VA had told me of those possible side effects I 
would not have continued taking Varenicline Tartrate/
Chantix' and would have withdrawn from the study.

                                 

                                     Committee on Veterans' Affairs
                                                    Washington, DC.
                                                      July 14, 2008
Lieutenant Colonel Roger Charles, USMC (Ret.)
Vice-Chairman, Soldiers For The Truth
 Editor, DefenseWatch
2605 Russell Road
Alexandria, VA 22301

Dear Roger:

    In reference to our Full Committee hearing ``Why Does the VA 
Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?'' on 
July 9, 2008, I would appreciate it if you could answer the enclosed 
hearing questions by the close of business on August 20, 2008.
    In an effort to reduce printing costs, the Committee on Veterans' 
Affairs, in cooperation with the Joint Committee on Printing, is 
implementing some formatting changes for materials for all full 
committee and subcommittee hearings. Therefore, it would be appreciated 
if you could provide your answers consecutively and single-spaced. In 
addition, please restate the question in its entirety before the 
answer.
    Due to the delay in receiving mail, please provide your response to 
Debbie Smith by fax at 202-225-2034. If you have any questions, please 
call 202-225-9756.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

                        Questions for the Record
                Questions from the Honorable Bob Filner
          For Lieutenant Colonel Roger G. Charles, USMC (Ret.)
              Vice-Chairman, Board of Trustees, and Editor
                              DefenseWatch
           Before the Committee on Veteran's Affairs Hearing
                  ``Why Does the VA Continue to Give a
             Suicide-Inducing Drug to Veterans with PTSD?''
                              July 9, 2008
    Question 1: Could you tell this Committee your experience with Mr. 
Elliot and how you got involved with the veteran?
    Response: Mr. Elliott and his fiance, Ms. Hilburn, contacted Eilhys 
England Hackworth, Chairperson of SFTT's Board of Trustees. Ms. England 
told me to check into the merits of their story and provided me contact 
information on Mr. Elliott and Ms. Hilburn. I initially met with Ms. 
Hilburn, and subsequently with both her and Mr. Elliott. After 
validating the essential elements of the information they provided, I 
decided that Mr. Elliott's story deserved wider attention than what my 
posting a story in our cyber-based newsletter, DefenseWatch, could 
provide.
    I then contacted the Executive Editor of the Washington Times, Mr. 
John Solomon, and provided him my assessment that this was a 
significant news story. He put me in contact with a member of his 
staff, Ms. Audrey Hudson, who took the story for further action.
    Question 2: While writing the story, did you interview or talk with 
any of the VA staff regarding Mr. Elliott? If so, could you tell us 
what type of reaction you received from the staff?
    Response: I did not contact the VA staff regarding Mr. Elliott.

                                 

                                     Committee on Veterans' Affairs
                                                    Washington, DC.
                                                      July 14, 2008
The Honorable James B. Peake, M.D.
The Secretary
Department of Veterans Affairs
810 Vermont Avenue, NW
Washington, DC 20420

Dear Mr. Secretary:

    In reference to our Full Committee hearing ``Why Does the VA 
Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?'' on 
July 9, 2008, I would appreciate it if you could answer the enclosed 
hearing questions by the close of business on August 20, 2008.
    In an effort to reduce printing costs, the Committee on Veterans' 
Affairs, in cooperation with the Joint Committee on Printing, is 
implementing some formatting changes for materials for all full 
committee and subcommittee hearings. Therefore, it would be appreciated 
if you could provide your answers consecutively and single-spaced. In 
addition, please restate the question in its entirety before the 
answer.
    Due to the delay in receiving mail, please provide your response to 
Debbie Smith by fax at 202-225-2034. If you have any questions, please 
call 202-225-9756.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

           Questions from the Honorable Bob Filner, Chairman,
                  House Committee on Veterans' Affairs
                              July 9, 2008
        Why Does the VA Continue to Give a Suicide-Inducing Drug
                         to Veterans with PTSD?
    Question 1: This incident is merely the latest incident in a series 
of events, from the suicides in Dallas to the e-mail suggesting VA 
providers downgrade the diagnosis of PTSD to ``adjustment disorders'' 
to the e-mail downplaying the epidemic of suicides in the VA that have 
caused this Committee to question the VA's accountability measures. 
What actions do you plan on taking to address what seemingly are 
process issues and communications problems within the VA?
    Response: The Department of Veterans Affairs (VA) clinical response 
to new information about varenicline demonstrates effective and 
responsible action. On November 21, 2007, one day after the Food and 
Drug Administration (FDA) issued an Early Communication about possible 
psychiatric side effects of varenicline, VA's pharmacy benefits 
management (PBM) program distributed this information to pharmacists 
and providers throughout the system. Notification of patients through 
their physicians, who prescribed the medication, started happening 
almost immediately. Warning labels affixed to every prescription for 
varenicline were changed in December 2007 to advise patients to, ``Call 
your doctor immediately if you experience mood changes, such as new or 
worsening feelings of sadness, depression, or fear.''
    On January 18, 2008, VA issued further guidelines based on new 
information received from the European Medicines Agency (EMEA) and FDA 
stating, ``Health care providers should educate veterans prior to 
starting varenicline about the possibility of changes in behavior or 
mood and that the veteran should report any changes of behavior or mood 
to the provider. Health care providers should monitor veterans taking 
varenicline for changes in mood and behavior.'' This guidance also 
noted both EMEA's preliminary warning about the risk of suicidal 
ideation and suicide attempt within the context of smoking cessation 
attempts and FDA's preliminary assessment of additional cases of 
suicidal ideation and depressed mood for those taking varenicline. 
After the FDA issued a Public Health Advisory on February 1, 2008, VA 
notified clinicians on February 5 and called specific attention to the 
risk of suicidal ideation.
    After FDA changed labeling on the medication on May 16, 2008, VA 
issued a national Bulletin (May 30) to all practitioners informing them 
of the new warnings, and also sent a patient letter for formulary 
leaders and pharmacy chiefs to provide to their patients.
    In addition, following the recent news reports, VA sent a letter on 
June 20 to all patients using varenicline, asking them to contact VA if 
they experience any changes in mood or behavior or thoughts of suicide, 
and offering to find another way to help them quit smoking.
    Within the context of VA's research program and cooperative studies 
program (CSP) study number 519, on June 25, 2008, the Secretary of 
Veterans Affairs directed the Under Secretary for Health to conduct 
four evaluations:

        1. The Secretary requested a comprehensive review of CSP-519, 
through VA's Office of Research Oversight (ORO). These results and an 
action plan with recommendations were presented to the Secretary on 
August 11, 2008.
        2. Despite the fact that CSP-519 is not a drug study, the 
Secretary directed that there be Institutional Review Board (IRB) 
reviews of all post traumatic stress disorder (PTSD) drug protocols in 
our system to ensure that there is appropriate sensitivity to the study 
population in the context of FDA alerts and warnings. The Secretary 
also directed a review of the risks of medications that are likely to 
be used in the study population and the proper subject notification of 
associated risks. With ORO to report results to the Secretary, and the 
Under Secretary for Health to provide an action plan on September 5, 
2008.
        3. The Secretary tasked Office of Research and Development 
(ORD) and the Office of Pharmacy Benefits Management (PBM) to conduct a 
review of VA's adverse event reporting system to ensure that there is, 
in fact, timely reporting and analysis of data, and that the system 
supports the appropriate escalation of reporting and sensitive issues 
for subject safety. The Veterans Health Administration (VHA) presented 
these results and action plan to the Secretary on July 29, 2008.
        4. The Secretary required PBM to review VHA's medication 
notification policies to ensure the system's support timely 
communications to patients and providers, including those in research 
programs. Results and action plan were reported to the Secretary on 
July 29, 2008.

    In addition, the Inspector General investigated human subject 
protections in CSP-519 at the Washington, DC VA Medical Center (VAMC). 
The Office of the Inspector General has discussed its findings with the 
Secretary and prepared its draft report.
    VA recently created a central IRB to enhance the efficiency of IRB 
review of multi-site research projects, including the review and 
approval of notices to be sent to research participants (for example, 
new information about the project, changes in the protocol and/or 
informed consent).
    Question 2(a): On February 13, the Cooperative Studies Program 
(CSP) sent a consent addendum and a letter to each of the Institutional 
Review Boards (IRBs) at the 11 different sites to serve as a baseline 
for notification to all study participants. The IRB at the Washington, 
DC VAMC approved the letter and consent addendum on March 3, 2008, a 
reasonable turnaround time. However, IRB approval at Houston did not 
occur till April 30, in New Orleans it did not occur till May 28, and 
in Portland it did not occur till June 13. In April 2008, there were 42 
study participants on Chantix' between the Houston, New 
Orleans and Portland sites. This was nearly one-third of the total 
study participants taking Chantix'. Don't you think that IRB 
approval for the consent addendum and letter was much too slow at these 
sites?
    Response: VA is concerned about the time that elapsed at a number 
of study sites between the receipt of the letters and consent addendums 
by IRBs and when they were received by veterans, as well as the lack of 
follow-up by study coordinators to ensure that their directions were 
carried out. There is a clear need for improvement in these areas. VA 
is conducting several investigations into these research practices and 
has recently created a central IRB to enhance the efficiency of IRB 
review of multi-site research projects, including the review and 
approval of notices to be sent to research participants.
    Question 2(b): Who is responsible for ensuring that each site's IRB 
approves the consent addendum and letter in a timely manner?
    Response: The Chair(s) of the IRB are responsible for ensuring each 
site's IRB approves the consent addendum and letter in a timely manner. 
The facility director is ultimately responsible for ensuring the 
integrity of the program. In CSP-519, the timing of mailings of the 
letter and the consent form addendum were left to the individual IRBs. 
VA's agreement with study participants indicated that if any new 
specific information became available related to the study we would 
inform them, and study leaders determined that the FDA's Public Health 
Advisory (dated February 5, 2008) met that standard.
    Question 2(c): What is reasonable turn around time for IRBs to 
approve and send the letters to study participants?
    Response: Each IRB decides when and how to approve any consent 
addendum or letters. However, VA is conducting investigations into 
these research practices and has created a central IRB to enhance the 
efficiency of IRB review of multi-site research projects, including the 
review and approval of notices to be sent to research participants 
(such as new information about the project, changes in the protocol 
and/or informed consent).
    The Secretary directed the Under Secretary for Health to conduct a 
review of the risks of medications that are likely to be used in the 
PTSD study population and that there is proper notification to research 
participants of associated risks. The ORO is to report their findings 
to the Secretary, and the Under Secretary for Health will provide an 
action plan on September 5, 2008.
    IRBs are established by the Federal Policy (Common Rule) for the 
Protection of Human Subjects at 38 CFR Part 16 and by FDA regulations 
at 21 CFR Part 56 and all processes for reviews and approvals are the 
responsibility of the respective IRB. With regard to reasonable 
turnaround times, these vary according to the circumstances of the 
study and the seriousness of the new information. For example, an FDA 
or manufacturer recall would demand immediate notification of all 
affected patients, while a new advisory that provides previously 
disseminated information could be considered less urgent.
    Question 3: The letter [states] that side effects of 
Chantix' may include ``an increase in psychiatric symptoms 
such as anxiety, nervousness, tension, and depression as well as 
untoward changes in behavior.'' It failed to include suicidal ideation 
or attempted suicide. However, they were listed in the informed consent 
addendum that was included with the letter. Why were the most dangerous 
side effects omitted from the letter but included in the consent 
addendum?
    Response: The cover letter was provided to inform study 
participants of the need to review the informed consent addendum, which 
did mention ``suicidal ideation'' as a side effect. The informed 
consent is the regulatory document of record for participants in 
research. Because the study participant's doctor would be the most 
qualified professional to discuss the use of varenicline specifically 
with their patient, the cover letter informed the study participants 
that the risks of varenicline would be discussed in depth at their next 
study visit and that they could call study staff with concerns or 
questions before then. The letter also informed participants that they 
should contact their provider or study staff immediately if they 
experienced changes in behavior/mood, or if they would like to stop the 
medication.
    The cover letter was not intended to serve as a stand-alone 
document that would duplicate the consent addendum, which was attached. 
Instead, the purpose of the cover letter was to provide a brief and 
concise introduction to the addendum--an addendum that explicitly 
listed all the potential side effects identified by the FDA's warning, 
including suicidal ideation and suicidal behavior.
    Question 4: In retrospect, looking at the steps that were taken to 
notify study participants and other veterans who were taking 
Chantix', should the VA have done more to confirm 
notification or expedite the process?
    Response: VA is concerned about the time that elapsed at a number 
of study sites between the receipt of the letters and consent addendums 
by IRBs and when they were received by veterans. VA can and will be 
more directive to IRBs about the time in which actions and decisions 
are made, should the need arise again in the future. We are also 
concerned about the lack of follow-up by study coordinators to ensure 
that the IRB's directions are carried out. There is a clear need for 
improved follow-up in this area. The Secretary directed the Under 
Secretary for Health to conduct a review of the risks of medications 
that are likely to be used in the PTSD study population and that there 
has been proper notification of associated risks. ORO is to report its 
findings to the Secretary, and the Under Secretary for Health will 
provide an action plan on September 5, 2008.
    Moreover, the Secretary required PBM to review VHA's medication 
notification system to ensure the system's policies support timely 
communications to patients and providers, including those in research 
programs. Results and an action plan were reported to the Secretary on 
July 29, 2008.
    Question 5: The Washington Times reported that a VA internal report 
completed on March 18 found ``that among 27 patients taking 
Chantix' who were admitted to VA hospitals for psychiatric 
problems since the drug was approved for the market in 2006, 11 had 
attempted suicide, one attempted homicide, nine had suicidal thoughts, 
and six were suffering from hallucinations, according to an internal 
report completed on March 18.'' Are you aware of this report? What 
actions did the VA take after completion of this report? Were the 
results of this report shared with physicians prescribing 
Chantix' or those involved in the smoking cessation study?
    Response: VA is aware of the draft rapid cycle analysis report, 
dated March 18, referenced in The Washington Times article. This 
information was the preliminary product of an analysis of data gathered 
between September 2006 and September 2007. The varenicline analysis 
using the integrated database is set to run every 6 months to search 
for suspected severe adverse medication events of interest.
    The results of the internal analysis were shared with some but not 
all providers. Specifically, results were shared with the Medical 
Advisory Panel on March 12, 2008, FDA on March 18, 2008 (by telephone) 
and again on April 10, 2008 (in a face-to-face meeting), the veterans 
integrated service network (VISN) formulary leaders, representatives 
from the smoking cessation technical advisory group, representatives 
from the mental health group and one of the principal investigators of 
CSP-519. Rapid cycle analyses such as this one are put in place to 
identify potential signals; they are not designed to determine 
causality, so the results are not distributed to providers across the 
system like drug safety warnings from FDA.
    We began this analysis because the characteristics of the 
population within the varenicline clinical trials did not fully 
resemble VA's patient population, which tends to be older to experience 
more health problems. In October 2007, PBM and VA center for medication 
safety (VA MedSafe) added psychosis because of comments from field 
practitioners to the ICD-9 codes of interest. Specifically, VA's 
pharmacy benefits management group received early reports of central 
nervous system adverse medication events from several medical centers, 
which suggested the need for vigilance in our monitoring and tracking. 
Prior to that time, VA MedSafe was only tracking atrial fibrillation 
and severe dehydration, the known severe side effects associated with 
varenicline. The psychosis codes that were used, included specific 
codes for psychosis, these were not e-codes or specific codes for 
suicidality.
    In this report, VA MedSAFE tracked the adverse medication events 
associated with varenicline by using and assessing VA's spontaneous 
adverse drug event reporting database and through administrative, 
integrated databases. The analysis showed,

         ``a greater crude rate of severe psychosis with varenicline 
        compared to nicotine/buproprion but do not reach statistical 
        significance. These data show a signal for potential increased 
        psychosis and warrant further examination to determine actual 
        incidence and potential causality compared to control. A large 
        number of patients receiving all of these agents (nicotine 
        replacement, buproprion, or varenicline) have a history of 
        psychiatric disease as identified by agents used to treat 
        psychiatric illness or a diagnosis of psychiatric illness. This 
        confirms our need to continue to track (the) use of varenicline 
        and adverse medication events in our patient population as 
        minimal data were available on the use of varenicline in this 
        patient population upon FDA approval.'' \1\
---------------------------------------------------------------------------
    \1\ VA MedSafe. ``Draft: National Varenicline Integrated Database 
and Validation Rapid Cycle Analysis Results.'' U.S. Department of 
Veterans Affairs (Internal Document).

    The majority of the patients in the validated group (for all three 
cohorts) had a psychiatric history and over one half had a history of 
suicidal behavior.
    Question 6(a): In October 2007, the Association for the 
Accreditation of Human Research Protection Programs (AAHRPP) conducted 
a site visit to the Washington, DC VA Medical Center. The Council 
deferred making a decision about accreditation and instead placed the 
medical center in Accreditation-Pending. One of the standards described 
as ``Not Met'' by AAHRPP was developing ``an informed consent process 
and method of documentation appropriate to the type of research and the 
study population, emphasizing the importance of participant 
comprehension and voluntary participation.'' What is VA doing to fix 
the deficiencies in the informed consent process at the Washington, DC 
VAMC?
    Response: The Washington, DC VA Medical Center (VAMC) has 
systematically responded to the concerns in the informed consent 
process identified in the October 3031, 2007 AAHRPP report. 
Specifically, AAHRPP noted the template document did not have 
investigators include the following information when appropriate: a 
statement that if the participant was or became pregnant, the 
particular treatment or procedure might involve risks to the embryo or 
fetus, which were currently unforeseeable, and that additional costs to 
the participant might result from participation in the research. They 
have revised their IRB policies and procedures (revised standard 
operating procedures were adopted June 30, 2008), developed new consent 
templates (which address both of the issues raised above), and revised 
IRB review forms. These procedures have been put in place by training 
IRB members, researchers, and study staff in these new procedures and 
in the use of the revised forms. Training has occurred through face-to-
face meetings, by e-mail, and by communication of IRB findings. The 
Washington, DC VAMC has instituted an audit program that includes 
review of consent documents and observation of the consent process.
    Information regarding the consent template was sent in an e-mail to 
principal investigators and study coordinators on July 9, 2008. An 
information session regarding the changes was held for principal 
investigators and study coordinators on Wednesday, July 30, 2008.
    Question 6(b): How many other medical centers have received 
Accreditation-Pending from AAHRPP?
    Response: Currently, 18 VA facilities, representing 26 VA 
facilities with Federal Wide Assurances (FWA), are in the AAHRPP 
accreditation-pending category. This includes the Washington, DC VAMC. 
The Washington, DC VAMC received a 3 year accreditation by National 
Committee for Quality Assurance (NCQA) in March 2005. In VA's 
experience, 62 percent of facilities applying for accreditation have 
received accreditation-pending status at the time of their first AAHRPP 
Council review. Thirty-eight percent received full or qualified 
accreditation after the first Council review.
    VA leads all Federal agencies in accreditation of human research 
protection programs. There are a total of 115 VA facilities with FWAs 
to perform human research. Between December 2003 and January 2006, 59 
VA facilities representing 71 VA facilities with FWAs were accredited 
by NCQA. NCQA contract expired in January 2006 and, under the new 
contract, AAHRPP has accredited 49 VA facilities representing 57 VA 
facilities with FWAs. This includes re-accreditation of all but 19 
NCQA-accredited facilities, which have submitted AAHRPP applications 
and will have site visits this summer. In total, 112 out of 115 VA 
facilities have at least submitted applications to AAHRPP.
    To date, 78 non-VA sites are listed on AAHRPP's Web site as having 
achieved AAHRPP accreditation.
    Six VA facilities were not accredited by NCQA, and have not yet 
obtained AAHRPP accreditation status. Three of the six (Little Rock, 
Fayetteville and Lebanon) have new IRB arrangements and will apply for 
AAHRPP accreditation in 2009. The other three have submitted their 
applications to AAHRPP, but have not yet been reviewed by AAHRPP's 
Council.
    AAHRPP requires that accredited organizations meet 20 demanding 
standards covering five distinct domains that address the:
      Organization (the entity assuming responsibility for the 
human research program and applying for accreditation);
      Research review unit, including IRBs;
      Investigator;
      Sponsor; and
      Participants.
    There are four actions that may be taken by AAHRPP on an 
application for accreditation.
         Full Accreditation--An organization placed in this category 
        meets all Standards.
         Qualified Accreditation--An organization placed in this 
        category meets almost all of the Standards. Issues requiring 
        corrective action are minor and administrative in nature.
         Accreditation-Pending--AAHRPP places an organization in this 
        category when the organization does not meet the criteria for 
        full or qualified accreditation, but AAHRPP considers the 
        organization to be able and willing to take corrective actions 
        within a reasonable time period.
         Accreditation Withheld--An organization placed in this 
        category does not meet a substantial number of accreditation 
        Standards and the Council on Accreditation believes that the 
        organization will not commit to undertake corrective action or 
        otherwise be unable to meet the criteria for qualified or full 
        accreditation in a reasonable time. There are no VA facilities 
        in the accreditation withheld category.

                                 

                                     Committee on Veterans' Affairs
                                                     Washington, DC
                                                      July 14, 2008
Paul Seligman, M.D., M.P.H.
Associate Director of Safety Policy and Communication
Center for Drug Evaluation and Research
Food and Drug Administration
WO51 Room 6133 HFD-001
10903 New Hampshire Ave.
Silver Spring, MD 20993

Dear Paul:

    In reference to our Full Committee hearing ``Why Does the VA 
Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?'' on 
July 9, 2008, I would appreciate it if you could answer the enclosed 
hearing questions by the close of business on August 20, 2008.
    In an effort to reduce printing costs, the Committee on Veterans' 
Affairs, in cooperation with the Joint Committee on Printing, is 
implementing some formatting changes for materials for all full 
committee and subcommittee hearings. Therefore, it would be appreciated 
if you could provide your answers consecutively and single-spaced. In 
addition, please restate the question in its entirety before the 
answer.
    Due to the delay in receiving mail, please provide your response to 
Debbie Smith by fax at 202-225-2034. If you have any questions, please 
call 202-225-9756.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

                       U.S. Department of Health and Human Services
                                       Food and Drug Administration
                                                     Rockville, MD.
                                                 September 16, 2008
The Honorable Bob Filner
Chairman
Committee on Veterans' Affairs
House of Representatives
Washington, D.C. 20515

Dear Mr. Chairman:

    Thank you for providing the Food and Drug Administration (FDA or 
the Agency) the opportunity to testify at the July 9, 2008, hearing 
entitled ``Why Does the VA Continue to Give a Suicide-Inducing Drug to 
Veterans with PTSD?'' before the House Committee on Veterans' Affairs. 
Dr. Paul Seligman, M.D., M.P.H., Associate Director of Safety Policy 
and Communication, Center for Drug Evaluation and Research (CDER), 
testified for the Agency. We are responding to your letter of July 14, 
2008, containing questions for the record.
    We have repeated your questions below in bold, followed by our 
responses.

    1. How many reports of suicidal ideation and attempted suicide did 
FDA receive priorto issuing the Early Communication?

    FDA issued an Early Communication about Chantix' 
(varenicline) on November 20, 2007. Below is a chart containing data 
from FDA's Adverse Event Reporting System (AERS) for suicidal-related 
events for varenicline. The first column lists the ``Preferred Term,'' 
describing the reported behavior. FDA arrives at the preferred term 
using terms described in the Medical Dictionary for Regulatory 
Activities (MedDRA). The second column, ``Individually Reviewed 
Reports'' spans the time period from the start of varenicline 
marketing, July 10, 2006, until November 27, 2007.
    Reports from a ``crude count'' search were individually reviewed 
\1\and duplicates and irrelevant cases were removed. Therefore, these 
reports represent unique patients.
---------------------------------------------------------------------------
    \1\ The main utility of a spontaneous reporting system, such as 
AERS, is to provide signals of potential drug safety issues. Hence, 
when considering crude counts from AERS, it should be realized that 
accumulated case reports cannot be used to calculate incidence or 
estimates of drug risk for a particular product, as reporting of 
adverse events is a voluntary process and underreporting exists. 
Further, because of the multiple factors which influence reporting, 
comparisons of drug safety cannot be made from these data. Some of 
these factors include the length of time a drug is marketed, the market 
share, size and sophistication of the sales force, publicity about an 
adverse reaction, and regulatory actions. It also should be noted that 
in some cases, the reported clinical data is incomplete, and there is 
no certainty that the drugs caused the reported reactions. A given 
reaction may actually have been due to an underlying disease process or 
to another coincidental factor. Further, crude counts may reflect 
duplicates.


          AERS DATA FOR SUICIDAL-RELATED EVENTS FOR VARENICLINE
------------------------------------------------------------------------
                                        Individually Reviewed Reports 7/
            Preferred Term                     10/06 to 11/27/07
------------------------------------------------------------------------
Completed suicide                                                    18
------------------------------------------------------------------------
Suicide attempt                                                      14
------------------------------------------------------------------------
Intentional self-injury                                               3
------------------------------------------------------------------------
Self-injurious behavior                                               0
------------------------------------------------------------------------
Suicidal behavior                                                     0
------------------------------------------------------------------------
Suicidal ideation                                                   111
------------------------------------------------------------------------
Self-injurious ideation                                               6
------------------------------------------------------------------------
Multiple drug overdose                                                0
------------------------------------------------------------------------
Depression suicidal                                                   0
------------------------------------------------------------------------
Gun shot wound                                                        0
------------------------------------------------------------------------
Intentional drug misuse                                               0
------------------------------------------------------------------------
Overdose                                                              1
------------------------------------------------------------------------
Total number of reports                                             153
------------------------------------------------------------------------


    2. Given that Chantix' was a newly approved drug when it 
was included in the Smoking Cessation Study, should the VA have 
considered reporting both adverse events and serious adverse events?

    Because this study is not being conducted under an Investigational 
New Drug (IND) application, and because the VA is not the New Drug 
Application (NDA) holder for the drug, the VA is under no obligation to 
report adverse events to FDA. There are no mandatory reporting 
requirements for this situation.
    The VA clinical study involving Chantix' is a study 
comparing different treatment strategies for smoking cessation, some of 
which included drug therapy. Based on our understanding of this study, 
we believe that the study meets the criteria for an exemption from the 
IND requirements in Title 21 Code of Federal Regulations (CFR) 312.2 
because:

      Chantix' is a lawfully marketed drug.
      The study is not being conducted in support of a new 
indication for use for Chantix' or to support any other 
significant change in labeling.
      The study is not intended to support a significant change 
in the advertising for Chantix'.
       The study does not involve a route of administration or 
dosage level or use in a patient population or other factor that 
significantly increases the risks (or decreases the acceptability of 
the risks) associated with the use of Chantix'.
      It is our understanding that the study is being conducted 
in compliance with the requirements for institutional review set forth 
in 21 CFR Part 56 and with the requirements for informed consent set 
forth in 21 CFR Part 50.
      It is our understanding that the study is being conducted 
in compliance with 21 CFR 312.7, regarding promotion and charging for 
investigational drugs.

    3. The VA did not change the reporting requirements to include both 
Adverse Events (AEs) and Serious Adverse Events (SAEs) until after the 
February 1 warning. Should the VA have changed its policy after the 
Early Communication?
    The reporting requirements for adverse events observed in clinical 
trials are established in 21 CFR 312.32 for studies that are conducted 
under an IND. This study does not require an IND; hence, the study 
sponsor (the VA) and the Institutional Review Board (IRB) are 
responsible for determining what reporting should be employed for the 
study. This responsibility reflects their familiarity with the trial 
design and the ethics of the study in the particular patient population 
being studied.

    4. In your opinion should the Early Communication have prompted the 
VA to modify the protocol given the unique population of the study?
    The VA, as the sponsor of the study, is responsible for overseeing 
this trial, including obtaining the informed consent of study subjects 
and making sure new information is provided to study subjects (where 
appropriate), with oversight by the IRB. This local application of the 
regulations guiding research is appropriate and essential. For 
instance, 21 CFR 50.25 describes the basic elements of informed 
consent, listing eight basic elements, each of which requires some 
interpretation. The second element states that the following 
information shall be provided to each subject in a study: ``A 
description of any reasonably foreseeable risks or discomforts to the 
subject.'' What is ``reasonably foreseeable'' is a matter of judgment, 
including important insights that the study sponsor and the IRB can 
bring to bear about the ethics of a study in a specific population. 
With this in mind, for preliminary communications of emerging safety 
issues, the study sponsor and the IRB must play a critical role in 
determining whether or not a given study protocol or informed consent 
procedures or information, would need to be modified as new safety 
information was made available to them.
    In the Early Communication about Chantix', FDA stated 
that it had received, and was evaluating, reports of neuropsychiatric 
symptoms in patients who had taken Chantix', but had not 
reached a conclusion about whether this information warranted 
regulatory action. The Early Communication did not draw any conclusions 
regarding a causal relationship between Chantix' and these 
symptoms. It was appropriately within the discretion of the study 
sponsor, with oversight by the IRB, to determine whether the 
information contained in the Early Communication required modification 
of the informed consent procedures or information for study subjects or 
changes to the study protocol.

    5. How many reports of AEs or SAEs has the FDA received from the 
VA?
    A search of the AERS database revealed 10 adverse event reports 
from various VA facilities from the time the drug was marketed, July 
10, 2006, to June 19, 2008. One case reported an outcome of death, but 
the available information did not cite a suicide. Not all reporters who 
submit AERS reports indicate which institution or facility they are 
reporting from. Therefore, it is possible that the number of cases 
being reported from the VA may not be fully represented.

    6. What action should physicians take when the FDA issues an Early 
Communications or Public Health Advisories for a drug?
    Early Communications are issued to keep healthcare professionals 
and the general public informed of postmarked safety issues that are 
currently being evaluated by FDA. Early Communications are issued at 
the beginning of FDA's assessment, prior to conclusive determination of 
the clinical or public health significance of the information under 
evaluation, and before a decision has been made about what regulatory 
actions, if any, should be taken. They reflect FDA's current analysis 
of available data concerning these drugs, but posting the information 
as an Early Communication does not mean that FDA has concluded a causal 
relationship between the drug and the emerging safety issues. It also 
does not mean that FDA is advising healthcare professionals to 
discontinue prescribing these products. The intent of an Early 
Communication is to inform healthcare professionals and patients about 
how best to use a marketed drug, so that they can make individual 
decisions.
    Public Health Advisories are issued to provide information 
regarding important public health issues to the general public, 
including patients and healthcare professionals. For example, Public 
Health Advisories may highlight an emerging drug safety issue, announce 
the implementation of methods to manage the risks identified for a 
marketed drug, or provide other important public health information. 
Public Health Advisories regularly include recommendations to mitigate 
a potential risk and often are issued in conjunction with other drug 
safety communications, such as Healthcare Professional Sheets. However, 
selection of specific drug products or treatment regimens for 
particular patients are decisions to be made between the patient and 
physician familiar with the individual's current health status and past 
medical history. These decisions are considered the practice of 
medicine and are not regulated by FDA.

    7. What is the requirement for Black Box warnings?
    Certain contraindications or serious warnings, particularly those 
that may lead to death or serious injury, may be required by FDA to be 
presented in a box. According to 21 CFR 201.57(c)(1), a boxed warning 
ordinarily must be based on clinical data, but serious animal toxicity 
may also be the basis of a boxed warning in the absence of clinical 
data. A boxed warning is ordinarily used to highlight for prescribers 
one of the following situations:

      There is an adverse reaction so serious in proportion to 
the potential benefit from the drug (e.g., a fatal, life-threatening or 
permanently disabling adverse reaction) that it is essential it be 
considered in assessing the risks and benefits of using a drug.
      There is a serious adverse reaction that can be prevented 
or reduced in frequency or severity by appropriate use of the drug 
(e.g., patient selection, careful monitoring, avoiding certain 
concomitant therapy, addition of another drug or managing patients in a 
specific manner, avoiding use in a specific clinical situation).
      FDA approved the drug with restrictions to assure safe 
use because it concluded that the drug can be safely used only if 
distribution or use is restricted (e.g., under 21 CFR Part 314, Subpart 
H, Sec. 314.520, ``Approval with restrictions to assure safe use'').

    A boxed warning can also be used in other situations to highlight 
warning information that is especially important to the prescriber. 
Information included in the WARNINGS AND PRECAUTIONS and 
CONTRAINDICATIONS sections should therefore be evaluated to determine 
whether it should also be placed in a boxed warning.
    Boxed warnings are more likely to be based on observed adverse 
reactions, but there are instances when a boxed warning based on an 
expected adverse reaction would be appropriate. For example, a 
contraindication during pregnancy, based on evidence in humans that 
drugs in a pharmacologic class pose a serious risk of developmental 
toxicity during that time, would usually be in a boxed warning for all 
drugs in that class, even those in which the adverse reaction has not 
been seen.
    A boxed warning can also be considered for a drug that has 
important risk/benefit information that is unique among drugs in a drug 
class (e.g., to note that a drug is the only one in its class to have a 
particular risk that makes it inappropriate for use as a first line 
therapy).

    8. Is the FDA considering a Black Box warning for 
Chantix'?
    FDA is still reviewing data, and a decision regarding the addition 
of a boxed warning has not yet been made.
    Thank you again for the opportunity to testify. Please let us know 
if you have any further questions or concerns.
            Sincerely,
                                                   Stephen R. Mason
                      Acting Assistant Commissioner for Legislation

                                 

                                     Committee on Veterans' Affairs
                                                    Washington, DC.
                                                      July 14, 2008
Ponni Subbiah, M.D., M.P.H.
Vice President, Medical Affairs
Pfizer Inc.
325 7th Street, NW, Suite 1200
Washington, DC 20004

Dear Ponni:

    In reference to our Full Committee hearing ``Why Does the VA 
Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?'' on 
July 9, 2008, I would appreciate it if you could answer the enclosed 
hearing questions by the close of business on August 20, 2008.
    In an effort to reduce printing costs, the Committee on Veterans' 
Affairs, in cooperation with the Joint Committee on Printing, is 
implementing some formatting changes for materials for all full 
committee and subcommittee hearings. Therefore, it would be appreciated 
if you could provide your answers consecutively and single-spaced. In 
addition, please restate the question in its entirety before the 
answer.
    Due to the delay in receiving mail, please provide your response to 
Debbie Smith by fax at 202-225-2034. If you have any questions, please 
call 202-225-9756.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

                                                        Pfizer Inc.
                                                  Corporate Affairs
                                                    Washington, DC.
                                                    August 20, 2008
VIA FACSIMILE AND EMAIL
ATTN: Ms. Debbie Smith

The Honorable Bob Filner
Chairman
Committee on Veterans' Affairs
U.S. House of Representatives
335 Cannon House Office Building
Washington, D.C. 20515-6115
    Dear Chairman Filner:

    The enclosed attachment (``Attachment 1'') is submitted on behalf 
of Dr. Ponni Subbiah, in response to your letter, dated July 14, 2008, 
requesting that Dr. Subbiah provide follow-up answers to your hearing 
questions for the hearing record.
    In addition, Pfizer Inc (``Pfizer'') respectfully submits that the 
attached records (PFIZER-CVA-000000001 through 000000003) contain or 
constitute confidential and proprietary information of Pfizer provided 
to the Committee pursuant to your requests for such information as 
Chairman of the Committee on Veterans' Affairs (``Committee''). 
Accordingly, Pfizer has marked all records produced today with the 
legend ``PFIZER CONFIDENTIAL TREATMENT REQUESTED.''
    We respectfully request that the Committee afford these records the 
maximum protection available to information provided to the Committee. 
Pfizer respectfully requests that the Committee, your staff, and all 
those who may review Pfizer records on behalf of the Committee protect 
against the disclosure of this confidential and proprietary 
information. The intentional or inadvertent disclosure of information 
that Pfizer has expressly designated as confidential and proprietary 
may cause substantial harm to Pfizer. We also respectfully request 
advance notice of any contemplated disclosure of Pfizer's confidential 
and proprietary information, and a reasonable opportunity to object. 
Please direct any such notice to me directly.
    If you have any questions, or need additional information, please 
do not hesitate to call me at (202) 783-7070.
            Sincerely,
                                                        Dolly Judge
                               Vice President, Government Relations
    cc: Hon. Steve Buyer, Ranking Member
       Committee on Veterans' Affairs

                               __________

                              ATTACHMENT 1
     1. You said that [the] clinical trial program for 
Chantix' involved more than 5,000 patients over a 10-year 
period. Did any of those patients have PTSD or underlying psychiatric 
illnesses?

      The development program for Chantix' involved 
more than 5,000 patients over a span of 10 years.
      Patients who disclosed that they were receiving treatment 
for (or had a history of) serious psychiatric illnesses such as 
schizophrenia, bipolar disorder, and depression did not participate in 
the pre-approval clinical trial program for Chantix'.
      Pfizer has not conducted a study of the use of 
Chantix' in patients with PTSD.

     2. How many reports of suicidal ideation and attempted suicide did 
Pfizer receive prior to the FDA issuing the Early Communication?

      FDA Early Communication was issued on November 20, 2007.
      Prior to the FDA releasing an early communication 
regarding Chantix', Pfizer received the following numbers of 
post-marketing suicide-related adverse event reports (worldwide) 
through November 19, 2007:

          Reports of Suicidal ideation--322
          Reports of Suicide attempt/Suicidal behavior--37
          Reports of Completed suicide--16

      Based on estimated global exposure, approximately 5.2 
million patients had been prescribed Chantix' through 
November 2007.
      According to the Centers for Disease Control, there are 
11 completed suicides per 100,000 persons per year in the United 
States.1
      According to surveys conducted by Harvard Medical School, 
between 2.8-3.3 percent of U.S. residents aged 15-54 years have had 
suicidal ideation in a 12-month period.2
      According to a German epidemiology study, a smoker is 2.6 
times more likely to commit suicide than a non-smoker.3

     3. Do you think this drug is appropriate for use for veterans with 
PTSD?

      Pfizer cannot make a judgment in the abstract whether a 
particular medication is appropriate for a particular patient.
      We can say that the smoking rate in PTSD patients has 
been reported to be up to 60 percent and 48 percent of combat veterans 
with PTSD are also heavy smokers (25 cigarettes per 
day).4-5
      It is important to note that patients with psychiatric 
illnesses such as PTSD also may have other comorbidities that can lead 
to serious health consequences. Due to the high rate of smoking in 
patients with PTSD and therefore higher risk of smoking-related 
comorbidities such as cardiovascular disease, cancer, and lung 
diseases, it is important to continue to improve the standard of 
medical care and provide treatment options for PTSD patients to quit 
smoking.6
      Smoking cessation, with or without treatment, is 
associated with nicotine withdrawal symptoms and has also been 
associated with the exacerbation of underlying psychiatric 
illness.7-9

      Whether a medication is appropriate for a particular 
patient is a decision that can be made only by that patient's doctor, 
after consultation with the patient. When considering the use of 
Chantix' for their patients, healthcare providers should 
discuss the risks of smoking, the health benefits of quitting smoking, 
and the product's efficacy and safety profile, including the potential 
for psychiatric symptom exacerbation. Symptoms experienced in prior 
quit attempts, with or without Chantix', should also be 
discussed. Health care practitioners managing patients with concurrent 
psychiatric disorders who are quitting smoking should take this 
information into consideration when advising their patients.

     4. In your testimony you state that the report of an adverse event 
does not necessarily mean there is a causal relationship between the 
product and the event. Are there a certain number of adverse events, of 
maybe a certain nature, that have to be reported to establish a causal 
relationship?

       a. What would have to happen to establish a causal relationship?

      Causality assessment relies on the medical and scientific 
review of the totality of available evidence rather than purely on the 
number of events.
       The information needed to assess causality comes from 
multiple sources including randomized controlled clinical trials, and 
observational studies. Post-marketing reports, preclinical mechanistic 
experiments, and individual case reports may generate hypotheses to 
test in clinical trials and observational studies but typically cannot 
establish causation.
      It is important to understand the nature of spontaneous 
adverse event reporting. These reports can come from any person or 
source ranging from consumers to healthcare providers, and from phone 
calls to Internet postings. Often these reports lack sufficient medical 
information to enable meaningful assessment of causality. As a result 
of this variability in reporting, any analysis of the numbers of 
adverse events should be considered hypothesis-generating only, and 
should be considered within the overall context of an existing body of 
scientific and public health knowledge. Despite the limitations of 
adverse event reporting, Pfizer actively follows up on adverse event 
reports to obtain as much information as possible.
      In the case of Chantix', a causal relationship 
between these post-marketing reports and the use of Chantix' 
has not been established. However, in some reports related to 
Chantix', a causal relationship could not be excluded.

     5. Please provide to the Committee a list of all the paid Pfizer 
consultants to VA along with their salaries.

      The type of information requested is not typically 
available in the payment systems and databases kept by Pfizer. We do 
not maintain a single database for all payments to consultants. 
Further, our databases do not provide the granularity of detail 
requested, i.e., the relationship of a consultant to the VA. We have 
used our best efforts to be as accurate and responsive as possible. 
Therefore, our response today is based on Pfizer's current information 
and belief.
      In the records submitted to the Committee, we have 
included a list of individuals paid by Pfizer, including, but not 
limited to, clinical investigators, speakers, or individuals paid for 
teaching, writing, or other consulting services (``Consultants''), who 
have a known affiliation with a VA medical center or institution. The 
speaker Consultants payment information covers all Pfizer products 
spanning the period of January 1, 2007 to the present. (see PFIZER-CVA-
000000001 thru 000000003). In summary, Pfizer made payments to 68 
Consultants totaling approximately $895,000.
      Pfizer sponsors a variety of research conducted by 
outside healthcare providers to research Pfizer medicines. To ensure 
compliance with various laws and industry standards, all forms of 
research activities, including those related to clinical trials, should 
have genuine scientific value, include investigators selected on the 
basis of criteria relevant to the research effort, and involve 
compensation consistent with the value of the research actually 
provided. In most instances, Pfizer contracts with a full service 
Contract Research Organization (CRO) to manage study sites and 
investigators.
      Pfizer typically makes the clinical trial payments to the 
CRO, who then pays the investigator or institution pursuant to the 
agreement between the CRO and the investigator or institution. 
Therefore, it is difficult to track payments at the individual 
investigator level for Pfizer-sponsored research related payments made 
to CROs. However, the information provided to the Committee represents 
our best effort to identify all Pfizer-sponsored clinical protocols in 
which the Consultants listed participated as an investigator.
      With regard to our speaker programs and other consulting 
services, Pfizer requires all speaker Consultants to sign an agreement 
under which the Consultant represents and warrants that he/she has the 
full power and authority to enter into the agreement. The agreement 
also requires that the consultant will perform all services and 
preparation activities in accordance with all applicable laws, 
regulations, and other criminal and civil legal requirements and in 
compliance with relevant Pfizer's policies on speaking consultants.

     6. How much money has Pfizer invested in the development, testing, 
and marketing of Chantix'?
      At this time, Pfizer is unable to provide a reasonable 
cost associated with the development, testing, and marketing of 
Chantix'.
      The information requested is not typically available in 
the databases kept by Pfizer. Calculating the total cost for any single 
drug would be extremely burdensome and challenging. Any attempt to 
estimate a total cost within any valuable degree of precision would 
have to rely upon numerous factors, complex calculations, multiple 
assumptions, and involve highly confidential and proprietary data. 
Pfizer believes that the figure would likely be in the hundreds of 
millions of dollars. In fact, the Pharmaceutical Research and 
Manufacturers of America estimates that discovering, developing, and 
obtaining FDA approval of a new prescription drug, on average, takes 
between 10-15 years and costs between $800 million and $1 billion 
dollars.10
     7. How much money does Pfizer stand to lose if Chantix' 
were pulled from the market?
      Pfizer respectfully disagrees with the premise of the 
question. Pfizer cannot reasonably speculate about the inestimable 
costs and lost revenues associated with withdrawal of a product from 
the market.
      Based on all the data currently available including 
clinical trials, epidemiology, post-marketing reports, as well as on 
the collective professional opinion of Pfizer's Medical team, Pfizer 
continues to believe that the benefits of Chantix' outweigh 
the risks and that this important medicine is appropriately labeled for 
both healthcare professionals and patients.
    [The attachment to the letter will be retained in the Committee 
files due to confidential personal information included in the 
attachment.]
References
     1.  Centers for Disease Control and Prevention. 2005 Suicide 
injury deaths and rates: Web-based Injury Statistics Query and 
Reporting System (WISQARS); 2005.
     2.  Kessler RC, Berglund P, Borges G, Nock M, Wang PS. Trends in 
suicide ideation, plans, gestures and attempts in the United States, 
1990-1992 to 2001-2003. JAMA. 2005;293(20):2487-2495.
     3.  Schneider B, Schnabel A, Weber B, Frolich L, Maurer K, 
Wetterling T. Nicotine use in suicides: a case-control study. Eur 
Psychiatry. Mar 2005;20(2):129-136.
     4.  Beckham JC. Smoking and anxiety in combat veterans with 
chronic posttraumatic stress disorder: a review. J Psychoactive Drugs. 
Apr-Jun 1999;31(2):103-110.
     5.  Beckham JC, Kirby AC, Feldman ME, et al. Prevalence and 
correlates of heavy smoking in Vietnam veterans with chronic 
posttraumatic stress disorder. Addict Behav. Sep-Oct 1997;22(5):637-
647.
     6.  U.S. Department of Health and Human Services. The Health 
Consequences of Smoking. A Report of the Surgeon General. Atlanta: U.S. 
Department of Health and Human Services, Centers for Disease Control 
and Prevention, National Center for Chronic Disease Prevention and 
Health Promotion, Office on Smoking and Health; 2004.
     7.  Diagnostic and Statistical Manual of Mental Disorders. Fourth 
Edition, Text Revision. Washington, DC: American Psychiatric 
Association; 2000.
     8.  Hughes J. Effects of abstinence from tobacco: Valid symptoms 
and time course. Nicotine & Tobacco Research. 2007;9:315-327.
     9.  Covey LS GA, Stetner F. Cigarette smoking and major 
depression. J Addict Dis. 1998;17(1):35-46.
    10.  Drug Discovery and Development: Understanding the R&D process. 
(PhRMA Report 2007) Innovation.org

                                 

                                     Committee on Veterans' Affairs
                                                     Washington, DC
                                                      July 14, 2008
John D. Daigh, Jr., M.D., CPA
Assistant Inspector General for Healthcare Inspections
Office of the Inspector General
U.S. Department of Veterans Affairs
Washington, DC 20420

Dear John:

    In reference to our Full Committee hearing ``Why Does the VA 
Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?'' on 
July 9, 2008, I would appreciate it if you could answer the enclosed 
hearing questions by the close of business on August 20, 2008.
    In an effort to reduce printing costs, the Committee on Veterans' 
Affairs, in cooperation with the Joint Committee on Printing, is 
implementing some formatting changes for materials for all full 
committee and subcommittee hearings. Therefore, it would be appreciated 
if you could provide your answers consecutively and single-spaced. In 
addition, please restate the question in its entirety before the 
answer.
    Due to the delay in receiving mail, please provide your response to 
Debbie Smith by fax at 202-225-2034. If you have any questions, please 
call 202-225-9756.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

                                U.S. Department of Veterans Affairs
                                                    Washington, DC.
                                                    August 22, 2008
The Honorable Bob Filner
Chairman
Committee on Veterans' Affairs
United States House of Representatives
Washington, D.C. 20515

Dear Mr. Chairman:

    This is in response to your July 14, 2008, letter to Dr. John 
Daigh, Assistant Inspector General for Healthcare Inspections, Office 
of Inspector General, following the July 9, 2008, hearing on ``Why Does 
the VA Continue to Give a Suicide-Inducing Drug to Veterans with 
PTSD?'' Enclosed are Dr. Daigh's answers to the additional hearing 
questions.
    Thank you for your interest in the Department of Veterans Affairs.
            Sincerely,
                                                    GEORGE J. OPFER
                                                  Inspector General
    Enclosure

                               __________

                Questions from the Honorable Bob Filner
                   For John D. Daigh, Jr., M.D., CPA
         Assistant Inspector General for Healthcare Inspections
    Office of Inspector General U.S. Department of Veterans Affairs
           Before the Committee on Veterans' Affairs Hearing
                  ``Why Does the VA Continue to Give a
             Suicide-Inducing Drug to Veterans with PTSD?''
    Question 1: In your testimony, you state that the revised consent 
form was only given to patients that entered the study after April 9, 
2007, and that individuals who had signed the original second consent 
form were not re-consented during the research study. Is this normal 
procedure? Even if the known risks at the time were changes in dreams 
and nausea, shouldn't study participants have been re-consented?
    Response: There are four Informed Consent Documents referred to in 
the written statement:

      The first Informed Consent Document (screening ICD) was a 
screening form, which, if the veteran qualified, was signed to bring 
the veteran into the study.
      The second ICD (original second consent form) detailed 
the risks and benefits of participating in the treatment and identified 
possible smoking cessation drugs that could be used in the study. 
Chantix' was not one of the drugs listed in the second ICD.
      The third ICD (revised consent), approved by the 
Washington, DC, VA Medical Center Institutional Review Board (IRB) in 
April 2007, identified the option of using Chantix' as one 
of the study drugs and listed the side effects as nausea and changes in 
dreams.
      The fourth ICD (addendum), approved by the IRB in 
February 2008, was an addendum to the second and third ICDs, which 
listed the more serious side effects of Chantix', suicidal 
ideation, and erratic behavior.
    The Veterans Health Administration (VHA) Handbook 1200.5 requires 
that all patients be advised of new risks that might affect their 
willingness to participate further in the study. The IRB had approved a 
revised consent form in April 2007 and then approved an addendum in 
March 2008. All 15 patients enrolled in the study who were taking 
Chantix' should have been informed of the new risks twice 
and given the opportunity to withdraw from the study or continue by 
signing the revised ICD in April 2007 and again in March 2008.

    Question 2: Given that the Smoking Cessation Study included 
Chantix' during the post-market monitoring period should 
site investigators have reported all adverse events along with serious 
adverse events?
    Response: The Food and Drug Administration and the VHA Handbook 
requires investigators to report serious adverse events not all adverse 
events.
    Question 3: You said in your testimony that ``the facility's 
research service did not ensure that patients involved in the smoking 
cessation study were notified of the risk of suicidal thoughts or 
behavior in a timely manner.'' What do you consider timely?
    Question 3(a): Do you think patients should have been notified of 
the risk after the Early Communication?
    Response: VHA Handbook 1200.5 states that ``significant new 
findings developed during the course of the research which may relate 
to the subject's willingness to continue participation will be provided 
to the subject.'' We do not have an opinion on whether the early 
communication was considered a significant new finding.
    Question 3(b): Should the patients have been notified by phone 
rather than by mail?
    Response: The principal investigator was responsible for ensuring 
that notification occurred. Whether that notification is accomplished 
by telephone, mail, or other method is not as pertinent as the lack of 
follow up action to verify that study participants ever received the 
notice. After the beginning of our review, a number of patients came in 
person to the medical center to sign the fourth ICD. We did not 
consider this to be timely notification of the risks associated with 
Chantix'.
    Question 3(c): Whose responsibility is it to ensure the patients 
are notified.
    Response: It is part of the principal investigator's responsibility 
and the IRB's responsibility to determine if the information is a 
significant new finding. If the IRB and the principal investigator 
decide that new findings warrant notifying the study participants, they 
need to take steps to ensure that the information reaches the study 
participants.
    Question 4: Did the Site Investigator, any member of the IRB, or 
study coordinator explain why they failed to list the most dangerous 
side effects in the letter?
    Response: The Palo Alto Cooperative Studies Program Coordinating 
Center explained that there was a desire not to unduly alarm 
participants.
    Question 5: If there were so many issues with this study at the 
VAMC DC, how do we know that the other sites involved in this study do 
not have similar problems?
    Response: Due to time limitations, we focused on the Washington, 
DC, VAMC and we did not review other sites. The Secretary directed the 
Office of Research Oversight to review the other sites.

                                 

                                     Committee on Veterans' Affairs
                                                     Washington, DC
                                                      July 14, 2008
Gerald P. Koocher, Ph.D., ABPP
Dean and Professor
School of Health Sciences
Simmons College
300 The Fenway
Boston, MA 02115

Dear Gerald:

    In reference to our Full Committee hearing ``Why Does the VA 
Continue to Give a Suicide-Inducing Drug to Veterans with PTSD?'' on 
July 9, 2008, I would appreciate it if you could answer the enclosed 
hearing questions by the close of business on August 20, 2008.
    In an effort to reduce printing costs, the Committee on Veterans' 
Affairs, in cooperation with the Joint Committee on Printing, is 
implementing some formatting changes for materials for all full 
committee and Subcommittee hearings. Therefore, it would be appreciated 
if you could provide your answers consecutively and single-spaced. In 
addition, please restate the question in its entirety before the 
answer.
    Due to the delay in receiving mail, please provide your response to 
Debbie Smith by fax at 202-225-2034. If you have any questions, please 
call 202-225-9756.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

                Questions from the Honorable Bob Filner
                      for Gerald P. Koocher, Ph.D.
     Professor and Dean, School of Health Sciences, Simmons College
           Before the Committee on Veterans' Affairs Hearing
                  ``Why Does the VA Continue to Give a
             Suicide-Inducing Drug to Veterans with PTSD?''
                              July 9, 2008
    Question 1: In your testimony you highlight that obtaining consent 
does involve documentation, but is best conceptualized as a process by 
which the investigator makes certain that potential participants know 
what will be asked of them, what risks or hazards may be involved, what 
benefits may result. What is your professional opinion of the fact that 
the VA OIG could not find documentation regarding informed consent of 
the patient in the research trial that was being done and when there 
was a change, i.e. Chantix', that there was no documentation 
regarding re-consenting?
    Response: I described consent as a process because offering a 
document for signature does not necessarily imply that the people 
participating in the study understand what they have been asked to 
sign. Not everyone can or does read and understand a written form 
fully. The conversation between the research team and participants 
forms a critical communication bridge.

      If the VA OIG reported that it could not find 
documentation regarding consent of participants in a research trial I 
and/or when a change in protocol occurred, I would want to ask several 
questions:
      Where did the OIG look (e.g., in patients' medical 
records, in the investigators' research files at each site, in the 
minutes or IRB meetings, etc.)?
      What did the investigators at each site report regarding 
the notation of consent and storage of that notation?
      How did the investigators at each site explain the 
missing documentation?
      Did the OIG inquire of the IRB officials at each site 
about the IRB monitoring, auditing, and recordkeeping for all research 
protocols; and if so, did the IRB officials behave differently in the 
case of this particular study.
      When were IRBs asked to approve the introduction of 
Chantix' to the research protocol, and how long did it take 
each IRB to approve the revised protocols and consent forms?
      After such protocol changes occurred, what did the IRB 
require the site investigators to do by way of notification and what 
deadlines were specified?
      Because the studies in question involved multiple sites, 
was a DSMB in place? If so, what do the DSMB minutes reflect about any 
required notifications, or changes in procedure? If no DSMB was in 
place, why not?

    By listing these questions I hope to underscore the complexity of 
your question. I cannot reach a conclusion about the adequacy of the VA 
OIG investigation or the thoroughness of the standard protections that 
one would expect to find at each clinical site (i.e., local IRBs or an 
over-arching DSMB). I simply have no basis to reach any conclusion 
about who ``dropped the ball'' or even whether ``the ball was 
dropped.''
    My understanding some of the testimony before the Committee 
suggested that some physicians may have prescribed Chantix' 
to individual patients who also happened to be enrolled as study 
participants. In such circumstances the prescribing of that medication 
could fall beyond the scope of the study (i.e., the investigators may 
not have had no way of knowing that some of their research participants 
had been prescribed the drug by physicians not associated with the 
study). Three types of protections might have prevented such problems:

      Most studies involving vulnerable populations have ``rule 
out'' requirements that would disqualify some type of vulnerable people 
from participating (e.g., people on certain medications or with certain 
pre-existing medical or mental conditions that would contraindicate 
participation). You may wish to determine whether the research project 
had such criteria.
      In studies that run for many months investigators 
typically ask patients if their medical condition has changed in any 
way during return visits. You may wish to ascertain whether such 
questions were part of the research protocol. Of course, this step will 
only prove useful if research participants remember and report any such 
changes.
      Private physicians writing a prescription for 
Chantix' would normally ask patients what other medications 
and treatments they were receiving. If a patient informed their 
personal physician about research participation and treatment for PTSD, 
I would expect such a physician to investigate the protocol or speak 
with the investigators before initiating a new drug regimen that might 
potentially interact adversely with the protocol. You may want explore 
whether those physicians who prescribed Chantix' made such 
inquiries.

    Question 2: Do you believe that common sense and good judgment 
should be exercised by the researchers? In the instance where there was 
no followup ensuring that patients had been informed, who and how would 
you hold the participating parties responsible?
    Response: Standard practice in any research involving people as 
participants demands that the investigators seek institutional 
approval, through their IRB: 1) of any research protocol and consent 
forms/processes prior to beginning data collection; and 2) on any 
changes in the research protocol or consent form. In addition, 
investigators must notify their IRBs and any over-arching DSMBs of all 
adverse incidences. The investigators should retain copies of all such 
notifications. IRBs and DSMBs must keep minutes that reflect their 
deliberations and actions. One would expect such minutes to include 
notification dates or instructions, action steps, and monitoring plans, 
if any.
    If an investigator failed to notify an IRB/DSMB of protocol 
changes, consent form changes, or adverse events, I would be inclined 
to hold the investigator responsible. I suspect his/her IRB would do so 
as well.
    If an IRB or DSMB failed to address such changes or notifications 
in a timely manner, I would be inclined to hold the respective Boards' 
administrators responsible.
    The key problem in the study of concern to the Committee is a 
determination of who had relevant information regarding protocol 
changes, who passed on that information, who received that information, 
what actions did they take based on the information available to them, 
and whether they were acting in a reasonable timeframe.
    I have no data on which to form an opinion on these points in the 
case at hand.
    I hope you find these comments to your questions responsive and 
helpful.

            Sincerely,
                                     Gerald P. Koocher, Ph.D., ABPP

                                 

                                      Committee on Veterans Affairs
                                                    Washington, DC.
                                                      July 29, 2008
The Honorable James B. Peake, M.D.
Secretary
U.S. Department of Veterans Affairs
810 Vermont Avenue, NW
The Fenway
Washington, DC 20240

    Dear Secretary Peake:

    Thank you again for your testimony at the U.S. House of 
Representatives Committee on Veterans' Affairs hearing that took place 
on July 9, 2008, on ``Why Does the VA Continue to Give a Suicide-
Inducing Drug to Veterans with PTSD?''
    As Chairman of the Committee, I formally request a list of the 64 
patients who were given the smoking-cessation drug Chantix' 
by the Department of Veterans Affairs (VA) and who have not signed an 
addendum to the informed consent form that the VA had given to 
Chantix' users. These 64 patients were mentioned in your 
testimony at the hearing.
    Thank you again for taking the time to answer this request. The 
Committee looks forward to receiving your answers by August 29, 2008.
            Sincerely,
                                                         BOB FILNER
                                                           Chairman

                               __________

                                  The Secretary of Veterans Affairs
                                                    Washington, DC.
                                                 September 26, 2008

The Honorable Bob Filner
Chairman
Committee on Veterans' Affairs
U.S. House of Representatives
Washington, DC 20515

    Dear Mr. Chairman:

    This is in response to your letters formally requesting a list of 
patients given the smoking-cessation drug Chantix' and who 
were mentioned in my testimony at the Committee's July 9, 2008, 
hearing. I regret the delay in this reply.
    The Department of Veterans Affairs (VA) is providing the Committee 
with the signature pages of the informed consent addendums of 91 of the 
120 veteran patients participating in the smoking-cessation study who 
were known to receive Chantix' after February 1, 2008. The 
patients' names and the witness' names are withheld to protect patient 
privacy. We are also providing documentation of notification for the 27 
other participants who have not yet signed an informed consent 
addendum. These individuals have been notified of the potential side 
effects of Chantix' by their physician or a member of the 
research staff, or have received a copy of the consent addendum 
(documented by FedEx or United States Postal Service receipt). These 
records have also been redacted to ensure patient confidentiality. Two 
patients are no longer participating in the study. All patients 
currently participating in the study and receiving Chantix' 
since February 1, 2008, have signed the addendum or received 
information about the Food and Drug Administration warning.
    At the time of the hearing, there were 64 veterans who were known 
to receive Chantix' after February 1, 2008, who had not 
signed the addendum to the informed consent. Thirty-five of these 
patients have now signed consent addendums, either as a result of these 
contacts or in the course of a routine study visit. These 35 are 
included in the 91 signature pages we have provided.
    The patients' names are redacted because the researcher had 
obtained a Certificate of Confidentiality (enclosed) from the 
Department of Health and Human Services for the smoking cessation 
study. Under title 42, United States Code, Sec. 241 (d)), the signed 
Certificate of Confidentiality protects the researcher from being 
compelled to release the names or identifying characteristics of any 
research subject in any Federal, State, or local civil, criminal, 
administrative, legislative, or other proceedings. Section 241 (d) 
protects the privacy of human subjects who participate in research for 
the betterment of science and medicine.
    Individuals participate as subjects in research because they know 
the Certificate of Confidentiality protects their identities. The 
release of identities could have a chilling effect on voluntary 
participation in research, particularly in the area of mental health.
            Sincerely yours,
                                               James B. Peake, M.D.
    Enclosures

    [The attachments to the letter will be retained in the Committee 
files due to confidential personal information included in attachment.]

                                 
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