[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
U.S. GOVERNMENT PRINTING OFFICE
43-998 WASHINGTON : 2009
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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.
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\1\ Houston, Hampton, Minneapolis, New Orleans, Philadelphia,
Portland, Providence, San Diego, Tuscaloosa, and Washington, DC.
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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.]