[House Hearing, 111 Congress]
[From the U.S. Government Publishing Office]
INSTITUTIONAL REVIEW BOARDS THAT OVERSEE EXPERIMENTAL HUMAN TESTING FOR
PROFIT
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED ELEVENTH CONGRESS
FIRST SESSION
__________
MARCH 26, 2009
__________
Serial No. 111-22
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
_____
U.S. GOVERNMENT PRINTING OFFICE
67-819 WASHINGTON : 2012
-----------------------------------------------------------------------
For sale by the Superintendent of Documents, U.S. Government Printing
Office Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800; DC
area (202) 512-1800 Fax: (202) 512-2104 Mail: Stop IDCC, Washington, DC
20402-0001
COMMITTEE ON ENERGY AND COMMERCE
HENRY A. WAXMAN, California, Chairman
JOHN D. DINGELL, Michigan JOE BARTON, Texas
Chairman Emeritus Ranking Member
EDWARD J. MARKEY, Massachusetts RALPH M. HALL, Texas
RICK BOUCHER, Virginia FRED UPTON, Michigan
FRANK PALLONE, Jr., New Jersey CLIFF STEARNS, Florida
BART GORDON, Tennessee NATHAN DEAL, Georgia
BOBBY L. RUSH, Illinois ED WHITFIELD, Kentucky
ANNA G. ESHOO, California JOHN SHIMKUS, Illinois
BART STUPAK, Michigan JOHN B. SHADEGG, Arizona
ELIOT L. ENGEL, New York ROY BLUNT, Missouri
GENE GREEN, Texas STEVE BUYER, Indiana
DIANA DeGETTE, Colorado GEORGE RADANOVICH, California
Vice Chairman JOSEPH R. PITTS, Pennsylvania
LOIS CAPPS, California MARY BONO MACK, California
MIKE DOYLE, Pennsylvania GREG WALDEN, Oregon
JANE HARMAN, California LEE TERRY, Nebraska
TOM ALLEN, Maine MIKE ROGERS, Michigan
JAN SCHAKOWSKY, Illinois SUE WILKINS MYRICK, North Carolina
HILDA L. SOLIS, California JOHN SULLIVAN, Oklahoma
CHARLES A. GONZALEZ, Texas TIM MURPHY, Pennsylvania
JAY INSLEE, Washington MICHAEL C. BURGESS, Texas
TAMMY BALDWIN, Wisconsin MARSHA BLACKBURN, Tennessee
MIKE ROSS, Arkansas PHIL GINGREY, Georgia
ANTHONY D. WEINER, New York STEVE SCALISE, Louisiana
JIM MATHESON, Utah PARKER GRIFFITH, Alabama
G.K. BUTTERFIELD, North Carolina ROBERT E. LATTA, Ohio
CHARLIE MELANCON, Louisiana
JOHN BARROW, Georgia
BARON P. HILL, Indiana
DORIS O. MATSUI, California
DONNA CHRISTENSEN, Virgin Islands
KATHY CASTOR, Florida
JOHN P. SARBANES, Maryland
CHRISTOPHER MURPHY, Connecticut
ZACHARY T. SPACE, Ohio
JERRY McNERNEY, California
BETTY SUTTON, Ohio
BRUCE BRALEY, Iowa
PETER WELCH, Vermont
(ii)
Subcommittee on Oversight and Investigations
BART STUPAK, Michigan, Chairman
BRUCE L. BRALEY, Iowa GREG WALDEN, Oregon
Vice Chairman Ranking Member
EDWARD J. MARKEY, Massachusetts ED WHITFIELD, Kentucky
DIANA DeGETTE, Colorado MIKE FERGUSON, New Jersey
MIKE DOYLE, Pennsylvania TIM MURPHY, Pennsylvania
JAN SCHAKOWSKY, Illinois MICHAEL C. BURGESS, Texas
MIKE ROSS, Arkansas
DONNA M. CHRISTENSEN, Virgin
Islands
PETER WELCH, Vermont
GENE GREEN, Texas
BETTY SUTTON, Ohio
JOHN D. DINGELL, Michigan (ex officio)
C O N T E N T S
----------
Page
Hon. Bart Stupak, a Representative in Congress from the State of
Michigan, opening statement.................................... 1
Prepared statement........................................... 4
Hon. Greg Walden, a Representative in Congress from the State of
Oregon, opening statement...................................... 6
Prepared statement........................................... 8
Hon. Diana DeGette, a Representative in Congress from the State
of Colorado, opening statement................................. 10
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 11
Hon. Donna M. Christensen, a Representative in Congress from the
Virgin Islands, opening statement.............................. 12
Hon. Gene Green, a Representative in Congress from the State of
Texas, opening statement....................................... 13
Hon. Edward J. Markey, a Representative in Congress from the
Commonwealth of Massachusetts, opening statement............... 13
Hon. Joe Barton, a Representative in Congress from the State of
Texas, opening statement....................................... 14
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, prepared statement.............................. 115
Witnesses
Gregory Kutz, Managing Director, Forensic Audits and Special
Investigations, Government Accountability Office............... 17
Prepared statement........................................... 19
Joanne Less, Director, Good Clinical Practice Program, Food and
Drug Administration............................................ 40
Prepared statement........................................... 43
Jerry Menikoff, M.D., Director, Office for Human Research
Protections, Department of Health and Human Services........... 59
Prepared statement........................................... 61
Daniel Dueber, Chief Executive Officer, Coast IRB, LLC........... 76
Prepared statement........................................... 78
Submitted Material
Subcommittee exhibit binder...................................... 117
INSTITUTIONAL REVIEW BOARDS THAT OVERSEE EXPERIMENTAL HUMAN TESTING FOR
PROFIT
----------
THURSDAY, MARCH 26, 2009
House of Representatives,
Subcommittee on Oversight and Investigations,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 10:03 a.m., in
Room 2123 of the Rayburn House Office Building, Hon. Bart
Stupak (chairman) presiding.
Members present: Representatives Stupak, Markey, DeGette,
Christensen, Green, Waxman (ex officio), Walden, Burgess,
Gingrey, Barton (ex officio), and Blunt.
Staff present: Karen Lightfoot, Communications Director,
Senior Policy Advisor; David Rapallo, General Counsel; Theodore
Chuang, Chief Oversight Counsel; Dave Leviss, Deputy Chief
Investigative Counsel; Scott Schloegel, Investigator, Oversight
& Investigations; Stacia Cardille, Counsel; Erik Jones,
Counsel; Ali Golden, Investigator; Jennifer Owens, Special
Assistant; Caren Auchman, Communications Associate; Paul Jung,
Public Health Service Detailee; Kenneth Marty, Detailee; Karen
Christian, Counsel; Alan Slobodin, Chief Counsel; and Peter
Kielty, Legislative Analyst.
OPENING STATEMENT OF HON. BART STUPAK, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Stupak. This meeting will come to order. Today we have
a hearing entitled Institutional Review Boards that Oversee
Experimental Human Testing for Profit. The chair and ranking
member and chairman emeritus will be recognized for 5 minutes
for opening statements. All other members of the subcommittee
will be recognized for 3-minute opening statements. I will
begin. Experimental medical testing on human beings has a
troubling history. From the atrocities perpetrated by the Nazis
in World War II to the famous Tuskegee study in the 1970s when
subjects were denied treatment for syphilis, we have learned
that we need strong controls in place to protect the health and
safety of people who participate in medical experiments.
Under current federal law, medical testing of human
subjects that is federally funded or relates to federally
regulated drugs or medical devices cannot proceed without the
approval of an Institutional Review Board, a panel of doctors,
scientists, and non-scientists charged with ensuring the health
and safety of the people participating in the study. Our
committee began investigating IRBs in 2007. We learned that
Copernicus IRB allowed the study of an antibiotic Ketek to
continue without examining reports of fraud it had received. As
part of our continued investigation, we asked the Government
Accountability Office, GAO, to conduct undercover testing of
the IRB review process. We wanted to know whether IRBs are
rubberstamping research studies, whether clinical researchers
are IRB shopping or choosing IRBs based on how quickly and how
inexpensively they approve studies, and whether government
oversight of IRBs is adequate.
Today we will hear the results of GAO's investigation, and
they are not reassuring. GAO will explain how Coast IRB, a for-
profit company, approved a fictitious study led by a fictitious
doctor and submitted by a fictitious company. It called for a
full liter of a fictitious product, in fact, the same amount in
this bottle here, to be poured into a woman's abdomen cavity
after surgery supposedly to help healing. GAO's fake protocol
was based on an actual high risk study for a product that the
FDA ultimately withdrew from the market because of deaths and
infections among patients. Besides Coast IRB, GAO also sent its
fictitious study to two other IRBs that they both rejected our
proposal out of hand.
Here are some of the things that two other IRBs said after
reviewing the fake GAO study. The experimental design was the
most complicated thing that I have ever seen. During a surgery,
a major operation on a patient, a mystery guy walks in and
dumps the solution in the body. Where is the safety for the
patient? It appeared that people were just going to go out and
start injecting. We realized it was a terrible risk for the
patient. It is the worse thing I have ever seen. But Coast IRB
approved the protocol unanimously 7 to nothing.
The doctor with primary responsibility for reviewing the
study told other board members that the protocol looks fine,
and that the substance to be injected in the abdominal cavity
was probably very safe. Nobody at Coast IRB ever reviewed any
of the data cited in the proposal to support those claims. If
they had, they would have discovered it did not exist. A doctor
who reviewed the study did raise a question about if the
study's claim was accurate and that the substance had been
approved previously by the FDA, but no one ever followed up
with the FDA to answer this question, and in an e-mail to the
rest of the board members, the doctor stated it would not have
made any difference, that he would have approved the study
anyway and that the lack of FDA approval won't affect my
recommendation.
The board chair told us she relied on this recommendation
and voted to approve the study even though she did not read the
full protocol. Why was this review so shoddy? The evidence
suggests that Coast was more concerned with its financial
bottom line than protecting the lives of patients. According to
Coast's CEO, who will testify today, Coast had a practice of
voting on research protocols within 48 hours of the board
receiving them. One of the testimonials that Coast sent to
prospective customers reads thank you very much. You guys are
the quickest IRB I ever worked with, and I have done this 7
years. Coast even sent a coupon offering to give free IRB
review so researchers could coast through your next study.
After this committee wrote to Coast IRB requesting
documents associated with their approval of this fictitious
study, Coast officials took pride in that they were able to
discover the study was bogus, but this was 5 months after they
approved it. Coast CEO, Mr. Dueber, told our staff within
seconds they were able to determine that this was not an actual
medical device, and within 4 to 5 hours they determined that
this was a sham. Had any of the staff done the research before
they approved our bogus protocol 5 months ago, Coast IRB would
not be testifying today. GAO's investigation also exposed other
problems with the IRB system. GAO was able to create a
fictitious IRB that it registered with the U.S. Department of
Health and Human Services, HHS, with no questions asked.
The president of this fake IRB was this dog, Trooper, who
is, sadly, now deceased. Trooper didn't know anything about
protecting human testing, but for a three-legged dog he sure
could catch a Frisbee. GAO created a fake web site for
Trooper's IRB called Maryland House. It received real inquiries
from real researchers and actually had one research protocol
submitted for review. When asked why it selected GAO's fake IRB
and Trooper to conduct its study, a research coordinator stated
that it was because of the low price and the quick turnaround
time.
GAO's findings raise serious questions, not only about
specific IRBs involved in this investigation, but with the
entire system for approving experimental testing on human
beings. As a society, we have a moral obligation to ensure that
human testing is done in the most responsible and ethical
manner. I look forward to the testimony today, and I hope we
can discuss ways for both government and industry to fulfill
its obligation. That concludes my opening statement.
[The prepared statement of Mr. Stupak follows:]
Mr. Stupak. I next go to the ranking member, my friend, Mr.
Walden, for his opening statement, please.
OPENING STATEMENT OF HON. GREG WALDEN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF OREGON
Mr. Walden. Thank you, Mr. Chairman, for convening this
hearing. It is another example of the kind of investigative
work that is possible when we work together in a bipartisan
manner as we most always do. The subject of this hearing, the
oversight of human subjects in clinical trials by Institutional
Review Boards or IRBs, grew out of a drug safety investigation
in the last Congress. Working together we identified what we
thought might be problems in IRB oversight of clinical trials.
We made a joint request to the Government Accountability
Office, the GAO, to take a closer look into what was going on.
Now we are here today to learn about the results of that
investigation.
As we meet today, literally millions of Americans are
engaged in clinical trials taking place in more than 350,000
locations across America. Right now people who have volunteered
for these trials are walking into a doctor's office or a
hospital or some other setting, and they are taking
experimental medicines or allowing new devices to be used on
their bodies so that scientists and doctors can determine
whether and how a new treatment will work. Without their
willingness to volunteer for a trial, all of us would not
benefit from the new drugs or devices to treat illness and
disease. But they volunteer believing that an independent
government-sanctioned process is reviewing the protocols and
products to maximize their safety.
And I have to tell you that after reading the report of the
GAO that explains how easy it was for the undercover
investigators to fake their backgrounds and get approval for
human trials and create their own fake IRB something is
horribly wrong. Mr. Dueber, I have read your testimony for
today, and I find it to be the most pathetic example of trying
to spin your way out of taking responsibility for a serious
approval error I have ever seen. The fact that your board
unanimously approved this fake company to turn fake tests using
a witches' brew recipe for a gel that doesn't exist, I find to
be outrageous. Two other IRBs rightfully rejected the
application saying the plan was awful, a piece of junk, and the
riskiest thing I have ever seen on this board.
So why did your company unanimously approve it? And would
you want your family members to participate in a trial using
this gel? No, rather than discuss how your board reached
unanimous approval and said the gel is probably very safe and
that a risk assessment is not required, you chose to attack the
investigators and even called this oversight effort tyranny.
Well, sir, your approach is misguided. It reminds me of the old
ruse used by parents on their children to draw their attention
away going, look, bright shiny object. I don't care how many
bright, shiny objects you tell us to look at, your PR firm and
your lawyers, to draw attention away from the real issue, your
company still has to answer for this decision that would have
allowed patients to spend 5 months taking a fake and
potentially lethal product from a fake company with a fake
doctor.
And to HHS, what in the devil is going on in your agency
that allows you to think you can ignore the law and regulations
regarding adequacy of IRBs and simply enter whatever is e-
mailed your way and put the U.S. Government stamp of approval
on an IRB? You have three federal employees signing up 300 new
IRBs a month, according to the GAO, and the leadership of this
agency says it is not important to follow the federal rules
regarding a test of adequacy? Nobody picked up on names like
Phake Medical Devices, April Phuls, Timothy Wittless, and Alan
Ruse, or the town of Chetesville, Arizona? This didn't raise a
flag? And yet you give out the HHS stamp of approval. It is
unbelievable. Moreover, it could be lethal.
Is it any wonder the GAO says this system is vulnerable to
manipulation? I understand that more than 10 years after the
Inspector General's report, FDA recently announced a final rule
with respect to the IRB registry system that will go into
effect this summer. I am curious whether our witnesses believe
this new rule will address any of the problems we will hear
about today. It is our solemn duty to ensure that those who
participate in clinical trials can have confidence that their
safety is in trustworthy hands and that government
certification means something. We want to encourage
participation and support of clinical trials by protecting the
integrity of these studies and strengthening the public trust.
Thank you again, Mr. Chairman, for convening this hearing. I
look forward to today's testimony, and I yield back my time.
[The prepared statement of Mr. Walden follows:]
Mr. Stupak. Thank you, Mr. Walden. Ms. DeGette, for an
opening statement, 3 minutes, please.
OPENING STATEMENT OF HON. DIANA DeGETTE, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF COLORADO
Ms. DeGette. Thank you, Mr. Chairman. Chairman, patient
safety and research situations for this committee is really
like food safety. One thing you can be sure of is that a crisis
is looming just around the corner. In 1999, a young man named
Jesse Gelsinger died while participating in a gene therapy
trial at the University of Pennsylvania. An FDA investigation
concluded the scientist involved in the trial, including the
lead researcher, who had a potential financial interest in the
results of the trial, broke several rules of ethical conduct
including inadequate informed consent procedures. In 2006 the
antibiotic, Ketek, caused liver failure and death in patients
who used it. An investigation showed that investigators had
given fraudulent data to the FDA to gain approval of Ketek.
A whistleblower who learned of the fraud contacted the
Institutional Review Board that was responsible for approval of
the Ketek clinical trial, but the IRB allegedly did nothing to
report the fraud and stop the use of Ketek. And now here we are
again today. Research is the key to innovation and discovery
including curing deadly diseases, but as this whole panel
agrees, the research must be conducted ethically so that
participants understand the risk and make informed decisions
about volunteering. That is why we need to upgrade our entire
patient protection system in this country.
Mr. Chairman, I have introduced legislation in the last 6
sessions of Congress, the Protection for Participants in
Research Act, and it reforms federal regulation and oversight
of research on human participants by making federal regulations
applicable to all research that is in or affects interstate
commerce, that strengthens the education and monitoring of
Institutional Review Boards, that harmonizes FDA regulations
and the common rule, the two major sets of federal regulations
governing research participant protection, that strengthens
protection against conflicts of interest by investigators or
IRB members, that improves monitoring of research risks and
reporting of adverse events and unanticipated problems.
We have reintroduced this legislation this session of
Congress, and I would urge every member of this subcommittee on
both sides of the aisle to look at the bill and think seriously
about co-sponsoring it. The last session of Congress, we came
close to passing the legislation on the suspension calendar
because I think one thing we can all agree on in a bipartisan
way is that we need to encourage medical experimentation but we
need to do it in a way that both protects the patient and gives
them informed consent about what they are getting into. Mr.
Chairman, I don't want to be here for 13 hearings like we have
been on food safety. I want to get this done. We have been
working on it a number of years. We know the problem. We know
the solutions. And I am looking forward to working with
everybody on this committee to improving research so that we
can have a robust system but at the same time protect the
participants. Thank you, Mr. Chairman.
Mr. Stupak. Thank you. Mr. Burgess for opening statement,
please.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess. Thank you, Mr. Chairman. In a surprise move, I
am going to agree with the other side of the dais about the
number of hearings, not wanting to have the numbers of hearings
we have had on other areas before we do something. You know,
today's economic environment, there is a lot of investigative
activity that we could focus on, and we continue, continue, to
have FDA-related hearings. I mean this is the Committee on
Oversight and Investigations, not the committee to investigate
the FDA. But I believe this subcommittee has some jurisdiction
on what has happened with the financial services in this
country, and we have had no hearings on that. Secretary
Geithner might enjoy a visit to our committee and I would enjoy
having the opportunity to question him. So the extent that this
subcommittee has jurisdiction over the troubled asset relief
program, I believe we ought to be involved.
The Department of Energy, we had two hearings in this
subcommittee last Congress on the security of our national
labs. I recall us having questions for the head of the Lawrence
Livermore laboratory. Well, it turns out now he is just right
down the street at the Department of Energy. When are we going
to go have Secretary Chu in to provide answers to that
questions that we couldn't get answered last fall? Instead, we
are having yet another hearing on the Food and Drug
Administration, an agency that we all know is in desperate
shape, is broken. The morale of its workers is precariously
low. We acknowledge it. We are part of the cause. It is a 20th
century agency operating in a 21st century world, a world that
is global, commercial, and innovative with regards to food,
drugs, and medical devices, but it is regulated by an agency
that is underfunded, understaffed, under supported, and what
meager funds we do provide them, they have got to expend
preparing for the next congressional hearing.
Now these issues relating to the Institutional Review
Boards are serious. Any human subject testing should be
carefully overseen by the federal government to prevent abuses.
The types of products that were being discussed in the issues
before us today are products that I would have used in my--
might have used in my former life, so I understand the
seriousness of this issue, but I can also remember back right
before I started medical school hearing about the experiments
going on in Tuskegee, Alabama, with the former Department of
Health, Education, and Welfare and their involvement. That is
why the government now has the common rule to govern 17
different departments and agencies within the federal
government on human testing and why the Food and Drugs
Administration has similar regulations governing human subject
testing for medical devices and drugs.
There must be ongoing scrutiny of the internal review
boards. We must make certain the science is unfettered and
rigorous and the Office of Human Research Protection needs to
have the appropriate oversight. We need to make certain that we
don't politicize the process, that conflicts of interest are
being avoided, and all adverse events are thoroughly evaluated
and that there is a clear avoidance of the IRB shopping where
an Institutional Review Board will be removed from one
institution to another because the results were not favorable.
I am particularly concerned about the interaction of the common
rule with the Food and Drug Administration regulations
governing the investigational new drug applications. We all now
the failures of the IRB and Ketek. Their failure was the
impetus behind the GAO report being presented to us today
regarding the review and oversight of the Institutional Review
Boards.
But this is a problem that can be fixed. Let us fix it and
move on to the next thing. We should hold a hearing on the
entire approval process at the FDA. The IRBs, certainly they
need to be investigated, the registration system, but what
about the 510K exception for new drugs and the alleged
revolving door where FDA employees go straight to the drug
companies and then come back. We owe it to the American people.
We owe it to the scientific community to fix the FDA and fix it
right. Let us get on with that task. I yield back.
Mr. Stupak. I thank the gentleman. I would also note this
week you addressed to a letter to us on wanting to do hearings
on medical devices with the FDA, and that is something that we
are looking at closely so just so the record is clear, we will
probably have more FDA hearings unfortunately. Ms. Christensen
for opening statement, please.
OPENING STATEMENT OF HON. DONNA M. CHRISTENSEN, A
REPRESENTATIVE IN CONGRESS FROM THE VIRGIN ISLANDS
Mrs. Christensen. Thank you, Mr. Chairman. This is a very
important hearing, and I thank you, Chairman Stupak and Ranking
Member Walden for holding it. Because of the differences we
have seen in response to medications and other treatments by
African Americans, we, including the National Medical
Association who I see in the audience, have been encouraging
individuals and providers in our communities to become involved
in clinical trials. I even participated in one briefly before
coming to Congress. But in our community the specter of
Tuskegee still looms large in our minds, and then there have
been more recent incidents. I recall joining with other members
of the House to stop the testing of pesticides in children,
mostly African American poor children, just a few years ago.
So if we though that this was an aberration or that
Tuskegee could not happen again, obviously as we try to
convince our communities the GAO report tells us that we were
badly mistaken. The IRB process is supposed to ensure the
health and safety of individuals in clinical trials. We, who
have apparently misplaced our trust in the system are outraged
at the failures that are documented in the GAO report. This
system needs to be fixed, and I for one cannot in good
conscience encourage another person to participate in a
clinical trial until it is. Thank you, Mr. Chairman. I yield
back.
Mr. Stupak. Thank you, Ms. Christensen. Mr. Gingrey,
opening statement, please.
Mr. Gingrey. Mr. Chairman, thank you. Today this committee
has an opportunity to make sure that Institutional Review
Boards are taking every possible step to ensure the safety of
those who agree to participate in biomedical research.
Biomedical research and clinical trials are critical to
developing and perfecting the next generation of life saving
medicine and devices. Without question, the potential benefits
must outweigh the potential risks to participants. However,
these individuals must also be made fully aware of the
potential risks when they agree to participate. Mr. Chairman, I
look forward to listening to the testimony, and I would like to
reserve the balance of my time for questions, and I yield back.
Mr. Stupak. Thank you, Mr. Gingrey. Mr. Green for opening
statement, please.
OPENING STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Green. Thank you, Mr. Chairman. I thank you for having
this hearing today on the Institutional Review Boards, the
IRBs, and the federal government's oversight of these boards.
IRBs were created to protect individuals from harm or death
during an experiment and ensure individuals give informed
consent to the researchers. IRBs are in place to minimize the
risks to the subjects, that the risks of the study are
reasonable in anticipation of the benefits. Protection for
subjects during experimental research are vital. Unfortunately,
we have two painful incidents in our past to remind us just how
necessary these protections are, the formaldehyde distribution
in 1960 and the Tuskegee study in 1974. Both of these incidents
serve as painful reminders of the wrongdoing of researchers at
the expense of the health and well-being of the subjects.
Most recent, we have the Ketek incident, which the IRB
failed to investigate a whistleblower's allegations during
continuing review of the application. I was on this
subcommittee when we investigated Ketek and the flawed review
process that enabled the drug to come to market. Several deaths
have occurred during studies that received IRB approval. In
recent years, many called for reforms to the IRB system. IRB
regulations were created in the 1970's and have not been
reformed in recent years. Currently, HHS and the Office of
Human Research Protection has the jurisdiction over IRBs for
studies with federal funding. FDA has jurisdiction over testing
for medical devices and drugs.
HHS requires IRBs but the FDA does not. However, the FDA is
developing an IRB process. There are also independent IRBs not
affiliated with any institution operating in the U.S. These
IRBs are associated with the industry. The GAO and HHS have
issued several reports documenting problems with the current
IRB process. In 1998, GAO issued several recommendations for
IRB reform, and to date none of these recommendations have been
adopted by HHS or FDA. I am looking forward to the testimony of
the witnesses, particularly GAO, so we can see if our oversight
of IRBs is adequate and whether reforms of the system need to
be made. And I yield back my time.
Mr. Stupak. Thank you, Mr. Green. Member of the
subcommittee, Mr. Markey, for opening statement, please.
OPENING STATEMENT OF HON. EDWARD J. MARKEY, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF MASSACHUSETTS
Mr. Markey. Thank you, Mr. Chairman, very much. While
legitimate research is vital, human experimentation must be
conducted under the highest ethical standards. This is a very
important issue to me. In November of 1986, as chairman of the
Energy and Commerce Subcommittee on Energy and Power, I
released a report describing radiation experimentations on
human subjects by American scientists between the 1940's and
the 1970's. The people tested in these experiments were used as
nuclear human guinea pigs to determine the effects of exposing
humans to nuclear radiation. Most of those experiments provided
little or no medical benefit to the patients. In many cases
informed consent was not granted, yet, these individuals were
asked to ingest, inhale, or be injected with radioactive
materials, materials whose safety was not yet determined.
These scientists recklessly endangered human lives and much
of their work was kept hidden from the public until the 1980's
and 1990's. The good news is that although when I released my
report in 1986 the Reagan and then Bush administrations refused
to respond to it. President Clinton, in 1994, upon my urging
established the Presidential Advisory Committee on Human
Radiation Experiments, which issued this report which led to
the strengthening of regulations for research with human
subjects.
We are here today to discuss IRBs. IRB is supposed to stand
for Institutional Review Board. Unfortunately, with some
experiments, IRB stands for irresponsible, reckless behavior.
Unscrupulous IRBs have followed lax review procedures and
unethical practices when assessing the safety of clinical trial
experiments. As a result, participants have been put at risk of
injury or worse, death. Without proper review from IRBs, the
scientific integrity of clinical research work has been
compromised. This can lead to faulty evidence regarding the
safety of drugs and devices, and can further endanger the
safety of the public at large if these products gain approval
by the FDA.
When it comes to protecting the safety of consumers, we
must have the highest standards. In February of 2007 when I
called on the FDA through several of my letters and a hearing
by this subcommittee, and, again, Mr. Chairman, you have been a
real leader on this, to answer questions regarding the safety
of the antibiotic Ketek, the FDA approved Ketek partly based on
fraudulent studies of its safety. Later, we found that Ketek is
linked to severe liver damage and death. In this case, the IRB
responsible for approving the clinical trials of Ketek ignored
warnings from a whistleblower.
Mr. Chairman, you have really been a policeman, a watchdog,
on this issue. This hearing is another in the long process that
you have conducted, and I want to congratulate you for that. I
yield back the balance of my time.
Mr. Stupak. Thank you, Mr. Markey. Ranking member of the
full committee, Mr. Barton, has joined us. Opening statement,
please, Mr. Barton.
OPENING STATEMENT OF HON. JOE BARTON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Barton. Thank you, Mr. Chairman. Apparently, I am still
in time to do the digital transition opening statement too if
that subcommittee chairman is here for this hearing. I want to
echo what Congressman Markey just said about your leadership
and Mr. Walden's leadership on this issue in taking a look at
the Institutional Review Boards. We are following up today on
an issue that was uncovered during an investigation in the last
Congress. The question is whether these Institutional Review
Boards do a good job of protecting human subjects. When we
started looking into this, we were concerned that some of the
IRBs were not equipped to handle the amount of the complexity
of the work that comes up during the clinical trials.
As a part of our subsequent investigation was an undercover
work that the GAO conducted over the last year. GAO made up a
supposed clinical investigator, outfitted him with a
transparently suspicious resume, assigned him a fake medical
license number. GAO also concocted a verifiably false company,
devised med systems as a sponsor of the fake study. The study
protocol was straight from the Internet, and the device, the
company, and the doctor were 100 percent fictitious. Once this
particular IRB learned the committee was investigating to their
credit it took them less than a day to decide that something
was wrong. Instead of actually doing something, they put out a
news release that acted as if they had just been stung by James
Bond instead of the GAO.
The IRB is here today to explain why it decided to approve
the equally easy to detect fake protocol and whether it stands
by that decision. I suspect that this subcommittee will have
some very direct questions about the alleged science and the
patently false protocol that Coast IRB rubberstamped and why it
caused no apparent concern even though it had no supporting
data from clinical trials and the study devised matched
examples of significant risk devices on the FDA's own web site.
I think we should be careful not to over emphasize or to under
emphasize the significance of what this investigation has
shown. Coast IRB was sloppy and/or negligent, perhaps just flat
wrong, in its judgment about the protocol and the risk it posed
to its study's subjects.
But, fortunately, two other IRBs that were presented with
the same protocol rejected it, one without even considering it.
The vast majority of clinical trials, at least I hope, are
conducted without harm to patients. Even so, I am bothered by
the fact that two of the IRBs that GAO investigated and the
other IRBs who advertised in trade magazines and on the
Internet seemed to focus on the speed of their review and the
guarantees of a quick turnaround time. In some of those ads,
patient protection and safety seem almost like an after
thought. The bigger issue today may not be that one IRB made a
grade error and then tried to throw attention elsewhere, but
that the current set of regulations does little to prevent such
an error. That is our job if we need to review those
regulations.
We need to take a close look at those regulations and ask
whether they are meaningful in the current research and
clinical trial environment. Current regulations require that an
IRB must make a number of determinations before approving a
protocol, including that risks are minimized to the patient and
that the patient has knowingly consented to participating in
the study. But as GAO and the HHS Office of Inspector General
have been reporting for years, there is basically no test that
an IRB must pass before it opens for business to show that it
is qualified to review such clinical trials. It is frustrating
that the same problems keep popping up. These are problems that
the GAO and the Inspector General have discussed in reports
issued as long as 10 years ago.
I know that the FDA recently announced a rule that would
require IRBs to register with the FDA, but again that was a
reform that was called for years ago, and I don't think that
this rule would have made much difference with regard to
solving the problems that the GAO has identified in its most
recent undercover investigation. By putting the GAO findings in
proper context, we can strengthen bio-medical research and
innovation. If the public sees that our committee and federal
agencies are ensuring that the research committee is looking
out for the folks here confidence in clinical trials will be
boosted and participation will increase. This should be a very
meaningful hearing if we keep our discussion in perspective. I
want to thank our witnesses for testifying today, and, again,
you, Mr. Chairman, and Mr. Walden for leading on this issue. I
yield back.
Mr. Stupak. Thank you, Mr. Barton. That concludes the
openings statements of members of the subcommittee. We have out
first panel of witnesses before us. The panel that we have is
Mr. Gregory Kutz, who is the Managing Director of Forensic
Audits and Special Investigations at the Government
Accountability Office, GAO, Dr. Jerry Menikoff, who is the
Director of the Office for Human Research Protections at the
Department of Health and Human Services, Dr. Joanne Less, who
is the Director of the Good Clinical Practice Program at the
Food and Drug Administration, and Mr. Daniel Dueber, who is the
Chief Executive Officer at Coast IRB, LLC.
It is the policy of this subcommittee to take all testimony
under oath. Please be advised that you have the right under
rules of the House to be advised by counsel during your
testimony. Do you wish to be represented by counsel? If so,
would you have them--would you state your counsel's name? Mr.
Kutz. Dr. Less. Dr. Menikoff. Mr. Dueber.
Mr. Emord. Jonathan Emord.
Mr. Stupak. OK. During your testimony, if you want to stop
and confirm with that, that will be fine. He cannot testify but
he can give you advice. That is fine. It is the policy of this
subcommittee to take all testimony under oath, so I am going to
ask you to please rise, raise your right hand, and take the
oath.
[Witnesses sworn.]
Mr. Stupak. Let the record reflect the witnesses replied in
the affirmative. They are now under oath. We will proceed with
your opening 5-minute statement. Mr. Kutz, we will start with
you, please, sir.
TESTIMONY OF GREGORY KUTZ, MANAGING DIRECTOR, FORENSIC AUDITS
AND SPECIAL INVESTIGATIONS, GOVERNMENT ACCOUNTABILITY OFFICE;
JERRY MENIKOFF, M.D., DIRECTOR, OFFICE FOR HUMAN RESEARCH
PROTECTIONS, DEPARTMENT OF HEALTH AND HUMAN SERVICES; JOANNE
LESS, DIRECTOR, GOOD CLINICAL PRACTICE PROGRAM, FOOD AND DRUG
ADMINISTRATION; AND DANIEL DUEBER, CHIEF EXECUTIVE OFFICER,
COAST IRB, LLC
TESTIMONY OF GREGORY KUTZ
Mr. Kutz. Mr. Chairman and members of the subcommittee,
thank you for the opportunity to discuss Institutional Review
Boards. Our investigation relates principally to private IRBs
that authorize human subject testing. Today's testimony
highlights the results of our investigation of the IRB system.
My testimony has 2 parts. First, I will provide some very brief
background, and, second, I will discuss the results of our
investigation. First, as several of you have mentioned, federal
regulations governing human subject testing evolved from
society's horrified reaction to several cases.
For example, there were the forced medical experiments on
countless Holocaust victims. In the U.S., we had the 40-year
Tuskegee study. In this case, hundreds of poor, mostly
illiterate African American men, were not properly treated for
syphilis so that the effects of this disease could be studied.
Today, IRBs play a critical role in the safety and protection
of human subjects. With this background in mind, let me move on
to our results. Our investigation found that the current system
is highly vulnerable to unethical or incompetent actors. We
tested the IRB system with 2 separate but related undercover
operations. The objective of the first operation was to see if
an actual IRB would authorize our bogus medical device company
to conduct human subject testing.
The objective of our second operation was to determine
whether a real medical research company would hire our bogus
IRB. If successful, this would show that the bogus IRB could
have authorized human subject testing. First, our bogus medical
device protocol was approved by a real IRB even though we had
no medical expertise. Our bogus device, which we called
adhesive block, was a post-surgical healing device for women
that matched several FDA descriptions of a significant risk
device. We created our protocol and fictitious device using
information that was publicly available and on the Internet.
The monitors show excepts from the IRB board meeting where our
protocols were unanimously approved and adhesive block was
referred to as being probably very safe.
As shown on the monitors, some due diligence would have
shown a mailbox as our suite or office, a fictitious lead
researcher with a fabricated medical license and resume, a
fabricated FDA marketing approval for our device, and a cell
phone as the only number we provided. The next picture on the
monitor shows a coupon that this IRB provided which got our
attention. Given that we are dealing with experimental research
on human beings, we were surprised that anybody would offer
discount coupons for this service. This IRB is no fly by night
operation. They are currently the IRB of record for over 70
federally-funded projects, and according to their own press
release have overseen thousands of trials.
Two other IRBs we sent these very same protocols to had a
very different response. The monitor shows examples of their
comments, including this protocol was awful and a piece of
junk, the riskiest thing I have ever seen, the odds of approval
were 0 percent, and my favorite comment, if somebody approves
it, oh, boy. For the IRB that approved our study, the only due
diligence they appeared to perform was after they received a
letter from this subcommittee. After receiving this letter, the
IRB was able to determine, for example, that our lead
researcher and FDA marketing approval were, in fact, bogus.
However, this IRB had already approved our bogus device for
human subject testing 4 months before receiving your letter.
For our second operation, we created a bogus private IRB.
Once again, we used phony company officials and a mailbox as
our business address. We registered our IRB on line with HHS
and created a web site that looked like the web sites that
other IRBs used. Then we went fishing. We advertised our
services on the Internet and in newspapers to see if a real
researcher or researchers would contact us. The monitors show
our advertisements. Notice that we emphasized the speed of our
reviews, our HHS approval, and guaranteed results. We did
refrain from offering discount coupons as part of our
advertising campaign.
In response to these ads, our bogus IRB received protocols
from one company and inquiries from five others. The company
sending us its protocols was seeking approval to add a new test
site for ongoing trials. Our bogus IRB, which as I mentioned
had absolutely no medical expertise, could have authorized
human subject testing at this site. However, we told this
company that we couldn't review their protocols because we were
experiencing significant financial problems due to the current
economic crisis. In conclusion, every year millions of
Americans submit themselves to experimental research. These
people are among our nation's poorest and most vulnerable. I
can't tell you whether our 2 undercover successful tests are
isolated cases or the tip of the iceberg.
What I can tell you is given the history of human subject
testing, it is hard to believe that anybody could be
comfortable with the integrity of the current system. Mr.
Chairman, that ends my statement and I look forward to your
questions.
[The prepared statement of Mr. Kutz follows:]
Mr. Stupak. Thank you, Mr. Kutz. Dr. Less, your opening
statement, please. And for all the witnesses if you have a
longer statement than 5 minutes, it will be included in the
record.
TESTIMONY OF JOANNE LESS
Ms. Less. Good morning, Mr. Chairman, and members of the
subcommittee. I am Joanne Less of the Good Clinical Practice
Program at the FDA. I appreciate your invitation to appear here
today to discuss FDA's role in overseeing Institutional Review
Boards. For over 40 years, FDA has been committed to protecting
the rights, safety, and welfare of subjects who participate in
clinical trials of FDA-regulated products. The obligation to
protect individuals who volunteer for research and assume
research risks in order to advance public health and bio-
medical knowledge is integral to FDA's mission, and the agency
continually strives to strengthen and promote the human subject
protections. While measures to protect subjects are
incorporated into all aspects and all stages of clinical trial,
perhaps human subject protection is most clearly embodied in 2
critical activities.
The first is the requirement to obtain voluntary, legally
effective informed consent from each study subject. The second
is a requirement for independent ethical review of each
clinical trial. The responsibility for human subject protection
is one that FDA shares with sponsors, clinical investigators,
study monitors, and IRBs. Every party with a role in the
conduct and management of the trial has clearly defined
responsibilities under FDA's regulations. All of these parties
must fulfill those duties and be vigilant in doing so or
subjects could be put at risk. This network of overlapping
responsibility is key to protecting the rights, safety, and
welfare of subjects who participate in FDA-regulated trials.
IRBs are a critically important component of this
collaborative oversight system. The primary purpose of IRB
review is to assure the protection of the rights, safety, and
welfare of human subjects. An IRB has the authority to approve,
require modifications in or disapprove research. To approve a
study, the IRB must determine that all of the following
criteria are met. The risk to subjects are minimized, the risks
are reasonable in relationship to anticipated benefits,
selection of subjects is equitable, and informed consent will
be obtained and documented. The IRB may require modifications
to the protocol, informed consent or study procedures before it
approves the study.
An IRB may disapprove a study due to protocol deficiencies
or for reasons such as limited availability of suitable
subjects. Once a study begins, IRBs are responsible for
reviewing changes to research. IRBs have the authority to
suspend or terminate approval of research that has been
associated with unexpected serious harm to subjects. There are
different types of IRBs. Most IRBs are established and operated
by universities, hospitals, and other institutions. These IRBs
are comprised primarily of volunteers from the institution's
faculty and staff. A small number of IRBs, often referred to as
independent IRBs, are not affiliated with such an institution.
Independent IRBs may provide reviews for industry-sponsored
projects conducted outside a university or hospital, for
example, in a doctor's office. FDA applies the same oversight,
scrutiny, and inspectional practices to all types of IRBs. The
agency places a higher priority on inspecting IRBs that are new
that have not been previously inspected, that have previously
been found to be out of compliance or that are reviewing
research involving high risk products or vulnerable
populations. During these inspections, FDA investigators select
one or more studies in the IRBs inventory. The inspector
reviews the IRB procedures and records, follows the selected
studies through the entire process, and interviews key staff.
FDA also conducts for-cause inspections of IRBs for which
there have been complaints. During a for-cause inspection, FDA
focuses on the issue identified in the complaint and determines
if there is evidence to substantiate it. If an FDA investigator
uncovers a regulatory violation, the agency may take further
action. For minor deviations, FDA generally issues a letter
describing the deficiency and provides reference to the
relevant regulations or guidance. For more serious violations,
FDA may issue a warning letter requesting that the IRB submit a
corrective action plan within 15 days.
FDA generally conducts a follow-up inspection to ensure
that the violations were corrected. The agency may also impose
administrative sanctions on an IRB. For example, FDA may
withhold approval of studies that are reviewed by the IRB,
direct that no new subjects be enrolled in ongoing studies, or
terminate all ongoing studies. Because the clinical trials
process has significantly evolved since FDA issued some of its
regulations, FDA launched an initiative aimed at modernizing
and strengthening the agency's oversight of clinical trials.
FDA issued a number of guidances with the expectation that they
will reduce burdens, improve IRBs efficiency, and allow IRBs to
give more attention to critical human subject protection
activities.
Earlier this year, FDA issued regulations that would
require all IRBs to register through an electronic system. This
will enable the agency to more precisely identify IRBs that
review FDA regulated research, assist us in providing
educational information, and help us to identify IRBs for
inspection. DA has also established a task force to ensure that
all pending and future recommendations related to the agency's
oversight of clinical trials raised by Congress, the HHS Office
of the Inspector General, and the General Accountability Office
are fully addressed.
Finally, although FDA has traditionally conducted a
majority of its inspections in association with the submission
of a marketing application, the agency has been shifting more
of its resources to inspections of ongoing studies. This will
allow the agency to identify potential problems while the study
is still active enabling implementation of corrective actions
to minimize risk to subjects and preserve the integrity of the
trial. FDA has also been improving its follow-up of violative
inspections and working to identify alternative methods to
select IRBs for inspection. It is FDA's strong belief that
educating IRB members, chairs, and administrators fosters
understanding of the human subject protection regulations and
enhances their ability to protect subjects participating in
research.
To that end, in partnership with OHRP and other
organizations, FDA participates in numerous national and
regional conferences and workshops. In conclusion, FDA remains
committed to strengthening human subject protection and
improving its oversight of IRBs and other parties that conduct,
oversee, and manage clinical trials. FDA has taken steps to
ensure that recommendations regarding the agency's oversight of
clinical trials, including IRBs, are fully addressed. While FDA
has already implemented a number of changes to its clinical
trial oversight activities, the agency continues to look for
and welcome input about new approaches to fulfill these
responsibilities. This concludes my statement. I would be happy
to answer any questions.
[The prepared statement of Ms. Less follows:]
Mr. Stupak. Thank you. Dr. Menikoff, your opening
statement, please, sir.
TESTIMONY OF JERRY MENIKOFF, M.D.
Dr. Menikoff. Good morning, Mr. Chairman, and members of
the subcommittee. I am Jerry Menikoff, Director of the Office
for Human Research Protections which is within the Department
of Health and Human Services. I previously served as director
of the office that oversees the NIH's human research protection
program. Before that, for almost a decade, I chaired the
Institutional Review Board at the University of Kansas Medical
Center. The department's commitment to human subject
protections spans more than 3 decades. In 1974 what was then
known as the Department of HEW issued its first department-wide
human subject protection regulations. OHRP is charged with
enforcing the current regulations which are in 45 CFR part 46.
OHRP's mission is to protect the rights, welfare, and well-
being of subjects involved in research conducted or supported
by the department. The responsibility for protecting research
subjects is one that OHRP shares with the FDA, agencies that
fund research, institutions that conduct research,
investigators who carry out that research, and the IRBs that
review it. Everyone with a role in human subjects research must
fulfill their duty to protect the subjects or else those
subjects could be at undue risk. The core provisions of the
department's current human subjects regulations cover three
major areas. First, institutions conducting HHS funded research
must enter into an agreement called an assurance agreeing to
comply with the regulations. Second, a committee called an
Institutional Review Board or IRB must review and approve the
research before enrollment of any subject. The IRB plays a
central role in ensuring that the rights, safety, and welfare
of subjects are adequately protected.
Third, the research must be conducted consistent with the
regulations, which generally require obtaining the informed
consent of the subjects and the IRB's continuing review of the
research. The department's regulation in addition provides
special protections for various populations considered to be
vulnerable. Besides the regulations administered by OHRP, there
are other federal regulations protecting research subjects. The
FDA has its own set of regulations. These apply to clinical
trials involving products regulated by FDA. These regulations
are substantially similar to those administered by OHRP, though
there are some differences.
In 1991, 14 other federal departments and agencies joined
HHS in adopting a uniform set of regulations that are identical
to the core portion of the HHS regulations. This set of
regulations is often referred to as the common rule. For all
participating federal department and agencies the common rule
outlines the same basic provisions for IRBs informed consent
and assurance agreements. As I noted, the department's
regulations require that institutions that are engaged in HHS
funded research must sign an agreement with OHRP known as an
assurance. Through this assurance the institution commits
itself to have all its HHS-funded research conducted in
compliance with the regulations.
Assurances must also include designation of one or more
IRBs that will review the research covered by the assurance.
The institution holds primary responsibility for ensuring that
the IRBs it designates are appropriately qualified to review
the types of research studies it conducts. The Federalwide
Assurance, or FWA, was introduced in 2000 and has been the only
type of assurance accepted by OHRP since 2005. Previously, OHRP
reviewed assurances using procedures that often involved
lengthy discussions with institutions. In 1998, the HHS Office
of Inspector General recommended that OHRP shift its focus and
resources to other parts of the system so as to better protect
research subjects. The current largely automated system for
processing FWAs was implemented as a response to that OIG
report.
With the adoption of the FWA system in 2000, a new
requirement was added. Any IRB designated under an FWA must be
registered with OHRP. The process for registering an IRB with
OHRP is separate from the process for obtaining FWA but the two
are related. This registration process was implemented in
response to a recommendation from that same OIG report. The
report recommended a simple registration system which would
collect minimal descriptive information such as location and
contact information. This simplified registration system would
still allow OHRP and FDA to communicate effectively with IRBs
while maintaining the standards of protection for research
subjects.
The IRB registration process requires among other things
submission of a list of IRB members identified by name,
qualification, and affiliations. OHRP generally accepts all IRB
registration applications that include information showing
compliance with the following requirements, that there are at
least five IRB members, there is at least one person designated
as a non-scientist and one designated as a scientist, and then
there is at least one member designated as not affiliated with
the institution. On January 15 of this year both OHRP and FDA
issued IRB registration rules. The two sets of registration
rules are quite harmonious and will be implemented through a
single web-based IRB registration system.
In conclusion, the protection of research subjects remains
a highest priority for both the department and for OHRP. We
continue to work on ways to better achieve that goal and very
much welcome any recommendations that the subcommittee may
have. Thank you for this opportunity to address you. I will be
pleased to answer any questions.
[The prepared statement of Dr. Menikoff follows:]
Mr. Stupak. Thank you, Dr. Menikoff. Mr. Dueber, your
opening statement, please, sir.
TESTIMONY OF DANIEL DUEBER
Mr. Dueber. Good morning. Coast IRB recently submitted the
product in question, Adhesiabloc, to an independent forensic
toxicological lab. That lab determined, as we did, as our board
did on October 30, that the product was safe. Here is the
conclusion by two top forensic toxicologists in the United
States. It is my opinion within a reasonable degree of
scientific certainty there is no sound scientific foundation
for finding the constituents in the Adhesiabloc gel described
in clinical study protocol pilot study of safety and efficacy
of 2.5 percent Adhesiabloc gel to reduce adhesions following
peritoneal cavity surgery, device clinical study protocol
number P-D-15 version 1.4, unsafe at the dose recommended for
testing.
In October of 2008, the Government Accountability Office,
at the behest of this committee, perpetrated an extensive fraud
against my company, Coast IRB, LLC. It did so without probable
cause that Coast had committed any crime. Indeed, no one at
Coast has committed any crime. It did so without involving the
executive branch. It did so without satisfying any of the legal
safeguards that the Department of Justice and the federal
courts have in place. It acted without probable cause that a
crime had been committed.
If this committee's objective with this fraudulent and
illegal GAO sting operation was to demonstrate that IRBs need
to do more checking and verification of sponsor and PI
licenses, verify the existence of companies and so on, fine, we
will do that. And we have changed our SOPs to do just that
because of this illegal fraud. But did you have to take the
extremely negative approach of setting up an elaborate,
expensive fraud? Yes, your fraud was very sophisticated, and
you pulled the wool over our eyes. Congratulations. But you
need to understand the effects of this charade. I personally
have wasted 5 weeks of my valuable time defending the honor,
integrity, and reputation of both our company and of me. We
have spent many years building that.
My company has now spent over $100,000 defending itself,
and do you know what that means? That means that we now have to
lay off at least five people at our company to pay for this. A
much better and positive approach would have been for you to
call a conference together of key IRB industry leaders, FDA,
OHRP, and the committee to identify what needs to be fixed and
what laws, regulations are needed to fix the problem. No one
would have had to have been harassed as Coast has with this
sting. The GAO posed as a private business seeking review by my
company of a medical device. It represented the medical device
to be one that was substantially equivalent to a device
approved for market by FDA.
In an elaborate scheme, GAO violated federal and state
laws, one, by falsely representing itself to be a medical
device company, two, by submitting a fake clinical trial
address, three, by submitting a fraudulent protocol for a
fraudulent medical device, four, by submitting a forged CV for
a fake principal investigator, five, by falsely representing
the medical device to be substantially equivalent to a device
approved by FDA for market, six, by submitting a fraudulent FDA
510(k) number for the device, seven, by submitting a fraudulent
Federalwide Assurance number, and eight, by forging a
Commonwealth of Virginia medical license and license numbers
for its supposed principal investigator.
GAO also engaged in extensive verbal and e-mail
correspondence with Coast IRB in furtherance of the fraud. The
fraud would have persisted to this day had I not discovered it
and had Coast not terminated the clinical trial. Had I not
discovered it following receipt of this committee's request for
documents, I am confident it would have been discovered before
its next scheduled review of the trial in April, next month.
Mr. Chairman, it is the exclusive duty and province of the
executive branch of this government to engage in law
enforcement actions. By well settled precedent that branch
alone may engage in clandestine stings upon probable cause that
a crime has been committed. Innocent citizens of this country
cannot be lawfully defrauded by their government. To hold
otherwise replaces the rule of law with tyranny.
Mr. Chairman, what the GAO has done at the request of this
committee is unlawful. The actions here involve mail fraud,
wire fraud, forging of a Commonwealth of Virginia medical
license, false presentation of license numbers and 510(k)
numbers, and false holding out of people to be physicians in
the Commonwealth of Virginia. Coast has notified federal and
state law enforcement of these crimes. These are crimes whether
committed by the GAO or anyone else in the absence of probable
cause. They are crimes for which those responsible should
answer. Although we have informed law enforcement that GAO is
behind them, a fact never affirmatively confirmed by your
committee staff to me, we have asked that the crimes be
investigated and that those responsible be prosecuted.
Mr. Chairman, the question confronting me, and which I hope
will occur to you, is whether this committee and the GAO have
the lawful authority to defraud an innocent party to prove a
political point. My question, sir, is whether this committee
and the GAO are above the law. You know, I am just very, very
saddened and disappointed in our government right now. I cannot
believe my government did this to me and my company. It is
unconscionable. But Coast IRB shares everyone's concern in this
room about the need to improve our oversight system. We have
been at the forefront in the past about documenting the need
for improvements in ICFs and IRB shopping and other categories.
We want to work with FDA and this committee to improve the
system in a positive way. Thank you, and I will be happy to
answer any questions.
[The prepared statement of Mr. Dueber follows:]
Mr. Stupak. The members will be recognized for 5 minutes
for questions. I will begin. Mr. Dueber, I have to tell you how
disappointed I am, I think Mr. Walden said the same thing, and
the other members who are up here, with your opening statement.
Coast IRB could have come forward this morning and admitted
that they made numerous mistakes by not checking into the
credentials of a fake company, a fake doctor, and a fake device
that Coast ultimately approved for use in human testing.
Instead, like a kid who has got caught with his hand in the
cookie jar, you now come before Congress today to complain that
you were caught. Nowhere in your opening statement is there any
sense of concern that your company's approval could have led to
human subjects being exposed to a dangerous substance without
testing. Lives could have been injured or lost as a result of
your company's action, and all you do is complain that you were
caught.
Where is the first responsibility and where is the
corporate responsibility? So let me ask you this, Mr. Dueber,
you were interviewed on the record by committee staff last
week. They asked you some basic questions about your medical
review of GAO's experimental testing protocol. And let me put
them on the screen. Here are your answers. When our counsel
asked you, do you feel your company's medical review of the
protocol was adequate, you indicated yes. So is it fair to say
that none of the board members, including Dr. Dodd, who did the
primary medical review, has raised concerns with the medical
review of this protocol? Is that fair to say that you have no
concerns about the protocol?
Mr. Dueber. This was a sophisticated fraud, sir.
Mr. Stupak. My question is, is it your opinion that the
medical review was fair in this case?
Mr. Dueber. We reviewed--we did a safety review. Dr. Dodd
looked at the protocol.
Mr. Stupak. And you feel it is safe?
Mr. Dueber. We checked with--Dr. Dodd made the conviction--
made the conclusion that it was safe, and we have just proven
that it is safe with an independent review of----
Mr. Stupak. Sure, your independent review, you talk about
the 2.5 percent of the Adhesiabloc. What about the 97.5 percent
of the liter that would be left in the woman's abdomen? What
about that 97 percent? You don't even know that it is, so how
can you test to see if it is even safe in your little report
you have there from your expert?
Mr. Dueber. He looked at it and he said that----
Mr. Stupak. He looked at what? 2.5 percent, that is what he
looked at.
Mr. Dueber. He looked at the whole device.
Mr. Stupak. Look at your protocol. You are going to leave 1
liter behind. What about the other 97.5 percent of the liter
that you have no idea what it was in our protocol because you
never asked.
Mr. Dueber. Well, sir----
Mr. Stupak. So, therefore, you can't sit here and say the
other 97.5 percent has been tested and safe when you don't know
what the tests were because you don't know what the product
contains.
Mr. Dueber. Sir, I am not a scientist. I did not do the
primary----
Mr. Stupak. Neither am I.
Mr. Dueber. But what I can tell you is that Dr. Dodd told
me when I talked to him about this that this propylene glycol
substance----
Mr. Stupak. Which is 2.5 percent, 1 liter, is safe. Didn't
the doctor tell you what the other 97.5 percent was?
Mr. Dueber. We didn't discuss----
Mr. Stupak. You didn't ask? What if it is poison? So let me
go on. GAO submitted this fake protocol to 2 other IRBs that
came to exactly the opposite conclusion than you did. They both
rejected the study. The first IRB that rejected the study was a
company called Argus IRB. Here is what they said. We realized
it was a terrible risk for the patient. The concept of the
study was risky. It is the worse thing I have ever seen. Doing
a surgery, a major surgery, on a patient, then a mystery guy
walks in and dumps a solution in the body. Where is the safety
for the patient? Who is overlooking all these parts? Who is
looking for the patient--who is looking out for the patient? I
had a problem with propylene glycol gel. They said it was a
safe substance. I didn't see any data on it. There was no data
in the protocol indicating that propylene glycol gel was safe
internally. It was a serious problem.
Mr. Dueber, how is it possible that your company found that
this study wasn't risky at all when other IRBs rejected it? And
actually a second IRB called Fox Company, they said I could
have sent the protocol to Board of Review but I spared wasting
their time. There was no monitoring for safety. It appeared
that people were just going to go out and start injecting
people. Mr. Dueber, given what the other IRBs found, don't you
think your company made a major mistake here?
Mr. Dueber. Our company followed the regulations that FDA
requires.
Mr. Stupak. Really? Where is the due diligence in your
company? Where is the safety of the patient by injecting them
with a liter bottle and 97.5 percent----
Mr. Dueber. It had a 510(k) exemption for one thing.
Mr. Stupak. Did you go check that 510(k)?
Mr. Dueber. No, we did not.
Mr. Stupak. Is that part of due diligence, checking a
510(k)? You relied on it.
Mr. Dueber. It is now. We have changed our SOPs to
incorporate those since we have been now hoodwinked by our
government.
Mr. Stupak. My time is up. Mr. Kutz, let me ask you this
last question, if I can. Do you believe Coast's medical review
was adequate? Do you agree with Mr. Dueber that there was no
risk involved with injecting a liter of this mystery substance
into a woman's abdominal cavity?
Mr. Kutz. I don't have the expertise to say that, but what
I would say is this is if you have a system where two companies
can say this thing is the riskiest thing they have ever seen
and they rejected it even in some cases before it got to the
board, and at the same time we have an IRB that says this is
perfectly safe, we got a real problem here. So I think that
would be what I can say based on my expertise.
Mr. Stupak. Thank you. And I recognize Mr. Walden for 5
minutes, please.
Mr. Walden. Thank you, Mr. Chairman. Mr. Dueber, I want to
go to this report from I guess it is Kupeck Group, LLC, because
he says in my opinion within a reasonable degree of scientific
certainty there is no sound scientific foundation for finding
that constituents in the Adhesiabloc gel described in clinical
study protocol pilot study, blah, blah, blah, are unsafe at the
dose recommended for testing. Is that the same thing as saying
the entire grouping of those items in this proposed gel are
safe? Does his report actually say or this company's report
actually say that the entire compilation and usage of the gel
was safe or just that the two constituent ingredients alone are
safe?
Mr. Dueber. That is our understanding. We asked him to
review the gel at the 2.5 percent for this study and for the
amount left in the cavity and he said that it is not unsafe at
this dose recommended for testing.
Mr. Walden. And so is he saying to you then that he would
have approved it for use in human subjects?
Mr. Dueber. That is the way we understood it, yes.
Mr. Walden. And left in their stomach, sir, their belly for
up to 5 months?
Mr. Dueber. Yes.
Mr. Walden. Where does it say that in the report? I don't
see it in the conclusion, and where does it discuss the
procedures involved?
Mr. Dueber. I haven't had the opportunity to read the whole
report.
Mr. Walden. When did you ask for the report, sir?
Mr. Dueber. Several days ago.
Mr. Walden. So what report did you ask for that would have
shown this was safe when your board approved this gel 70?
Mr. Dueber. Well, as I--excuse me.
Mr. Walden. While you are consulting with counsel, I will
go to Dr. Menikoff. You can continue to consult if you need to.
Dr. Menikoff, obviously you are representing HHS. You heard my
comments. I heard yours in terms of more of a recitation of
what the rules and the procedures are for your agency and the
same from Dr. Less for FDA. What troubles me greatly, and I
think what troubles the people I represent, is that virtually
anybody even with the most silly of applications can register
as an IRB simply by e-mailing your agency and it gets entered
even if the name of the town you are from is Chetesville,
Arizona for which I assume there is no zip code. Is this
preventable?
Dr. Menikoff. Congressman, it is true that anybody could
enter information into the registration system. The
registration system was a response to the very OIG report that
several of you commented on, and it basically established the
registration system, a method of collecting minimal information
so there would be a list of IRBs.
Mr. Walden. What do you do with that information mostly?
Dr. Menikoff. We use it to contact IRBs to send information
to them.
Mr. Walden. Information about that?
Dr. Menikoff. About a change in the system. There may be a
compliance allegation alleged against a particular IRB, so we
will contact them using the contact information.
Mr. Walden. Do you use it to contact them about conferences
and things?
Dr. Menikoff. It could sometimes be used for that.
Absolutely.
Mr. Walden. Mr. Dueber, let me go back to you because I
sense you may have an answer to my question.
Mr. Dueber. Yes, sir. The primary reviewer on this, Dr.
Dodd----
Mr. Walden. Very distinguished credentials, by the way.
Mr. Dueber. Yes. And he is very familiar with propylene
glycol which is the basis of this substance, and he told me
that propylene glycol can be ingested in large amounts in the
body and is not toxic and that it is proven to be non-
cancerous. There has been no question about its toxicity in any
part of the body even remaining in the body for a period of
time. He is an expert medical reviewer for the California
Medical Board. He is chief of staff at the Lodi Medical
Hospital. He is chairman of his Institutional Review Board at
Lodi Medical Hospital. He is an OB/GYN also. He knows his
stuff.
Mr. Walden. All right. I am sure he does. Dr. Less, since
you are FDA, is there any problem with ingesting this chemical
in your body and having it sit there for 5 months and in
concert with the surgeries and all?
Ms. Less. Having not----
Mr. Walden. You can't answer that?
Ms. Less. I was just going to say having not seen the
device description pre-clinical test and by compatibility
testing, we wouldn't be able to comment on that.
Mr. Walden. Mr. Kutz, maybe you can help us here. What did
the other IRBs say about this procedure and the protocols and
the tests and all?
Mr. Kutz. I think it is important to know that because it
goes beyond just is the product safe. If could read a few of
their comments to you, if that is OK.
Mr. Walden. Please.
Mr. Kutz. The first one, as you mentioned, said that our
submission was so bad they weren't even going to give it to the
board. They also said that our protocol showed no evidence of
quality control for sterility or consistency of the product.
The next comment is very, very important. They said there was
no prior investigation report of the pre-clinical animal
studies we claimed to have performed, and they wanted to know
whether there had been any adverse events, whether our product
killed animals or hurt animals.
The second IRB said who is the manufacturer of Adhesiabloc
and where is it made? It seems like a logical question. We
didn't put that in our protocols. Where will these surgeries
take place? That wasn't in our protocols. How are the hospitals
and surgeons being selected? That wasn't noted. Has the surgeon
or hospital read the protocols and do they agree? We didn't
answer that. Provide the diagram used to record the incision
lines. And the last one that seems fairly relevant when you are
discussing it, who will be performing and taking the tissues
and biopsies? So those are some of the substantive comments.
Mr. Walden. Mr. Kutz, did this IRB, which by the way made
itself known to the public through their public relations
outreach efforts, you didn't do that, did you?
Mr. Kutz. No, we never used----
Mr. Walden. And we did not. And so did this IRB come back
to you with any questions about the protocols, any questions
about----
Mr. Kutz. Their initial focus was on the consent form, and
they wanted us to, if you will, dumb it down so 5th grade level
of reading could be done, so they were very focused on the
consent form, which is part of their--not a lot of substance on
the actual medical or the issues of the hospitals, who were
these surgeons, who is this person actually putting the item
into the woman's pelvic region after open surgery, no questions
at all of substance like that.
Mr. Walden. My time has expired.
Mr. Stupak. Thank you, Mr. Walden. Ms. DeGette for
questions, please.
Ms. DeGette. Thank you, Mr. Chairman. Mr. Dueber, how long
has Coast been in business?
Mr. Dueber. Since 2002.
Ms. DeGette. Since 2002. And since that time, you have
reviewed 352 protocols, correct?
Mr. Dueber. No. I don't know exactly how many we have
reviewed.
Ms. DeGette. OK. Have you declined any of the protocols
that you have reviewed?
Mr. Dueber. My understanding is yes, but I don't know how
many.
Ms. DeGette. OK. Mr. Chairman, I would ask unanimous
consent that Mr. Dueber supplement his response to tell this
committee how many protocols that they have reviewed and how
many they have approved and how many they have rejected.
Mr. Stupak. Without objection.
Ms. DeGette. Thank you. Now with this particular protocol
you took this on 5 months ago, correct?
Mr. Dueber. Correct.
Ms. DeGette. And you approved the protocol for testing on
humans within 48 hours, didn't you?
Mr. Dueber. On this particular study, I am not sure what
the turnaround time was.
Ms. DeGette. Well, your company advertises a 48-hour
turnaround on most cases, correct?
Mr. Dueber. What that refers to, ma'am, is that----
Ms. DeGette. Yes or no.
Mr. Dueber. I can't answer yes or no because I need to
explain it.
Ms. DeGette. All right. Go ahead.
Mr. Dueber. The turnaround time refers to the amount of
time it takes for the Coast administrative staff, which is
separate from the board, to review the documents presented by
the protocol sponsor and----
Ms. DeGette. OK, I got you. So it is the administrative
turnaround. How long and on average per protocol does it take
you to approve this protocol for human testing?
Mr. Dueber. I am not sure because the board--every member
of the board has to review thoroughly the protocol.
Ms. DeGette. So can you give me--how long did it take on
this case? Did it take 48 hours to approve it for human testing
on this case?
Mr. Dueber. Well, it probably took longer than that
because----
Ms. DeGette. Well, how much longer?
Mr. Dueber [continuing]. There were two board----
Ms. DeGette. Three days, 4 days, 5 days?
Mr. Dueber. Well, there was a week between the preliminary
approval and the final approval.
Ms. DeGette. A week. OK. Now, excuse me, sir, we can swear
in your lawyer if he would like to testify, but I would like
you to answer. Now so it took a week to approve this protocol.
At the time that the protocol was approved for human testing,
the report that was prepared by this very fine doctor that you
talked about, did he prepare that report at that time that the
protocol was approved?
Mr. Dueber. Are you referring to the minutes of the board?
Ms. DeGette. I am referring to the Kupeck Group LLC report
that you provided to this committee late last night.
Mr. Dueber. You are asking how long did it take him to do
this?
Ms. DeGette. No. I am saying did he prepare this at the
time, 5 months ago, when it was approved?
Mr. Dueber. No.
Ms. DeGette. No. Was there a written report by him approved
that went through all the scientific basis 5 months ago?
Mr. Dueber. No.
Ms. DeGette. Was there anything in writing analyzing the
scientific evidence and the risk and benefits?
Mr. Dueber. There was extensive discussion at the board
meeting itself between----
Ms. DeGette. Was there any written report prepared at that
time?
Mr. Dueber. There were minutes prepared for that.
Ms. DeGette. Does this committee have copies of those
minutes?
Mr. Dueber. Yes.
Ms. DeGette. OK. I would ask our committee staff if I could
get a copy of those minutes, please. Now this report, when was
this prepared, the report that you keep referring to as to the
scientific efficacy of the protocol, prepared?
Mr. Dueber. Yesterday.
Ms. DeGette. And why was it prepared yesterday?
Mr. Dueber. Because we contacted----
Ms. DeGette. Because you were coming in to testify today,
right?
Mr. Dueber. We contacted this individual and asked if he
would review this because we were----
Ms. DeGette. Because you were coming in to testify today,
right?
Mr. Dueber. Well, we were convinced because Dr. Dodd was
convinced that this substance was safe. He made that
determination. The board agreed. We have five doctors, high
quality doctors, on our board, and they agreed it was safe.
Ms. DeGette. OK.
Mr. Dueber. We just wanted before we came here to find out
if that was----
Ms. DeGette. To find out, in fact, if it was safe?
Mr. Dueber [continuing]. In fact the case.
Ms. DeGette. We could have been doing human testing for 5
months without that report.
Mr. Dueber. But, ma'am, no one in--we have never at Coast
ever had a fraudulent study submitted to us. There is no
economic reason for anybody to do such a thing.
Ms. DeGette. OK. I am sorry. First of all, let me stop you
and say I now have the minutes in front of me, and the whole
discussion is about a paragraph long. But as the chairman is
saying, the paragraph never talks about what is in that 95
percent of the substance, so how would they possibly know if
this would be safe?
Mr. Dueber. It is based on propylene glycol which is proven
to be safe.
Ms. DeGette. But that is 2.5 percent.
Mr. Dueber. Propylene----
Ms. DeGette. What is in the rest?
Mr. Dueber. The board reviewed that and felt that it was
safe and there was----
Ms. DeGette. OK. I am going to----
Mr. Dueber. --a 510(k) device upon which they were basing,
you know, the fact that that existed and therefore it should be
safe. And, of course, we didn't check the 510(k) device to see
if it was real, but we never had reason to do that, ma'am.
Ms. DeGette. Let me just stop you. Now Ms. Christensen-
Green and I are sitting here looking at this going we sure
don't want this in our abdomens, and I think all the other
women sitting here today are thinking that. That is the thing
about IRBs. We think that when we approve--when we ask IRBs to
review a protocol, we are doing it so that they can review the
safety of the entire protocol. And we have had situations like
this where--we had one situation where an IRB approved a
protocol where they performed one type of plastic surgery on
one-half of someone's face and another type on another half,
and that person was grossly disfigured. What would have
happened if this actually would have gone into human testing,
and they would have put something poisonous as the other 97.5
percent into women's abdomens?
Mr. Dueber. I can't speculate on what would have happened.
Ms. DeGette. I can't either. Dr. Menikoff, would you agree
that is a problem?
Dr. Menikoff. Congresswoman, this study is outside OHRP's
jurisdiction. It was not federally funded.
Ms. DeGette. Well, I understand that, but if there was a
study that put 97.5 percent of a substance as part of a human
trial into someone's abdomen, that would seem to be a problem?
Dr. Menikoff. Again, this is not under our jurisdiction. I
think FDA is in a better position to comment on the facts. We
saw no protocol.
Ms. DeGette. So you don't--OK. Dr. Less, what is your----
Ms. Less. We have not seen the protocol or device
description either. We would need to know what is in the
product before we could comment.
Ms. DeGette. Right, but you certainly wouldn't think that--
you certainly wouldn't approve some kind of a drug that put a
whole bunch of fluid like this where it wasn't specified what
it was as part of a surgical operation?
Ms. Less. We would need to know what is in the product, how
it is being used, a full device description.
Ms. DeGette. I just have----
Mr. Stupak. No, no, we got to move on. We have both former
chairs who would like to ask questions. Mr. Barton for
questions, please.
Mr. Barton. Thank you. You talk about a target rich
environment for questions. My first question is to our
representative from the GAO. The protocol and the device that
you all chose, you, not you personally, but your organization
consciously picked one that the FDA had already rejected and
then changed it to make it even worse, isn't that correct?
Mr. Kutz. We picked something that was available on the
Internet and altered it significantly. The 3 components of the
actual gel, we made up from stuff on the Internet so we had
never mixed it together. I can't--we don't know if it works or
doesn't work. We just put it together on paper.
Mr. Barton. But you tried to make it very easy for anybody
that was really trying to review the protocol to figure out
that it was terrible and reject it, which 2 of the IRBs did.
Mr. Kutz. Yes. We didn't know what we were doing.
Mr. Barton. And then this one rubberstamped it almost
before they got it, is that a fair statement?
Mr. Kutz. Well, they actually--I mentioned a coupon in the
opening statement. They gave us a pre-review with the coupon
and then the final review was where they authorized the
informed consent and than the actual protocols.
Mr. Barton. How did you pay for their review?
Mr. Kutz. Well, we gave them our credit card number. As it
turns out, they never actually charged us.
Mr. Barton. Really? I would have thought they would have
cashed the check almost as quickly as they certified approval.
Mr. Kutz. We were surprised they didn't. Everybody else
did.
Mr. Barton. Dr. Less and Dr. Menikoff, what can be done to
decertify this company right now? Why are they still in
business?
Ms. Less. Again, we don't have the--we have not seen the
GAO's report to be able to comment on what actually transpired.
Mr. Barton. I am not asking you about that. I mean I am so
mad at the company, I can hardly be civil, but I am almost as
upset with our government folks who are supposed to oversee
these IRBs, and this company has gotten 4 or 5 notice letters
in the last 2 to 3 years, and yet they are still in business,
and they have the gall to come here and threaten to sue the
government. They ought to have their butt being kicked out the
door within the week.
Ms. Less. I could provide some background to you on how the
process would generally work for a product such as this. This
would be considered a significant risk product subject to FDA's
jurisdiction that would require an investigational device
exemption in order for the study to proceed.
Mr. Barton. So basically as the representative of the FDA
you just say business as usual.
Ms. Less. No.
Mr. Barton. These folks are going to stay in business for
another 4 or 5 years, maybe approve a product that kills some
innocent person, and then we will have another oversight
hearing 3 or 4 years down the road. What steps are being taken
right now to decertify these charlatans that raised $4 million
in revenue last year scamming the public?
Ms. Less. Congressman, what I wanted to explain to the
committee is that for significant risk products such as this
there should have been FDA oversight as well as IRB oversight.
Mr. Barton. There wasn't.
Ms. Less. No. This product should have been submitted to
the FDA so we could have reviewed the product, looked at what
it was made of by compatibility testing, sterility testing, all
of that. That piece of this picture was not part of the
operation, so that piece of the human subject protection was
not invoked.
Mr. Barton. As the FDA representative, what are you going
to do to use whatever enforcement mechanisms the FDA has to
hold this particular IRB company accountable?
Ms. Less. We would have to go and look at----
Mr. Barton. What are you going to do?
Ms. Less. We need----
Mr. Barton. Are you going to do anything at all? Are you
going to make a report? Are you going to make a recommendation?
Ms. Less. We will take the information from the GAO, fully
evaluate it, do our own investigation and see what needs to
happen.
Mr. Barton. You will do that?
Ms. Less. We need to see the GAO's findings and see exactly
what happened and evaluate it and see what we need to do.
Mr. Barton. Do you have any sense of outrage about this?
Ms. Less. Without knowing exactly what went on----
Mr. Barton. So the answer to that is, no, you don't?
Ms. Less. We do. We are very concerned with human subject
protection.
Mr. Barton. Dr. Menikoff, you represent HHS. Do you have
any sense of outrage about this? Are we the only people--the
people that are elected, are we the only ones that seem to be--
--
Dr. Menikoff. First of all, I would certainly welcome on
OHRP's behalf obtaining information about what happened. We
have yet to see any actual information or documentation of what
happened. We would welcome obtaining that and reviewing it and
taking appropriate action.
Mr. Barton. So you are in a passive mode also? If we bring
a dump truck load of documents, you will review them? Are you
going to be an advocate for investigation, use the authority of
the Health and Human Services?
Dr. Menikoff. OHRP is an advocate for improving the
protection of research subjects. Again, nobody has provided us
yet any document that information about what happened. We
welcome that. We are eager to get it even before this hearing,
and we would welcome receiving it, and we have appropriate
procedures to protect subjects, and we would implement those
procedures and determine appropriate action.
Mr. Barton. Well, my time has expired, Mr. Chairman, but I
am outraged, and I am going to encourage you and Mr. Waxman and
Mr. Walden to use every authority of the United States Congress
and the Energy and Commerce Oversight and Investigations
Subcommittee to eliminate these bad actors. I have a sister-in-
law who is undergoing cancer therapy treatment. She is Stage IV
right now. And she is looking at submitting to some protocols
for some experimental drugs that would be subject to an IRB
approval, and it appalls me, it appalls me, that, you know, it
is apparently with the exception of GAO who seems to be pretty
intense about this, FDA and HHS appear to be almost
indifferent, and of course the IRB president is incense that we
are even asking questions. I mean that is just outrageous. So I
will work with you, Mr. Chairman, and we will----
Mr. Stupak. Mr. Kutz, if you want to respond to Mr. Barton.
Mr. Kutz. Yes. We have actually sent a letter to FDA as of
yesterday requesting them to do an investigation. The
interesting point is when the letter was sent by the committee
and Coast made the allegations against us, FDA had an
investigator with the U.S. Attorney to go after charges after
our fake company, so they were very aggressive at that point in
time----
Mr. Barton. Bless their little hearts.
Mr. Kutz [continuing]. About going after--without any
evidence except a letter from Coast they were ready to go to
the U.S. Attorney to go after us, so I just wanted to make sure
you understood that, Mr. Barton.
Mr. Barton. We have a company here that has received three
or four notice letters in the last several years. I mean it is
just ridiculous. I yield back.
Mr. Stupak. We thank the gentleman. Our hearing is going to
continue. As the former chairman noted earlier, this is our
second hearing on IRBs and something we have an interest in.
There will be legislation. I know Ms. DeGette has legislation.
There will be other legislative proposals after this hearing, I
am sure. We have seven votes on the floor. I am going to ask
members' patience and ask them to come back in approximately 1
hour. We will be in recess for 1 hour, and then we will come
back and continue this hearing. Thank you.
[Recess.]
Mr. Stupak. This meeting will come back to order. Witnesses
are reminded they are under oath. And, Mr. Dueber, Ms. DeGette,
hopefully she is going to come back, but she had asked you if
it was your policy to prove the protocol to board members
within 24 or 48 hours. You said, no, it was longer. She asked
specifically about this one but under testimony before the
committee the record should reflect on page 27 the question was
you tried to do this once if a protocol goes to the board or
board members turn around and make a decision within 24 to 48
hours, is that correct? Your answer was right, right, yes.
Mr. Dueber. Yes. I checked into that. Again, I am new to
the company. I have been there 5 months.
Mr. Stupak. Well, you shouldn't be new to the truth. Either
it is yes or not. I mean you have your testimony. Your attorney
has it. Just a caution, that is all.
Mr. Dueber. I was not intentionally telling----
Mr. Stupak. I didn't think so. OK. Ms. Christensen for
questions, please.
Mrs. Christensen. Thank you, Mr. Chairman. This is one of
my first hearings on the Institutional Review Boards, and I am
really shocked at some of what I am reading and hearing. And I
am concerned that the IRB can be listed and then utilized by
researchers without the Department of Health and Human Services
even having to do a cursory check and that if federal funds are
not involved or an FDA-regulated product is not involved there
doesn't have to be any federal oversight or research if I am
understanding correctly. And I also wonder listening and
reading if there should even be private for-profit IRBs. Maybe
they ought to be university-based or somehow more directly
under the purview of the department.
My first question, I will begin with you, Mr. Dueber. When
the committee staff interviewed you last week, you acknowledged
that your company did not verify the physicians leading these
experimental studies or that their credentials were accurate.
In fact, when the GAO submitted its fake protocol to your
company you didn't verify that Jonathan Kruger, the person
listed as the primary clinical investigator, in fact, had a
legitimate medical license, is that correct?
Mr. Dueber. Yes. What we did was we have never had the
experience of having a fraudulent group of people lying to us
about their existence and about their licenses. They did submit
a license copy but it turned out to be fraudulent too. So what
we have learned from this is we need to start checking that. We
have changed our SOPs accordingly, but we did in our review
what was required by regulations, and regulations do not
require that that be done but regardless of whether it is
required or not, we are doing that now.
Mrs. Christensen. But you did eventually once you were
asked to testify checked on the doctor. How long did it take
for you to make that determination?
Mr. Dueber. Well, this whole thing didn't come up until I
got the letter from the subcommittee on the 23rd of February so
some time after that, a day or two after that, we started
checking into----
Mrs. Christensen. Was it a long process to check to
determine whether he was----
Mr. Dueber. Well, the date that sticks in my mind where
most of the work was done was March 5, and it took a team of us
about maybe 3 to 4 hours to check all these things out, the
existence of the company which didn't exist, the phone numbers,
the licenses, and all that. It took quite a bit of time to just
go----
Mrs. Christensen. For all of it, but probably checking to
see whether the doctor was a duly licensed physician----
Mr. Dueber. That doesn't take long. That is why--you know,
that is prime example of why we are going to start changing
that and start doing it.
Mrs. Christensen. Mr. Kutz, let me turn to you. You
submitted a fake medical license to Coast IRB on behalf of Dr.
Kruger. I think it is in the binder that you might have there.
It is tab 2. It is the State of Virginia. The date on the
license is 1990.
Mr. Kutz. That is correct. I don't have the binder but that
is correct.
Mrs. Christensen. But Virginia requires medical doctors to
obtain a new license every 2 years like most places do so this
19-year old license would have expired back in 1992. Isn't that
something that the IRB should have caught?
Mr. Kutz. Since they weren't looking at that, I guess they
wouldn't have caught it, but certainly if they understood that
they had to be done every 2 years that would be something that
they could put in their protocols.
Mrs. Christensen. Well, Mr. Dueber, how come the company
did not catch the fact that this was an expired license? I am a
physician, so I am very sensitive to issues relating to
physicians.
Mr. Dueber. I don't know. I wasn't there. I don't know why
it wasn't caught.
Mrs. Christensen. But you would agree that if a doctor had
engaged in malpractice or had lost their license that it would
be the job of the IRB or Coast in particular to check that?
Mr. Dueber. After this experience, I would agree, yes.
Mrs. Christensen. And you would agree that if you realize
that that license had expired 19 years before that you would--
would you have approved that study if you had picked up that
the license had expired or that the person--well, that the
license had expired, just simply that?
Mr. Dueber. Well, that is speculating but if someone
submitted something like that and then it had expired we would
do a lot of other things then to check into the validity of
other things sent to us, which could end up resulting in us not
taking on the study or not approving it.
Mrs. Christensen. But the principal investigator not having
a valid license would be a reason to not approve, wouldn't it?
Mr. Dueber. Yes.
Mr. Stupak. Gentlewoman, would you yield on that point?
This license was invalid on its face, was it not? You didn't
have to check. It was invalid, 17 years old, 10 years old, so
it was invalid. There was no checking to be done.
Mr. Dueber. Yes, that is correct.
Mrs. Christensen. My time has expired, Mr. Chair. Thank
you.
Mr. Stupak. Any other questions?
Mrs. Christensen. I did have another one.
Mr. Stupak. Go ahead.
Mrs. Christensen. OK. To Dr. Less. In April of 2007, well
before our investigation of Coast began, HHS received a letter
containing allegations about Coast. They turned the letter over
to FDA because the accusations related to FDA-related research.
FDA initiated an inspection of Coast in July, 2007. In March,
2008, FDA issued a warning letter to Coast finding that Darren
McDaniel, who was the CEO at the time, improperly assigned
someone with only a high school education to conduct an
expedited review of a human testing protocol.
Dr. Less, I think it is commendable that the FDA took
action to investigate and address this allegation, but as the
GAO investigation has shown, Coast had numerous other problems
including a review process that approve protocols based on a
19-year old medical license, board members don't read
protocols, and these coupons that explicitly encourage IRB
shopping. Why didn't FDA identify some of these other clear
deficiencies at Coast?
Ms. Less. Congresswoman, FDA, when they go out and do an
inspection they generally spend a few days inside and they pull
two or three studies, follow those studies from approval
through continued review, look for adverse events, see whether
or not the IRB had appropriately addressed those adverse events
or changes to the protocol. When we went out on this, it was a
for complaint--a for-cause inspection. We had been out there
several times before, had not identified problems. So for this
case we went out specifically to look into the allegations that
expedited review had not been used properly, so we were
investigating that. And we did issue a warning letter and we
imposed sanctions because we had been out there before and had
found some minor violations so we imposed sanctions that they
not use expedited review anymore.
And generally what we will do when we do issue a warning
letter is follow up. We make sure that the IRB institutes a
corrective action plan within 15 days. We review that, look to
see if it has adequately addressed everything that we were
concerned about, and then we put them on our list for follow-up
inspection.
Mrs. Christensen. So you don't do a comprehensive review
generally when you visit an IRB, you just review the specific
complaints?
Ms. Less. It depends on why we are out there because we had
been there several times before and had done a more
comprehensive review and pulled a number of studies and looked
at those other studies. But in this particular case we just
focused on the complaint.
Mrs. Christensen. But the original letter also identified
other concerns including back dating, changing board meeting
minutes and not following through with board requests that the
FDA inspection investigate those issues while you were there?
Ms. Less. We did look into all of those. The ones that we
identified in our warning letter, I believe, were all related
to the abuse of expedited review and potential conflict of
interest that the CEO had inserted himself into the process and
had inappropriately used expedited review, and so we focused on
those issues.
Mrs. Christensen. Including the back dating and changing of
the board--you did. And, Dr. Menikoff, did the allegations
result in an evaluation of Coast's internal practices and
procedures?
Dr. Menikoff. Are you talking about the current
allegations?
Mrs. Christensen. No, the ones that I just referred to, the
19 year old doing the expedited review and the backdating,
changing board meeting minutes, not following board requests.
Dr. Menikoff. Well, Congresswoman, as noted earlier, OHRP
and FDA have separate jurisdiction. They began this
investigation on a study which was under FDA jurisdiction and
was not under OHRP jurisdiction. FDA and OHRP regularly
communicate, and we discuss issues relating to actions that one
agency or the other takes, and we will deal appropriately and
generally do deal appropriately in terms of this.
Mrs. Christensen. Well, I am going to stop here but my
question really was did you do an allegation as a result of
those set of allegations? Did you do an evaluation related to
this?
Dr. Menikoff. The evaluation was under FDA's jurisdiction
at the time, and we would normally at that point--it is the
same set of regulations. We would normally allow FDA to conduct
an appropriate investigation.
Mrs. Christensen. Thank you, Mr. Chairman. I appreciate the
additional time. Thank you.
Mr. Stupak. Thank you. Mr. Dueber, if we go back to that
license, that license that was 19 years old, if you could put
that back up on the board, could also indicate that maybe the
doctor had been malpractice, no longer licensed to practice
medicine, could it not, if the license was 19 years old?
Mr. Dueber. It could have been anything. The fact that we
didn't catch that it had expired was something we should have
caught.
Mr. Stupak. Right. Right. And the reason why we are doing
these hearings, and I have been on this committee now for 15
years, and Mr. Walden for quite a while too, back in 2002 we
had a veteran die during experimental drug testing conducted by
someone who was not credentialed to practice medicine in the
United States like this Jonathan Kruger technically is not
because his proof of license is 19 years old. So your
responsibility as an Institutional Review Board is to do due
diligence to protect the health and safety of the patient. You
are the gatekeeper between medicine and the patient. And you
testified earlier you had four--I think you had five, you have
four doctors and one registered nurse and two other people in
reviewing this. I am baffled as to why there is no due
diligence and why things like this are not caught.
If I had four doctors looking at a license, I think someone
would have caught it. You might talk about 2\1/2\ percent of
Adhesiabloc but 97.5 percent of it, we don't know what it is,
and then you are going to put this in a lady's abdominal cavity
but not by the doctor who performed the surgery but by an
assistant according to the protocol, and the doctor wouldn't
even know. And if I was a patient and I became sick after you
dumped this liter bottle in me, I would go to the doctor, and
the doctor who performed the surgery wouldn't know anything
about it because the protocol was real specific that the doctor
had to be out of the room when they applied the Adhesiabloc gel
to the patients. I would have thought someone--I am not a
doctor, but I thought that is pretty strange, isn't it, because
when I get sick, where am I going to go? I am not going to go
to the assistant who put the gel in me because I don't know who
it is because I am under anesthesia and I am out. I am going to
go back to my doctor. My doctor isn't going to know anything
about it according to this protocol. That is crazy, isn't it?
Mr. Dueber. I spoke further with Dr. Dodd, and he told me
that he was familiar with a product called Hisken. He said it
is a similar product used in surgeries, and is added to the
abdominal cavity in the same relative volumes as the protocol
here. Dr. Dodd said he is very familiar with Hisken and was
comfortable with that volume so----
Mr. Stupak. But you never verified the 510(k) process to
see what this junk is I am dumping in the woman's body. You
never looked. Now there might be something out there that maybe
in the surgical field someone may use but remember you are the
gatekeeper. You are the person who is protecting the patient
from some doctor whose license is 19 years old and you are the
gatekeeper, so just because there might be something out there
but since you don't know what 97.5 of this stuff is, you really
can't say it is safe.
Mr. Dueber. Well, that is precisely why after having
experienced this whole episode that we have gone through, we
have changed our SOPs to check the 510(k), to check on the
predicate device it is based on, to check the doctor's
credentials, to check the existence of the company.
Mr. Stupak. So what about the--you said you have done
thousands of these trials. Currently you are in 70 clinical
trials. Did you do those in those others? Did you check the
doctor's credentials? Did you check to see what the licensing
regulations are, the 510(k), whatever you call it?
Mr. Dueber. We did not, and, you know, we have never had a
fraud like this perpetrated on us. We have had----
Mr. Stupak. It is not a fraud on you. You didn't do your
work. We caught you. That is all. It is not a fraud. Where is
the fraud?
Mr. Dueber. No, that is incorrect, sir. We did our job. We
did what FDA regulations require.
Mr. Stupak. Really? I thought you said your job was to do
due diligence and protect the patient. How did you protect the
patient in Coast's IRB with this protocol?
Mr. Dueber. We were following the regulations that were
outlined in the FDA's regulatory----
Mr. Stupak. Does the FDA license say--regulations say you
have to check the credentials of the doctor?
Mr. Dueber. No.
Mr. Stupak. Does it say you have to check the substance?
Mr. Dueber. We never had to, sir, because we have never had
anyone try to----
Mr. Stupak. What expertise do you have, if you say now when
you are caught, well, the FDA didn't tell me to do this, but
the FDA doesn't tell you the basic stuff, so what is the
expertise of your Coast IRB to even run to review protocols? If
you can't catch simple things like this and if the FDA doesn't
tell you and you can't think of it, what qualifications then do
you have to be an IRB?
Mr. Dueber. We have a great deal of qualifications. We have
got some outstanding very educated, very experienced doctors
and nurses and laypeople on our board.
Mr. Stupak. Then why didn't they catch it? You had more
medical people, and I have looked at a lot of IRBs, of the
seven people, five of the seven have medical backgrounds and
they never catch any of this stuff. That is amazing, especially
since our protocol, as testimony was earlier, Mr. Kutz had
indicated, is truly based on a real study of a product that
killed people.
Mr. Dueber. Our review--well, this product wouldn't kill
people, and we know that. Our procedures are----
Mr. Stupak. Tell me what is in this bottle. How do you know
this won't kill anybody?
Mr. Dueber. I am not a scientist. I can't answer that.
Mr. Stupak. Well, you keep saying this product wouldn't
kill anybody, Adhesiabloc wouldn't kill anybody. You don't even
know what is in it. See, that is the part that baffles us up
here. You act like you did nothing wrong, it would not harm
anybody, but you don't know what is in here. Isn't that your
responsibility again to protect the patient? Isn't that your
responsibility? How can you protect the patient if you don't
know what is in it? I mean the other two IRBs that we have
spoke of and Mr. Kutz has talked about, man, that just said
this is crazy. You shouldn't do this. There is no patient
safety. We don't know what the substance is. No one should do
this. And then when they finally realize someone approved it,
they said, oh, boy. That was your famous quote, I think, there,
Mr. Kutz.
Mr. Dueber. We have had--you know, Dr. Dodd was the
original expert that reviewed this, and now we have this other
outside party that reviewed it who is an expert and----
Mr. Stupak. This outside party, did he review--he reviewed
Adhesiabloc, he reviewed this, your expert there you mentioned?
Mr. Dueber. The expert reviewed that, yes.
Mr. Stupak. Oh, yes? What is in here? What does your expert
say is in here?
Mr. Dueber. I don't have his report in front of me.
Mr. Stupak. You just paid for another bad report because no
expert has ever reviewed this. You know why? Because we made it
up last night. There is 2.5 percent, the stuff on the top, we
made this up. So if your expert--if you paid someone money to
review this they never contacted us to get what the contents we
are talking about. How can you review something if you don't
even know the chemical formula of the stuff you are supposed to
be reviewing? Let me ask you this. Let me ask you something you
should know something about. This is your coupon that Mr. Kutz
testified to that was delivered to him after you had your first
contact with him where Coast, here is your coupon, good for one
time research protocol review worth $1,300. Take a free test
drive on us. And here is the back of your coupon.
So let me ask you, take a free test drive. There is a
picture of a car and all that here, and there is a smiley face
looking--here is the car. Here is the smiley face looking at me
in the rear view mirror in my car, and it says coupon good for
one time research protocol review worth $1,300. And then it
says coast through your next study. So it sounds like to me
that your study is more likely to be approved if you go with
Coast. Am I reading that wrong?
Mr. Dueber. No--yes, you are reading it wrong because what
that is is a marketing piece. It is just trying to get
different companies, new companies, to try out Coast and try
out Coast's customer service. You know, there is nothing wrong
with using some kind of a promotion to gain new business. It
doesn't have anything to do--this is the business side of the
business. This has nothing to do with the review board and the
decisions they make. Those are 2 separate businesses.
Mr. Stupak. Coast through your next study. We coasted
through in 48 hours and there are all kinds of problems with
our study, right?
Mr. Dueber. We are not using that marketing piece anymore
but, you know, that is just a piece that was used to try to
generate some new business. It has nothing to do with the
actual review of the studies. That is done by a separate review
board that are independent contractors, and they have nothing
to do with the business side. They don't know anything about
money that we make or money that we don't make. They are not--
--
Mr. Stupak. Well, speaking of the money you make, you made
what, grossed $9.3 million last year. At $1,300 a pop, that is
a heck of a lot of reviews.
Mr. Dueber. Most of them are a lot more than that because
that is a single study rate. You know, there are protocols that
have hundreds of sites, generate a lot more revenue because
there is a lot more work involved to review it.
Mr. Stupak. Sure. Let me ask FDA or HHS, how many
Institutional Review Boards come on line every month?
Dr. Menikoff. Each month we process about 300 applications.
Some of those are amendments or renewals.
Mr. Stupak. So basically how many are new ones a month?
Dr. Menikoff. I don't have an exact number on that.
Mr. Stupak. Are you concerned that people are seeing this
as sort of a quick way to get rich? Do you need 300 a month?
That is 3,600 a year.
Dr. Menikoff. Again, Mr. Chairman, many of those are likely
to be amendments or renewals of an existing IRB.
Mr. Stupak. But don't you think we should have some kind of
limitations on IRBs? Shouldn't they have some qualifications
before you become an IRB?
Dr. Menikoff. If you would like me to address the
registration system, the registration system that OHRP runs was
put into place as a result of the OIG 1998 report. The goals of
the registration system were modest to have a list of the
number of IRBs out there and to have some contact information.
Mr. Stupak. This is your registration system. This is
Trooper dog, remember, at Maryland House?
Dr. Menikoff. Mr. Chairman, the system is such that we
verify that people put in the information for requested piece
of information.
Mr. Stupak. Really? How do you verify it with Trooper dog
here?
Dr. Menikoff. By registering an IRB the government, federal
government, is in no way endorsing that IRB or in any way
saying that IRB----
Mr. Stupak. Don't you think when an IRB is registered with
the HHS there is sort of like a seal of approval authentic
because I have this approval, like fake medical devices sent up
by Mr. April Fuhl.
Dr. Menikoff. OK. Mr. Chairman, again, we in no way--the
system is not designed to be any endorsement of an IRB, nor do
we intend it to be, and to the extent any of the evidence you
revealed during this hearing or the GAO has revealed----
Mr. Stupak. Yes, but my question was doesn't it give people
an aura of authenticity because you----
Dr. Menikoff. I understand that. We were not aware that
this was a problem that people out there were thinking----
Mr. Stupak. Really?
Dr. Menikoff [continuing]. Because an IRB was registered
that the federal government was endorsing it. The federal
government has many systems by which it has lists of--again,
this is sort of like a contact phone book.
Mr. Stupak. This is an IRB that is supposed to be set up to
protect patient safety. This isn't a phone book.
Dr. Menikoff. I understand that, and there are many parts
of the system that actually help ensure that IRBs are operating
appropriately. The registration system----
Mr. Stupak. Tell me one thing you do after you register an
IRB, what do you do to make sure they are valid IRBs or doing
it properly?
Dr. Menikoff. OHRP has several divisions that work at this.
We have a compliance division that we accept reports of non-
compliance from anybody who wants to report.
Mr. Stupak. So nothing until somebody complains like if
someone dies?
Dr. Menikoff. If you are asking whether the current system
basically puts a stamp of approval on an IRB at the moment it
is created, it was not designed to do that.
Mr. Stupak. Mr. Kutz, what did your investigation find when
people would register? Was that a seal of authenticity,
approval or something? Why did you undertake that part of
registering fake IRBs with HHS?
Mr. Kutz. Obviously, he is saying it is not intended to,
but one of the IRBs, for example, that we submitted our
protocols to, said that it gave us an aura of legitimacy. And
so, yes, I believe people out there would--and plus it is
called assurance, but it is really self-assurance, and so it
doesn't really provide anything except registration, as he
said, of what is in the system. So maybe we shouldn't be
calling it assurance either. It depends on how you perceive
that. I could perceive assurance to mean someone has actually
reviewed and approved an application.
Mr. Walden. Mr. Chairman, will you yield on this point
because I thought the CFRs, the regulations of the federal
government in 45 CFR part 46.101(d) state that as part of
evaluating assurances the department ``will take into
consideration the adequacy of the proposed IRB in light of the
anticipated scope of the institution's research.'' Is that not
part of your rules?
Dr. Menikoff. Yes. Now that rule dates back to 1974. It was
implemented at a time when this whole system was first being
created and people didn't understand the complexity of how the
system works, how you best protect research subjects, and how
an IRB should function. Over the decades as the system was
implemented, people discovered basically that the efforts being
spent in implementing that provision essentially amounted to
verifying, for example, that an IRB that reviewed medical type
studies had one or two doctors on it, and a lot of effort was
being spent at assuring that fact. This was then reviewed by
the OIG in the 1998 report I described, and it actually
concluded that the way that provision was being implemented was
not actually advancing human protections, that a better way to
do this was to create a more streamlined system that basically
what you needed was----
Mr. Walden. And we are 10 years later, and that system is
due to come on line this summer?
Dr. Menikoff. No. Part of that system have already been
implemented.
Mr. Walden. And so if you had had to follow this regulation
that is still on the books, correct?
Dr. Menikoff. Yes.
Mr. Walden. Would not that check of assurance to make sure
that the fake IRB created by GAO was legitimate, wouldn't that
regulation have caught that? These folks listed themselves as
from a city in Arizona named Chetesville. I mean come on. Do we
have nothing in place that would have caught a fake IRB?
Dr. Menikoff. Congressman, the system is currently designed
in a way that you gave a registration with some cute names that
again had spelling errors and other things that unless somebody
sat there and tried to pronounce the names and the addresses,
they would not pick up the things that seem incredibly obvious
right now, and the system wasn't designed to do that. We do not
have our staff going through the names to see whether people
have put funny names on the list, nor indeed would we know
what----
Mr. Walden. So what good is it to register with your agency
when you put a stamp of approval on an IRB that then is system
wide usable for others to go through to certify human tests? Is
it a pointless purpose?
Dr. Menikoff. Congressman, we are not putting a stamp of
approval on the IRB. If the federal government----
Mr. Walden. But people market it that way. We have examples
of advertisement where they say, this one, I won't read you the
name, you can count on IRB standard for high quality review and
documentation, full AAHRPP accreditation, good standing with
FDA, registered with OHRP.
Dr. Menikoff. OK. And, again, it is mentioning several
other entities. One of those is AAHRPP which is an
accreditation entity that is in the business of accrediting
IRBs. But in terms of the federal government aspects of this,
we are not in the business currently--that would be a different
system, and we welcome your input in terms of whether or not
you think that would be a good thing to do. That would be a
dramatic change from the system. The system is never designed
to basically have us from the outset endorsing and putting some
sort of stamp of approval----
Mr. Walden. So you think the system works well today?
Dr. Menikoff. Right now we think we have a well-functioning
system. There is certainly room for improvement but in terms of
the part of the system that OHRP deals with, it is interesting
that GAO, for example, we deal with the funded studies. GAO was
not able to create a fake study that went through and got
federal funding.
Mr. Walden. No, but GAO could have created a privately--a
study through private funding that would have your HHS stamp of
approval on an IRB, right?
Dr. Menikoff. Again, it is not a stamp of approval. It is a
registration.
Mr. Walden. Well, you don't call it that but you could say
I am registered with HHS.
Dr. Menikoff. You are a problem. We welcome the information
and we will look into this in terms of making sure that people
out there know that the government currently is not putting a
stamp of approval. It is a registration list. Anybody could
sign up on the list. That is exactly what----
Mr. Walden. Clearly.
Dr. Menikoff [continuing]. OIG intended when it asked for
this list to be created. They wanted a quick and dirty way to
put people on our list so we would know vaguely how many IRBs
are out there and contact information.
Mr. Walden. Mr. Kutz.
Mr. Kutz. Well, I think the Federalwide Assurance which
includes the IRB and the medical device company, this is
necessary for federally funded research so it is, I assume,
meaningful for federal people applying for federal grants with,
I believe, 19 agencies, so I would believe those agencies
potentially put some credibility behind people that have
Federalwide Assurance.
Mr. Walden. Because what you are getting when you register
with Mr. Menikoff's office is Federalwide Assurance.
Mr. Kutz. Correct, for federal funded projects.
Mr. Walden. That is the gate. You got to get through that
gate in order to even go to the next step, right?
Mr. Kutz. Correct.
Mr. Walden. And then there may be a check or balance that
catches you there?
Mr. Kutz. There could be beyond that, yes, but just to get
that--you have to get that to even apply is my understanding.
Mr. Walden. So it does serve more than just a place to
register to get mail for future conferences or other updates.
It is actually something that is required elsewhere in the
government?
Mr. Kutz. For federally-funded projects, not for privately
funded. That is my understanding.
Mr. Walden. Do you disagree with that?
Dr. Menikoff. OK. If I could clarify, we are talking about
two things here. There is a registration system which is a
registry, a list of some information about each IRB. There is
an assurance process, the Federalwide Assurance. They are
different things. The registration list, yes, an IRB to be used
by an entity that wants to get federal funding or HHS funding
has to be listed on the registration list. If I could describe
the Federalwide Assurance, that is essentially an agreement by
which before you take federal funding, you have to agree, you
have to sign on the dotted line that your entity agrees to
abide by the federal regulations. So essentially by getting
Federalwide Assurance an entity is actually committing itself
and putting itself under a legal burden that it will abide by
the regulations.
The federal government is in no way endorsing the entity,
but it is just that a federal funding agency at HHS cannot give
funds to them until it has basically sworn and said, yes, we
will protect human subjects. We agree that we will have to
abide by the federal regulations. That is a good thing, and the
intent of the system is to encourage, make sure people could
get Federalwide Assurance and could basically be willing to
swear that they will indeed abide by the federal regulations.
Mr. Walden. I will tell you, I guess when I get back home
and try and explain how you register an IRB or whatever you
want to call it, and it is up here on the chart, fake medical
device, easy reviews. They are clever names, I don't doubt
that. And that that gives you then the authorization to oversee
the protocols on the human tests and that that seems to be all
it takes.
Dr. Menikoff. If I could clarify, in terms of the
jurisdiction side that OHRP deals with a major part of the
picture has been left out, which is that the IRB is not working
in a vacuum. As we noted again, GAO was actually not able to
get federal funding. An IRB reviewing a study, is it hard to
get federal funding.
Mr. Walden. But they did get approval on the other side of
the coin. They were able to go to an IRB and get approval for
human tests.
Dr. Menikoff. Yes. And I am just pointing out an IRB that
is reviewing a study that is getting federal funding, getting
federal funding itself involves a very detailed process of
checks and balances----
Mr. Walden. I understand that.
Dr. Menikoff [continuing]. That again that is a part of the
research world that is under OHRP's jurisdiction. Much of the
vetting that you are concerned about will actually happen, for
example, before NIH gives funds. Barely 20 percent of the
studies actually get funded these days. It is very competitive.
These things are reviewed by panels of the most eminent----
Mr. Walden. So you don't see that there is any real problem
with what you have learned from GAO, is that----
Dr. Menikoff. Up to now, everything you have indicated GAO
has done, I would think would be highly problematic for that to
have happened in terms of the studies that get federal funding.
Again, we are open to looking at the information on what
happens but----
Mr. Kutz. We didn't apply for federal funding and I am not
sure--and I don't think we actually would because we might
actually displace a legitimate applicant so that would not be
necessarily an appropriate undercover test in this case, but we
didn't apply. So I am not sure if we couldn't but we didn't
apply, and I assume there are a lot of other controls there
that would have had to have been tested, but just for the
record we did not try to get federal funding. We just used this
to give us an aura of credibility up there amongst the people
that were medical device and IRB companies.
Mr. Walden. So where in your fake IRB ad, you felt like you
got that stamp of approval, and it meant something in the
marketplace when you advertised?
Mr. Kutz. We used it as that, and certainly again as I
mentioned at least one of the IRBs that we sent our protocols
to said it gave us legitimacy. And I understand what HHS is
saying here, but that is the perception out there, so that is
an important--whether they like it or not that is what the
reality is out there amongst people.
Mr. Walden. Thank you, Mr. Chairman.
Mr. Stupak. Mr. Burgess, questions?
Mr. Burgess. Thank you. Mr. Dueber, let me just ask you,
was this product ever used? Are there any patients who received
this product?
Mr. Dueber. No, not that I know of.
Mr. Burgess. The board approval came in October, the end of
October.
Mr. Dueber. The first approval did and then November 6 they
approved the total project including the ICF form.
Mr. Burgess. But no patients had been enrolled? Is there
any way to know that absolutely for certain?
Mr. Dueber. No. We have not--we did not receive any SAEs or
PD, protocol deviations, or anything of that sort like a
sponsor would be required to send us if there was a need to
send that to us.
Mr. Burgess. But say there wasn't any protocol deviation.
Say everything went just as smooth as silk. Would you know that
a patient had or had not received the 4 250 milliliter vials of
stuff?
Mr. Dueber. Not until we did a continuing review, which the
board set for 6 months later, which would be next month, then
we would have to go back and have resubmission to us of all the
documents. It basically is a full review again of the protocol
and the ICFs and what not.
Mr. Burgess. Well, Mr. Chairman, I am going to ask that
that information be made available to us, and I would hope it
would be made available to us before a month from now. In light
of everything that we have heard today, patient safety should
be critical and uppermost in everyone's mind. If we have got
people out there who have been treated with a product that
wasn't even a product----
Mr. Stupak. Mr. Kutz could probably answer it.
Mr. Burgess. That is a real issue.
Mr. Kutz. But there is no real patients. The whole thing
was bogus so there were no people signed up. Now they could
have been but they weren't. There were no surgeries performed.
Again, everything that we provided was fabricated.
Mr. Dueber. And on March 6, I might add, we convened the
board of our company not knowing that this was still--not
knowing what this was, we convened the board and rescinded
approval for the study and notified the study sponsor of that,
but never could get hold of anyone on the phone or what not.
And who we had to send it to was a post office box so it was a
phony site to begin with.
Mr. Burgess. So there was no actual product produced.
Mr. Dueber. No.
Mr. Burgess. This looks like a big----
Mr. Dueber. This was all a big setup.
Mr. Kutz. We never actually mixed the product together,
never, ourselves.
Mr. Burgess. OK. Now the issue that was of concern to
people about the 2.5 percent active ingredient, the propylene
glycol, and then I guess 97.5 percent diluent. Do we know, was
that just made-up stuff too? There was no actual diluent that
was used in those 250 milliliter vials?
Mr. Kutz. Correct. We didn't say what the other 97.5
percent was. Our protocols were silent on that.
Mr. Burgess. OK. I will just point out that is unusual to
pick a product up off the shelf and not know what the rest of
it is because the vehicle is important to--it is important to
be aware of what the vehicle is. Let me just ask you this. If
this had gone forward, if this has been a real product or
whatever, who would have paid for the surgery? This is a
product that could only be placed at the time of an operation,
presumably an anesthetic. Day surgery or hospitalization, all
of that entails some cost so to get to that point where you can
actually administer the product, who was going to pay for the
rest of everything else that was happening that day, lab work,
hospitalization, day surgery, surgeon's time, anesthesia time?
Mr. Dueber. I believe the way this was set up was that the
patients were people that were going to have surgery anyway,
and they would have had to have paid for that surgery through
whatever means they had to pay it. They were not receiving----
Mr. Burgess. OK. Let me just interrupt you on that thought.
Would you have actively excluded the patient on the Medicaid
system? We made a big deal about no federal funds were used,
but would you have excluded a Medicaid patient from this
protocol?
Mr. Dueber. That would have been the sponsor's decision,
and we wouldn't have had any involvement in that, so I don't
know.
Mr. Burgess. So there could have been federal funds used in
the installation of this product in the peritoneal cavity?
Mr. Dueber. If it were a real--yes, that could be the case.
Mr. Burgess. Right. It is hard when you are dealing with a
make-up world, and I do understand that and I sympathize with
you but we shouldn't be here in the first place, so I am going
to press on. The second surgery, the second look operation 20
weeks later, so 6 months later we are going to have another
look to see whether or not our product worked, who is going to
pay for that surgery?
Mr. Dueber. I am not sure, sir. I don't know. I don't know.
Mr. Kutz. I don't believe our protocol said. That was one
of the questions we got from one of the other IRBs, who is
paying for the surgery, who are the physicians, who are the
surgeons, who are the people that are going to actually apply
Adhesiabloc to the women's pelvic area. That was all silent in
our protocols. Those were serious questions we got from the
other IRBs.
Mr. Burgess. It just struck me because that is not a normal
course of events. You do a laparoscopy for pelvic pain
diagnosis endometriosis. You are not necessarily going to be
back in 20 weeks looking to see what things look like today, so
that is a little bit of an unusual situation just from my
recollection of clinical practice. I realize it has been a few
years but that would be a deviation. Someone has to pay for it.
Again, my concern there is if we involve the Medicaid system
then again federal dollars are used in this test protocol so we
can't really just say no federal funding was used so we can't
be interested. I think we should be interested from a patient
safety standpoint but there was a real possibility had this not
been a fake study that federal funds might well have been used
depending upon the part of the country where the study was
conducted because obviously we heard on this committee time and
time again about the greater and greater proportion of patients
that are being covered by Medicare given the state of the--I am
sorry, Medicaid, given the state of the economy.
Is there--I am not sure whether I need to address this to
Dr. Menikoff or Dr. Less, but here you have albeit a make
believe company and it got one positive response to several it
sent out. Does anyone sort of take the 30,000 foot level look
at this and say, wow, two IRBs turned this down and one bit? I
wonder why it only had a 33 percent acceptance rate out there
in the universe of IRBs. Would that trigger a red flag on
anyone's part in any of the federal agencies that have
oversight not necessarily of the federal funding but of the
patient safety aspects?
Mr. Dueber. Yes, I think it has a big bearing with all due
respect. I sit here, you know, feeling troubled that only three
were selected, and we were one of the three. I mean why not
select 40 or 50 of them? I mean I understand where you are
going, and I honestly have to say I am on your side. I want my
company to do an excellent job of protecting human subjects,
and of course we have work to do. We are not perfect. No one is
perfect.
Mr. Burgess. I am going to interrupt you in the interest of
time because the chairman is going to cut me off. He always
does and I can't stop him. But, Dr. Menikoff or Dr. Less, is
there any mechanism in place right now when you only have a 33
percent uptake rate that that raises a red flag, that maybe
this was a protocol that needs to be looked at more
scrupulously?
Ms. Less. Congressman, there is a check in place in our
regulations that when a study for a medical device, when it is
presented to an IRB, the IRB is supposed to make the
determination of whether or not an IDE is needed. If the IRB
disagrees with the sponsor who has presented it as a non-
significant risk product, if the IRB decides it is not a non-
significant and it is, in fact, significant risk, the IRB is
supposed to tell the sponsor that and the sponsor is supposed
to report it to FDA within 5 days. So there is that check in
place. FDA would be notified if an IRB, as they were supposed
to do, make a decision, and if they disagreed with the sponsor.
Mr. Burgess. Did that happen in this make believe world
that we are in today? Did any of that occur?
Ms. Less. No, that did not occur.
Mr. Burgess. I know I am a little slow on this, but who
should have picked that up? Where should that have occurred?
Ms. Less. Well, the sponsor, who was fake, should have been
reporting that to FDA.
Mr. Burgess. And does the FDA have any mechanism in place
to know that, oh, my goodness, this sponsor did not make any
sort of report at all. We wonder why. There is some curiosity
to go back and look and see why no report was made.
Ms. Less. We wouldn't necessarily know if the sponsor did
not comply with the requirement and not make that report. We
wouldn't necessarily know. If they did make the report then we
would go out and look at the study, decide whether or not we
agreed with the IRB or the sponsor, decide whether or not it
did in fact need an IDE.
Mr. Burgess. So there is no way to track, I will just call
them dropped cases for want of a better word, if the
investigations just don't come back to you, then you don't know
why they weren't pursued?
Ms. Less. Well, what could have actually happened if they
were a real case if a sponsor goes to an IRB and says my
product is low risk, the sponsor says, no, in fact, that is
actually high risk, that sponsor then could not conduct the
trial. They would make the report to us. They would not be able
to start the trial. If they went--and so there is that check in
place that they would be reporting to us and----
Mr. Burgess. What is they were venue shopping on this and
went to several IRBs simultaneously as the fake company did?
Ms. Less. Well, hopefully when they went to the second IRB
they wouldn't lie and say that it is still a low risk product.
They would fix their protocol or go in and say this is a
significant risk product because again that second IRB would
have to ask the sponsor of the trial is this a significant
risk, does it require an IDE? The product could not be shipped
and the study couldn't be started without our approval too for
this kind of product so there is that second check in place
that the trial could never have gotten--or should never have
gotten started without coming to FDA.
Mr. Burgess. Mr. Kutz, was that your finding as well?
Mr. Kutz. We said it was significant risk and for the one
IRB we provided a 510(k) which would have been a prior
marketing approval but, no, we said it was a significant risk.
We did not say it was low risk.
Mr. Burgess. So should the FDA have picked up on that fact
and gotten back to you and said hold the phone?
Mr. Kutz. We never contacted the FDA.
Mr. Burgess. Oh, you did not?
Mr. Kutz. No.
Mr. Burgess. But in the real world it would be your
obligation as an investigational company to contact the FDA?
Mr. Kutz. I am not aware of the regulations on that.
Mr. Burgess. Right, but it was GAO in charge of the fake
company so you were CEO of a fake company. If you were a CEO of
a real company, would that have been the obligation of the real
company to do that?
Mr. Kutz. FDA knows the--I don't know the answer to that.
Mr. Burgess. I need a yes or no or the chairman is going to
whack me.
Ms. Less. Yes. The fake company should have reported to FDA
that the product was determined to be a significant risk. These
types of products, we have a guidance document that lists
significant and non-significant risk products. This type of
product is listed as significant risk.
Mr. Burgess. It is voluntary at this point. No one is
required to do that so if somebody slipping under the radar a
time or two, we really got no way to go back and do any sort of
internal check on that. I would be interested if I were the FDA
today, are there any others that have slipped under our radar
like this? How many other bad studies have we missed?
Ms. Less. It is not voluntary. It is mandatory that the
sponsor report to us within 5 days of the IRB tells them that a
product that they presented to them is significant risk.
Mr. Burgess. What penalty might they invoke if they don't
report?
Ms. Less. If they don't report, we would go after them. We
could issue a warning letter. We would go out and inspect,
issue a warning letter.
Mr. Burgess. What if you found that federal funds were used
such as in the Medicaid or S-CHIP system, would HHS become
involved at that----
Mr. Stupak. Last one now, Mr. Burgess. We have been more
than generous with time. We have another member waiting.
Mr. Burgess. All right. If the federal funds were used to
pay for the surgeries or the procedures, Dr. Menikoff, would
that get your interest?
Dr. Menikoff. When you are referring to federal funds being
used, the general sense of that is basically that the funding
for the study taking place, in other words, an investigation
that is funded by NIH or CDC or FDA itself may be running a
study. Normally probably the fact that one of the procedures is
paid through Medicaid, for example, wouldn't implicate that.
The key is that somebody in getting federal funds to run one of
these studies, if this study was done with NIH money, GAO again
didn't fully respond, but the odds are extraordinarily low that
any of this could have happened because in getting those funds
the legitimacy of this entity would have been vetted this way
and that. You would have had top scientists asking who is this
person? What knowledge does he have to do this? Is he a well-
trained physician? What papers has he written?
Many, many parts of this system work together and
particularly on the HHS funded side to make sure that we have
legitimate things happening and this information then works
together with the IRB in terms of making sure that there are
substantial protections in place. So again the facts do speak
for themselves. GAO didn't end up producing a fake, federally-
funded study. I think it would have been very, very difficult
to do that. There are many, many protections in place.
Mr. Burgess. And yet still federal funds could have been
put----
Mr. Stupak. Mr. Burgess, I really do have to in all
sincerity--Mr. Markey has been waiting patiently. You are more
than 7 minutes over.
Mr. Markey. Thank you, Mr. Chairman, very much. Mr. Dueber,
based on the review that your company conducted here, would you
have been comfortable with your wife or your mother being
treated in her abdomen with the solution your company approved?
Mr. Dueber. I can't answer that. I do not know.
Mr. Markey. You don't know if you would be comfortable
recommending to your wife and mother something that you
recommended for all of these other----
Mr. Dueber. You know, it is speculating. I would have to--
you know, I don't know. The doctor that I talked to that was on
our board that approved this does this surgery, uses a similar
product. He felt it was safe. We have had it reviewed by an
expert, outside expert, and he says it is safe. I mean the
ingredients that supposedly were in it are supposed to be--the
active ingredients are supposed to be safe. The inactive
ingredients have no interference with the effectiveness of
active ingredients so absent any other information to prove
them wrong, I guess if I was in a decision-making mode, I would
probably say, yes, go ahead and use it on them. But of course
that is their decision, not mine.
Mr. Markey. Well, if you look at your record the committee
requested information on all of your reviews for the past 5
years, and this is what you provided, that your company
reviewed a total of 356 proposals for human testing, and you
approved all of them. So that means you approved 100 percent of
all the studies that you reviewed.
Mr. Dueber. I am not sure the numbers you are looking at,
356, what----
Mr. Markey. You approved--356 protocols were approved and
the board voted----
Mr. Dueber. For what time period? I am sorry.
Mr. Markey. Over a 5-year period.
Mr. Dueber. No, we have approved more studies than that,
sir.
Mr. Markey. These are the records that you submitted to the
committee, and I am working off of your documents that you
provided to us.
Mr. Dueber. I believe you may be looking at the audit
numbers that we sent to you.
Mr. Markey. We have every--you provided to us every vote
which the board cast over the last 5 years, and of the 356
protocols you approved every single one of them, 7 to 0 on each
vote, except on one occasion when 1 single board member
dissented, so that means out of 2,492 votes cast by board
members all but one were in favor of approval.
Mr. Dueber. We have been requested to provide you with a
list of all of our protocols since the inception of Coast and
which ones were approved, which ones were not approved, and we
will work on that and send that information to you. I can tell
you that we do audit a fair number of protocols. In the last 3
years we have done about 50 to 60 audits, and some of those
audits, we have overturned the original ruling of the original
approval of those studies.
Mr. Markey. Mr. Kutz, let me read to you from their web
site. Here is what it says. It says Coast IRB's quick document
turnaround will save you valuable time and ensure that you can
seamlessly move on to the next steps quickly and efficiently.
Our superior service guarantees your site approval documents
will be sent to you the next day following every board meeting.
In this case, do you believe that emphasis on speed contributed
to the company's failure to conduct even cursory due diligence
which if it had been done by the firm would have been as a
result of a basic documentation review found that there was
ultimately a fictitious nature to this entire enterprise?
Mr. Kutz. The answer is probably yes. One of the reasons we
picked the three we picked were because they appeared to have
the less stringent documentation requirements. That is why we
picked them. So we were testing the system. We were picking
ones that we thought would have the less stringent paperwork
requirements. And, in fact, as I mentioned also, the other
thing that this IRB was selected is because they offered us a
coupon.
Mr. Markey. Well, I think that it is pretty clear that--I
know Mr. Dueber doesn't see it that way at this particular
point in time, but I think the GAO and this subcommittee are
providing a real service to your company, sir. I think that we
are trying to help to protect against such a lackadaisical
system harming human beings. And you seem to be outraged
actually in our pointing out this deficiency in the way in
which your company conducts business. I just think it is
important for you, sir, to reconcile yourself to this as an
intervention in underlying corporate pathology and that we are
trying to help you correct your business practice so that the
public is protected.
I know you don't see it that way right now, but I think
when you look back years from now you will see it that way, and
I just think that perhaps now you are being advised by counsel
to take the position which you are taking in your testimony
here today, but it is not helpful to you to be denying the
obvious which the GAO and our subcommittee chairman have
identified to you. That is my advice to you. Try to start out
where you are going to be forced to wind up anyway. It is going
to be a lot prettier. This testimony that you are delivering
today is not helpful to yourself or to the cause of insuring
that there are real processes that protect the public. Thank
you, Mr. Chairman.
Mr. Stupak. Thank you, Mr. Markey. A couple questions I
want to ask to follow up Mr. Burgess, and I think Mr. Walden
hit on it too. On IRB shopping, IRB shopping, this is a
practice in which researchers shop their protocol around to
different IRBs until they get an approval. In 2002 the previous
administration considered issuing regulations to require
researchers to disclose prior IRB decisions so people would
know if the study had been rejected in the past. On January 17,
2006, the previous administration withdrew this proposal,
concluding that IRB shopping does not occur or does not present
a problem to an extent that would warrant rulemaking at this
time, so 4 years later they withdraw it.
According to this decision, the administration apparently
felt they had no reason to believe IRB shopping was occurring
with any regularity. Dr. Less, that came out of the FDA. Who
would have made that decision in the FDA? Would it have been
the FDA, HHS, the administration, who would have made that
decision to withdraw this form shopping--IRB shopping
requirement?
Ms. Less. Mr. Chairman, after we issued the Advance Notice
of Proposed Rulemaking, we evaluated all of the comments
received. We had a working group involving experts from across
the agency including our Office of Chief Counsel, all of the
centers, and we looked at the comments and made that decision
based on the information that we received and also in light of
current regulations and the protections that we think that our
regulations offer.
Mr. Stupak. So you asked IRBs and they said, no, we don't
do that?
Ms. Less. No. We put it out for public comment and we got
55 comments. We reviewed all of those very carefully. We looked
back at the IG report, which said that they were aware of a few
case of IRB shopping, and the comments that we received, we
also didn't have any real reason to believe that there was any
concern over IRB shopping. There are a number of reasons why
companies will go to multiple IRBs for legitimate reasons.
Sometimes a company will go to more than one IRB at the same
time simply to get their study up and running more quickly.
That doesn't necessarily mean they are shopping for the
fastest or the least stringent IRB. We also can--we were
concerned with the burden that it would put on IRBs in the
sense that if you had a study with multiple sites, say 10, 20,
40 sites, if all of those IRBs had to share previous reviews,
we felt it could overwhelm the system. And without knowing the
other IRBs review practices, you would have no basis for
deciding on the merit of that review. And we have seen that as
an instance with say adverse event reporting.
Mr. Stupak. So when Mr. Dueber--let me ask you this. We
asked you when you were interviewed last week by the committee
staff, you disagreed. You said that IRB shopping, and I quote--
in fact, if you want to look at your testimony it is front of
Dr. Menikoff there on page 83, I believe it is. It has a green
tab on it there. When asked about IRB shopping, you said, ''Has
been a problem of IRBs, I understand for quite some time.'' So
IRB shopping is a concern then, right, amongst IRBs, that they
are going to go get a bad decision from one IRB, so they go to
another IRB until they get it, that is a problem?
Mr. Dueber. From my perspective and my company's
perspective, it is a problem and----
Mr. Stupak. Then answer me this. This is your coupon that
you gave out to Mr. Kutz. On the bottom of the coupon it says,
and I am going to read directly now, it says Coast IRB's free
test drive offer applies towards initial protocol informed
consent form and investigator's drug brochure reviews only,
$1,300 value. Coast IRB, LLC pledges to protect the full
confidentiality of all research studies sent to us for review.
In 2005, the FDA removed the guidance prohibiting IRB shopping.
As such, you are free to use our free test drive offer to
compare Coast services with another IRB's concurrently if after
comparing our services to those of another IRB, you choose not
to continue with Coast IRB, we will destroy all documentation
we have on file associated with your study.
Neither your money, research time or confidentiality will
ever be at risk. It sounds like to me you are encouraging with
this free coupon IRB shopping, the practice that you say you
are against.
Mr. Dueber. Sir, that marketing piece was created before I
arrived at Coast, and we are no longer using that for that
particular reason. But, you know, our position is that--and the
company's position has been that IRB shopping is a problem, and
there needs to be some kind of a database that everyone can
refer to to see if someone has submitted--a sponsor has
submitted a protocol to some IRB and other IRBs can check that
before we approve a study because----
Mr. Stupak. Do you think there should be a ban on IRB
shopping, and if a stud is rejected should be sent to the FDA?
Mr. Dueber. I think the last part probably, yes, but we are
in favor of improving the system and making it more difficult
for people to do that because obviously that is not healthy.
Mr. Stupak. Right. Mr. Kutz, under current law if you had
been a real company, you would have been allowed to ignore
these two rejections you received and continue with your
approval from Coast, isn't that right?
Mr. Kutz. I believe so, and actually one thing I would
mention on the shopping in our initial e-mails to the IRBs we
sent this to, we said very specifically that we were shopping
for an IRB.
Mr. Stupak. OK. So they all knew you were shopping, you
were IRB shopping?
Mr. Kutz. That is what our e-mail said, yes, the e-mails
from the requests you got from the IRBs.
Mr. Stupak. OK. And after you got the approval from Coast,
could you have begun your experimental testing on human beings?
Would there have been any other steps in the FDA or HHS review
before you started your experimental test on real people and
putting this fluid here, our liter bottle of Adhesiabloc in the
pelvic abdominal cavity of women?
Mr. Kutz. As I mentioned, because there is no federal
dollars associated with it, my understanding is yes.
Mr. Stupak. Thank you. Mr. Burgess, I know you always have
questions.
Ms. Less. Mr. Chairman, if I could clarify.
Mr. Stupak. Sure.
Ms. Less. That study should not have been started. It was a
significant risk product. It would have required approval from
FDA so the sponsor should never have started the study without
coming to FDA.
Mr. Stupak. Who should have come to FDA?
Ms. Less. The sponsor. The sponsor would go to the IRB, get
IRB approval, and they also would be required to get FDA
approval before that study could start and before any product
could be shipped, so the sponsor----
Mr. Stupak. What is the requirement to do that?
Ms. Less. Pardon me?
Mr. Stupak. What was the requirement to do that? I got my
protocol approved. I got my consent form approved. So why would
I have to go to the FDA?
Ms. Less. Under the IDE regulations and investigational
device exemption regulations at 21 CFR part 812 for a
significant risk product, which this is, the sponsor would be
required to get both FDA and IRB approval before it ships the
product or starts the trial.
Mr. Stupak. That is because Mr. Kutz misrepresented, but
what if it was some other project already approved? There was
no requirement to go to the FDA because we had what, a 510(k)
there, right?
Mr. Kutz. We faked the 510(k).
Mr. Stupak. We had a 510(k) so we don't have to go to the
FDA on this one. He could have started on real patients if it
was a real one.
Ms. Less. Well, hopefully the sponsor, if it was a real
sponsor, would have understood that this product is not subject
to 510(k).
Mr. Stupak. And what do you do to make sure a real sponsor
does that?
Ms. Less. A real sponsor is supposed to come to FDA----
Mr. Stupak. I know. There is a lot of assumption in these
laws, aren't there, that people are being above board. We
proved today they are not.
Ms. Less. Actually we have a number of programs in place
where sponsors can come to FDA, ask if they need an IDE. We
have a pre-IDE process where they can submit a pre-IDE to us,
have us look at the protocol, look at the device, look at the
testing that they have done to see whether or not it needs an
IDE.
Mr. Stupak. With all due respect, FDA hasn't been doing
their job. That is why we are having this hearing because when
we did Copernicus study 3014 which there was criminal fraud and
your own CID asked FDA to do criminal charges against
Copernicus and the doctors who were doing this, FDA refused to
do it. You rejected it. So there is very little faith on this
side of the dais that FDA is doing it right. So when we suppose
people are going to do it and we suppose the FDA is going to do
their job, we know what the end results are. Unfortunately,
people die. I will go to Mr. Burgess.
Mr. Burgess. Mr. Kutz, let me just ask you, my
understanding is you based this fictitious product on another
product that actually existed but didn't have a good track
record, is that correct?
Mr. Kutz. We got it on the Internet off of FDA's web site
and then we substantially altered the entire--we had a format.
We didn't know what a protocol actually was supposed to look
like so we got one just so we could know what it looked like,
and then we changed it completely and then we actually made up
the ingredients.
Mr. Burgess. How many FDA protocols did you have to look at
before you found one that struck you as a good one to proceed?
Mr. Kutz. We just wanted one. I don't know if there were
any more or not. We just found one on the Internet and once we
found that, we just used the format. We didn't use the actual
details of it. We created our own. It just showed us what one
looked like.
Mr. Burgess. Was it hard to find one that led you in the
right direction?
Mr. Kutz. Yes. I don't think there were a lot of them out
there.
Mr. Burgess. OK. Dr. Less, Dr. Menikoff, I am assuming that
the Inspector General at HHS has been notified of this
situation, is that correct? I mean does HHS have----
Dr. Menikoff. No. We referred this to FDA's investigators.
Mr. Burgess. OK.
Dr. Menikoff. That is the letter we sent.
Mr. Burgess. Will it at some point go to HHS IG?
Dr. Menikoff. No, we plan to refer it to the FDA and we
talked to the investigators that work under Dr. Less.
Mr. Burgess. Had there been Medicaid funds used on any
patient who received this compound inappropriately, would that
have triggered HHS' involvement?
Dr. Menikoff. I don't believe so. Again, the HHS
jurisdiction that OHRP has relates to there being a funding
agency for the study so basically NIH or CDC----
Mr. Burgess. Or CMS?
Dr. Menikoff. Excuse me?
Mr. Burgess. Or CMS?
Dr. Menikoff. CMS could act as a funding agency for the
study. The fact that one patient in the study got paid and----
Mr. Burgess. We heard testimony by Mr. Dueber that the
funding for the study was going to come from the third party
coverage of the patient essentially. Perhaps there was no
charge for the study protocol or the protocol drug but there is
a substantial amount of activity that has to occur to get to
the place where the drug is administered and all of that
activity was presumably going to be paid for by a third party
payer, so in a way CMS would have been funding this study had
it proceeded if Medicaid patients had been enrolled or S-CHIP
patients.
Dr. Menikoff. My understanding is that is not the way in
which something becomes HHS funded in terms of OHRP's
jurisdiction. The basic issue is has somebody applied for a
grant from an HHS grant making agency and they then approve
this. I mean that is the protection, and it is actually a very
strong protection. Again, this would not have happened if
somebody tried to get HHS funding. I think it is
extraordinarily unlikely, and people who are enrolling in HHS
funding studies should actually be relatively confident that--
--
Mr. Burgess. This whole deal is extremely unlikely and yet
we find ourselves here in a parallel universe that the GAO made
for us, and now we are having to try to pick our way through
it. I just find it--I personally find it unbelievable that HHS
is not more interested in the fact that funding sources could
have been diverted into a bogus study and the patient required
to have a second procedure, a second look procedure, 20 weeks
later. I mean this is a big dollar item that we are talking
about, 50 patients receiving a second look laparoscopy. There
is no way to know how many of those would have been Medicaid,
but that is a significant expenditure.
Dr. Menikoff. Congressman, it sounds as if you are talking
about use of federal funds for an inappropriate purpose, that
is--I don't know what unit of HHS would deal with that
basically. OHRP is dealing with the human subjects protection
aspect of it, not misappropriation of federal funds or misuse
of federal funds in some way. I can't comment on what part of
HHS does deal with that.
Mr. Burgess. Well, give us some comfort. Now what are the
next steps that are going to be taken here? Clearly, there are
things that need to be improved but are there some enforcement
steps that are going to be taken? What happens next?
Mr. Kutz. Only with respect to the one referral. I think
the bigger picture is that you had the set of protocols that
went to three IRBs and you get two completely different answers
at the same time. That is the part I think that should concern
the subcommittee here. On the one hand, two IRBs said this was
a ridiculous protocol, unsafe to patients. It should have never
been approved. Another one is still testifying as we speak that
it was perfectly safe. It is hard to believe you could have
that divergent of a situation and that raises questions to me
about the whole IRB system, especially the private IRB system.
Mr. Burgess. And, Dr. Less, would you concur that from
FDA's perspective that there is reason to be concerned about
the whole system?
Ms. Less. No, sir, I would not. I think under this
circumstance from what I have heard this product was a
significant risk product. It should have been submitted to FDA
for review. The study would not start without FDA and IRB
review, and in this case there would have been that safeguard
in place with having both the IRB approval and FDA approval
needed before any patients could be put at risk or the study
could have even started.
Mr. Burgess. So any enforcement activity would be directed
toward a company that doesn't exist that was made up by the
GAO, would any enforcement activity be directed in Coast's
direction for proceeding with a study with tenuous
underpinnings?
Ms. Less. Without seeing the report, I can't comment on
that but in general FDA has taken action when an IRB has failed
to make the determinations that it is supposed to make meaning
they found significant risk determinations and looking to see
whether an IDE is required for the study.
Mr. Burgess. OK. Well, so what would happen? What would
that action be?
Ms. Less. We would go out and do an inspection of the IRB,
look at their studies, their processes, see whether there were
other studies that perhaps a wrong decision was made and if we
found a problem, we would issue a warning letter. We could
impose sanctions. And then we would see if they put a
corrective plan in place to take care of that. If not, then we
could pursue other activities.
Mr. Burgess. Do you ever make a silent pact with yourself
that we will never use this IRB again? Do you keep a list? Is
there a watch list?
Ms. Less. Well there is a--all of our warning letters are
public. They are on the web site so any sponsor doing a study
should be looking at that web site to see----
Mr. Burgess. Is there any way to know that one side is
talking to the other on this because this seems to be one of
the problems we have encountered today. You had to say this was
a bad deal, one said it is OK. Nobody talks about it, so it
potentially could have gone forward with a very, very difficult
study from the standpoint of a patient.
Ms. Less. Well, warning letters are public. IRBs are
obviously not happy to receive those. They take them very
seriously and do some corrective actions. We require that they
submit a corrective action plan within 15 days if we issue a
warning letter, and we do follow up to make sure that those
corrective actions are taken.
Mr. Burgess. Well, now Coast had on its web site Q and A,
have you ever been investigated from the FDA, and they said,
well, they had but they got a commendation, but in fact that
wasn't accurate, I understand now, is that correct?
Ms. Less. I have not seen the information on their web
site. I am sorry, Congressman.
Mr. Burgess. This is again a printout of Coast's web site.
Do we have that to project? The frequently asked questions----
Mr. Stupak. Coast's web site, do you have it? No, they
don't.
Mr. Burgess. Under the frequently asked questions section,
have you ever been audited by the FDA? Answer, December 15-17,
2003, Coast IRB was selected for a routine surveillance
inspection. We received a commendation from the FDA
investigator regarding the thorough and effective oversight
provided by our IRB operations. A follow-up audit was conducted
in 2005 at which time no further action was required by the FDA
investigator. Do you think that is a true statement?
Ms. Less. We inspected Coast four times. The first three
times we did issue letters saying that voluntary action was
indicated, meaning that we found minor deviations from the
regulations and we asked them to--in the letter we pointed out
what those deviations were, pointed them to the appropriate
regulation or guidance. They did submit a letter back to us
stating that they had taken care of the issues that we
addressed in each of those three letters.
Mr. Burgess. Were those warning letters? Would those be the
equivalent of warning letters?
Ms. Less. No. they did not rise to the level of a warning
letter. They were what we call voluntary action indicated. We
have no action indicated, voluntary action, and then official
action, which is the warning letter level.
Mr. Burgess. Have they ever received a warning letter?
Ms. Less. Yes. Their most recent inspection that we
conducted in 2007, we issued a warning letter to the IRB.
Mr. Burgess. And we had this approval in October, 2008 by
the board so presumably they were under a warning when this
study, proposed study, was to be undertaken, is that correct?
Ms. Less. We had issued a warning letter, and they
submitted a corrective action plan, told us that they had put
training in place for their safe and were testing their staff
on the conduct under the regulations of what would be required,
and so we had reviewed all of that information. They had also,
I believe, hired an outside consultant that was also supposed
to be overlooking their processes.
Mr. Burgess. Is that the basis on which you gave them a
commendation?
Ms. Less. We don't give commendations to anyone,
Congressman.
Mr. Dueber. In addition to that, Congressman, we----
Mr. Burgess. But that is misleading statement on your web
site then, isn't it? She said the FDA doesn't give
commendations.
Mr. Dueber. They sent us a letter reinstating our use of
expedited review. We had given them a corrective action plan
and acted very swiftly. In addition to that, our CEO----
Mr. Burgess. OK. I am going to interrupt you because I am
going to get cut off again. If you would be good enough to
provide that letter to the committee, we would very much like
to----
Mr. Dueber. The committee already has that letter. We
provided that in the package of materials we sent.
Mr. Burgess. Thank you, Mr. Chairman. I will yield back in
the interest of time.
Mr. Stupak. Thank you, Mr. Burgess. Dr. Less, you said
earlier that warning letters are more serious violations. In
fact, the FDA issued a violation letter--a warning letter,
excuse me, a warning letter on March 11, 2008, to Coast for
three different parts on expedited review of IRBs, isn't that
correct?
Ms. Less. Yes, sir, that is correct.
Mr. Stupak. And now Mr. Kutz has sent a letter about this
situation and how Coast had reviewed this IRB--or this
protocol, so will the FDA now invoke a more severe penalty then
on Coast based--they already have a warning letter sitting
there in their file. Now they got another allegation of
wrongdoing. What will the FDA action be?
Ms. Less. Congressman, we will need to take all that
information into account and do a thorough evaluation.
Normally, if we issue one warning letter, the next warning
letter would include sanctions and we would take more serious
action, but without knowing the specifics and having reviewed
the entire case, I can't comment on this particular one.
Mr. Stupak. Mr. Dueber, let me ask you this, and I will
wrap up this hearing here. Are all of the seven people who
approved this protocol, the bogus protocol, do they still work
for Coast?
Mr. Dueber. Yes, they do.
Mr. Stupak. OK. Has anyone at Coast lost their job because
of their failure to adequately review this protocol?
Mr. Dueber. One individual is leaving the company shortly.
Mr. Stupak. But not as discipline action for this matter?
Mr. Dueber. No, sir.
Mr. Stupak. OK. And how about the chair of the
Institutional Review Board here, your chair of this board that
reviewed this protocol. She indicated she didn't even read the
protocol. Is she still working for you and she is still a
member of the company?
Mr. Dueber. Yes, she is. We evaluate our board members once
a year.
Mr. Stupak. OK. You said a couple times that you have
changed your SOP. I take it that is standard operating
procedure review process, right?
Mr. Dueber. Right.
Mr. Stupak. So it sounds like a lot of good changes have
been implemented.
Mr. Dueber. Yes, that is correct.
Mr. Stupak. So a lot of good actually has come from being
caught here on this bogus----
Mr. Dueber. Yes, it has, and I might add that during our
lunch break I talked to Dr. Less and I basically pleaded with
her to bring FDA into my company and do a full top down, you
know, front to back audit of our company because since I
started with the company, I have done nothing but try to make
sure that the company does exactly what it should be doing and
do the best it can of any IRB.
Mr. Stupak. And in all fairness, you have been there since
December of 2008, right, basically 4 or 5 months?
Mr. Dueber. I started at the end of September.
Mr. Stupak. September.
Mr. Dueber. And, you know, my track record is totally
opposite of what we are talking about here so I need time to
improve things, and we are improving. We have done--we have got
an incredibly dedicated staff more so than I have ever seen in
any company I have worked for before that they really--
everyone, their first thing that they worry about is protection
of human subjects.
Mr. Stupak. Then how did they miss this one so bad? I guess
that is the part that baffles us.
Mr. Dueber. Well, we got hoodwinked. I mean, you know, this
was a pretty good----
Mr. Stupak. You didn't get hoodwinked. You took the bait
hook, line and sinker. I mean in your testimony in all fairness
you said that once you got the letter you started looking at
it. It took seconds to figure out that something was wrong
here. I think it was the doctor's credentialing that was 19
years old. It took you seconds to do that just by going on the
Internet. The procedure that we used, our magic elixir here,
was actually found on the Internet. All this could have been
discovered with a little due diligence. Hopefully, I am glad to
hear some good things have come from all this whole thing also.
Mr. Dueber. Definitely.
Mr. Stupak. I want to thank you all for coming here and
thank you for your testimony today. That concludes all
questioning. I want to thank all of our witnesses for coming.
The rules of the committee provide that members have 10 days to
submit additional questions for the record. I am sure there
will be some. I ask unanimous consent that the contents of our
document binder on the desk there be entered in the record
provided that the committee staff may redact any information
that is business proprietary, relates to privacy concerns or
law enforcement sensitive. Without objection, the documents
will be entered into the record.
[The information appears at the conclusion of the hearing.]
Mr. Stupak. This concludes our hearing. The meeting of the
subcommittee is adjourned.
[Whereupon, at 1:55 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]