<DOC>
[110th Congress House Hearings]
[From the U.S. Government Printing Office via GPO Access]
[DOCID: f:41026.wais]
ASSESSING THE SAFETY OF OUR NATION'S DRUG
SUPPLY
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED TENTH CONGRESS
FIRST SESSION
__________
MAY 9, 2007
__________
Serial No. 110-43
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
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COMMITTEE ON ENERGY AND COMMERCE
JOHN D. DINGELL, Michigan, JOE BARTON, Texas
Chairman Ranking Member
HENRY A. WAXMAN, California RALPH M. HALL, Texas
EDWARD J. MARKEY, Massachusetts J. DENNIS HASTERT, Illinois
RICK BOUCHER, Virginia FRED UPTON, Michigan
EDOLPHUS TOWNS, New York CLIFF STEARNS, Florida
FRANK PALLONE, Jr., New Jersey NATHAN DEAL, Georgia
BART GORDON, Tennessee ED WHITFIELD, Kentucky
BOBBY L. RUSH, Illinois BARBARA CUBIN, Wyoming
ANNA G. ESHOO, California JOHN SHIMKUS, Illinois
BART STUPAK, Michigan HEATHER WILSON, New Mexico
ELIOT L. ENGEL, New York JOHN B. SHADEGG, Arizona
ALBERT R. WYNN, Maryland CHARLES W. ``CHIP'' PICKERING,
GENE GREEN, Texas Mississippi
DIANA DeGETTE, Colorado VITO FOSSELLA, New York
Vice Chairman STEVE BUYER, Indiana
LOIS CAPPS, California GEORGE RADANOVICH, California
MIKE DOYLE, Pennsylvania JOSEPH R. PITTS, Pennsylvania
JANE HARMAN, California MARY BONO, California
TOM ALLEN, Maine GREG WALDEN, Oregon
JAN SCHAKOWSKY, Illinois LEE TERRY, Nebraska
HILDA L. SOLIS, California MIKE FERGUSON, New Jersey
CHARLES A. GONZALEZ, Texas MIKE ROGERS, Michigan
JAY INSLEE, Washington SUE WILKINS MYRICK, North Carolina
TAMMY BALDWIN, Wisconsin JOHN SULLIVAN, Oklahoma
MIKE ROSS, Arkansas TIM MURPHY, Pennsylvania
DARLENE HOOLEY, Oregon MICHAEL C. BURGESS, Texas
ANTHONY D. WEINER, New York MARSHA BLACKBURN, Tennessee
JIM MATHESON, Utah
G.K. BUTTERFIELD, North Carolina
CHARLIE MELANCON, Louisiana
JOHN BARROW, Georgia
BARON P. HILL, Indiana
<RULE>_________________________________________________________________
Professional Staff
Dennis B. Fitzgibbons, Chief of
Staff
Gregg A. Rothschild, Chief Counsel
Sharon E. Davis, Chief Clerk
Bud Albright, Minority Staff
Director
(ii)
Subcommittee on Health
FRANK PALLONE, Jr., New Jersey, Chairman
HENRY A. WAXMAN, California NATHAN DEAL, Georgia,
EDOLPHUS TOWNS, New York Ranking Member
BART GORDON, Tennessee RALPH M. HALL, Texas
ANNA G. ESHOO, California BARBARA CUBIN, Wyoming
GENE GREEN, Texas HEATHER WILSON, New Mexico
Vice Chairman JOHN B. SHADEGG, Arizona
DIANA DeGETTE, Colorado STEVE BUYER, Indiana
LOIS CAPPS, California JOSEPH R. PITTS, Pennsylvania
TOM ALLEN, Maine MIKE FERGUSON, New Jersey
TAMMY BALDWIN, Wisconsin MIKE ROGERS, Michigan
ELIOT L. ENGEL, New York SUE WILKINS MYRICK, North Carolina
JAN SCHAKOWSKY, Illinois JOHN SULLIVAN, Oklahoma
HILDA L. SOLIS, California TIM MURPHY, Pennsylvania
MIKE ROSS, Arkansas MICHAEL C. BURGESS, Texas
DARLENE HOOLEY, Oregon MARSHA BLACKBURN, Tennessee
ANTHONY D. WEINER, New York JOE BARTON, Texas (ex officio)
JIM MATHESON, Utah
JOHN D. DINGELL, Michigan (ex
officio)
C O N T E N T S
----------
Page
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 1
Hon. Nathan Deal, a Representative in Congress from the State of
Georgia, opening statement..................................... 3
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, opening statement............................... 3
Hon. Lois Capps, a Representative in Congress from the State of
California, opening statement.................................. 4
Hon. Diana DeGette, a Representative in Congress from the State
of Colorado, opening statement................................. 6
Hon. Joe Barton, a Representative in Congress from the State of
Texas, opening statement....................................... 7
Hon. John D. Dingell, a Representative in Congress from the State
of Michigan, opening statement................................. 8
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 10
Hon. Hilda L. Solis, a Representative in Congress from the State
of California, opening statement............................... 11
Hon. Mike Rogers, a Representative in Congress from the State of
Michigan, opening statement.................................... 12
Hon. Edolphus Towns, a Representative in Congress from the State
of New York, opening statement................................. 13
Hon, Tim Murphy, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 13
Hon. Jan Schakowsky, a Representative in Congress from the State
of Illinois, opening statement................................. 14
Hon. Marsha Blackburn, a Representative in Congress from the
State of Tennessee, opening statement.......................... 15
Hon. Gene Green, a Representative in Congress from the State of
Texas, opening statement....................................... 16
Hon. Anna G. Eshoo, a Representative in Congress from the State
of California, opening statement............................... 17
Hon. Tom Allen, a Representative in Congress from the State of
Maine, prepared statement...................................... 18
Hon. Barbara Cubin, a Representative in Congress from the State
of Wyoming, prepared statement................................. 18
Witnesses
Steven K. Galson, M.D., Director, Center for Drug Evaluation and
Research, Food and Drug Administration......................... 19
Prepared statement........................................... 22
Answers to submitted questions............................... 161
Marcia Crosse, Director, Health Care Issues, U.S. Government
Accountability Office.......................................... 36
Prepared statement........................................... 38
Lisa Van Syckel, Flemington, NJ.................................. 78
Prepared statement........................................... 78
Ellen Sigal, chairperson and founder, Friends of Cancer Research. 81
Prepared statement........................................... 83
Susan Ellenberg, University of Pennsylvania School of Medicine,
on behalf of the Coalition for a Stronger FDA.................. 87
Prepared statement........................................... 88
Caroline Loew, senior vice-president, scientific and regulatory
affairs, Pharmaceutical Research and Manufacturers of America.. 90
Prepared statement........................................... 92
Diane Thompson, vice-president, public policy and communications,
Elizabeth Glaser Pediatric AIDS Foundation, on behalf of the
Alliance for Drug Safety and Access............................ 122
Prepared statement........................................... 123
John Theriault, chief security officer and vice president, global
security, Pfizer............................................... 125
Prepared statement........................................... 127
Sharon Levine, M.D., associate executive director, Permanente
Medical Group, on behalf of the Kaiser Permanente Medical Care
Program........................................................ 129
Prepared statement........................................... 132
John Powers, M.D. assistant professor of medicine, the George
Washington University School of Medicine, and University of
Maryland School of Medicine.................................... 143
Prepared statement........................................... 144
Submitted Material
Drug Safety & Drug Efficacy Two Sides of the Same Coin........... 172
ASSESSING THE SAFETY OF OUR NATION'S DRUG SUPPLY
----------
WEDNESDAY, MAY 9, 2007
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 10:00 a.m., in
room 2123 of the Rayburn House Office Building, Hon. Frank
Pallone, Jr. (chairman) presiding.
Members present: Representatives Waxman, Towns, Eshoo,
Green, DeGette, Capps, Schakowsky, Solis, Matheson, Dingell,
Markey, Deal, Buyer, Pitts, Ferguson, Rogers, Murphy, Burgess,
Blackburn, and Barton.
Staff present: Ryan Long, Chad Grant, John Ford, Virgil
Miller, Bobby Clark, Jack Maniko, Melissa Sidman, Lauren
Bloomberg, and Nandan Kenkeremath.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Today the subcommittee is holding a hearing to
assess the safety of our Nation's drug supply, and I feel very
strongly that today's hearing is long overdue. For far too
long, the subcommittee has not paid enough attention, I think,
to the issue of drug safety, despite the growing concerns that
the health and well-being of millions of Americans may be at
risk due to a broken and inadequate drug safety system.
In recent years, there have been a number of revelations
about drug safety that have shaken public confidence in the
FDA's ability to ensure that consumers have access to safe and
effective medications. From Vioxx to Paxil, tens of thousands
of patients have been placed in harm's way due to the failings
of our current drug safety system. And as a result, the
American people have steadily begun to lose faith in the FDA.
That should change.
We must restore public confidence in FDA's ability to
protect people from harmful products and to safeguard the
public health. But first, the FDA itself must change. There are
a number of issues we must consider as we move forward. First
and foremost, FDA is woefully underfunded. This was
highlighted, as you know, in the hearing that we had a couple
weeks ago on the reauthorization of PDUFA. More money is
necessary for FDA to carry out its responsibility to protect
consumers from harmful drugs.
However, it is an issue of where that money is going to
come from. And obviously there is a lot of debate. There is
growing concern regarding the increasing amount of user fees
that FDA relies on to fund its budget. And as I have said
before, if given the option, I think everyone would agree that
FDA should be funded more, if not entirely, by annual
appropriations. But realistically speaking, we are not in a
place where we can't rely on user fees to help support the
functions of the FDA.
That is not to say that we should give the drug industry
carte blanche on how these fees should be applied. FDA should
have more flexibility about what functions these monies can be
used for, such as postmarket and surveillance.
For far too many years, the focus of FDA has been to
approve the amount of time it takes to improve new drugs. And
this is, of course, a direct result of previous PDUFA
agreements in which industry provides a new revenue stream to
FDA and in exchange establishes benchmarks for a more timely
drug approval process.
Unfortunately, however, this has caused an imbalance
between the pre-approval process and the post-market monitoring
of drugs. We have to fix this imbalance and focus more of our
attention on what happens with drugs once they reach the
marketplace. Assessing the risk of the drug once it is on the
market is just as important, if not more, than before it is
approved.
Now, how are we going to achieve a more robust post-market
drug safety system? Fortunately, we seem to already have many
of the answers. First, we need to give the FDA greater
authority and flexibility to manage the risks associated with a
new drug once it has been approved. Currently FDA has little
authority to control how a drug is marketed and how the risks
and benefits are communicated to consumers.
FDA should have more options to mitigate the risks
consumers face from a particular drug other than pulling it off
the market entirely. Let us give the FDA the ability to require
label changes, should it deem them necessary. Similarly, FDA
should have the authority to require, as a condition of
approval, that manufacturers follow through on their
commitments to conduct and publish phase-four trials.
Even more important is ensuring that information about the
clinical trials, including the results, is made public. It
makes no sense that we would allow such information to remain
locked away at the discretion of the industry. If my Republican
friends are keen on transparency in the health care market, as
they say, then let us start with full transparency of clinical
trials. Let the consumers and their doctors decide what they
think is safe or not based on complete information. The results
of these clinical trials contain valuable information for
patients and their physicians, and we should demand that they
be made available.
Finally, I want to voice my concern about direct-to-
consumer advertising. I realize that this is a very contentious
issue, and I appreciate the industry and FDA's willingness to
work out a compromise, which was included in this year's PDUFA
proposal. However, as I said a couple of weeks ago, I am not
certain that the new program outlined in the PDUFA proposal
will suffice.
The fact that the program relies on voluntary participation
from the industry strikes me as a program with no teeth. I am
skeptical of these advertisers and the alleged value they bring
to consumers. We will have to look at this program further and
ensure that consumer's best interests are being served well.
There are many other issues that need to be discussed as we
talk about drug safety. That is why today's hearing is an
important one. And like I said at the beginning of my
statement, it is long overdue that we have these hearings. I am
looking forward to hearing from today's witnesses, and I thank
you all for being with us and now recognize my friend from
Georgia, Mr. Deal, for an opening.
OPENING STATEMENT OF HON. NATHAN DEAL, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF GEORGIA
Mr. Deal. Thank you, Mr. Chairman. Thank you for holding
this hearing today on an issue that certainly will be a
component of our discussions on other FDA-related legislation
that comes before our committee this year. Recent incidences,
such as the recall of Vioxx that highlighted the importance of
FDA's role in evaluating the safety of products both pre- and
post-market, these events undermine consumers' confidence in
the safety of medications they are taking and remind us that,
while drugs provide useful life-saving treatment, there are
risks associated with any medication.
In February 2005, the FDA announced the creation of a new
independent drug safety oversight board to oversee the
management of drug safety issues and provide information to
help providers and patients about the risks and benefits of
medicines.
I hope that our witnesses will be able to tell us about
some of the work this board has been doing to monitor drug
safety in addition to the FDA's other drug safety efforts. I
also look forward to hearing about the role of databases in
studying drug safety. I believe one of these studies was
instrumental in highlighting that Vioxx increased the risk of
heart disease. Studies like these show promise and demonstrate
some of the possibilities for the FDA make use of existing drug
data.
I want to thank our witnesses for their time and attendance
today, and I look forward to your testimony as we evaluate the
best means for ensuring patients have access to safe
medications. Thank you, and I yield back.
Mr. Pallone. Thank you, Mr. Deal. Mr. Waxman.
OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Mr. Waxman. Thank you, Mr. Chairman. I want to applaud you
for holding this hearing today, for taking up the issue of drug
safety at an opportune time. The Prescription Drug User Fee
Act, or PDUFA, must be reauthorized this year, and everyone
knows that in the end, it will pass. There is no realistic
argument that it won't.
So we have a vehicle that will move, and as recognized in
the administration's own PDUFA proposal, this vehicle could
serve as a means to strengthen FDA's oversight of drug safety.
We need to ensure that FDA not only has the ability to collect
fees that help to finance its oversight in our drug supply, but
it also has the authority it needs to do this job well.
There is recent and mounting evidence that FDA's ability to
oversee drug safety is a pale shadow of its ability to review
drugs before they are approved. We are familiar with the series
of post-market safety problems in the past year with drugs like
Vioxx and Ketek. They demonstrate beyond a shadow of a doubt
that FDA's post-market drug safety oversight is in serious need
of repair.
The Institute of Medicine, the GAO, have examined this
situation. Both concluded that FDA cannot protect Americans
from unsafe drugs unless Congress provides more resources and
more legal authorities. For example, right now, FDA cannot
require post-market safety studies, even when FDA believes they
are necessary to fully understand the drug's risk. FDA's only
choice is to ask a company to perform these studies and hope
they will agree. And in the case where the companies do commit
to doing the studies in advance, if they don't do it, the only
option is to take the drug off the market completely, which is
a very serious one called a nuclear option, in fact. It is too
tough for FDA to actually pursue.
According to the FDA's own figures in 2006, manufacturers
submitted only 11 percent of the 1,200 open study commitments.
71 percent of these studies hadn't even started. The FDA also
can't compel companies to make labeling changes after approval,
as the case of Vioxx illustrates. FDA must haggle with
companies, often for many months on end about the wording that
should be used to notify the public about what are often very
serious risks associated with taking their drugs. And
throughout this process, the American public continues to take
these drugs without any knowledge of these risks.
I have my own ideas for drug safety. Congressman Markey and
I have introduced a bill, which incorporates the
recommendations of the IOM and GAO. It is a counterpart to the
drug safety legislation being debated on the floor of the
Senate this week as part of its consideration of PDUFA. H.R.
1561 represents the blueprint for what we should be working on
to fix the FDA's ailing drug safety system. I hope the
committee will have an opportunity to consider it.
Thank you, Mr. Chairman.
Mr. Pallone. Thank you, Mr. Waxman. Mr. Buyer.
Mr. Buyer. I will waive my time.
Mr. Pallone. The gentlewoman from California, Mrs. Capps.
OPENING STATEMENT OF HON. LOIS CAPPS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Mrs. Capps. Thank you, Mr. Chairman, and thank you for
having this hearing, as others have said. I thank our witnesses
for being here. I know the issue of drug safety has to be front
and center as we discuss ways to go forward with PDUFA
reauthorization. It is vitally important for the millions of
people who depend upon pharmaceuticals and reasonably assume
that they will do no harm.
FDA is charged with the responsibility to ensure that there
are safe and effective drugs, and that is the purpose of our
hearing today, to discuss ways to ensure that this
responsibility is fulfilled. Drug safety must be addressed
before clinical trials and continue not only through the
approval process but extend to post-market activity as well.
In the pre-approval period, we have to make sure that
clinical trials are conducted with the highest scientific and
ethical standards, ensure also that the members of the advisory
committees, who make such important decisions about drug
approvals, are free of ties to the industry.
The FDA has taken a supposed first step in this direction.
I understand they have proposed a regulation which prohibits
voting advisory committee members from holding more than
$50,000 in stock in a drug before being considered or any of
its competitors.
But do we really believe that goes far enough? Certainly we
know that it hasn't yet been implemented. We must have
confidence that drug approval decisions are based on scientific
data, not on financial interests. As my colleague has
mentioned, the high profile cases of Ketek and Vioxx and many
others were fateful reminders about the importance of post-
marketing studies and data collection.
I also hope we can discuss direct-to-consumer
advertisements. It is a great concern to me that so many
consumers who are patients rely on these ads and that proper
oversight of their content does not exist. Perhaps most
importantly, I believe we must equip the Food and Drug
Administration with adequate resources. User fees have been
instrumental in reducing drug approval time, but we must make
sure that fees do not make up such a large proportion of FDA
funding that it becomes a conflict of interest.
So I thank you, Mr. Chairman, again for holding this
hearing. I look forward to ways in which we can work together
to improve drug safety. I yield back the balance of my time.
Mr. Pallone. Thank you. Mr. Ferguson.
Mr. Ferguson. Thank you, Mr. Chairman. I am going to waive
my opening statement for additional time in questioning, but I
do just want to welcome constituent and friend Lisa Van Syckel.
She will beon the second panel today. I am delighted that she
is here today. I know she has several folks with her, including
Ellen Liversage and Vera Sheral and Kim Witsack also here with
her today. And because of the many, many meetings that she and
I have had talking about drug safety over the course of the
last several years, I have become very involved in the
medication guide issue. We have been doing an investigation in
our office and working with FDA and others. So I am looking
forward to getting into that today, and I will look forward to
using my extra time during questioning. I yield back.
Mr. Pallone. Thank you. Ms. DeGette. I didn't count that. I
guess I should have. Yes, we are going to have to watch----
Mr. Ferguson. I think I am owed a little latitude by a
chairman from my home State.
Mr. Pallone. I will do better in the monitoring this in the
future. Ms. DeGette.
OPENING STATEMENT OF HON. DIANA DEGETTE, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF COLORADO
Ms. DeGette. Thank you, Mr. Chairman. I think it is
important that as we prepare to mark up legislation affecting
regulation of pharmaceuticals and biologics that we put the
safety of patients as paramount. And so I know these drugs will
save countless lives, but we have to do what we can to mitigate
unintended harm.
I really have three concerns today. The first one has been
mentioned by several of my colleagues, and that is how we can
make systemic changes to the FDA to make sure that they are
really approving drugs that are safe. And our own
investigations of Vioxx and Ketek as well as a number of other
drugs over a period of years have shown that we really can't
have that confidence that the safety is paramount.
The second issue that I have is that the FDA just really
doesn't have the resources to adequately address drug safety
concerns. And the most PDUFA agreement provides a significant
increase in resources for post-market surveillance, but the
fact remains that Congress still has to provide additional
funds.
Also because of the drug safety problems, the American
public has lost faith in the FDA and its ability to protect
them from adverse effect. And this problem has been exacerbated
by the ambiguous nature of the drug safety process. The general
lack of transparency to the American public means that they
don't see how decisions are made, and therefore they don't see
why the drug companies are accountable to the FDA.
And finally, the full Senate is currently considering
legislation to reauthorize PDUFA as well as a seemingly endless
array of other drugs included in it. Though watered down, the
Senate bill includes drug reimportation. Those of you who read
the New York Times this last weekend saw the front page article
that should make us all think twice about that policy.
According to that article, counterfeit drugs made in China were
exported to Panama for sale, and they included a deadly toxin.
Last year, 365 families reported deaths as the result of the
tainted cough syrup and fever medication. And they think that
that number is vastly underreported.
Mr. Chairman, the dangers from counterfeit and contaminated
drugs are frighteningly real, even under the current construct.
Permitting reimportation would significantly increase the risk
of counterfeit, misbranded and adulterated drugs that would end
up in my constituents home. I hope we keep this in mind as we
mark up-
[Applause.]
Ms. DeGette. I might have to take that back given the
response from the other side. But seriously, I hope we keep
this in mind as we mark up legislation on prescription drugs.
If we have a problem with drug prices being too high in this
country, we need to confront that problem head on and not allow
reimportation policies that may affect the efficacy and safety
of our drug supply in this country.
Mr. Pallone. OK, now we have applause. Our ranking member
of the full committee, Mr. Barton.
OPENING STATEMENT OF HON. JOE BARTON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Barton. Thank you, Mr. Chairman. It is good to have
this hearing. I just got back from the trilateral committee
hearing in Ways and Means where we had Ways and Means,
Financial Services, and Energy and Commerce. Their opening
statements will go on until about 5:00 this afternoon, I guess.
So it is good to be here with one committee and one
subcommittee and focus on one subject.
We do appreciate this hearing today. When I was full
committee chairman of this august committee, I took the issue
of drug safety very seriously. I am glad to see that Mr.
Dingell and Mr. Pallone are continuing this. I requested a
Government Accountability Office review of how the FDA
approaches issues related to drug safety. I am looking forward
to hearing from that agency today about what steps it has taken
to improve the safety of our drug supply.
Where action is needed to improve drug safety, I think that
Congress should be prepared to act. I do hope that we do it
right instead of just in a hurry. I can testify personally that
the development of new prescription drugs have revolutionized
medicine and is saving lives.
Forty years ago, a person who had a heart attack like I had
a year and a half ago would have been given nitroglycerin, a
pat on the back, and sent home. Now, modern pharmaceuticals can
help prevent attacks from occurring or even reoccurring. I know
because each morning when I get up, I take six prescription
drugs before I begin my day.
We must take steps to ensure that the drugs that we are
taking are safe when they are approved and remain safe as they
are put into commercial use. No drug can be 100 percent safe
for every person who might take it. Even aspirin, the
ubiquitous miracle drug that does everything from curing
headaches to stopping heart attacks, has to be avoided by some
people.
No responsible authority insists on absolute 100 percent
safety because that standard would have the reverse effect of
increasing the likelihood that many people would suffer or even
die because they didn't have access to that particular drug.
As a drug used in the general population, less common side
effects may be evident. Congress could impose Draconian new
regulations that provide marginal benefits so that we appear to
address the problem. What we would actually be doing in that
case, in my opinion, is severely limiting access to life-saving
drugs for tens of thousands or hundreds of thousands of people,
lives that might be lost without that particular drug.
The history of drug regulation in this country reflects a
conscious weighing of the drug's risks versus the drug's
benefit. If more needs to be done to bring this balance into
equilibrium, this Congress and this committee should and must
explore those options, but we should never lose sight that
millions of Americans depend on these medications to preserve
and improve their lives.
Twenty-first century medicines must come with 21st century
surveillance. Our health care system produces large quantities
that can and should be used to monitor drug safety issues. We
should have systems in place that can link up clinical data
with prescription drug use. Pre-market clinical trials are
useful to determine the safety and efficacy profile of a drug,
but if rare side effects occur, they must not become known
until after the drug has been taken by a larger population.
It is my understanding that the FDA has begun to use
clinical databases as a methodology to monitor safety concerns.
I believe we should enhance that ability to tap into the
existing health information. I am pleased that the agreement on
Reauthorization of Prescription Drug User Fee Act will provide
the FDA the ability to obtain access to additional drug safety
information, including population-based epidemiological data
and other types of observational data resources. I look forward
to hearing from the FDA on their efforts in this area.
I also am looking forward to hearing from the testimony of
Mr. John Theriault who will discuss the issue of prescription
drug counterfeiting. It is shocking and unacceptable that the
maximum penalty for counterfeiting a prescription drug in this
country is 3 years in prison. Three years in prison. Phony
drugs are the ultimate bad medicine. Impurities in the
counterfeit drugs pose dangerous consequences for patients, and
intentionally giving a serious ill person a drug that does not
contain the active ingredients that they think it does could
actually be considered to be murder.
Addressing counterfeit drugs requires public and private
entities working together. Unfortunately, our anti-
counterfeiting drug problems are not nearly as smart as the
counterfeiters are. A first step to address the problem would
be for the House to pass Congressman Rogers' legislation to
substantially increase the criminal penalties for drug
counterfeiters.
Second, we should look at new technologies that will allow
us to better track these drugs in our supply system. I look
forward to hearing from the company Pfizer about what steps
that they are taking in this area.
Again, Mr. Chairman, thank you for holding this hearing. I
look forward to participating.
Mr. Pallone. Thank you, and I will recognize the chairman
of our full committee, Mr. Dingell.
OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Dingell. Mr. Chairman, thank you for holding this
important hearing. The committee is here today to discuss the
safety of our Nation's drug supply. And included in that is the
competence and ability of FDA to carry out its very important
mission.
The question here is what does it mean to say that a drug
is FDA approved. Good government would say that the Food and
Drug Administration approval should be the gold standard
throughout the world, that the drugs approved provide needed
therapies for consumers without causing further medical
complications or worse, death.
Unfortunately, Food and Drug approval of pharmaceuticals as
the gold standards has been called into question. Incidents
highlighted by the recall of the arthritis drug Vioxx have
created a crisis of confidence in the Food and Drug
Administration.
It should be observed, however, that problems with Food and
Drug go more broadly than this. It is an agency which has
inadequate resources, inadequate numbers of personnel,
inadequate financial support, and inadequate ability to carry
out its responsibility, over both drugs manufactured and food
manufactured in this country, and over imports, something which
has shaken my confidence in a very real way in the agency.
I publicly express my dissatisfaction with the way in which
Food and Drug has handled the important issue of drug safety.
FDA's lack of transparency and recent recalls have greatly
contributed to the loss of public confidence. The agency must
aggressively monitor and assess safety and efficacy throughout
the entire life cycle of a product. Simply stated, FDA must
ensure that just as much time, resources and energies are
invested in the aggressive post-market observation as is spent
in pre-market trials, consultation, and meetings with the
industry.
Unfortunately, it appears that there is a singular lack of
resources at Food and Drug to carry out these responsibilities
as it is to carry out other important responsibilities of that
agency. A recent Institute of Medicine report concluded FDA and
the pharmaceutical industry do not consistently communicate
safety concerns in a timely and efficient and effective manner.
In addition to insisting on structural and resource changes
within the agency, the country must also see to it that FDA
continues to push for significant improvements in cultural
changes at that agency. Public health policy is ultimately a
human enterprise, and all facets of FDA's drug programs must
work in a coordinated fashion for a common purpose, thereby
ensuring consumers that the drugs they take are safe and
effective. Again this will require a cultural change, but more
importantly, it is going to require adequate funding and
support for the agency which it currently lacks.
FDA has taken steps to boost consumer confidence. In 2004,
they introduced a new drug safety initiative that promised to
promote a cultural of openness and enhanced oversight within
the agency. And it has included additional drug safety
provisions in its recent PDUFA proposal.
The agency also asked the Institute of Medicine to evaluate
its current system of drug safety and make recommendations for
improvement. The Government Accountability Office, GAO, has
also weighed in, and in 2006, released a report on FDA's
ability to ensure a safe drug supply. The report included a
number of recommendations. I am pleased that a representative
from GAO is here to discuss this report. We will also want to
discuss it with representatives of FDA and of higher officials
in the Department of Health and Human Services.
It is, I think, appropriate that we should appreciate these
efforts, but it is not clear to me that they, when coupled with
the budget shortages of the agency, are sufficient. We are here
today to see what additional steps that Congress may need to
take so that American citizens are protected and the confidence
in the agency is restored.
I appreciate this hearing, and I look forward, Mr.
Chairman, to the testimony of our witnesses and the input of
our members as we discuss the safety of the U.S. drug supply
and the reasons why it is not as safe as it should be and what
steps we will take to improve it. Thank you, Mr. Chairman.
Mr. Pallone. Thank you, Chairman Dingell. The gentleman
from Texas, Mr. Burgess.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess. Thank you, Mr. Chairman, and frankly about the
referenced aspirin, I guess I can't help but wonder if we were
to send aspirin now through the Food and Drug Administration
process if it would survive the approval studies or whether it
would survive the post-market surveillance.
But this is a good hearing. This is an important panel of
witnesses. I believe that we must strive to seek a balance
between the safety measures that we put in place, at the same
time allowing and facilitating new drugs coming to market. I
believe that the FDA has done a good job with the resources
available to it, but we can make it better. And Chairman
Dingell may be correct about the allocation of resources.
Senator Mike Enzi from Wyoming has made a reasonable start
to this discussion over in the other body by introducing his
bill. His legislation would bring the risk/benefit analysis in
at the beginning of the drug approval process. It would
facilitate a lifetime approach to drug evaluation through the
establishment of a drug safety oversight board.
Senator Enzi's bill also addresses two topics that are of
particular interest to me, the critical path initiative and the
establishment of databases. The critical path initiative
strikes me as having great potential to fundamentally improve
the way that we approve new drugs by utilizing the science that
the research has yielded. If we could make our approval process
more personalized, more efficient, safer, and faster, than I
certainly support this.
In reading the materials supplied by the general
accountability office, they raise a question what safety action
that the FDA lacks--or rather they raised the point that the
FDA lacks the information about what safety actions to take and
when to take them. I believe that additional databases and data
mining can help utilize information that is already available
but needs to be collected properly. This can be helpful
whatever we are examining, whether we are looking at the
results from clinical trials or searching for adverse drug
events through, for example, the Permanente patient population.
Data mining and rapid learning techniques are tools that
are available but not being used to their full potential. Mr.
Chairman, there is lots of information out there. It is a time
of rapid change in the medical field. Going on
clinicaltrials.gov Web site this morning, you can see that they
have had 143 new hits during last week alone. And that is the
pace at which information is coming into the FDA. This deals
with illnesses as varied as asthma and appendicitis, pulmonary
hypertension, and magnetic therapy for depressed adolescents.
Innovative therapies must reach the clinical applicability
stage with greater speed, but there also has to be the
collection of data, the utilization of that data, and the post-
marketing studies. Data collections should be available to
arrive with greater speed and clarity for the clinician.
Finally, I do have to agree with my colleague from Colorado
about reimportation. If the debate is over cost, then let us be
honest and have that debate. Don't reimport drug price controls
from countries who refuse to participate in paying for the
research and development of those products in the first place.
Thank you, Mr. Chairman. I will yield back my time.
Mr. Pallone. Thank you. The gentlewoman from California,
Ms. Solis.
OPENING STATEMENT OF HON. HILDA L. SOLIS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Ms. Solis. Thank you, Mr. Chairman, and good morning. I am
very pleased that you are having this hearing today and have an
opportunity to talk about this important issue. Hundreds of
millions of Americans rely on FDA's judgment regarding the
safety of prescription drugs.
In 2005, the number of prescriptions purchased was about
3.6 billion, on an average, about 12.3 prescriptions per
person. And FDA regulates daily 25 percent of gross domestic
product and is sometimes called the largest consumer protection
agency. It is critical that our consumers are actually being
protected.
Each decision made by FDA is crucial and has life or death
consequences for many of our constituents. In the past, drug
safety may have been taken for granted. Patients have great
trust and faith in FDA. However, the publicity surrounding many
several drug recalls in the Institute of Medicine's report
``The Future of Drug Safety: Promoting and Protecting the
Health of the Public'' shows that much work is needed to
improve the safety of our medicines. The Institute of Medicine
identified serious problems in monitoring drug safety and
created numerous recommendations.
FDA has a difficult balancing act indeed. So I am pleased
that FDA has taken the initiative to strengthen and improve the
drug safety efforts. We know that FDA has to deal with external
constraints, including significant funding gaps at the Center
for Drug Evaluation and Research. However, FDA has a
responsibility to evaluate and address the safety of
prescription drugs after they have reached the market.
We must enable providers and patients to make the best
possible decision about using medicines to improve their
health. I have serious concerns regarding the transparency of
the drug approval process, specifically adverse event reporting
and the fact that FDA lacks authority to require that a
manufacturer conduct a rigorous clinical trial to investigate
post-market safety. Even if FDA requests a trial to be
conducted, it has no way of enforcing the completion of that
study. The fact that the completion rate of the post-market
studies was less than 25 percent between 1991 and 2003 is
disturbing.
The Adverse Event Reporting System is not an adequate drug
surveillance system and does not capture all the adverse drug
events. We need greater transparency and better communication
in order to protect American consumers.
I thank the witnesses for coming today, and I look forward
to hearing their recommendations, and I yield back the balance
of my time.
Mr. Pallone. Thank you. Mr. Rogers.
OPENING STATEMENT OF HON. MIKE ROGERS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Rogers. Thank you, Mr. Chairman. I have a long
statement, and I would like to waive it at the end so that I
can get more time in questions. Just kidding. If you are from
New Jersey, you think that is funny, Mr. Chairman.
I want to bring your attention to an article published in
The New York Times on May 6, 2007. It highlighted an
investigation into the global and often deadly epidemic of
counterfeit drugs. The investigation by the Times examined how
counterfeit glycerin, a product often used in cough syrup,
fever medication, and injectable drugs made its way via a
poison pipeline stretching halfway around the world.
The counterfeit product was diethylene glycol, an
industrial solvent and prime ingredient in antifreeze. Through
shipping records and interviews, the counterfeit product from
Panama was traced back through trading companies in Barcelona,
Spain, a permitted country, I might add, under the legislation
currently being considered--and back through Beijing, China.
Seventy years ago, when medicines laced with diethylene
glycol killed more than 100 people in the United States. It led
to the passage of the toughest drug regulations of that era and
creation of the modern Food and Drug Administration. This
creates an interesting contrast to the current debate over the
potential drug safety and reimportation legislation. This has
to be a component of that discussion, Mr. Chairman.
Last year, in Panama, 365 deaths were attributed to this
poisoning with diethylene glycol in cough syrup. The World
Health Organization estimates that global sales of counterfeit
drugs were $32 billion in 2003. That is the last best year we
have information. 10 percent of all those medicines sold
worldwide, the value seized for counterfeit and diverted drugs
in the United States alone was almost $200 million in 2003. And
that was a sevenfold increase from the previous year.
Authorities have encountered significant difficulty in
tying deaths to the actual consumptions of fake drugs mainly
for the reporting system that is in place today. In Canada, it
is currently investigating the death of a British Columbia
woman, who died apparently after taking counterfeit pills she
ordered online from what she believed was a Canadian Internet
pharmacy. Officials have linked the death to pills purchased
from this alleged Canadian Internet pharmacy about a month
before she died. Her toxicology tests revealed that the
counterfeit pills contained dangerous high levels of heavy
metals strontium, uranium, and lead.
The World Health Organization estimates that 50 percent of
the medicines purchased over the Internet from sites that
conceal their address are counterfeit. This is a serious and
growing problem, Mr. Chairman. The five top countries ranked
for counterfeit incidents to the FDA are: one, China; two,
Columbia; three, Russia; four, India; and five, the United
States. So I have introduced H.R. 780, a counterfeit drug
protection act to strengthen the criminal penalties against
those who participate in the production, distribution, and sale
of counterfeit drugs, understanding the prevalence and dangers
of counterfeit drugs is absolutely necessary, Mr. Chairman, in
determining the safety of prescription medications in our
Nation. And would yield back the remainder of my time.
Mr. Pallone. Thank you. Mr. Towns.
OPENING STATEMENT OF HON. EDOLPHUS TOWNS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF NEW YORK
Mr. Towns. Thank you very much, Mr. Chairman, for having
this very important hearing today. Making sure that drugs are
safe means making sure that they are safe for the diverse
segments of our population as well. That simply is not the
case. Minority participation in clinical trials has been cut in
half over the last decade from 12 percent to 6 percent. And
African-Americans represent less than 8 percent of those
enrolled in cancer clinical trials, while Hispanics make up
just 3 percent.
While pharmaceuticals are largely an effective means for
addressing a wide range of health care needs, I am concerned
that minority patients have not been adequately represented in
many clinical trials. This means that as we seek to reauthorize
the FDA, that we take into account the needs of diverse
populations. To do this, we must increase the number of racial
and ethnic minorities in clinical trials, particularly for
diseases and conditions where there are health disparities.
This will increase public confidence in the FDA's ability
to ensure drug safety. We must also make sure that the FDA
itself is diverse. In addition, data from diverse populations
must also be included in both pre- and post-marketing reports
on safety and effectiveness to ensure that these studies look
like America. Mr. Chairman, if we are to serve a diverse
America, we cannot continue a one-size-fits-all approach to the
development of new drugs and ensuring patient safety. Thank
you, Mr. Chairman, for bringing this critical subject before us
today, and I look forward to the testimony coming from the
witnesses.
Mr. Pallone. Thank you. Mr. Murphy.
OPENING STATEMENT OF HON. TIM MURPHY, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
Mr. Murphy. Thank you, Mr. Chairman. The recent case, the
tragedy at Virginia Tech, and actually the less publicized but
equally problematic problems throughout our universities with
mental health issues remind us that we have a large mental
health problem nationwide that is not being adequately
addressed. And when it comes to FDA and drug safety, and given
my career as a psychologist, I want to emphasize some of the
problems with this that I hope the FDA will address.
Today we are scheduled to hear some rather tragic testimony
from a mother about her daughter, about some of the problems
she had with antidepressant medication. And I want to emphasize
this for the FDA. That dealing with safe drugs is not just a
matter of running clinical trials and posting more news in the
PDA. It is also making sure that careful trials on adults and
children and any of the population that will be using the
medication is done, that research is ongoing, and that
information is readily available and sent to all those who are
prescribing the medications.
In the example of psychiatric medications, I find it
disturbing to note that 75 percent of psychiatric medications
are prescribed by non-psychiatrists. Even though we also know
that a combination of medications with regular psychotherapy
provided by trained licensed professionals is the most helpful,
very often what happens with patients, they are given some
medication and have little or no additional follow-up.
I believe it is critically important, whenever the FDA
looks at approving drugs, they also make it absolutely clear
under what context medication should be used, not only
providing information on the use and side effects and regular
and rapid updates to positions, but also making sure that
information on the full context of treatment under which that
medication is used is part of the prescribed regimen and not
just the idea of handing off a pill.
It is also essential that messages continue to go out to
the prescribers that clear communication must be ongoing with
the parents when dealing with the pediatric population.
Unfortunately we have set up so many barriers where parents are
not aware of what is happening with their children's medication
and with treatment, we are actually contributing to the
problems of these children, and that is wrong.
Good health care has never been just a matter of taking a
pill. Our culture, our whole health care system, has too often
supported this past approach of take a pill and call me in the
morning. We have to make sure that the FDA, in approving any
medication, makes it absolutely clear the context that
medication is prescribed and make sure that all involved are
part of that communication system. And parents of the pediatric
population, psychologists, psychiatrists, and others who are
involved. Failure to do so will mean that more families will be
harmed, and I hope that is one of the outcomes of what the FDA
will be working on. Thank you.
Mr. Pallone. Thank you. The gentlewoman from Illinois, Ms.
Schakowsky.
OPENING STATEMENT OF HON. JAN SCHAKOWSKY, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF ILLINOIS
Ms. Schakowsky. Thank you, Mr. Chairman. I first want to
associate myself with the remarks of Mr. Towns, the clinical
trials are to look like America. I know that women weren't
included in cardiovascular trials until women were present in
the Congress. And so now that we are a grand number of 72, I
was surprised to hear at one of our last hearings that still
the clinical trials, only 25 percent are women that are being
tested. And yet we know already that there are great
differences, as we know with African-Americans as well when it
comes to cardiovascular disease and others.
I also wanted to talk about the approval process. The fact
that it has been trimmed down from over 29 months in 1987 to
cut in half since then is a good thing for many people who are
facing serious illness or chronic disease. But as we move
forward with this conversation, it is very important to
consider the other end of this approval process, the proposed
approval process, which is essential to the health and safety
of our constituents. If we accelerate pre-approval procedures,
then tracking a drug in its post-approval lifespan becomes ever
more important.
Relying on the current Adverse Events Reporting System, the
AER System, is not sufficient. Not all adverse reactions are
obvious to those who experience them. In cases like Vioxx, they
only become apparent after months of use. Additionally a person
won't always make the correct connection between a prescription
drug and the side effect they are experiencing. Or they will
fail to make any connection at all.
Furthermore, one has to consider how often a person or
doctor will take the time to actually report a serious side
effect. How many adverse effects are we missing with this
process? We need to make sure that the right mechanisms are in
place at the FDA to deal with these adverse events information
in an efficient, objective, scientifically sound way and that
the reported data is accessible to those who can use it to help
avoid further incidents down the road.
One other concern I want to mention, we are relying on
patients, many of whom are frail, elderly to understand
complicated medical advisories, unclear directions issued by
pharmaceutical manufacturers. Who is making sure that this
information makes sense to them? Can they understand the
relevant safety information on the drug inserts that come with
their prescription medications? Is this information in the
appropriate language? Are seniors and other relying on
advertisements in the paper or able to read warnings that may
be in four-point font? I am concerned with the dependency on
adverse reporting to recognize post-market problems, troubled
by the lack of oversight and authority on FDA's part to monitor
the information on prescription drugs that is received or we
think is received by those who need them. So I look forward to
hearing from our witnesses, and I thank each of you for being
here. I yield back.
Mr. Pallone. Thank you. The gentlewoman from Tennessee,
Mrs. Blackburn.
OPENING STATEMENT OF HON. MARSHA BLACKBURN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TENNESSEE
Mrs. Blackburn. Thank you, Mr. Chairman. Thank you for the
hearing, and I did want to say welcome to our witnesses. We do
look forward to hearing from you, and we look forward to the
information you are going to give us.
According to the GAO, the FDA lacks a clear and effective
process for decision making about and providing oversight of
post-market drug safety issues. I have often thought it would
be interesting if the FDA were a patient to see what kind of
diagnosis we would provide the agency.
The situation is exactly what my constituents complain
about when they reference those bureaucrats in Washington, DC.
We have two FDA offices functioning without clear guidelines
and duplicating each other's work. And it is unfortunate that
the Federal Government both allows and tolerates this kind of
bureaucracy. And it is amazing that it comes at the risk of
public safety.
I would hope that there are some best practices that
someone is looking at implementing. Any private sector company
would be out of business if they ran their business like the
FDA runs the public's business. However, our drug review system
is not totally broken, as many would believe, and sometimes it
is as if we are trying to scare people to death by chipping
away at the public's trust in this drug review process that we
have. The U.S. has the best pharmaceuticals in the world and
will continue to ensure that all drugs are properly vetted
using the highest safety and review standards. And I hope that
the FDA has the institutional will to reform their process and
work toward restoring this trust.
While I understand the need for oversight and increased
transparency in the FDA's drug review process, Congress should
work toward a system with appropriate checks and balances. We
must refrain from tactics, such as imposing a litany of
needless regulation on the drug review system, which will
prevent access to lifesaving drugs. Expediency, transparency,
efficiency should be a big part of the discussion.
As we continue to learn about drug safety issues, we must
not forget that it is our duty to protect the public from
unsafe drug approval and post-market review tactics.
I am looking forward to hearing from our witnesses. Mr.
Chairman, I thank you, and I yield back.
Mr. Pallone. Thank you. I recognize our vice chair, Mr.
Green.
OPENING STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Green. Thank you, Mr. Chairman, for holding this
hearing on the safety of our drug supply. This hearing will
complement this subcommittee's work on the Reauthorization of
Prescription Drug User Fee Act as well as the Oversight and
Investigation Subcommittee work on drug safety lapses at the
FDA.
And the O&I subcommittee has uncovered serious problems
with the FDA's handling of Ketek, antidepressants, and, of
course, Vioxx. These cases have shed light on the structure and
cultural and administrative problems at the FDA with regard to
drug safety. They also have contributed to a decline in the
American people's confidence in the FDA's ability to ensure the
safety of our drug supply.
According to a Harris poll, 58 percent of Americans gave
the FDA a negative rating when it came to public confidence, a
number that has increased from 39 percent 2 years ago. To
improve the public's confidence in the safety of our drug
supply, there needs to be some big changes in the FDA. Some of
the drug safety concerns can be addressed administratively at
the FDA. I know that Dr. von Eshenbach has made significant
effort to implement many of the Institute of Medicine's
recommendations.
To correct other problems, however, the agency needs
expanded authority from Congress. And it is our job to give the
FDA the resources it needs to improve drug safety. We need to
take a serious look at the Adverse Events Recording System and
its ability to identify adverse drug reactions following the
drug's approval. The system is plagued with underreporting, and
the FDA currently has a very high threshold for action. When
taken together, these two factors unfortunately result in too
many Americans being subject to harmful drugs for too long
before the FDA steps in.
While the high profile cases make the nightly news, we know
that problems continue beyond Vioxx, Ketek, and
antidepressants. According to the GAO, 51 percent of all
approved drugs have had at least one serious adverse drug
reaction that wasn't caught during the approval process. There
is no question we should be catching more of these adverse drug
reactions before approval, but we should also have a robust
post-market system that is nimble enough to recognize problems
and act quickly to correct it.
Unfortunately, the scope that the FDA has authority to
react is currently severely limited, and I hope that we change
that in the PFUDA. If we are going to expand the FDA to ensure
safety of our drug supply, they need to have the authority to
require changes to drug labels when their scientists determine
that black box warnings are necessary or that products should
be restricted.
The FDA also needs the authority to enforce post-market
study commitments made by drug manufacturers. With 71 percent
of post-market study commitments not even begun by drug
manufacturers, it is clear that the FDA lacks an enforcement
mechanism with any teeth. Otherwise, the drug sponsor wouldn't
show such blatant disregard for their post-market commitments
to the FDA.
I would like to commend my colleagues, both Mr. Waxman and
Mr. Markey for addressing many of these issues in their current
legislation, a good portion of which is currently being
considered on the Senate floor. I look forward to hearing from
our witnesses on these issues and many others surrounding drug
safety, and we appreciate their being here today. And I yield
back my time, Mr. Chairman.
Mr. Pallone. Thank you. Ms. Eshoo.
OPENING STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Ms. Eshoo. Thank you, Mr. Chairman, for holding this
important hearing. I think that the issues that we are dealing
with in this hearing are amongst the most important for the
American people because there isn't a person in the country
that, on their own, on their very own, can guarantee in any
way, shape, or form that what they are taking, what they are
ingesting is absolutely safe. They know that they have to
depend on really the government and its blue chip agency, the
Food and Drug Administration for it.
Now, we know that we have a problem, and it lies, I think,
more in the post-marketing phase of drugs. The FDA actually
does not have an active drug surveillance system. So I think
now is the time. We are reauthorizing PDUFA, and we need to
build in a process by which and an authorization, a direction
for the FDA to actually have an active drug surveillance
system.
The drugs that have caused problems or high profile Vioxx
and Ketek, first of all, the agency has to have the funding to
do this. I think that we have gotten to a point now where there
is an overreliance on user fees. And the Congress has to step
up to the plate to make sure that the agency has the resources
it needs to carry out what, I believe, we need to do, and that
is to set up a post-marketing drug surveillance system.
So I look forward to what the witnesses are going to inform
us. I would like to thank publicly the IOM for the work that
they have done on this. I think it has been useful and
instructive to us. And I look forward to a reauthorization of
PDUFA that is going to very clearly define the responsibilities
for the FDA in this very particular area, as well as our
recommendation relative to the resources for it. I think if we
do one without the other, that it simply won't happen, and this
is just too critical.
So thank you, Mr. Chairman. This is important, and we have
had, since you have taken over as the chairman of this
subcommittee, I think the hearings that we are having are the
hearings that really matter on the most important things that
are challenging us in the health arena. Thank you.
Mr. Pallone. Thank you very much. I believe we are done
with the opening statements, and any other statements for the
record will be accepted at this time.
[The prepared statements of Mr. Allen and Mrs. Cubin
follow:]
Prepared Statement of Hon. Tom Allen, a Representative in Congress from
the State of Maine
Mr. Chairman, thank you for calling for this important
hearing to examine efforts to improve the current drug safety
system.
I want to commend Representatives Waxman and Markey for
their work on this issue and for the introduction of H.R. 1561,
the Enhancing Drug Safety and Innovation Act, which will make
the critical changes necessary to improve our current process
for ensuring the safety and effectiveness of prescription
drugs.
A pillar of U.S. policy on prescription drugs is the
protection of the individuals who use them. Public confidence
in our Nation's drug supply has been shaken in recent years by
recalls of heavily marketed and widely prescribed drugs such as
Vioxx. A new poll by Consumer Reports indicated that the vast
majority of Americans want stronger drug safety laws and
believe that more authority should be given to the FDA to
protect consumers.
The Institute of Medicine report issued last fall offered
25 recommendations to improve the FDA's pre-approval processes.
One of the most important recommendations, in my opinion, is
the need for continuous safety monitoring throughout the life
of the drug, including post-marketing surveillance.
The study found that ``the FDA lacks the clear, unambiguous
authority needed to enforce compliance with regulatory
requirements and instead relies on the prospect of productive
negations with industry.''
This is troubling, and a clear indication that the system
is broken.
I look forward to working with my colleagues to address
this and other important issues; including improving public
access to clinical trial results and ensuring that the FDA has
adequate staff and funding to fulfill their mission to protect
the public health.
I look forward to hearing the views of our distinguished
panelists on ways to improve the current system to protect
consumers from unsafe prescription drugs and restore their
confidence in the FDA.
----------
Prepared Statement of Hon. Barbara Cubin, a Representative in Congress
from the State of Wyoming
The Food and Drug Administration's safety activities are
directly relevant to the everyday lives of every U.S. citizen.
The 10,000 person agency is charged with monitoring roughly
124,000 firms that manufacture or process FDA-regulated
products, which compose roughly one-fifth of our Nation's gross
domestic product.
With this in mind, the notion that the public may be losing
faith in the FDA's drug safety activities is unsettling at
best. Over the last few years, the heavily publicized removal
of drugs from the marketplace has cast a shadow of public doubt
over the FDA's ability to protect the American people from
harmful products. 64,000 seniors in Wyoming now have access to
affordable Medicare prescription drug coverage, but this means
little if our drug supply is not safe.
In response to public and congressional concern, the FDA
asked the Institute of Medicine to assess and make
recommendations for our Nation's drug safety system, in
addition to their own ongoing drug safety assessment. I am
hopeful that today's testimony will help our committee
understand both the extent of the safety reforms the FDA and
industry have embarked upon, as well as steps that may need to
be taken by Congress.
I would urge my colleagues to keep in mind that the FDA is
charged not only with assessing drug safety, but also drug
efficacy. These two prongs of the FDA's mission are not
mutually exclusive, and should not be separated as we consider
legislative changes to the agency's structure and authorities.
The agency does not just conduct risk management. It must
also conduct risk-benefit analysis. Risk-benefit analysis can
and should vary based on the severity of an illness and the
availability of alternative therapies. We must consider the
cancers and neuro-degenerative disorders for which patients
have few, or even no, existing treatment options.
The acceptable risk for a drug treating mild arthritis will
not be the same as for a drug treating Alzheimer's or Lou
Gehrig's disease. There are seriously ill patients whose access
to innovative treatments would be jeopardized by regulatory
overreach, now matter how good intentioned. Their voices
deserve to heard in this debate.
While I believe there is no one-size-fits-all regulatory
solution for drug safety, there is no question that drug safety
assessment should be based, to the greatest extent possible, on
sound science.
Perhaps the greatest room for improvement in drug safety
lies with post approval monitoring. Rare and serious side
effects may not emerge until after a drug has been approved
based on clinical trial data, in particular, drugs that treat
smaller populations.
I hope today's panels will have suggestions for the tools
and resources the FDA needs to conduct science-based, risk/
benefit analysis throughout the market life of a drug. The dire
need for innovative medicines among the seriously ill does not
start and stop with the FDA's approval time-line, nor should
serious efforts to ensure the health and safety of the American
people.
Thank you Mr. Chairman. I yield back.
----------
Mr. Pallone. I will turn to our witnesses and ask the two
for the first panel would come forward if you would. Now, let
me introduce the two of you.
First, we have Dr. Steven Galson, who is Director of the
Center for Drug Evaluation and Research at the Food and Drug
Administration. And next is Dr. Marcia Crosse, Director of
Health Care Issues at the U.S. Government Accountability
Office. You have 5 minutes each. Your statements will be made
part of the record, and you may, at the discretion of the
committee, submit additional brief and pertinent statements in
writing for inclusion in the record. And I will now recognize
first Dr. Galson.
STATEMENT OF STEVEN GALSON, M.D., DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION
Dr. Galson. Thank you very, very much, Mr. Chairman and
members of the committee. I am Rear Admiral Steven Galson,
FDA's director for the Center for Drug Evaluation and Research.
I am very pleased to be here to talk about FDA's drug safety
program and to reemphasize our continued commitment to drug
safety.
As a physician, I have dedicated my career to serving
public health. As a career medical officer in the U.S. public
health service since 1986, I have worked in the Nation's public
health agencies to assess scientific data and make health
recommendations and regulatory decisions that protect and
promote the health of the American people. In my current
position as director of CDER, I am deeply committed to leading
an organization that inspires the trust and confidence of the
people we serve.
My detailed testimony submitted for the record talks about
the many initiatives CDER has on the way to strengthen drug
safety. Modernizing the science of drug regulation, improving
our internal operations, and enhancing our communications. I
will focus my brief remarks today on describing my vision for
the center and our vital role in protecting and promoting the
public health with an increasingly complex health care system.
As you know, no drug is risk-free, and FDA plays a key role
in assuring that a drug's benefits outweigh its risks,
beginning with our determination whether a drug can be approved
for marketing. And if so, ensuring that is it truthfully and
adequately labeled.
Scientific progress is key to improving drug safety. CDER
is meeting this challenge in many ways, including partnerships
with outside groups who can assist us in developing new tools
to improve safety. One example is an ongoing FDA scientific
collaboration intended to yield better tests for toxicity than
our current screening techniques. Such new tests would detect
toxicity problems earlier in drug development than our current
approaches.
Our responsibility continues, as you know, post-marketing
when our programs identify adverse events not previously
brought forward. To meet this challenge, CDER has taken a
number of steps to strengthen the science that underpins these
regulatory decisions. These scientific activities include
developing and incorporating new tools to assess benefit and
risk, upgrading our adverse event reporting system, and
expanding our database resources. One example of the work we
are doing to support the science of post-marketing drug safety
assessment is exploring opportunities for linking private
sector and public sector post-marketing safety monitoring
systems to create a nationwide medical product safety network.
Such a system could enable better safety information about
medical products to get to health care professionals and
patients at the point at which they are providing and receiving
their care.
Communicating about marketed drugs is one of our key
responsibilities, and health communications technology is
rapidly evolving in this century. We too must change as this
technology changes and improves. In this area, we have recently
issued final guidance that describes our approach to
communicating drug safety information, including emerging drug
safety information to the public quickly, even if, in some
cases, we are still evaluating this data.
Another part of improving our approach to drug safety is to
listen to people outside FDA for ideas. Next month, on June 25
and 26, we will hold a public workshop to seek input from
outside experts to discuss how risk management plans are
working to enhance patient safety. In addition, we plan to
establish a new advisory committee to obtain input on how to
improve our external communications.
Lastly, I would like to address the steps we are taking to
affect a culture change within CDER to become the kind of
effective, efficient and integrated center I am committed to
leading. We are addressing tensions between our pre-approval
and post-approval staff. We have enlisted the help of external
experts to help to identify opportunities for improvement and
assist us with implementation of these steps. We are examining
ways to improve our handling and resolution of scientific
disagreements.
CDER has employed process improvement teams to recommend
changes to our drug safety program. A number of their
recommendations have already been implemented, including the
establishment of new safety-related positions in each of our
drug review divisions and conducting regular safety meetings
between groups.
We are also developing pilot projects to evaluate models of
integrating our surveillance staff more into our drug review
process, including having the staff participate in new drug
reviews. We are firmly committed to ensuring that our
surveillance staff have a strong voice pre- and post-marketing
in safety decisions.
In conclusion, CDER's mission is to ensure that Americans
have access to safe and effective drugs. Toward that end, our
regulatory decisions must be based on sound science, applied
with consistency and integrity. My personal commitment is to
ensure that these decisions are informed by diverse points of
view and vigorous academic debate.
We are committed to creating a comprehensive, systematic
approach to improving the drug safety system, as quickly and
efficiently as available resources allow. As always, we value
input from Congress, the public, and the medical community as
we develop and refine these drug safety initiatives.
Thank you for the opportunity to testify in front of the
committee today, and I am happy to respond to questions after
the next person. Thank you.
[The prepared statement of Dr. Galson follows:]
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Mr. Pallone. Thank you, Doctor. Am I supposed to refer to
you as Admiral or Doctor?
Dr. Galson. Either.
Mr. Pallone. Well, I guess we will stick with Doctor, I
guess. And, Dr. Crosse, If you would give us your statement,
thank you.
STATEMENT OF MARCIA CROSSE, DIRECTOR, HEALTH CARE ISSUES, U.S.
GOVERNMENT ACCOUNTABILITY OFFICE
Ms. Crosse. Mr. Chairman and members of the subcommittee, I
am pleased to be here today as you examine the safety of the
drug supply. My remarks today are based on GAO's March 2006
report on FDA's process for decision making regarding post-
market drug safety and on steps FDA has taken that respond to
the recommendations we made in that report.
Our work focused on two FDA offices that are involved in
post-market drug safety: the Office of New Drugs, OND, and the
Office of Drug Safety, ODS, which has since been renamed the
Office of Surveillance and Epidemiology. Consistent with our
report, I am referring to this office as ODS.
As we reported in March 2006, we found that FDA lacked a
clear and effective process for making decisions about post-
market drug safety issues. We found a lack of clarity about how
decisions were made and about organizational roles. There was
insufficient oversight by management. There were significant
data constraints, and the agency lacked sufficient resources
and authority to effectively ensure the safety of marketed
drugs.
The decision-making process for post-market drug safety is
complex, involving input from a variety of FDA staff, drug
sponsors, the public, and many other information sources.
Central to the process is the iterative interaction between OND
and ODS, and many of the problems we identified derived from
the ways these two offices managed their drug safety
responsibilities. In particular, there was a lack of criteria
for determining what safety actions to take and when to take
them, which contributed to disagreements over decisions about
post-market safety.
We found that insufficient communication between ODS and
OND was an ongoing concern and hindered the decision-making
process. For example, ODS did not always know how or whether
OND had responded to safety analyses and recommendations for
safety actions. ODS management did not systematically track
information about the recommendations its staff made and OND's
response. This limited the ability of ODS management to ensure
that safety concerns were resolved in a timely manner.
Moreover, FDA faced data constraints that contributed to
the difficulty in making post-market safety decisions. FDA's
access to post-market clinical trial and observational data is
limited. FDA does not have authority to require that a drug
sponsor conduct a study for the purpose of investigating a
specific post-market safety concern.
In the absence of such authority, FDA has relied on drug
sponsors voluntarily agreeing to conduct these studies.
However, as we heard, these studies have not consistently been
completed. FDA was also limited in the resources it had
available to obtain data from outside sources. Annual funding
for this program was less than $1 million a year for 2002
through 2005 and was $1.6 million in 2006, which allowed for
four data contracts.
Today, just over a year after our report was issued, FDA
has begun to take steps that could address the goals of three
of our four recommendations to the agency. First, we
recommended that FDA systematically track post-market drug
safety issues, and the agency is in the process of implementing
a tracking system.
Second, we recommended that FDA revise and implement its
draft policy on the decision-making process for major post-
market safety actions. And FDA has made revisions to, but not
finalized, its draft policy.
Third, we recommended that FDA clarify ODS's role in
scientific advisory committees, and the agency is developing,
but has not finalized, guidance to clarify their role.
And fourth, we recommended that FDA improve its process to
resolve internal disagreements, but FDA has not taken action in
response to this recommendation.
In addition, we suggested in our 2006 report that Congress
consider expanding FDA's authority to require drug sponsors to
conduct post-market studies as needed to collect additional
data on drug safety concerns.
In conclusion, while FDA has taken positive steps, its
actions are not yet fully implemented, so it is too soon to
evaluate their effectiveness in addressing these problems. Most
importantly, the agency needs additional resources and
authority to be able to fully address the range of post-market
drug safety concerns.
Mr. Chairman, this concludes my prepared remarks. I would
be happy to respond to questions that you or other members of
the subcommittee may have.
[The prepared statement of Ms. Crosse follows:]
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Mr. Pallone. Thank you, Dr. Crosse, and we will start with
the questions. I will recognize myself for 5 minutes, and I
wanted to ask these questions of Dr. Galson.
In your testimony, you talked about all the things that FDA
is doing in response to the IOM report. For example, you cite
steps you have taken to improve communications and information
flows as well as improve operations and management, especially
between the Office of Surveillance and Epidemiology and the
Office of New Drug. And I think these are positive steps that
FDA has taken to reform itself administratively.
But as you know, there are some recommendations made by the
IOM report that FDA can't do administratively. And I would like
to know where the administration might stand on some of these
recommendations. It is important for us to know where the
administration stands as we move forward with reforming our
drug safety system and whatever legislation we are going to put
forward.
So I have three questions. Let me begin with the clinical
trials. Does the administration agree with the IOM report that
Congress should require industry sponsors to register in a
timely manner at clinicaltrials.gov, at a minimum, all phase
two through phase four clinical trials wherever they may have
been conducted if data from the trials are intended to be
submitted to the FDA as part a MBA, SMBA or to fulfill a post-
market commitment? This goes on. Why or why not? And if
Congress were to include this in our drug safety reform
package, do you know whether or not the administration would
object? That is my first question.
Dr. Galson. Yes, as you know, provisions changing the way
that we register and require registration of clinical trials
has been part of the debate and the discussions going on in the
Senate. And we are very actively participating in providing
technical assistance to those provisions, and it has changed as
time has gone by. We have supported some and not supported
others, so we look forward to continuing the work----
Mr. Pallone. I haven't necessarily followed the Senate.
Sometimes we take pride in not following the Senate. Do you
just want to comment, as best you can, on what you have been
saying over there in this regard?
Dr. Galson. We are very much in favor with providing as
much transparency as possible, concerning clinical trials that
are underway. There has been a huge amount of progress made
over time in getting more of these trials registered, and I am
sure you are going to hear more about this from the
pharmaceutical representatives that are up here. But if you
look on that Internet site now, there is a lot more information
on there than it used to be, and we are in favor of that.
Mr. Pallone. Well, what about the mandate though, the
mandatory aspect?
Dr. Galson. With regard to the specific provisions, we will
continue to discuss that with staff, and the administration
hasn't taken a firm position on exactly where we stand on each
one of those provisions.
Mr. Pallone. OK. Well, let me go to No. 2. The IOM
recommended that Congress ensure that the FDA has the ability
to require such post-marketing risk assessment and risk
management programs as needed to monitor and ensure safe use of
drug products. They go on to recommend that FDA should have the
ability to impose these conditions before and after approval of
a new drug, as well as having increased authority and better
enforcement tools, such as fines, injunctions, and withdrawal
of approval to ensure compliance by drug sponsors. Are these
recommendations something that the administration would
support, and again why or why not with regard to the risk
management assessment?
Dr. Galson. Thank you. As you know, I am sure, there are
risk management plans that are currently part of approval of a
number of drugs that are on the market, and we thought them
through very carefully. And after the drugs are on the market,
we evaluate those plans to see whether they are working. This
is another area we have been very active providing technical
assistance to the Senate and other Members of Congress that are
interested in talking about this. And we think when there are
drugs that have special risks, they do require special
attention and special risk management plans for the drugs to be
approved and for us to carefully follow up afterwards.
Mr. Pallone. But again in those cases, you have mentioned
special cases, would you think the FDA should have the ability
to require the risk assessment and the risk management in those
cases?
Dr. Galson. We don't feel comfortable approving drugs that
have special risks, unless there is a way to manage that risk.
And it is very much on a case-by-case basis that we make that
assessment. We are concerned about a one-size-fits-all approach
in the discussions that we have had with the Senate on this
provision because the work is very time consuming for our
staff. And we want the ability to focus our attention on the
most pressing public health problems. So, in general, we
haven't favored a one-size-fits-all approach but our ability to
make a case-by-case assessment. And that could include, in some
cases, being able to make sure that some studies get done.
Mr. Pallone. OK, I have to ask one more question only
because I didn't get a chance last time. This is about the new
DTC user fee program that was included in PDUFA Four Proposal.
That was negotiated between the FDA and industry. I wanted to
ask this at the PDUFA hearing, but I ran out of time, and again
I am running out of time. What assurances do we have that drug
companies would actually participate in this new program, given
that it remains voluntary? And would the administration support
a program that requires all advertisements for new drugs be
reviewed by the FDA?
Dr. Galson. Again, this is a complex regulatory and legal
area, and as you may be aware, there are a large number of
television ads and, of course, even much larger number of
printed materials that are produced by the pharmaceutical
industry. And we have a fairly modest staff that is able to
review those as it is. So again we are concerned that if we are
asked to review more materials that we have adequate ability to
do that, and that has been a challenge between the resources
and the number of products that have come in.
What this new program does is give us additional staff so
that we can do a lot more comprehensive job of looking at this
particular subset as they come in. And we are very, very
interested in making sure that they are truthful and they are
not misleading. And I suspect that the industry is interested
in that as well.
Mr. Pallone. So it is a question of money as always. All
right, thank you very much. I yield to the gentleman from
Georgia, Mr. Deal.
Mr. Deal. Thank you. One of the issues that has come up
before this subcommittee on other hearings as it relates to
approval of products has been the question of where
intellectual property rights become an impediment to making
information more available.
With regard to clinical trials, both pre-approval and post-
approval, one of the discussions has been to make more
information about those clinical trials available to the
public. Are intellectual property rights one of the constraints
that you encounter in those environments? And if so, would you
elaborate on that?
Dr. Galson. Absolutely. One of the challenges in all the
work that we do is having our scientists able to look at all
the vast information that is available concerning products. We
digest this. We evaluate it. We sometimes debate it, and in the
end, we come out with assessments and communication that helps
both practitioners and patients make the right decisions about
risk and benefit.
Putting every single piece of information that may be in
that drug company application down to the patient level does
raise intellectual property issues. And we are obligated by our
laws to protect the intellectual property, and I am not sure
that it would really benefit patients as well because they
don't want the undigested data. They want to know what is FDA's
assessment of this data.
An additional point on that is that we do think very
carefully about patients who need new products, patients who
have cancer and other chronic conditions. And we don't want to
do anything that is going to stand in the way of getting those
products through the development process and evaluated by us in
making those appropriate products available.
Mr. Deal. One of the tools for post-market determinations
and safety, of course, is in mining data that may be available.
To what extent has the FDA utilized whatever resources, if any,
might exist in mining data collected by CMS, since they have a
huge bank of data? Has there been any correlation between the
two agencies in that regard?
Dr. Galson. Yes, there has. As you know and you have heard,
some of the statements that you all have made have indicated
the very, very exciting frontier really in drug safety--our
ability to look at large data sets as they are being developed
specifically, electronic medical records, more records from
these larger payer databases, such as CMS. And as you all are
very, very aware, the new provisions in Medicare drug benefit
are going to make a lot more data available in the Medicare
system that will allow us to link eventually medical outcomes
with the drugs that are prescribed.
And to prepare for that very optimistic future of being
able to use more of this data, we have been engaged in an
interaction with the Medicare program, looking at the existing
data to try to see how can we work with that and learn lessons
with that interaction. We have been working with our sister
agency, AHRQ as well, and I just got a briefing on this earlier
in the week. And we are making some good progress and hopefully
will learn some lessons that will allow us to move forward as
we get more funds from Congress to be able to use this data and
hire our staff so we are prepared to mine any available data
sets that are valuable for patients.
Mr. Deal. Dr. Crosse, have you had the opportunity to look
at what other countries are doing on post-market surveillance
of drugs, and how does that compare with what we are doing in
the United States?
Ms. Crosse. Sir, I am afraid we have not done any recent
work at all looking at drug safety systems in other countries.
As you know, there are a number of differences in the review
and approval process in those countries and also in the kinds
of data that may be available to them because of the national
health systems they have. But we have not done any recent
reviews that would help you on that.
Mr. Deal. Dr. Galson, with regard to imported drugs, does
the law, as it is currently written, in your opinion, give FDA
sufficient authority to deal with drugs that are actually
manufactured in other countries? What are the limitations that
you incur in dealing with those imported drugs?
Dr. Galson. Right. I assume you mean the legally imported
drugs that are part of our current system, and there is a
significant portion of the drug supply that is currently
manufactured by some of the same companies that are household
names, but they happen to be manufactured overseas.
All of our requirements for drug approval generally apply
for drugs that are imported, as they do here. So we go
overseas, and we inspect foreign manufacturing facilities when
those companies are importing their product to the United
States. When clinical trials are done overseas and those
clinical trials are used in our application process, we go
overseas and inspect them. So we have good authorities to do
that.
Mr. Pallone. Thank you. Mr. Waxman.
Mr. Waxman. Thank you, Mr. Chairman. Dr. Galson, if you
look at the drugs where there have been problems or drugs that
have been withdrawn from the market, it looks like a pattern
where the risks appeared before approval, and the agency got
caught off guard. To fully address this trend, I think it is
clear you need some help from Congress. You need more
resources. You need more authorities. But within the confines
of FDA's current authorities and resources, what are you going
to do to fix this problem?
Dr. Galson. That is a very challenging issue, and I think
the first thing is we have to be very wary about looking
backwards and trying to figure out what we may have done wrong
in the past when the situation was very different back when you
were looking at data initially, but your point is well taken.
And I think the real future of improvements in drug safety lie
in scientific areas, and we are very invested in that and our
critical path initiative and talking to many of you working on
projects with not just the industry but also with academic
groups and non-profit organizations to try to make sure that
the information that we are getting before approval gives us
the best possible data so that we do a better job of being able
to predict which drugs are going to work and which drugs are
going to cause adverse events in other people. And so that 10
years down the road, we will be able to stand on our laurels
and say that these sort of surprises after approval have been
avoided. Now, we do sometimes get signals before a drug is
approved, as you said, that there may be a safety issue. And
each time we see that, based on clinical trial data, we look
carefully into that, and we try to make an assessment about
whether that signal is going to result in a problem post-
approval. The way to do a better job of that and to avoid what
you are pointing out is better techniques, techniques like
pharmacogenomics that will allow us to understand better
individual differences between patients.
Mr. Waxman. In the meantime, there are problems that are
discovered after the drug has already been approved. FDA asks
the manufacturer if they would be willing to do a drug
surveillance after approval. And especially if you have those
signals, you want the manufacturer to do that because you think
there may be a problem down the road. When FDA identifies,
after a post-market survey, a need to change the drug's label,
including adding a black box warning, can you describe the
process FDA uses to compel a drug company to make a change? Can
you compel a drug company to make that change?
Dr. Galson. We feel pretty strongly that when we need a
black box, or we feel like a drug has to be labeled better,
either with a black box or another kind of warning for the drug
to stay on the market--we have a very good process of sitting
down with the company and saying look, there is this new
information that has come out. We are really not comfortable--
--
Mr. Waxman. When you negotiate in this process with the
company, that can take a long time, can't it?
Dr. Galson. We are committed to reducing that time, and it
has been reduced. And the other thing that we are doing related
to that is that if there is not agreement there, we will go
ahead--and we have done this in numerous cases over the last
couple years. We will go ahead and put that information out
without discussing it with the company. We will put out patient
or physician information sheets. We will issue a public health
advisory.
Mr. Waxman. But how about that label, even a black box
label, if the company refuses as you are negotiating, and it
takes months to negotiate. Meanwhile the public is unaware of
these problems. If the company refuses to make the labeling
change that FDA believes is necessary, what are your options?
Isn't it just simply to take the drug off the market?
Dr. Galson. We could take the drug off the market, but we
push the companies, and in general, they respond. It doesn't
take months, and once we say we are going to go out and put
this information in the public realm, whether or not you move
quickly enough, they usually move.
Mr. Waxman. Dr. Crosse, from what Dr. Galson has told us,
it seems like he feels comfortable with the situation. Yet you
made a recommendation that Congress provide FDA with the
authority to require post-market studies and to be able to put
these labels on and to insist that these studies be done.
Ms. Crosse. Yes, sir. The information that we have reviewed
over a number of years has found that it can be a lengthy
process. I think it is a very positive step that FDA is now
taking to more publicly notify physicians and individual
patients of concerns that have arisen. In the past, that was
not their general practice. And so I do think that that is a
positive step that the agency is taking to put the information
out publicly if the company is not moving expeditiously to make
these changes.
But our understanding is that the FDA's options are limited
if the company is not cooperating. And while I agree that
pressure can be brought to bear, and making this information
public helps to bring that pressure, still the options
available are quite limited if FDA feels that there is a
positive benefit of this drug and that there are patients who
need to continue to be able to receive it, and they don't
therefore want to enforce the withdrawal from the market.
Mr. Waxman. Just a last comment. I know my time is up, but
I am in a situation now where I am chairman of the Oversight
Committee, try to get information to conduct investigations.
But knowing that I have the authority to issue a subpoena
doesn't mean I have to issue subpoenas. But it does mean that
those who have to deal with me are more forthcoming. I would
rather have FDA be able to deal from a position of strength
rather than pleading for information, which they need and ought
to have in order to protect the public health and to make sure
the public is aware of the problems once they are discovered.
Thank you, Mr. Chairman.
Mr. Pallone. Thank you. Mr. Barton.
Mr. Barton. Thank you, Mr. Chairman. Back in August 2007,
Mr. Whitfield and I wrote a letter to the Department of
Justice, asking for them to review current law in terms of FDA
authority with respect to imports of drugs both legally and
illegally into this country. And their response back to us was
this past December. And in that letter, the Assistant Attorney
General, a Mr. Klinger, said that they, the Department of
Justice, would support a change in the Food, Drug, and Cosmetic
Act that would make sure that that Act gave the FDA explicit
jurisdiction over conduct that occurs outside the United States
for drug products that are subject to the Food, Drug, and
Cosmetic Act when they are imported into the United States. I
would assume that the FDA supports that. Is that correct?
Dr. Galson. Yes, we do, as well as stiffer fines in those
circumstances.
Mr. Barton. And if we did give this authority, this
explicit authority, how would the FDA and would that give the
FDA the authority to inspect facilities overseas on a random,
surprise basis like you have here in the United States? My
understanding is when you inspect a pharmaceutical factory in
China, you have to get permission before the fact and they
actually announce sometimes 2 to 3 months in advance so that
the day you show up, everything is sparkling clean and smiley-
faced.
Dr. Galson. I am not an expert at international comparative
regulatory law; however, it is very important that we are able
to go into foreign factories. The current situation is we do
work with foreign countries, governments, when we make these
visits. Even to get into many countries, they have to be aware
that FDA officials are coming in.
On the other hand, we do do a lot of these inspections, and
we send teams over, and they successfully inspect and identify
problems. And those problems are addressed or we move forward
to take the next step.
Mr. Barton. In the United States, you can just show up and
flash the badge, so to speak, and do the inspection. Isn't that
correct?
Dr. Galson. That is correct.
Mr. Barton. But overseas, you can't do that. Is there any
country that you can inspect as you do here in the United
States? Or do you have to pre-clear it?
Dr. Galson. I am happy to look into that to see whether
there are any countries where we have the capacity to do that
and get back to you.
Mr. Barton. And on counterfeit drugs, what is the current
status of trying to prevent the counterfeit drugs in terms of
number of inspectors and things like that?
Dr. Galson. We do focus some resources on counterfeit
drugs, and we are very concerned about this. We work with
pharmacies, with States, to move forward when we identify
problems and to make sure that we have an open policy wherein
people hear about counterfeit drugs. They are reported to us.
We investigate it. We are concerned about counterfeits that are
available on the Internet. And of course, if there are more
drug imports coming in, that would be something we have to
focus on more.
Mr. Barton. Dr. Crosse, would you like to comment on any
suggestions for combating counterfeit drugs?
Ms. Crosse. Well, we had undertaken a review about 2\1/2\
years ago of Internet pharmacies, and we placed a number of
orders from pharmacies over the Internet, both in the United
States and in Canada and other foreign countries. We found a
number of problems including counterfeit drugs. Some of the
samples that we received were counterfeit medications, and a
very small sample of drugs we purchased, out of about 63
purchases, we have four counterfeit drugs. And we had other
drugs that were provided without any instructions for use,
without appropriate labels or warning information or directions
on how many tablets to take and at what interval. There are a
number of difficulties that we identified in that review in the
use of foreign pharmacies.
Mr. Barton. But four of the 63 purchases were counterfeit?
Ms. Crosse. Yes, sir.
Mr. Barton. That is pretty amazing. Well, Mr. Chairman, my
time has expired, but I hope that is something that, as we move
forward, this whole issue of counterfeiting is, I think, a very
great concern and based on what Dr. Crosse just said, I was
assuming it was maybe 1 percent, 1 out of 100. But 4 out of 60
is--what is that--about 8 percent, something like that. So that
is non-trivial. Thank you, Mr. Chairman.
Mr. Pallone. Thank you. The gentlewoman from Colorado, Ms.
DeGette.
Ms. DeGette. Thank you, Mr. Chairman. Following up a little
bit on Mr. Barton's question. Dr. Crosse, I think the time is
now to start looking at these counterfeit drugs because we had
some hearings in the Oversight Investigation subcommittee in
the last Congress where customs is just seizing all kinds of
these drugs coming in, and as Dr. Crosse described, they have
no description what they are and when they are tested. Some of
the drugs from South America were actually yellow paint, dyed
paint. And there is no indication if the proper climate
controls or other kinds of controls have been established.
And so I guess my question to you is what mechanisms do we
currently have in the U.S. to expose counterfeit drugs before
they reach a U.S. consumer? Do we have enough laws to do that,
and maybe more importantly do we have enough resources to do
that?
Dr. Galson. Let me talk about a couple of the things that
we have been doing. We have been focusing on this for quite a
few years, but there is no doubt that this is something that
probably needs more attention into the future. And you only
have to open up the newspaper to see some of the problems that
have occurred.
One of the things that we did is we were hearing that it
was cumbersome for people to figure out how to report when they
found a counterfeit or when they heard about a counterfeit. So
we modified our standard adverse event reporting form that
comes in to make it easier for people to explicitly say when
they find a counterfeit.
Ms. DeGette. When did you modify that report?
Dr. Galson. I believe it was 2005.
Ms. DeGette. And have you noticed an increased number of
reports coming in?
Dr. Galson. We haven't, but that probably reflects the fact
that the adverse reporting system is not that sensitive.
Ms. DeGette. It has probably been the least effective way,
waiting until the drug actually gets to the consumer. And then
they have to make a report.
Dr. Galson. Absolutely.
Ms. DeGette. So what else are you doing?
Dr. Galson. Well, one of the things that does concern us,
and we are going out with education efforts about this, is the
increase of number of drugs that have been purchased over the
Internet and the proliferation of Internet pharmacies and
people thinking that this is an answer to getting their drugs.
And clearly that makes it easier for people to get. Even if the
drug is advertised that it is ``from Canada'' it may come from
somewhere else.
Ms. DeGette. I know that, so what are those efforts?
Dr. Galson. Those efforts are trying to communicate with
people and with pharmacists and.
Ms. DeGette. And have those born fruit in finding
additional counterfeit drugs?
Dr. Galson. I don't think our detection of counterfeits is
robust enough to really know whether----
Ms. DeGette. And so what do we need to do?
Dr. Galson. Yes. Well, I think one thing is resources, and
we do expect to be getting more resources under PDUFA that we
will be able to put out in the field to detect more of these.
As you know, there is just a sea of drugs coming in through the
mail and through the borders. And it is a challenge for us to
open up every single package. But there is more that we could
do, and we will be focusing----
Ms. DeGette. Dr. Crosse, do you have any opinions what we
could do to beef up our detection of counterfeit drugs coming
in?
Ms. Crosse. I think it is a very difficult issue for FDA
alone to face because a lot of the drugs that are coming from
the Internet pharmacies from overseas are coming directly to
consumers.
Ms. DeGette. Right.
Ms. Crosse. They are not passing through the normal drug
supply chain in this country. And so, there really is very
little, short of intercepting packages at the border, that FDA,
I think, can do beyond these kinds of steps to monitor the
pharmacies that are on the Internet. We found Web sites popping
up and closing in a matter of days when we were undertaking our
work. It is very difficult to track all of the Web sites that
may be available to sell some of these drugs.
Ms. DeGette. So really consumer education will be
important?
Ms. Crosse. That is one of the steps, and certainly, I
think there are some technological solutions that are being
proposed to try to put in some sorts of tracers and other kind
of tracking information that would allow the drug supply system
to more adequately monitor when the drugs that are coming in
are authentic.
Ms. DeGette. Now, do you think that this problem we have
got right now would be exacerbated if more reimportation was
allowed by Congress?
Ms. Crosse. I am not aware of what the specifics are for
proposals that are under consideration for the limits that we
placed on that importation. In the small review that we did, we
did not find problems with the drugs we purchased from Canadian
pharmacies. But, as Dr. Galson has indicated, one cannot always
determine just from looking at a Web site whether a site that
identifies itself as being Canadian actually is.
Ms. DeGette. Dr. Galson.
Dr. Galson. Yes. A couple points. The first is just
following up on the technological solution. We do think that
there are some technological steps, and these radio frequency
identification tags, RFID, is one of the technologies that has
been identified that can mark packages so they can be tracked
and traced more efficiently. We have issued guidance on the use
of this technology, and we are going to be putting more effort
towards that. So that is a technological solution. On your
question about importation, I don't think there is any question
that if there are more drugs coming into the country from other
places, it is going to be more difficult. And I think about my
challenge in being responsible for all the currently legally
imported drugs. If the number of manufacturing facilities and
companies doubles or triples with drugs coming in from a lot
more countries or from countries that are difficult for us to
inspect, there is no question that it is going to be more of a
challenge to detect these counterfeits and go out and inspect
the sources.
Ms. DeGette. Thank you.
Mr. Pallone. Thank you. The gentleman from Indiana, Mr.
Buyer.
Mr. Buyer. I want to thank Ms. DeGette. I welcome her to
this issue. This is a pretty strong concern of members on this
committee. We reauthorized PDUFA, and we are now examining the
post-market review. I don't understand how a manufacturer out
there can do the very best they can, they are responsive to
these reports of adverse effects that are being sent on, yet
their ability to police the counterfeit--it is almost as if we
have a system--so what do we have in America? We have got this
system, and we have a leak. And the strength of the policing of
that leak is going to come from who? Those whom have the most
at stake. So it is going to come from, first would be the
manufacturers themselves. They are going to protect because
they have liability on the line. Second it is you, us, the
Federal Government because we have given this assurance to the
American people that we are going to have a closed system with
regard to our drug supply, and that it is that FDA stamp of
approval. It has got to mean something. So I think it is pretty
clear. An unapproved FDA drug lacks your assurances of safety,
effectiveness, quality, and purity. Now, if the FDA cannot
assure the safety and efficacy of a drug product line because
you can't gain access to the manufacturing process, we have
serious problems.
So if that drug is manufactured in a foreign country and
you gain access to that manufacturing process, there is not a
problem there, and you do that all the time. In the mid 1990's,
we had this political escalation and the attacks of our
pharmaceutical manufacturers and as if well, just run off to
Canada and get your drugs. And this reimportation issue began
to erupt.
And then we see this increase in the volume of adverse
event reports. So my question is do you know of any correlation
between this increase in adverse reports and the amount of FDA
unapproved drugs that are finding access into our country. Is
there a correlation between this? Do you know?
Dr. Galson. We are not aware of a correlation between those
two. There are a number of hypothesized explanations for why
that number is increased. One is there are more drugs out
there. More people are taking more prescription products. If
you look over time at the number of prescription drugs taken
per person in the United States, it has gone up. And similarly
there is absolutely more awareness of drug adverse events. I am
not at all trying to say that there is no correlation, but I
wouldn't want to blame that increase entirely on this issue.
Mr. Buyer. All right, let us bubbacize this. So last night,
I picked up the phone and I called an internist, Dr. Lauren
McClure in Muncie, Indiana, OK. Now, she is dealing with a
problem because the mayor of Muncie, he is going to reduce the
drug costs to the city of Muncie, Indiana. So what does he do?
He instructs the city employees and the workers and the
retirees to do what? Get their drugs from Canada. Now, as a
practicing internist, she has a challenge. She will do her
diagnosis, and in her prognosis, she will prescribe particular
drugs. And she doesn't know what is working and what is not
working and why.
So here we have someone that we as a country have invested
greatly into this medical expertise, and it is a scratch of the
head. She doesn't know whether the drugs the person is taking
are FDA-approved drugs, or are these the counterfeit drugs? And
so she has been challenged as she continues on. Now, this
happens to be a doctor that actually knows that a patient is
gaining access through Canadian pharmacies. How about if the
docs all across the country, you prescribe a drug, and they
don't even realize that their patients are out there. Ma'am,
when you said I don't have a problem with Canadian pharmacies,
what about these Canadian Internet sites? People think that
they are approved, and many of them are unapproved, and they
are the flow, the pathways of these illegal substances.
Now, our challenge is the person may not get better and die
if it doesn't get reported. Those who say well, let us go to
reimportation. People aren't dying from reimportation. You
never know. So now if we want to make sure that we really
understand about a drug that is out there, what do we in
Congress need to do here? Do we have to mandate that doctors
ask their patients that--I gave you that prescription. When you
come back and you are not better, we ask them where did you buy
your drugs? I hate to do something like that. Are we going to
have to do that? And No. 2, when you talk about tools and
modernization in the aftermarket, are you going to take into
account the knowledge that we have about this escalation of the
counterfeit drugs that are coming into the market? Those are my
two questions.
Dr. Galson. Yes. Well, we have identified one of our major
goals in drug safety is to improve how we communicate to the
public about drug risks, through the Internet, through other
types of media, through medical organizations, other
professional organizations, such as the pharmacists. There are
other players in this, as you may know. The pharmacy world is
regulated by and large by the State pharmacy boards, so talking
to State people. And there is no question that we need to do
more communication. We have a lot of activities underway in the
agency focused on this, particularly warning people about
Internet pharmacies and to get their drugs through a
traditional source. But there is no question we could do more.
Mr. Buyer. Here is how you stop the mandate. How about you
contact the AMA and through the continuing medical education,
advising counsel with regard about asking that question. Where
are you getting your drugs?
Dr. Galson. Yes, we do work with the AMA.
Mr. Buyer. In medical schools?
Dr. Galson. Yes.
Mr. Buyer. In the training? You work with the medical
schools?
Dr. Galson. We do some work with medical schools. That is
an excellent idea.
Mr. Buyer. Let us do more with our medical schools and
teaching so that they know it is part of their prognosis is
what I would recommend, and the continuing medical education
piece. And you can take that with you.
Dr. Galson. Thank you.
Mr. Buyer. The last is on the increase in surveillance. I
like the fact that you are checking our ports of entry and
working properly with customs. So in PDUFA, if we want a purity
with regard to that close market review sample, what in
resources do we need to put in this bill? Tell me what you want
and need to get the assurances of clients.
Dr. Galson. Right, the FDA staff who are out in the field
who are at the ports working with customs are not part of the
drug center. It is a different part of the agency. I would be
happy to go back and ask them exactly to let you know what they
think is needed to move forward here. We do provide technical
and other kinds of compliances systems and work together with
that group. And we are looking very much forward to additional
resources coming in through the PDUFA program so that we can do
more of this kind of assistance and participation in our
compliance efforts.
Mr. Buyer. What agency is it?
Dr. Galson. It is part of FDA. It is called the Office of
Regulatory Affairs.
Mr. Buyer. All right, thank you. Thank you, Mr. Chairman.
Mr. Pallone. Thank you. Recognize the gentlewoman from
Illinois, Ms. Schakowsky.
Ms. Schakowsky. Thank you, Mr. Chairman. I wanted to ask
Dr. Galson, you may have said this already. Maybe I missed it.
The GAO suggested that Congress expand or consider expanding
FDA's ability to require drug sponsors to conduct post-market
studies, and so what is your view on that?
Dr. Galson. Well, we have been working, as you know, with
providing technical assistance to the committees in Congress
and both sides that are working on issues of authority, so we
will continue to do that. We do feel like we are able to get a
lot of information post-marketing, and we are very committed to
what we have talked about, improved surveillance by getting
data sets and groups of data about drugs and how they are
prescribed and the adverse events that may result through them
that had nothing to do with even requiring drug companies to do
studies. This is kinds of surveillance data that other groups,
such as the health care payers--you are going to hear a little
bit from them in the afternoon--that I think is the future of
drug safety, looking at the databases that are out there.
Ms. Schakowsky. I understand you are talking about outside
groups, but if we maintain a voluntary infrastructure on this
in general, why would we as members of Congress or the public
have confidence when we have seen so many problems with failure
to report things and poor reporting of clinical trials and all
kinds of things that the pharmaceutical companies have done? I
mean I am trying to understand the source of your confidence
when you emphasize this relationship with the private sector
and pharmaceutical companies.
Dr. Galson. Yes, a couple points. First is that what many
people don't realize in the debate is that we can require some
studies to be done in several different categories. The first
of those are under the legislation that has promoted the
development of more information about drugs for children, and
we are able to require companies to do studies.
Ms. Schakowsky. How is it that many of them have been
started but incomplete?
Dr. Galson. In the pediatric area, I will get to that in a
second. The other second area is the program that we have under
our regulations called accelerated approval. When there is
something that is really needed to fulfill a medical need, such
as a cancer drug where there isn't another drug out there, we
can approve the drug and then require a company to do a study
after approval. And those studies do get done. And the third
area is in the counter-terrorism area where there is a drug
that we think needs to be made available in case of a terrorist
attack, but it wouldn't be ethical to do that study in humans.
We can approve the drug using animals and then require a later
study or a later collection of data.
But with regard to your main question, we are happy to
continue to discuss it with this committee and with others your
ideas for requiring more study to be done and give you our
views on the specifics.
Ms. Schakowsky. Dr. Crosse, I wondered if you wanted to
comment on that.
Ms. Crosse. Yes, we do believe that FDA would benefit from
having additional tools at hand to be able to take steps when
they believe they were necessary and they were not getting
voluntary cooperation. With regard to the pediatric studies,
that certainly has promoted a number of drugs being studied for
pediatric uses; however, almost 20 percent of those drugs that
FDA asked to be studied, the sponsors declined to study for a
variety of reasons.
But nevertheless, there still are a number of drugs out on
the market that FDA had indicated were important for review.
And it was at the option of the manufacturer whether to pursue
those. The alternative path that the pediatric--and
specifically Best Pharmaceuticals for Children Act--have
provided for the Foundation for the National Institutes of
Health to pursue the studies has not been effective. None of
the drugs that have been referred for study by that
organization have yet been studied.
Ms. Schakowsky. We have a problem here. I was intrigued
by--both Dr. Crosse mentioned that there were some problems
with the pre- and post-marketing divisions of the FDA. You
called it tensions, Dr. Galson. Do we have to really deal with
tensions here? I mean can you resolve those problems?
Dr. Galson. Well, there is tension inherent in drug
regulation, and I don't think we will ever get away with a
totally stress-free easy job. And that is really not what I am
looking for. And the fact is that two people looking at the
same scientific data may come to different conclusions, and so
it is not just between offices but even within the staff. And
again this is normal, and the other regulatory and scientific
agencies that I have worked in, you have had this same tension.
I am not meaning to diminish it or anything by calling it
tension. It is part of the regular scientific debate when we
make science-based decisions in public health agencies, and we
have to do our best. And we are working to improve how we
handle those disagreements to make sure that both sides are
able to articulate their views and that we document our
position in relation to those views and move forward and make
our decisions.
Ms. Schakowsky. I am out of time. Thank you.
Mr. Pallone. Thank you. Mr. Ferguson.
Mr. Ferguson. Thank you, Mr. Chairman. Thank you both for
being here, and thank you for your testimony. Dr. Galson, I
have a lot I want to try and get through, and I am just going
to try and get through it as quickly as I can. I appreciate
your cooperation as well.
As you are aware, I have been interested in this issue of
regulation and distribution of medication guides, med guides,
for a while now. I want to focus my time today on this alarming
situation in which young patients and their parents may not be
receiving the information that they need to make fully informed
decisions about the treatment of certain medications,
particularly including antidepressant medications.
Specifically, it has been brought to my attention by
constituents in New Jersey that the FDA-required med guides are
in many instances not distributed when antidepressant
medications are dispensed, even though such a distribution is
required under the regulations introduced by the FDA, by your
agency. In examining this issue, I contacted the FDA
representative from the National Association of Chain Drug
Stores, the National Community Pharmacists Association, the New
Jersey Pharmacists Association, the New Jersey State Board of
Pharmacy, and four different drug manufacturers of these
products, of antidepressant medications.
In fact, I have two letters that I sent to Dr. von
Eshenbach and the two responses that I received from the FDA.
Mr. Chairman, I would ask unanimous consent to submit them for
the record in this hearing. It has appeared to me throughout
this investigation that a significant breakdown is occurring
between the FDA and the State regulatory authorities, a
breakdown that is depriving parents of children for whom
antidepressant medications are prescribed, that their ability
to make these fully informed decisions, to have all the
information they really need. And med guides are so important
because it gives us information in English that normal people
can understand.
For example, it is impossible to determine with certainty
that the med guides are in fact being distributed with the
prescribed antidepressant medications because regulatory
authorities at the Federal and State levels are not enforcing
the FDA's Stated protocol on medication guides. I am going to
just read the portion of the statute that is relevant here, and
I quote,
Each authorized dispenser of a prescription drug product
for which a medication guide is required under this part shall,
when the product is dispensed to a patient or to a patient's
agent, provide a medication guide directly to each patient or
to the patient's agent unless an exemption applies under
208.26.
Did the FDA issue this regulation?
Dr. Galson. Yes.
Mr. Ferguson. Yes. Thank you. Can you or anybody tell me
with certainty that medication guides are being distributed to
patients and parents when they ought to be?
Dr. Galson. Right. I know you are in a hurry. I will be
quick.
We have invested a huge amount of time in determining what
should be in these medication guides. Every word is looked at
very, very carefully because we want these messages to get to
patients. So let me make it easier for you and tell you that we
share your concern and we are not denying this. We know that in
many cases, these medications are not being given out. The
challenge, like so many things at FDA, is what is the best
thing to do about it. They are required to be given out. On the
other hand, we don't regulate the practice----
Mr. Ferguson. Right, and we are going to get to that right
now.
Dr. Galson. Yes.
Mr. Ferguson. I appreciate your----
Dr. Galson. So it is really our interaction with the States
and the pharmacy organization.
Mr. Ferguson. That is exactly right. In my investigation, I
also contacted the New Jersey State Board of Pharmacy, and I
got this response from Joann Boyer, who is the board's
executive director in New Jersey, and I quote,
The board does have the authority to enforce the Federal
regulation regarding the distribution of these guides. An
overview of this Federal regulation will be included in the
Board of Pharmacy newsletter with a statement addressing the
need to be compliant and the fact that our inspectors will be
including this item in their normal inspection routines. I will
provide the inspectors with all necessary information regarding
medication guidelines and instruct them to ensure compliance
when they perform their inspections in our retail pharmacies.
Those pharmacies identified as being noncompliant will be
brought to the board's attention for review and action, which
may include financial penalties.
Before my inquiries, States like New Jersey were not using
their authority to monitor pharmacists and their distribution
of medication guides. Does the FDA have the authority to
contact and instruct State board of pharmacy to follow New
Jersey's example?
Dr. Galson. We certainly don't need any special authority
to contact the board of pharmacy and encourage them to action.
What we have heard from some of the people that we have
contacted is that they consider the regulations that we have
onerous, that there is a lot of paper, that they don't have the
capacity to store all the paper that is required to be given
out, and that there are some real logistic issues.
Mr. Ferguson. Right.
Dr. Galson. And it is because of this that we have
organized and announced a public meeting coming up this spring
so we can get the views of all the constituents involved with
pharmacies and States, hopefully the patients.
Mr. Ferguson. That is where I am going next.
Dr. Galson. They will come with suggestions----
Mr. Ferguson. We didn't even coordinate this, but that is
where I am going next.
Dr. Galson. Absolutely, yes. We agree this is a problem.
Mr. Ferguson. I would urge you to use the authority that
you say you don't even need, I would urge you to take those
actions to contact State boards of pharmacy because there are
actions that they could be taking to make sure that parents and
patients get these very important information.
Moving on, I have heard from pharmacists in our district
and elsewhere that they encounter problems getting the med
guides, as you were just saying, from manufacturers and storing
the adequate numbers of the med guides in their stores. Shelf
space can become an issue. Under the FDA's rule, medication
guides must be generated by manufacturers, then sent to the
pharmacists, in most instances via a wholesaler and then given
to the patient when the drug is dispensed.
Is the FDA monitoring whether manufacturers are actively
providing these med guides to pharmacists so they can dispense
them to patients? Is that something FDA does?
Dr. Galson. We certainly could do that. I would have to get
back to you. I don't know for sure whether there have been any
compliance or inspectional kind of activities specifically
focused on that.
Mr. Ferguson. If it not going on, I would urge the FDA to
take that step. That is another potential breakdown, and in
some cases I am sure has been a breakdown in the system. Does
the agency also monitor whether manufacturers of generic
versions of brand name drugs are distributing these as well?
Dr. Galson. They are required to give out the same forms as
the brand names.
Mr. Ferguson. OK, so they would be included in this
oversight as well? In our investigation, the National
Association of Chain Drugstores told me that they delivered a
proposal to the FDA 2 years ago, asking if they could
distribute med guides electronically, thereby greatly
simplifying the lengthy and unreliable distribution chain. Can
you tell me if the agency will allow pharmacists to print these
electronically, just sort of print them off the computer rather
than having to store reams and reams of paper in their
pharmacy?
Dr. Galson. Yes, this is one of the issues that we are
going to take comment on and talk about at this public meeting.
I am not certain whether the electronic provision of an
identical medication guide to the one that we require companies
to put out, I suspect there is no problem with that. The
problem is that the format sometimes changes. It is different,
and we have to look at those issues.
Mr. Ferguson. My time is almost up. I understand in my
letter from the FDA that you will be holding a public meeting
soon to discuss the distribution of medication guides. I am
delighted. That is a very important part of the process. I am
pleased the FDA has taken that important step.
My last question. In the last week, the FDA has drafted
many changes to the med guide for antidepressants, and I have
copies of each of the two. Most strikingly, the title of these
med guides was changed. The previous one said ``Medication
Guide about Using Antidepressants in Children and Teenagers.''
That title has changed, and I would like to submit both of
these for the record under unanimous consent, Mr. Chairman. It
was changed to ``Medication Guide: Antidepressant Medicines,
Depression, and Other Serious Mental Illnesses, and Suicidal
Thoughts or Actions.'' Just seems to me that the old version of
the medication guide was more thorough and sort of concentrated
exclusively on the potential adverse reactions that could occur
when taking antidepressants. The new version seems to sort of
delve into a whole discussion on depression. Can you tell me
why? Do you have any idea why these changes were made in that
way?
Dr. Galson. Yes, I have a very good idea, and it is not
easy to explain. If you could give me just a few minutes to do
it. This has been one of the most contentious and difficult
areas of drug regulation over the past few years in FDA but not
atypical in that new information has been developed about
potential risks related to these products since they have been
on the market, and those are the risks that are discussed in
the med guide with suicidality.
Now, we have taken steps going back a number of years to
add information to the labels and to the med guides, making
sure that patients and physicians are aware of this new
information and what it may mean to patients. And what we have
heard is some people think that this is great. Other people
think it is bad.
The psychiatric community, the American Psychiatric
Association has been very, very angry at the FDA because they
think that telling people about these risks is dissuading
people who really need these drugs for depression from taking
them and therefore contributing to the number of people that
are expressing suicidal activity. And this is, of course,
something that worries us a lot.
What we try to achieve in our communications products is to
balance benefit and risk, which is what is absolutely critical
in explaining the risks and the benefits of drugs so that
people can make the decisions. So what we have attempted to do
with these latest changes in the med guide is not to
excessively focus on the risk but also talk about the balance
of what these drugs are for, the risks obviously of feeling
suicidal, and to make sure that people understand.
And I know that it is a more complex task, but this isn't
an easy goal to communicate. We are working. We continue to
work with experts on how to communicate with patients and with
physicians, and we hope to continue to improve the messages
that we are getting across, the points we want to.
Mr. Pallone. Thank you. The gentleman from Texas, Mr.
Green.
Mr. Green. Dr. Galson, thank you for being here and
listening to all our opening statements before we could
actually ask questions.
It is correct that the FDA currently does not have the
authority to grant conditional approval for a new drug
application. Is that correct?
Dr. Galson. Yes.
Mr. Green. Can you comment on how the extension of your
authority to implement a conditional approval process would
offer the FDA additional tools to ensure that drug's safety.
Dr. Galson. Well, that is something that would have to come
from you all from Congress to do that. We are implementing a
new pilot program, in the center to look back at drugs a year
or 18 months after they are approved to see whether new
information that has been developed about them changes the way
that we balance benefit and risk and may require us to
communicate about changes.
Mr. Green. So would this stand in the place of a post-
market study, or would it just be implemented a second way----
Dr. Galson. What this pilot project does is it takes the
information that is available from the reports that have been
submitted by companies from adverse event reports from any
information that has been developed in literature, and it has
us do an additional benefit/risk assessment to see whether
there has been any change and to see whether there are changes
that are required and how we communicate. If there is a post-
marketing study that has to happen, it wouldn't influence that
one way or another.
Mr. Green. OK, in your testimony, you indicated that the
responsibility for correcting many of the organizational
problems has fallen on you and your position. Can you expand on
your efforts to focus on the drug safety within the center,
particularly what protections as the FDA put in place to ensure
that any analysis of post-market data by the Office of Drug
Safety is accepted and acted upon in a timely manner? Is there
a process going on now?
Dr. Galson. Yes, there is a process going on now, but as
you have heard before, there is a challenge to making sure that
the decisions that we come out with at the end of the day
reflect the best possible input that we receive from people
across the center. And what I have heard is that some people in
the process sometimes feel undervalued. And my goal is to make
sure that that doesn't happen, that we improve that situation,
and that the people from all the different perspectives in the
center have those perspectives considered. If there is a
disagreement, it comes to light so that we can make sure that
the more senior people are the people that have to make those
decisions, can weigh the evidence on each side and come out
with the right decision.
Mr. Green. I think from our hearings in the Oversight and
Investigations Subcommittee, that is what we are hearing, that
there has been a discrepancy, and some of the FDA employees
feel like that their statements or status wasn't considered. So
I appreciate that.
Let me ask you a specific issue. I am concerned about the
safety of signing both the approval process and the post-market
surveillance. On the approval side, there is an issue that has
come up about safety issues and particularly surrounding RHLF,
recombine human lacto-ferin, which has been widely studied for
treatment of serious illnesses, including cancer. On the drug
safety side, I think that is on the drug side, but I also
understand there is a potential for using that as a food
additive. And I have some concerns because the food additives
are not as rigidly controlled as a pharmaceutical. Can you
speak to that issue?
Dr. Galson. Well, in general--and I don't want to refer to
a specific product that is under review--but in general, of
course, we don't want drugs to be put in food. And that would
concern me a lot. This particular product is a natural product
and, as you may recall a number of weeks ago, that the deputy
commissioner, Dr. Woodcock, came and testified to you about
follow on protein products.
We have to make sure that if there are products entering
the marketplace, they get the appropriate types of medical and
other testing that are necessary to make sure that we
understand well what the impacts are going to be. This sounds
like it is a very complex regulatory matter between the food
side and the drug side, and we will have to have our legal
experts look into that and follow through on it.
Mr. Green. But the concern is that using it as a food
additive, the regulation and the oversight is much less as
making that an actually prescription drug.
Dr. Galson. Yes. Well, we have to follow our procedures,
but just in general, as I said, the idea of a drug being in the
food supply doesn't strike me as a great idea.
Mr. Green. I agree, and that is my concern. Thank you, Mr.
Chairman. I yield back my 6 seconds.
Mr. Pallone. Thank you, and we have the other gentleman
from Texas, Mr. Burgess.
Mr. Burgess. Great, I will take the extra 6 seconds. Dr.
Galson, Dr. Crosse, thank you both for being here with us. Dr.
Galson, let me ask you, you mentioned in your testimony the
importance about communicating and drug safety and the emerging
data on drug safety. Do you get an annual report from a
manufacturer every year on the anniversary date of introducing
a new product?
Dr. Galson. Yes, we do.
Mr. Burgess. So we consider that post-marketing
information?
Dr. Galson. We get a huge amount of post-marketing
information.
Mr. Burgess. But that report on the anniversary date, would
that be fair to call that post-marketing information?
Dr. Galson. Of course.
Mr. Burgess. So how do you utilize that?
Dr. Galson. Well, we look at those reports. There is a
specific requirement that companies let us know about any
serious and unexpected adverse events. And those are the ones
that we spend the most time looking at very carefully to make
sure that what we aren't seeing is a new emerging kind of risk
with the product that we wouldn't see before.
So we look at those. We combine it with almost half a
million adverse events reports that we get that come into our
spontaneous reporting system, separately from that. And we have
safety evaluators look at those data and then meet with other
staff if there is a concern that is developing.
Mr. Burgess. So you would regard this information as
helpful?
Dr. Galson. Yes.
Mr. Burgess. And you have developed the computer algorithms
and protocols to help you sift through all that voluminous
information?
Dr. Galson. We need to do a lot more in that regard, and we
are moving forward but it is--yes.
Mr. Burgess. Let us come back to that thought if we have
time, but there is also a lot of information that is just out
there in the--we might call open source information that is not
necessarily the purview of the FDA or even necessarily the--
well, we could reference the CMS database, and I am sure NIH
has their own databases and their private databases. Do you
peruse those sources for information about products,
particularly when something has come to your attention?
Dr. Galson. We look at any available data. I do want to
emphasize though that the number of staff that we have been
able to devote to this activity traditionally has been limited
by our resources, and that is why we have been working through
the user fee program with Members of Congress to beef up in
particular that part of our operations so----
Mr. Burgess. Since you brought that up, so how many FTEs do
you devote to that? Can you tell us?
Dr. Galson. Well, it is difficult to say but----
Mr. Burgess. Perhaps you can provide it after the fact--the
number of people who are actively working on that and in an
ideal perfect world what that number would be so this committee
could perhaps deal with that----
Dr. Galson. We will get it to you.
Mr. Burgess. The stuff that is it the open source, do you
ever go out and purchase information from private sources?
Dr. Galson. Yes, we do.
Mr. Burgess. And is that important?
Dr. Galson. Extremely important and will be more important
in the future.
Mr. Burgess. And does funding play a role there? Is price
important? Is price a benefit for purchase of that private
source information?
Dr. Galson. Price has been important, so that is another
way that I am looking forward to more progress.
Mr. Burgess. Could you possibly again provide us with some
actual data on the specifics of what we are talking about so we
perhaps could make informed decisions?
Dr. Galson. Yes.
Mr. Burgess. And I know in the past, you brought up the
question of tension. The folks that do the pre-market and the
post-market testing and the tension that exists between them.
Is any of this--and I worked in offices. I am well aware of the
front office/back office tension that is going to occur. But is
any of the tension related to any perceived financial impetus
that is placed on either hastening the approval or
strengthening the post-market surveillance? Does that enter
into the equation at all? Is that something this committee
needs to be concerned about?
Dr. Galson. Well, I haven't seen any evidence----
Mr. Burgess. Well, let me change the context a little bit
because it keeps coming up, and I think that it is a good idea.
And I think it is something that we should continue to do, but
this concept keeps coming up. It is fair to ask the question is
this a problem? Is this entering into the tension equation that
you referenced? And if so, could you help us quantify it? And
could you help us by providing areas where--if that is an
issue, and I don't know that it is--but if it is, how can it be
mitigated? How can it be qualified?
Dr. Galson. Yes, I may have misunderstood you. You mean the
disparity in funding issue, but that is a factor if that is
what you mean. I am not sure what you mean by financial.
Mr. Burgess. The theme keeps recurring that there is a
problem with how the FDA does its work because of undue
influences that are placed on it by outside industry because of
the funding mechanism, and I don't know. Is that the situation
or not?
Dr. Galson. I wanted to make sure I understood what you
were saying.
Mr. Burgess. Is that a source of the tension that you
alluded to?
Dr. Galson. I don't think so. There are 2,300 people in the
drug center, and no matter which office they are in, they are
very, very dedicated to doing the right thing for public health
regardless of where their source of funding is. Individual drug
reviewers don't know if their salary is coming from user fees
or from appropriations. I haven't seen any evidence that that
is a factor.
Mr. Burgess. Thank you. That is a very direct answer, and I
appreciate that. Mr. Chairman, I will yield back.
Mr. Pallone. Thank you. Ms. Eshoo.
Ms. Eshoo. Thank you, Mr. Chairman, and thank you, Drs.
Galson and Crosse for your testimony and the answers that you
have given to the questions that have been posed by my
colleagues. I want to make a couple of comments before I ask my
questions. Number 1, the whole issue of advertising, of drugs.
I can't help but think it is kind of in the middle of this. I
mean the heavier something is marketed, the more pressure there
is to buy, and obviously, this pipeline to examine and for
efficacy and then the pressure that I think justifiably is
brought on the Congress and the agency for post-market
surveillance.
For the life of me, I really don't know what good
advertising has done except for, I mean for corporate reasons
to market. And I can't help but think that we should revisit
this. We should take a look at this and not only examine, in my
view, the genesis but all the issues that surround it. To see
someone skipping through a meadow, and the tagline being buy
such and such a product. I remember my mother used to say,
``what is it that they are advertising here?'' So I think that
we should take a look at that.
It is curious to me of the whole issue of reimportation
being raised by Members here. I have always thought that it was
a very important issue, and there is the bastardization of
drugs by others and the attempt to bring them into the country.
But I also think it is a political curiosity about what the
Congress did in the name of trying to save money to bring other
drugs into the country. I never thought that was a good policy.
I didn't support it. I don't support it now, and I think that
we have our hands full because there is more and more coming
into the country. And we have to take a look at what to do with
it.
Now, my questions. In your testimony, Dr. Crosse, you found
that FDA's access to post-market clinical trial and
observational data is limited by both resources and by
authority. This is a softball issue, but do you think that the
FDA should have such an authority?
Ms. Crosse. Yes, we do. We have recommended to Congress to
do that.
Ms. Eshoo. Right. Now, would the administration's PDUFA for
a proposal include this authority, and specifically what types
of post-market observational and clinical studies will FDA be
permitted to exercise under the administration's plan?
Dr. Galson. Right, in our PDUFA proposal and in the
legislation that is on the Hill, we will get important new
sources of resources----
Ms. Eshoo. Does the Waxman-Markey legislation match what
the administration has proposed?
Dr. Galson. I don't believe it does.
Ms. Eshoo. It doesn't?
Dr. Galson. Yes, I am not an expert.
Ms. Eshoo. OK. One, I think, is stronger than the other?
Dr. Galson. I believe so, yes.
Ms. Eshoo. OK, so it is Waxman-Markey that is the stronger
of the two. I think we should know that. I mean in my view it
is. Do you agree?
Dr. Galson. It depends which provision specifically you are
talking about here.
Ms. Eshoo. Well, overall, is it weaker or is it stronger?
Dr. Galson. I don't like that characterization.
Ms. Eshoo. OK, I think we know what the answer is here. All
right. Now, thank you. I want to go to something that I feel
strongly about, and that is health information technology. Your
testimony, Dr. Galson, indicates that an additional $4 million
is adequate to upgrade FDA's current drug review system. Is it
really? I mean what is an additional $4 million going to buy?
And how long will it take to go to full implementation?
This is about, my colleagues, I think this is about expeditious
review. I mean I don't know. Someone is sitting in a back room
and going through this sheet by sheet. Or is it all part of a
technology system? First of all, what is the $4 million going
to buy? Is it really enough, and how soon does that get the
agency to full implementation?
Dr. Galson. We are in the middle of a very rapid
transformation from a paper environment to--there are some
areas, depending on what you are talking about, where the
technology is there.
Ms. Eshoo. Help us. We want to help you accomplish this.
So what is the $4 million going to buy?
Dr. Galson. The $4 million is helping us move from a paper
system to an electronic system.
Ms. Eshoo. How much of the system is still paper, using
percentages?
Dr. Galson. A lot of it is still paper.
Ms. Eshoo. But give me--come on.
Dr. Galson. I think we are getting about half of all our
applications in by paper, but again that is from the
pharmaceutical industry. We need to get there faster.
Ms. Eshoo. I think we need to revisit this, and I think
that you are tremendously low balling the amount of money that
needs to be invested in this. We should really take a look at
it. You tell us what you need to move to full implementation
and over what period of time. $4 million, my sense is,
represents snail's pace.
Dr. Galson. We will be happy to get you there.
Ms. Eshoo. OK, good. Thank you, Mr. Chairman.
Mr. Pallone. Thank you. Mr. Murphy.
Mr. Murphy. Thank you, Mr. Chairman. Doctor and Doctor, I
don't know if you heard some of my opening comments about my
concerns about the breadth of the kind of warnings and comments
made when FDA approves a product. That currently it is one that
focuses, I think, a lot of the other reactions and things, but
part of my concern as a psychologist, at least when it comes to
psychiatric medications, particularly pediatric ones, that I am
concerned that 75 percent of drugs are prescribed by non-
psychiatrists and that oftentimes there may not be coordination
with other people providing consultation with the family and
therapy, et cetera. What kind of actions does and can the FDA
do to make sure that the proper use of the medications and not
just prescribing them is part of the plan?
Dr. Galson. Right. We, as you know, we don't regulate the
practice of medicine. So what goes on in the prescribing room
and all sorts of other questions having to do with the way
physicians work is not under our purview. But what we do do and
what we are very, very committed in is making sure that
physicians have the best possible information as quickly as
possible when we develop new recommendations or new views about
safety and efficacy, the benefit and risk of products.
And we see our role here in making sure that the
information accompanying products, the information that is
available to the public, is as accurate as possible. We also
work with professional organizations, the people who provide
different, some specialty organizations. When there are issues,
we bring them in. We talk to them, so that is the way that we
work with the medical community, but we don't actually have
regulatory authority over that operation.
Mr. Murphy. Dr. Crosse, do you have some comments on that?
Ms. Crosse. No, we are well aware that this is an issue for
the FDA and that many of the problems that have arisen with
drugs and some of the post-marketing safety concerns that have
arisen have been in instances where medications have been
prescribed that are not in accordance with the label
indications or for populations for whom they are not indicated.
And FDA, in a number of instances, has taken additional steps
to try to add warnings to the labels of those drugs to try to
put out information to the public and to try to put on some
other kinds of controls on who can prescribe these medications.
But it remains a problem of great concern.
Mr. Murphy. Certainly, Dr. Crosse, you are involved with
some of the labels and some of the information that goes to
physicians on things even though you can't regulate them and
tell them who has to do it. When it comes to some of these
psychotropic medications, however, what kind of commentary goes
into the warnings, et cetera, with regard to, I guess, the pool
of knowledge someone should have or that medications should be
used in conjunction with other types of treatment.
Dr. Galson. Well, we have a team of people who are experts
and psychiatrists who look specifically at the labeling and the
information that we provide to the public about that kind of
medication, as we do oncologists for cancer drugs. And we get
together, and for a new drug, we look at the information that
is available from the clinical trials.
And we determine the best way to communicate about that,
having to do with the dose, having to do with
contraindications, other types of warnings or precautions,
concomitant diseases that may affect the use of the drug. And
we endeavor to make sure that all that information is put
together in the drug label, and if there are special ways that
that has to be communicated, we will get together and discuss
that as well.
Mr. Murphy. But is it done, again the psychotropic
medications, where it is described that the medication--the
volumes of research indicate it should be done, provided, in
the context of a sort of structurally trained psychotherapy and
monitoring these cases, No. 1. The second issue is that in many
cases, I don't know if these drugs are really evaluated on a
pediatric population.
What is done to communicate those issues of the full
spectrum of treatment under which these medications seem to
work best?
Dr. Galson. Our authority doesn't, in most cases, extend to
some of the things that you are mentioning. When we do think
that there is a drug that has such severe risks that we think
that only a physician with a certain kind of training should
give it. Or there is a drug, for example, that has risks that
we think it should only be administered in a hospital, we can
require that.
Mr. Murphy. Well, I am not saying just in terms of who
prescribed it, but also other components of therapy that go
with that. Many medications may have other side effects. Take
insulin for diabetics. It is not enough just to say here is the
insulin, but it should be used in accordance with a strict
dietary and exercise information.
Dr. Galson. We can put that information in our labels, and
we do all the time.
Mr. Murphy. I am not sure that is done adequately when it
comes to psychiatric medications, especially when it comes to
recognizing a lot of these medications have not really run
through proper trials on a pediatric population.
Dr. Galson. Right. We have under our authorities to require
and to urge that studies be done in pediatric populations. We
have succeeded in having more of the studies looked at for
younger age groups, but there is no question this is a
challenge.
Mr. Murphy. I would hope, Mr. Chairman, as we pursue this
because our culture is becoming so much giving kids drugs, and
it is amazing how many youth are given drugs for psychiatric
reasons to quiet them down, to stabilize them. And the almost
explosion of diagnosing these things. I really hope this is an
area that you continue to investigate. Thank you very much.
Mr. Pallone. I appreciate your comments. I agree with you.
I recognize the gentleman from Massachusetts, Mr. Markey.
Mr. Markey. Thank you, Mr. Chairman, and again I appreciate
your giving me this opportunity. Mr. Galson, Mr. Waxman and I
have introduced the House counterpart to the Kennedy-Enzi drug
safety legislation, which includes many of the recommendations
of the Institute of Medicine and GAO. And we are hopeful that
it will be included as part of PDUFA reauthorization on the
House side. So Dr. Galson, if I may, my wife is a doctor. So I
apologize for calling you mister.
Dr. Galson. I am a doctor.
Mr. Markey. Doctor, yes, I apologize. Let me begin with
you. In response to Chairman Pallone's questions about clinical
trials, you stated that there has been tremendous improvement
in registration of clinical trials. However, companies aren't
in 100 percent compliance with registration of required trials.
Is that correct?
Dr. Galson. I am not sure that is exactly what--you are
quoting my response from just a few minutes ago?
Mr. Markey. Yes, they are not in 100 percent compliance.
Dr. Galson. I would have to look specifically at the rules.
What I believe I was trying to convey is that not all the
detailed information that some people think should be put on
public databases, going down to patient-level data, is on
there. I am not aware of compliance issues.
Mr. Markey. OK, would you agree that if registration is not
mandatory and the FDA does not have any enforcement mechanisms
to require registration, that we will never get 100 percent
compliance?
Dr. Galson. I don't know really and wouldn't want to
speculate.
Mr. Markey. And I appreciate that.
Dr. Galson. Yes.
Mr. Markey. If we are trying to ensure that we know about
all of the trials that have been conducted on a product after
phase one and eliminate the problem of selective disclosure of
trial results, which can give the public a distorted view of
the risk of benefits of the drug getting most of the trials
doesn't really fix the problem because the trials the companies
are registering may be the most important for the public to
know about. By only selecting the answers that you want to
give, the public might be denied information that could be
useful, or the physicians could be denied the information. Do
you agree with that?
Dr. Galson. I agree that it is very, very important when
there is a marketed product, if there is a clinical trial that
is done that is relevant to patient care and drug safety, that
it is important that the information that could have an impact
on whether patients and physicians want to use a drug, that
that be available.
Mr. Markey. OK. And, Dr. Galson, some people have raised
the concern that emphasizing post-market safety could slow down
the approval process. However, it would seem to me that if FDA
is confident in its ability to detect and manage problems after
approval, then the FDA should actually be able to approve the
drugs faster even if there are some lingering questions about
the safety preapproval because there will be a strong system to
monitor and invest those issues, if necessary, after the drug
is on the market.
Do you agree that having a stronger post-market safety
system, a safety net if you will, is important to giving the
FDA the confidence that they don't have to catch everything
pre-approval because the approval is not the last chance to
address the safety issues.
Dr. Galson. That is a complex, multi-part question. Let me
just say starting that it is not possible to catch everything
with the current state of knowledge. If we want new products
for patients who need them, we are going to sometimes find out
things after approval that we didn't know when the drugs were
approved.
Mr. Markey. So the point I am making is don't you think a
stronger post-market safety system would give people more
confidence?
Dr. Galson. Yes, I am a very strong supporter of a stronger
post-market safety system.
Mr. Markey. OK, Dr. Crosse, in your testimony, you
described some major gaps that currently exists in the FDA's
post-market safety net system. In his statement, Dr. Galson
testified that the FDA's PDUFA proposals will transform the
drug safety system at FDA. Do you believe that additional
resources for post-market safety without additional authority
to require post-market studies and changes is enough to
transform the post-market drug safety program in FDA?
Ms. Crosse. We believe that additional authority is
warranted for FDA to give them all the tools that they need to
be able to effectively oversee this process.
Mr. Markey. How does FDA's current lack of authority to
require post-market studies affect the FDA's ability to assess
safety problems after a drug is on the market?
Ms. Crosse. I think it complicates and slows the
availability of information that is needed to be able to fully
understand certain types of problems. Absent certain types of
information, the agency often cannot make a determination
quickly or possibly even at all about what kind of action ought
to be taken.
Mr. Markey. I thank you. I think of it as a trainer for
tightrope walkers. Before the walker steps off the platform,
the FDA is in a strong position to make sure the walker will
succeed by requiring a harness, if necessary. But once the drug
is approved and the walker leaves the platform, the FDA can do
little to require protections if companies don't want to accept
them.
Knowing this, the FDA is unlikely to let products go if
felt a little wobbly. However, if the FDA had a strong safety
net in place to catch problems and prevent a major crash, the
FDA is more likely to feel comfortable in getting products to
patients who need them. That is what the Waxman-Markey safety
bill would do. It would create a strong but flexible drug
safety net, and it is something that, I believe, at the end of
the day is actually essential to having a good drug approval
system. I thank the chairman for allowing me that little extra
time.
Mr. Pallone. Thank you, Mr. Markey. That concludes our
questions, and thank you both for being here today. I thought
it was a very good questions-and-answers series. Let me just
say though that we are going to take a break before the second
panel goes in. We have 11 minutes left on one vote, and then
there will be three 5-minute votes after that. So figure about
half an hour we will be back and start with the second panel.
But we are now in recess. Thank you.
[Recess.]
Mr. Pallone. The subcommittee hearing will reconvene, and I
will ask the panelists to come forward and sit down. Welcome to
all of you. Let me introduce each of you actually. We have a
pretty large panel here today.
We will start on my left with someone from New Jersey, Lisa
Van Syckel, who is from Flemington, New Jersey. We are going to
have a video that she has brought us. And then we have Dr.
Ellen Sigal, who is chairperson and founder of the Friends of
Cancer Research. And Dr. Susan Ellenberg from the University of
Pennsylvania School of Medicine. She is speaking at the request
for the Coalition for a Stronger FDA. Dr. Caroline Loew, who is
senior vice-president for scientific and regulatory affairs of
the Pharmaceutical Research and Manufacturers of America. Diane
Thompson, who is vice-president for Public Policy and
Communications at the Elizabeth Glaser Pediatric AIDS
Foundation. She is speaking on behalf of the Alliance for Drug
Safety and Access. John Theriault, chief security officer and
vice president, global security at Pfizer. Dr. Sharon Levine,
associate executive director for the Permanente Medical Group,
speaking on behalf of the Kaiser Permanente Medical Care
Program. And Dr. John Powers, who is assistant professor of
medicine at George Washington University School of Medicine,
and I guess also at the University of Maryland School of
Medicine. So thank you all for being here today. We are going
to start with Ms. Van Syckel, and does the video go first, or
how does that work? We will do the video first? Now, we were
going to try to put it on the big screen, but it didn't work.
So we are using the TV. Thank you.
[Video shown.]
Mr. Pallone. First of all, let me thank you for being here
and for bringing us the video and relating your own story of
your daughter. I know it has got to be tough, but we really
appreciate your being here.
STATEMENT OF LISA VAN SYCKEL, FLEMINGTON, NJ
Ms. Van Syckel. Yes, it is very tough, and I just want to
make sure that no family ever has to endure what our family
endured. The FDA and pharmaceutical industry continues to
downplay the risks of antidepressants in children. They have
gone from causal low to increased risk and to most recently the
Johns study, saying that the benefits of antidepressants
outweigh the risks.
When we hear about increased suicide within the media, they
think that it is something that is very quiet. And that is why
I thought it was important to come and play the tape so
Congress can actually see it for themselves, hear about it,
because it is a violent suicide. It is not something quiet, and
I think it is very disturbing for this FDA to allow the
pharmaceutical industry to negotiate the labels that are placed
on antidepressant medications.
They should never be allowed to negotiate the lives of our
children, and I think that is what the very important issue
here is. And, Mr. Chairman, we have another serious concern,
especially in the State of New Jersey where infants are being
given antidepressant medications, not only antidepressants but
antipsychotics to medicate children as young as infants, 12
months. And we need to ask why.
So with the FDA and their failure to provide the medication
guides, which is an issue I have been speaking with Mr.
Ferguson, it is quite clear that the FDA is incapable of doing
their job and notifying the public of severe side effects. And
I am begging you, as parents from the State of New Jersey, from
district 6 and district 7, because I represent all of New
Jersey, we need an independent office of drug safety.
We need better control of direct consumer marketing, and we
need a better med watch program. I want to give you an example.
My brother had a severe condition and was critical, and a nurse
had stated to me--I said ``well, what about the side effects.''
And it was the particular drug Zocor. And she says you can
actually get the side effects from the television, from the
commercial. And I said to the nurse you are telling me, as a
caregiver, that I should look to the television, to a
commercial for side effects. That was ridiculous, and I said I
think you are saying that to the wrong person.
So I am really concerned as to the direct consumer
marketing. I realize they have a right to free speech, but
medical professionals should not be telling patients to watch
it on TV.
[The prepared statement of Ms. Van Syckel follows:]
Statement of Lisa Van Syckel
Mr. Chairman, members of the committee, thank you very much
for inviting me to testify at today's important hearing.
I would like you to hear how corporate greed, our woefully
inadequate mental health system and over-reliance on pharma-
psychiatry, and the little pink pill, Paxil, have forever
altered the life of my most precious gift from God, my daughter
Michelle.
Michelle was raised in a loving, stable home in the small
town of Dunellen where she participated in many community
events and was proud to be a girl scout.
In 1995 American Standard transferred my husband to their
European Division in Brussels, Belgium.
Michelle, who had always been an honor roll student,
attended St. John's International School in Waterloo. Michelle
traveled and explored many European countries. She became
fluent in the French language.
Our family returned to the United States in the summer of
1999. Our life, as we once knew it, would change dramatically.
Michelle began complaining of ill health and missed her friends
in Belgium. She was also upset over the declining health of her
grandmother.
In April 2000 Michelle continued to complain of ill health,
she was losing weight and had stopped eating. She was admitted
to Somerset (New Jersey) Medical Center's eating disorder unit,
where she was diagnosed with depression and anorexia nervosa
and was prescribed the antidepressant Zoloft. Within hours of
digesting Zoloft, she reported to hospital staff that she had
the urge to hurt and cut herself and two days later, again
reported she was uncomfortable taking the medication. Her
complaints were dismissed. Several weeks later, Zoloft was
discontinued due to dramatic orthostatic changes and
bradycardia. (very slow heart beat). Michelle became very
hyperactive and was diagnosed with a personality disorder. No
one apprised me of what was happening to her. She was fourteen;
I should have been informed.
In June 2000 Michelle was placed on Paxil. Within a few
weeks she began to self-mutilate with knives, razors and broken
plastic CD cases. She became verbally abusive and was
displaying extreme oppositional behavior, along with severe
insomnia, diarrhea, chest pain, weak muscles, and on a few
occasions vomited blood and had rectal bleeding.
In August 2000 the Paxil was increased to 40 mg along with
a diagnosis of major depressive disorder with psychotic
features.
In September Michelle's self mutilating behavior was
increasing. During one episode, she had inflicted over 23
wounds and cut the word ``die'' onto her abdomen. She became
violent and suicidal and was hospitalized because she was
deemed to be a danger to herself and others. Her Paxil was
reduced from 40 to 20 mg and Depakote was prescribed.
On October 6, 2000 my daughter Michelle attempted suicide
and became extremely violent. She assaulted her brother as he
was desperately trying to keep her from killing herself. He was
just 4 days shy of his 12th birthday. She then viciously
attacked three police officers and managed to escape from her
handcuffs twice. She was kicking, spitting and screaming
obscenities. She even attempted to kick out the rear window of
the patrol car. When they arrived at the hospital, it took five
men to place her in leather humane restraints. The next day
Michelle awoke dystonic and unaware of her surroundings. Again,
she became violent and had to be restrained.
Michelle was transferred to UMDNJ Behavioral Health. Paxil
was discontinued, but she was then prescribed Celexa and
Risperdal (what I didn't know then, but have since learned, was
that Michelle was placed in a clinical trial of these drugs
without my knowledge or consent). Within 36 hours, Michelle
again became violent and self mutilated. She was injected with
Thorazine for her out-of-control behavior.
Approximately two weeks later, she was released from UMDNJ
with a 3-day supply of medication (what I know now and didn't
know then, was that this was a very dangerous thing to do). In
an abrupt withdrawal, Michelle again became violent and
threatened to kill me. She thought I was the devil and told me
I was evil.
In April 2001 Michelle was removed from all psychotropic
medication. Recovery was a long, tedious process. Everything
Michelle endured while on the drugs was suffered through the
withdrawal process.
Michelle's Paxil-induced psychosis, self-mutilation,
violent, and suicidal behavior are gone now. What remains
upsetting is that the physical scars of her self mutilation
will be with her forever.
Michelle's beautiful smile and sweet disposition were
returned. Michelle never had violent and suicidal behavior
prior to taking antidepressants, nor displayed this behavior
after recovering from withdrawal.
I believe, without question, drug companies and their
apologists are putting a great deal of pressure on the FDA.
Despite all of the controversy and exposed failures surrounding
the FDA in the last few years, it appears that the FDA simply
cannot muster the guts to act without industry influence.
Absent this influence, there would be no reason why the FDA
wouldn't insist on label warnings for all ages on anti-
depressants. No doubt drug companies are a formidable force,
but the FDA must remember whose interests it is supposed to
protect. If it does not, the representatives of the people,
Congress, will have to step in and do it for them.
I would like to show you about a minute and half of a video
of Michelle and other families' children who have suffered
because the FDA failed to better warn the public about
dangerous side effects.
Legislative Suggestions
So that other families are saved from the tragedy and
heartbreak that my family and other families in this hearing
room have endured, I urge you to approve--as part of the must-
pass user fee legislation--the strongest possible FDA drug
safety reform legislation.
PDUFA: Break the ties that are distorting the FDA's
mission. First, on the extension of the Prescription Drug User
Fee Act (PDUFA IV), I know that the FDA needs the resources,
and more, that the user fees bring. The user fees need to be
continued, and expanded to provide more resources for safety.
But under the current law, the industry's user fee money
comes with a huge cost. It comes with detailed requirements to
serve the drug industry--and that is a cancer that is eating at
the culture and integrity, both real and perceived, of the FDA.
If anyone doubts that the user fees are having a corrupting
influence on the culture of the FDA, I urge them to read last
summer's poll by the Union of Concerned Scientists, to which
about 1000 of the FDA's medical scientists responded. Many
poured out their frustration at being pressured to approve
drugs on which they had serious safety concerns, and a number
cited PDUFA as an inherent conflict of interest. A recent study
by a group of Harvard researchers has found that drugs approved
just in time to meet the PDUFA time goals have many more post-
market safety problems than drugs which receive more review
time. An earlier study by Harvard Professor Daniel Carpenter
pointed out that the FDA's time-to-approve drugs was declining
in the years before PDUFA's first passage in 1992; the study
found that the FDA staff was being increased through regular
appropriations, and that every 100 person increase in staff was
resulting in a 3.3 month decline in approval times. I think
this study shows that while the FDA does need more resources,
it does not need the rigid framework of PDUFA.
This committee is famous for its tough oversight. I am sure
that you can make sure that the user fee money is well spent
and that the FDA continues to give priority, timely attention
to truly life-saving drugs. Therefore, I urge you to break the
entangling webs of obligations that come with the user fees and
just let the FDA use the fee money to do its job. Congressman
Hinchey has previously introduced legislation that would
achieve this reform.
Kennedy-Enzi (S. 1082), and Waxman-Markey (H.R. 1561)
The bill the Senate is passing makes important improvements
for safety. And in many ways, the bill by Representatives
Waxman and Markey is even better, because it
<bullet> requires a warning signal for the first 2 years a
drug is on the market (an important fact for consumers, since
the real test of a drug's safety comes once it is mass marketed
and used by the general population);
<bullet> requires a review of a drug's safety history after
7 years (important because only about half of a drug's side
effects and labeling changes are detected in the first 7 years
it is on the market);
<bullet> provides much more meaningful civil monetary
penalties than the Senate bill;
<bullet> protects the public from overuse of particularly
dangerous drugs by limiting direct-to-consumer ads for up to
three years; the First Amendment does not give the drug
companies the right to kill Americans, and moderation of ads on
a new drug with serious warning signs of danger should be one
of the FDA's tools;
<bullet> ensures that the results of all clinical trials
(other than phase 1 trials) will be made publicly available in
a timely manner.
To save other families from future drug safety disasters, I
urge you to take this best opportunity in the next five years
to pass this kind of legislation, and I urge that it be made
even stronger.
We need a better Adverse Event/MedWatch Reporting system.
The Senate bill includes a major new monitoring of huge medical
databases to detect quickly problems with drugs. It is said
that the problems with Vioxx might have been detected in about
3 months under such a system.
But I believe we also need to educate and involve the
American consumer more in reporting adverse events. Today, the
average citizen has no idea how or where to report a problem
with a drug. I urge you to require all drug ads to prominently
display a 1-800 number where problems can be reported. The FDA
should also start using the tools of the Internet and e-mail
to, with patients' permission, periodically query people who
are taking a new drug whether they notice any adverse
reactions. Instead of passively waiting for reports of trouble,
a modern FDA should be seeking out the areas of danger.
We need someone responsible and accountable for safety at
the FDA. I support a separate Office of Drug Safety in the FDA,
one that will be free of the control and overwhelming presence
of the Office of New Drugs.
The FDA Commissioner and many others have said that a
separate office would be duplicative, expensive, and hold up
approvals. If that is a problem, the same goal of
accountability for safety could be achieved by giving the head
of the Office of Drug Safety the power to call for a safety
action (a REMS adjustment in HR 1561). If the head of the
Office of New Drugs disagreed, the Commissioner would decide
between them, all within a week or so (so that there can be no
charge that we are delaying the approval of vital new drugs).
There needs to be a locus of safety accountability in the FDA.
This proposal, or a wholly separate office, would achieve that
goal.
No Conflicts of Interest (COI) in FDA Advisory Committees.
The FDA recently announced guidance that makes major
improvements in the Advisory Committee (AC) process: no
participation in an AC if one has over $50,000 in conflicts,
and participation in the AC, but no vote if one has any
conflict. I hope you will codify the FDA's action, but go
beyond it by requiring the active recruitment of COI-free
experts, and prohibiting those with conflicts from sitting with
the AC (they can testify, but they should not be part of the
camaraderie-building AC process where they can influence
outcomes even though they can not vote).
Thank you for your consideration of these legislative
ideas. If enacted, you could give the American people the FDA
they need and deserve.
----------
Mr. Pallone. Thank you. And we are going to ask you some
questions later, but thank you for being here today. I
appreciate it. Dr. Sigal.
STATEMENT OF ELLEN SIGAL, CHAIRPERSON AND FOUNDER, FRIENDS OF
CANCER RESEARCH
Ms. Sigal. Thank you, Mr. Chairman, members of the
committee. Thank you for the opportunity to testify today about
drug safety. It is an extremely important issue.
My name is Ellen Sigal. I am chair of Friends for Cancer
Research. Friends is a coalition of all of the major groups in
cancer research. Our mission is the importance of cancer
research. We represent patients, scientists, clinicians, cancer
center directors, and we care deeply about research.
The issue of drug safety is very personal to me. My own
sister died 21 years ago of toxicity of a drug for breast
cancer. So I know personally what this means. She left a 4-
year-old child. So this is a very important issue to me and to
all of us.
My testimony will cover four major points today that are
extremely important to the patient community and the science
community. Patients needs for life-improving therapies and a
crucial pipeline and access to drugs, providing additional
resources for FDA--you have heard that before, and you have
heard it here again--establishing a systematic routine and
easily accessible safety monitoring system, and finally
integrating science into the regulatory process, the critical
path initiative and the proposed FDA foundation. I also do want
to point out that the president of Friends, Molly Mallick, is
here today, and I thank her for coming here and supporting us.
Millions of other people have shared my experience and care
deeply about this issue of drug safety, just as Ms. Van Syckel
and others that you will hear today. So this is a concern that
the patient community cares about deeply. I am going to read a
quote from Meryl Wineberg, who is the chair of the National
Health Counsel. ``Speaking on behalf of 100 million Americans
with chronic conditions and disabilities, it is equally
important that patients whose quality of life or indeed life
itself are not deprived of the medications they need.'' I did
have other testimony for the record from the American Cancer
Society and other patient groups.
When the issue of drug safety was surfacing and it was
clear there were going to be hearings and legislation about
it--we are very research oriented at Friends of Cancer
Research, and we convened a group of experts in cancer and
outside of cancer, clinicians, scientists, epidemiologists,
patients, to look at the issue because we wanted to have an
informed position on this. And we wanted to make sure that we
looked at the position from a scientific point of view. We are
science oriented, and we thought it was important to have
clinicians, people that actually treat patients, weighing in on
this issue.
Our major recommendations--the White Paper is drug safety
and drug efficacy. I would like it to be submitted to the
record. Thank you. The paper highlights three major areas:
active surveillance, systems of the life cycle of a drug. We
don't have all the information up front in preclincal
environment. We really find most of it in post-surveillance.
Resources for the FDA and training, training for FDA personnel.
That is absolutely critical. The integration of science through
critical path, and the public/private partnerships. We can't,
as much as we need to fund FDA, and we support substantial
increased funding, partnerships through this critical path
initiative and this hopefully relief from foundation will be
critical to it.
We also think that we have to use existing networks, such
as the VA, Kaiser, Blue Cross and others. The database and the
information they have are critical. I want to read a quote from
the recent IOM report. The recent IOM report on drug safety
states ``to expect a pre-market studies or FDA review of these
studies can reveal all the information about the risks and
benefits of new drugs that is needed to make optimal treatment
decisions with occasion and reasonable delay in approval.''
Authority is fine for the FDA. We support additional
authorities. We do not support those authorities without the
resources crucial to make these informed decisions. FDA is a
chronically underfunded agency that is continually assigned
more responsibilities without matching resources. It is
unreasonable to starve an agency of the resources it needs yet
hold it solely accountable for protecting the health of
Americans.
One thousand five hundred people a day die of cancer. Four
thousand will be diagnosed today. They cannot afford to wait.
They need new treatments. Other patients with chronic diseases
need treatments too. They deserve better treatments and more
informed treatments. They should be safe, and they should be
effective.
The pipeline for these new patients is critical. They must
be informed and must have choices, and allow them to
participate in the process. Patients are crucial to the
process. Patient needs are not monolithic, nor do all patients
respond the same to a particular treatment. Only science and
evaluation of patients will really make us understand that and
why that happens.
In conclusion, we remain extremely supportive of the goal
to improve our drug safety system, and we believe that we can
best achieve this goal through a science-based approach, taking
into full account the voice and perspective of patients. We
applaud the committee for holding these hearings, and we
welcome further thoughtful policy discussions. Thank you.
[The prepare statement of Ms. Sigal follows:]
Statement of Ellen V. Sigal
Mr. Chairman and distinguished members of the committee, I
thank you for the opportunity to discuss the important topics
of drug safety and efficacy as the committee begins to take
important steps to strengthen FDA as part of the upcoming
reauthorization of the Prescription Drug User Fee Act.
My name is Ellen Sigal, and I am the Chair and founder of
Friends of Cancer Research. Friends is a non-profit
organization that over the past 10 years has pioneered
innovative public-private partnerships, organized critical
policy forums, educated the public, and brought together key
communities to develop collaborative strategies in the field of
cancer research. We are a coalition of major cancer groups
representing patients, researchers, physicians, and survivors.
It is our belief that a science-guided approach will best
enable us to improve drug safety and efficacy in this country.
We urge this committee and Congress to pursue a legislative
course that provides FDA with the resources it needs to conduct
systematic risk assessment across a drug's lifespan while
protecting patients' access to needed treatments. Specifically,
we believe that any legislative approach to strengthening FDA
must give priority consideration to:
<bullet> Patient need for life-improving therapies
<bullet> Providing additional resources for FDA
<bullet> Establishing a systematic, routine and easily
accessible safety monitoring system
<bullet> Integrating science into the regulatory process
through the Critical Path Initiative and the proposed FDA
Foundation
We all want the safest possible drugs. But we recognize
that no drug is 100 percent safe or 100 percent effective. We
also realize that each patient responds differently to
medication. Like the patients I speak on behalf of, and many of
you in this room today, I have encountered this reality in a
very personal way.
Twenty years ago, my own sister died of toxicity associated
with a bone marrow transplant to treat metastastic breast
cancer. She was 40 years old and left behind a 4-year-old
daughter. This was a tragic event that clearly changed my life.
While I hope that no one would have to go through such an event
themselves or with their loved ones, this was a risk that we
knowingly accepted based upon what was best for my sister at
the time.
As emotional as my experience was, I recognize that
emotions cannot be the guiding force behind decisions about
what treatments should and should not be available to patients.
We believe that a science-driven approach to drug development
and approval will help to ensure that each person receives the
treatment that is most likely to be effective and safe for
them.
In examining treatment options, all patients must weigh the
benefits and risks when determining their own course of
treatment. Legislation aimed at strengthening drug safety must
take care to preserve patients' access to a wide array of
treatment options while not impinging on the development of new
treatment options or removing existing options for patients in
need--bearing in mind that for many diseases, including many
cancers--patients still have few or no treatment options
available to them at all.
We are confident that increased funding for FDA and policy
that is grounded in science can achieve an optimal balance
between protecting patients and expanding treatment options. A
benefit-risk approach conducted across a product life cycle--
guided by sound and systematic data collection and careful,
regular assessment of a drug's safety and efficacy across
subpopulations, dosage levels, and other factors--is the
cornerstone of drug development and should be the foundation of
drug regulation.
In any treatment decision, consideration must be given to
the condition the drug is meant to treat as well as to the
extent of the patient's disease, its duration and its impact on
the patient's functional status and quality of life. Depending
on the particular illness, drugs can potentially be designed
for and used at a specific point in the continuum of disease
from prevention to terminal illness. Patients' needs are not
monolithic, nor do all patients respond the same to a
particular treatment.
Legislation should acknowledge the great variability across
diseases, patient preferences, and individual circumstances and
facilitate continued access to a wide array of treatment
options accordingly. Indeed, across the board, one need stands
paramount for patients--it is the need for more and better
options to fight disease and improve disability. We believe
that any legislative initiative that limits patient choice and
access to treatments in the name of safety would be
counterproductive and not achieve the goal of improving patient
outcomes.
As this committee considers ways to enhance the FDA's
ability to monitor drug safety to help patients make the most
informed decisions about their treatment options, it is of the
utmost importance that patient needs and voices be at the
forefront of discussions and that all decisions pertaining to
drug safety be driven by sound scientific data.
Dr. Jerry Yates, National Vice President of Research for
the American Cancer Society, describes a scientific foundation
for FDA:
``Based on the course of cancer--from prevention to
terminal illness--improving the science of safety will help
identify the proper balance between risk and benefit for each
stage of the disease and assure optimal investments in both
cancer research and the care of patients.''
This issue, of course, impacts not only the cancer
community, but the entire patient community as well. For
example, Myrl Weinberg, president of the National Health
Council, expresses her community's needs:
``Of course, prescription drug safety is of paramount
importance, and--appropriate measures should be taken to ensure
the public is not unnecessarily exposed to--potential harm.
However, speaking on behalf of 100 million Americans with
chronic conditions and disabilities, it is equally important
that patients--whose quality of life,--or indeed life itself--
are not deprived of the medications they need.''
Lauren Roberts, a multiple sclerosis (MS) patient who was
directly affected by the temporary removal of Tysabri from the
market, described her experience by saying:
``MS progresses on its own timetable, not the FDA's. In the
course of 90 days, there will be, on average, 2,160 more people
who hear the words, ``You have multiple sclerosis.'' My own MS
continues to ravage my body--Tysabri was the first and only
therapy that helped me--the small risk from Tysabri pales in
comparison to the risks created by not having Tysabri available
to us as a choice--As for me, I am willing to take that risk,
in exchange for having an improved quality of life, my life,
back.\1\
---------------------------------------------------------------------------
1 Roberts, Lauren. Multiple Sclerosis Patients v. FDA Over-Caution.
Washington Legal Foundation. May 19, 2006
---------------------------------------------------------------------------
FDA must have the best tools to make these important
assessments and effectively communicate with physicians and
patients as they together make individual treatment decisions.
New policy to expand the authority of FDA alone will not
sufficiently strengthen the agency. Simply put, FDA needs more
dollars from Congress. This is a chronically under funded
agency that is continually assigned more responsibilities
without matching resources. It is unreasonable to starve an
agency of the resources it needs, yet hold it solely
accountable for protecting the health of Americans.
Now, in a time when public perception is declining, user
fees are not the best answer. Due to the current budget
climate, user fees are a reality, but a strong FDA is an
investment in patient and public health. Congress should find
the money to invest.
Drug Safety & Drug Efficacy: Two Sides of the Same Coin
Several months ago, we convened an independent committee of
expert academic scientists and clinicians, research advocates,
and representatives of the patient community to examine and
recommend ways to further strengthen the agency and its product
evaluation process.
It is extremely important that the patient voice be heard
along with the perspective of expert clinicians experienced in
clinical trial design and translational research. The members
of this committee are distinguished experts in diseases such as
cancer, infectious disease, and diabetes. They are experts in
drug development but also have first hand knowledge in patient
care and patient needs. This is a vital perspective that cannot
be excluded from the drug safety debate.
I would like to thank Dr. Robert Young, president of the
Fox Chase Cancer Center in Philadelphia and chairman of the
board of Scientific Advisors of the National Cancer Institute,
for his leadership of the authoring committee. The resulting
document, entitled, ``Drug Safety & Drug Efficacy: Two Sides of
the Same Coin'' is a proposal for improving drug safety,
ensuring new drug access, and strengthening the FDA. I would
like to ask that a copy of the full report be submitted to the
record as an addendum to my testimony, and I would like to
briefly discuss some of the recommendations.
A Systematic Approach to Safety Surveillance
It is most important for patients that FDA continuously
evaluate both safety and efficacy when determining public
access to new products. At the level of medical practice,
safety and efficacy are always considered together by the
treating healthcare professional in the context of a patient's
specific circumstances and preferences. The regulatory process
should reflect this essential balance that is fundamental to
all medical decision-making.
Because it is impossible to know everything about a drug at
the time of approval, it is important to monitor the safety and
effectiveness of drugs as they are used in the general
population. To strengthen the effectiveness of the current
post-market system, the agency needs to develop and implement a
more systematic and automated approach to safety surveillance.
By utilizing drug safety and efficacy information from a
variety of sources, such as established healthcare networks
like Kaiser or UnitedHealth Group, the FDA could actively
identify, evaluate and respond to signals more efficiently. New
policy should shift the emphasis of drug safety away from
solely risk management, and instead focus upon systematic
benefit-risk assessment based on comprehensive and valid
information provided by the healthcare community.
Currently, a great deal of drug safety evaluation is based
upon the limited data available in the New Drug Application. A
locked focus on safety at this early point in a drug's life
cycle would increase the amount of pre-market data required,
with the likely result of stifling or unnecessarily slowing
patients' access to potentially beneficial medicine. The recent
IOM report on drug safety states, ``to expect that pre-market
studies or FDA review of these studies can reveal all the
information about the risks and benefits of new drugs that is
needed to make optimal treatment decisions would occasion
unreasonable delay in approval.'' \2\
---------------------------------------------------------------------------
2 Institute of Medicine of the National Academies. ``The Future of
Drug Safety: Promoting and Protecting the Health of the Public'' Sept.
26, 2006.
---------------------------------------------------------------------------
It would be far better to utilize available data mining
techniques and other potential new information sources to
identify unanticipated adverse events sooner following product
launch and adoption in medical practice.
New policy should focus on efficiently and accurately
identifying unexpected serious adverse events in a
scientifically rigorous manner. Once a serious signal has been
identified, FDA should have the tools to react in a proper
manner that will protect the public while ensuring responsible
access for patients who may depend on a particular drug. Such
an approach would benefit all stakeholders.
Enhanced Technology Infrastructure
With the proper resources to improve the technology
infrastructure, FDA could routinely and systematically evaluate
data from completed and ongoing clinical trials and registry
studies, perform useful epidemiological studies, and
characterize population subtypes and their response to
treatments.
In addition, greater ability to compare and combine data
across different sources would result in greater flexibility
and improved efficiency and the potential to generate novel
insights about vulnerable populations. This includes the
ability to share information regularly with the Center for
Medicare and Medicaid Services and with sister agencies within
the Public Health Service, including the National Institutes of
Health and the Centers for Disease Control and Prevention.
Increase Training and Personnel
Just as FDA needs enhanced infrastructure and information
systems, it also needs adequate personnel training to meet
emerging technology advances. Increasing the number of IT
trained staff is essential for the overall advancement of the
bioinformatics systems. As the agency strives to monitor and
evaluate the treatments of the future, it is imperative that
FDA have the resources to effectively manage and interpret the
wealth of information currently available.
FDA needs to attract and retain a greater number of
professional staff with the training required to perform
accurate benefit-risk assessment, evaluate new therapies and
implement scientific initiatives. As the FDA workload grows, so
too must the resources to recruit and increase staff with
critical competencies. Increased training of FDA personnel will
also enhance agency effectiveness and standards.
FDA experts could play an integral role in the development
of advanced clinical trial designs that achieve greater
efficiency and permit definitive conclusions to be obtained
more quickly. Such advancements to the current clinical trial
system could result in improved pre-market product evaluation,
smaller trial sizes, more efficient dosing determinations, and
ultimately, safer products reaching patients faster.
Integrating New Science through the Critical Path Initiative
As science progresses and new treatments emerge from
laboratories and clinics around the world, FDA must be equipped
to perform accurate and efficient evaluation and continue its
science-based tradition. It is imperative that resources be
devoted to increase the support for the Critical Path
Initiative to modernize FDA.
A central goal of the Critical Path Initiative is to
provide tools to identify patients who will most likely respond
to particular treatments, thereby improving the risk to benefit
ratio. As this is accomplished, there will be new ways to
diagnose, treat, cure or prevent disease and allow life-saving
therapies to reach patients faster while reducing the overall
cost of healthcare in the country.
Legislation introduced by Senators Kennedy and Enzi, and
recently considered by the Senate, would create the Regan--
Udall Foundation for the Food and Drug Administration. This
will establish a leading organization for the advancement of
the Critical Path Initiative and foster the advancement of the
science of drug safety through public-private partnership.
NIH initiatives and collaborative research partnerships
should place high priority upon the identification and use of
biomarkers to (1) determine the role of genetic polymorphisms
in causing drug toxicities; (2) establish effective strategies
for selecting patients for treatment with specific drugs and
(3) identify early biomarkers of drug benefit. The sub-
populations most susceptible to an adverse event could be
identified by detecting the presence or absence of a biological
indicator.
Further integrating science into the regulatory process
will aid researchers who design drugs, experts who evaluate
their safety and efficacy, health care providers who prescribe
medicine, and most importantly patients who will benefit from
continued medical discovery and more effective application of
new treatments.
Conclusions
In conclusion, we remain extremely supportive of the goal
to improve our drug safety system and we believe that we can
best achieve this goal through a science-based approach, taking
into full account the voice and perspective of patients.
Scientific advancements have led to better methods of disease
treatment, early detection and prevention, and such
technological advancements can translate to identifying safety
signals more accurately and efficiently.
Increased funding for the FDA will help the agency access
and utilize these tools to assess the benefits and risks of
medical therapies and, in turn, help patients make the most
informed decisions about the treatment options available to
them.
A wide range of treatment options should and must remain
available to patients. While we, of course, want safer drugs,
we caution against unintentional consequences that could remove
or slow access to valuable therapies without actually improving
their safety. Of even greater detriment would be discouraging
the future innovation of potentially life-saving new products
altogether.
We applaud the committee for holding this important hearing
and we welcome further, thoughtful policy discussions toward
ensuring that FDA has the resources and tools it needs to
advance the science of drug safety while it continues its
important work to evaluate and approve new therapies for
patients in need.
We look forward to continuing to work with all of you to
ensure that the lives and hopes of patients continue to improve
through sound, science-based, and patient-focused FDA policy.
Thank you for the opportunity to speak to you today. I look
forward to answering any questions you may have.
----------
Mr. Pallone. Thank you. Dr. Ellenberg.
STATEMENT OF SUSAN ELLENBERG, UNIVERSITY OF PENNSYLVANIA SCHOOL
OF MEDICINE, SPEAKING AT THE REQUEST FOR THE COALITION FOR A
STRONGER FDA
Ms. Ellenberg. Mr. Chairman and members of the committee, I
am Susan Ellenberg, professor of biostatistics and associate
dean for clinical research at the University of Pennsylvania
School of Medicine.
Prior to my current appointment, I directed the
biostatistics and post-market surveillance programs at the
FDA's Center for Biologics Evaluation Research from 1993 to
2004. I also recently served on the Institute of Medicine
committee on the assessment of the U.S. drug safety system.
During my career with the FDA, I was deeply involved in one
of FDA's most important functions, monitoring the safety of
medical therapies after they had been approved for marketing.
As such, I want to thank the committee for inviting me here
today to testify on the important issue of drug safety.
Although there are many aspects of drug safety that the
committee is looking at, I am going to speak particularly from
my own knowledge and experience about one aspect of FDA's drug
safety program that I feel most strongly about, and that is its
resource needs to carry out its congressionally-mandated
responsibilities.
As you know and as others have said today, there is no such
thing as a totally safe drug. All drugs pose some risk to
patients. Drugs are deemed safe when it appears that their
benefits outweigh their risks in a given population, safe
enough.
The approval for marketing a new drug or vaccine is only
the beginning of a drug's lifecycle. It is critical drugs be
monitored once on the market. Drug manufacturers', physicians
and the FDA continuously watch for signals that a drug poses
greater risks than originally believed or it may be unsafe in
certain patient populations, or require special restrictions to
control hazards that would otherwise cause FDA to remove it
from the market.
For some years now, FDA scientists have recognized a
growing resource imbalance between the agency's pre-market drug
review program and its post-marketing safety surveillance
capabilities. This imbalance has resulted from enactment of
Congress of the Prescription Drug User Fee Act, which has
greatly enhanced and enlarged FDA's pre-market drug review
program and a parallel lack of increased funding for FDA's
post-market drug safety program.
The recent Institute of Medicine report, ``The Future of
Drug Safety: Promoting and Protecting the Public Health,''
which I am sure many or all of you have seen, noted this
resource imbalance and concluded that our drug safety system
was severely underfunded. The User Fee Act has required the
drug review staff at FDA to grow steadily larger to allow much
more rapid review and approval of drugs than ever before. That
has been a great boon to the citizens of this country,
resulting in more new drugs to prevent and treat illness. But
the drug safety programs at FDA have received only very limited
increases in staff and funding, and thus these programs have
continually lost ground in their ability to monitor the rapidly
increasing number of new drugs on the market.
Further, the volume of adverse event reports submitted to
the FDA has increased steadily. As you can see on the monitor,
the numbers of reports of adverse events submitted to the FDA
has climbed so rapidly that they threaten the ability of drug
safety staff to review and process them effectively. And we
discussed this earlier, the various reasons. But in any case,
the numbers have gone up quite dramatically.
One of the initiatives of which I was most proud during my
tenure at FDA was a thorough reevaluation of FDA safety
monitoring systems, an effort commissioned by then Commissioner
Jane Henney. That assessment, which was completed in 1999,
resulted in a series of recommendations for major changes in
our post-marketing safety programs including, among other
things, intense monitoring of newly marketed products during
the initial period on the market, obtaining access to health
care databases, such as those of Medicare and the VA that we
have talked about today, developing a new active surveillance
capacity to complement existing passive surveillance system,
which also need to be improved, funding for research to improve
FDA's tools for monitoring the study of medical product risks,
more intense intervention such as stronger warning labels or
restricted distribution of higher-risk products, and funding to
conduct focus safety studies when needed.
Commissioner Henney's request for a substantial boost in
FDA appropriations to fund these recommendations unfortunately
were not successful. But these recommendations made by FDA
staff 8 years ago are very similar to the drug safety
provisions of the current Senate and House bills that are
currently being considered, and are entirely consistent with
the recommendations of the recent IOM report. If the necessary
funding had been provided at that time, the proposed programs
would be up and running today and might have permitted much
more rapid identification of many, if not all, of the recent
drug safety problems that we have been experiencing, meaning
far fewer individuals would have been exposed to excess risk.
And so, Mr. Chairman, I urge you to set as one of your
highest priorities this year provision of the necessary
resources to FDA's drug safety programs. I thank you very much
for inviting me to present my views.
[The prepared statement of Ms. Ellenberg follows:]
Statement of Susan S. Ellenberg
Mr. Chairman and members of the committee. I am Susan S.
Ellenberg. Prior to my current appointment as professor of
biostatistics and associate dean for clinical research at the
University of Pennsylvania, I directed the biostatistics and
postmarket surveillance programs at the Food and Drug
Administration's Center for Biologics Evaluation and Research
from 1993 through 2004. That Center, as you may know, is
charged with assuring the safety of biological drugs, blood and
blood products, and vaccines, and works closely with FDA's
other programs for approving and monitoring pharmaceuticals. I
also served on the recent Institute of Medicine Committee on
the Assessment of the U.S. Drug Safety System, and am associate
editor of Clinical Trials (the official journal of the Society
for Clinical Trials) and of JNCI (Journal of the National
Cancer Institute).
During my career at the FDA, I was deeply involved in one
of FDA's most important functions--monitoring the safety of
medical therapies after they have been approved for marketing.
As such, I wish to thank the Committee for inviting me here
today to testify on the important issue of drug safety, an
issue that the Committee will be considering this year as part
of its effort to reauthorize the Prescription Drug User Fee
Act. Although there are many aspects of drug safety that the
Committee is examining, I have been requested by the Coalition
for a Stronger FDA to speak in particular, from my knowledge
and experience, about one aspect of FDA's drug safety program--
its resource needs to carry out its Congressionally-mandated
responsibilities.
Background
As you know, there is no such thing as a totally ``safe''
drug--all drugs pose some risk to patients. Drugs are deemed
``safe'' when it appears that their benefit outweighs their
risks in a given population. The approval for marketing of a
new drug or vaccine is only the beginning of a drug's ``life
cycle.'' It is critical that drugs be monitored once on the
market--drug manufacturers, physicians and the FDA continuously
watch for signals that a drug poses greater risk than
originally believed, may be unsafe in certain patient
populations, or requires special restrictions that must be
imposed so as to control hazards that would otherwise cause FDA
to remove it from the market.
A Resource for Imbalance
For several years now, FDA scientists have recognized that
there has been a growing resource imbalance between the
agency's premarket review program for drugs and its postmarket
surveillance capabilities. This imbalance has been occasioned
by two developments: the enactment by Congress of the
Prescription Drug User Fee Act, which has greatly enhanced and
enlarged FDA's pre-market drug review program, and a parallel
lack of increased funding for FDA's postmarket drug safety
program.
The recent Institute of Medicine Report, The Future of Drug
Safety: Promoting and Protecting the Health of the Public, of
which I was a co-author, confirmed those internal FDA concerns
by concluding that our drug safety system was ``severely
underfunded.'' As the IOM report noted, the user fee act has
required the drug review staff at FDA to grow steadily larger,
which has allowed much more rapid review and approval of new
drugs than ever before. That has been a great boon to our
citizens, resulting in more new therapies that can prevent or
treat illness. But the drug safety programs in FDA have
received only very limited increases in staff or funding, and
in fact have been largely held to their pre-PDUFA levels. Thus,
FDA's postmarketing safety programs have continually lost
ground in their ability to monitor the rapidly increasing
number of new drugs on the market. Further, the volume of
adverse event reports submitted to the FDA has increased
steadily. As you can see from the attached FDA graphic, the
number of required reports from drug sponsors of adverse events
they received from physicians has climbed so rapidly that they
threaten the ability of drug safety staff to review and process
those reports effectively.
Resource Limitations Greatly Affect FDA'S Capacity
One of the efforts of which I was most proud during my
tenure at the Food and Drug Administration was a study
commissioned by then-Commissioner Jane Henney, in which she
charged senior drug, device and biologics officials with a
thorough re-evaluation of FDA's safety monitoring systems. That
assessment, completed in 1999, resulted in a series of
recommendations for major changes in our post-market safety
programs, including:
<bullet> Closer monitoring of newly marketed products,
particularly those for which safety ``signals'' suggest greater
risk
<bullet> Obtaining access to health care databases, such as
those of the Medicare program and the Veterans Administration
<bullet> Development of a new active surveillance capacity,
to complement the existing passive surveillance systems (which
would also be improved)
<bullet> Funding for epidemiological and methodological
research to improve FDA's tools for understanding medical
product risks
<bullet> More intense intervention in higher risk products
identified by postmarket surveillance as needing special
attention, such as stronger warning labels or restricted
distribution, and
<bullet> Funding to conduct focused safety studies when
needed
Commissioner Henney requested a substantial boost in FDA
appropriations to fund these recommendations, the
implementation of which would clearly have required a
substantial increase in FDA's safety surveillance staff, but
these requests unfortunately did not yield any additional
funding .
Ironically, those recommendations are very similar to the
drug safety provisions of the current Senate and House bills
that are being considered along with the Prescription Drug User
Fee Act. I ask you to imagine, Mr. Chairman, the frustration of
the FDA drug safety staff who were denied the capacity to make
those improvements, only to see the very same concepts emerge
years later in Congressional legislation. One can also imagine
that we as a nation would be in a far better place if the
necessary funding had been provided by Congress in those years
past, as the proposed programs could be up and running today,
and might well have permitted much more rapid identification of
many, if not all, of the recent drug safety problems that we
have experienced, meaning that far fewer individuals would have
been exposed to excess risk.
In conclusion, Mr. Chairman, while there are many, many
issues that the Committee must grapple with in considering drug
safety legislation this year, I urge you to make resourcing the
drug safety programs at FDA one of your highest priorities. The
agency's scientists very much want to make the kinds of
improvements you are contemplating, and will do so with
intensity and enthusiasm if you provide to them the staff and
resources to carry out your mandate.
Thank you for inviting me to present my views on this
important matter.
----------
Mr. Pallone. Thank you. Dr. Loew.
STATEMENT OF CAROLINE LOEW, SENIOR VICE-PRESIDENT, SCIENTIFIC
AND REGULATORY AFFAIRS OF THE PHARMACEUTICAL RESEARCH AND
MANUFACTURERS OF AMERICA
Ms. Loew. Thank you. Mr. Chairman, Ranking Member Deal, and
members of the subcommittee, I want to thank you for the
opportunity to testify today about the vitally important issue
of maintaining the safety of Americans' medicine supply. My
name is Dr. Caroline Loew, and I am the senior vice president
of scientific and regulatory affairs at the Pharmaceutical
Research and Manufacturers of America, or PhRMA.
PhRMA shares the view of the importance of drug safety. It
is also a top priority for all our member companies. PhRMA is
committed to working with the Food and Drug Administration and
all other stakeholders to continually improve our drug safety
system in a way that preserves innovation and patient access to
medicine.
As we address this critical topic, however, it is important
to remember that drug safety fundamentally involves a balance
between benefit and risk. Neither can be considered in
isolation. Firstly and most importantly, we support the FDA's
proposal to reauthorize the Prescription Drug User Fee Act,
also known as PDUFA, because it most effectively addresses the
issues that are critical in improving drug safety in America
today.
The PDUFA proposal will make a good system even better by
addressing FDA's most pressing drug safety needs: additional
resources and access to the latest scientific tools and
technologies. The current drug safety is stronger but could be
made even stronger by the passage of PDUFA. The agency already
has robust and effective systems in place for drug approval and
monitoring of medicines once they are on the market. Drug
safety is an extensive ongoing process that starts long before
a medicine enters the market and continues long after it has
been made available. It does not begin with or end when the new
medicine is approved.
Before patients can receive new medicines, they undergo
rigorous safety and effectiveness testing and evaluation. It
often spans 10 to 15 years. Drug safety, or more precisely the
benefit/risk balance, is only determined after extensive
testing in laboratories, animals, patients, and after FDA
regulators have studied tens of thousands of pages of
scientific data for each drug.
In fact, fully one-half of FDA's drug review project is
devoted to drug safety. Agency officials also have broad
statutory authority to monitor and ensure the safety of drugs
after they are approved. There are extensive adverse event
reporting requirements, annual reports filed by companies, and
for the vast majority of approvals, post marketing studies are
conducted.
The impact of this systems is undeniable. Over the last two
decades, only about 3 percent of the medicines approved for the
American market have been withdrawn for safety reasons. That is
an enviable record by any estimation. It is also important to
note that drug safety assessments today are more effective than
ever before, thanks to new scientific tools and technologies.
What we need to do now to improve drug safety is to
continue developing and better utilizing these new modern
techniques, and we need more resources devoted to drug safety.
The PDUFA proposal that FDA has put forward would help advance
these crucial goals. It would provide about $150 million over 5
years to hire 82 additional staffers for post-market drug
safety activities, and it would increase the use of large
medical databases, which contain a wealth of drug safety
information.
The proposal put forward by the FDA also addresses all of
the Institute of Medicine's most important recommendations for
more agency resources and improvements in the science of drug
safety. Any additional drug safety reforms considered by
Congress should strengthen FDA's product oversight capabilities
without harming innovation or access to medicines.
PhRMA would support very targeted legislative revisions
that clarify FDA authority in the areas of clinical drug
exposure, post-market studies, labeling and distribution
restrictions. For their part, PhRMA and its member companies
have contributed to the drug safety improvement effort in
recent years by initiating a number of major programs from
clinical trial disclosure to biomarket research to research
studies on new drug safety tools and methodologies to training
programs for better adverse event detection and reporting.
In the end, we all want the same thing: the timely delivery
of safe and effective medicines to patients suffering from a
wide range of medical conditions and diseases. We have a system
that is accomplishing that critical goal. FDA does need more
resources to increase the use of today's modern technology. And
that is what the FDA's PDUFA proposal would provide, and we
urge Congress to reauthorize the PDUFA proposal as quickly as
possible.
Thank you for this opportunity to inform the subcommittee
about PhRMA's perspectives in this critical public health
arena. Thank you.
[The prepared statement of Ms. Loew follows:]
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Mr. Pallone. Thank you. Ms. Thompson.
STATEMENT OF DIANE THOMPSON, VICE-PRESIDENT, PUBLIC POLICY AND
COMMUNICATIONS, ELIZABETH GLASER PEDIATRIC AIDS FOUNDATION,
SPEAKING ON BEHALF OF THE ALLIANCE FOR DRUG SAFETY AND ACCESS
Ms. Thompson. Good afternoon, Mr. Chairman, Ranking Member
Deal, and members of the committee. Thank you for the
opportunity to participate in today's hearing. I am Diane
Thompson, vice president for public policy and communications
at the Elizabeth Glaser Pediatric AIDS Foundation. Today I am
testifying on behalf of the Alliance for Drug Safety and
Access, a coalition of 11 patient and provider organizations,
whose members advocate on behalf of over 30 million patients,
suffering from hundreds of serious and life-threatening and
rare diseases. Alliance members also represent over 100,000
providers of care to children and individuals with mental
illnesses.
The Elizabeth Glaser Pediatric AIDS Foundation has been
focused on speeding patient access to safe medicine since its
inception in 1988. The foundation's creation was sparked by
Elizabeth Glaser's outrage over the lack of safe and effective
options for treating her two HIV-infected children. We know
this committee shares our goals of ensuring that patients
continue to have timely access to new therapies while
strengthening and improving the drug safety system. Simply put,
we do not accept that patients should have to choose between
safety and speedy access to new medications. The history of our
foundation, of the HIV/AIDS community and that of many in our
coalition is the story of the power of patients' contributions
to regulatory and scientific decision-making.
One mom's determination to fight for her child's survival
helped transform drug development for children. No one stands
to benefit or lose more than patients in drug safety decisions,
and patients must have a strong voice in decisions about safety
and risk management.
In its September 2006 report on drug safety, the Institute
of Medicine proposed a fundamental paradigm shift in this
country's approach to drug safety. We agree. Attention to
safety must be integrated throughout the life cycle of every
drug, and it must be recognized that continuous assessment of
benefit and risk is every bit as important once a product is on
the market and in the hands of patients as it is during the
drug review phase.
FDA must be given the authority to require drug
manufacturers to continue to study the safety of products after
approval, to force changes to drug labels when safety issues
are uncovered, and to require that the results of clinical
trials be shared with patients who, after all, are the people
who make the clinical trials possible.
Giving the FDA adequate authorities and flexible tools to
enforce them, including civil money penalties, will benefit
both patients and the industry. By providing FDA the
flexibility to impose fines for noncompliance, we can avoid the
worst possible outcome for everyone: having to pull a drug from
the market that still holds some benefit for some group of
patients.
We also agree with the IOM's recommendation that FDA safety
staff must have a greater formal role in drug review and in
risk management decisions. Finally, safety-related performance
goals must be added to PDUFA. The IOM report notes that a
recent study found that 21 percent of prescriptions are written
for off-label uses. Any effort to reform the drug safety system
that fails to address one-fifth of the use of drugs in real
world settings would leave a significant safety gap, a safety
gap that would particularly affect children since still far too
few drugs are ever tested in children before they are allowed
on the market.
The FDA's authority to require post-market safety studies
must clearly and unequivocally extend to both on-label and off-
label uses. We ask that the subcommittee make the public
dissemination of trial results a cornerstone of its drug safety
efforts by establishing a clinical trials results database. By
linking the registration of new trials with final outcomes, the
database would provide patients and providers with additional
information with which to assess benefits and risks and could
help prevent selective reporting of positive results and the
problems that have resulted from the withholding of negative
trial results. Given that clinical trials would not exist
without patients' willingness to give of their time and health,
such a mechanism could help restore patients' trust in the
integrity of the clinical trials process.
For FDA to succeed in implementing these reforms, it is
essential that new and expanded safety activities be explicitly
paired with increased resources, both in user fees targeted to
drug safety activities and in appropriations. The need for new
authorities and for the increased funding are inextricably
linked, and we strongly urge the subcommittee to consider these
issues along with legislation to improve the safety and access
of pediatric drugs and devices as a part of a single package.
Mr. Chairman, members of the committee, the committee has
before it an historic opportunity to finally match our Nation's
success in speeding new therapies to patients with a system
that can better ensure the safety of those products once they
are on the market. We appreciate your interest in the patients'
perspectives on these critical issues and look forward to
working with you to accomplish these goals. Thank you again for
the opportunity to share our views.
[The prepared statement of Ms. Thompson follows:]
Statement of Diane E. Thompson
Mr. Chairman, Mr. Deal, and members of the subcommittee,
thank you for the opportunity to participate in today's
hearing. I am Diane Thompson, vice president for public policy
and communications at the Elizabeth Glaser Pediatric AIDS
Foundation. Today, I will be testifying on behalf of the
Alliance for Drug Safety and Access (ADSA), a coalition of 11
patient and provider organizations. Collectively, members of
ADSA advocate on behalf of over 30 million patients, including
those suffering from HIV/AIDS, Parkinson's disease, spinal cord
injuries, paralysis, multiple sclerosis, leukodystrophies,
Tourette Syndrome, and over 6,000 known rare diseases. In
addition, our members represent over 100,000 providers of care
to children and individuals with mental illnesses.
As a representative of the Elizabeth Glaser Pediatric AIDS
Foundation, I am also proud to offer the perspective of an
organization that has been focused on speeding patient access
to safe medicines since its inception in 1988. This issue is at
the heart of our mission--the Foundation's creation was sparked
by Elizabeth Glaser's outrage over the lack of safe and
effective options for treating her two HIV-infected children.
Although Elizabeth's efforts were too late to save her
daughter, Ariel, who died from AIDS at the age of 7, her legacy
includes her son Jake, now 22 years old, and the thousands of
HIV-infected children around the world who now have the chance
to grow up healthy and even start families of their own, thanks
to the search for lifesaving pediatric medicines that Elizabeth
Glaser and the Foundation championed.
I would like to thank the chairman, the ranking member, Mr.
Waxman, Mr. Markey, and other members of the subcommittee for
your leadership on this issue, for moving beyond the headlines
to examine our nation's current drug safety system and discuss
meaningful solutions to ensure that the Food and Drug
Administration (FDA) remains the world's gold standard for
public health protection. Your task is not an easy one and we
appreciate the historic nature of this undertaking.
We have the opportunity before us to both maintain timely
access of patients to new therapies, while strengthening
oversight of drugs already on the market. We believe that with
sufficient resources both goals are achievable. Simply put, we
do not accept that patients should have to choose between
safety and speedy access to new medications.
Patients with serious illnesses understand that bringing
drugs to market in a timely way means that not every risk can
be identified in advance. What they also demand, however, is
sufficient information for themselves and their providers to
assess risks and benefits on an ongoing basis--which often
means further testing of the drug after approval. Yet, the FDA
has virtually no authority to compel drug manufacturers to
continue to study the safety of products after they have been
approved, force changes to drug labels if dangerous side
effects are uncovered, or require that the results of clinical
trials be shared with the patients who make them possible.
Giving FDA these authorities and flexible tools to enforce
them, including civil money penalties, as legislation pending
before the Committee would do, ultimately benefits both
patients and drug manufacturers. Allowing FDA to require
additional testing of drugs postmarket could actually allow the
FDA to approve drugs more quickly, knowing it will have the
ability to act if there are new safety concerns once the drug
is in the hands of patients. Also, by giving FDA the
flexibility to impose fines for non-compliance, we can avoid
the worst possible outcome for everyone: pulling a drug from
the market that still holds some benefit for some group of
patients.
We believe that the core of any effort to improve drug
access and safety must be a shift to a ``life-cycle'' paradigm,
with an emphasis on the continuing pursuit of knowledge about a
drug's risk-benefit profile and timely communication of that
information to patients and providers. This approach, which is
recommended by the Institute of Medicine (IOM), has been
included in drug safety legislation introduced by Mr. Waxman
and Mr. Markey. In our view, individualized risk evaluation and
mitigation strategies, rather than a one-size-fits-all approach
to patient safety, will be key to the appropriate balancing of
drug risks and benefits that is so critical to patients with
life-threatening illnesses.
To further improve the depth and breadth of input into drug
safety decision making, we ask the Committee also to adopt the
IOM's recommendation that the Office of Surveillance and
Epidemiology (OSE) be given a greater role in drug review and
the development of safety plans. The lack of communication and
cooperation between that office and the Office of New Drugs,
highlighted in both the IOM report and a March 2006 report by
the Government Accountability Office, is deeply troubling. At
minimum, we recommend that the Committee formally assign OSE
staff a role in the review of new drugs applications and post
approval regulatory actions, as the IOM recommends.
We ask the subcommittee also to ensure that any drug safety
legislation includes mechanisms for greater public input and
transparency. The history of our Foundation and of the broader
HIV/AIDS community is the story of the power of patients'
contributions to scientific decision making. Although they
began as three mothers around a kitchen table with no formal
training in science and medicine, Elizabeth Glaser and the
other founders of the Foundation ultimately changed the
accepted thinking of both the National Institutes of Health and
FDA about the risks of not studying AIDS drugs in children--a
success story that is repeated throughout the histories of
patient organizations. Given that no one stands to benefit or
lose more than patients in drug safety decisions, we ask that
you consider a significant role for patients in the assessment
and management of drug risks.
We also urge the committee to clarify that any new
authority of FDA to require studies of post-market safety
concerns is not confined to on-label uses of the drug. In our
efforts to improve the drug safety system, we need to pay
particular attention to not only what happens inside the FDA,
but also what goes on in the real world. A recent study found
that 21 percent of prescriptions written in 2001 were for off-
label uses. Any effort to reform the drug safety system that
fails to address one-fifth of the use of drugs in real-world
settings leaves a significant safety gap.
Children would be left at particular risk by the failure to
clarify this authority, since as much as three-quarters
pediatric prescribing is off-label. Thanks to the efforts of
many on this Subcommittee, there are mechanisms available to
both encourage and require manufacturers to study their
products for children. However, there are gaps in those
mechanisms. The existing pediatric study requirement does not
apply to off-label uses. While the existing incentives can be
applied to off-label studies, they are voluntary--and we are
seeing that manufacturers are increasingly opting not to
conduct the studies FDA requests. Unambiguous authority to
require such studies when the off-label use is significant will
help ensure that children too can reap the benefits of an
improved drug safety system.
In our view the subcommittee must make the public
dissemination of trial results a cornerstone of its drug safety
efforts. The establishment of a results database would be a
significant step forward in giving patients and providers
additional information with which to assess benefits and risks.
By linking the registration of new trials with final outcomes,
this database also could help prevent selective reporting of
positive results and the problems that have resulted from the
withholding of negative trial results. And, not incidentally,
given that clinical trials could not exist without patients'
willingness to give of their time and health, such a mechanism
could help restore patients' trust in the integrity of the
clinical trials process.
While we work toward providing the FDA additional
authorities and enforcement tools, we must acknowledge that
chronic under-funding is severely straining the ability of the
Agency to perform even its current functions. Years of
essentially flat funding, coupled with new challenges such as
increasingly global markets, the threat of bioterrorism, and
the promise of personalized medicine, have left the Agency
struggling to meet its obligation to protect the public health.
We--Congress, the Administration and patients--must work
together to give the FDA the resources it needs to accomplish
its critical mission. We suggest the combination of an increase
in user fees targeted to drug safety activities and an increase
in appropriations. Because we believe that the need for new
authorities and for increased funding are so inextricably
linked, we strongly recommend the subcommittee consider these
issues, along with legislation to improve the safety and
availability of pediatric drugs and devices, as part of a
single legislative package.
Mr. Chairman, you have before you a historic opportunity to
finally match our nation's success in speeding new therapies to
patients with a system that can better ensure the safety of
those products once on the market. We appreciate your interest
in patients' and providers' perspectives on these critical
issues and look forward to working with you to accomplish these
goals.
Thank you again for the opportunity to share our views.
----------
Mr. Pallone. Thank you. Thanks a lot. Mr. Theriault.
STATEMENT OF JOHN THERIAULT, CHIEF SECURITY OFFICER AND VICE
PRESIDENT, GLOBAL SECURITY, PFIZER
Mr. Theriault. Thank you, Chairman Pallone and Ranking
Member Deal and members of the subcommittee. My name is John
Theriault. I am the vice president of global security at
Pfizer. Prior to joining Pfizer, I was a special agent with the
FBI for 25 years, retiring in 1995 as a member of the Bureau's
Senior Executive Service. It is a pleasure to appear before you
today to talk about a critical issue: drug safety and efforts
to protect the U.S. pharmaceutical supply from counterfeit
medicines.
When I joined Pfizer in 1996, the company did not have an
anti-counterfeiting program, frankly because there were no
indications that any of our products were being counterfeited.
That changed in 1998 when we launched Viagra, and I think that
understanding what happened with that product at that time will
help in understanding the counterfeit medicines industry that
has evolved since then.
Viagra was a unique product in 1998, and it was in great
demand all over the world. But because of regulatory
requirements, it was not legally available in many countries.
So what we saw immediately was a global demand that was filled
by entrepreneurs who purchased the product in a country where
it was available and resold it sometimes at 10, 20 times what
they had paid for it in countries where it was not available.
Very soon thereafter, we saw our first counterfeiting case.
It involved a UK organized crime figure who was convicted of
conspiring to import counterfeit Viagra from a legitimate
Indian company. Now, over the next few years, we conducted
several investigations to identify Viagra counterfeiters and
distributors. But in doing so, what we discovered was that they
were counterfeiting and distributing other counterfeit
medicines that we were not aware of. The Viagra investigations
actually opened a door for us to look into a very robust
counterfeiting industry that we didn't know existed.
Since the inception of our anti-counterfeiting program, we
have discovered counterfeit versions of our medicines in more
than 60 countries. The medicines span a wide range of
therapeutic areas, and they include Aricept, Lipitor, Norvasc,
Diflucan, Ponstan, Cabaser Celebrex, Dilantin, Vibramycin and
Zoloft. This is an issue that goes well beyond erectile
dysfunction drugs. It is a counterfeiting issue that affects
virtually every therapeutic area you can think of.
Now, it is Pfizer's goal to make sure that every patient
who buys a Pfizer product receives an authentic Pfizer product,
and we consider the counterfeiting problem to be so serious
today that our program to investigate and deal with it has
increased from one security professional in New York in 1999 to
17 security professionals based in the United States, Mexico,
the United Kingdom, Germany, Turkey, mainland China, Hong Kong,
India, Thailand, and Malaysia.
To give you some idea of the scope of the problem, in 2006
alone, law enforcement and customs authorities, with whom our
investigators are working, conducted 238 raids, made 501
arrests, seized over 8.1 million units of counterfeit Pfizer
products and enough active pharmaceutical ingredient to
manufacture more than 15 million counterfeit Viagra tablets and
more than 20 million counterfeit Norvasc tablets.
During those raids, counterfeit versions of other
companies' medicines were discovered as well. Counterfeiting is
a serious crime, and as you can see from this display,
counterfeiters take great care in replicating the appearance of
genuine product. The counterfeit product there is on the left.
The authentic is on the right, and it is virtually impossible
to differentiate those by visual inspection.
But what you can see from the next display is that the
counterfeiters don't really take quite as much care in the
manufacturing process. Counterfeits are inherently dangerous.
They are manufactured in unknown locations using unknown
ingredients. We have seen counterfeits that contain no active
pharmaceutical ingredient and therefore did not deliver the
therapeutic benefits for which they were prescribed. Some
contain super potent amounts of active ingredient, which
increase the risks of adverse events, and yet others contain
toxic ingredients that are harmful in themselves.
Our experience indicates that the counterfeit medicines
problem is growing, and it is being facilitated by the
Internet, which provides both business-to-business distribution
capabilities as well as retail opportunities, via bogus online
pharmacies.
Counterfeiters are also exploiting a loose distribution
channel to get their bad medicine into the hands of patients.
The evidence clearly reveals that the more times medicines
change hands in the distribution system, the more opportunities
there are to introduce counterfeits.
Now, I said the problem is growing, and the reason for that
is simple. This is a very, very high-profit, low-risk criminal
enterprise, and we shouldn't lose sight of the criminal nature
of this as we debate drug safety. How profitable is this for
counterfeiters? That graphic shows that if you were to invest
$20,000 in a kilo of cocaine--not that anybody would do that,
but that is about what it costs these days. $20,000 for a kilo
of cocaine would yield $60,000 in sales. Subtract the cost, and
you have got a $40,000 profit. You can buy from any Indian
company on the Internet the active ingredient for Viagra, $64.
That would produce 14,000 50-milligram Viagra tablets at $10
apiece, $140,000 in revenue. Subtract the $64, and you have got
a much greater profit margin doing counterfeit drugs. This is a
crime that attracts serious criminals.
Now, the facts here are irrefutable. The importation of
counterfeit, infringing, misbranded, non-approved,
pharmaceutical products in the United States is increasing
exponentially. Those products, by definition, pose a risk to
public health and safety. The response by regulatory and law
enforcement agencies to this growing crisis has to be reviewed,
analyzed and modified at all levels.
To sum up quickly, instead of discussing ways to deregulate
the current safety system, we think that we ought to be
discussing ways in which the current system could be improved
to mitigate these threats to patients. Mr. Chairman, Ranking
Member, members of the committee, thank you for the opportunity
to share this with you.
[The prepared statement of Mr. Theriault follows:]
Statement of John Theriault
Chairman Pallone, Ranking Member Deal, and members of the
subcommittee, my name is John Theriault. I am the chief
security officer and vice president of global security at
Pfizer Inc, the world's largest pharmaceutical company. It is a
pleasure to appear before you today to discuss an issue of
critical importance: drug safety and efforts to protect the
United States pharmaceutical supply from contamination with
counterfeit products.
Prior to joining Pfizer, I spent more than 25 years as a
Special Agent of the Federal Bureau of Investigation. During my
FBI career I had substantial experience in international law
enforcement and served for a number of years as the Legal
Attache in Ottawa, Canada and London, England.
Mr. Chairman, while my testimony today focuses on our
experience with counterfeit Pfizer products, I wish to impress
upon the subcommittee that these problems are not limited to
Pfizer. They threaten the entire pharmaceutical industry and
most importantly, the U.S. patients who depend upon that
industry.
As the subcommittee is well aware, there is already
importation of counterfeit and diverted medicines into the
United States through the mail, courier services, and some
unethical re-packagers and wholesalers. Millions of Americans
who assume that the prescription medicines they buy online are
safe and effective are at risk. Regardless of the method of
obtaining drugs from Canada or other countries, there is a real
potential for fraud or harm. I would emphasize that every time
a medicine changes hands represents--an additional opportunity
for counterfeit products to be introduced into distribution.
Counterfeit Pharmaceutical Products: What is the Scope of the Problem?
The problem of counterfeit medicines, once thought to be
limited to developing countries with weak regulatory systems,
is now recognized as a global problem from which no country is
immune. The manufacture of counterfeits is not limited to China
and India. They are produced in at least twenty-four countries,
including Canada, the United Kingdom, and four other members of
the European Union--Belgium, the Netherlands, Poland, and
Portugal.
Since 1998, when the first counterfeit Viagra tablets were
discovered in the United Kingdom, Pfizer has developed a
focused anti-counterfeiting program to protect the integrity of
our products and supply chain. Staffing for that program has
increased from one security professional based in New York, to
seventeen security professionals based in the United States,
Mexico, the United Kingdom, Germany, Turkey, China, Hong Kong,
India, Thailand, and Malaysia. Our Product Integrity Steering
Committee has set as Pfizer's goal ensuring that every patient
who buys a Pfizer product receives an authentic Pfizer product.
We are waging a fierce battle against these
counterfeiters. Pfizer products targeted by counterfeiters now
include Aricept (Alzheimer's disease), Lipitor (cholesterol),
Norvasc (hypertension), Diflucan (antifungal), Ponstan (anti-
inflammatory) and Viagra (erectile dysfunction), Cabaser
(Parkinson's disease), Celebrex (pain), Dilantin (epilepsy),
Vibramycin (antibiotic), and Zoloft (depression).
Although it is difficult to measure the true scope of the
counterfeiting problem, the number of reported seizures by law
enforcement of Pfizer products serves as a useful baseline.
During 2006, authorities from 36 countries reported seizing
more than 8.1 million counterfeit tablets, a 20.8 percent
increase over 2005. That increase was most significant in
Europe, the Middle East and Africa, where seizures increased by
more than 332 percent
A Case in Point: Deadly Poison Masquerading as Medicine
Fake medicines are costing lives. In March 2007, we heard
of a tragic story of a woman's death which, according to press
reports, was caused by drugs she ordered online from a bogus
Canadian pharmacy. Instead of treatment for her arthritis and
allergies, Ms. Marcia Bergeron was slowly poisoned by products
that contained dangerously high levels of strontium, uranium,
and lead, heavy metals that had apparently been used as a cheap
filler. Ms. Bergeron started losing her hair and had blurred
vision and died a few days after Christmas in 2006.
We fear that there may be more terrible stories like this
one. I'm sure you all have read the story from Sunday's New
York Times about the hundreds of deaths in Panama from cough
syrup from China that contained diethylene glycol.
It is virtually impossible to see differences between
counterfeit and genuine medications. If you visited the
manufacturing facilities, the differences would be shockingly
obvious. Drug counterfeiters do not care about safety or
sanitation. They only care about profits, and counterfeiting is
highly lucrative. The profitability of drug counterfeiting far
exceeds that of the illicit drug trade. However, there is a
lower chance that these counterfeiters will get caught, and if
they do, the penalties are less punitive.
RxNorth: Profits before Patients
Another case involves the Internet pharmacy RxNorth. A
company whistleblower told a Canadian Television (CTV) news
program that customers had received expired drugs, and that the
expiry dates had been covered up on packages. In addition, the
drugs were not Canadian. In fact, RxNorth was filling
prescriptions for US citizens with counterfeit versions of
Lipitor, Celebrex and other products. The CTV news program
reported that many of the drugs RxNorth sold came from sources
in the UK or Australia and were shipped to a dispensing
facility in Freeport, the Bahamas, where Internet orders were
filled and shipped to US customers.
Counterfeiters often use a convoluted shipping path to
evade the authorities and trick customers. For example, on May
22, 2006, UK Customs intercepted a four-pallet shipment of
pharmaceuticals, which had come to the UK from the United Arab
Emirates (UAE). The shipment consisted of eight products
manufactured by five major pharmaceutical companies: Pfizer,
AstraZeneca, Novartis, Merck, and Proctor & Gamble. The shipper
was the Oyster Corporation, of Sharjah, UAE. The intended
recipient was Missouri-Bain Thomson, of the Personal Touch
Pharmacy, in Freeport, the Bahamas. Investigation by the
authorities determined that Personal Touch Pharmacy computers
were connected to Rx North's servers. This is commonplace:
according to a 2005 FDA study, fewer than two percent of the
thousands of Web sites advertising cheap Canadian drugs are
actually based in Canada.
Our infrared spectral analysis of the seized Lipitor
tablets showed that the Lipitor was counterfeit, and contained
about 82 percent-86 percent of the claimed concentration of
active pharmaceutical ingredient (API). The lot number printed
on the packaging of the counterfeit Lipitor' was legitimate for
a product produced for the Middle East market, and the
counterfeit packaging was elegant. Pfizer analysts examined the
packaging and determined that the ``i'' in the word
``atorvastatin'' on the blister foil was placed differently,
indicating a difference in font size; and the breakage-line
between the single cavities showed that the authentic blister
has a tighter punching line than the sample. The counterfeit
packaging also contained a patient information leaflet,
although it was smaller than a genuine leaflet, and missing a
page. The fact that the counterfeiters are using legitimate lot
numbers is concerning, since it demonstrates a level of
sophistication in their deception that makes the counterfeits
that much harder to detect.
On June 1, 2006, Pfizer investigators notified the Bahamian
authorities of the facts in this case, and on June 9th the
Bahamian authorities raided the Personal Touch Pharmacy in
Freeport. There they seized $3.7 million worth of products,
spanning numerous different brands from 13 different
manufacturers. The total amount of product seized amounted to
3.025 million dosage units of products. The Bahamian
investigation determined that approximately $8 million worth of
business was conducted at Personal Touch Pharmacy on a yearly
basis. The investigation is ongoing.
We remain concerned that there are thousands of similar
situations that remain undetected, and that consumers like Ms.
Bergeron will be victims to this fraud and greed. As Congress
develops drug safety legislation, it is essential that you
carefully consider this very dangerous situation that has yet
to be adequately addressed.
The facts are irrefutable. The importation of counterfeit,
infringing, misbranded, and unapproved pharmaceutical products
into the United States is increasing exponentially, and those
products, by definition, pose a risk to public health and
safety. The response by regulatory and law enforcement agencies
to this growing crisis must be reviewed, analyzed, and modified
at all levels. The public health and safety depend upon the
FDA's vigilance. The FDA and Customs must receive the
additional resources necessary to fulfill their current
mandate. Regulations currently in existence must be fully
funded and fully enforced. The notion that somehow importation
can be done safely by implementing so-called anti-counterfeit
technology is to ignore everything we know about counterfeiting
and counterfeiters. Similarly, the notion that importation on
any scale will be as safe as the current system is to ignore
all of the available evidence. Again, any time a medicine
changes hands presents a new opportunity for the introduction
of counterfeits into distribution. Instead of discussing ways
to ``de-regulate'' the current safety system, we ought to be
discussing ways in which the current system can be improved to
mitigate these threats to patients.
Mr. Chairman, Ranking Member Deal, and distinguished
members of the subcommittee, thank you for this opportunity to
express our concerns about this critical issue. I would be
happy to answer your questions.
----------
Mr. Pallone. Thank you. I recognize Dr. Levine.
STATEMENT OF SHARON LEVINE, M.D., ASSOCIATE EXECUTIVE DIRECTOR,
PERMANENTE MEDICAL GROUP, SPEAKING ON BEHALF OF THE KAISER
PERMANENTE MEDICAL CARE PROGRAM
Dr. Levine. Mr. Chairman, distinguished committee members,
I am a physician with Kaiser Permanente in northern California,
and I oversee the Permanente Medical Groups' efforts on drug
use management in partnership with my Kaiser pharmacist
colleagues.
Our shared goal is the delivery of high-quality, safe and
effective drug therapy and pharmaceutical services to our
members. In order to do this, our physicians and pharmacists
need the best available information on the safety and
effectiveness of the drugs we prescribe and dispense. The
importance of this issue is increasing every year. New, more
powerful drugs are being approved and released to the market,
and prescription drug therapy is playing an ever-increasing
role in therapy.
An important benefit of our efforts to fully integrate
pharmacy services with health care delivery is that we are able
to capture detailed and very complete information about the
drugs we prescribe and dispense since almost 98 percent of
prescriptions written for Kaiser members are filled in our
pharmacies at our facilities, and we are able to match that
information with robust clinical and demographic data that is
captured in our delivery system and our health plan.
Because of our large and stable population, we have the
ability to generate enormous statistical power in research
studies that we do. We have begun in earnest to utilize these
data to learn more about the safety and effectiveness of
specific prescription drugs and to answer questions which, when
applied clinical practice, will protect consumers from drugs
that pose an unacceptable risk compared to the benefits the
drugs provide.
We believe strongly that there is a need for an
intentional, careful, and systematic data collection and review
of a drug's use, which begins with its introduction into the
market. This will enable faster identification of safety
problems that result from the use of the drug outside the
carefully controlled circumstances of phase one through three
trials--ideally before rapid uptake of the drugs in the market
exposes more people than necessary to unanticipated risks.
Our researchers have access to and analyze data from
multiple sources; membership records, hospital discharge
records, outpatient and inpatient prescription data, outpatient
clinic data, and laboratory and x-ray results. My written
testimony provides detailed information on these data sources
and how they are used. And I want to share with you today two
examples.
The Vioxx story is obviously very well known to this
committee. Almost everyone has mentioned it, and it has become
the poster child for the call to protect the public from
unacceptable risk. A relatively limited population of Kaiser
Permanente members were exposed to this drug. We had in place a
Web-based tool to enable physicians to identify the small
subset of patients who actually stood to benefit from the
theoretical advantage that the drug provided, that of avoiding
serious gastrointestinal side effects Yet millions and millions
of patients in the general population received this drug.
Almost 107 million prescriptions for Vioxx were filled before
the drug was pulled from the market.
In collaboration with the FDA, Kaiser Permanente
researchers and clinicians were able to confirm that Vioxx
increased significantly the risk of coronary events, 5 years
after introduction of the drug into the market and 5 years
after the VIGOR trial which first raised the issue of vascular
events.
Equally important, the same prescription drug and clinical
data can be used to erase safety concerns that are raised by
spontaneous reports of adverse events. In March 2005, the FDA
issued an advisory to physicians urging caution in prescribing
topical tachrolinus and pimecrolimus, two topical agents used
to treat eczema and other skin conditions, because of concerns
raised by animal studies and isolated case reports in a small
number of patients. Matching up our pharmacy database with our
cancer registry, we were able to identify those patients who
had received those two drugs and were also diagnosed with
cancer. Our researchers actually found no increase in the
overall cancer rates but did find an increase in cutaneous T-
cell lymphoma, a skin malignancy, among the drug users.
By examining the medical records of these patients, and
excluding those that the physicians suspected of having cancer
prior to the drugs, our researchers were able to find no
increased risk either of cancer in general or of cutaneous T-
cell lymphoma.
These are just two examples of what is possible using
existing data, and my written testimony contains many more
examples. In systems like Kaiser Permanente and the Veterans
Administration today, the rapidly approaching future of
complete clinical data capture with electronic medical record
systems will significantly enhance the ability of researchers
to identify and quantify problems and assess associated risk,
which will inform better risk/benefit analysis.
I want to thank the committee for taking these issues under
consideration and for your interest in this, and I look forward
to answering your questions.
[The prepared statement of Dr. Levine follows:]
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Mr. Pallone. Thank you, Doctor. Dr. Powers.
STATEMENT OF JOHN POWERS, M.D. ASSISTANT PROFESSOR OF MEDICINE,
THE GEORGE WASHINGTON UNIVERSITY SCHOOL OF MEDICINE, AND
UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE
Dr. Powers. Thank you, Mr. Chairman and members of the
committee. My name is John Powers, and I am a physician
scientist who worked at the Food and Drug Administration for
the last 8 years. My background is that of a practicing
clinician and academic investigator and researcher, a scientist
in the field of drug development, a consultant for several drug
sponsors, and most importantly, I have been a patient myself. I
would like to thank you for the opportunity to discuss with you
today my perspective on the issues of evaluating the risks and
benefits of medical intervention.
The Institute of Medicine report on drug safety points out
that the current reauthorization of the Prescription Drug User
Fee Act is a golden opportunity to address long overdue
improvements needed in our system of evaluating drug safety.
The GAO report points out that there have been at least five
separate reports since 1971 related to these issues. Therefore
PDUFA should not be reauthorized without simultaneously
addressing the important public health issues related to drug
safety that have persisted for some time.
Previous drug legislation addressed the issues of pre-
approval safety in 1938 and pre-approval effectiveness in 1962.
But it is now clear that we need more focus on continuously
evaluating drugs even after approval.
For instance, the example of the inevitable emergence of
antibiotic resistance points out how the assessment of both
safety and effectiveness of drugs can change over time. The
standard we should use to judge proposed changes in drug safety
should be would these changes prevent another safety episode
like Vioxx of Ketek? Tying pre-approval review that brings
medical interventions to patients and appropriate post-approval
evaluations of those same interventions are not mutually
exclusive goals, and we can do both.
I would like to divide the issues related to addressing
drug safety into three categories. First, inputs of resources
in authority into FDA. Second, internal use of science
resources and processes inside FDA. And third, outputs of
decisions and communications with the public from FDA.
In terms of inputs into FDA, Congress should authorize
adequate funding for general appropriations, and any PDUFA fees
should have no strings attached, and their use should not be
negotiated with regulatory industry. FDA needs the authority to
require post-approval studies, to mandate labeling changes, and
to assess simple monetary penalties for not fulfilling risk
management activities.
The legislation proposed by Mr. Markey and Mr. Waxman is a
start in this direction by providing more meaningful penalties.
FDA needs access to modern databases and active surveillance to
more efficiently gather information on drug use and potential
adverse events.
Any organization is only as strong as the people who work
there, so FDA needs to hire adequately trained staff and ensure
the staff remain engaged as a part of the scientific community.
This leads to issues involving science and process inside of
FDA. FDA scientists should be free to participate as members of
the scientific community by having the right to publish and
share their information and participate in scientific meetings.
There needs to be a culture of professionalism at FDA. And
if, on rare occasions, after attempting to reach internal
agreement, FDA staffers need to seek help outside of FDA in
order to protect the public's health, there needs to be
enhanced whistle-blower protections, such as those outlined in
Mr. Markey's Swift Approval Full Evaluation Act.
There also needs to be accountability for FDA staff who
attempt to retaliate against their colleagues or who do not
uphold the laws and regulations. For instance, in cases where
drugs have been knowingly approved without substantial evidence
of effectiveness.
Any system should have checks and balances, and the Office
of New Drugs and the Office of Surveillance and Epidemiology
should have joint decision-making authority regarding post-
approval decisions. FDA needs to define what they mean by best
use of science and define the criteria used for making risk/
benefit decisions in general.
In terms of outputs from the FDA, we need transparency of
decision making in the form of summary bases of approval
published on the FDA Web site in a timely fashion, which
explain the scientific rationale for regulatory decisions. This
would be helpful for both regulated industry and for patients.
All clinical trials and their results should be included in a
registry.
It is FDA's job to communicate with the public, and FDA
needs the resources to evaluate the effectiveness of all of the
methodologies used to try to accomplish this goal, as it is
well known that changes in labeling alone have little effect on
prescribing behavior.
The IOM report reinforces that now is the time to address
sorely needed improvements in evaluating drug safety. Congress
should include provisions for strengthening drug safety in any
reauthorization of PDUFA. We can address issues in evaluating
drug safety in an efficient way without hindering access to
important medical advances for patients.
Making these changes today will help us to avoid another
Vioxx or Ketek tomorrow. Congress can help FDA start down the
road of being the foremost authority on pharmacoepidemiology,
to help them work closely with the scientific community, and to
develop scientifically-based approaches to evaluating the
balance of risk and benefits for drugs.
This will help FDA achieve its stated mission of protecting
and advancing the public health. Most FDA staffers are
incredibly hard workers and courageous public health servants.
Please give them the tools they need to do their jobs for all
of us. Thank you.
[The prepared statement of Dr. Powers follows:]
Statement of John H. Powers, M.D.
Good morning Mr. Chairman and members of the committee. My
name is John Powers. I am a physician-scientist who worked at
the Food and Drug Administration for the last 8 years. My
background is that of a clinician in internal medicine and
infectious diseases, an investigator and researcher in clinical
trials, a scientist in the field of drug development, and a
consultant for several drug sponsors. Perhaps most importantly,
I have been a patient myself. I would like thank you for the
opportunity to discuss with you today my perspective on the
issues of evaluating the risks and benefits of medical
interventions.
As the Institute of Medicine report on drug safety points
out, the current reauthorization of the Prescription Drug User
Fee Act is a golden opportunity to address long-overdue
improvements with drug safety in order to adequately protect
the public's health. PDUFA should not be reauthorized without
simultaneously addressing the important public health issues
related to drug safety. The standard we should use to judge
proposed changes to the evaluation of drug safety should be:
Would these changes prevent another drug safety episode like
Vioxx or Ketek? Bringing medical interventions to patients in a
timely way and appropriate post-approval evaluations of those
same interventions are not mutually exclusive goals, and
addressing post-approval drug safety need not slow bringing new
medications to patients. Indeed, the FDA Critical Path
initiative points out that better tools for pre-approval
evaluation of potential safety issues may allow more efficient
drug development, earlier cessation of drug development
programs of drugs with toxicities before spending precious
resources, and more focused evaluation of drug toxicities post-
approval.
The passage of the Food, Drug and Cosmetic Act (FD&C) in
1938 shifted the burden of the evaluation of pre-approval
safety of drugs from the government to drug sponsors. From that
time forward there was no assumption that a drug was safe, and
sponsors had to provide evidence of the potential adverse
events associated with drug use. This reflected a notion that
is clear today; no drug is completely safe in that all drugs
are associated with some adverse events. In 1962, Congress
amended the FD&C Act to require substantial evidence of
effectiveness based on adequate and well-controlled trials,
codifying the logic that there must be evidence of benefit in
order to justify any risks of drugs, no matter how rare.
Both these provisions focused on the pre-approval
evaluation of medical interventions, which was appropriate for
that time. However, it is now clear that we need to focus on
the entire life-cycle of medicines with a greater focus on
post-approval evaluations. This is eminently sensible as we
cannot learn all we need to know about medical interventions
given the limited number and types of patients and the short
time span in which drugs are studied pre-approval. The vast
majority the life-cycle of a drug is spent post-approval, and
it follows we can learn much about a drug during this time. FDA
must play a crucial role in continuing to evaluate drugs once
they are approved.
The need for regulation is two fold: first, regulation is
needed when market forces tend to guide businesses in a way
that may be contrary to public interest, and second, regulation
provides a uniform standard for public health and consistency
and fairness for the regulated industry. In regards to the
first point, there is little incentive for drug sponsors to
rigorously evaluate potential safety issues with a drug once it
is approved since from a business perspective this evaluation
has the potential to decrease sales. This is in contrast to
providing evidence of drug effectiveness prior to approval
which is necessary both for FDA approval for marketing and to
convince clinicians to use the drug. Many drug sponsors
certainly do include protecting the public's health in their
decision making. But as James Madison stated in the Federalist
#51 in 1788, if all men were angels no government would be
necessary. Even one sponsor who decides that profits trump
public health is one too many and it is the FDA's job to ensure
all sponsors are held to the same standard. This relates to the
second point, which is that FDA is supposed to ensure a
scientifically based and consistent standard of public health
both for the sake of the public health, and out of fairness to
drug sponsors so that every sponsor is subject to the same
rules. This allows less uncertainty in drug development, and
allows sponsors to plan their studies accordingly. The only way
to ensure both protecting and advancing the public health and
fairness to drug sponsors is to base laws and regulation upon
the best science. Since science changes over time as we learn
new things, regulations need to adapt as well. The prior focus
on pre-approval evaluations is still needed, but we now need to
focus our attention of post-approval evaluations as well.
One can view the issues related to addressing drug safety
as divided into three categories: inputs of resources and
authority into FDA, internal use of resources, science and
functioning inside FDA, and outputs of decisions and
communications with the public from FDA.
I. Inputs into FDA
FDA staff need the resources in terms of funding, manpower,
knowledge, data and authority to do its job properly.
Congress should authorize adequate funding for FDA from
general appropriations and PDUFA fees should have ``no strings
attached'' and not be negotiated with regulated industry: FDA
has been severely under-funded for some time, even to do the
job it already has to do. Indeed, the original intent of PDUFA
in 1992 was to bring greater funding to FDA to provide it the
resources it needed at that time. To address the larger issues
of post-approval evaluations of drugs it will need greater
funding. It seems logical that regulated industry should pay
for a fee for licensing of drugs to defray the costs to the
government, similar to how drivers pay a fee for their drivers'
license of doctors pay a fee to State medical boards for a
license to practice medicine. However, drivers and doctors do
not negotiate the uses to which those fees are put with
Division of Motor Vehicles or the State Medical Board. In
addition to the obvious appearance of conflict of interest of
allowing the regulated to help decide where the regulator
appropriates funds, the long time frame between PDUFA
negotiations--done only once every 5 years--does not allow FDA
to adapt and shift resources to where they are most needed.
Again, there is a need for regulation when there is no
incentive for the regulated to address issues of public health,
and previous negotiations of PDUFA in which FDA was barred from
applying fees to post-approval safety evaluations are evidence
of a desire by some to avoid performing these evaluations.
FDA needs adequate authority to ensure the public health
including ability to assess sufficiently stringent civil
monetary penalties for non-adherence and sufficient authority
to ensure device effectiveness--FDA needs the authority to
require post-approval studies and ensure sponsors complete
those studies. As noted previously, there is an obvious
incentive for drug sponsors to submit data in support of drug
effectiveness. Since there is less incentive to perform post-
approval studies, FDA needs the ability to require studies and
impose meaningful penalties on drug sponsors who do not fulfill
their stated commitments. The Enhancing Drug Safety and
Innovation Act (H.R. 1561) is a start in this direction by
providing for more meaningful penalties beyond those that
sponsors could just write off as the cost of doing business.
Penalties need to be appropriate in order to provide an
incentive to comply. In addition, the current legally mandated
standards for effectiveness of devices are quite different for
those from drugs. It is not clear from a scientific point of
view why this should be so, as patients who receive devices
should receive the same protection under the law as those who
receive drugs. Recent approvals of some devices have left
outstanding questions regarding their effectiveness, such as
the vagal nerve stimulator for depression. This seems to
contradict the basic principle that there needs to be
substantial evidence of effectiveness in order to justify the
risks of any intervention. Congress should address this by
changing the law to hold devices to the same standard of
substantial evidence of effectiveness from adequate and well
controlled trials as for drugs.
FDA needs adequate data upon which to base decisions--The
use of modern databases to more efficiently gather information
on drug use and potential adverse events is desperately needed.
FDA cannot rely on the good graces of busy clinicians for
spontaneous reports of adverse events. Many medical schools do
not teach their trainees about the need to report adverse
events, so there is a need for education as well. FDA always
needs to stay in touch with practicing clinicians, but they
cannot be the only source of information in evaluating medical
interventions post-approval. In addition, for reasons discussed
previously drug sponsors cannot be the sole source of
information. There is little incentive for them to report
adverse events and there are recent unfortunate examples in
which important information was withheld from FDA. If FDA had
independent sources of information this would be less of a
concern.
FDA needs to hire adequately trained staff--It is
important that FDA hire, train and keep staff who have a
background and training in drug development and evaluation. It
is sad to say that many in academic medicine view a career at
FDA for their trainees as ``a waste of time'' and
``unscientific''. FDA needs to be on the same scientific par as
the National Institutes of Health and the Centers for Disease
Control and Prevention in terms of scientific reputation and in
terms of appropriately applying science. The only way to
accomplish this goal is if the scientific community has
positive interactions with FDA staff, instead of the current
``black box'' that clinicians see as the current FDA.
FDA needs close contact with the scientific community--FDA
has to have a symbiotic relationship with clinicians and
scientists. As science is ever-changing, FDA staff need to keep
abreast of the latest scientific developments. In addition, FDA
staff have much to teach the scientific community about
clinical trials and the pharmacoepidemiology, and much of the
view that FDA is ``unscientific'' comes from a lack of
understanding of the scientific principles upon which
appropriate drug evaluation is based. This means that FDA staff
need to be able to interact with scientist in their fields, an
issue I will address in terms of outputs from FDA as well.
II. Science and Process Inside FDA
FDA has become too focused on ``process'' to the exclusion
of the reason for why process is needed. The process as FDA
should serve good science which in turn protects and advances
the public health. Science should not serve process.
Appropriate processes are needed in order to drug sponsors to
submit data and for FDA staff to review this data in an orderly
way. However, on the Center for Drug Evaluation and Research
guidance page there are 53 guidances under the heading of
``process'' and 3 under the heading of ``drug safety''. Clearly
this balance seems tilted in the wrong direction. FDA managers
needs to treat the scientists and review staff with
professionalism and the basis for decision making needs to be
good scientific principles
FDA managers need to treat staff with professionalism--
Science is based on the scientific method, and as such, any one
who uses this method, from the medical student to the senior
attending, can make equally valid analyses and draw equally
valid conclusions. As with school teachers, if most of their
class fails the examination, they must take part of the blame.
If FDA managers believe their staff is not using appropriate
scientific analyses, then it is incumbent on these managers to
train staff in these same principles and provide mentoring for
them and career development paths. It is inappropriate and
unprofessional to characterize scientists who raise scientific
issues as ``disgruntled'' or to characterize a scientist work
as ``junk science''. FDA managers need to realize that there
are substantial issues with the relationships between managers
are staff at FDA that need to be addressed. A Union of
Concerned Scientists poll of FDA staff showed that 44 percent
of FDA scientists did not respect their managers' integrity. A
substantial shift in culture at FDA is needed, and this can be
accomplished by making FDA place where people who follow the
scientific method and who treat their peers with respect want
to work and those who choose not to behave professionally don't
want to work
Joint authority of Office of New Drug and Office of
Surveillance and Epidemiology regarding post-approval decision
making. It is part of the scientific method that data, analysis
and conclusions undergo peer review and re-analysis by others
to confirm the conclusions of a given set of scientists. Also,
it is only human nature that when one makes an important
decision that may affect the lives of thousands or million of
persons it is very disheartening to learn that decision may
have resulted in people being harmed. However, it is also part
of science that we learn more as more evidence accumulates.
Lastly, systems function best when there are checks and
balances and no one person or group of persons exerts absolute
authority. The framers of the Constitution set up a bicameral
legislature and three branches of government for exactly this
purpose. For all these reasons there needs to be joint decision
making authority between the Office that approves new drugs
(the Office of New Drugs) and the Office responsible for
evaluating drugs after approval (the Office of Surveillance and
Epidemiology). The Enhancing Drug Safety and Innovation act
could be strengthened by including provisions for this joint
authority.
Accountability for decision making and behavior at FDA and
increase ``whistleblower'' protections -There needs to be
accountability for FDA managers who treat staff
unprofessionally, both from within FDA by senior managers and
from oversight from Congress to ensure that accountability
takes place. Increased transparency of the operations at FDA
would discourage some from inappropriate behavior, and all of
FDA would benefit from changing the perception held by many
clinicians, academics and those in industry that FDA is a
``black box'' in which operations, decision making and the
scientific reasoning behind decision making seem unclear. There
is no blind acceptance of data in science, and statements that
``FDA cannot be second-guessed'' do not take into account that
``second-guessing'' (also called peer review and confirmation
of evidence) is part of science. One of the basic premises of
the scientific method is we can never be sure we are correct,
but we can always be proven wrong, so one needs to keep an open
mind at all times. No one questions that FDA managers have the
authority to render decisions, but with the authority comes
responsibility. There is no such thing as the FDA, as FDA is
made of up individuals. It would be best if no staff person at
FDA ever has to ``blow a whistle'' on inappropriate use of
science or failure to protect the public's health, but should
this be necessary, FDA staff need to know they will not be
risking their livelihood to protect patients. Therefore there
needs to be increased whistle-blower protections such as those
in the legislation proposed in the Swift Approval Full
Evaluation act.
Best Use of Science and Consistency of Decision Making
within FDA and publication of guidance on risk-benefit
analysis--One of the major complaints of drugs sponsors is that
they receive inconsistent advice from FDA. While in some cases
advice can and should change as science advances during the
course of drug development program, some sponsors feel that
they do not receive consistent scientifically-based advice from
Division to Division within FDA across similar drug development
plans in different therapeutic areas. This would seem at odds
with using appropriate scientific methods to make decisions.
FDA needs to train staff on the scientific and legal bases for
drug evaluation, especially in that there are legally mandated
standards for drug effectiveness that must be followed in order
to justify the potential adverse events of drugs. FDA needs to
formulate guidance which explains the scientific decision
making process of balancing risks and benefits. While there
needs to be some flexibility to accommodate individual cases,
there are some basic principles which would apply to all
situations, such as evaluating the frequency, severity and
seriousness of adverse events weighed against the nature and
magnitude of the benefits of a medical intervention. FDA
reviews need to explain the scientific as well as legal basis
for decision making and conclusions so that sponsors,
clinicians and the public can understand the scientifically
reasoning behind a decision. FDA reviews include a tremendous
amount of data and analysis but is it not always clear how this
data is synthesized into an overall decision.
III. Outputs from FDA
FDA serves the public and therefore needs to communicate
with the scientific community, clinicians and patients as well
as drug sponsors.
Transparency of decision making and reviews at FDA--The
Belmont Report in 1979 on the protection of subjects in human
research pointed out that research is the pursuit of
generalizable knowledge. For research to be ethical the
knowledge obtained must be generalizable in order to justify
exposing subjects to the risk of the research. If research is
not generalized, that is, shared with others in the scientific
community then it is inherently unethical. Therefore it is
incumbent upon FDA and drug sponsors to share the information
from all clinical trials. A registry that includes a listing of
all clinical trials including the results of these trials would
allow knowledge to be generalized. The Enhancing Drug Safety
and Innovation Act includes such a provision. It is important
that data from earlier phase trials be included in such
registries and databases as these earlier phase trials often
form the basis for evaluation of further adverse events post-
approval. In addition the results of these trials, not merely
that fact that they are ongoing or completed, need to be
included in any database in order for the results to be
generalizable. FDA reviews should be published on the FDA
website within a reasonable period of time (no longer than a
few weeks) in order for the scientific community to evaluate
the basis for FDA decision making. This form of peer review is
part of the scientific process.
FDA staff should have a right to publish and participate
in scientific meetings--As noted previously, FDA reviewers need
to keep current with the science in their field. This means FDA
staffers need to share their knowledge with those outside FDA
as well as gaining knowledge themselves from scientists outside
FDA. FDA reviewers need to be able to share their analyses with
the scientific community and the need to FDA managers to ``make
one decision'' should not bar a scientific discussion among the
scientific community. The Supreme Court ``make one decision''
and yet members of the Court still publish a minority as well
as a majority explanation of their findings. Therefore, FDA
should publish a Summary Basis of Approval (SBA) for each
medical intervention which would include a discussion of any
and all scientific differences during the review process and an
explanation and scientific reasoning for the final conclusions.
The IOM report tells us that now is the time to address the
important issues in evaluating drug safety that have needed to
be addressed for some time. In order to address this urgent
public health issue, we need to act now. Congress should
include provisions for strengthening the evaluation of drug
safety in any reauthorization of PDUFA. A recent Harris poll
showed that the public is losing confidence in FDA, and the
only way to restore that confidence is by action, not merely by
words or reshuffling of the structure of FDA and without new
resources and authority. We can address the important issues in
evaluating drug safety in an efficient way without slowing
bringing important medical advances to patients. Safety and
efficiency and not mutually exclusive goals and more focus on
post-approval activities need not slow pre-approval
evaluations. However, we need to learn from recent events and
take action today to avoid another Vioxx or Ketek tomorrow.
Congress can help FDA start down the road to being the foremost
authorities on pharmacoepidemiology, to work closely with the
scientific community to gather data and to develop new methods
and analyses, to come up with cogent scientifically based
approaches to evaluating the balance of risks and benefits of
drugs, and help FDA achieve its stated mission of protecting
and advancing the public health. Most FDA staffers are
courageous public health servants. Please give them the tools
they need to do their jobs for all of us.
----------
Mr. Pallone. Thank you. And we will take questions of the
panel now. Thank all of you again for being here. I am just
going to recognize myself for 5 minutes for some questions, and
I wanted to ask a couple questions of Ms. Thompson.
First of all, let me thank you for all the good work you do
with the Elizabeth Glaser Pediatric AIDS Foundation. I am
familiar with it, and I really know that you do a great job.
But I found your testimony interesting because you suggest that
the goals of a strong and robust drug safety system and at the
same time, innovative medicines are not necessarily mutually
exclusive, that you could possibly do both. And I am wondering
if you could elaborate more on why you think that doesn't have
to be an either/or scenario? In other words, if we were to pass
drug safety legislation that built upon what is already
included in the PDUFA IV proposal, that included stronger
monitoring and enforcement provisions--in other words, like if
we did what Mr. Waxman and Mr. Markey have included--do you
think that would kill innovation? Or would we still be able to
be innovative, so to speak?
Ms. Thompson. Well, I think we strongly believe that it
won't, in fact, kill innovation. What the IOM has proposed and
what, I think, has been picked up both in the Waxman-Markey
bill and the Kennedy-Enzi bill is to address this new paradigm
of looking at safety concerns throughout the life cycle of the
drug. So it is really taking the FDA back, in some senses, to
its roots under the original 1938 statute, which was all about
safety. Of course, efficacy wasn't added until 1962.
So by providing FDA the resources that it needs to maintain
its scientific excellence, the resources that it needs to
integrate more fully safety concerns both into the drug review
process and into the post-market surveillance process, I think
you have got the perfect recipe for enabling innovation to
continue and, in fact, supporting it because one of the areas
that has suffered under PDUFA is the FDA science base.
And FDA, in order to support the innovation that is coming
out from industry, needs to be the leader in terms of
regulatory science and in terms of advancing the tools and
techniques that are going to support regulatory discovery and
how that discovery gets translated into new therapies.
Mr. Pallone. Thank you. In your testimony, you call for
giving FDA authority to require testing for off-label uses of
drugs. But if Congress granted FDA such authority, how would
that match up with the Pediatric Incentive Program? How exactly
would those two programs work together? Would granting such
authority obviate the need for the incentive program? If you
would explain.
Ms. Thompson. Well, the answer is no, it would not obviate
the need, but we begin with the position that three-quarters of
the prescriptions that are written for children are written off
label. And the Pediatric Incentive Program, the program you
referred to, BPCA, Best Pharmaceuticals for Children Act,
provides a voluntary mechanism where FDA can go out and, if the
drug is still on patent, it can recommend to a manufacturer
that the manufacturer conduct certain studies to determine
effectiveness and/or safety in children.
But that only applies on a voluntary basis. Obviously under
the stick part of that equation, the pharmaceutical research
side, that legislation for the most part applies only to new
drugs. And there is a very high standard that FDA has to meet
to require studies now, very high safety finding or danger
finding that the FDA has to make.
So providing new authorities in combination with the
existing carrot-and-stick approach under pediatrics is really
essential if the FDA is going to be able to identify safety and
effectiveness for children.
Mr. Pallone. Thank you. I am just going to try to get in a
couple questions here to Ms. Van Syckel. Thanks again for being
here. But in your testimony, you don't specifically call for
the repeal of the user fee system. In fact, you suggest that it
should be expanded, but you call for it to be decoupled from
obligations made to the industry. Would you just comment
further on that? And then I am going to ask you also a second
question. You have been very vocal about improving
communications about medications to patients and providers, and
you have focused on the availability of the distribution of med
guides. Is there something that you think Congress could do to
improve communications about medication risks through changes
to the med guide system? So second, the med guides, and third
this whole idea of decoupling the user fee system.
Ms. Van Syckel. OK, let us start with the med guides first.
Mr. Pallone. OK.
Ms. Syckel. First we have a bill, S. 2364, in New Jersey
that is sponsored by Senator Codey and Senator Lance. We have
got two good guys there. And what we are trying to do is these
medication guides, we don't want to find them, if we get them,
in the bottom of a pharmacy bag. So what we would like is to
have parental informed consent. Look at the med guide with the
doctor, go over the med guide, don't just put it in the bottom.
I took this off the Internet. It is that simple. Doctors can do
that.
And I asked Assemblyman Conaway, because we had discussed
this issued. And I said Doctor, have you seen the med guide?
And he said yes, and I guess he assumed he had. And I said
well, could you please tell me what to look for? And he
couldn't tell me, and this is a doctor within New Jersey on the
assembly.
And I think it is important because everybody is so
concerned about the thoughts of suicide. There is a lot more of
side effects than just the thoughts of suicide, and those are
newer, worse irritability, acting aggressive, being angry or
violent, and acting on dangerous impulses. And I will give you
an example from New Jersey. There was a young teenager who was
an honor roll student, participated in peer groups. He was
over-medicated, and he brought a cache of weapons to school,
loaded guns, to even the point that the father, the parents
didn't even know where he got the guns.
So violence issue with the anti-depressants has become
very--is something that we should all be concerned about, and I
was so concerned that I attended a White House conference on
school violence and school safety. And I did have an
opportunity to speak to Attorney General Alberto Gonzales
concerning this issue, and I have even spoken to Mr. Ferguson
because I saw how my daughter attacked three police officers,
assaulted her brother. I see how violent the children become.
And the Attorney General asked Secretary Leavitt, sent him a
letter back in October to look at the violence issue concerning
the antidepressants.
So if parents don't have this med guide, and I think it is
very insulting for the FDA to say that there are some outsiders
who should determine what parents need to know. This is what we
need to know so if we make a decision to give them an
antidepressant, we can monitor them. The doctor can't do it.
The school district can't do it. It is up to the parents, and
we need this vital information.
I guess I was kind of being diplomatic with PDUFA. If it
were up to me in the great world, I would like to have it
repealed. But it is not the perfect world, and I believe we
need to focus more on an independent office of drug safety. I
am trying to be diplomatic but I sometimes can't. I truly
believe we need an independent office of drug safety. I agree
with Senator Grassley and Senator Dodd on this issue. They have
been at this issue for 4 years. They are knowledgeable.
Mr. Pallone. OK, thank you so much. Mr. Deal.
Mr. Deal. Mr. Theriault, I share your concern for
counterfeit drugs. In a previous hearing that we had where the
issue came up about adverse events, a questions was asked as to
whether or not there was any way, with our current information,
to distinguish adverse events that might have been caused by
counterfeit drugs as opposed to brand-name drugs. And the
general answer was no, there was not. Is there anything that we
should to do to try to deal with that particular issue? And are
there things that we might do that would--might have adverse
consequences, thinking we were doing the right thing?
Mr. Theriault. The adverse event reporting issue is
something that I think is difficult, and I am not sure how you
can differentiate between adverse events that are caused by
counterfeits as opposed to legitimate medicine. From our point
of view, the safety issue is addressable on a number of fronts.
I think that stopping these personal use amounts of
prescription medicines that come into the country, via the mail
services and that sort of thing, is almost a no-brainer.
We conducted a study about 2 years ago, and at the New York
City mail facility alone, there were over 40,000 packages a day
coming into that one mail facility that were identified as
unapproved pharmaceuticals. Tightening the supply chain,
requiring pedigrees, enforcing the pedigree aspect of PPNA. I
think you can't regulate the Internet, but I think you can
regulate the flow of products that are ordered on the Internet.
Mr. Deal. Could you give us some idea what proportion you
think are coming in from outside of the country versus
counterfeiters who are operating within our own country?
Mr. Theriault. In the last 10 years that I have been at
Pfizer, we have had probably the most aggressive anti-
counterfeiting program in the industry. And I can't recall one
counterfeiting manufacturing operation that we found in the
United States. I would say the very, very high percentage of
counterfeits in the 1990s comes from outside the United States.
And that is why, when we address importation and issues like
that, I think that unless we deal with the drugs coming in from
outside the United States we are going to have a problem.
Mr. Deal. Your written testimony indicates one particular,
I think it was an Internet pharmacies supposedly in Canada. How
big a problem is Internet pharmacy in this overall problem of
counterfeiting?
Mr. Theriault. Well, I think it is a huge problem. And to
your earlier point, the woman who died in Canada, I think, was
a U.S. citizen residing in British Columbia. As I understand
the facts, the medicine she received came in an unmarked vial.
There was no label, no safety information. There was very
little possibility to determine where she bought those, and the
Internet pharmacy that sell those things are up and down in a
matter of days.
So I think if you buy prescription drugs on the Internet,
you are taking about a 50 percent chance of getting either
counterfeit or unapproved generic medicines.
Mr. Deal. And I suppose you would support increasing the
penalties for the counterfeiting of drugs, would you not?
Mr. Theriault. Yes, sir, I would. I think Congressman
Rogers' bill is an excellent step in that direction.
Mr. Deal. OK, I would like to briefly explore the
procedures that are embodied at FDA now. I believe we refer to
them as the critical path. Dr. Powers, since you have worked
there, would you briefly comment on that initiative and whether
you think it is appropriate?
Dr. Powers. Sure, the critical path was initiated in March
2004, which is an attempt for FDA to partner with folks outside
the FDA, both academics and people in practice, to try to
develop tools that would more efficiently help drug
development, both in terms of measuring safety and
effectiveness. It is a great idea, but it is one in which FDA
is left in the position of having to suggest things to people
outside the agency and really doesn't have funding at this
point to be able to accomplish those things.
So they published several, including one last week on
generic drugs, saying here are some great things we would like
to know the answers to, but are left without the resources to
be able to do that in a lot of cases.
For instance, let us take the issue of biomarkers. The way
for us to explore whether those biomarkers are helpful in
selecting which patients may benefit or which patients are at
risk would mean looking at studies to see whether those
biomarkers make any sense or not. And right now, FDA is left in
the position of suggesting saying wouldn't this be a good idea.
Mr. Deal. Money would help.
Dr. Powers. It sure would.
Mr. Deal. Thank you.
Mr. Pallone. Mr. Ferguson.
Mr. Ferguson. Thank you, Mr. Chairman. Thanks to all of our
witnesses on our second panel. As most or some of you know, I
spent my time in the first panel talking about medication
guides. It is something I have spent a great deal of time on,
and Lisa and I have actually worked on the issue a lot
together.
Lisa, we have heard your testimony today. Of course, I am
very familiar with your own family's story. It is important
that you continue to share that with folks, including in this
setting, so people can just understand one family's situation
and ordeal. And you had said before you represent kind of
families in New Jersey, but you are not an official
organization or group.
Ms. Van Syckel. No, I am a mom.
Mr. Ferguson. You are a mom. You are a parent like I am and
so many of us are, trying to make sure you are taking care of
your child and having information to take care of Michelle----
Ms. Van Syckel. And Chris who is down in Florida.
Mr. Ferguson. Yes. Now, with regard to the medication
guides, you know that in 2004, we had our Oversight and
Investigation Subcommittee hearings and investigations into
this particular issue. And subsequent to that, these
medications, SSRIs, who are prescribed for kids now are
accompanied by or supposed to be accompanied by medication
guides. That was after your family situation.
Ms. Van Syckel. That is right.
Mr. Ferguson. If you can hypothesize, I guess, or----
Ms. Van Syckel. Finding out that the med guides weren't
being distributed?
Mr. Ferguson. Well, actually how would that have affected
your own family situation? If you had been presented with a med
guide when you filled that prescription for your daughter--I
mean it is tough in hindsight to be able to go back and figure
out what you would have done but----
Ms. Van Syckel. And I don't believe I, at that time, would
have known what to do because Michelle really didn't have
depression or anorexia. It turned out she had Lyme disease, so
we were desperate to help her. So would I have done this? I
don't know. I may have, but armed with this information at
least, I could have prevented the self-mutilation, the scars
that are on her body today.
We have a young girl who came to your office, and no one is
immune to the side effects of the antidepressants, and this
young girl, both of her parents work for the pharmaceutical
industry. And if you look at her arms, do those look like
little scratches to you? Cutting the word ``die'' onto the
inside of your arm? Is that an acceptable side effect? I don't
think so.
Mr. Ferguson. Now, you----
Ms. Van Syckel. But it is not here.
Mr. Ferguson. You obviously are in touch with and work with
other families who have had similar situations that we have met
with.
Ms. Van Syckel. They call me desperately seeking answers
because they said my doctor told me it was safe and not to
listen to the stories in the media, that they are parents that
are--they are actually labeling parents like me.
Mr. Ferguson. What do they say? And I have heard some of
them talk. But what is the general sense among some of the
families and parents that you know about the specific
information that they could have with medication guides if they
were being gotten into their hands properly?
And we have obviously had a breakdown in the system, and it
is normal and natural for parents or anybody who is concerned,
who has a conscience, to want to try and figure out who is to
blame and where to lay blame about this whole problem. But as
we have found, there is a big breakdown in communication and
responsibility and jurisdiction.
And that is what we are trying to get to the bottom of. But
at the end of the day, what we are finding is that there aren't
assurances in the system as we would like them to be today,
that every parent who has an SSRI prescribed for their child is
getting this information.
Ms. Van Syckel. Right, actually the parents in New Jersey
are angry with the doctors because they said the doctors should
know when they say it has a black box warning, I heard about
increased risk of suicide, and the doctor downplays the side
effect. But both parents, one who is a pediatric emergency room
nurse at a large hospital in New Jersey, who lost her niece
Brittany to a Prozac-induced cardiac arrest and then, of
course, with the other teenager, they said had they been
provided this information, the horror and the tragedy they
endured never would have happened.
And it has weakened the parents who have to make the
decisions with their children. It is not the FDA's job. It is
not the pharmaceutical companies' job. Parents, we don't want
to harm our children. We want the best medical care for them,
but I find it insulting that they believe that we don't know
how to handle this type of information. Give me the worst
scenario, and I will always pray for the best scenario.
Mr. Ferguson. Mr. Chairman, I know I am out of time, but I
think one of the reasons we work so hard on this issue is
because at the end of the day, parents are ultimately
responsible for the health care of their children. And that is
why they go to doctors. That is why they perhaps take
medications. That is why you consult with the widest variety
and try and gather as much information as you possibly can to
make the right decision for your own child. But you are
handicapped from making that decision if you don't have all the
information. That is why I think this med guide issue is so
important.
Ms. Van Syckel. Or if they choose to try the medication at
least they have the information to monitor their child.
Mr. Ferguson. That is right.
Ms. Van Syckel. Because that is really important because we
are with our children, 24/7. It is that important, and I have
to say this because I believe it is very important. But back
during the 2004 oversight and investigation, it was determined
by the FDA and by Congress that antidepressants was a causal
role in suicide. They used the word causal, but FDA negotiated
the label.
And now it is increased risk, and then we have the JAMA
study that just came out where they say there is no increase
and that the benefits outweigh the risks. But what that JAMA
study failed and what the FDA failed to do was when the child
stops taking the medication abruptly, cold turkey, that is when
we see our suicide attempts. That is when we see our violent
behavior. And FDA, during the adult hearings in this past
December, they stopped with their method analysis, their
investigation, day 1 of withdrawal. Now if they went for the
next 30 days or 4 to 6 weeks, you would have seen some violent
behavior, and you would have seen suicide.
And we also have 150 percent increase of prescribing
antipsychotics and Strattera to our kids. They also carry
suicide labels, and I mean it is pretty sad when I look at the
Medechi record in New Jersey and our new doctors, a
psychiatrist, is giving it to newborn babies. Risperdal and
Effexor, two deadly drugs, how were they administering that to
a baby? We need to look into Zyprexa and Risperdal and why they
feel the need that they have to medicate our toddlers.
Mr. Pallone. Thank you so much. Mr. Waxman.
Mr. Waxman. Thank you, Mr. Chairman. Dr. Ellenberg, I want
to ask you what are the provisions in the administration's
PDUFA proposal that allow user fee dollars to be put toward
increasing FDA's access to outside population-based
epidemiological databases. Information from these databases
would obviously be useful for FDA in its efforts to detect
safety signals earlier. This is an extremely positive
development, and I am encouraged to see that it was included in
the negotiated package.
But I think we need to go further in terms of providing FDA
with additional tools and authorities. One of IOM's
recommendations to Congress was to provide FDA with the
authority to require post-market studies. Can you tell us about
the benefits and limitations of data mining? Can you also
explain why, even if it has the enhanced ability to conduct
this so-called data mining, FDA still needs to have the ability
to require post-market studies?
Ms. Ellenberg. Yes. Well, there are a number of different
facets to understanding of risks of drugs post-marketing. Data
mining is a tool that people have been trying to implement with
the passive surveillance system, the reports that people send
in. And that can be a useful tool. With several hundred
thousand reports coming in every year, you can appreciate there
has got to be some kind of automated way to pull out patterns
that might need further investigation. And that is what data
mining is. So that is one piece of post-marketing surveillance.
And that might be the fastest way to actually identify a very,
very strange, unusual, very rare adverse event because it could
be reported from anywhere.
That is not a good way to identify an increase in a fairly
common background rate. So, for example, increased rates of
heart attacks with a widely-used drug, you will not find that
from a passive reporting system with data mining.
Access to health care databases where you have information
on thousands or hundreds of thousands of people and their
ability to follow them over time, taking drugs, you might be
able to get some information there. So I don't think it is one
or the other. And sometimes----
Mr. Waxman. You think both are very----
Ms. Ellenberg. You need both, and you need the ability to
sometimes carry out perspective studies that might even need to
go beyond existing databases.
Mr. Waxman. IOM also concluded that Congress needs to
provide FDA with other authorities the agency currently lacks.
For example, one, the authority to place a moratorium on DTC
advertising and to require the specific warnings be
incorporated into DC ads. Two, the ability to require that
labels of new drugs carry a special symbol to indicate their
newly approved status. Three, the ability to require that
companies make label changes instead of just asking them to do
so.
Additionally, the IOM has said Congress should enhance
FDA's enforcement tools to include things like civil monetary
penalties, so that the FDA had other choices besides using its
bully-pulpit to threaten using its only real enforcement tool,
the nuclear option of removing the drug from the market.
Obviously the administration's PDUFA legislation proposal does
not incorporate these recommendations.
In your view, if Congress were to act this year only on the
drug safety-related provisions included in the administration's
PDUFA proposal, would the very serious drug safety oversight
problems that the IOM describes in its report be resolved?
Ms. Ellenberg. Well, as a member of the IOM committee that
put the report together, we all felt strongly that the whole
package really ought to be adopted, and it was not something to
pick and choose, use this one, use that one. So I do believe
that these authorities would be helpful.
It is very hard for me or probably anybody to assess really
what will happen with this aspect, without this aspect. It
would be very hard to predict, but it seems to me that those
additional tools could be used by the FDA. Most of the things
that you mentioned relate to adequate communication of risk to
the public and the issues of what is in the label, ability to
regulate DTC advertising. Those are all how do we get
information on risks out to the public.
Mr. Waxman. Well, along those lines, IOM recommended
Congress pass legislation that would require companies to
register and report the results from their clinical trials and
public available database. Can you tell us what lead to this
recommendation and why the IOM felt it was necessary to create
a mandatory system?
Ms. Ellenberg. Well, the concern is that studies may be
done that suggest that there may be an increased risk or
suggest something that is not favorable about a drug and that
if nobody knows that study was done, if that is hidden under
regulations, and then other studies are done that maybe don't
show that, well it would be hard to know if you have a whole
picture, whether this is something we should worry about or
not. If we don't see the studies that suggest that there might
be a problem, they don't know that there might be a problem.
So there certainly has been a move toward making these
public. I think there was a provision----
Mr. Waxman. But do you think it ought to be mandatory?
Because it could be voluntarily be made public.
Ms. Ellenberg. I think that many companies are voluntarily
making these public. I don't know the extent to which they are
doing that now so----
Mr. Waxman. Mr. Chairman, if you permit, I have one last
question, and I would like to pursue it. We heard from Dr.
Galson on the first panel about FDA's system for handling the
steadily increasing number of AERs the agency receives, and you
describe this trend in your testimony also. He told us they got
a half million AERs, and I understand that approximately
200,000 were for serious and unexpected conditions. He said
that the staff available to review those reports has been
limited by resources. In fact I understand that there are only
20 epidemiologists who review all of those reports.
Dr. Galson also described the upgrades to the agency's IT
system that would help to review these reports that FDA would
make with an increase of PDUFA dollars for that purpose. But he
said it would be only $4 million. I am concerned that that may
not be enough. Can you describe in more detail the situation
with respect to the agency's review of AERs and comment on
whether you think $4 million would be enough to complete what
would be a massive overhaul of FDA's IT infrastructure?
Ms. Ellenberg. No, I don't think $4 million would be enough
at all. I think you need probably more than that just to do a
reasonable overhaul, a reasonable redo of the adverse event
reporting system to incorporate the data mining, making that
routine, training reviewers, having enough reviewers to look at
it. But as I said before, that is just a single piece, a single
component of the needed system. The Centers for Disease Control
has a series of databases that they use from the Kaiser
Permanente system, and I think they spend something like $10 or
$15 million a year to maintain that system so that if there are
vaccine adverse events that people are concerned about, vaccine
safety issues, they can really go right to that system and try
and get answers very, very quickly.
And it is that kind of a linkage of databases that FDA
needs to have access to investigate drug safety problems as
well.
Mr. Waxman. OK, thank you. Thank you, Mr. Chairman.
Mr. Pallone. Thank you. Dr. Burgess.
Mr. Burgess. Thank you, Mr. Chairman. Dr. Levine, let me
just ask you since this question just came up and you were
referenced, do you have a concept of what the dollar
expenditure was to develop the data operation that you have at
Permanente?
Dr. Levine. To develop the data operation?
Mr. Burgess. Right, the continual data observation that you
have.
Dr. Levine. I know that the development of our fully
automated medical record system, including the inpatient and
outpatient pharmacies, is in the billions of dollars. The piece
in terms of vaccine safety, which was developed with our
Vaccine Center and the CDC, I don't know the cost of the
implementation. That was a stand-alone system.
We are currently involved in trying to roll all of our
legacy and stand-alone systems into a single fully-automated
medical record, which will actually enable projects like the
one we did with the FDA and the ones we are doing with the CDC
to be done much less expensively because the maintenance of
those legacy systems is extraordinarily expensive. And I share
the concern about what you can do with $4 million, just based
on what it costs us to do anything in IT.
Mr. Burgess. Let me ask you a question just to put it in
context. How many covered lives are there in Permanente?
Dr. Levine. In the present Kaiser Permanente Medical Care
Program, there are 8.7 million covered lives. In northern
California, it is about 3.35 million.
Mr. Burgess. But that system which you described that cost
X million dollars, that covers----
Dr. Levine. All 8.7.
Mr. Burgess. How long did it take to develop that?
Dr. Levine. We are midway through the implementation, and
development is going hand and hand. We are using software from
the Epic Systems, which is one of the largest medical record
systems based in Madison, Wisconsin. It was developed for
outpatient systems, and we are working with Epic to adapt their
product to our very large population.
Mr. Burgess. And that is probably a topic for another
hearing, Mr. Chairman, but it does show the size and the scope
of the problem. Dr. Loew, let me ask you, you referenced a
figure of 3 percent of medications that were taken off the
market. Is that the correct way to phrase that?
Ms. Loew. That is correct. In the past 20 years, the
withdrawal rate has been consistently around 3 percent.
Mr. Burgess. The withdrawal rate. That is the term you
used. Now, of that, can you just give us an idea of what the
number of products were that were withdrawn, say, in the last 5
years?
Ms. Loew. Actually, I don't have that figure, but we can
get that data.
Mr. Burgess. Can you get that for us?
Ms. Loew. Absolutely.
Mr. Burgess. And would you have an idea as to how many of
those were voluntarily withdrawn by the manufacturer, what
problems came to light, and how many of those were enforcement
actions by the FDA?
Ms. Loew. I believe that in many situations, it is a
voluntary withdrawal on the part of the manufacturer. A safety
issue comes to light. They discuss it with the FDA and decide
to withdraw the product from the market, but we will get you
the exact data on that.
Mr. Burgess. OK, I was just thinking back, and I can't
recall an instance where there was an actual FDA recall. But I
am sure it must have happened, but most of----
Ms. Loew. The majority of the situations, if I recall, were
all situations where the manufacturer had voluntarily taken it
from off the market. But I can't verify that.
Mr. Burgess. Great. If you could get that for us, that
would be wonderful. We heard testimony from another witness on
the panel that the drug manufacturers, in fact, they don't even
pay attention to safety issues after the product has been
approved because they have no incentive to do so. Is that an
accurate statement?
Ms. Loew. I would argue that the opposite is completely
true. Pharmaceutical manufacturers take the safety of our
products extremely seriously. There are, in fact, some
extensive requirements for manufacturers to monitor their
products in the marketplace, and there are a number of
different tools. There are, of course, the adverse effects
reporting systems that we have heard about today. If there is a
serious adverse event that is detected that is an event that
hasn't been previously seen, manufacturers have an obligation
to report that to the FDA within 15 days and then to follow up
15 days later with a full report. An additional report
quarterly in the first 3 years of production on the
marketplace, to quarterly submit reports to FDA on the adverse
events that have been detected around the product.
In addition to that, there is an annual report requirement
where companies submit all new information that has become
available on the product. The manufacturing rate of
information, new clinical data, observational data, and so on.
They are required to report that, so they take the obligations
of monitoring the product in the marketplace extremely
seriously. And it is, of course, in their best interest to
ensure that is the case and, of course, the best interest of
the patients.
Mr. Burgess. Thank you. Mr. Theriault, let me just ask you,
you talked about a number of things that are being done. A
company that I became familiar with several years used a
labeled isotope in like the parts per billion range to ensure
that products were what they said they were, and I think they
were talking about rap CDs at the point that they could put
this isotope in ink that was on the label and that way, detect
whether or not the counterfeit product had found its way into
the supply chain.
And I asked the question at that time could this apply to
pharmaceutical agents as well because we are talking about a
molecule that again would be in the parts per billion range.
And the question obviously came up, well, how would the FDA
look upon that? Have you had any experience with investigating
those types of technologies?
Mr. Theriault. We haven't looked at that technology. I
think the FDA's preference right now is for RFID tracking, and
we have got a pilot project around that right now. But I think
one of the issues there is where does the authentication occur?
Is it the patient who authenticates the product, the
pharmacist, or somebody else in the supply chain? But to answer
your question directly, I think that technology probably could
apply.
Mr. Burgess. There was a news story probably 4 or 5 years
ago now from New Orleans where they did an analysis of not so
much the active ingredient of the medication, but just the
inert part of the pill, the vehicle that the medicine was
contained in and found significantly high--for medicines
purchased over the Internet--and found significantly high
quantities of heavy metals, cadmium, liquid chromium. To your
knowledge, is that still an ongoing problem?
Mr. Theriault. It is. We have seen a number of cases
involving heavy metals recently, and I think that the woman who
died in British Columbia, I think the coroner said her death
could possibly be related to heavy metals that probably she was
taking.
Mr. Burgess. Thank you, Mr. Chairman.
Mr. Pallone. Let me thank our entire panel for being here
this afternoon. I felt this was a good opportunity to hear from
you and ask some questions that were really pertinent, and we
appreciate it. A number of people asked if they could submit
things for the record, both members and panelists. And, of
course, we will do that. We will include those things in the
record. And you may get additional written questions from some
of us in the next 10 days, which we would like you to answer as
well in writing. And again thank you all, and I thought it was
very good today. We appreciate your help. And with that, the
subcommittee meeting is adjourned.
[Whereupon, at 3:05 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
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