[House Hearing, 113 Congress]
[From the U.S. Government Publishing Office]
FDA CHECKUP: DRUG DEVELOPMENT AND MANUFACTURING CHALLENGES
=======================================================================
HEARING
before the
SUBCOMMITTEE ON ENERGY POLICY,
HEALTH CARE AND ENTITLEMENTS
of the
COMMITTEE ON OVERSIGHT
AND GOVERNMENT REFORM
HOUSE OF REPRESENTATIVES
ONE HUNDRED THIRTEENTH CONGRESS
FIRST SESSION
__________
DECEMBER 12, 2013
__________
Serial No. 113-101
__________
Printed for the use of the Committee on Oversight and Government Reform
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COMMITTEE ON OVERSIGHT AND GOVERNMENT REFORM
DARRELL E. ISSA, California, Chairman
JOHN L. MICA, Florida ELIJAH E. CUMMINGS, Maryland,
MICHAEL R. TURNER, Ohio Ranking Minority Member
JOHN J. DUNCAN, JR., Tennessee CAROLYN B. MALONEY, New York
PATRICK T. McHENRY, North Carolina ELEANOR HOLMES NORTON, District of
JIM JORDAN, Ohio Columbia
JASON CHAFFETZ, Utah JOHN F. TIERNEY, Massachusetts
TIM WALBERG, Michigan WM. LACY CLAY, Missouri
JAMES LANKFORD, Oklahoma STEPHEN F. LYNCH, Massachusetts
JUSTIN AMASH, Michigan JIM COOPER, Tennessee
PAUL A. GOSAR, Arizona GERALD E. CONNOLLY, Virginia
PATRICK MEEHAN, Pennsylvania JACKIE SPEIER, California
SCOTT DesJARLAIS, Tennessee MATTHEW A. CARTWRIGHT,
TREY GOWDY, South Carolina Pennsylvania
BLAKE FARENTHOLD, Texas TAMMY DUCKWORTH, Illinois
DOC HASTINGS, Washington ROBIN L. KELLY, Illinois
CYNTHIA M. LUMMIS, Wyoming DANNY K. DAVIS, Illinois
ROB WOODALL, Georgia PETER WELCH, Vermont
THOMAS MASSIE, Kentucky TONY CARDENAS, California
DOUG COLLINS, Georgia STEVEN A. HORSFORD, Nevada
MARK MEADOWS, North Carolina MICHELLE LUJAN GRISHAM, New Mexico
KERRY L. BENTIVOLIO, Michigan Vacancy
RON DeSANTIS, Florida
Lawrence J. Brady, Staff Director
John D. Cuaderes, Deputy Staff Director
Stephen Castor, General Counsel
Linda A. Good, Chief Clerk
David Rapallo, Minority Staff Director
Subcommittee on Energy Policy, Health Care and Entitlements
JAMES LANKFORD, Oklahoma, Chairman
PATRICK T. McHENRY, North Carolina JACKIE SPEIER, California, Ranking
PAUL GOSAR, Arizona Minority Member
JIM JORDAN, Ohio ELEANOR HOLMES NORTON, District of
JASON CHAFFETZ, Utah Columbia
TIM WALBERG, Michigan JIM COOPER, Tennessee
PATRICK MEEHAN, Pennsylvania MATTHEW CARTWRIGHT, Pennsylvania
SCOTT DesJARLAIS, Tennessee TAMMY DUCKWORTH, Illinois
BLAKE FARENTHOLD, Texas DANNY K. DAVIS, Illinois
DOC HASTINGS, Washington TONY CARDENAS, California
ROB WOODALL, Georgia STEVEN A. HORSFORD, Nevada
THOMAS MASSIE, Kentucky MICHELLE LUJAN GRISHAM, New Mexico
C O N T E N T S
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Page
Hearing held on December 12, 2013................................ 1
WITNESSES
Scott Gottlieb, M.D., Resident Fellow, American Enterprise
Institute
Oral Statement............................................... 2
Written Statement............................................ 5
Peter Huber, Ph.D., Senior Fellow, Manhattan Institute
Oral Statement............................................... 13
Written Statement............................................ 15
Mr. Paul Hastings, President and Chief Executive Officer, Oncomed
Pharmaceuticals, Inc.
Oral Statement............................................... 20
Written Statement............................................ 22
Janet Woodcock, M.D., Director, Center for Drug Evaluation and
Research, Food and Drug Administration
Oral Statement............................................... 42
Written Statement............................................ 45
APPENDIX
Opening Statement by Rep. Speier................................. 74
Opening Statement by Rep. Cartwright............................. 76
Department of Health and Human Services Response to Questions for
the Record..................................................... 77
FDA CHECKUP: DRUG DEVELOPMENT AND MANUFACTURING CHALLENGES
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Thursday, December 12, 2013
House of Representatives,
Subcommittee on Energy Policy, Health Care and
Entitlements,
Committee on Oversight and Government Reform,
Washington, D.C.
The subcommittee met, pursuant to call, at 1:35 p.m., in
Room 2154, Rayburn House Office Building, Hon. James Lankford
[chairman of the subcommittee] presiding.
Present: Representatives Lankford, Gosar, Meehan, Speier,
Duckworth, and Lujan Grisham.
Staff Present: Will L. Boyington, Press Assistant; Molly
Boyl, Deputy General Counsel and Parliamentarian; Daniel
Bucheli, Assistant Clerk; Katelyn E. Christ, Professional Staff
Member; John Cuaderes, Deputy Staff Director; Linda Good, Chief
Clerk; Emily Martin, Counsel; Sharon Meredith Utz, Professional
Staff Member; Sarah Vance, Assistant Clerk; Jaron Bourke,
Minority Director of Administration; Krista Boyd, Minority
Deputy Director of Legislation/Counsel; Aryele Bradford,
Minority Press Secretary; Courtney Cochran, Minority Press
Secretary; Yvette Cravins, Minority Counsel; Adam Koshkin,
Minority Research Assistant; Juan McCullum, Minority Clerk; and
Daniel Roberts, Minority Staff Assistant/Legislative
Correspondent.
Mr. Lankford. Committee will come to order. I would like to
begin this hearing by stating the Oversight Committee mission
statement. We exist to secure two fundamental principles.
First, Americans have the right to know that the money
Washington takes from them is well spent. And second, Americans
deserve an efficient, effective government that works for them.
Our duty on the Oversight and Government Reform Committee
is to protect these rights. Our solemn responsibility is to
hold government accountable to taxpayers because taxpayers have
the right to know what they get from their government, we will
work tirelessly,in partnership with citizen watchdogs, to
deliver the facts to the American people and bring genuine
reform to the Federal bureaucracy. This is the mission of the
Oversight and Government Reform Committee.
I am going to waive our opening statements today from the
ranking member and myself because we have votes that are coming
very soon and I want to make sure that we get the opening
statements from our guests that are here on the first panel. It
looks like those votes will be called fairly shortly. When they
are called, we'll slip away, vote, and then we'll come back and
we'll do questions from then and then obviously move on to our
second panel.
But with that, I would like to recognize Ms. Speier. One of
the panelists is from her district, actually. I want to give a
chance for her to be able to recognize him.
Ms. Speier. Mr. Chairman, thank you, and I, too, will
submit my opening statement for the record.
I do want to take great pleasure in introducing someone who
I have known professionally for a number of years. He is the
CEO of OncoMed Pharmaceuticals, and that's Paul Hastings, who
is with us this afternoon. OncoMed is located in my district
and is doing groundbreaking work on stem cell therapies that
could provide important alternatives for the treatment of
cancer. And Mr. Hastings is what you would refer to as a serial
startup CEO and has done great work over many decades.
So, thank you, Mr. Chairman.
Mr. Lankford. All members will actually have 7 days to be
able to submit opening statements for the record as well.
Let me introduce the other two panelists as well. We have
two prolific writers that are here. Dr. Scott Gottlieb is the
resident fellow at the American Enterprise Institute, and Mr.
Peter Huber is a senior fellow at the Manhattan Institute, all
done significant work and research in the area. If you are not
familiar with our topic today, we are dealing with the FDA and
the drug approval process.
And so glad to have all three of you here as experts in
this conversation.
So, pursuant to committee rules, all witnesses are sworn in
before they testify, so if you could please stand. Raise your
right hand.
Do you solemnly swear or affirm the testimony you are about
to give will be the truth, the whole truth, and nothing but the
truth, so help you God?
Thank you. You may be seated.
Let the record reflect all the witnesses answered in the
affirmative.
In order to allow time for discussion, I would ask you to
keep your testimony, your oral testimony to about 5 minutes.
You'll see the clock in front of you. All of you are veterans
at this table before, and so we would ask you to do that oral
statement, as you know full well. All of you have submitted a
tremendous amount of written information as well. That will go
into the permanent record also.
Mr. Gottlieb, be glad to be able to receive your opening
statement.
WITNESS STATEMENTS
STATEMENT OF SCOTT GOTTLIEB
Dr. Gottlieb. Thanks a lot, Mr. Chairman, Ms. Ranking
Member. Thank you for the opportunity to testify today before
the committee. My name is Scott Gottlieb. I am a physician and
resident fellow at the American Enterprise Institute. I
previously worked at FDA as the agency's deputy commissioner
and at CMS as a senior adviser to the administrator.
I want to address the issues related to FDA's review and
approval of novel treatments for serious diseases that aren't
adequately addressed by available medicine. The FDA has been
effectively implementing provisions included in the last
reauthorization of the Prescription Drug User Fee Act related
to breakthrough therapies. I believe these provisions are
having a noticeable impact on FDA's willingness to embrace new
approaches to expedite the development of these sorts of new
treatments, but I still believe there is more that can be done.
The drug development process itself has become long and
costly owing to regulation that serves to add to premarket
burdens, but often without meaningfully improving the safety of
drugs or what we know about their effectiveness, and we are not
taking full advantage of what science has made available, not
only in terms of new and more targeted therapies, but better
ways for evaluating them.
The review staff at FDA is a dedicated and well-intentioned
clinical group of people who are often leading experts in their
respective fields, but they are also heavily influenced by
outside voices, and it's often the critics talking the loudest.
Years of complaints about FDA's oversight of drug safety, about
the high cost of drugs relative to their perceived benefits at
the time of initial market entry, and criticism about the
science that FDA uses in its review processes from vocal
academics who often have their own parochial views in these
matters, all of these things have taken a toll on FDA's
culture.
Over time, it is sanding down people's willingness to take
the risk of adopting new approaches to the agency's work, even
around areas of unmet medical needs that might not have
anything to do with the concerns that incited the initial
concerns.
The result is that a fear of uncertainty now pervades the
review process. When it comes to drugs targeted to unmet
medical needs, I believe it's a fear of uncertainty around
efficacy that is having the most profound impact of how drugs
are being developed. FDA staff is often unwilling to take risk
when it comes to observations around drug efficacy. They
require experiments that leave little doubt that the magnitude
of the benefit observed in a trial is not a function of any
statistical chance. In short, they want to conduct pristine
experiments that leave little uncertainty about the results
describing a drug's efficacy that they are precise and beyond
any statistical doubt.
Here it's important to distinguish between the magnitude of
the benefit being observed and the believability of that
result. I am not talking here about FDA's concern that a drug
must show a certain amount of benefit. Some threshold of
measurable benefit is always necessary to provide a proper
balance against known risks.
Rather, it's how FDA guarantees the believability of that
observation of benefit that I believe is having the most
significant delay on the development of new drugs. FDA requires
longer, larger trials to get pristine statistical results. This
makes their ultimate decision around the approval easier since
evidence is clear, but it also adds to time and cost.
I believe there are ways to enable faster development of
new drugs for unmet diseases and timelier access, while still
ensuring that future patients will have appropriate
information. We need to focus on reforms that will help the
review culture at FDA evolve when it comes to these issues. I
want to offer some suggestions that are aimed towards these
ends.
First, we should consider changing how clinical
effectiveness is defined in the setting of rare diseases. FDA
insists that there is a single standard for establishing safety
and effectiveness. I think the FDA needs clearer direction
around when we as a society want it to exercise its existing
discretion to streamline development programs. This doesn't
mean that safety and effectiveness isn't firmly established for
the drugs aimed at rare disorders. It only means that we are
making a much more explicit acknowledgment of FDA's existing
discretion to adjust trial requirements based on the
circumstances.
Second, the breakthrough therapies pathway has been a
successful legislative effort and its implementation by FDA has
had a palpable impact on the review process. But a full-
throated embrace of the spirit of this legislation requires a
cultural change at FDA that is invariably slow to unfold. For
these reasons, we might also consider changing the
organizational structure of FDA to hasten the adoption of these
provisions.
Specifically, rather than allow drugs aimed at very rare
disorders to be reviewed alongside drugs targeted to more
common maladies, we might consider carving out the novel
breakthrough drugs into a separate group inside FDA, a sort of
skunk works charged with implementing novel review requirements
and regulatory science. Such a group might more readily embrace
concepts that can change how we develop drugs, introducing
greater efficiency, ideas like the use of adaptive trial
designs, Bayesian statistical techniques, and wider use of
molecular profiling and targeting of medicines.
These are not new concepts, but they are very slow to gain
adoption. In an agency where reviewers are under constant
political pressure and time constraints, they don't feel a lot
of liberty to incorporate unfamiliar and new approaches, or
take new risks in embracing concepts that are untried. So they
stick with familiar constructs, even if these traditional
approaches are unnecessarily costly and burdensome.
These are just a few ideas on how to advance FDA's science
and make the process for the consideration of drugs aimed at
vexing and unmet medical diseases more efficient. FDA has made
great strides towards these ends through its recent
implementation of breakthrough therapies. I would argue that to
make further reforms, it would require measures that start to
change the culture of FDA as it relates to these challenges.
Thank you.
[Prepared statement of Dr. Gottlieb follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Lankford. Mr. Huber.
STATEMENT OF PETER HUBER
Mr. Huber. Mr. Chairman, Madam Ranking Member, among
Federal regulators, the FDA plays a uniquely strong role in
regulating not just the product, but the development of the
core science that allows the industry to design the products
that do what we want them to do.
The science at stake here is not drug science. There is no
such thing. It is drug patient science. It is how the drug's
chemistry interacts with the patients. And drug designers can
learn quite a bit by just studying biology, but at the end of
the day, to get the science right, you do have to start
prescribing the drug to patients and study what happens.
So before it licenses a drug, the FDA issues something
called an investigational license that scripts how we set about
systematically and scientifically developing drug patient
science, and those scripts have simply not kept pace, in recent
years particularly, with what the best scientific
investigations can now do and should be doing.
The blinded, randomized trial protocols that the FDA still
relies on overwhelmingly to this day were first used in 1938.
They were expanded and formalized in the 1960s. They begin with
conventional clinical definitions of the disease. The criteria
used to select the patients to participate in the trials must
be specified before the trial begins, or to a limited extent
resolved in the very early phases of the trial when very few
patients are involved. The doctors involved aren't allowed to
systematically explore molecular factors that affect how one
patient may respond well to a drug and another may respond
badly to the same drug even if they are presenting the same
clinical symptoms.
The only issues that these protocols address systematically
are something called selection bias, which is a deliberate or
inadvertent stacking of the data by doctors, or the placebo
effect, which is wishful thinking by patients. The trials teach
us next to nothing about how variations in patient chemistry
affect responses to the drug.
The FDA's concerns about selection bias are legitimate, but
modern molecular medicine hinges on the deliberate scientific
selection of the right drug-patient molecular combinations.
Patients suffering from the same clinically defined disease
often present different clusters of molecular targets deep
down. There is no such disease as breast cancer. There are at
least 10 biochemically distinct breast cancers down there. We
treat some with estrogen blockers and we treat others with
estrogen itself. One of the estrogen blockers, its performance
depends on liver genes, which determine whether the patient
metabolizes that drug properly or not.
And I could go on and on. There are diseases that change
rapidly on the fly. The chemistry of cancer cells changes at a
wild pace as it progress. So do HIV infections. Many of these
fast-changing diseases require multi drug regimens and
cocktails. Side effects add still more relevant patient side
variation in the chemistry.
A good trial of a good drug should culminate in
prescription protocols that will make it possible for future
doctors to prescribe the drug to the patients who present the
molecular profiles that will interact well with that drug. When
we don't do that, there are two major consequences. The first
one is little noted but deserves a lot more attention. During
the trials themselves, we may quite often be doing real harm
unnecessarily to significant numbers of the patients involved.
A consensus report issued a few years ago by a coalition of
cancer experts drawn from the industry, academia, and the FDA
itself says the FDA still relies on, ``traditional population-
based models of clinical trials...that may form the antithesis
of personalized medicine, and accordingly these trials expose
large numbers of patients to drugs from which they may not
benefit.''
If you are saying that you are exposing large numbers of
patients to cancer drugs from which they won't benefit, you are
saying quite something, because these drugs are very often
toxic and powerful drugs, and you really don't want to be
prescribing them to the wrong patients for long.
The second consequence follows directly from the first. If
we are testing drugs in many of the wrong patients, many drugs
that we do in fact need, because they would benefit significant
numbers of patients, will not make it through these trial
protocols, because to perform well, a drug has to be prescribed
well. We know how to design what are called adaptive trials. In
brief, you gather a great deal of data tracking, genomes, and
proteins and other biomarkers that may affect the trajectory of
the disease and side effects and cause different patients to
respond in different ways. Patients can be added or removed
from trials or treatment regimens can be altered to improve our
understanding of the drug-patient molecular science.
There are sophisticated statistical profile processes and
algorithms that can handle this very complex data. Because the
adapters learn and because the investigators learn and adapt as
they go, the patients involved receive on average much better
treatments. It really is high time to dispense with these old
trial protocols and use the statistical methods of the future
and the modern molecular tools that let us track and learn
about all these factors.
Mr. Lankford. Thank you.
[Prepared statement of Mr. Huber follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Lankford. Mr. Hastings.
STATEMENT OF PAUL HASTINGS
Mr. Hastings. Thank you, Chairman Lankford.
Mr. Lankford. Mr. Hastings, do you mind turning your
microphone on there? Thank you.
Mr. Hastings. Sorry about that.
Chairman Lankford and Ranking Member Speier, members of the
committee, My name is Paul Hastings, chairman and CEO of
OncoMed Pharmaceuticals, headquartered in Redwood City,
California. I also serve as chairman of the BIO Emerging
Companies Section Governing Board, which represents the small
entrepreneurial and emerging biotechnology companies that often
do not yet have a product on the market, and we are the
majority of BIOs over 1,000 members.
I personally have 27 years of experience in biotechnology
and the pharmaceutical industry. My current company, OncoMed
Pharmaceuticals, is working at the cutting edge of oncology
research, focused on antibodies that target a specific set of
cells within tumors known as tumor initiating cells. These
cells drive the growth and metathesis of the tumor of the
spread, and they can differentiate into various cell types
within the tumor. Currently we have five products in clinical
development, all discovered at OncoMed, and over 13 completed
or ongoing clinical trials, with more than 280 patients
receiving our investigational agents.
We continue to pursue the discovery of additional
disruptive and novel antitumor initiating product candidates.
The U.S. biotechnology industry is working on treatments and
therapies that have the potential to deliver new solutions to
our most pressing healthcare needs and is a key element of an
innovation-driven economy. We've come a long way in turning
incurable disease to treatable disease, increasing the ability
of patients to maintain independent lives. With the number of
people over 65 increasing, improving the quality of life and
ability for patients to maintain independence is a national
imperative. Hundreds of companies like mine are working on
these solutions with over 400 clinical trials currently
underway focused on developing the next generation of medicines
for over 200 diseases.
This is also an industry poised to be a major contributor
to a 21st century innovation-driven economy in the United
States. However, we continue to face intense competition from
other countries, as well as increasing R&D costs, regulatory
challenges, and a contracted funding environment.
This year, working with the FDA, we have seen positive
signs that the biotechnology industry is recovering not only
from some of the regulatory hurdles, but also from the economic
crisis. Thirty-nine biotech companies have gone public this
year, including my own, marking the most active IPO market in a
decade. Additionally, in 2012 the FDA approved 39 new molecular
entities, the most approvals we have seen in 16 years.
Now, while this is good news, the financial and regulatory
environment continues to pose significant challenges to
innovation and drug and biologic developers like ourselves. For
example, first-time private financings, not public financings,
but private financings, venture capital financings, the
lifeblood of the innovation biotechnology industry, these
first-time financings for new companies are actually at the
lowest we've seen since 1995. And while we've seen an increase
in the number of approvals, we have also seen a steep increase
in research and develop cost, much of which is associated with
increased requirements and costs to run clinical trials.
FDASIA contains several provisions designed in cooperation
with industry and the FDA specifically to provide FDA with the
resources and processes that encourage the utilization of
modern tools and approaches, such as adaptive clinical trial
design, and allow for more interactive scientific dialogue
between the FDA, the industry, and patients. Some of the most
exciting provisions in FDASIA now include an expanded
accelerated approval pathway designed to improve on the
historical success this program has had with developing game-
changing medicines to treat HIV and AIDS and other cancers, as
well as other diseases, and expand its utilization in other
disease areas, and a new breakthrough therapy designation
designed to get the most promising medicines to patients much
more efficiently.
However, while FDASIA included an agreement by the industry
to significantly increase user fee funding for the FDA to help
support FDA's drug review activities and enable them and these
new programs, sequestration has diverted a portion of these
industry fees to an escrow account that has no practical
purpose for the FDA, industry, or patients. This has severely
hindered FDA's ability to fully implement critical provisions
of FDASIA that would improve our ability to more effectively
develop and deliver innovative medicines to patients. This is
the equivalent of our paying our utility bills and then being
told we can't access power, lights, or heat.
BIO would like to thank Congress for proposing a 2-year
delay in sequestration of user fees in the proposed budget
agreement but urges Congress to rectify this irrational and
counterintuitive situation by passing the FDA Safety Over
Sequestration Act of 2013, sponsored by Representatives Leonard
Lance and Anna Eshoo, with broad bipartisan support.
While many new measures have been embraced and encouraged
by Dr. Hamburg, Dr. Woodcock, and their colleagues and
management at the FDA, it's yet to be seen if the regulatory
flexibility afforded by FDASIA is being fully embraced at and
across the FDA reviewer level to advance the development of new
therapies for unmet medical needs. Releasing user fees from
sequestration, successful implementation of FDASIA, and
enabling our colleagues at the FDA could significantly improve
the ability of our industry to more effectively develop new
medicines and get them to patients who need them.
These actions could also help stimulate investment in early
stage companies that are working on the next generation of
medical discoveries and breakthroughs. The Biotechnology
Industry Organization is committed to working with FDA and
Congress to ensure these goals are achieved. Thank you for this
opportunity, and I look forward to your questions.
Mr. Lankford. Thank you.
[Prepared statement of Mr. Hastings follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Lankford. I recognize myself for the first round of
questions, and we will go through the questions as we can, and
we're still not called for votes yet. You'll hear the bells and
the lights and everything else go off when that happens, and
we'll have a little bit of time to be able to move from there.
Let me ask a couple of quick questions on this. I think I
am going to work in reverse.
Mr. Hastings, you talk about the venture capital being the
lowest it's been since 1995 on that. Do you have a gut feeling
on why that is, why is the venture capital suddenly drying up
when we have a record number of IPOs happening?
Mr. Hastings. It's a cycle. So, while now the public
markets are doing well, the venture capitalists who have fueled
all these early stage companies, had fueled them for so many
years before the IPO market was open, that they drained
themselves of a lot of their resources. They weren't able to
provide the returns to their investors.
So when the public markets opened up and the public
investors embraced the public markets, everybody on the public
side did really well, but there's a lot of catchup that's being
done now by the venture capitalists. So they now look like they
haven't provided their returns over the course of the 10 or so
years prior to the public market opening up that their
investors required, so those same investors invest in the
public markets as well.
Mr. Lankford. Okay. So, what's your gut on how quickly that
turns around? You've tracked this for a while, it sounds like.
Yes, I track this constantly. It's going to take a few
years. So once the public markets continue to reward the
venture capitalists for delivering these companies. So now, by
the way, all those private investors, all the investors that
are in OncoMed Pharmaceuticals on the private side, they won't
be able to cash out until the lockup period is over, and even
then they have to see the company do well on the public markets
in order for them to get their exit. All that takes a little
bit of time, probably a couple of years before people start
reinvesting now in the early stage venture financing.
Mr. Lankford. Mr. Huber and Dr. Gottlieb, they are both
recommending different ways of doing some of the trials and
processes and things, and I want to be able to get to both of
those in a moment.
Mr. Hastings, though, what is the most expensive part or
the most difficult or cumbersome part of the clinical trial or
the R&D or approval process--you can broaden that as broad as
you need to make it--of getting the actual drug through the
research to development. What is the pricey, cumbersome part of
that?
Mr. Hastings. I'll give you one example. There are many
places along the development cascade where it gets expensive.
In the early stages, for young companies, it gets expensive
even in the Phase I or Phase II portion of the trial,
particularly in Phase I when there is a lot of communication
back and forth with regard to safety of the drug. And one of
the areas that we've been working on is this informal
communication where rather than having a letter-writing
campaign back and forth, there is more dialogue between the
reviewer and the company. Saving a month on that communication
process could save a small company, and there has been a lot of
effort from both the FDA and the industry to work on that
together. That's been an example of something that's improved
dramatically.
Mr. Lankford. Okay.
Mr. Huber, let me ask you a quick question on it as well.
The statement is interesting to me, the molecular profiles. How
would that work for them, and expand that somewhat is what I'm
saying, as far as the FDA, because that's obviously a
completely different paradigm than what they are currently
doing on it. So how would that function in real life for them.
Mr. Huber. I was having dinner last night with a prominent
oncologist from MD Anderson in Houston, and he said the real
clinical trials begin after the drug is licensed. Now, I will
emphasize, first of all, that cancer a very distinctive
disease. It's wildly dynamic. The cells are constantly
mutating. And by the time a tumor grows at all, you don't have
one disease in there. You have a whole bunch. That's what makes
it so hard to attack it and why so often drug cocktails are
used and so on.
But in any event, the fact is that oncology has been the
beneficiary of the accelerated approval quite often as one of
two diseases. The other are HIV infections have gotten this.
And the main advantage of accelerated approval in my book is
that it releases oncologists to practice and to work out what
the patient needs step by step. The answer is you begin
prescribing drugs. These are targeted drugs increasingly that
target one molecular receptor. And you can track very early on
with modern diagnostic tools what's going, not up at the
clinical level, which takes quite a lot longer to surface, but
much deeper down inside the patient's body. I mean, it can be
things that are not that much deeper down, like tumor shrinkage
or so on, but you can also be looking at densities of cancer
cells being shed from the tumor and circulating in the
patient's blood. The FDA calls these surrogate end points or
intermediate end points.
And you get feedback much faster. If you begin getting
that, you can early on begin saying, look, we begin seeing
different patterns of response. And it gets eye glazing when
you talk about the statistics, but the fact is the
statisticians know how to handle multidimensional trials where
you're exploring multiple factors as you go. We have
mechanistic understandings of why certain receptors should be
accelerating the progress of the disease, or if you inhibit
them, slowing it down. You study these things and you adapt.
I could give you one vivid example, if you will allow me.
Memorial Sloan-Kettering in New York some years ago launched a
trial using a kidney cancer drug to treat bladder cancer. It
was an abysmal failure. Almost everybody that was treated with
this drug did not respond well. However, one 73-year old woman
responded extraordinarily well. In fact, 2 years later she is
completely cancer free.
Now, in the past, and certainly if this were all within the
confines of one trial, you'd ignore that. I mean, one patient
does not license a drug. Memorial Sloan-Kettering doctors went
in and they searched for the biomarkers associated with cancer,
they explain this, they couldn't find one. They then did a
whole tumor sequence. They just looked for everything that was
in this one patient's tumor and they found the receptor that
was being targeted by the kidney cancer drug. One patient in
that group. It turns out about 8 percent of bladder cancers
have this receptor. And so then they launched a new trial.
That is a slow motion adaptive trial. You learn something
and then you change. You can do that internal to a single trial
if you are working hard at it, but you have to do things that
the FDA doesn't allow. You actually have to be saying these are
the people who are being treated with the drug. Let's look at
what's the details. I mean, if you have toxicity problems and
metabolism problems, same thing, we've got biomarkers for
livers that metabolize things well or badly. You can look for
them, and you can then converge on treatment protocols that
work better.
Mr. Lankford. Okay. We will follow up with FDA in the days
ahead. Let me yield to Ms. Speier for her questions. They have
called votes now. We have around 11 minutes or so on the vote
count. I think what we will do is take Ms. Speier's questions,
then we'll take a quick recess. We'll have three different
votes that are happening, and then we'll come back and we'll go
at you with some more questions. Okay with that? So we get a
quick break.
Ms. Speier.
Ms. Speier. Mr. Chairman, thank you.
And thank you all for your testimony.
The sequestration has really cut the limbs off of NIH
funding to the tune of about $1.2 billion a year. From your
perspectives, each of you, I want to know how that affects your
ability to do your science.
Mr. Hastings. Well, that's a wide open question. So to me
it goes all the way back to what and how we want to be
perceived as a Nation, right? If we're not getting behind STEM
education from kindergarten through grade 12, all the way up
through our university system and the NIH and getting behind
innovation, it's not then going to leave the technology
transfer offices of our universities or the halls of the NIH
and come with a license to an entrepreneur who then can develop
that drug.
So it's a little hard to pinpoint exactly what
sequestration does with the NIH in terms of what it might bring
to our industry other than to say it's huge, very broadly. You
can't really look at any one drug that came out recently and
say that wouldn't have happened under sequestration. I can't
think of one off the top of my head. But that's the kind of
thing that comes out, the thought process, the focus on
innovation. And without that and without those jobs for those
people to do those things, they are going to go to other
places.
Dr. Gottlieb. I'm less focused on NIH, just to pick up on
what Mr. Hastings said about FDA. I think the sequestration has
been problematic for the FDA insofar as what I see, and I wrote
an article about this. A lot of the sequestered funds were
funds that would have been targeted towards the areas of new
regulatory policymaking, the things that were embedded in
PDUFA, in particular, where FDA was going to advance or try to
advance some of the scientific principles that we're talking
about here today.
There were unfilled positions at the time that the
sequester was imposed that will continue to probably go
unfilled, but a large chunk of the money that was taken out was
taken out of the programs of new regulatory policymaking.
Ms. Speier. Dr. Gottlieb, you suggest that there is a
certain amount of risk that we should just be willing to
accept, and I'd like to know what you think that percentage of
risk should be in terms of the FDA process.
Dr. Gottlieb. Yeah, I'm not sure you can, you know,
articulate it in terms of a percentage. There is obviously a
certain level of palpable risk we are always willing to
tolerate, and it adjusts based on what the clinical
circumstances are. And if you are facing a grave disorder and
you don't have other options, you're willing to embrace quite a
bit of risk.
I cited in my written testimony the case of
mucopolyscaccharide diseases, diseases that are inborn, there's
a metabolism where children are born, these are largely fatal
diseases, they are terribly debilitating. I think families who
have children with those disorders would be willing to embrace
a large degree of uncertainty around a new drug, but in many
circumstances say they are not able to because the clinical
trial requirements are getting more difficult.
Remember, I'm talking here about, in particular, risk
around the benefit, not the safety. I'm talking about
situations where the magnitude of the benefit that's observed
in a clinical trial can't be firmly established because the
statistical rigor hasn't reached a high enough degree of, you
know, suredness, if you will. So you see a certain magnitude of
benefit and you have to probability address that and say, well,
since it wasn't a large trial and there were these flaws in the
trial, we can be 70 percent certain that it's going to deliver
that 40 percent benefit. That's the situation.
Ms. Speier. But my understanding is that--and I've actually
accessed compassionate use for the FDA for a number of
constituents from time to time--my understanding has been that
they have been very willing to allow the drugs to be used for
compassionate use, which typically you would say in a case of a
young child would be embraced. So do you find that at all being
restricted in its availability?
Dr. Gottlieb. No. I think FDA has been very flexible when
it comes to individual patient INDs, but keep in mind there is
two challenges there. One is that only certain physicians are
going to be able to navigate that process in collaboration with
their patients. It takes a certain level of sophistication and
resources to work through that process. And that's not a
criticism of FDA. It's just a hard process. So it is putting at
a disadvantage a whole lot of patients who will never have
access to that.
The other thing is that if that's what we're dependent upon
to make therapeutics available in these kinds of, you know,
sort of grave situations, situations where there's a real unmet
need, the framework, the sort of framework on the industry side
won't be in place to make the drug broadly available. In
today's environment, especially with a lot of
biopharmaceuticals, the manufacturing isn't available until the
time of approval.
Ms. Speier. All right. Thank you.
Dr Gottlieb. And so we are dependent upon that approval.
Ms. Speier. I am going to try to get one more question to
Mr. Hastings.
Dr Gottlieb. All right.
Ms. Speier. Mr. Hastings, if there is one thing that you
would recommend that we do to assist the emerging BIO companies
to be successful in their interactions with the FDA, what would
that be?
Mr. Hastings. Enable the FDA, through some of the policies
that we've put forth, some of the breakthrough therapeutic
areas, which would allow us to, with appropriate risk, also see
the reward for these patients. So taking some of the risk that
Dr. Gottlieb was just talking about. There are certain
diseases, like cancer, there are other diseases, chronic
diseases, chronic inflammatory diseases where patients
recognize some of the risks associated with therapies. And so
enabling some of these breakthrough areas where we can get
drugs approved quickly, safely to patients faster is the way to
go, and there's a number of those initiatives that I outlined
in my testimony.
Ms. Speier. Thank you. My time is up.
Mr. Lankford. Actually all of our time is up for this
point. I would like to take a recess for about 20 minutes. We
have three votes in the series. Each one of the votes is about
5 minutes apiece in between. We'll go over and do the votes,
we'll come right back, and then we'll jump right back into
pummeling you with some more questions if that's all right with
you. So let's take a short recess.
[recess.]
Mr. Lankford. The committee will come back to order. I
apologize for the delay on that one. We should not have votes
again until about 4:30 or so, so that will be in the middle of
the time period that we will have our FDA witness, so we will
still have her on the stand at least until 10 I would assume
tonight. Thanks for the delay on that. I would like to
recognize Dr. Gosar for the next line of questioning.
Mr. Gosar. Thank you very much. Mr. Hastings, how much
would you say the typical biopharmaceutical company spends
annually on drug research and development?
Mr. Hastings. It depends on the size of the company. But an
innovative company, our company has 90 employees, roughly $55
million to $60 million a year. You could spend, companies with
400 or 500 employees with multiple drugs in the clinic, you
could spend $1 billion a year in R&D.
Mr. Gosar. And has that gone up over the years?
Mr. Hastings. Yes.
Mr. Gosar. And what are driving those factors of raising
those costs, R&D costs?
Mr. Hastings. So in certain instances, it is what trial
designs have turned into, the numbers of patients one needs to
go into clinical trials, the amount of time it takes to file an
I&D and get your first patient treated on a therapy, to
enrolling patients in Phase I, II, and III clinical trials, not
only in the U.S., but also globally. So it is a very large
undertaking to do, even randomized Phase II clinical trials
today. I call the randomized Phase II clinical trials today the
old randomized Phase III trials of the past. They are roughly
the same size as Phase III's used to be.
Mr. Gosar. Got you. Mr. Huber, in his written remarks Mr.
Hastings cites a 2012 Manhattan Institute study that found as
much as 90 percent of the development cost for many drugs
approved by the FDA are incurred during Phase III clinical
trials. Are you aware of this study?
Mr. Huber. I do definitely remember seeing it, but those
numbers are not of my origin and I cannot speak further about
them.
Mr. Gosar. So what would be your thoughts on those
findings?
Mr. Huber. Clinical trials and certainly the time value of
money are a very large component of the cost of getting a drug
to market. I could not be any more specific than that.
Mr. Gosar. Got you. I am going to stay with you, Mr. Huber.
How would you define a good clinical trial?
Mr. Huber. A good clinical trial is one that if the drug is
good, ends up with enough guidance on prescription protocols
that future doctors with high confidence prescribe the drug in
ways that are likely to do more good than harm. Likewise, I
might add one that rejects drugs that aren't going to be able
to meet that criterion.
Mr. Gosar. So do you think that randomized control trials
are out-of-date?
Mr. Huber. Well, yes, I think they are. Yes. Yes is the
answer. Not--I mean, there are some exceptions to every general
statement, but, yes, they are not making full use of the tools
we should be using.
Mr. Gosar. So what steps would you use to update those?
Mr. Huber. Well, President Obama's Council of Scientific
Advisors on Science and Technology issued a report last year
that I cite in my written testimony. It is a pretty good
starting point. I think things should go further. Others will
be testifying before you today saying they have already gone
further, and if they are, terrific, and the faster they move,
the better.
I do know that we should have been heading down this road a
decade ago and high officials with excellent qualifications who
I greatly admire who were sketching out what needs to be done
to develop multi-dimensional data on how drugs operate. If it
is happening, it sure is happening slowly.
Mr. Gosar. Very slowly. Dr. Gottlieb, can you define the
clinical end point that the FDA requires in its trials?
Dr. Gottlieb. Well, clinical end point is an end point. You
know, the simple way to define it is it is something that can
be experienced by a patient, so some kind of measure of
clinical improvement that is going to be of benefit that the
patient can appreciate. So the ability to breath better, a
reduction in pain, certainly living longer, changes in
morbidity and mortality, as opposed to a surrogate end point,
which is an interim measure that presumably could correlate
with a clinical outcome but isn't something that is perceivable
by the patient. It is a marker.
Mr. Gosar. Would you enhance that or enlarge that from your
personal experience?
Dr. Gottlieb. Enhance the use of surrogate measures?
Certainly. I mean, FDA, I think, over a period of time, made
wider use of surrogate measures, particularly in oncology,
things like tumor shrinkage. I think the agency's experience
with that was mixed insofar as some of the surrogates that they
relied on didn't necessarily correlate with clinical benefit
when they did the larger studies, and so it left somewhat of an
unhappy experience, and the agency became more skeptical of
using surrogates generally.
So I think where I would try to advance this is in trying
to create some kind of pathway to better validate these
surrogates more quickly. There is a lot of surrogates that make
a whole lot of clinical sense, there is good theoretical
reasons why they should correlate with a clinical benefit, but
FDA is unwilling to rely on them or reluctant to rely on them
because nobody has demonstrated that, and it is very hard to
demonstrate that until you actually do the very long trial in
the context of a drug, and by then you have sort of, you know,
put a drug through an enormous clinical development program.
Mr. Gosar. Do you see any interim type of facility or group
that could actually mitigate that?
Dr. Gottlieb. Well, you know, people always talk about
having independent entities like the NIH invest in trials just
for the purposes of validating surrogates. You know, I think
the FDA has flexibility, has a lot of authorities that it could
use to, you know, take some risk around the uncertainty that
pervades these surrogate measures to allow drug trials to go
forward.
You know, one of the examples that I cited recently was
polycystic kidney disease where it is a genetic disease. You
inherit it over the course of a lifetime. You develop cysts in
your kidneys and eventually your kidneys fail and you go on to
end stage renal disease. The question is could a reduction in
the accumulation of these cysts be a valid surrogate for a
clinical trial?
FDA has been reluctant to accept cyst reduction or
reduction in the propagation of cysts as a valid surrogate in
the past, although it makes a whole lot of theoretical sense
that if you can reduce the accumulation of these cysts,
obviously it is going to, you know, prolong the length that
your kidneys function.
These are the kinds of things I think we need to look for
these opportunities where there are these surrogates that make
a whole lot of clinical sense and theoretical sense and either
take the risk of allowing the trials to go forward on the basis
of them or find a way to validate them more quickly.
Mr. Gosar. You kind of breached my next question. How
important is it for the FDA to use its accumulating experience
when conducting clinical trials as outlined in your written
remarks?
Dr. Gottlieb. Right. And I cite the example of
mucopolysaccharide diseases where if you look at--this is a
sort of cluster of related disorders, but they are each treated
by distinct drugs. Very rare. Some of them only have hundreds
of afflicted patients. If you look at the initial drug that was
approved in this broader class, it was approved on the basis
of, I think, about a 20-patient open label non-randomized
study, probably as least rigorous as you can conceive of. And
then there were subsequent approvals for a number of other
drugs and with each approval, the theoretical basis for
understanding why a replacement enzyme would work in one of
these diseases was more firmly established, yet with each
subsequent approval, the clinical trial requirements got harder
and not less. And you can't argue that it was a function of the
fact that there was available therapy because there wasn't.
Each disease was distinct, so the subsequent therapies were
only going to treat one of these diseases.
I think those are situations where when the agency has
knowledge that it is accumulating in a clinical setting like
that, it needs to find a way to make wider use of that so that
it can lower barriers to entry as it gains more knowledge in an
area and not raise them.
Mr. Gosar. Got you. Thank you, Chairman.
Mr. Lankford. Ms. Duckworth.
Ms. Duckworth. Thank you, Mr. Chairman.
Mr. Hastings, thank you for appearing here today and
offering your testimony. I want to touch on a few points you
highlighted where you speak to FDA's regulatory environment has
improved in recent years, but you noted that there are
additional ways to improve efficiency, timeliness and
consistency of drug evaluation. I am specifically interested in
how the FDA communicates with you and your members.
I understand that according to your internal survey, the
majority of your member companies believe that communications
with FDA, while it has improved, it has really been affected by
sequestration, especially recently. Have your members, Mr.
Hastings, expressed disappointment that the Industry Liaison
Office that was anticipated by PDUFA V has yet to be fully
staffed because of sequestration?
Mr. Hastings. So, yes. The Office of Enhanced
Communication, I am paraphrasing it, was an attempt to create
an office whereby folks could call in if there were
communications issues. But one of the things I was just sharing
with Dr. Woodcock earlier is that the whole intention of the
enhanced communication provision we had in PDUFA was for a
cultural shift to occur inside the agency such that we actually
wouldn't need that office to communicate with our reviewers.
What has interestingly happened and could be a side effect
of sequestration, there is only one person in that office that
I know of right now versus the five or six that were going to
be there, but some of the communication between reviewers and
companies has gotten better. And when you look at the survey,
in areas like oncology, which is the area that we are studying,
that communication has gotten markedly better. So rather than
writing letters back and forth and taking 30 days each time a
letter gets written to have the other person have the
opportunity to respond, a simple phone call takes place. So a
cultural shift has been very beneficial.
The issue that we have right now is we would like to that
very positive example and make it extend across all the
division and all the reviewers so that each company, no matter
what therapeutic area they are, is benefiting from that same
enhanced communication. Now, would that office, the Office of
Enhanced Communications, had it been staffed up without
sequestration, would that have helped? It probably would have
in some of those other areas.
So I think the main beef we have about sequestration,
again, is that these are fees that we are paying on top of what
we pay in taxes and everything else, and we are paying those
fees in order to enable. And like I mentioned, it is a little
bit like paying your electric bill and then being told you
can't have power.
Ms. Duckworth. No, the power is there. You are just not
allowed to access it.
Mr. Hastings. Right. But I think--and we have been working
on this for many, many years now, enhanced communications, and
we are seeing some good progress. So I don't want to pin this
all on, well, it is that one office that is going to solve this
issue. It is more a reviewer cultural issue. And I will say for
the Office of Oncology, there is an openness to communication.
Now, again, what is going to help them communicate more openly
with us is that they are effectively staffed, they are
effectively funded, so they actually have time to pick up the
phone and have a conversation with us.
Ms. Duckworth. So I am just a teeny bit confused. So you
said that office should be staffed at--should have four or five
people right now only has one because FDA can't staff it up due
to sequestration. But you are saying just that one person is
more responsive. Or are you saying because they are not there
you are just talking directly to the reviewer and not going
through the office?
Mr. Hastings. What I am saying is it is great to have that
office and that office is going to be helpful, but the whole
concept was to have open communication with reviewers which are
not in that office.
Ms. Duckworth. Okay. But that is happening now and that has
improved?
Mr. Hastings. Right. So the mere fact that we are paying
attention to the issue on both sides has made the issue better,
right?
Ms. Duckworth. Right.
Mr. Hastings. And so the fact that--it would be great for
the office to be staffed because I think in general being
staffed appropriately is going to help, but equally important
as that office are individual reviewers in individual divisions
having good communications with sponsor companies.
Ms. Duckworth. Are there any fears that if that office
staffs up completely, there will be another layer of
bureaucracy and that the communications directly with the
reviewers will stop because people will feel like they have to
go through that office?
Mr. Hastings. No.
Ms. Duckworth. No fears of that?
Mr. Hastings. Absolutely not. No. I mean, companies don't
work that way. You have a relationship with your reviewer and
you have communication with that reviewer. If a hiccup should
occur, there are a number of ways one can help to remedy that,
including talking to that office about ways to enhance the
communication.
Ms. Duckworth. Great. Thank you very much. I yield back,
Mr. Chairman.
Mr. Lankford. Thank you. Mr. Meehan.
Mr. Meehan. Thank you, Mr. Chairman, and I want to thank
this very distinguished panel for taking your time and giving
us your expertise in this area. I represent an area in which
there are a higher degree than normal of businesses associated
with bio and technology and others and have actually tried to
work with some of my constituents as we have negotiated the
process of dealing with the agencies, and I also worked as a
prosecutor acting on behalf of the agencies at certain times.
So I have seen it from both sides. But if I was to look
from 500 feet, there is just a tremendous frustration with the
inability to have people make decisions, and I am not sure that
I understand exactly why that is. What I see, frequently, is
the process being used as a mechanism to avoid decisionmaking.
And I can appreciate that if a wrong decision is made, there
can be implications. But the very process we have is designed
to somehow negotiate that fine area.
My experience, in a number of cases, was the concern of
clients, when I say clients, I mean constituents, who were
afraid to be too aggressive in dealing with the FDA for the
very fear that what would happen is now we will be further
pushed back in their efforts. And every time a new order is
made for a new trial, you are implicating potentially millions
of dollars and longer periods of time. So why does it take so
much time to make decisions?
And I will conclude my questions with what I would find
would be these 30-day periods, Mr. Hastings, you are talking
about the communication, no communications would take place.
There would be substantial amounts of information put together
by very qualified people, the best in the business, in the form
of making the case. And on the 29th day, they would get another
letter asking for more information. So it was almost like every
time the clock would reach the moment, something else would be
put into place, the time would toll and there would be more
requests, until ultimately you got to a point there was a
decision-maker and somebody would say you know, what you are
right, and a few times we broke through. But I am struggling
with this problem. And I want to see both sides. But you are
out there too. What do you see? What is the solution?
Dr. Gottlieb, your written testimony speaks to, I think
what you said was a failure for people to--you know the
language--the fear of uncertainty pervading. So you understand
my questions. Maybe you could each in order respond to my
concerns and tell me what you think.
Dr. Gottlieb. Well, I think generally there is a lack of
appreciation for the time and cost of capital inside FDA, and
it is probably not something you would expect them to be very
cognizant of. But there is a significant time--cost to time
when you are running a development program, even more so than
getting advice back from the FDA that you have to run a bigger
clinical trial. That can be funded and financed if you are a
biotech company, but the time itself is a lot of lost capital.
And the cycling has always been a problem. The multiple
cycles has always been a problem. In FDA, there has been over
time various efforts to try to address multiple cycle reviews
but it is a significant problem.
I would argue the process isn't just used to avoid
decisions. I think the process is used to try to tee up easy
decisions. From my perspective, the reviewers in the early
development stages of a drug program have a lot of autonomy or
a fair measure of autonomy to prescribe what they think the
clinical trial requirements should be to the companies. And
when the companies get advice back from the medical reviewer
they are very reluctant to challenge it in many cases. They
follow it.
So if you are a medical reviewer and you know you are going
to be ultimately responsible for making an approval decision or
a decision to reject the drug, what you want is very clear
evidence to make that decision. And so if you have discretion,
you could prescribe a very rigorous clinical trial that is
going to lead you to a place where you are ultimately are going
to have very clear evidence. But there is a significant cost to
that.
So I think the process is used to try to make easier
decisionmaking and that is what--and that is what ends up
delaying the development programs.
Mr. Meehan. Let me ask the other panelists to respond to
sort of the sentiments that I expressed. Mr. Huber.
Mr. Huber. Well, I would like to try answering from a
slightly different perspective. In 1981, or 1982 it was, that
HIV surfaced as AIDS, people hadn't yet identified the virus,
it was a real sense of panic. I arrived in Washington right
around that time and there was a palpable sense of, gee,
something really terrible is happening once people realized
what is going on.
In the late '80s as AZT emerged and through the 1990s, the
FDA was remarkably agile and willing to bend its rules. It
carved--the accelerated approval rule was spawned during that
time. They began doing treatment INDs during that period,
basically a parallel track of actually prescribing the drugs
through hospitals and clinics and so on to make what was
available, and there wasn't that much available, broadly
available.
It is astonishing what was accomplished during that period
of a substantial number of drugs to treat the secondary effects
of HIV, the AIDS-related disorders, and then a whole series of
HIV drugs. We needed a whole bunch because the virus is so
nimble you have to attack it from multiple points to subdue it.
And also a number of cancer drugs were also the beneficiaries
during that decade.
And I think anybody who looks retrospectively at this
believes that--you know, medicine was really advancing very
well. We accomplished fantastic stuff. There was--despite talk
of the biases of one side or the other, there was really quite
a bipartisan coalition to do this, and we beat what was thought
to be and what was, in fact, an extraordinarily difficult
virus.
You know, it is possible to make decisions fast in this
city when people are really sufficiently united and scared. And
the President's own, the PCAST report I mentioned earlier, by
all accounts the accelerated approval process overall, which
does what it says, it is a conditional approval, but it does
approve drugs much faster, has had--I think very few people
think it has done anything other than more good than harm,
okay? You can move these things quickly if you want to and you
can get, I won't say invariably good results, but many more
good results than bad ones.
Mr. Meehan. Thank you. Mr. Hastings.
Mr. Hastings. I would like to first speak to the fear of
retribution comment you made earlier. If I was fearful of
retribution, I wouldn't be sitting here, I have to say.
Mr. Meehan. Was it a fair comment? Do you think others may
feel that way?
Mr. Hastings. I think it is. I think it is. I just want to
say I think it is a very individual thing, but I do believe
with good dialogue and adults in the room, decisions can get
made. And I will tell you that in my experience, now having
been doing this for a number of years, what we need to do in
Washington now is become 25 percent of our jobs as CEOs of
biotechnology companies, and that engagement, when you have
that engagement and there is good dialogue, good things can
come out of that.
Now, I will just give you an example from my company and I
will juxtapose that to an example from a colleague of mine. One
of the benefits of being the chairman of the Emerging Company
Section of the Biotech Industry Organization is I am with a
roomful of CEOs as big as this room every quarter.
So we had a situation not too long ago where there was a
30-day period and on the 30th day we got an answer and it was
yes, where you might get an answer and it could be no. So if
the answer is no, invariably they are going to ask for more
information if they want you to turn it around to a yes.
But what we are seeing, what I was seeing recently was that
particular case took 30 days. I have had situations where it
has happened sooner, okay? But 30 days I got a yes. Great. Now
I have a colleague who didn't get an answer in 30 days in
another division. So I think that inconsistency needs to be
dealt with. But I also think that part of that inconsistency
has to do with the volume of work people have and the proper
staffing and the proper funding of the agency, and, again,
going back to user fees, making sure that user fees are being
spent to actually enable the FDA.
So I do think there is variability. I think the retribution
thing, there are mechanisms now within the FDA that if there is
a person who is behaving in a way which is professionally
inappropriate, that you can go and get that issue solved. And I
don't know how many folks may have mentioned to you the fear of
retribution if you had asked them what did you do about that,
but that is what I often do. And sometimes there are--you know,
they are not aware of the mechanism or they don't partake in
the mechanism and then all of a sudden this becomes a big
problem.
Mr. Meehan. I think they often make cost benefit analysis
of the things.
Mr. Hastings. Could be. Could be.
Mr. Meehan. I don't want to overstep my time, so I
appreciate the time you gave me, Mr. Chairman.
Mr. Lankford. Thank you. To the panel, let me recognize Ms.
Speier again.
Ms. Speier. Thank you, Mr. Chairman. I just want to thank
our panelists for participating today under what are difficult
circumstances at the end of the year with everything else being
equal.
I do want to make a point though as they have presented. I
think that we here in Congress have to take a certain amount of
blame for the period of time, and I don't believe it is right
now, but the period of time when the FDA started to hold back,
because the first thing that would happen when there was a bad
outcome with a drug is that the FDA was hauled up here by us
and scrutinized and beaten up and pummeled about their process
and how could this have happened? And I think the result was
that these FDA representatives would go back and say, all
right, then, you know, we will just put the brakes on many of
these approvals. So we have got to take some responsibility I
think for what has happened.
I think more recently, and I think it has been testified to
today, there has been a loosening of the process within the FDA
and strategies employed that show that there are new pathways
that are working, maybe not in every area, but certainly in
some that show promise. And I guess the silver lining in the
sequestration is that if it gets to the point where people
actually get on the phone and talk to each other, that is
really a good sign. So maybe we can enlist more of that in the
future.
Mr. Lankford. And the good news of that comment for me, Ms.
Speier, is that Mr. Meehan and I, we were not here earlier
during that time in Congress, so we can--I am grateful for your
time here. Thank you for what you have contributed both in
written form and oral form. We will continue to tap on your
research in the days ahead, both in what is being written and
the insight you can bring. So I appreciate you very much. We
will take a short recess in order to reset the panel and to
have our second panel.
We now welcome our second panel of witnesses. Dr. Janet
Woodcock is the Director of the Center For Drug Evaluation and
Research of the Food and Drug Administration. I am very glad
you are here and that you sat in obviously on the first panel
as well, and I look forward to just some of the conversation
about that.
Pursuant to committee rules, we do swear in all of our
witnesses before they testify, so if you would please rise and
raise your right hand. (Sworn.)
Mr. Lankford. Let the record reflect that the witness
answered in the affirmative. Since you are the sole witness on
this panel, we typically do a 5 minute time period on the
clock. You are welcome to do that. We are going to receive your
written testimony which will be part of the permanent record.
We will be glad to be able to receive your oral testimony now.
We won't be as attentive to the clock, and we will follow up
with questions from there. Thank you.
STATEMENTS OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION
Dr. Woodcock. Thank you. Mr. Chairman, Ranking Member
Speier and distinguished members of the committee, I am Janet
Woodcock. I am head of the Center For Drug Evaluation and
Research at FDA. This hearing explores current challenges in
drug development and manufacturing. And given the critical role
that medicines play in the health of our population, these, I
think, are very important and timely issues.
One challenge that the other panelists already alluded to
is the escalating costs and time required to develop new
therapies. This problem was identified in FDA's report on the
critical path identified in 2004, but has only really gotten
more serious since that time.
The root cause, in my opinion, probably in
contradistinction to some of the panelists can be boiled down
to two major factors. The first is most investigational drugs
that are taken into clinical trials are not successful. Perhaps
10 percent of the drugs get to the market. And about half of
the drugs that are taken into Phase III trials don't work or
are too toxic and are dropped at that point, which is a very
expensive point.
This extremely expensive failure rate has been difficult to
address, although companies have been trying to address this in
the last decade. And also over this decade, we have been
working with academia and the industry to try and improve drug
development tools, including biomarkers and other tools, that
could help raise the success rate over this 10 percent mark.
Until this happens, there are huge opportunity costs generated
by this large scale of clinical failure.
Now, the second factor is the hugely escalating cost of
clinical trials, which have already been alluded to. Clinical
development programs are plagued with multiple problems,
including slow or no accrual at some sites, ever-increasing per
patient cost, patient shortages and lack of data standards. The
traditional clinical development program is inefficient and
does not utilize most up-to-date technologies. Patient access
is limited because only sites at major medical centers enroll
patients typically.
FDA has been working on these problems. We have been
working in the clinical trial transformation initiative, which
is a consortium we have with Duke University and multiple other
stakeholders. We have been working on data standards. And we
have been working very intensively with groups that are doing
new trials, such as the I-Spy trial which is an adaptive trial
that is being done in breast cancer, and a new master protocol
for lung cancer. And both of these trials are innovative
because they study multiple different drugs in the same trial,
and thus enable a lot of savings of setting up one trial after
another for each investigational drug, and I am happy to
discuss any of this with you.
Also we have been talking about the use of telemedicine to
better reach patients who live outside of major medical
centers.
Now, a second issue and challenge relates to modernizing
drug manufacturing. The United States is no longer the world
leader in drug manufacturing, like many other manufacturing
sectors that we have lost. We rely on foreign sources around
the world for drugs critical to the health of U.S. citizens.
The trend of moving drug manufacturing offshore is continuing.
However, we now may have a chance to reverse this trend.
Modern manufacturing methods that have only recently become
technically feasible allow for continuous manufacturing from
drug synthesis to the final drug form such as tablets or
capsules. So you put in the raw chemicals at one end and you
can get out pills at the other end. Such manufacturing requires
much smaller but high-tech facilities staffed by a highly-
educated workforce. There is also a trend toward using
disposable manufacturing for the biologics, which again
provides much savings. Environmental burdens for both of these
are greatly diminished, and this was one of the barriers to
continuing to building pharmaceutical plants in the United
States.
I believe the U.S. Should do whatever is needed to
incentivize this type of manufacturing sector growth in the
United States, both because we need better security of our drug
supply, and because it would provide a manufacturing sector
that would be very valuable. The FDA has been encouraging and
collaborating on this for about a decade, but I think there is
now a unique opportunity.
So there are multiple areas in which drug development
continues to be a big challenge in also manufacturing and
maintaining the drug supply, and I would be happy to discuss
all of this with the committee.
[Prepared statement of Dr. Woodcock follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Lankford. Thank you. Let's run through a few questions.
We will take 5 minutes at a time and then come back and do a
second round of conversation as well.
The sequestration issue has come up multiple times in this,
the sequestration of the user fees itself. These are paid by
the companies to be able to expedite this. You and I have
spoken on this before as well. What has been done at this point
from FDA? Has there been communication with OMB to have a
discussion about this? Because that is a user fee, and there is
a lot of bipartisan frustration with OMB to say why has that
been sequestered as well. That was different from the start.
Tell me about the communications that is happening right now
between the FDA and OMB?
Dr. Woodcock. Well, I believe the administration certainly
has communicated within itself. This was a ruling by OMB that
according to how the budget was structured, that the user fees
would be subject to sequestration, and that was done at the
time the original sequestration was put into effect.
Now, I realize Members of Congress have written to OMB
about this and there has been multiple discussions, but it
seems to be that it is felt that some type of overt action by
Congress might be necessary to change this situation.
Mr. Lankford. Has there been communication between FDA
directly to OMB to talk about that, or is there just the
assumption that that conversation was at OMB?
Dr. Woodcock. No, I am sure that OMB--I personally haven't
had those conversations, but I believe those conversations have
been--OMB is quite aware of this situation.
Mr. Lankford. Oh, yes. Several comments have also come up
on the President's recommendations--the recommendations. There
are several of them again that have been itemized as we have
gone through the earlier panel as well. One of them,
recommendation number three; expand the use and practice of
FDA's existing authorities for accelerated approval and
confirmatory evidence. The FDA should make full use of
accelerated approval for all drugs meeting the statutory
standard of addressing an unmet need for a serious or life-
threatening disease and demonstrating an impact on clinical end
points other than survival or irreversible morbidity, or on a
surrogate end point likely to predict clinical benefit.
How is that coming in the conversation? I know you all
already looked at this as well. Where is that?
Dr. Woodcock. Yes. Well, some of that was substantiated in
FDASIA that was passed last year. So we have issued a guidance
on our expedited programs that further defines what unmet
medical need is to make a standard definition of that. We
certainly have talked about and are working on the issue of
clinical endpoints short of clinical benefits, but likely
predict clinical benefit. And we have full intent of applying
accelerated approval to any area of unmet medical need. And I
believe our breakthrough drug program that also was put in
FDASIA demonstrates that we are very interested in this. Many
of those have had potential clinical benefits based on
surrogates and so forth.
Mr. Lankford. So the guidance is being written currently on
that. Tell me the timeframe on this as far as when this moves
from conversation and we are drafting to done.
Dr. Woodcock. The draft guidance is out for comment and we
should issue a final guidance soon.
Mr. Lankford. Soon being tomorrow? Soon being six months?
Dr. Woodcock. Within months I would expect.
Mr. Lankford. Okay. Great. And then this ongoing
conversation that has happened earlier that you are extremely
aware of as well, this balance between safety and efficacy,
access from patients coming in, whether it be the compassionate
use that Ms. Speier had mentioned before or other methods to
get patients that are terminal access to drugs faster, or even
the information about the clinical trials out.
So let me do two different sets of questions on that. One
is the compassionate use and getting the information to doctors
about how to go through that process and connecting and what
the steps would be. So that is an information part of it. And
the second part of it is the clinicaltrials.gov site, the
information there, the access to that, helping more patients
get involved in the trial process so they can be in the
structure which not only helps them but helps others as well.
Where are we on those two issues?
Dr. Woodcock. Well, clinicaltrials.gov is intended to--is
run by the National Library of Medicine and is intended to,
among other things, alert patients or caregivers to where a
trial might be opening up that they might be eligible for.
Mr. Lankford. Do you consider that site up-to-date and the
information accurate?
Dr. Woodcock. I think the site is up-to-date on the
existence of the trials. There has been a lot of controversy
about the results section of that and whether that is up-to-
date. But if you are talking about patients being able to enter
into the trials, except for Phase I trials were not included,
so there may be some Phase I trials. But those are dose
escalation, early safety trials.
Mr. Lankford. It has all the beauty of Craigslist when you
go there as far as the site itself and its functionality, but
the access to some of the results and the information is part
of what my consideration is. How do we make sure that people
not only get good accurate information there, but there is the
possibility of they know about this early enough to get
involved, and that physicians have access to that information.
They know it is very, very timely.
Dr. Woodcock. Well, I think that would be a matter of more
publicity about the site through various patient groups,
through other professional organizations that treat those given
diseases, so that the information is disseminated out in that
manner.
Mr. Lankford. Does FDA have a good relationship with those
patient advocacy groups? Is there an ongoing communication
there?
Dr. Woodcock. I have recently set up in the Center for
Drugs a new group office for patient advocacy relations and
professional relations, so we plan to be building that capacity
within the Center For Drugs.
Mr. Lankford. Okay. That would be very helpful, not only to
patients, but also to physicians as well.
Dr. Woodcock. Agreed.
Mr. Lankford. And I want more information on that. I am
going to try to honor time on this and recognize Ms. Speier.
Ms. Speier. Mr. Chairman, thank you.
Dr. Woodcock, thank you for your decades and decades of
service to our country and to the health of our country.
Mr. Huber had mentioned in his testimony that the FDA
clinical trials process is not suitable for new biologic and
molecular medicines, and it essentially results in economically
incurable diseases. How is the FDA responding to these new
medical technologies?
Dr. Woodcock. Well, I had a conversation with Mr. Huber. I
don't agree with his analysis. We have been in the forefront of
pushing molecular medicine since 2000. FDA, I can offer this
for the record, recently put out a booklet on all the things we
are doing on personalized medicine. But for example, I think in
2003 I accepted the first award from the Personalized Medicine
Coalition really on behalf of the center for our work, the
first award they had ever given, for our work in driving
personalized medicine along.
And why would we do that? Because personalized medicine
allows--because you try to eliminate people who don't respond,
you increase the size of the treatment effect so that you
actually see how well a drug works in people and has a chance
in working. Then on the safety side, you can eliminate people
in advance who are at risk so the drugs can become safer by
screening out people who are at high risk of side effects.
So from our point of view, and I think from the patient's
point of view, personalized medicine can only be a positive. We
have, in fact, been criticized by some in the community for
pushing it too hard. So I believe we really--and I believe it
is paying off now. It is paying off with the targeted
therapies. A lot of the breakthrough drugs are targeted
therapies, and I think that we are going to see increasingly
targeted medicines over the next decade.
Ms. Speier. I appreciate that clarification. Now, Mr.
Gottlieb also stated that he saw one of the greatest challenges
for the FDA in terms of innovation was the culture, and he
believed that there is significant influence exerted by outside
groups upon the FDA clinical group. I would like to give you
the opportunity to respond to that.
Dr. Woodcock. Well, I certainly read Dr. Gottlieb's
testimony. I have had conversations with him about this. And,
of course, FDA has considerable flexibility in applying the
safety and efficacy standards, and we basically use a sliding
scale. So for a headache, a drug has to be pretty safe because
no one wants to risk their life to cure their headache, right?
On the other hand, for serious and life threatening diseases
where there isn't any alternative, there is a lot of tolerance
of risk, and there is also greater tolerance of uncertainty
about the effects, which is what Dr. Gottlieb was talking
about. And as I understand his comment, it is very similar to
what you said, which is that a lot of the criticisms over the
years about drug safety issues have, in his mind, led to
conservatism, even in the area where a lot of flexibility is
indicated.
Ms. Speier. So give us some good news, because I think
there is some good news coming out of FDA, and particularly
your area. So tell us from your perspective some of the good
news.
Dr. Woodcock. Well, I think from my point of view the good
news is that the industry, we are really seeing, I think, a
renaissance in the industry. We are approving a lot of drugs
now that are first in class or that are treating untreatable
diseases, or that are advances in therapy and they are treating
bad diseases better.
The breakthrough program that was put in place by Congress
last year, we have had over 100, I believe, requests and we
have granted 34. And those designations that we give are where
we think the drug is really a game changer in that disease, and
if we grant that designation, we offer to really do a full
court press on that drug and do everything we can to get it
developed basically in the most, I call it parsimonious manner
possible. In other words, what is the shortest path between
where the drug is now, what we know about it, and what we need
to know to get it on the market in the hands of doctors and
patients. And I think there is a lot of enthusiasm, both
internally and externally, about this breakthrough drug program
and the promise of these drugs.
Ms. Speier. Okay. Let's talk about manufacturing for a
moment. It is pretty stunning, and I think if the American
people knew that 40 percent of the drugs that we take are
manufactured outside of the country, and 80 percent of the
ingredients are manufactured outside of the country, they would
be pretty appalled because there is just consternation about
the supervision and oversight that goes on overseas.
So tell us, and to your point, when there are shortages and
there are tsunamis and there are other conditions that prevent
us from accessing the drugs that our population needs, we are
really left with a very difficult position to be in. So, how do
we create more opportunities for manufacturing, or what is it
going to take?
I mean, I am thrilled that Apple computer has decided to
bring jobs back to America. I might actually buy more Apple
products now. But that was a ways in coming, and part of it is
because we are now seeing transportation costs are more
expensive. There are lots of reason why on the bottom line they
are doing that. How can we create incentives for manufacturers
to be manufacturing in the United States?
Dr. Woodcock. Well, that is a very good question, and
because I am not an economist, I am not like probably the best
person to consult. What I am going to say is that FDA is trying
to provide encouragement for advanced manufacturing, wherever
it might be, because it is going to be safer, it is going to be
reliable, it is going to enable personalized medicine because
it is going to be much more agile than the kind of
manufacturing that we have right now.
But I do believe that it should be considered--incentives
should be considered and States should consider this as perhaps
an industry they would want to put in place incentives to bring
back into the State, because I believe this will be a viable
sector for a very long time, making drugs.
But the technology, I am here to say that the technology
has reached a point where this is reality; where we can see
these plants can be built, they can decrease our vulnerability
in the sense that we are relying on foreign sites of supply
that may have many different things that might happen that mean
a drug might become unavailable in the United States, and yet
it is also a very good, I think, source of jobs.
Ms. Speier. Thank you. My time has expired.
Mr. Lankford. Mr. Meehan.
Mr. Meehan. Thank you, Mr. Chairman.
Dr. Woodcock, I want to thank you too for your long
distinguished career working in this area, and congratulations
for your recognition. It is nice to receive an award. That is
one of the few benefits of public service, that you don't get
the compensation sometimes in other ways.
But I want to step off of the questioning that my good
friend and colleague from California was asking you because you
made a comment about the industry now expanding in Europe and
other places and not here. But why do you think that is?
Dr. Woodcock. My understanding is it is primarily they are
setting up plants in India, China and many other parts of the
developing world. And I don't know, as I said, I am not an
economic expert, but the analyses that have been published
about this say that it is the environmental regulations,
certain tax advantages, a lower cost labor force and the usual
kind of factors that we see with manufacturing moving offshore
from here.
However, the new manufacturing methods require a high-tech
labor force. They will have low environmental impact. It will
be much diminished, all right? And it will require not a very
large footprint of size of a factory to operate. So it is more
like the kind of innovative high-tech industries that we really
do see coming back to the United States or we would like to
retain in the U.S.
Mr. Meehan. What do we do? I mean, I accept the analysis. I
don't have a better analysis of it, and I suspect and do
believe that it includes all among those, including tax
policies and other things. But I do hear as well the time that
it takes from somebody who has effectively a start-up concept
to have it moved through Europe and approved and put into, you
know--the chain of treatment, so-to-speak, is much shorter than
what we deal with in the United States. And you talked about
time and cost being an expanded aspect of FDA, or at least the
process here which FDA participates in here. And since we can
hopefully deal with those other issues as well at some point in
time, tax policy and those sorts of things, what can we do to
do a better job of enabling the FDA to be timely in their
response, or are you doing it correct? I am moved by your point
that only 10 percent of the drugs actually get approved, that
there are good reasons why it is appropriate to make sure we
don't put bad products out. But what is the difference between
what Europe is doing and here? Why can they do it faster than
we can?
Dr. Woodcock. Which part do you say they are doing faster?
Mr. Meehan. Well, it is my understanding, and maybe correct
me if I am wrong, that there is an ability to take a start-up
idea and move it through the clinical trials and get it to a
point where it can be approved and put into commerce quicker
than is done here, and that that is one of the driving forces,
is the tremendous cost associated and the time delay. That if
you can manufacture--get the drug approved and begin to
manufacture and get it in, once it starts to work, it will find
its way back here to the United States. But we have lost jobs
and the other kinds of things that are associated with the
development of the industry.
Dr. Woodcock. Well, we keep figures on what we call the new
molecular entities, the novel drugs, right, and where they are
approved first in the world. And consistently over the past, at
least 5 years, we have led the world in approvals of first on
the market and we are above Europe. We are not in any
competition with Europe, but we are about 50, 60 percent
compared to all other markets, and then each sector, Japan,
Europe, has a smaller percentage up to 100 percent. Last year I
think we were at 60 percent of all new molecular entities. I
can get you that figure. So I am not sure. That used to be,
before the user fee program PDUFA, FDA approved drugs much
later than in Europe. But that hasn't been true for some time.
Now, as far as manufacturing, we have more or less the same
manufacturing regulations as the Europeans. So if a plant can
be got up quicker in Europe, it would do with other permitting
and, you know, other regulations related probably. But
generally the manufacturing is going to India, China, other
places, Brazil.
Mr. Meehan. Okay. My time has expired, Mr. Chairman. I look
forward to a round of follow-up questions.
Mr. Lankford. And we will. And, Dr. Woodcock, if you don't
mind, we are just going to open the microphones and just have
an ongoing conversation, so there may be multiple of us instead
of a structured time period. That has been our habit I would
say here once we get into the second round. So we will start
throwing questions at you back and forth.
You had mentioned first about the approval process faster
here for some of the types--faster than Europe or Japan, and
that has changed over the last several years. Is that still
true for all types or are there certain types where Europe and
Japan are still approving drugs faster than we are?
Dr. Woodcock. Well, since I am under oath, my impression is
that we--because of the user fee program we have deadlines. We
approve most of the drugs on the first cycle, all right? So it
is submitted in. The companies have really figured out what
they need to give to us to get an approval and we have
timelines for when. And I think my impression is for all the
types of new drug applications, we are ahead of other
countries.
Mr. Lankford. Okay. Your ideas to bring down the cost, as I
walked through the several issues of this particular hearing
and got a chance to explore where FDA is moving on this and
what is happening, the cost of drugs is significant, and every
one of those companies say it is because of the cost of
actually the trials process and everything else. So your idea
is that you have seen to bring down the cost of that. I also
want to ask you several other questions. But can we spend a
little time on that?
Dr. Woodcock. Certainly. To bring down the costs, we have
been working on this for at least a decade, and recently, my
idea of having these standing trials where many drugs could be
tested in the same trial and you just keep running them through
instead of setting up a new trial for every drug, which is
extremely expensive and time-consuming. And the goal then would
be to reach out to the community and enroll patients all
through the United States, not limit it to major medical
centers, so more patients have the opportunity. It decreases
the time taken to recruit patients.
Mr. Lankford. Who has done that at this point? How many
have done that? Is that a pilot issue that you are working with
or how would companies know they can try that?
Dr. Woodcock. It has to be done by consortia, and the I-Spy
trial, the I-Spy 2 trial was the pioneer in this, okay.
Ms. Speier. Where was that done?
Dr. Woodcock. It was led out of UCSF through the foundation
for NIH as a consortium, all right. So many companies, the FDA,
NIH, everybody would be a part of that, set up that trial. It
is a screening trial, and they screen breast cancer drugs with
a bio-marker to the point about personalized medicine. So they
take high risk breast cancer patients and they are trying to
improve the treatment so they can screen many drugs, and I
won't go into how that is designed.
And then another one is now being set up by the National
Cancer Institute, the FNIH, and FDA is participating in this,
for lung cancer, where many patients can be recruited and they
already have five drugs, and all investigational drugs, that
they will be testing using biomarkers in that trial. So those
are prototypes. But it is not widely adopted yet.
Mr. Lankford. But that is obviously in an area where you
are having a lot of patients and a lot of opportunity. You
mentioned breast cancer. Lung cancer. Unfortunately, we have a
lot of people in that. What can be done in some of the other
drug processes where we don't have as many people?
Dr. Woodcock. Well, in rare diseases, I think certain
groups like the Cystic Fibrosis Foundation have led the way. We
recently approved a drug for cystic fibrosis, and that is a
rare disease to start with, but it only treats 7 percent of
those patients. But that Cystic Fibrosis Foundation already had
the patients genotyped so we were able to identify--the company
who was developing the drug was able to identify which patients
that drug might work in and rapidly test them. So that drug is
approved and on the market for cystic fibrosis.
Mr. Lankford. So what kind of time period and cost did that
change for that? That went from 12 years, 10 years I would
assume is a typical process?
Dr. Woodcock. Yes. I think it was remarkably shortened, but
I can't tell you how short that was. They did randomized trial,
because this is a very novel approach, and they were able to
show in a 48-week trial that they really improved markers for
cystic fibrosis, lung function, and the children gained weight.
So another idea that we have also is we have been
discussing, and I know you all have been discussing with the
community is a way to speed the introduction of antibiotics for
drug resistant organisms. And that is a different idea that has
been discussed, which is putting some kind of mark or logo or
having Congress speak to a special mechanism that we would have
a very limited drug development program, get those drugs into
the hands of doctors, who are serious drug resistant organism
infections, and have some kind of notation or mark on those
drugs so that the doctors knew they had been developed by a
very limited program and that good antibiotic stewardship
should be used with them.
Mr. Lankford. Okay. Only antibiotics in that program,
though.
Dr. Woodcock. It's been discussed wider, and I think that's
a matter for ongoing discussion. But that would be one way to
do it. Because the need is very great. The CDC said, I think,
last year, I believe, they said 23,000 people died from
infections with drug resistant organisms, and we are behind
that epidemic. As you have said, it takes a while to develop a
drug, even if we shorten the time, and so we don't have time,
you know, anymore. We're running out of time to get a handle on
this epidemic.
Mr. Lankford. Okay. So clarify that for me because you said
``we're working on'' several times there. Is this a process
that is set, that you've done guidelines for, that's done, or
again, what is the timeframe on this? Is this done tomorrow? Is
this done 6 months, 6 years from now?
Dr. Woodcock. What we've been discussing is that Congress
would speak on this and tell us to establish a program.
Mr. Lankford. You do not have the statutory authority to do
that right now you feel?
Dr. Woodcock. It would require regulations.
Mr. Lankford. But if we did statute, you would have to
promulgate regulations off that statute as well.
Dr. Woodcock. I'm not a lawyer. Being under oath, I want to
give you an exact answer. But I think we could probably do it
with the statute. We might have to do guidance to help
companies figure out how to do the programs, but I believe that
we could probably implement something if we're directed to in a
statute directly.
Mr. Lankford. Okay. I'll just make sure.
Congresswoman Speier.
Ms. Speier. Dr. Woodcock, the experience that Gilead just
had where it had their hepatitis C drug approved with the
recommendation by FDA to do additional trials, I believe, with
a different cohort, maybe you could just explain. Because it
was unusual but it showed flexibility within FDA, and Gilead
was thrilled with the opportunity to kind of move that process
quickly.
Dr. Woodcock. Uh-huh.
Ms. Speier. And I think it would be good for all of us to
understand it.
Dr. Woodcock. I would have to get back to you on that
because I don't know the details of it, but I will say that you
asked for good news, I think the new generation of drugs for
hepatitis that we are going to see is really good news because
we have a lot of patients in this country who develop liver
failure from hepatitis or develop liver cancer, and we believe
the new generation of drugs may well be curative of hepatitis
C, and that's really big news.
Ms. Speier. And it's big news on a lot of levels because
they become disability insurance recipients and Medicaid
recipients and Medicare recipients, and that is a very costly
procedure that they then go through in terms of dialysis and
the like. So that's good.
Let me ask you this. You said that only 10 percent of the
drugs that are considered actually get approved because there's
a failure in Phase III. Can you explain that to us? Is there
some way we can find that out sooner so there's not as much
money invested by the drug companies?
Dr. Woodcock. That's the $64,000 question. All right. What
happens is there's attrition all the way through the drug
development process. The attrition, before you get into people,
so you do animal studies or something and you find toxicity,
that's not that expensive. But once you start doing trials,
losing a drug somewhere during the clinical development program
is very expensive, and the longer you go and study the drug,
the more sunk costs you have in that drug.
And so in Phase I there is attrition often for toxicity. In
Phase II there may be attrition because a drug doesn't work.
But remarkably, in Phase III, at least several years ago, the
last time this was studied, there's about 50 percent of
attrition is in Phase III when you've spent a huge amount,
maybe, you know, upwards of a billion dollars on developing the
drug, and you find out it doesn't work. Some of the drugs in
Phase III don't have any effect compared to placebo.
Ms. Speier. But is that because for the first time they are
being used or human beings? They are being used on human beings
in Phase II, are they not?
Dr. Woodcock. Uh-huh.
Ms. Speier. So what is happening?
Dr. Woodcock. It's hard. For some diseases you can't tell
in Phase II. All you're doing in Phase II is trying to get the
dose right, maybe using a biomarker to try and figure out, you
know, are you affecting the disease? But the disease may be a
longer-term disease or it may take a while, and so you have to
do a Phase III trial to see whether or not it actually works or
not, and then you're very sadly disappointed.
For example, we just had a couple trials in Alzheimer's
disease, you know, that did not affect Alzheimer's disease, and
that is a bitter disappointment because we need treatments for
Alzheimer's disease, but it's hard to tell in earlier trials
whether or not you're affecting dementia.
Mr. Lankford. I'm jumping on this as well.
Ms. Speier. Sure.
Mr. Lankford. Going back to a statement, Doctor, that Mr.
Huber made earlier where he talked about the drug that was set
up for kidneys and they were using it for bladders and it was
not successful on anyone but one, and it was flawless on that
one.
Dr. Woodcock. Uh-huh.
Mr. Lankford. Is that the type of thing that we're finding
or we're finding it's effective on some so we're looking for
the molecular markers for that group and why you had, you know,
500 people in the study and it worked great on 12 and not on
the rest, and so now you're studying it, or you're blanket
saying this doesn't work for everyone?
Dr. Woodcock. It really varies by the disease. In
Alzheimer's we have don't really have any good molecular
markers yet. That's what those biomarkers are working on. So
those studies are what you call empirical. In other words, they
are trial and error. And that's a lot of the problem with drug
development, it's still trial and error.
But in cancer, because we did the war on cancer that you
all funded, and we have a tremendous amount of information
about what makes that cancer a cancer. And as Mr. Huber was
saying, it's molecular changes, genetic changes in the tumor
that do that, and some of them are driving the cancerous
behavior. And if we can target that and turn it off, then the
cancer subsides to some extent. And so that's a new way of
developing a drug where you actually understand the mechanism
and you can target that mechanism.
And so, in cancer, we used to talk about breast cancer and
colon cancer, but now we really talk about what is the driver,
what mutation is driving that tumorous behavior and how can we
turn that off. So that's been a revolution, and I think that's
going to get better and better, but we need to focus on curing
cancer.
Mr. Lankford. Right. No, the point I'm trying to drive at,
though, is in a large-scale study, it's a Phase III, you have a
lot of people that are involved in it. What do you do if you
have a small group in there that it is successful for, that it
is effective, but statistically, across the size of the group,
it's not? Is that something the drug company goes back and goes
back to the drawing board and tries to determine that, or is it
something FDA is involved in? What happens?
Dr. Woodcock. Usually companies will submit subgroup
analyses and they would give them a hypothesis, well, maybe it
works in this group, okay, we don't know why, but maybe it
works in this group. And they would have to do more trials.
Why? Okay, well, in a famous example, Richard Peto, who's a
statistician in the UK, did a subset analysis of a trial, and
he showed that people with the astrological sign Virgo, okay,
did much better than all the other people. And, you know,
people say we should approve the drug based on these subset
analyses, but the actual fact is you can do many of them and
there's always going to be one that the drug appears to work,
and we see this all the time. That doesn't necessarily mean it
actually does work, just like the astrological sign Virgo is
not a predictor of better cardiovascular outcomes.
So, yes, if there is a convincing molecular marker, though,
okay, that's a hard scientific thing, not some kind of fishing
expedition, then we might have a different approach.
Ms. Speier. Could we talk about your staffing. Is all of
your staffing--I should know this and don't--subject to user
fees or is there a percentage that is not subject to user fees?
Dr. Woodcock. We have S&E funding that is subject to
sequestration. We have PDUFA funding, and we have GDUFA, the
generic drug user fee program has just set up funding, and
funding for biosimilars drug user fee. The S&E is maybe about
30 percent of our funding.
Ms. Speier. S&E is?
Dr. Woodcock. The appropriated taxpayer's dollars.
Ms. Speier. It's about 30 percent.
Dr. Woodcock. Uh-huh.
Ms. Speier. So what has that meant in terms of
sequestration. I mean, how many jobs are no longer being----
Dr. Woodcock. I wish I could remember these figures, but
it's been a pretty significant hit that we've taken. Now, we're
able to hire under GDUFA anyway, but what you've been talking
about here about the interaction of companies, innovator
companies with the review divisions, has been hampered because
those review divisions did not get the hires they expected
under the new PDUFA program because of the sequester.
Mr. Lankford. The generic group, you're still able to hire.
That money was not sequestered?
Dr. Woodcock. I'm very confused about this. I know that we
had so many hires that we had to make, that we certainly are
able to hire under GDUFA. I don't understand. We could get back
to you on the impact of the sequester.
Mr. Lankford. Yeah, the question is whether user fees
sequestered for the generic are not sequestered for the
generic, do you know? You've made some hires there. I just
didn't know if that's a function of the user fees.
Dr. Woodcock. I think the answer is yes and no. I think the
first year weren't maybe because it was a new program. That's
why I'm confused.
Mr. Lankford. Okay.
Dr. Woodcock. And then it will be, but we can----
Mr. Lankford. Can we follow up on that? Because obviously
it has been this ongoing conversation should the user fees have
been sequestered at all. Okay.
Dr. Woodcock. Yeah, okay. Uh-huh.
Mr. Lankford. Pat, did you have anything you wanted to add?
Jump in any time.
Mr. Meehan. Well, I don't want to jump in while you're on a
roll. And I kind of laughed to myself when you were hesitant to
answer the question because you said, I'm not a lawyer. I was
just with a guy who said, he saw the high priced lawyer and he
asked him, he said, I've got two quick questions. If I give you
a thousand dollars, can I ask you? And the guy said,
absolutely, what's your second question? So a bit of levity to
help us. As a recovering lawyer, I have to take chances.
The sort of the dialogue I exchanged with Dr. Gottlieb,
among others, was not just anecdotal, dealing with the concerns
about the timeliness of responsiveness, and you didn't really
have a chance to talk to it.
Dr. Woodcock. Uh-huh.
Mr. Meehan. And I think it has sometimes to do with the
ease with which it is just to ask one more question and send it
back. What can be done to assure that those who are managing
their portfolios, particularly in light of the fact that PDUFA,
MDUFA, have been put in place to ameliorate just this issue,
that we are getting timely and responsive communication? And
maybe it is just as, you know, Mr. Hastings identified, better
communication all along. But I'm talking from knowledge of
specifics where there would be communication, and in effect,
send me what you have, 28 days, no response, 29th day, the
whole new raft of questions. So how as an agency can you
oversee to assure that those who are managing their portfolios
are doing it effectively?
Dr. Woodcock. Well, it is a complicated question. These
interactions are governed by agreements that are made under
PDUFA, many of them, all right, and we track something like
25,000 transactions, right, every year. Don't quote me on this.
Something like that, or I can't give you the exact number,
right, but it is a very large number of transactions that
occur, because we track not only all the filings for the
marketing applications, but we have type A, B, and C meetings,
we track how timely the meeting minutes are to get back on
these meetings, how timely scheduling of the meetings are, et
cetera, et cetera. So it's very micromanaged, but again, that's
the process. It's not the content.
And I will say, in my opinion, if you pay too much
attention to process, you often give short shrift to content,
and to me that seems to underlie your question, too.
Mr. Meehan. It did. I mean, I think that was the example,
that once they got somebody else to step in and took the time
to evaluate it, they realized the information was there and it
was sufficiently explained.
But I just appreciate the process, but I do think it's this
balance of when people feel comfortable to make decisions. And
I do adopt my colleagues' concerns that obviously people have
come and been lambasted for having made the wrong decision, and
it creates an environment in which people say, well, no
decision is easier on me, so they don't do it. How do we have
to work together to assure that that happens?
I just have a couple of follow-up questions. The
President's Council on Science and Technology put together
their innovation package, and they had eight recommendations.
I'm looking forward to going into greater detail into that. But
you've been through it. What do you think, what stood out with
you, to you, in that report, and what do you think we can work
with you on to help do a better job of getting, you know, more
effective cures to the market?
Dr. Woodcock. Well, I think some of the things that
Congress has already sort of instantiated in FDASIA around
accelerated approval already alluded to have been helpful in
having us pay more attention to our expedited programs. The
other thing that struck me about the proposals in the PCAST
report called for more translational science, because it's hard
for us to make decisions, you know, if the science isn't there.
Mr. Meehan. What do you mean by translational science?
Dr. Woodcock. Well, you know, there's basic science you can
say, well, this pathway inside of a cell does this and that and
the other thing, and then there is translational science which
said this biomarker really is predictive of a good outcome. The
more data a company or we have on that, the more confident
everyone feels that we can, you know, put our money down on
that, right. But if we have no data or say the rare diseases
you're talk about, we don't have any data on the natural
history of the rare disease, what people do is get a bunch of
experts together and say, in my opinion, the disease progresses
in this manner.
Now, that's been a problem not just for us, for the
companies, because it turns out the disease does not progress
in that manner and therefore their study they designed, you
know, didn't work. It wasn't long enough, or, you know, it
didn't measure the right things or whatever. And so that's
translational science, is the science that supports actually
studying the drug in people and actually enables you to study
the drug effectively and quickly.
So PCAST called for formation of a consortium where
everyone would work together to enable this translational
science and move it along, and I think that would be very
helpful. I also think this other mechanism I already talked
about for antibiotics would also be helpful in dealing with
some part of that epidemic.
Mr. Lankford. Can now jump in as well? Help me understand
again why you think you need a statute for the antibiotics in
the new process, why you don't feel like you already have
statutory authority to do that, based on so many other areas,
with the breakthrough, with the accelerated process, with all
those things that are already in place, why do you need another
statute for that?
Dr. Woodcock. I think we have statutory authority or we
could claim we did and do a regulation. That would take many
years, in my experience nowadays.
Mr. Lankford. Have you noticed how long it takes to get a
bill through Congress?
Dr. Woodcock. Well, I just have great faith in you.
Mr. Lankford. That makes one.
My concern is, as deadlocked as we are in so many different
areas, my preference, and I'm not going to speak for all of us,
would be you get started on what you feel like you have
statutory authority for now and so we can have something in
process.
Dr. Woodcock. Right.
Mr. Lankford. We have a responsibility to get our stuff
done as well, but that has not gone as smoothly as it should
and that we are capable of, obviously. And I would hate for FDA
to sit back for 2 or 3 years and wait on us to get something
done, and then once it's done, you have to promulgate rules
based on that, and then we're even farther behind.
Dr. Woodcock. We had a public meeting on this, which is
often a prelude to rulemaking. We have certainly been in
discussions with companies that are interested in utilizing
this pathway.
Mr. Lankford. Okay. I do not want you to try to feel like
I'm saying to you, though, leave statutory authority. If you do
not have statutory authority, obviously don't go outside of
statutory authority. But if you have it and you feel like you
already have it, validate it, and I would encourage you to get
moving on it.
Dr. Woodcock. Uh-huh.
Mr. Lankford. So, again, I'm not going to try and speak for
all of us, but while we do have a responsibility, things have
bogged down significantly here. Fairly obvious, I think.
Ms. Speier. I have a question. There was a period of time
in the not-so-distant past when a number of companies had come
to me with questions about their approval when they had two
drugs that had been previously approved by the FDA. They were
combining them for obesity and were having either a difficult
time getting it approved or actually getting it denied, even
though both of those drugs independently had already been
approved by FDA.
Can you talk about that on the one hand, and also about
where we are in terms of obesity drugs? Because we all know
this is a huge issue in terms of American health.
Dr. Woodcock. Certainly. Well, when you----
Ms. Speier. And I need a quick fix.
Dr. Woodcock. We've had a lot of obesity drugs have to be
pulled off the market for safety problems, and primarily they
were cardiovascular safety problems. And so, I think the FDA is
trying to exercise caution on new obesity drugs but recognize
this is another epidemic that we're facing that needs some kind
of new thinking as far as how to deal with it.
The sliding scale I talked to you about before. So if you
have a drug that's indicated for seizures, say, that drug's
benefit risk will be looked at in the light of what is
epilepsy, what are the available treatments, who might use it,
how much risk would they be willing to take, okay, to control
their seizures. If you move a seizure drug or a drug for heart
failure or something over to obesity, you say to yourself 30
percent of all adult Americans have obesity. How much risk of
uncertainty of, say, heart attacks or strokes are we willing to
take in that population--all right, that's just an example--
versus where you're treating epilepsy where the people are
facing risks if they continue to have seizures, right. And
that's the conundrum that we're in. These drugs that we would
approve for obesity, millions of Americans might be exposed to
them, and they need to be relatively safe, unless, again, we
were able to restrict them to the very people suffering from
the most severe types of obesity. But that would be unlikely
given the prevalence of the condition in the United States.
In fact, we initially talked about this limited use
scenario that we're talking about for antibiotics also for
obesity because the benefit risk for somebody who is severely
obese is different than someone with mild obesity, or somebody
who is severely obese and has a lot of morbidities from it.
Heart disease. They have severe arthritis, mobility problems,
and so forth.
So the problem with, I think, obesity drugs is that eating
is such a basic human instinct and function, any drug that's
going to significantly interfere with that is going to have
powerful effects and may have effects in multiple domains, and
we need a lot of creativity in that area to move forward.
Mr. Lankford. We get into the issue of FDA making decisions
for doctors and the labeling issues and the warnings and that
kind of such, and I know that's a constant struggle for you
because you're testing for a certain thing and you haven't
tested for other things. You put that into the market and
physicians may use it off label.
Dr. Woodcock. Uh-huh.
Mr. Lankford. How is that moving within FDA? And quite
frankly, with your opinion, in the culture of FDA? Do you feel
like you're clamping down on labeling and adding more because
there's this barrier between do you restrict more or do you
give more information to doctors and just overload them with
information and say, read it, make the decision, because you're
going to go off label anyway, or is it stronger off label,
don't use it, restrict it, from FDA's perspective?
Dr. Woodcock. Well, generally speaking, and I think this
isn't well understood, but FDA accepts the fact that off label
use can be appropriate, and that's a part of the practice of
medicine for most drugs, okay.
There are drugs that we have special restrictions that are
called REMS, and these were put in as part of the FDAAA
legislation 6 years ago, I believe, and we had them before
through regulation where you'd restrict distribution of a drug,
and sometimes you have to say we're only using it for this.
And a premier example is, like, the drug Accutane is for
severe acne. It's a very effective drug, and severe acne can be
a really bad condition, but it was widely used for all kind of
acne because it works, right. But it's a major human teratogen,
and so it causes major birth defects if used in a pregnant
woman. And we were getting reports every year of use in
pregnant women every year, every year, even women who were
started on the drug and never had a pregnancy test.
So we, you know, put gradually more and more restrictions,
and now that drug is highly restricted in that you have to get
pregnancy tests before or not be of childbearing potential to
get Accutane if you're a woman. And we hate to do that because
that really burdens the healthcare system. On the other hand,
we have some of these very dire side effects that the
healthcare system has not shown itself to be capable of
managing without further intervention.
So you're right, we walk a narrow line there. We don't want
to overly restrict, but sometimes the side effects are so dire,
and it might be that the drug might not be available unless he
had that restricted program in place.
Ms. Speier. Can we speak about pediatric cancer for a
moment? Within the NIH budget less than 4 percent of the
funding goes to the research around pediatric cancer, and
there's a lot of off label use of drugs for pediatric cancer.
So can you just give us a sense of where FDA is in terms of
evaluating drugs for paeds, as they refer to them.
Dr. Woodcock. Well, we've had a strong pediatric program
because the Best Pharmaceuticals for Children Act, BPCA, and so
there has been quite a response by the pharmaceutical industry
to those programs. And, you know, they get extra exclusivity if
they fulfill certain requirements. We just celebrated 500 drug
labels that have been updated with pediatric information.
Now, that said, though, pediatric cancer is different, and
why? Because the cancer arising in a child is usually not the
same as the adult condition. And these pediatric programs were
set up to study conditions that occur in adults and then study
them lower and lower ages and then get that information. But it
stands to reason that the kind of mutation that would occur in
a child, you know, when they are just born or when they're
young, is different than the kind of mutations that occur over
a lifetime in a cell type and cause cancer. So that progression
that we see in other diseases hasn't happened as much in the
pediatric diseases, and I believe the pediatric cancer
community is concerned about this.
We've tried to encourage companies to study right away
drugs in childhood cancers if they seem appropriate. Often
you'd study a disease in adults first and then study children,
but in fact, when you have a life-threatening disease like
cancer it's appropriate to study the children right away also.
But the question is, what is the right drug for that cancer in
children?
I personally believe that the genomic revolution that we
were talking about earlier where we begin to understand the
sequences, the driving mutations in the cancers is really going
to help us, but we also are finding some of the pediatric
cancers are actually multiple diseases put together, just like
an adult cancer is.
So we have a pediatric oncologist, a very senior pediatric
oncologist on staff at the Center for Drugs, and we are really
trying to encourage development in this area.
Mr. Lankford. Mr. Meehan, you had a question?
Mr. Meehan. Just a final question, and maybe it's not fair
to even ask it, and if you don't want to respond don't. But
thinking outside the box, I mean, you labor in the vineyard,
and there must be times where you sit and think, you know, if
we built the mousetrap a little different way, maybe we could
have success. And I'm asking the question sort of guided by the
fact that you're hearing some of these wealthy industrialists
or others who are saying that with their life's savings now
they want to be the person, for instance, that cures
Alzheimer's, and they're going to put everything into this
effort. And I don't know whether that is the kind of thing that
we ought to be encouraging, where we say, let's just cure
Alzheimer's, let's create this Center for Excellence that does
it, let's keep it here in the United States so they don't send
it overseas to do it, which they're referring to. Does that
make sense or are we better off doing what we're doing trying
to not choose winners and losers?
Dr. Woodcock. That's a really profound question, I think. I
mean, I really can't give advice to Congress. I believe that
patient advocacy groups in many diseases have made tremendous
strides in advancing the treatments and cures for their
diseases. So that disease focus can be very beneficial in
getting treatments advanced and so forth, and they've done a
great job, partly because they understand what's needed. And
often what's needed is these clinical trial networks getting
the outcome measures, doing the natural history, really
understanding the disease very well, so when treatments come
along they don't fail, you know, they can be tested rapidly and
figure out how desirable they are.
Mr. Meehan. You have mentioned communication a number of
times. Are we missing opportunities in this age of the ability
of the NSA to drill down into the most intimate details
anywhere? But no, we're collecting more information than we've
ever done before. We've got the ability to assimilate
information better than we have before, and we are creating
more medical records, albeit they're still too much on paper
and other kinds of things. But with this bulk of records out
there, are we losing an opportunity to mine what we already
know to significantly enhance or advance the ability to
understand the things that we're trying to take on?
Dr. Woodcock. I don't know. Often the medical records, for
example, aren't detailed and standardized well enough to
provide these natural history outcomes that we'd really like to
have. We have the Sentinel System that we've set up, which is
really pretty, I think, novel and innovative. We have 120
million lives of data all behind the firewalls of the data
partners, the insurance companies, or healthcare system. But we
have it all standardized, we can query it, and we use that for
drug safety analysis, okay. So we use that existing data. And
they're starting to randomize, cluster randomize within these
kind of systems and answer important questions by doing
experiments out there.
I believe that telemedicine and recruiting people through
social media and so forth is probably something we really
should do, and that would be a way to really reach patients who
are out there and whose doctors aren't telling them or they
don't know about availability of trials and so forth. I think
we've just started to scratch the surface on how well that can
serve us.
Mr. Meehan. Well, I thank you. I guess we could go on all
day. But I am very, very grateful for the work that you do and
for your presentations here today. Thank you.
Thank you, Mr. Chairman and Ranking Member, for holding
this hearing.
Ms. Speier. Actually, the gentleman from Pennsylvania just
triggered, and your response triggered a question for me. The
ClinicalTrials.gov. At Google you can actually elevate your
status, so to speak, by paying for it. And so if you were to
Google cancer, you can have ClinicalTrials.gov come up first.
Who would be responsible for making that decision as to whether
or not that should be an expenditure we make?
Dr. Woodcock. That site is maintained by the National
Library of Medicine, it's part of NIH.
Ms. Speier. Okay. So that's a question to ask them.
Let me just conclude, Mr. Chairman, by saying that I think
we've got just a gold mine in you, Dr. Woodcock, and I thank
you for the competency and professionalism that you've showed
for so very long. And I hope that this will be a beginning of
an opportunity for us to find more ways to work together, and I
really think that pursuing the manufacturing of drugs here in
the United States is worthy of our time and attention, and your
assistance would be greatly appreciated.
Dr. Woodcock. Absolutely.
Mr. Lankford. I'd agree with that as well. And I also want
to thank you for the time to be able to spend here and the
time, both in preparation of your written statements. You made
a comment earlier that you don't give advice to Congress.
Again, that would be one of the few Americans that doesn't do
that. That's the wonderful thing about a republic, everyone can
give advice to Congress.
But through this there were a lot of to-do's that come out
of this. Let me give one statement just from me on it. You're
doing a lot of pilots, you're doing some outside-the-box
thinking of what can we do on that. We want to encourage that
and to say continue to do that. The companies, we have a lot of
companies that are now IPOs that are jumping in with different
ideas.
Dr. Woodcock. Uh-huh.
Mr. Lankford. We want to continue to encourage the
innovation that helps everyone. I'd also like to continue to
encourage you, as you've already started in your office, in
communicating with the advocacy groups for each of these
different diseases. They want the communication with you.
Dr. Woodcock. Yes.
Mr. Lankford. As much as you can spur that and then also
connect the dots between groups, for instance, what's happened,
as you mentioned before, with the cystic fibrosis organization.
There may be others that are interested in that that may not
even know that is occurring, but if it fast tracks that and if
there are ways that these different outside groups can do, they
are looking for things that will help. If there are things you
can clearly articulate that would help, they would like to know
that, and they need to be able to hear that from you. They are
very connected to NIH in the funding. They need to be connected
to you in the same way to know not only what's the research out
there that's being done, once the research is done, how can we
fast track solutions.
Dr. Woodcock. That's right.
Mr. Lankford. So, I would encourage that, as well as
increased information to physicians on clinical trials so that
for these rare diseases, especially, physicians know about the
clinical trial process and can get their patients into it. Be
much better than the compassionate use and other ways, and we
can have the research ongoing on it.
So those are quick admonitions in that, but you need to let
us know as well what we need to do statutorily, and we'll
continue the conversation about the antibiotics. But if there
are things that you need from us, we want to help in that.
Dr. Woodcock. Thank you.
Mr. Lankford. And we'll work in a bipartisan way to be able
to get that done.
So with that, with no other questions on the dais on that,
this hearing is adjourned.
[Whereupon, at 4:25 p.m., the subcommittee was adjourned.]
APPENDIX
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Material Submitted for the Hearing Record
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