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SCIENTIFIC OPPORTUNITIES AND PUBLIC NEEDS:

BALANCING NIH’S PRIORITY SETTING PROCESS

HEARING

BEFORE THE

SUBCOMMITTEE ON HEALTH

OF THE

COMMITTEE ON ENERGY AND

COMMERCE

HOUSE OF REPRESENTATIVES

ONE HUNDRED EIGHTH CONGRESS

SECOND SESSION

JUNE 2, 2004

Serial No. 108–131

Printed for the use of the Committee on Energy and Commerce

(

Available via the World Wide Web: http://www.access.gpo.gov/congress/house

COMMITTEE ON ENERGY AND COMMERCE

JOE BARTON, Texas, Chairman

W.J. ‘‘BILLY’’ TAUZIN, Louisiana

RALPH M. HALL, Texas

MICHAEL BILIRAKIS, Florida

FRED UPTON, Michigan

CLIFF STEARNS, Florida

PAUL E. GILLMOR, Ohio

JAMES C. GREENWOOD, Pennsylvania

CHRISTOPHER COX, California

NATHAN DEAL, Georgia

RICHARD BURR, North Carolina

ED WHITFIELD, Kentucky

CHARLIE NORWOOD, Georgia

BARBARA CUBIN, Wyoming

JOHN SHIMKUS, Illinois

HEATHER WILSON, New Mexico

JOHN B. SHADEGG, Arizona

CHARLES W. ‘‘CHIP’’ PICKERING,

Mississippi, Vice Chairman

VITO FOSSELLA, New York

STEVE BUYER, Indiana

GEORGE RADANOVICH, California

CHARLES F. BASS, New Hampshire

JOSEPH R. PITTS, Pennsylvania

MARY BONO, California

GREG WALDEN, Oregon

LEE TERRY, Nebraska

MIKE FERGUSON, New Jersey

MIKE ROGERS, Michigan

DARRELL E. ISSA, California

C.L. ‘‘BUTCH’’ OTTER, Idaho

JOHN SULLIVAN, Oklahoma

JOHN D. DINGELL, Michigan

Ranking Member

HENRY A. WAXMAN, California

EDWARD J. MARKEY, Massachusetts

RICK BOUCHER, Virginia

EDOLPHUS TOWNS, New York

FRANK PALLONE, Jr., New Jersey

SHERROD BROWN, Ohio

BART GORDON, Tennessee

PETER DEUTSCH, Florida

BOBBY L. RUSH, Illinois

ANNA G. ESHOO, California

BART STUPAK, Michigan

ELIOT L. ENGEL, New York

ALBERT R. WYNN, Maryland

GENE GREEN, Texas

KAREN MCCARTHY, Missouri

TED STRICKLAND, Ohio

DIANA DEGETTE, Colorado

LOIS CAPPS, California

MICHAEL F. DOYLE, Pennsylvania

CHRISTOPHER JOHN, Louisiana

TOM ALLEN, Maine

JIM DAVIS, Florida

JANICE D. SCHAKOWSKY, Illinois

HILDA L. SOLIS, California

CHARLES A. GONZALEZ, Texas

BUD ALBRIGHT, Staff Director

JAMES D. BARNETTE, General Counsel

REID P.F. STUNTZ, Minority Staff Director and Chief Counsel

SUBCOMMITTEE ON HEALTH

MICHAEL BILIRAKIS, Florida, Chairman

RALPH M. HALL, Texas

FRED UPTON, Michigan

JAMES C. GREENWOOD, Pennsylvania

NATHAN DEAL, Georgia

RICHARD BURR, North Carolina

ED WHITFIELD, Kentucky

CHARLIE NORWOOD, Georgia

Vice Chairman

BARBARA CUBIN, Wyoming

JOHN SHIMKUS, Illinois

HEATHER WILSON, New Mexico

JOHN B. SHADEGG, Arizona

CHARLES W. ‘‘CHIP’’ PICKERING,

Mississippi

STEVE BUYER, Indiana

JOSEPH R. PITTS, Pennsylvania

MIKE FERGUSON, New Jersey

MIKE ROGERS, Michigan

JOE BARTON, Texas,

(Ex Officio)

SHERROD BROWN, Ohio

Ranking Member

HENRY A. WAXMAN, California

EDOLPHUS TOWNS, New York

FRANK PALLONE, Jr., New Jersey

BART GORDON, Tennessee

ANNA G. ESHOO, California

BART STUPAK, Michigan

ELIOT L. ENGEL, New York

GENE GREEN, Texas

TED STRICKLAND, Ohio

DIANA DEGETTE, Colorado

LOIS CAPPS, California

CHRIS JOHN, Louisiana

BOBBY L. RUSH, Illinois

JOHN D. DINGELL, Michigan,

(Ex Officio)

(II)

C O N T E N T S

Page

Testimony of:

Fauci, Anthony S., Director, National Institute of Allergy and Infectious

Diseases ......................................................................................................... 21

Volkow, Nora D., Director, National Institute of Drug Abuse ...................... 26

von Eschenbach, Andrew C., Director, National Cancer Institute ............... 23

Zerhouni, Elias A., Director, National Institutes of Health .......................... 10

(III)

(1)

SCIENTIFIC OPPORTUNITIES AND PUBLIC

NEEDS: BALANCING NIH’S PRIORITY SETTING PROCESS

WEDNESDAY, JUNE 2, 2004

HOUSE OF REPRESENTATIVES,

COMMITTEE ON ENERGY AND COMMERCE,

SUBCOMMITTEE ON HEALTH,

Washington, DC.

The subcommittee met, pursuant to notice, at 2:10 p.m., in room

2123, Rayburn House Office Building, Hon. Michael Bilirakis

(chairman) presiding.

Members present: Representatives Bilirakis, Greenwood,

Shimkus, Pitts, Rogers, Barton (ex officio), Brown, Waxman, Stupak, Green, Strickland, and Capps.

Staff present: Chuck Clapton, majority counsel; Cheryl Jaeger,

majority professional staff; Jeremy Allen, health policy coordinator;

Eugenia Edwards, legislative clerk; and John Ford, minority counsel.

Mr. BILIRAKIS. The hearing will come to order. Good afternoon.

Today’s hearing, which we have entitled ‘‘Scientific Opportunities

and Public Needs: Balancing NIH’s PrioritySetting Process,’’ is the

fifth hearing that this subcommittee has held during this Congress

in order to highlight research activities at the NIH. These bipartisan hearings have educated members and others about the work

that the NIH is doing so we can access how to help the support and

research entity better meet its stated mission.

In many respects all of the hearings that we have previously conducted have been leading up to today’s hearing. Now that members

understand hopefully what the NIH is doing, we need to understand how they choose what research to conduct and how that research is funded.

The NIH is the world’s leader in conducting important research

that will unlock critical information and lead to discoveries beneficial to patients suffering from many diseases.

Over the years the NIH has seen significant increases in its

funding and the development of many new programs.

What began as a one-room laboratory of hygiene in 1887 now

consists of 27 Institutes and Centers that have been created in response to legislative or executive decisions.

When an institute is created, it has typically been provided a

separate annual budget from Congress. With this individual budget

comes the responsibility of setting priorities and making budget decisions within the Institute’s domain.

2

I am very interested, as we all are, I think, in hearing from today’s witnesses about how they balance setting priorities in their

institute and then how they coordinate those decisions across the

entire NIH.

The priority setting process at NIH and within every individual

institute has drawn questions, God knows, from Members of Congress as well as patient advocacy groups and others. I believe that

much of this criticism has arisen because the priority setting process is extremely complicated, especially the grant approval process,

and because NIH lacks transparency in many of their decisionmaking procedures.

Hopefully today’s hearing will give members an opportunity to

really understand what criteria is used to determine which grants

are funded and why.

To address these issues, we have an excellent panel of witnesses

before us. I would like to welcome them.

First, Dr. Elias Zerhouni, Director of the NIH, who is here today.

Doctor, you have been so gracious with your time over the past

year. You have been here before us, what, the second or third time,

I think, over the past few months, and we certainly appreciate all

of your efforts to assist the subcommittee’s work on NIH.

In addition to Dr. Zerhouni, we have three very distinguished institute directors: Dr. Anthony Fauci, who has been the Director of

the National Institute of Allergy and Infectious Diseases since

1984. Dr. Fauci, we look forward to hearing about your experience

over these years.

Dr. Andrew von Eschenbach, the Director of the National Cancer

Institute; and Doctor Nora Volkow, the Director of the National Institute of Drug Abuse, will also be able to discuss the unique challenges they face. Thank you both for coming, and I know that all

of you have had to rearrange your schedules to be here this afternoon, and you are some of the busiest people in our world, and we

certainly appreciate you taking the time.

In addition to hearing your individual testimony, I would also

like to initiate a dialog. I would like to see a dialog between and

among each of you as to how you have been working together to

ensure that the grants elected for funding measure up in importance to not only your institute but the entire NIH and the degree

that you have been effective in your collaborations.

Again, thanks for being here. I know that we have all been very,

oh, sometimes quizzical, if you will, concerned, whatnot, in terms

of how the NIH allocates their resources for research. And I would

hope that we could keep our opening statements as brief as possible so we can give these gentlemen and lady an opportunity to

explain all of that to us.

I would now yield to the ranking member of the subcommittee,

the gentleman from Ohio, for an opening statement.

Mr. BROWN. Thank you, Mr. Chairman. I especially appreciate

Dr. Zerhouni being here and his terrific work, the terrific work of

all three of you on the panel. And I want to single out Dr. Fauci

for his excellent work on infectious disease and what that means

for Americans, and especially in the developing world, especially on

tuberculosis and malaria and all that you have done that way.

3

I think all of us receive letters every day from constituents urging support for specific—to deal with specific illnesses, for cancer

research, Alzheimer’s, diabetes, arthritis, lupus, cystic fibrosis.

Every one of these health conditions and thousands of others compromise equality and length of our constituents’ lives. It is incumbent upon Members of Congress to ensure that NIH resources are

allocated in a manner that is reasoned, that is efficient and fair,

but this responsibility doesn’t exist in a vacuum. We have a requisite obligation to ensure ample funding overall for NIH.

A memo recently leaked to the press indicates that the President plans to cut $600 million from NIH in 2006 to make room for his

continued request for tax cuts. Let me place that in context. We

have been increasing NIH funding. Mr. Bilirakis has played a

major role in the doubling of NIH funding, as we all have

bipartisanly, but we have been increasing funding by a billion or

so each year.

I am sure that, Dr. Zerhouni, that these cuts didn’t come from

your desk, and I don’t believe the Chairman or my fellow colleagues on either side of the aisle would support that kind of request from the President to make these kinds of cuts in the National Institutes of Health, but we need to be aware that NIH cannot evolve without the resources to do so. Prioritizing research

doesn’t mean anything if you can’t fund it, obviously.

You all don’t have an easy job, nor does Congress. Both of us

walk a fine line in terms of how much influence to exert on the

general direction of medical progress and the priority given to researching various diseases.

Should we invest in diseases that are most prevalent, the most

deadly or disabling to Americans, to the poor in the developing

world, or for those which have the greatest chance of finding a

cure? Should we focus more dollars on the here-and-now concrete

answers to concrete questions or in paradigm shifts such as those

represented by human genomics?

As a rule, I think most of us, and I will speak obviously for myself, have tried to steer clear of any effort by Congress to compromise the flexibility NIH has to allocate the tens of billions of

dollars it received. However, a few years ago I made an exception.

I raise the example here because it illustrates, I think, three

points:

One, that it is in fact important for NIH to revisit and refind a

way that allocates funding on a regular basis.

Second, that Congress as a representative of the public must continue to play an oversight role and challenge NIH to respond to

public concerns about the agency’s funding decisions.

And third, what if NIH is not sufficiently responsive to the public, it doesn’t matter how the agency sets its priorities, because

those priorities will almost there, by definition, be wrong.

In 2001 I cosponsored legislation that required NIH to pay more

attention to Duchenne muscular dystrophy. Specifically, NIH was

to expand and intensify research related to Duchenne and other

forms of MD and support centers of excellence that would foster external muscular dystrophy research. It required HHS to establish

an interagency committee to coordinate all Federal muscular dystrophy programs and activities.

4

I joined this effort because—and this is one of the few times it

has happened in a major way I think—it was abundantly clear that

Duchenne has somehow fallen through the cracks at NIH, despite

the fact it is the world’s most prevalent childhood killer. Still today,

resources devoted to this disease represent less than .0005 percent

of the NIH budget.

The MD Care Act was signed into law by President Bush in

2001. The CBO scored it at $56 million in new spending over 5

years. My understanding is NIH has barely begun to fund the research in surveillance programs established under the new law,

and it has been 3 years, and that the CDC surveillance program

is off to a sluggish start.

Congress is very reluctant, as I said earlier, and as Mr. Bilirakis

has said in the past, to be prescriptive in appropriations report language with NIH, but the fiscal 2004 Labor-HHS appropriations bill

calls for full funding in this fiscal year of three additional centers

of excellence.

I understand NIH has solicited proposals for, ‘‘2 or 3 centers,’’

and the funding won’t be released until well in the next year. The

coordinating committee created under the new law has met only

twice since the bill’s enactment.

It is my understanding the NIH has contributed to the funding

of only one clinical trial focused on Duchenne muscular dystrophy.

NIH has publicly stated it has received only three clinical trial requests for Duchenne over the years. However, scientists interested

in this condition have told us that that number is not accurate.

The NIH in the past, certainly, and in other diseases is not just

a passive recipient of research proposals. The agency also obviously

solicits proposals from the research community. It is my understanding that no such solicitation has been made in regard to

Duchenne, even though established clinical trial and research center networks exist and important research opportunities have been

identified.

I am confident, Dr. Zerhouni, in your dedication and sincere interest in moving forward in NIH and the public interest as you always have, but I also contend that NIH can’t ignore concerns

raised by the public in Duchenne and other things.

Mr. Chairman, if the public loses confidence in NIH, it doesn’t

matter how we set our priorities and how you set your priorities,

Congress will be unable to secure the funding ultimately needed to

sustain this crucial agency, especially if the President gets his way

to slash spending in this agency.

We mustn’t let that happen.

Mr. BILIRAKIS. I thank the gentleman.

The chairman of the full committee, Mr. Barton, good to have

you.

Chairman BARTON. Thank you, Mr. Chairman. And I have a formal statement that I would ask unanimous consent that it be in

the record.

Mr. BILIRAKIS. Without objection, it will be.

Chairman BARTON. I am going to speak extemporaneously, because I want to try to be very clear. This is the fifth hearing that

this subcommittee has held on the structure or the goals of NIH,

5

and Dr. Zerhouni has been cooperative in all of these hearings, and

I want to thank you.

Today we want to look at the mission statement of how NIH sets

its priorities. That is the official title, and I want to thank our

three institute directors for coming.

I had lunch with Dr. Von Eschenbach not too many weeks ago,

with former Congressman Archer, and it is good to see you again.

But our oversight subcommittee is also holding hearings on NIH,

and the oversight function of this committee, and the Congress is

to kind of serve as a watchdog, and so we are kind of on a dual

track here. We are in the oversight function looking at the way certain things are being done, and Dr. Zerhouni is cooperating in that,

but this subcommittee is looking at the general structure of NIH

and how we can maybe reorganize, reprioritize, reform to make it

better.

There are certain things that the committee is not at all concerned about. We are not concerned about your peer review process. You all have thousands of reviewers that do tens of thousands,

probably, of peer reviews every year, and I think that is a good system. We are concerned that the NIH as it has evolved—we now

have 27 institutes and centers and they have kind of grown up

serendipitously.

We have one director appointed by the President, Dr. Zerhouni

right now, and he doesn’t have a lot of control over the centers and

the institutes. And I would like to see if we can, on a bipartisan

basis, through these hearings come up with a legislative package

to reauthorize NIH. Most of the programs at NIH have not been

reauthorized in a number of years, and that is a lack of discipline

on the committee. That is not a problem in NIH. That is our problem. We have not reauthorized your functions, and we have thrown

that on the appropriators; in this case, Chairman Ralph Regula’s

appropriation subcommittee.

So what we want to do in this subcommittee, with Mr. Bilirakis’s

leadership and Mr. Brown’s leadership, is see if we can’t work on

a bipartisan basis to come up with some legislative reforms that

make it easier for NIH to do its function. We are not opposed to

the function. We are not opposed to using the best scientific brains

in the world to try to find cures and treatments for all the many

diseases and afflictions that you folks deal with. But we are also

not just going to turn a blind eye and say, you know, business as

usual is okay, because the dollars are too big and the consequences

are too big. And, quite frankly, the assets at the disposal of NIH

are significant, and if we can channel them in a more comprehensive, coordinated fashion, we are going to do great deeds in the

years ahead. So that is what these hearings are about.

So I know it is—you know, we are beginning to see in the press,

because of what is happening on the oversight subcommittee, you

know, that the Congress is out to get NIH or—nothing could be further from the truth. You know, it is just the opposite. We want the

most effective state-of-the-art NIH for the 21st century, that gets

the biggest bang for the taxpayer bucks and the private sector dollars that are coordinated with what NIH does. That is what these

hearings are about, and I want to thank Chairman Bilirakis for

6

holding them. And our goal is to have an NIH reauthorization

package ready to move through this committee in this Congress.

[The prepared statement of Hon. Joe Barton follows:]

PREPARED STATEMENT OF HON. JOE BARTON, CHAIRMAN, COMMITTEE ON ENERGY

AND COMMERCE

Thank you, Chairman Bilirakis, for holding this hearing today. I am pleased that

the Energy and Commerce Committee continues to invest so much time and energy

in reviewing the operation of our most important public health agencies.

Today’s hearing is the fifth in a series that examines different aspects of the National Institutes of Health. The more I learn in these hearings, the more concerned

I become about the existing NIH priority-setting process. In particular, I am troubled by the relative lack of authority possessed by the Director to set priorities and

manage the research portfolio of the entire agency.

Over the years, the organizational structure of NIH has been arbitrarily expanded. This organizational structure largely determines the priority-setting process

at NIH. What we are here to figure out is whether or not the current priority-setting structure at NIH is adequate to meet the nation’s medical research needs. Congress needs to be able to evaluate if funding allocation decisions are made on the

basis of the best assessment of scientific opportunities and equity, in light of existing public health priorities.

Let me be clear: we are not holding this hearing today to argue that some of the

science conducted by NIH lacks merit. The scientific peer review process at NIH

works remarkably well considering the volume of grant applications reviewed each

year. I’m certainly not interested in picking and choosing among the thousands of

diseases that afflict Americans, to determine who should be the ‘‘winners’’ and ‘‘losers’’ of NIH funding. But to ignore the directions that Congress has already made

in dictating how research priorities are set at NIH would be a mistake.

Dr. Zerhouni, given the current problematic NIH structure, you should be commended for your leadership. Your efforts to design an NIH Roadmap to link all of

the research activities at the 27 separate institutes and centers towards shared research goals is a particularly important step.

In addition to Dr. Zerhouni, the Committee is privileged today to hear from three

Institute directors, who are also some of the top scientists in the world. Several of

them rescheduled travel and other commitments to attend today’s hearing, which

underscores the importance of the topic. Dr. Fauci, for over two decades your leadership has helped to control the rapid spread of infectious disease and prepare our

country to respond to potential bioterrorist attacks. In addition, Dr. Von

Eschenbach, and Dr. Volkow are nationally recognized experts in the fields of cancer

care and drug abuse, respectively. I look forward to today’s testimony and again

want to thank all of the witnesses for rearranging their schedules to attend the

hearing.

Mr. BILIRAKIS. The Chair thanks Chairman Barton.

Without objection, by the way, the opening statement of all members of the committee will be made a part of the record, and now

I recognize Mr. Waxman for an opening statement.

Mr. WAXMAN. Thank you very much, Mr. Chairman.

The NIH is the most important and successful medical research

organization in the world. It has produced more cures, more breakthrough treatments, and more hope for millions of patients around

the world than any other group of scientists.

I think we can all agree that Congress and NIH must work together to set NIH’s research agenda and priorities in the broad

sense. Congress, with NIH’s guidance, must decide how much to

appropriate to the general research areas covered by each of the institutes and centers, and of course Congress must exercise oversight.

After that, however, Congress should step back and allow NIH

scientists to decide what specific research projects will produce the

greatest gains for humanity. I am increasingly concerned about

congressional interference in NIH decisions to fund specific reVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00010 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
7

search grants. In making those decisions, NIH employs a rigorous

and highly respected peer review process. NIH uses over 11,000 scientific experts, all of which have had—all of whom have had many

years of scientific training and are recognized in their fields, to

staff 170 peer review panels.

As the members of this subcommittee look into NIH’s work, I

hope that we will all exercise self-restraint. In the past, some Members of Congress have given in to the temptation to substitute their

scientific judgment for that of the peer review process, and I think

that is a very perilous activity.

The fact that social conservatives disapprove of certain kinds of

sexual behavior or drug use cannot be the basis for deciding whether scientific research on that behavior is worth funding. Funding

decisions must instead be based on whether such research will or

will not help us learn how to stop the spread of serious diseases

and reduce human suffering.

And I am very pleased that Dr. Zerhouni has affirmed both the

scientific importance of research on sexual behavior in his continuing support for the peer review process at NIH, and I hope that

from this subcommittee that we will have a continuation of the policy to support a process whereby our best scientists pursue the research that they have determined offers the best chance to save

many lives.

I know that we are looking at other issues with NIH in the Oversight Subcommittee, and I am part of that subcommittee, and those

issues that have been identified ought to be dealt with and we

ought to make sure that the NIH lives up to the requirements in

the public interest of transparency and accountability. But let’s understand NIH is too important and too successful and too valuable

for us to in any way interfere with the important scientific work

that it is pursuing.

Thank you, Mr. Chairman.

Mr. BILIRAKIS. I thank the gentleman.

Mr. Rogers for an opening statement.

Mr. ROGERS. Mr. Chairman, I am going to yield for questions

later.

Mr. BILIRAKIS. Thank you very much.

Mr. Green.

Mr. GREEN. Thank you, Mr. Chairman.

And, again, I would—like the chairman of the full committee, I

would like to welcome Dr. Zerhouni back to us, and appreciate your

patience.

But I also would be remiss if I didn’t welcome my good friend,

Dr. Von Eschenbach, who we miss at M.D. Anderson at the Texas

Medical Center and your research successes you had in all those

years, but I told you earlier I will can our 95 degree temperature

and our 95 percent humidity and bring it to you here in DC. Just

in case you have missed it so much.

But, Mr. Chairman, I want to thank you and our ranking member for this series of hearings so we can gain knowledge on the important research NIH does, and I thank you for your leadership.

The work being performed at NIH has proved invaluable. The

groundbreaking research provided a lifeline of hope to countless

Americans living with diabetes, cancer and AIDS and many other

8

illnesses. As a testament to our support for NIH, Congress has

completed a 5-year effort to double NIH’s funding. Yet as NIH’s authorizing committee, it is important for us to understand how the

NIH utilizes this funding, how it determines its priorities, and

which strategies it sets to meet the goals.

I am particularly interested in NIH’s research on diabetes. I represent a district in Texas, it is over 65 percent Hispanic, and nationwide 24 percent of Mexican Americans age 45 to 74 live with

diabetes. Mexican Americans are also twice as likely to have the

disease as the Anglo population, which is why diabetes treatment

and prevention is so important to not only myself but to the district

I represent.

Diabetes research and treatment cannot be performed in a vacuum, though, and that is what we know about research in general.

Obesity plays such a large role and genetics and race play a role.

The disease can lead to a host of other conditions such as kidney

failure and cardiovascular disease.

I want to make sure NIH’s priority setting process includes a

truly collaborative effort—and I know we had this at other hearings—with the myriad of institutes that we have involved, to ensure that we are leaving no stone unturned in the research to find

treatments and a cure for this deadly disease.

Stem cell research also provides us with a great promise in finding cures for devastating diseases, diabetes, Alzheimer’s and cancer. While it is no secret that NIH’s stem cell research is constrained by the President’s policy on the issue, I appreciate, Dr.

Zerhouni, your candor when you recently wrote that from a scientific perspective, more cell lines may well speed some areas of

human embryonic stem cell research. Stem cell research offers a

tremendous hope to patients with diabetes, Alzheimer’s, Parkinson’s and cancer treatment.

Speedy research is exactly what these patients need and this policy is simply a roadblock along the path of research and discovery

at the NIH that could lead to cures for many illnesses.

Again, I want to thank the witnesses for being here today and

their effort for a number of years, and, again, Mr. Chairman, thank

you and our ranking member for your leadership to make sure we

continue to have this oversight, and I am glad to hear the Chairman of the committee has the goal of doing the reauthorization, so

I am looking forward to that.

Mr. BILIRAKIS. I thank the gentleman.

Mr. Strickland for an opening statement.

Mr. STRICKLAND. Mr. Chairman, I look forward to hearing the

witnesses, and I will forego an opening statement. Thank you.

Mr. BILIRAKIS. The Chair thanks the gentleman.

Mrs. Capps.

Mrs. CAPPS. Thank you, Mr. Chairman.

I also want to thank Director Zerhouni, Directors Fauci, Volkow,

and von Eschenbach for making yourselves available to us today.

We appreciate your time and the fact that you are willing to share

your expertise with us.

It is a matter of great pride, I believe, in a bipartisan way that

we have over the past few years doubled the funding for NIH, and

we in Congress often focus on the benefits that the public gets from

9

the billions of dollars that are devoted to the NIH. This is a good

work that we fund but that you carry out. There is no doubt that

this investment has paid off in spades.

But there is an issue that I want to bring up today, hoping that

this committee and the NIH could begin to discuss, and that is

public access to the fruits of federally funded research. It is complex, and I don’t have a black or white answer, but many results

of federally funded research are published only in very expensive

journals that most of the public has no access to. Many universities, libraries and organizations such as the Howard Hughes

Medical Institute, the Welcome Trust, and the Susan G. Coleman

Breast Cancer Foundation would like to see this research opened

up more fully to the public.

To be sure, there are many questions that have to be answered

before this approach is endorsed by Congress or the NIH. I believe

that this is an appropriate place to carry out some of this discussion. I hope we can do so in the near future.

And again I want to address an issue that my colleague Mr.

Waxman has brought up. I have addressed it before, and maybe it

will come up today in some testimony. Some of our colleagues who

have little or no scientific or medical expertise—and actually that

has nothing to do with that—have raised questions about NIH

grants on human sexuality. Congressional oversight is important,

but it is critical, I believe, that we be very serious about keeping

politics from interfering with science.

NIH was set up to dramatically improve the lives of Americans

by increasing the quality and amount of biomedical research conducted, and NIH does this job admirably. We here should not try

to micromanage scientists about how to conduct their research, and

we should not engage in witch hunts to discourage research into

particular areas. I believe there is no question that some Americans engage in self-destructive behavior. If we want to help them

to make their lives better, we cannot pretend that that behavior

does not exist. So we must come to understand it and its effects

on public health in order that it can be addressed more scientifically and more effectively.

I believe that is what scientific research is for. The Congress

should not hamper the excellent work of the NIH by trying to impose any kind of ideology onto science.

So I look forward to hearing the testimony that you are going to

present to us, yield back the balance of my time.

Mr. BILIRAKIS. The Chair thanks the gentlelady.

I believe that completes the opening statements, and the Chair

is grateful for that so we can move right into the witnesses’ testimony.

I am going to set 10 minutes for each one of you, if I may, and

hopefully you can stay within it. Your written statement is, of

course, part of the record. And hopefully you will have an opportunity for dialog among yourselves.

Dr. Zerhouni, please proceed, sir.

10

STATEMENTS OF ELIAS A. ZERHOUNI, DIRECTOR, NATIONAL

INSTITUTES OF HEALTH; ACCOMPANIED BY ANTHONY S.

FAUCI, DIRECTOR, NATIONAL INSTITUTE OF ALLERGY AND

INFECTIOUS DISEASES; ANDREW C. von ESCHENBACH, DIRECTOR, NATIONAL CANCER INSTITUTE; AND NORA D.

VOLKOW, DIRECTOR, NATIONAL INSTITUTE OF DRUG ABUSE

Mr. ZERHOUNI. Thank you, Mr. Chairman. I am pleased to appear in front of your subcommittee and I am pleased to be accompanied today with my esteemed colleagues.

It is an important topic that I think you are addressing, and that

is reviewing the NIH research portfolio and discussing our priority

setting processes. I have submitted written testimony. What I

would like to do is summarize on slides what I think are the salient components of what NIH does to allocate resources to the best

extent possible to address the disease burden in our population.

There is no doubt that NIH has been and continues to be at the

leading edge of discovery. For example, in the area of infectious

diseases we identified the SARS virus in less than 3 weeks. In

1985 it took 3 years to identify the HIV virus, and influenza took

30 years to be identified. This is due to the investment that Congress and the administration have made over the years in NIH.

Clearly, we can also see progress being made in other areas of

research besides infectious diseases. This year, for example, we

have now discovered over 12 genes which were never suspected before to be the cause of mental illness, including schizophrenia. We

are now at the edge or the threshold of understanding how schizophrenia develops in the human population, reminding you that

schizophrenia in young adults 25 to 44 years of age is one of the

main causes of disability.

We continue to uncover basic principles of human biology. The

human genome is just one step in the process of understanding

how all of our molecules and cells are organized, and we are continuing to make progress in this area at a very rapid pace, which

is being applied across all disease areas.

In addition, I think that life expectancy continues to increase,

and it is the result of many factors. Clearly, some of the impact of

the research of NIH has changed the landscape of the diseases that

we have to deal with and therefore changes the mechanics and the

strategies for priority setting in the country.

For example, if you look just at the impact of our research on

cardiovascular disease over the past 30 years, it has been remarkable. Mortality from heart disease and stroke has decreased by

over 50 percent.

How does that translate in numbers? If you looked at coronary

heart disease between 1950 and 2000, and if we had projected in

1970 what the number of deaths would be in 2000, it would be

1,329,000 deaths experienced in 2000 if we hadn’t discovered that

hypertension was a risk factor, or high cholesterol was a risk factor, or discovered all of the new treatments and therapies that we

are using in cardiovascular disease.

So in fact you can say that 815,000 deaths have been prevented

in 2000 because of this 30-year investment in cardiovascular disease with this rapid decrease in mortality.

11

What is the impact of that on life expectancy? Obviously life expectancy increases, but at the same time this acute disease, which

used to kill many of our patients very quickly, is transferred into

a more chronic acute condition. And if there is one word I can give

you as to the scientific priorities of NIH is this transformation of

disease from more short-term lethal acute diseases to more longterm chronic conditions, including, for example, cancer where much

progress has been made to the extent that survivorship in cancer

is unprecedented at this time in history, and we have over 9 million individuals who survived cancer in this country.

So when you look at that, you obviously see a changing environment, and the resource allocations and the budget allocations have

to reflect that changing environment in some ways.

Just to go quickly over the NIH budget, there are four ways to

look at our budget. First and foremost, you can look at it by mechanism: Do we fund grants, do we fund centers, do we fund contracts?

The second is by research area: How much do we fund in cancer

versus infectious disease or pediatric research? The other is to look

at how we fund the structures of NIH that have been authorized

over the years by Congress, the institutes and centers and offices,

and how much funding is in each one of these institutes.

And obviously we can also look at it in terms of scientific effectiveness. In other words, what is the likelihood that we can fund

the research enterprise in the country and the capacity that is committed to finding the treatments and prevention strategies that we

need?

If you look at that this way, I can show you very quickly that

about 85 percent of the NIH budget is spent outside of NIH. About

10 percent of the budget is spent intramurally here in Bethesda.

We spend about 4 percent of our dollars on research management

and support, which is the administrative expenditures, and about

a billion dollars on activities like the National Library of Medicine,

education, and so on. But the rest of it is spent on academic institutions, and we support over 212,000 scientists in the country at

over 2,800 institutions throughout the country.

So if you wanted to look at the budget by mechanism, where is

it intramurally, where is it extramurally, by institutes, you can see

the very large range of funded institutes and the levels of funding.

NCI, my dear colleague Dr. von Eschenbach leads, is funded at

$4.87 billion. NIAID, under the direction of Dr. Fauci, is $4.4 billion. And you can see the FIC at the bottom right is the Fogarty

International Center, which is our international operation, $67 million. So you can see a wide range of allocation of resources for different institutes with different missions and different scope of missions. And this is the complexity that you have to deal with as an

institution, and you have to balance that relative to the opportunities in science and the good ideas that come from our scientists.

America is unique in the world, in that it uses a peer review system that is fundamentally based on the ideas of scientists, where

investigator-initiated grants come in and we review them and fund

a small percentage—about a third of them are funded. So if you

look at our likelihood of success to be funded, if you are a scientist

in the United States and you came up with a good idea and you

came to NIH, in 1996 your funding chances would be 28 percent.

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And then it went up during the doubling period, all the way to 32

percent. It remained very competitive. And currently in 2002, 2003,

it went to 30 percent, and we project 27 percent for the 2004-2005

period.

Why is it that despite the doubling, the success rate has remained very competitive? Most of the answer is in this graph. We

have had more and more scientists drawn to biomedical research

because of the long-term commitment and investment of the American people to medical research. In 1996 we had about 23,800 research project applications that year. In 2003 we had 34,700, a

huge increase in the research capacity of the United States, which

is obviously a good indicator that, A, there is attraction to the field

and, B, we remain very competitive in who we grant and how we

grant our research dollars.

When you look at priority setting, what I would like to do is

show you the entire wheel of how priority setting should occur and

occurs in practice. And as the Chairman said, it is a complex process. It is not something that you can explain with one parameter

and say this is how we allocate our resources. But at the top of the

list is obviously our intent to reduce both disease burden as we

know it today, but also potential disease burden as may occur in

the future.

A good example is Dr. Fauci’s investment in biodefense and the

increasing funding in biodefense. I mean, we are doing this not because there is an existing disease burden. We are doing it because

of a potential disease burden, and other areas can be illustrated.

So first and foremost, we try to evaluate the disease burden that

we are dealing with through a variety of mechanisms. CDC has the

National Center for Health Statistics. The National Cancer Institute has a program called Surveillance, Epidemiology and End Results to track cancer progress. Other institutes have different

mechanisms. We don’t have an established national way of measuring burden for all diseases; however, we do it for the most important ones.

But let’s say now that a disease burden is emerging, like obesity,

for example, as a new threat, or chronic disease, which we did not

experience in the past which are now becoming very important.

How do we then adjust the portfolio, adjust the strategy?

First and foremost, we need to have, obviously, a public investment in the area. What is the public investment used for? First,

we have to build scientific capacity. You cannot advance in the field

of research for any one disease if you do not have the people, the

resources, the ideas, the buildings, the laboratories. And that is the

first thing that NIH does. A good example of that is what Dr. Fauci

will talk to you about. Today he is engaged in building scientific

capacity for biodefense research. They are building laboratories

across the country at NIH and in different areas.

Once that is done, the next step is to obviously build the research

capacity itself in the area of interest. Research in tuberculosis and

malaria, versus cancer, versus other areas, requires different disciplines and different combinations of disciplines. That research capacity then hopefully leads to discoveries and breakthroughs that

can be then used as new opportunities.

13

So this is where we see scientific opportunities for therapies

occur, and these scientific opportunities then have to be translated,

and sometimes this is where I think a lot of the discussion occurs.

How much emphasis do we place on scientific opportunity versus

why don’t we just go and create a lot of clinical trials and do the

translation? And the message I like to give to everyone is you can’t

translate a language you do not understand very well. To the same

extent in science, the timing of translation depends on how well

you understand the disease process and how much progress you

have made at that time and balance the research capacity with the

opportunity and with the ability to translate successfully. Hopefully once we have translated that to practice, it is what I call the

cycle, lab to life, that essentially underlies every research enterprise that you could analyze at NIH, and you will hear how my colleagues do so within their own mission area. And this is what we

need to do also at the NIH level.

So let’s talk about how well are we doing relative to the disease

burden. Let me show you an independent study that was led by Dr.

Cary Gross in 1999 where they evaluated the disease burden, calculated with modern methods of computation of burden, and the

modern method is called disability-adjusted life years.

Just to give you a simple example of how that works, if you had

a child 1 year old who had a disease and didn’t survive, that child

would have lost their life expectancy. So that would be 80 years of

life lost. If somebody is 98 years old and has a cancer, that is computed really maybe as 2 years of life lost, depending on the actuarial tables. That is the computation that epidemiologists make.

When you look at the diseases studied, the red line is about

where the average disease burden versus investment would be. On

the left-hand side is the funding in NIH dollars, and the horizontal

is the disability-adjusted life-year component.

And as you can see, by and large, the investment is around the

mid-life for these diseases. But you will also see outliers, and question the outliers. For example, you can see AIDS at the top of the

curve, and this is a common question: Why is AIDS, relative to the

current disease burden, higher in funding than other areas? Well,

this is a judgment that is made not on the basis of existing disease

burden, but potential future disease burden both here and in the

world and the potential impact this may have on the economy of

the United States.

And I will let Dr. Fauci comment on that. So there are logical

ways that we use to correlate, if you will, the disease burden, the

scientific opportunity with funding, but those are not precise.

As you can see, there are variations across all diseases.

Now, how do we answer your question, which is, how do we know

that NIH has methods that allow it to not only do good peer review

but effectively manage its research portfolio? And there are three

factors there that we take into account: science, public health requirements, and societal needs. And we get inputs, as you mentioned, from many, many sources, including the public.

One of the things I would like to attach to my testimony is the

last report of the Council of Representatives of the National Institutes of Health who studied the transparency issue and how can

14

we improve our processes to have public input at NIH to a greater

degree than we have had in the past.

Mr. BILIRAKIS. Without objection, that will be the case.

[The report appears at the end of the hearing.]

Mr. ZERHOUNI. Thank you, Mr. Chairman.

A good example of adaptation is the example of obesity research.

So what mechanisms do we have to make sure that nothing falls

through the cracks? Clearly, the burden is going up. CDC is reporting it now as the second preventable mortality after smoking. So

we have created a trans-NIH task force last year to review all of

NIH’s strategies and portfolio. Then the new plan was developed

this year. And just to give you an example, we decided to increase

funding for obesity research by 10 percent, even though the rest of

NIH grew by 2.6 percent. So there are ways for us to use both disease-specific planning.

The second example I can give you is the neurological institutes

have now come together and are in the process of developing a

blueprint for neurosciences, which is another mechanism where a

cluster of like institutes can work together. And last is a trans-NIH

process which we implemented over 11⁄2 years ago called the NIH

roadmap, which is a way for NIH to explicitly analyze where it is

on the horizon of research and where it is that we need to make

investments.

In this case we decided that the three areas would be molecular

understanding of biological systems, new research teams and reengineering the clinical research enterprise.

So what are the next steps from my point of view that I could

share with the committee in terms of how do we improve these

processes that are there, that are operating? Can we make them

better? Obviously we can always make them better, and we welcome all of the work that the committee is doing and that we are

doing in trying to improve the processes as much as possible.

So how can we improve? One is we think—and all the directors

agree—that we need to create better information systems to analyze the NIH portfolio of research. In one word, I think NIH has

world-class peer review. We can make some advances if we invested in the information systems needed to analyze not just each

grant but the totality of the grant portfolio both within institutes

and across institutes.

The second recommendation would be that, just like the roadmap

which I think worked well, we need to institutionalize a more regular process of trans-NIH priority review and planning with a common pool of funds.

The issue I think everyone raises is that the rigidity of the funding mechanisms do not allow institute directors, as well as the NIH

director, to jointly and aggressively fund emerging areas of research. The fact that we have come together for the roadmap shows

it is possible. I think this is a process; from my standpoint, I would

increase tremendously the effectiveness of the agency. But it has

to also come with a much more integrated governance and management system that includes all directors. We have started to do this

with a transformation of how decisions are made at NIH.

And, obviously, we need to measure outcomes and have better

measures. So I wanted to quickly go over the rationale that we folVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00018 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
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low, Mr. Chairman, and I would like to have my colleagues continue the presentation. Thank you.

[The prepared statement of Elias A. Zerhouni follows:]

PREPARED STATEMENT OF ELIAS A. ZERHOUNI, DIRECTOR, NATIONAL INSTITUTES OF

HEALTH, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Mr. Chairman, Members of the Subcommittee, I am Dr. Elias Zerhouni, the Director of the National Institutes of Health. I am pleased to appear before you today

to provide an overview of the NIH research portfolio and discuss priority setting.

NIH’s mission is to conduct research that will lead to better methods of diagnosing, treating, preventing, and curing disease. The research that we support has

resulted in improvements in detecting disease, better therapies, and more effective

vaccines.

As one example, our ability to fight infectious diseases is greater than ever before.

Consider how research advances enabled the world to quickly identify and contain

the SARS virus. We will produce treatments and vaccines for other diseases, such

as West Nile Virus, in record time. We have also developed a single dose, fast-acting

experimental vaccine to prevent one of the most feared viruses of all, Ebola. The

vaccine has proven successful in animals and human trials are under way.

In the area of mental illness, NIH-supported researchers recently discovered

genes associated with schizophrenia, a tragic illness that affects 1 percent of the

adult population. This research, which brings us closer to better treatments for this

disorder, was cited by Science Magazine as the number two scientific ‘‘breakthrough

of the year’’ in 2003.

Much of our progress is attributable to basic research advances furthering the understanding of human biology. NIH and its collaborators have sequenced the human

genome, one of the greatest scientific achievements in history. Now we are moving

forward with research into molecules and proteins to gain knowledge leading to new

therapies that will alter the way medicine is practiced and result in even greater

improvements in public health. We are on the cusp of an era of medical practice

that will identify and prevent diseases before the symptoms appear.

In short, we are living much longer and significantly better as a result of biomedical research. And while we have come very far, we have even farther to go. Despite our extraordinary successes, there is still a great deal we do not know about

human biology. In areas where we have reduced death and suffering, we can do

even more. Consider the case of cardiovascular disease. One of the greatest public

health success stories of the last half-century is the dramatic reduction in mortality

from stroke and heart disease. In the year 2000, the number of deaths from cardiovascular disease was nearly 40 percent less than we had projected in the same year.

Research identifying risk factors and new therapeutic interventions to control the

risks were largely responsible for this remarkable lifesaving achievement. Yet cardiovascular disease still accounts for about 38 percent of all deaths in the United

States every year. If we sustain our research effort, imagine how many more lives

we can save over the next 50 years.

The Nation remains committed to the support of biomedical research. Congress

and the President appropriated a little more than $28 billion to NIH in FY 2004,

and the President’s Budget Request for FY 2005 is $28.7 billion, a $729 million or

2.6 percent increase. Of the funds appropriated in FY 2004, an estimated $5.6 billion will be spent on cancer research and $4.9 billion on neurosciences research. We

expect to spend $3.6 billion on research affecting women’s health and $3.2 billion

on pediatric research. We plan to spend $1.6 billion on biodefense research, and $2.4

billion on cardiovascular research. Another major investment is aging research,

which will receive $2.3 billion. Vaccine development research will total $1.4 billion.

There are several ways to view the NIH budget. The most relevant picture is the

snapshot of the individual Institute and Center budgets because Congress appropriates funds on the basis of allocations to these 27 organizations. In FY 2004, their

budgets range from $4.7 billion for the National Cancer Institute to $65 million for

the Fogarty International Center.

Another common way to view NIH’s budget is by the funding ‘‘mechanisms’’, such

as grants, contracts, cooperative agreements, or in-house programs. About 80 percent of the NIH budget is awarded to extramural research institutions throughout

the United States. The largest grant mechanism is our Research Project Grants,

which comprise 54 percent of NIH’s budget in FY2004, or $15.1 billion. Another important funding mechanism, research centers, supports groups of investigators

working on common disease or research areas. This mechanism accounts for 9 percent in FY 2004, or $2.6 billion. Another vital mechanism is our research training

16

programs, which comprise 3 percent of our total budget, and will help ensure that

we will have the skilled workforce needed in the future to continue making progress

in research. Our intramural research program accounts for 10 percent of our total

budget, or $2.7 billion.

Our budget can also be viewed by funding of specific diseases, several of which

I have already mentioned. Research projects can often contribute to advances in

multiple diseases; thus, our estimates of research expenditures by disease necessarily contain overlap and are not mutually exclusive.

The public can also view the NIH budget from the perspective of the success rate

of grant applications. However, looking at the budget from this perspective results

in many misleading conclusions. Success rate alone is not indicative of the number

or size of grants being funded; the number or quality of grant applications received

in a given year; and research mechanisms that NIH may be funding other than

grants. In addition, our estimates of the projected number of applications submitted

and the number actually awarded have undergone significant revisions from earlier

predictions, creating some difficulties in making grant budget projections.

Over the decades, the allocation of NIH dollars has adapted to public health

needs. In fact, much of our spending focus recognizes the shift in disease burdens

that has taken place in recent decades. For example:

NIH is increasingly targeting chronic diseases, which have overtaken acute conditions as the Nation’s leading health problem.

We are responding to a new epidemic—obesity—which, if continued unabated,

threatens to undermine our progress against disease in similar ways to tobacco

use. Part of this response has been a proposed trans-NIH funding increase of

10 percent allocated for obesity research in the FY 2005 President’s Budget.

We are quickly expanding our research efforts to protect the Nation against lethal

bioterrorist acts by identifying the threats and developing vaccines, diagnostics,

and therapeutics to address them.

We are committed to NIH’s infectious disease research on problems such as AIDS,

SARS, West Nile Virus, influenza, malaria and tuberculosis.

We remain committed to research on other long-standing problems, such as the

health disparities that exist among racial, ethnic, and disadvantaged populations.

As the most influential force in the U.S. biomedical research community, NIH exercises its leadership by continually surveying public health needs and the scientific

landscape to identify new biomedical research areas that require attention. Simultaneously, we search for emerging scientific opportunities. To maintain the vibrancy

of our scientific enterprise, NIH also actively supports strong basic and clinical research training programs. Our programs are unique in both igniting and complementing private sector research and development efforts.

NIH undertakes studies for which the risks are too high or the financial incentives too low to attract private investment. Tailoring therapies for the special needs

of vulnerable populations and evaluating treatments for rare diseases are other

NIH-led investigations where the intervention of a public agency is essential. With

the massive responsibility of advancing knowledge across such a wide landscape,

whenever possible NIH marshals efforts of academic institutions, industry, research

organizations, disease foundations, and patient groups to maximize its efforts.

This focus on vulnerable populations and rare diseases is an essential part of

NIH’s mission, and must be a component of priority setting. Instilled in all of us

at NIH is the human dimension that drives us to help the helpless, whether their

suffering is from a disease that affects millions or a disease that affects only a few.

This is why I became a physician, and it is why I was eager to come to NIH.

To maintain a research portfolio that balances public health needs and scientific

opportunities, NIH seeks input through multiple channels, including the Advisory

Committee to the Director and the NIH Council of Public Representatives. NIH uses

an unparalleled peer review system involving its Center for Scientific Review as

well as separate vetting programs within each Institute and Center. These programs

are part of a two-tiered system of advisory bodies and specialized review committees

that guarantees funding of the best applications from among the nearly 50,000 research and training applications reviewed annually.

NIH’s priorities are driven, in part, by the ideas and opportunities presented to

us through the grant applications we receive. By placing most of our resources in

investigator-driven research, NIH ensures that federal dollars track the latest

science. But allowing the scientific community to drive research is only one factor

in how NIH sets priorities.

Determining research priorities is a complex, multifaceted process. One cannot

easily quantify the various factors and questions that surround priority setting at

NIH. Some of the variables in the determination of resource allocations include pubVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00020 Fmt 6633 Sfmt 6621 95440.TXT HCOM1 PsN: HCOM1
17

lic health needs and the burden of disease, scientific opportunities, the quality of

research proposals, the experience of applicants, and the ability to sustain research

through adequate staffing and infrastructure. These factors are often lost in the

public debate about NIH funding, in which the discussion is simplified by focusing

attention on apparent funding inequities between the toll of certain diseases and the

amount spent on research about those diseases.

Although burden of disease should not stand alone as a factor in setting priorities,

there are indications that NIH funding generally tracks disease burden data. A

study published in the New England Journal of Medicine five years ago concluded

that there is a significant—although not absolute—correlation between the burden

of disease and NIH funding. The genome project, development of instrumentation,

training in clinical research, and new developments in basic science all have high

values in the treatment of specific diseases, even though they lack a disease-specific

orientation. Nonetheless, the study is evidence that NIH resources reflect the burden of disease in measurable terms.

Do these successes mean we are doing everything we can to ensure that the NIH

research portfolio is balanced, is focused on the most urgent needs, and is based on

irrefutable data? Let me answer that question with the following observation: Great

organizations can maintain greatness only by continuous reassessment and adaptation.

I believe that we cannot be static. NIH must enhance the current process for determining priorities and allocating resources as part of a balanced research portfolio

across the Agency and within each Institute and Center. The system of funding research by allocating resources directly to disease, organ, or special-population-based

Institutes and Centers has served NIH and the public well. We plan to continue this

approach to funding programs at the Institute and Center level. But science is

changing, driven by new technologies and discoveries. Modern research is often best

conducted by teams, which may include mathematicians, chemists, physicists, engineers, bioimagers, computer scientists, behavioral scientists, and physicians, and

which may cut across the expertise of many different NIH Institutes and Centers.

Several fertile areas of research—genomics, proteomics, molecular engineering—

serve all fields of endeavor and cannot be pigeonholed according to specific diseases.

As the Institute of Medicine noted last year in its review of the structure of NIH,

consideration should be given to refinements in the priority setting process and the

management of our portfolio. There is a particular need for new and sustained approaches to evaluating NIH’s crosscutting science. While maintaining the support

for existing Institute and Center research programs, I think we should consider

ways of using resources that may not be controlled by a single Institute or Center,

but by a priority-setting process with input from outside and inside NIH. I am encouraging each Institute and Center to evaluate their own priority setting and portfolio management processes and seek best practices or other methods of enhancing

their systems. I have also asked the Institute and Center directors to strive to pool

resources, as they have done in research areas such as obesity and neuroscience.

An expanded approach to priority setting would enable NIH to ensure balance in

our research portfolio, identify appropriate cycles of change, maintain proper turnover rates for grants and provide much more accountability to Congress and the

public. Under such processes, we would identify crosscutting research that requires

common investments from the various NIH Institutes and Centers. This approach

must include a regular horizon scan of all research so that we can have sufficient

information to manage the NIH research portfolio.

Two years ago, soon after I arrived as the Director of NIH, we convened a summit

of the Nation’s scientific experts to determine obstacles to the advancement of research and methods to overcome them that could not be addressed by any single

Institute or Center. Teams comprising the NIH’s leadership, working with their

counterparts in the extramural scientific community, discussed new ideas. From

these deliberations, the NIH Roadmap emerged. The Roadmap is focused on three

goals: Identifying new pathways of discovery; Building the research teams of the future; and Re-engineering the Clinical Research Enterprise. As a modest but significant step forward, the Roadmap is supported by voluntary funding from all of our

Institutes and Centers, with the goal of supporting research that will benefit all

NIH programs and research into multiple diseases.

As I said, the Roadmap is a modest attempt at progress. It has an initial investment of less than 1 percent of NIH’s total budget. The Roadmap is an example of

a better-integrated mechanism for priority setting at NIH. My expectation is that

we will build on the Roadmap, and it will serve as a model for future determinations of resource allocations.

In summary, I believe the confidence of the American people in NIH to lead biomedical research has been and will continue to be deserved. Our processes for idenVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00021 Fmt 6633 Sfmt 6621 95440.TXT HCOM1 PsN: HCOM1
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tifying priorities and ensuring sound science have worked well. But reassessment

and adaptation should occur and lead to a priority setting process that has greater

public input, is more transparent, and lead to a research portfolio that will keep

NIH at the leading edge of biomedical research.

I intend for the process to contain the following essential elements:

A transparent process characterized by a defined scope of review with broad input

from the scientific community and the public.

A solid database of information, including uniform disease coding and accurate, current and comprehensive information on burden of disease.

An institutionalized process of regularly scheduled evaluations based on current

best practices to be used by Institutes and Centers.

The ability to weigh scientific opportunity against public health urgency.

A method of assessing outcomes to enhance accountability.

Thank you for the opportunity to testify. I will be pleased to answer your questions.

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Mr. BILIRAKIS. Thank you very much, Doctor. Your general but

very well-done presentation, I think, sets up all the other three, so

I have allowed you to go well over your 10 minutes’ time.

Dr. Fauci, please proceed with your statement.

STATEMENT OF ANTHONY S. FAUCI

Mr. FAUCI. Thank you very much, Mr. Chairman, and thank you

for giving me the opportunity to discuss with this committee—and

thank you, committee members, also—the priority setting process

of an individual institute that in some respects represents all of the

institutes but in many respects is unique because of the mandate

of our mission to respond to emerging threats of infectious diseases.

On this first poster, as you see on your right, the mandate for

the NIAID, the National Institute of Allergy and Infectious Diseases, as Dr. Zerhouni pointed out, the second largest institute

with a budget of about $4.4, $4.5 billion, is research in immunology, microbiology and infectious diseases.

Now, if you look at the red arrows, these are the areas that we

are responsible for. We are responsible for diseases of the immune

system, infectious diseases in general, and then there are other

issues that are thrown upon us by events. For example, the HIVAIDS epidemic, emerging microbes, such as the threat of a pandemic flu and, most recently, biodefense. We set our priorities, just

as Dr. Zerhouni mentioned, by the delicate balance that we continue to fine-tune because it is a dynamic process involving the scientific opportunities as well as the public health needs.

I would like to point out that both of those can change dramatically, because sometimes scientific breakthroughs create opportunities that just a year or 2 ago we didn’t have, and sometimes public

health needs like SARS comes along that you had no way of predicting.

So let me show you the history, the funding history of this institute, and how it has dramatically grown over the last several

years. Not only because of the doubling of the NIH budget—because the scientific opportunities in immunology and infectious diseases are rather dramatic—but also as I mentioned, the HIV epidemic, the emerging and reemerging diseases like SARS, and then

finally the rather dramatic increase that we experienced with the

biodefense responsibility that has been given to us to develop countermeasures.

Let me just show you the dramatic metamorphosis of an institute

that had to take place in the context of very serious continuing priority setting. Let me go back now to 1980 when things were, as we

would say, stable. We had 60 percent of what we did with infectious diseases, about 40 percent in immunology, and that includes

transplantation, asthma, and others. The budget, looking at our

budget now, was relatively small, about $215 million.

Then let’s fast forward to what we essentially say is the middle

of the HIV epidemic. You know, we started to get significant funding right at the beginning of my directorship in the early 1980’s.

But let’s take 1999, where AIDS, just as Dr. Zerhouni said, was

something that was out of control. It isn’t necessarily the numbers

that we have now but the numbers that might occur. So it grew

in a way that was in many respects disproportional if it crowded

22

out other areas; but because of the increases in funding, the other

areas, which we refer to as ‘‘non-AIDS,’’ also grew. But if you will

look at that, more than half of the institute then was AIDS, half

non-AIDS.

September 11, 2001, the anthrax attack, and biodefense, and

here’s what you have now; the institute in 2004, the current fiscal

year, where it is about roughly one-third each of biodefense, AIDS

and non-AIDS, non-biodefense.

Let me just spend a moment about emerging and reemerging infections. This is a slide that is a favorite of mine because I show

it at many congressional hearings, as I am doing today, and the

reason I like this slide is because I change it each year with one,

sometimes two, and sometimes three additions. And what it tells

us is the dynamic nature of how we need to prioritize. And, again,

I gave you some examples. HIV-AIDS; West Nile in New York,

when that was well off our radar screen many years ago; the everpresent threat of a pandemic flu that we had to address this year

with the cases in Vietnam and in Thailand of bird flu jumping from

a bird to a human. If it developed the capability of going human

to human, we would have had to move very quickly. And in fact,

we did. We made that prioritization right in the middle of a fiscal

year.

Next.

So what is this prioritization process that I talked about? Well,

as alluded to by Dr. Zerhouni, it is, again, a very dynamic process

with input, from scientists particularly, to help us with understanding the scientific opportunity, but also involving lay public,

the administration as well as the Congress, which is very sensitive—and we respect that—to many of the needs of the constituency. So we take that into account.

We have a number of processes. We have meetings. We have continual back-and-forth with blue ribbon panels. We have our council.

But what I instituted about 15-plus years ago was two annual retreats, one a program retreat and one a policy retreat, in which we

continually reevaluate not only the new initiatives—and I think

this is important—but we do what Dr. Zerhouni referred to as a

programmatical portfolio review, so that we don’t get locked into

something that is just getting funded because we have traditionally

funded that.

That ultimately leads to the priority setting and the strategic

planning and then the initiatives. What are initiatives? Initiatives

are requests for applications or steering the field in a certain direction. We had to jump-start biodefense. There weren’t a lot of people

out there that were just dying to get into biodefense research. We

had to cultivate the infrastructure, both human capital as well as

physical.

This is the fruits of that process, and this is available on our

Web site, but let me just point it out to you because I think it is

an example of how we have been able to move quite rapidly. In the

process of understanding that we were going to assume the responsibility for biodefense, we put together a strategic plan with input

from many, many of our scientific colleagues, not only NIH-funded

colleagues, but colleagues in the military and colleagues in other

arenas.

23

We then developed the strategic plan-related research agenda for

the Category A and the Category B agents, and then last summer

we published our first progress report, and just a couple of months

ago another progress report; together they encompass the Category

A and B and C agents. Again, to underscore what Dr. Zerhouni

said, this required our building the kind of infrastructure that

years from now will allow us to make use of the scientific opportunities, but also to create scientific opportunities, which again, is a

dynamic process that we continue to fine-tune.

Finally, your staff had asked me to address an issue that I

briefed them on when they came to visit us at the NIH, and I want

to spend the last minute or so on that. And that is again an example of the spectrum of going from fundamental basic research to the

expanded paradigm for the NIH, namely assuring that we don’t

have a dead end with a very interesting observation that doesn’t

get translated into something for the public.

So if you look at basic research on the far left and look at where

we want to go, and that is, we want countermeasures for biodefense, we want diagnostics, therapeutics, we want vaccines, we

want the same thing for HIV-AIDS, and we want it for things like

SARS.

We must take the initiative, and we are doing that now with our

prioritization, and pushing the process more toward the

preadvanced development so that we can meet industry halfway or

beyond.

On the one hand, we have created incentives. Let’s take biodefense as an example, with Project BioShield, with a secure source

of funding to buy products that we engage very heavily in the concept development and basic research. Now we find in our analysis

of our budget—and we have had intensive discussions with Dr.

Zerhouni on this—now that the pipeline for many things that we

invested in basic research are getting robust, we need to push that

process forward. So we need to reprioritize now the balance between the fundamental basic research portfolio and how we push

that to development so that we wind up meeting the needs of the

general public which have put in our trust the money for the research that we are doing.

So this is a process that I think is an example of how the NIH

in a dynamic way continues to evolve to meet the challenges, be it

challenges of fundamental diseases that have been around for a

very long time, or the unexpected, like SARS, like AIDS, like biodefense.

So I will end my comments there, Mr. Chairman, and be happy

later to answer any questions. Thank you.

Mr. BILIRAKIS. Thank you so much, Doctor. Fascinating.

Dr. von Eschenbach.

STATEMENT OF ANDREW C. VON ESCHENBACH

Mr. VON ESCHENBACH. Thank you, Mr. Chairman and distinguished members. It really is not only a great privilege for me, but

an important opportunity to address this prestigious committee on

scientific opportunities and public needs and balancing those priorities.

24

As we sit here today, one American every minute is dying of cancer. More than a half a million people will die from this disease

this year, and more than 75 percent of families are affected. One

in two men and one in three women will be told during their lifetime that they have cancer.

Congress recognized the horror of cancer and the need to make

the conquest of cancer a national priority in 1971 when it passed

the National Cancer Act, which authorized the NCI Director to

build and lead our Nation’s cancer program. Thanks to the wisdom

of Congress and your continued support, I am pleased to follow up

on the efforts of my predecessors and report to you that scientific

progress is now impacting on the greatest public health concern of

the American people, the fear and problem of cancer.

During the past decade, for the first time ever, we have seen

mortality rates from cancer decline. This has been especially true

for the most prevalent cancers, lung, breast, prostate, colon and

rectal. In 1971, there were only 3 million cancer survivors alive in

the United States. As Dr. Zerhouni indicated, that number today

is almost 10 million. But the greatest progress is yet to come.

Progress in cancer research that has been made possible by the

authorizations of the National Cancer Act of 1971 and the continued appropriations provided by Congress has really created an opportunity both scientifically as well as with regard to the delivery

of care that is really at this point transformational. It is now making it possible for us to envision a future in which no one will suffer and die as a result of cancer.

The National Cancer Institute is committed to continuing to fulfill the promise of bringing that reality about. We can do that now,

and we have established a goal of eliminating the suffering and

death due to cancer and making that a reality by 2015 because we

now are beginning to understand cancer as a disease process. We

now recognize that there are steps at the genetic, molecular and

cellular level that are responsible for our susceptibility to cancer,

that are responsible for the early premalignant changes that occur,

and then those processes continue to result in the overt development of a tumor, and then that tumor’s growth and dissemination

and spread until ultimately it takes a patient’s life. Progress in biomedical research that has come about because of the effort of the

National Cancer Institute in leading our national cancer program

is not only unraveling the steps in this process, it is also providing

the insights into the development of interventions that can preempt this process. We now can envision prevention, detection,

elimination and modulation of cancer in a way that people will either not develop cancer in the first place; if they do develop cancer,

we can detect the disease early and eliminate it much more safely;

or we are able to treat and modulate established cancers such that

people will live with but not die from cancer.

In order to bring this goal about, in order to establish the priorities and the investments that are necessary to achieve this goal,

we have created a priority-setting process and a planning process

that really defines, if you will, a balanced portfolio, a portfolio of

initiatives that are involved in discovery, initiatives involved in development, and those that are involved in delivery. Across the entire portfolio of the National Cancer Institute, there are strategic

25

priorities and initiatives in all of these areas such that through the

process of discovery, development and delivery, we will create those

opportunities and deliver those opportunities to patients in need to

achieve that goal of eliminating the suffering and death due to cancer.

In the process of establishing the portfolio, we engage in a very

elaborate and continuous process of providing and obtaining input

into the establishment of priorities and in processes that review

those priorities prior to implementation, and then also processes

that determine the impact of those priorities. In order to give you

an insight into that, I would like to just lead you through how that

ongoing planning and budgeting process occurs.

It begins with a constant set of opportunities for input into the

establishment of those priorities. Those inputs come from a variety

of places and from a variety of organizations. We have mechanisms

in place that help us develop our annual planning document and

budget document that we call the bypass budget. There are a series

of targeted advisory groups and disease focus groups that provide

specific input, one of which has been the ongoing series of the

progress review groups which has looked at opportunities and

needs in areas like breast cancer, prostate cancer and others. We

have efforts that are under way with regard to state-of-the-science

meetings in which we can look at some of those emerging scientific

opportunities that Dr. Fauci and Dr. Zerhouni alluded to, and we

make certain that we have significant input from the world community, especially cancer survivor groups and organizations like

the American Cancer Society.

All of that input is then synthesized into an internal planning

document that then becomes the basis of both our strategic plan as

well as our business plan or budget. That internal document is prepared by senior NCI leadership with broad input from the entire

NCI and is processed by our executive committee. That is then reviewed on an ongoing basis by initiative and by priority by formally

chartered advisory committees including our National Cancer Advisory Board, our Board of Scientific Advisers and our Board of Scientific Counselors as well as individual groups of expertise.

Once the programs have been vetted, they are then implemented

and approved by passage through the National Cancer Advisory

Board, which serves as our council, and then disseminated and implemented throughout the entire cancer community. With the implementation of those programs, we have the opportunity for continued monitoring and surveillance that gives us opportunities to

determine measured outcomes and results, which then feed right

back into the ongoing planning process.

It is through this decisionmaking process that is focused on making strategic decisions about the balance in our portfolio and making sure that that portfolio is constantly being directed toward our

mission that is the process by which we establish and set priorities

and balance the scientific opportunities with the public need. Our

ability to disseminate that information through the professional

judgment budget or the bypass budget on an annual basis provides

opportunities for insight into both the strategic plan as well as the

budget or business plan that is required. This is not, however, our

budget submission process. That occurs directly through the mechVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00029 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
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anisms that are available within the NIH and directly to the Director of the NIH and then on to the Department of Health and

Human Services.

In addition to these formal processes, we have also looked at opportunities to significantly increase our communications with the

community and have recently launched a weekly cancer bulletin

that is available on the Web as a way of communicating to the entire community our scientific priorities and also the scientific

achievements that those investments are bringing about. In doing

so, we hope to continue to fulfill the mandate and mission of the

Congress to conquer cancer and eliminate its suffering and death.

Thank you, Mr. Chairman.

Mr. BILIRAKIS. Thank you very much, Doctor.

Dr. Volkow.

STATEMENT OF NORA D. VOLKOW

Ms. VOLKOW. Thank you very much, Mr. Chairman and members

of the subcommittee. It is a privilege for me to be here and participate in this hearing.

I will not describe the process by which we set priorities because

it is similar to those described by my colleagues. Instead I will

share with you our research priorities and will highlight the unique

collaborations that NIDA has had to cultivate in order to translate

science to communities.

Like the other institutes, NIDA receives input about its research

priorities from a wide variety of sources, including our National

Advisory Council, scientific and health professionals, and policymakers. However, unlike many other medical diseases, addiction

does not have many patient and family advocacy groups. This is in

part due to the fact that drugs of abuse in most cases alienate the

addicted person from his family and his community rather than

eliciting support. This places additional importance on NIDA’s ability to support science that helps us identify national needs and

emerging priorities.

The disease burden attributed to drug addiction is enormous. It is estimated to cost for both legal and illegal drugs more than $484

billion a year. However, even as large as this number may seem,

it pales in comparison to the devastating consequences of drug

abuse to the individual and to society.

Drug addiction is a disease that targets the brain, modifying its

function in ways that limit the individual’s ability to make decisions on his or her behavior. The results are widespread and devastating and can include family disintegration, child abuse, loss of

work and income, accidents, criminal behavior, mental illness and

suicide. Moreover, because drug addiction develops during adolescence and even sometimes in childhood, it can shatter the life of

an individual from its early beginnings. Drugs of abuse not only affect the brain, but many organs in our bodies, thus also contributing to the burden of many medical diseases including cancer; cardiovascular, pulmonary, and infectious disease; even obesity.

Research priorities at NIDA are set by the urgent need to decrease drug abuse and its consequences while at the same time

taking advantage of scientific opportunities to increase our knowledge about addiction.

27

Prevention and treatment of drug abuse and addiction are

NIDA’s top priorities. Prevention is particularly relevant since adolescents and children are the most vulnerable victims for drugs of

abuse. Moreover, research has shown that prevention works, and

this is illustrated on this poster from a study that monitors, in

teenagers, the perception of the harmful effects of drugs versus the

prevalence of drug abuse. When students perceive drugs to be

risky, their rate of drug abuse drops. In fact, we are finding that

through our monitoring mechanisms, we can often predict the prevalence of drug utilization on the basis of the perception of drug risk

detected the year prior.

Unprecedented scientific opportunities on prevention research

have emerged from the identification of genes that affect the responses to drugs of abuse and also by the development of technologies that now allow us for the first time to evaluate the function of the human brain. We can now investigate questions that

were heretofore inaccessible, such as how does early drug exposure

affect the development of the human brain, such as what is the relative contribution of genes versus environment in drug addiction,

such as how do environmental factors and genes affect our brain

and how that in turn affects behavior.

In treatment our priorities include the development of medications that can counteract the effects of chronic drug utilization

while at the same time developing research that optimizes our ability to bring the science into the community.

Another priority in treatment is addressing the medical consequences of drug abuse. Drug abuse is frequently comorbid with

mental illnesses and with other medical diseases. In many instances this comorbidity results from the role that drugs of abuse

have as a contributing factor on the medical illness. For example,

drug abuse is one of the leading contributors to the spread of HIV/

AIDS in our country, not only by injection drug use, which accounts

for 36 percent of the new HIV cases, but also by drug intoxication,

which interferes with the judgment of the person and increases the

likelihood of risky sexual behavior. Thus, treatment of addiction

and prevention will have an impact on the prevalence and the

prognosis of other medical diseases.

Scientific opportunities on treatment research have also emerged

from information derived out of the genome project, which has allowed us to identify a wide array of new compounds that in animal

models interfere with drug administration. However, notwithstanding the series of very promising compounds, a major roadblock into their testing for clinical utility has been the limited involvement of the pharmaceutical industry on the development of

medications. Issues such as stigma, lack of reimbursement for drug

abuse treatment and the perception of a lack of a large enough

market are some of the variables that make companies reluctant

to get into the development of antiaddiction medications.

For science of prevention and treatment of drug abuse to have

an impact, NIDA relies on its collaborations with other NIH institutes as well as its partnerships with other agencies and organizations to help bring this knowledge into the community. Indeed, the

successful 11 percent reduction in teen drug use during the last 2

years reflects the power of several agencies working together toVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00031 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
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ward a common goal. These collaborations include not only the

medical community such as pediatricians and general practitioners

for early drug abuse detection, but also partnerships with agencies

such as the Substance Abuse and Mental Health Services Administration, or SAMHSA, and the White House Office of National Drug

Control Policy, or ONDCP. It also reaches to the Department of

Education to bring prevention interventions into the school environment and the Department of Justice to bring treatment strategies that will minimize the chances of recidivism and reincarceration once inmates with drug abuse problems leave the jail or the

prison system. We also work with State and local agencies to bring

science into the communities.

Though we have made significant progress in our understanding

of drug abuse and addiction, there is still much more we need to

know. Fast advances in knowledge and technology provide us with

opportunities to exponentially expand our understanding of how

our brain works and how it molds behaviors. In the case of drug

abuse where drugs directly affect brain function and where the environment can play either a permissive or protective role, new

knowledge will help us develop more effective prevention and

therapeutic strategies.

I will be happy now to answer any questions you may have.

Mr. BILIRAKIS. Thank you very much, Doctor.

Let me ask you, I believe it was Dr. Zerhouni who addressed obesity. Would the obesity research that is conducted be spread

throughout more than one institute?

Mr. ZERHOUNI. It is.

Mr. BILIRAKIS. It is, right?

Mr. ZERHOUNI. It is. The trans-NIH Obesity Task Force is actually a multi-institute effort. It was led by Dr. Spiegel, the head of

NIDDK, diabetes and digestive disease institute and heart and

lung. The reason it is many is because it affects children, so

NICHD is involved. It has an impact, obesity, on influencing the

rates of cancer, so NCI is involved. There is obviously a component

of neurobiology, so the Neurological Institute is involved. So it involves a large number.

Mr. BILIRAKIS. The reason I pick on it is sort of to help me to

try to get the picture. You indicated—I think you said there was

a 10 percent increase in obesity research funding as against an average of 2.5 percent increase or something like that. Did that 10

percent come about independently? In other words, these institutes

determined how much money should go toward obesity research in

these particular institutes so that the ultimate total increases of all

those turns out to be 10 percent?

Mr. ZERHOUNI. Both ways. The total portfolio in 2003 was nearly

$400 million of research. It grew from about $85 million 8 years

ago to almost $400 million in fiscal year 2003 because of the burden of the disease. The second is that obesity has been declared an

area of priority for all of medical research a while back. So how are the nearly $400 million distributed? Fifty-five percent

of that money on average, and I am not exactly accurate about obesity, but 55 percent will be distributed because scientists come to

us with ideas about how to understand obesity better. This is what

we call the investigator-initiated funding. About a third will come

29

from clinical trials that we are doing. For example, NIDDK conducted a trial in children with obesity comparing diet versus exercise in the appearance of diabetes in obese children. That was

about a third of the expenditures. Those tend to come from what

we call initiatives. So the institute, for example, NIDDK, issued

what we call a request for application to have people come forward

and conduct trials that we are interested in conducting.

As you can see, there are two components. There is a directed

component of the portfolio. This is what we call initiatives that Dr.

Fauci mentioned. And there is an undirected component which responds to scientific proposals that come to us. The 10 percent that

we did by which we increased the portfolio came from this planning

process which I insisted be done, asking the directors to come together and look at the obesity portfolio across whole institutes, and

it was decided that there would be two priorities, two new priorities. One, we think it is very important to accelerate our research

in obesity in childhood. All the evidence suggests that obesity is determined very early in life. We thought we didn’t have enough investments in early childhood obesity, so we increased our investment there. The second is obesity really harms an individual not

because of obesity itself, but because it increases the chances of

cardiovascular disease and diabetes and other what we call

comorbidities. So what we are thinking is that research needs to

be done to disconnect very quickly as much as we can in the population obesity from the emergence of diabetes and other

comorbidities.

Mr. BILIRAKIS. So there was—I think you used the word ‘‘we’’ a

number of times.

Mr. ZERHOUNI. At the end of the year when the budget came,

when we presented our budget to the Department, we set aside $40

million; $22 million of that $40 million was dedicated to these new

areas that were deemed unserved at that point, the childhood obesity and the comorbidity research.

Mr. BILIRAKIS. Would we say then that ‘‘we’’ was your advisory

council along with you that made those decisions? Did you make

them in coordination with the 27 institutes and centers?

Mr. ZERHOUNI. That is correct. What we did since I became Director, we have reorganized the way we make decisions at NIH. We

had 27 directors. It is very complicated to have that many, so we

created a steering committee of nine directors, a smaller number

that look over all the major corporate decisions that NIH has to

make. The budget is decided obviously between the NIH Director

and all of the directors that participated in this NIH initiative, the

trans-NIH obesity.

But it is limited. Our ability to move dollars from one portfolio

to another is limited. It is not something that you can do arbitrarily, because programs tend to go over for 3, 4 years, and they

are committed for that period of time. We need to do it with the

appropriate oversight. What I think needs to be more encouraged,

and we are encouraging it, and the institute directors can comment, is more planning not within the institutes, which is done

very well, in most cases it is the way to go, but planning across

diseases that affect more institutes, and areas of research that afVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00033 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
30

fect more institutes, and areas that affect all of NIH with dollars

attached to it.

Mr. BILIRAKIS. My time has expired, but hopefully we can get

back into that as time goes on.

Mr. Brown.

Mr. BROWN. Thank you, Mr. Chairman.

Dr. Zerhouni, would you briefly comment on my opening comments about Duchenne? They actually funded only one clinical

trial. Just give us a fairly brief answer to that, if you would.

Mr. ZERHOUNI. Sure. First of all, I know that muscular dystrophy has increased in funding. The funding is about $40 million, so it

is about 15 percent of the NIH budget. I understand that the MDCARE Act is the mechanism, the vehicle by which we are coordinating all of the portfolios of muscular dystrophy.

You mentioned the issue of centers. I understand that three were

funded in 2003, and up to three will be funded, 2 to 3 will be funded in 2005.

I also can tell you that we have to be very careful when you

ramp up research capacity, you have to make sure you have the

people and the ideas there to make it happen. So review is very

important. In the previous cycle, our review was indicating some

reservations about the maturity of some of the centers. But by and

large what I think needs to happen is more investments in a coordinated fashion in a set of centers that would focus on that aspect.

I don’t have information about what you said about clinical trials

and having three applications. I really can’t comment. I would like

to get the information and forward it on to you.

Mr. BROWN. Thank you.

Dr. Fauci, in Dr. Zerhouni’s written testimony, he spoke, and I

am quoting, of NIH undertaking, quote, studies for which the risks

are too high or the financial incentive is too low to attract private

investment. A lot of us on the subcommittee are concerned about

a couple of things. One is that the lack of research or the inadequate research on infectious disease, especially in the developing

world where it is hard to imagine it would be very profitable for

a prescription drug company, a pharmaceutical company in this

country; second, the emptiness, if you will, of the antibiotic pipeline.

Could you comment on this? How much of the NIH budget typically is devoted to that kind of research; how we can assist you to

do better, especially in the area of antibiotics, with antibiotics, with

antiparasitics, with antiretrovirals, and especially with drug resistance in much of our antibiotic, antiparasitic supply?

Mr. FAUCI. That is an excellent question, Mr. Brown. We take

the responsibility in our emerging and reemerging diseases program to address issues such as antibiotic resistance. This is one of

those areas where we absolutely need to deal on a closer basis with

our industrial partners. That is the delicate balance that I was

talking to you about, because they have incentives to get into areas

that are high profit margins for them. That has to do not only with

antibiotics, but also with vaccines.

What we have been trying to do, and that is the reason I showed

that slide and why the committee staff wanted me to show it at

31

this particular hearing, was that we need to figure out ways—and

I can’t give you a list of one, two, three things that you can do visa`-vis legislation or what have you, but I would be very happy to

work with you and your committee staff to figure out ways how we

might be able in a better way and in a more facile way to deal with

our industrial partners so that we can get them interested in the

things that we can do in the normal interaction that we have.

One of the steps forward was the bioshield initiative was very

specific for biodefense. It created ways of dealing—in a much more

streamlined way of dealing with the industrial partners, but also

for giving them the incentive to get involved in something even

though it was not a guaranteed profit margin for them. I think we

need to look at that model as it applies to all emerging and reemerging diseases, particularly diseases that we refer to as the neglected diseases.

We have a portfolio of research, but we need to get the companies involved. We cannot do it all ourselves. That is the reason

why, as the months and years go by, we continue to interact with

the companies, and we are doing it much more now than we have

done years ago.

Mr. BROWN. What are the neglected diseases, TB, malaria, those

that don’t have much of a market in this country?

Mr. FAUCI. There are two types of neglected diseases, infectious

diseases I am referring to now. There are those in which the burden of disease is extraordinary, but there is not necessarily a lot

of research going on. Malaria and TB are the two big ones on that.

Do you know that we have, for example, the vaccine for tuberculosis, BCG, which is quite ineffective in preventing the adult type

of infectious tuberculosis that spreads from person to person, but

is pretty effective in preventing meningitis complications in children. Yet we now on our own initiative—and this is one of the

things that we talked about—when we looked at the portfolio, there

wasn’t a lot of action going on in TB vaccine research. So we seized

the opportunity of the capability of the sequencing of microbes that

we can do right now and the ability to use proteomics and

postgenomic function to develop a vaccine that we are now testing

in clinical trials which, believe it or not, it is amazing to say this,

the first new tuberculosis vaccine trial in this country in 60 years,

which we just started this year. We did it because we were able

to translate the opportunities that we had with the new capabilities of sequencing the genomes of microbes with the new modernday molecular biology. It isn’t the old vaccine, based on the entire

microbe, but a very small molecular component that we call a fusion protein that will allow us in a much safer way to do a vaccine

trial for tuberculosis. If that is successful, I think we are going to

be able to transform the entire landscape of tuberculosis.

Mr. BROWN. What is an optimistic assessment or estimate of how

long from where you are now until it can be used in the worst TB

places in the world like India?

Mr. FAUCI. When you talk vaccine development and ultimate approval, you are always talking several years, 8 to 10 years. I would

imagine that if we accelerate the process, which we are doing right

now, we might be able to shave a year or 2 off of that. But you

are not talking next year or the year after. If you are talking about

32

full FDA approval, the kinds of things we need to do for safety, it

is going to take several years. It is being tested now in our network

of clinical trials.

Mr. BROWN. Thank you.

Mr. BILIRAKIS. Mr. Shimkus to inquire.

Mr. SHIMKUS. Thank you, Mr. Chairman. Mr. Greenwood was

here way before I.

Mr. GREENWOOD. I am not sure that I was.

Mr. BILIRAKIS. That is not what the staff tells me.

Mr. SHIMKUS. Okay. I am ready. Thank you. Thank you, Mr.

Chairman.

I have great respect for my friends Ms. Capps and Mr. Waxman

and in their statements. They are noted health observers and professionals in the field. But speaking from a very conservative area

of the country, we talked about this at the last bicameral hearing

we had on the Senate side last year, that it helps us in rural America if the grants that are issued pass the common-sense test.

The question is, is there a way that you can through this evaluation process bring some sense or explanation on those that don’t?

We don’t have to go through them. They have been publicly written

about for years now. All of us get lobbied strongly in support of the

research done. It was Speaker Gingrich who really pushed to double the size of NIH, and we have made great investments. When

we are asked for more and more dollars in periods of tight dollars,

we want to make sure that those dollars are best spent. So how do

we address again—where is the common-sense application on some

of the research dollars?

Dr. Zerhouni, if you would answer that first, and then I would

probably like to follow up with Dr. Fauci.

Mr. ZERHOUNI. This is a very important question. We are very

concerned. In fact, the Chairman mentioned the term transparency.

I think in this area we found after our review that we could do a

lot better in making sure that we communicate transparently and

also fully about the importance or lack thereof of the particular research. So one of the things that I have done after reviewing this

field, in conjunction with all of the directors in our extramural office, is to issue new requirements for explaining, in plain language,

both the public relevance as well as the importance of the research

scientifically. This information will be available in clearly understandable language both to the public and to the multiple review

levels that we have in place so that there will be more transparency and more explicit understanding of all areas of research.

The common sense test that you rightly bring up is something

that we are quite concerned about because we depend on the support of all taxpayers and we need to make sure that whatever we

do makes scientific sense and public health sense. In that context

I have asked all of the institute directors to make sure that the two

level of reviews are done fully. I know it is a lot of work, but that

there is a full discussion of the grants at the advisory council level,

because there are public members in those mandated by law in

these advisory councils, and I think they should play their role.

This is why I had this report made by the Council of Public Representatives called, ‘‘Enhancing Public Input and Transparency in

the National Institutes of Health Priority-Setting Process’’ that adVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00036 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
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dresses it, but I don’t think that we can weaken the peer review

process in trying to answer the concerns. We need to make sure

that we accomplish both.

Mr. SHIMKUS. I applaud that. Somehow I would just hope that

as we move to more transparency, that that helps and doesn’t

hinder. Again, as many of us would question the common sense of

the application of some of these grants, more transparency may

make it more difficult for us to defend the NIH.

Mr. ZERHOUNI. Although when I reviewed the grants, frankly,

the language was highly scientific with terms of art that were not

explained as well as they should be or could be. I think we should

do better and then obviously review the question.

Mr. SHIMKUS. I did mention Dr. Fauci, but I guess any of the directors if they want to. It is up to you. My time is almost out, so

if someone else wants to add, you may do that. The same area.

Mr. FAUCI. We do the same thing. Obviously in areas such as

HIV/AIDS, it is a sexually transmitted disease, it is a disease that

is transmitted by injection drug use, by a variety of other mechanisms. We cannot avoid addressing the issues that are at the very

foundation of why millions and millions of people are getting infected. That is the reason why we are sensitive to the issues that

you bring up, really quite sensitive, and I mean that sincerely. But

we need to let the science drive the questions if we are going to

be able to get a handle on this very devastating sexually transmitted disease.

Mr. BILIRAKIS. Mr. Strickland, you have 8 minutes.

Mr. STRICKLAND. Thank you very much.

Dr. Fauci, I have read and have been concerned for a number of

years about what some say is the potential for a pandemic, an influenza pandemic, occurring across the world that could perhaps

consume the lives of millions of people. I don’t know if what I have

read is just reason to be concerned or not, but the question I would

like to ask you, is this a concern, is it a possibility, and if it is, do

you feel like we are doing everything we can to be ready for such

an occurrence?

Mr. FAUCI. It is a possibility because it has happened in 1918;

to a lesser extent in 1957 and 1968. It is of concern.

In science and public health, it is very rare that we can say we

are doing absolutely everything that can be done, but I can tell

you, Mr. Strickland, that we have put this at the very highest priority. This is one of the things that I mentioned to you in midstream we had to make adjustments in our priority setting. For example, and I will be very brief on this, but it is important because

you are interested in this, and it needs to be understood. There is

what is called interpandemic influenza, which the NIH and the

CDC and the FDA have been involved with for decades and decades, where you look at the burden, and you look at the particular

microbe that is circulating, and you work together to have a vaccine for the next interpandemic flu. Each year—it is very

unappreciated: 36,000 people a year die from plain old flu, 114,000

hospitalizations. It is a very serious disease. I think it suffers from

the semantics of, oh, I have the flu, when you don’t really have the

flu. You probably have a relatively benign rhinovirus or something

like that or a coronavirus.

34

What we are doing now in our preparation is that something different happened over the last few years that started in 1997 when

a bird flu jumped from a bird to a human. By killing and culling

the birds in Hong Kong, the lid was put on that. And then successfully over the next few years until this particular winter, 2003-

2004, nine countries in Asia had the emergence of a virus among

flocks. In two countries, in Thailand and in Vietnam, there was a

total of 34 cases of which 23 died. That is nearly a 70 percent mortality. The concern we in the Department, particularly the NIH

and the CDC, have is that that microbe has the ability now to

jump from chicken to human. The reason it isn’t a disaster is because it hasn’t yet learned how to go from human to human. So the

potential epidemic has kind of smoldered and stopped.

What we have been doing now is that we have been doing basic

research as well as developing a seed virus vaccine that our grantees and contractors have developed. We have taken the responsibility, even though we had to do midstream corrections. This is

something that I discussed in some detail with Dr. Zerhouni and

got his encouragement to move ahead with it, and to now start

making a pilot lot, which we are in the process of doing.

Again related to the question that Mr. Brown asked, we had to

get very much involved in our industrial partners, in this case it

was inventors Pasteur and Chiron, in developing a pilot lot and

then to have that be able to scale up if necessary at commercial

levels. So we are doing everything within the resources that we

have right now because we put it as a very high priority.

It is an example—again, just to get back to what Dr. Zerhouni

said a few minutes ago, the disease burden right now in the United

States for pandemic flu is zero, yet we are putting resources into

it, and we plan to do more next year because we know the potential

for that is enormous. We are part of the whole Department. We

have an HHS-based pandemic influenza plan that is led at the

level of the Department that we, the NIH and the CDC and the

FDA, are a very important part of.

Mr. STRICKLAND. Do you feel that the communication or that the

data-gathering infrastructure around the world is sufficient to enable you to be alerted and to act as quickly as possible based on

what you currently have in existence?

Mr. FAUCI. Yes and no. I will tell you what the yes is, and then

I will explain the no. The yes is that we have a number of collaborating WHO centers of which the Department, namely the FDA

and the NIH and the CDC, play an important role at. We have a

grantee of ours who has a major program in Hong Kong. So when

you talk about flu, almost invariably it is going to emerge from

China, Hong Kong.

Mr. STRICKLAND. Because of their agricultural practices?

Mr. FAUCI. Because of the sociological and economic conditions

there. You have pigs and ducks and chickens and people working

on the farm together, a natural mixing bowl for a virus that would

jump from one species to another. That is the yes. So we do have

these people in communications. For example, when the bird flu

came out, we immediately dispatched a person to Hong Kong to

start working on it.

35

The no to maybe is that we have not had complete transparency

up to now, but it is getting better and better with our Chinese colleagues. We saw that with SARS, which was recognized months

and months before in China until we knew about it, and we only

knew about it when it got to Hong Kong where we had our people

on the ground. With the flu now it is getting better, but I don’t

have 100 percent confidence about the transparency yet. But it is

certainly much better than it was before.

Mr. STRICKLAND. I want to thank you for your answer. If the potential consequences are so great, it is something that I think we

certainly should put all the resources that are needed into it.

I would just like to say a word about the comment my good

friend on the other side made about the common sense test. It

seems to me that the common sense test is not relevant because

it is common, and that which is easily or readily understood or appreciated is not, it seems to me, the major domain of the scientific

inquiry. You want to look at that which is not common or easily

or readily appreciated or understood. It seems to me that is what

the scientific inquiry is all about.

I have appreciated you being here. I wish we could spend hours

because there are so many issues. What you do, I think, is as important as anything that we consider in this committee or in this

Congress, because you have cancer potentially being cured in 15

years. I mean, with all due respect, I asked my colleague if she

thought you were maybe a little off to think of that. I am speaking

facetiously and trying to be humorous here, I guess, but to think

of that, it is overwhelming. How great it would be. And then I said

to her, it would absolutely destroy our Social Security system. But

what you do is so integral to everything else we consider in this

Congress, economically, socially. We could talk forever about the

social implications of the stem cell research policy or of the abstinence only education policy or the drug policy.

Mr. Chairman, I just wish we could do this more often and for

a longer period of time.

Mr. BILIRAKIS. You have had more time than anyone else.

Mr. STRICKLAND. Thank you, sir. I appreciate it.

Mr. BILIRAKIS. Mr. Barton to inquire.

Chairman BARTON. Thank you. My questions are going to be

more operational and structural and not going to be policy so much.

But my first question to you, Dr. Zerhouni, if you were starting

from scratch with a clean sheet of paper to create a National Institute of Health, would you come up with 27 institutes and centers?

Mr. ZERHOUNI. No.

Chairman BARTON. Is there a magic number?

Mr. ZERHOUNI. No. I think you really would like—if I had my

magic wand, I think what you would want is an evolving structure

that evolves easily and flexibly according to its priorities. History

dictates a tremendous amount of the structure of NIH, history, congressional actions, legislation, which really creates a degree of rigidity, which, from my standpoint, needs to be thought through. A

process is needed by which that structure needs to be reviewed at

regular intervals to ask the obvious question, do we have structures that still fit the reality of today. The rigidity, sir, is something that I think would be a good topic of interaction.

36

Chairman BARTON. Under current law, do you as the Director

have the authority to restructure, recombine institutes and centers,

or are they set by law and you have to go with what is there right

now?

Mr. ZERHOUNI. I would say it is almost completely limited. I can

do some restructuring within the structure. That is very difficult

to do. Remember, we have institutes and centers. In my office, for

example, we have program offices. Of the about $290 million budget that you see within the Office of the Director, there are mandated offices with their own budgets: the Office of AIDS Research,

Office of Behavioral Science, Office of Rare Diseases, of which I

have very little to say in terms of programmatic spending. So at

the end of the day, you end up with about $120 million all together

that the Office of the Director directly controls.

But I think the lack of a process of adaptation, and to speak in

terms of policy and long-term future, there is no such process that

would allow a reasoned, learned evaluation of appropriateness of

structure relative to mission.

Chairman BARTON. As we move toward reauthorization, would it

be appropriate for the legislation in conjunction—working with the

stakeholders to create a new structure, or would it be more appropriate to give the Director’s office the ability to do the restructuring, the authority to do the restructuring?

Mr. ZERHOUNI. I think, in my view, since you have the reality in

this institution, NIH is still a wonderful institution that performs

very well in most aspects. I think what would be more important

is the process, with authority, obviously, to look at certain structural elements and the need for them to change. But it should be

mandated in some fashion.

Chairman BARTON. I want to give the center directors and institute directors a chance on that last question. You may not want to

change the structure. You may think 27 is great. That is a fair policy position. But if you think there needs to be a reorganization,

do you three ladies and gentlemen want us to provide it, or do you

want us to in some way give the institution the authority to do it?

Mr. FAUCI. I think it would be fraught with danger, sir, if you

legislate structural changes as opposed to providing the kinds of

flexibility that would allow the NIH to evolve with the scientific

evolution of things, the way Dr. Zerhouni mentioned. The difficulty

with legislating something that is a structural change is then it is

there, and if you want to move and have the flexibility that virtually all of us alluded to, that would only create a different model

that would be as inflexible as the concerns we have now with the

inflexibility of the model. So I would be much more in favor of providing the NIH, through the Office of the Director, the flexibility

to do certain things——

Chairman BARTON. If the Congress provides it, it will be done.

If we give the authority to do it, and we let the various stakeholders interact, it might not be done. We may create a process

that has no end, where obviously if we do it in law, almost by definition it is going to be imperfect, but at least something will be

done.

Mr. FAUCI. But I would submit to you, sir, that the authority

would be in law, and then I believe, at least in my rather extensive

37

experience in dealing with the Congress, is that the Congress looks

at us carefully, as they should, because we get what we get from

the Congress, and that you have ample opportunity in the future

once you give the authority to the NIH to be able to be flexible with

those changes that if the kinds of flexibility that are evolving are

something that you are concerned about, you can get us in front

of you and say, well, let’s explain that; what are you talking about.

Chairman BARTON. Of course, the reason you have 27 centers

and institutes is over time the Congress has dictated that.

Mr. FAUCI. Right.

Chairman BARTON. We have mandated that this or that be set

up, so we are the ones who created the structural problem we are

trying to address.

Mr. FAUCI. So help us to be able to have the flexibility of fixing

it rather than trying to legislate a fix.

Chairman BARTON. That is why I asked the question.

We have got two more directors, if you would wish to comment.

Mr. VON ESCHENBACH. I come from the perspective that the

structure really should be driven by function. I think the authority

to define functions and to involve trans-institute and center collaborations is something that I think would be very important for

the NIH Director to have. That would allow flexibility without dismantling the structure that is there. You could work with that

structure. When it is appropriate and necessary for integration, you

would be able to create that. When it was most appropriate for

those institutes and centers to stay very mission-focused, that

would also then be possible.

I think in that regard it perhaps then approaches it not from

making structural changes, but making certain that the authorities

allow functional activities to be able to occur in a fluid way.

Ms. VOLKOW. I would agree with my colleagues. I think one of

the things that we have seen over the past 10 years in science is

that the boundaries, the categories, the labels given to specific

fields, are no longer so clearly delineated, and so we see a tremendous overlap across areas in science.

The same thing is happening across our institutes even though

we are dealing with different diseases. For example, we are starting to recognize that much of the basic knowledge pertains to multiple disease processes. To me the important aspect is how do you

ensure an infrastructure that will allow you to optimize the information and resources required in order that you do not become redundant to the point that you are wasting your resources. How to

achieve that, though, is not straightforward.

I think that the element to me is not predefining rigid structures,

and again I bring forth the concept that my colleagues have voiced

of flexibility that will allow us to drive the organization as the new

discoveries and the new emerging trends develop. What I think is

important is to recognize the need in a scientific organization like

the NIH of having that flexibility. And it will not be automatic, so

your help will be required in order to, in certain instances, allow

it to proceed more easily.

Chairman BARTON. I have a number of questions, and I will submit them for the record.

38

Mr. BILIRAKIS. I am gathering before I go to Ms. Capps that you

all agree in your responses to Mr. Barton, because you went into

these very lengthy responses, you apparently feel that some fixing

does need to be done. I don’t know when you shake your head yes

or no to that effect. Anyway, that is what I get out of that.

Mrs. Capps to inquire.

Mrs. CAPPS. Thank you, Mr. Chairman.

If I am not mistaken, I believe Galileo was either excommunicated or threatened with excommunication for daring to posit a fanatical belief that the Earth revolved around the Sun. My colleague

who brought up common sense has had to leave, but I wonder, if

common sense had dictated, if we would have ever had a man on

the moon or if we would have ever undertaken mapping the DNA.

I know that most of us here are very supportive of the work that

you do and the way in which you do it.

I will start with you, Dr. Zerhouni, but this really relates to any

of the people on the panel to explain to us how the peer review

process works and why it is considered the gold standard worldwide for determining scientific quality. Some of us get ahold of the

grant applications, and they may sound inappropriate when it is

one paragraph. Some of this supports science around esoteric

projects, but underlying it is the need to understand the millions

of Americans who suffer from HIV/AIDS, sexually transmitted disease, sexual dysfunction, mental health consequences of abuse and

various hard topics to get hold of. That is what I would like you

to address.

Mr. ZERHOUNI. Sure. I will summarize.

What I can tell you is one of the most common questions I get

as I travel around the world, how is our peer review process so effective in identifying areas of science. Over the years, as you know,

we have had over 105 Nobel Prizes that have come through the

peer review process. The process is as follows: We have two systems that work in succession and sometimes in parallel. There is

a center for scientific review which is independent of the institutes,

so Dr. Fauci or Dr. von Eschenbach do not directly control the reviews that are done for grants in NCI or NIAID that go through

the center for scientific review. So when a scientist proposes an

idea, it goes to that center, and that center combines multiple review sections that are categorized according to fields of science.

In 1999 this was reviewed and restructured, because science

evolves. So we have review sections which are made up of members

which are under the FACA rules, the Federal Advisory Committee

Act rules, and the members have to represent a diversity of regions, disciplines, and gender. The members rotate every 4 years.

So those sections are the ones who do what we call the first review, and they score the grants according to scientific merits. Our

administrators then compare all the scores across and give a percentile ranking. Those grants then go to the institutes and our

Center for Scientific Review will look at a grant and will say this

is most appropriate for cancer, or this is most appropriate for NAID

or NIDA. It will then go there and undergo the second level of review, which is the advisory council of the institute. The advisory

council is, again, a FACA committee made up of usually 18 memVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00042 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
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bers, 12 scientific members and 6 public members, and they have

the final say in what gets funded or doesn’t get funded.

They can’t not fund things that have received high review. They

can also fund things that are at the borderline of grants.

The second—this is about 60 to 70 percent of our grants come

through this—the second is what we call special initiatives, where

there are special review programs that are organized by the institute. So Dr. Fauci organized last year a competition for having universities create biodefense research centers.

In this context it is such a specialized initiative, that the NIAID

puts together an independent peer review panel focused on that

area.

For example, Mr. Brown was mentioning muscular dystrophy. If

we have a special competition for muscular dystrophy center, that

will be reviewed by a special emphasis panel. So 70 percent is independent of the institutes, done independently by scientific review,

reviewed again at the advisory council. Thirty percent is done by

the institutes, or thereabout, and then reviewed at the advisory

council as well.

Mrs. CAPPS. And at some level the public has representation on

those committees as well, and all of this—are the names of people

on the screening committees, are those made public?

Mr. ZERHOUNI. Right. The names of all the study review panel

members are made public. The first degree of review, which is a

scientific review, is not open to the public. The second is always

open to the public. All advisory councils are open to the public.

Mrs. CAPPS. And then finally——

Mr. ZERHOUNI. I am sorry. But the scientific review portion can

be closed to the public; but the members are known, who participates and how.

Mrs. CAPPS. The members are well known?

Mr. ZERHOUNI. They are known.

Mrs. CAPPS. And the professional community respects this. Is

this an internationally understood process that is accepted worldwide, or understood at least?

Mr. ZERHOUNI. I can tell you I just—the latest communication I

had is the Chinese Government wants to create an NIH in China,

and one of the first questions was, tell us how to organize peer review. We get that all the time so it is the gold standard of review

worldwide.

Mrs. CAPPS. Thank you. I yield back.

Mr. BILIRAKIS. Mr. Greenwood to inquire.

Mr. GREENWOOD. Thank you, Mr. Chairman. Hello to all.

Dr. Zerhouni, this is a very basic question, and perhaps naive,

but something I don’t fully understand. I think the number is

something like 80 percent of the dollars that flow to NIH then continue out to the universities and health centers and so forth, and

something like 20 percent remains inside.

What fundamentally distinguishes the research that is done inside NIH versus outside?

Mr. ZERHOUNI. That is an excellent question. The reason why

NIH has created what we call an intramural program was to address historically issues of public health which could not be adVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00043 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
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dressed. There was no research capacity. There was no talent out

there to really address it.

Let me give you a specific example: safety of the blood supply.

In the 1960’s, you may remember, all the blood collection agencies

and so on, and in the 1960’s the rate of transmission of a disease

through transfusion was 30 percent. We didn’t know about hepatitis B and C and all the infections that could be carried through

blood transfusions. It was clear at the time that you needed a very

dedicated government-driven process to understand all these viruses, and Dr. Harvey Alter has led this program over 30 years.

You can’t do this in the system of extramural granting, where

every 5 years you have to come in and have your grants reviewed,

and if it is a process that takes years, you can’t fund it. So typically

that is the——

Mr. GREENWOOD. I have three questions I am trying to sneak in

here in 5 minutes. Do I not get 8 minutes, Mr. Chairman? Don’t

I get 8 minutes instead of making an opening statement?

Mr. BILIRAKIS. No. You get 5 minutes.

Mr. GREENWOOD. The investor-initiated applications of research.

On the one hand we pretty much have decided as a matter of congressional policy that we try to minimize the micromanagement.

We don’t want to say, listen, we have had constituents ask us to

have more research done on this rather than that, and we have left

it to the peer review process.

On the other hand, I am not—when the requests for research are

coming from the research community, to some extent that is a function—what they want to study is a function of what they want to

study, not necessarily a function of what needs to be studied. So

how does your process have an overarching plan and still respond

to the not exactly random but somewhat random inputs?

Mr. ZERHOUNI. I will make three short comments. No. 1 is other

governments have tried to more micromanage research worldwide,

and it hasn’t worked. The pharmaceutical industry is a good example of how you do targeted research. They spend twice as much

money than NIH and we hear about the productivity of that. So

whenever you focus energy at a difference from what the scientists

themselves know they can do, you have a loss of efficiency.

How do we know it is really relevant? Well, look at the system.

We fund primarily academic health centers. Well, you get promoted

because you make a difference in life. You don’t get promoted because you are studying some, you know, disease of the right toe.

You are trying to solve cancer and you are trying to—that is how

the system has a culture that pushes our investigators toward relevant questions.

At the review panel, the public relevance of the program is a

component of the evaluation. So it is relevant to public health

needs as expressed both by NIH and by the CDC or other components. That is how the integration gets done.

Mr. GREENWOOD. One more question——

Mr. FAUCI. Can I answer? You asked the question, how does research that may be important get done if the investigators don’t

want to do that? We have been faced with that in the early years

of HIV-AIDS when no one was interested in it and in the early

years which we are in right now with biodefense. There is a mechaVerDate 11-MAY-2000 11:19 Dec 22, 2004 Jkt 000000 PO 00000 Frm 00044 Fmt 6633 Sfmt 6602 95440.TXT HCOM1 PsN: HCOM1
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nism called a request for application and a request for proposal,

which are program-driven, that we are interested in this area. We

let the investigators come in with their own creative ideas, but we

tell them we have money that we want to invest in this area, and

that is how you get people involved in things that they may not

otherwise spontaneously get interested in.

Mr. GREENWOOD. Got it.

Last question, what my oversight investigation had on. How do

you make sure that there are no conflicts of interest between your

reviewers who are deciding which grants get approved if they may

have consulting arrangements?

Mr. ZERHOUNI. Right. So all appointments to these review panels

are under the Federal Advisory Committee Act rules, so every appointee is a temporary government employee and subject to all of

the disclosures of conflict of interest.

So the way we do it, if you are a member of those sections, you

have to disclose all of your financial arrangements; not publicly disclose, but disclose internally. If you have a conflict, you are recused

from—a good example of a conflict is a case that—a grant gets reviewed from a university at which you yourself are a faculty member. You get excluded from those. So it is the regular processes that

we use as mandated by the Federal rules.

Mr. GREENWOOD. Thank you. Thank you, Mr. Chairman.

Mr. BILIRAKIS. Mr. Stupak to inquire.

Mr. STUPAK. Thank you, Mr. Chairman. Thank you to our panel,

thank you for coming and testifying today. I think NIH does a remarkable job and look forward to working with you on the many

endeavors you undertake. And I think it is just great that our

country invests in life-saving and life-better work at NIH.

I am particularly interested, though, in ensuring that the American public has access to safe and effective drugs. Dr. Zerhouni, as

you know, back in 2001 Congress passed the Best Pharmaceuticals

for Children Act to authorize the 1997 law to grant patent extensions to drug companies in exchange for doing pediatric safety and

effectiveness studies.

I opposed this legislation, because I think we have got it backwards. I think it is wrong that we continue to grant these patent

extensions once they do a study. I think two things should occur,

and I am going to ask your opinion on it. Not only should they do

the study; should they not change the labeling on the medicine, on

its effectiveness or in effectiveness or safety concerns of children

before you grant the extension of a patent?

Mr. ZERHOUNI. Let me make sure I understand the issue. You

are suggesting that the drug should be labeled not for pediatric use

prior to——

Mr. STUPAK. Granting the extension of the patent.

Mr. ZERHOUNI. I do not know how to answer that question. This

is really an FDA-type of authority, but I will really look it up and

respond to you on the record.

Mr. STUPAK. Well, we show on average it takes them 14 months

after they get the extension to change the labeling. That is 14 more

months that we put children at risk—health at risk.

Let me ask you this question, then. The act also gave, and NIH

was mandated to research certain on-patent and off-patent drugs.

42

How many off-patent drugs need to be studied? Do you have any

idea?

Mr. ZERHOUNI. The list is made up in coordination—if I——

Mr. STUPAK. With the FDA?

Mr. ZERHOUNI. With the FDA and NIH. The list is primarily the

responsibility of NIH.

Mr. STUPAK. Okay.

Mr. ZERHOUNI. And then this list is used in our BPC

program——

Mr. STUPAK. Do you have any idea how many are on this list?

Mr. ZERHOUNI. No. I don’t have the exact number.

Mr. STUPAK. How about the on-patent drug——

Mr. ZERHOUNI. I will provide you that number, sir.

Mr. STUPAK. Is it safe to say, given the resources available to you

today, that a lot of these drugs that need to be studied are not

being studied?

Mr. ZERHOUNI. That is a fair statement.

Mr. STUPAK. Didn’t NIH just complete a report on the gap on the

on-patent and off-patent studies and what needs to be done? Did

you not just do a report?

Mr. ZERHOUNI. We actually did review the BPCA implementations. So there is a report that I think we sent to Congress, if I am

not mistaken, but I will——

Mr. STUPAK. We haven’t seen that yet. Could you provide that

to this committee, because I would like to see those numbers and

what drugs are and are not——

Mr. ZERHOUNI. Definitely.

Mr. STUPAK. The Best Pharmaceuticals for Children Act also included a provision to create an independent foundation. It was

called a foundation for pediatric research, to collect funds and

award grants for research on on-patent drugs when the drug companies do not want to do the studies themselves. And, again, I

think those results have been submitted to you and to the FDA

commissioner.

Could you also provide us a copy of that?

Mr. ZERHOUNI. I will.

Mr. STUPAK. In choosing the studies on on-patent drugs, the ones

that are targeted to be studied, what is your involvement in it, or

NIH’s involvement in it?

Mr. ZERHOUNI. Primarily looking at the importance of the drug

and how utilized is it in the population under—you know, the pediatric population. You will see that, for example, one area that

NIMH, the National Institute on Mental Health, is very interested

in is the use of antidepressants, and that has become a major

issue; so institutes have a way to weigh in and give their advice

in terms of what they think should be tested.

FDA, however, has the primary role, because if they receive information about it, adverse events, and they know what post-market surveillance data is available for——

Mr. STUPAK. On the antidepressant, actually, with children lately, we have been seeing a lot of reports on that. So what involvement would you have on that? I mean, there has been a lot of controversy with the British studies and one gentleman at FDA not

being allowed to testify publicly. What involvement would you as

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NIH say to the FDA to try to get these studies out and get them

up there?

Mr. ZERHOUNI. Directly, I don’t have a lot of personal involvement in it. But NICHD, which is our lead institute for children’s

research, is the lead, and that is the institute that really interacts

with the FDA.

Mr. STUPAK. And who heads that institute?

Mr. ZERHOUNI. Dr. Duane Alexander.

Mr. BILIRAKIS. The gentleman’s time has expired.

Bart, do you have something you can go through real quickly?

Mr. STUPAK. They are pretty long ones. I will submit the rest of

them in writing. And if you would just submit those studies to us,

I would appreciate it, especially on the on-patent and off-patent

drugs.

Mr. ZERHOUNI. I will certainly do that.

Mr. BILIRAKIS. Mr. Pitts to inquire.

Mr. PITTS. Thank you, Mr. Chairman.

First I think I ought to try to make a clarification. Some of my

colleagues on the other side seem to question the intent of some

members who question NIH on the merits of particular studies,

and the position of the other side seems to be that sexually transmitted diseases affect a lot of people, and that is why it is an important study. And I want to be clear; no one ever questioned

whether STDs are important to study. I think we all agree with

that.

What some question was how paying people to watch pornography is related to STDs and how is it related to HIV-AIDS, and

how, as one NIH spokesman claimed, it has anything to do with

abstinence education.

I think we all agree that we need to find a cure for HIV-AIDS,

but there is some question about what is the best way to do it; is

there a better way than paying people to watch pornography? That

said, let me move on to my questions.

Over the years there have been questions raised about some of

the grants that NIH has awarded and whether or not these grants

were appropriate uses of taxpayer dollars. And while some grants

arguably have scientific value that may not be apparent to a

layperson, there are also some grants that are arguably of questionable priority when reviewing the entire NIH research portfolio.

And, Dr. Zerhouni, I am pleased to hear that you are working toward more transparency issues, as you stated. And I want to be

clear; I prefer not to go grant by grant and bring congressional

grants up at every hearing, but I can’t help but mention one. I saw

a study of dorm-room wall decorations, Web pages of college students. It was funded 1 year.

How can we convey to constituents, taxpayers, who have family

members with Parkinson’s or leukemia or diabetes, who are concerned about ensuring the safety of the blood supply, that studying

dorm-room wall decorations was more worthy than finding a cure

for their diseases? When a multiyear grant is awarded by an institute, what if any authority do you have as NIH director to make

a change if it is determined at a later date that this project is of

less significance, given current public health needs?

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Have any of you ever stopped funding of an awarded grant based

on an unexpected budgetary need? And, Dr. Zerhouni, you can

start.

Mr. ZERHOUNI. Sure. Obviously, this is an issue. As I said, we

need to work on and make sure that we review these grants. The

dorm-room grant study was funded over 3 years ago, is no longer

active. I looked into that because of the questions that were raised,

and what I am told is that the reason the study was performed is

that you can tell the likelihood of mental health disorders according to the decoration that student in a college will put up in their

room and what kind of analysis—personality analysis this will be.

So the way I understand why the research was thought useful

at the time by the committee that reviewed it was that it could provide you with a diagnostic test of children, students—college students that may be getting in trouble from the mental standpoint,

and their personality disorders and so on. This is what I am told

was the reason for that.

But the question you are asking is a much more profound question, and that is relative allocation of resources. And that is something, as I mentioned, to do that better, I think you will need to

have, A, a better understanding of the portfolio and the relative importance of the portfolio, and this is why I suggested that we need

to have a portfolio review mechanism, both within institutes and

across institutes, because each program obviously evolves over

time, and has the budget that they need to spend according to both

the primary and secondary review.

So I want to make sure that we have processes in place that will

give you the assurance that it has been reviewed, that its scientific

merit is established, that it is explained in clear terms so that

there is no—like, if you read this title, obviously it makes no sense,

but if you look into it, you realize that psychological tests that look

at drawings, for example, that children use on their wall tell us

something about the mental state of an individual. And this is

something you can argue in terms of is it right to spend that dollar

on that thing instead of spending it on something else. This is why

I suggested that we need to have better mechanism.

The authority that the director has to stop a grant is, I would

say, very limited; because if it has passed review, has been approved by the advisory council of an institute, unless two things

happen, one, that the progress reports indicate that the research

is not making any headway or that, two, there is an inappropriate

use of Federal funds, we will terminate the studies. That is pretty

much the authority of the director of the NIH, but I will let my colleagues comment as well, because they have greater authorities

within their own portfolio.

Mr. BILIRAKIS. Very briefly, if you would like to comment.

Mr. VON ESCHENBACH. Just to give you a specific example of the

importance of managing the portfolio and making shifts to strategic

priorities, one of the things we did this very year was make a decision with regard to a study that had been going on with regard to

looking at mammography and its utilization and standards for interpretation. That study was coming up for reissuance and rereview, but the analysis indicated that we had received significant

input and information about the outcomes of that question that

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was first raised, and essentially that grant had reached its fulfillment. And rather than reissue it and continue it on, we stopped

that and redeployed those dollars to other initiatives where we can

look at even more effective ways of detecting breast cancer earlier.

So we do make those kinds of strategic shifts in decisions.

Mr. FAUCI. Another example would be human subjects issues. We

have stopped grants that if you look at the design of a clinical trial,

for example, in a developing nation, that although the science

would be compelling to get the answer to the question, it could not

be done under the proper ethical circumstances, so we would stop

it even though it got a good scientific score. I have done that.

Mr. BILIRAKIS. The gentleman’s time has expired. . And then I

appreciate the patience the gentleman has shown throughout the

entire hearing.

You know, Mr. Waxman made a—focused on keeping politics out

of science and research, and I will tell you, and I have said this

before—I know Dr. Zerhouni at least has heard me say it a number

of times—I think probably maybe the toughest part of my job—and

I will bet I am speaking for Mr. Brown and virtually every member

of this committee—is when someone comes wheeling into our office

as an ALS patient and tells us that there isn’t enough research on

ALS and then knows about some of these other areas that Mr.

Pitts and others have mentioned. I lost my youngest brother to

Parkinson’s in his mid-fifties, and you know where—Mohammed

Ali has come in and testified.

I think I am losing something here. I think I need some NIH

right about now.

I guess what I am saying is it is a tough thing for us to tell

them, thank you; to tell them that we believe very strongly that we

should not micromanage; we believe very strongly that we are not

in a position to determine where the funding should go in terms

of what specific disease, things of that nature. So we are staying

out of it. But I would also strongly suggest there is probably a hell

of a lot more politics being played within NIH and among the institutes than ever comes out of the Congress in this regard.

Whether you agree with me or not, I don’t know, but I think if

you kind of search your experiences, you would find that that is the

case.

So we intend to continue to do this tough thing of telling these

many patients, these people who come in here and testify, that we

don’t think it is our role to determine what funding should go—research funding should go to what disease, but we also like to think

that you are helping us in that regard, too, through some of the

grants.

I mean, the word ‘‘common sense’’ was used, and issue was taken

with that by another member and that sort of thing. I don’t know

what is right and what is wrong. All I know is, put yourselves a

little bit in our shoes when we have to tell these people and they

know what some of this funding award is going to.

Your explanation in terms of the painting of the dorm walls and

whatnot, well, I can see where there is something behind that. But

when you have that patient out there who is dying, I think they

would rather see that money, rather than go to studying the painting of those walls, go into something involving ALS or whatever.

46

So that is the position that we are always in, and I appreciate

your coming here today. I think you have worked awfully hard to

answer our questions and our inquiries. I am not sure Mr. Brown

is satisfied as far as Dechenne muscular dystrophy is concerned.

For instance, I am not sure that any of us are completely satisfied,

but transparency I think is the answer, and we depend upon you

for that. And you are just the magicians in our society, your research and all your work and whatnot. And all of us are strongly

supportive of that, contrary to some of the statements made in this

hearing up here.

We have a number of questions, as usual, to submit to you. We

would appreciate it—as you heard Mr. Barton say, we haven’t reauthorized NIH for quite a few years. It hasn’t affected your work,

because you have gotten the money, but it looks like we may be

advancing toward that. I mean, discussions have taken place between the minority and the majority on maybe some issues and

things of that nature. So I guess what I am saying is, no, we

shouldn’t take the flexibility away from you, in my opinion, but we

also need recommendations from you on what we should be doing

that you would need to see legislative changes in order to take care

of some of the problems that you all know of much better than we

do.

Mr. Brown, do you have any closing statements? Please feel free.

Mr. BROWN. Only to add that—and thank you, Mr. Chairman—

I appreciate this hearing, and I always appreciate so much what

NIH has done. I hope we can get our government to pay the same

attention to the CDC that we do the NIH, but I also hope that we

don’t make decisions in the next few years that cripple this Nation’s ability to do research, not just the research that you do but

also research with—we are doing better with math and engineering

and where we go in that direction. And I am afraid, just as we look

at budget questions that come about because of policies that people

in this Congress make, that we think more of the future than we

seem to be thinking right now. And I applaud all four of you and

applaud all your colleagues out of each institute, and especially the

employees of NIH and the contractors at places like Cleveland—in

Cleveland with Case Western Reserve University and other great

institutions around the country that benefit from the decisions you

make, and only the public benefits from the decisions both you and

they make. So I thank you for that.

Mr. BILIRAKIS. Thank you very much. Thank you, Doctors. The

hearing is adjourned.

[Whereupon, at 4:30 p.m., the subcommittee was adjourned.]

[Additional material submitted for the record follows:]

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