The 73rd meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December
12, 1996. Dr. Harold Varmus, Director, NIH, began by noting the Administration's commitment to biomedical research. He provided
an update on personnel changes at the Department of Health and Human Services (DHHS) and the NIH and summarized the status of
the NIH budget for fiscal years (FY) 1997 and 1998. For FY 1997, the NIH budget will increase by 6.9 percent and include funds
to begin construction of a new clinical center. The NIH budget for FY 1998 is being developed. Dr. Varmus noted that several
other legislative items that will affect the NIH are being discussed by Congress.
Relating recent NIH activities, Dr. Varmus commented on Government oversight of scientific conduct, the Recombinant DNA Advisory
Committee, public support for biomedical and behavioral research, outreach to universities, NIH advisory groups, and the
International Conference on Malaria in Africa. He noted three issues that the NIH is specifically addressing: information
technology at the NIH; priority setting by the NIH institutes, centers, and divisions (ICDs); and clinical research. He
highlighted several recent scientific achievements in genetics research and the treatment of Human Immunodeficiency Virus (HIV)
infection and Acquired Immunodeficiency Syndrome (AIDS), and he noted that investigators in the NIH Intramural Research Program
contributed significantly to these and other advances.
During the past year, the NIH, in conjunction with DHHS, reviewed and began implementation of the recommendations in the January
1966 report, "Opportunity: Revitalizing the NIH Clinical Center for Tomorrow's Challenges," prepared by the Reinvention of
Government (REGO) II Options Team. Three presenters commented on this report.
Dr. Helen L. Smits, who chaired the Options Team, summarized the report and recommendations. The team focused on improving the
efficiency of the Clinical Center's operations without compromising the quality of the science conducted or patient care. The
team presented four primary areas of recommendation: governance, funding, strategic planning, and flexibility. Dr. Smits noted
that probably the most important recommendation was to establish a Clinical Center Board of Governors. Other recommendations
highlighted the need for predictable and stable support for the center's activities, development of a strategic plan, and
increased flexibility in financial and administrative management.
Dr. John Gallin elaborated on the Clinical Center's strategic planning framework and described five key projects initiated in
response to the Option Team's report and recommendations. In these projects, the NIH is pursuing new approaches for streamlining
procurements and controlling costs, plans for a new and smaller Clinical Research Center, recovery of costs through third-party
reimbursement, expanded interaction with the NIH-supported General Clinical Research Centers (GCRCs), establishment of new
facilities to strengthen NIH's clinical research infrastructure, expansion of NIH's clinical research training efforts, and use
of telemedicine and other information technology to link the intramural and extramural research communities.
Mr. John Finan summarized NIH's efforts to implement a new governance structure for the Clinical Center. As proposed, the new
Board of Governors will have very specific functions limited to the operation of the center and not its scientific activity.
Acting like the board of a hospital, it will advise, consult, and make recommendations on the center's activities and functions.
It also will oversee the center's Medical Executive Committee which assures quality practice. At its first meeting, the Board
accepted a budget proposal for the center, endorsed a feasibility study for a new cost accounting system, and decided to
establish subcommittees.
Following these presentations, Dr. David G. Nathan reported on the NIH Director's Panel on Clinical Research (CRP). Three panel
members joined him in this presentation. Convened in spring 1995, the CRP has met four times and has reported previously to the
ACD; it will continue to meet during 1997 to complete its work. Dr. Nathan noted that the funding and continuity of clinical
research are threatened by changes occurring in academic health centers in response to the country's movement toward managed
care. Focusing on the funding of clinical research, Dr. Judith L. Swain noted that the lack of funds for clinical research is
more a result of external pressures on academic health centers than of decreased NIH support. A panel subcommittee analyzed NIH
data on all clinical research awards made during FY 1996 and found that these awards account for about 30 percent of NIH's total
support for research and for research training. This finding contrasts with the much smaller percentage previously estimated by
the Institute of Medicine. Dr. Swain stated that the panel's definition of clinical, or patient-oriented, research is fairly
conservative and has been well received. The subcommittee is continuing to analyze NIH data and will recommend additional
analysis as well as dissemination of the results to all ICDs.
Dr. Guy McKhann summarized the findings of another CRP subcommittee, which focused on GCRCs and the Clinical Center. He noted
the important role of GCRCs in promoting and supporting clinical research. He also noted that, because this role will become
increasingly valuable in the future, the subcommittee is recommending that the GCRCs be made available to all clinical
researchers, including those not funded by the NIH. Other recommendations are directed to the expansion of GCRC leadership and
activities to include non-NIH-funded investigators, the broad range of clinical research areas and settings, and increased
emphasis on training. With respect to the review of clinical research grant applications at the NIH, this subcommittee endorsed
the report and recommendations of the NIH Clinical Research Study Group, which were published in November 1994, and is
recommending that these grant applications be assigned to study sections experienced in reviewing such applications. During
1997, the subcommittee will be addressing the interface between the Clinical Center's intramural programs and the GCRCs.
Dr. Nathan presented the panel's 11 draft recommendations. He agreed with Dr. Swain that the level of NIH support for clinical
research is appropriate; however, he suggested that attention should be given to the strategic distribution of this support
across ICDs. Summarizing the recommendations of a third subcommittee, which focused on training and job opportunities, Dr.
Nathan noted the importance of clinical research training, the need for formal training that includes a strong didactic
component, the need for new support mechanisms for newly independent and mid-term clinical investigators, and the possibility of
collaborations with the private sector. He highlighted as crucial the panel's recommendation for a medical student training
program in clinical research.
Presenting the results of another subcommittee's deliberations, Dr. William T. Friedewald emphasized the importance of
disseminating information to the public on the importance and results of medical research. This subcommittee has been studying
the magnitude of non-NIH funds for clinical research (e.g., funds received for patient care services in academic health
centers), which appear to be very large. Because these funding sources are threatened by the move to managed care, the
subcommittee is encouraging the NIH to develop and strengthen partnerships with private for-profit and nonprofit funding
organizations.
On another topic, Dr. William E. Paul presented an update on NIH's implementation of key recommendations in the report of the
NIH AIDS Research Program Evaluation Working Group (the "Levine Report"), which was published in March 1996. Dr. Paul described
five major recent advances in AIDS research and summarized current estimates of the extent of HIV infection and AIDS. Among the
implementation steps being taken by the NIH in response to the Levine Report, Dr. Paul noted the following actions: the NIH is
increasing support for investigator-initiated research on HIV and AIDS, exploring ways of improving peer review, planning to
increase funding for vaccine research, planning for increased investigator-initiated research on the human immune system, and
developing a comprehensive NIH HIV Prevention Science Agenda. The NIH also is discussing the creation of a unified clinical
trials agenda, reviewing the recovery effort of its drug discovery, reviewing the operations and activities of NIH-supported
regional primate centers, and expanding access to these centers for non-NIH-supported investigators. Importantly, the NIH has
asked Dr. David Baltimore to lead a comprehensive, trans-NIH vaccine effort.
Dr. Joshua Lederberg summarized the recommendations of an external advisory panel convened by Dr. Varmus to review the
international programs and activities of the NIH and, specifically, the Fogarty International Center (FIC). This review is one
of several already completed, under way, or being organized to review the functions and activities of the ICDs; a report on each
review will be presented to the ACD. Dr. Lederberg noted that the panel felt that the NIH could not fulfill its mission without
attending to global concerns related to biomedical and behavioral research and that the FIC should be retained as a separate
unit at the NIH. International programs and activities are extensive at the NIH and involve all ICDs. By far, the greatest
expenditures in this area are made by the individual ICDs, and the largest component of these expenditures is the NIH Visiting
Program of foreign scientists and researchers in NIH's intramural laboratories. To assure more effective coordination of NIH's
international activities, the panel recommended that an Associate Director for International Research be appointed to report
directly to the Director, NIH, and to serve as Director, FIC.
Dr. Wendy Baldwin reviewed NIH's support of the Small Business Innovation Research (SBIR) and Small Business Technology Transfer
(STTR) programs. In January 1997, the NIH will convene a meeting to assess the effectiveness of these programs and to identify
strategies for strengthening them. Funding for the SBIR and STTR programs is mandated by Congress; it was 2.0 percent of NIH's
research budget in FY 1996 and is expected to increase to 2.5 percent in FY 1997. Dr. Baldwin noted that the success rate for
SBIR applications is higher than for R01s and has increased in the past when funding for the program has increased. The NIH is
taking several steps to assure that only the most meritorious applications are funded in FY 1997.
Dr. Robert J. Levine and Dr. Ting-Kai Li presented the report of an expert panel convened by Dr. Varmus to review a
controversial research grant application recently approved and funded by the National Institute on Drug Abuse (NIDA). The study
in question is one of a number of research projects on the use of needle exchange as an intervention to reduce transmission of
disease (hepatitis B, hepatitis C, and/or HIV) among intravenous drug users. The panel was asked to address the appropriateness
of the study design, the adequacy of the interventions provided to the control group, and the review process for assessing the
study's scientific merits and protection of human subjects. Dr. Li described the study design. Dr. Levine summarized the panel's
review, findings, and recommendations. The panel noted that the proposed study would be the first to evaluate systematically the
safety, efficacy, and effectiveness of two approaches for making clean, sterile needles available: needle exchange and pharmacy
access. The panel concluded that the proposed study design is scientifically and ethically appropriate, the interventions are
adequate, the subjects will be treated appropriately, and the previous reviews of the study followed appropriate procedures.
OPENING REMARKS
Dr. Harold Varmus, Director of the National Institutes of Health (NIH), began the 73rd meeting of the Advisory Committee to the
Director (ACD) by introducing new members of the Committee, most of whom were present.
Dr. Varmus noted that, during the election campaign, President Clinton frequently made reference to the progress being made in
biomedical research, particularly research in the areas of genetics, Acquired Immunodeficiency Syndrome (AIDS), and breast
cancer. The President, in reaffirming his commitment to research on breast cancer, cited a collaborative arrangement that is
being developed between the NIH and the Department of Defense to study genetics as it pertains to breast cancer. Since the
election, Dr. Varmus and other Government officials participated in an intense, 1-hour briefing with President Clinton on recent
progress and future opportunities in AIDS research and treatment. In addition, Dr. Varmus and Dr. William Paul met with Vice
President Gore to discuss new developments in AIDS therapies.
As commonly occurs following an election, the leadership of many agencies will change. Dr. Varmus noted that the NIH is
particularly pleased that Secretary Donna Shalala will continue to lead the Department of Health and Human Services (DHHS). This
continuity will enable the Department to move forward immediately and avoid a difficult transition period. In response to a
request from Dr. Shalala, Dr. Varmus asked the Committee members to suggest topics to which Secretary Shalala could devote her
energies and talents during the next 4 years.
Several personnel changes will be made within DHHS during the next several months. Dr. Philip Lee, Assistant Secretary for
Health, will be returning to the University of California at San Francisco at the end of January. Dr. David Kessler,
Commissioner, Food and Drug Administration, and Dr. Clifford Gaus, Administrator, Agency for Health Care Policy and Research,
will both be leaving their respective agencies. No replacements have been named for either of these positions. In addition, Dr.
Varmus announced two personnel changes at the NIH: Dr. Marvin Cassman, who has been serving as Acting Director, National
Institute of General Medical Sciences, was appointed Director of this Institute as of August 15, and Dr. Elvera Ehrenfeld, whose
appointment as the new Director of the Division of Research Grants, was announced at the June 1996 ACD meeting, will begin
working on a full-time, permanent basis as of January 1.
Presenting an update on the NIH budget, Dr. Varmus said that the appropriations hearings for the fiscal year (FY) 1997 budget,
which took place in June 1996 following the previous ACD meeting, were reasonably successful. The NIH received a budget increase
of 6.9 percent for FY 1997. This budget includes $90 million to begin construction of the new clinical center, which will be
named the Mark O. Hatfield Clinical Research Center. The $90 million represents about one-fourth of the expected cost of the
center. Congress also gave NIH the authority to negotiate a contract for constructing the building at the full expected cost,
anticipating that the appropriations in ensuing years will cover this cost.
As in the previous 2 years, Congress gave Dr. Varmus authority to transfer up to 1 percent of funds from one institute or center
(IC) to another to capitalize on new scientific opportunities. Dr. Varmus requested and received from the IC directors many
proposals for using this transfer authority. To advise on which proposals to fund, a panel of outside experts will convene on
December 21 to hear presentations from the directors and to discuss funding decisions with Dr. Varmus.
In recent years, the Congress and NIH have made particular efforts to control administrative costs at the NIH. As requested by
Congress, the institute, center, and division (ICD) directors tried to reduce research management and support (RM&S) costs
by 7.5 percent in FY 1996. For FY 1997, the House Appropriations Committee has asked NIH to maintain these costs at the same
level as in FY 1996 without an increase for inflation. Congressman John Porter (R-IL) has also asked NIH to conduct a
comprehensive review of its administrative structures and costs, which includes RM&S costs as well as other administrative
costs associated with the Office of the Director, other ICD directors' offices, and the intramural program. NIH is organizing
this review and developing a long-range plan for research management and other administrative activities.
Preparations for the FY 1998 budget continue. In coordination with DHHS, the Office of Management and Budget, and the White
House, the NIH is developing its part of the President's Budget for presentation to Congress.
Among other legislative items, Dr. Varmus reported that the NIH reauthorization bill, which was written by the Senate's Labor
and Human Resources Committee, passed the committee and full Senate but was never considered by the House and thus died in the
104th Congress. This committee was chaired by Senator Nancy Kassebaum (D-KS) who has since retired from the Senate. Senator Jim
Jeffords (R-VT) will chair the committee in the newly realigned 105th Congress; a friend of the NIH, Senator Jeffords recently
visited the NIH and has met with many of the staff on campus. Because of the many new members on the committee, it is not clear
whether the NIH reauthorization will be considered a high priority on the legislative agenda.
Two other bills, which were passed by the 104th Congress, are of interest to the NIH. The Health Insurance Portability and
Accountability Act of 1996, also known as the Kassebaum-Kennedy bill, has two important components related to genetic
information. The bill prohibits discrimination based on genetic information and asks the Secretary, DHHS, to make
recommendations to Congress on how to control the privacy of health information. The NIH played an active part in developing the
first component and is participating in preparing the recommendations for Congress, which are due within 12 months. Other bills
that address privacy issues also were introduced during the 104th Congress and could resurface for consideration by the 105th
Congress. Another bill that affects the NIH is the Traumatic Brain Injury Act, which was introduced by Representative Jim
Greenwood (R-PA). This bill addresses issues pertinent to the National Institute of Child Health and Human Development, which is
organizing a workshop and some expanded research studies influenced by this bill.
Presenting an update on topics considered at the Committee's June 1996 meeting, Dr. Varmus described two activities related to
Government oversight of scientific misconduct. First, the Committee on Fundamental Science has developed a working paper that
includes a definition of scientific misconduct and principles for investigating allegations of misconduct. This committee is
cochaired by Dr. Varmus, Dr. Neal Lane, Director, National Science Foundation, and Dr. Ernest Moniz, Associate Director for
Science, Office of Science and Technology Policy. The committee's paper is being circulated among the agencies for comment.
Second, at the request of the Secretary, DHHS, Dr. Philip Lee is chairing a small committee that is reviewing the functions of
the DHHS Office of Research Integrity. Dr. Varmus serves on this committee, which is developing specific recommendations on the
handling of scientific misconduct by DHHS.
Dr. Varmus briefly reviewed a number of other NIH activities. He reported that the NIH received a wide variety of responses to
the Federal Register notice about replacing the Recombinant DNA Advisory Committee (RAC). Most of the respondents
objected to the dissolution of RAC which was perceived as having international respect and a strong tradition of good
decision-making. In response to these concerns, the NIH wrote a revised notice of intent to retain a smaller RAC constituted not
to approve or disapprove applications for gene therapy research, as originally it had done, but to hold public discussions of
worthy protocols, to maintain oversight of the gene therapy database, and to recommend topics for policy conferences on gene
therapy. On December 9, Dr. Varmus met with the RAC and a final notice of intent will be published shortly.
Following up on Dr. Eric Lander's suggestion at a previous Committee meeting, the NIH convened a group of academic and industry
advocates of NIH who met on July 31 and December 10 to discuss ways of generating and publicizing convincing arguments for
public support of the NIH. The economic, scientific, and health benefits of biomedical and behavioral research need to be
promoted widely and clearly. To publicize the NIH message, staff met recently with representatives of
The Washington Post and the Public Broadcasting System, which are jointly developing a series of television shows about
medical research.
The NIH continues to seek other opportunities for outreach. On September 26, staff, in conjunction with the American Association
of Universities (AAU), organized a visit of university presidents to the NIH. This full-day visit of presentations and
discussions was useful and generated many interesting ideas. The NIH hopes to coordinate, with the AAU, similar visits to the
NIH campus at least once a year.
The NIH also benefits from the work of various advisory groups. The National Advisory Council and Board Representatives Group,
initially convened by Dr. Varmus, continues to meet and has formed four subcommittees to address specific issues. The National
Bioethics Advisory Commission (NBAC), which is chaired by Dr. Harold Shapiro, President of Princeton, met for the first time and
is defining key issues to pursue in subsequent meetings. The NBAC is administered by DHHS.
On January 1, Dr. Varmus and other NIH representatives will travel to Dakar, Senegal, to participate in the International
Conference on Malaria in Africa. The aims of this conference are to develop multilateral collaborations among funding
organizations and to weave a closer network of malarial research stations in Africa. Preparations for this conference have been
under way for several years, beginning with early discussions at the NIH that included European and U.S. research sponsors and
African scientists. The meeting has attracted much high-level international attention and will be attended by about 150
individuals who are conducting or funding research on malaria.
This year again, Dr. Varmus convened the annual retreat of NIH leadership. The retreat has become a useful forum for the
exchange of information among ICD directors and senior staff of the Office of the Director. At the meeting this year, two
important issues emerged: information technology, and priority setting at the NIH. Dr. Larry Smarr explained the importance of
having a useful infrastructure for information technology at institutions like the NIH. During the discussion that followed, a
number of suggestions were made about developing an information system that would maintain privacy of information and yet be
intercompatible for all NIH components. Subsequently, Dr. Varmus established a central NIH committee that has made specific
suggestions for restructuring NIH's information technology and for recruiting an NIH chief information officer. This recruitment
is under way and important changes will be made during the coming year.
The second issue emerged from presentations and discussions and showed that the process of setting priorities differs markedly
among ICDs. This variability and the inherent complexity of setting priorities, which involves many elements and stages, make it
difficult for the public, Congress, scientists, and advocacy groups to understand the criteria and process by which NIH decides
how to spend its resources. Subsequent to the meeting, Dr. Varmus established a Priority-Setting Committee, composed of NIH
staff, which is compiling a small booklet that describes priority setting at the NIH. The draft booklet will be circulated on
request to Committee members for their review and comment.
An area of special concern to the NIH in recent months is clinical research. Two efforts were highlighted later at the Committee
meeting, revitalization of the NIH Clinical Center and the NIH Director's Panel on Clinical Research. In addition to these and
other efforts, Dr. Varmus has been meeting with representatives of the managed care industry, specifically to discuss approaches
to useful research interactions involving this industry, academia, and the NIH. Possible areas of mutual concern and joint
funding include epidemiology, clinical trials, and health services research. To emphasize the importance of clinical research on
campus, the NIH will be hosting, on February 10, a Clinical Research Festival Day that will feature many presentations from NIH
clinical investigators and discussion of future directions for clinical research.
Clinical research also is a target area for the recently formed National Foundation for Biomedical Research, which received a
congressional appropriation of $200,000 in FY 1996 to support NIH activities. The Foundation's board of directors met on
September 24 and decided, as its first major project, to create a new program that would enable medical students to come to the
NIH for 1–2 years for a clinical research experience. Foundation support will complement NIH's Intramural Research and
Training Award (IRTA) funds and enable NIH to offer the students an in-depth exposure to clinical research activities. It is
hoped that this program will become as popular and beneficial as the scholars program of the Howard Hughes Medical Institute.
Dr. Varmus highlighted several scientific achievements made during the past 6 months. Prominently featured among these
accomplishments is the availability of the human gene map on the World Wide Web. With this remarkable and powerful tool, both
the public and the scientific community can explore the code of life, moving across the chromosomes to examine the available
information on genes, diseases, databases, support groups, and so on. Within the first few days after the announcement that the
map could be accessed electronically, more than 100,000 inquiries were recorded, demonstrating the wide appeal of this type of
information. At the same time, scientists are continuing to discover genes associated with specific diseases. The sites of two
new genes were identified recently, one for Parkinson's disease on chromosome 4 and one for prostate cancer on chromosome 1. One
of the most exciting discoveries recently is spectral karyotyping. Using this technique, investigators can designate specific
colors for different chromosomes, making it possible, for example, to track rearranged chromosomes in cancer cells or the
origins of chromosomes among different species.
In addition, progress has been made in understanding and treating Human Immunodeficiency Virus (HIV) infection and AIDS.
Scientists isolated new coreceptors for HIV and identified mutations in the genes that encode these coreceptors. Also, new
reports documented successful treatment of severe combined immunodeficiency syndrome in a fetus and a newborn using bone marrow
transplanted from their respective fathers.
Investigators in the NIH Intramural Research Program have contributed to many of these research advances. Among the awards
received by intramural investigators recently is this year's Lasker Award, given to a team of researchers, including two
intramural scientists, for developing the Haemophilus influenza B vaccine. In recognition of the accomplishments and
promise of newly independent investigators, the Government will award, on December 16, the Presidential Early-Career Awards to
60 investigators, including 10 NIH grantees.
These recent advances in research and treatment are complemented by recent announcements that deaths have declined for Sudden
Infant Death Syndrome and for cancer in general. To protect patients unable to give consent, the NIH and the Food and Drug
Administration have jointly announced guidelines for research involving these patients, for example in hospital emergency rooms.
CLINICAL CENTER UPDATE
Introduction
In January 1996, the Reinvention of Government (REGO) II Options Team published its report, entitled "Opportunity: Revitalizing
the NIH Clinical Center for Tomorrow's Challenges." This report was prepared for the Secretary, DHHS. Over the past year, the
NIH, in conjunction with DHHS, has reviewed the report and taken steps toward implementing its recommendations. An update of
these activities was presented to the ACD.
Dr. Helen L. Smits, who chaired the Options Team, reviewed the team's goals, organization, and recommendations. Dr. Smits was
previously Deputy Administrator of the Health Care Financing Agency and is currently President and Medical Director of
HealthRight, Meridan, Connecticut.
Dr. John Gallin, Director of the Warren G. Magnuson Clinical Center, NIH, described the Clinical Center's strategic planning
framework and five key projects initiated in response to the report and recommendations of the Options Team. Dr. Gallin was a
member of the Options Team.
Mr. John Finan, President and Chief Executive Officer, Franciscan Missionaries of Our Lady Health System, Baton Rouge,
Louisiana, concluded the update. Mr. Finan chaired a committee of external consultants to the Options Team and currently chairs
the Clinical Center Board of Governors. He described the governance structure of the new Clinical Center and the functions,
membership, and agenda of the Board of Governors.
Summary of the Options Team Report
Dr. Smits described the work of the Options Team. Chaired by Dr. Smits and composed of NIH staff, this team met regularly
throughout 1995 to consider options for managing and renovating the Clinical Center. Proposals already made by DHHS, including
"privatization" of the Clinical Center, were specifically addressed. In its work, the team consulted with a committee
of external consultants, gained insights from visiting academic health centers throughout the country, and formed various
subcommittees to address particular topics.
As noted by Dr. Smits, the team's primary goal was to improve the efficiency of the Clinical Center's operations without
compromising the quality of the science conducted or patient care. Two secondary goals were to designate the Clinical Center as
a reinvention laboratory, thereby gaining the flexibility needed to operate efficiently, and to generate funds through these
operational savings to help finance construction of a new clinical center. Six subcommittees focused respectively on governance
of the Clinical Center, information and reporting, budgeting, benchmarking (measuring outcomes and costs), options as a Federal
entity, and reinvention laboratories.
The Options Team, in consultation with the external group, defined four primary areas of recommendation: governance, funding,
strategic planning, and flexibility. Probably the most important recommendation, according to Dr. Smits, was to establish a
Clinical Center Board of Governors. As recommended, this Board would comprise 17 members, 9 from outside the NIH and 8 from
within NIH; it would be chaired by a non-Federal appointee, include an R.N., and involve the Director of the Clinical Center in
an ex officio capacity. The team recommended that the Board meet at least three times a year.
The recommendations regarding funding of the Clinical Center emphasize predictable and stable support for center activities; the
ability to reprogram across budget categories; retaining and reinvesting savings from year to year; access of all NIH ICDs to a
baseline level of research activity even if the research is "out of fashion"; and enabling ICDs that sharpen their budget
forecasts and improve their efficiency to increase their overall activity at the Clinical Center. In addition, the Option Team
recommended that the Clinical Center be allowed to actively solicit donations and to charge insurance companies for some
services. Dr. Smits noted that new payment models could help offset costs and ensure that all Americans can access Clinical
Center services, while protecting the privacy of patient information.
The Options Team also recommended that the Clinical Center should be given greater flexibility and be allowed to relax
administrative barriers in the following areas: procurement, personnel, and financial and administrative management. Flexibility
in these areas would enable the center to respond quickly to new directions and to improve its overall efficiency and
effectiveness. Another major recommendation is to develop a strategic plan that has clear goals and measurable objectives. In
making this recommendation, the Options Team emphasized the importance of engaging all constituents in the development of the
plan, obtaining the endorsement of these groups, and annually rethinking and reworking the plan.
Strategic Planning Framework
Dr. Gallin presented the Clinical Center's strategic planning framework. He noted that, in responding to the recommendations of
the Options Team, the NIH has given much attention to the strategic planning process. To develop the vision for the framework,
the NIH considered the center's environment, customers and stakeholders, and guiding principles and defined the following
mission statement: "The Clinical Center is the clinical research facility of the National Institutes of Health. As a national
resource, it provides the protocol-specific patient care, services, training, and environment needed to initiate and support the
clinical research sponsored by the individual NIH institutes." Long-range goals and strategies were developed, as well as
several operating plans, which include a series of key projects, an evaluation component, and identification of measures of
success. These plans will evolve over time, as appropriate for a dynamic enterprise that is responsive to a changing
environment.
To convey a flavor of the Clinical Center activities being implemented by the NIH, Dr. Gallin described five key ongoing
projects. Other projects are planned and will be implemented in a timely fashion. The project areas that have been identified
are reinvention activities, redesign of care and service delivery, clinical research training, public awareness and
collaboration, clinical research infrastructure, and information technology. A first key emphasis is streamlining and cost
control. To this end, the NIH has developed a budget plan for the Clinical Center that includes a 3-year commitment from each
ICD based on its historical use of the center. Dr. Gallin noted that the center's budget increased rapidly from FY 1985 through
FY 1992 but has been essentially flat since FY 1993. By instituting new approaches such as streamlining the procurement process,
creating efficiencies within the hospital (e.g., by consolidating beds, sharing resources), and reducing personnel levels, the
center will be able to reduce its costs and maximize its resources.
A second key project is the planning for the new Clinical Research Center. Showing an artist's rendition of this new center, Dr.
Gallin noted that it will have fewer (250) beds, a slightly increased number of day hospital chairs (100) for patients that
don't require in-hospital admission, and a much smaller space (850,000 square feet versus about 3 million square feet for the
current hospital). The schematic design work for the new facility will begin this winter, and groundbreaking is scheduled for
fall 1997 or early winter 1998. Construction is expected to be completed by fall 2001, with occupancy to follow in 2002. As Dr.
Varmus said previously, Congress has already provided initial funding for this project.
The third key project highlighted by Dr. Gallin was cost recovery, or third-party reimbursement. As he noted, this effort could
have a huge impact on all of the General Clinical Research Centers (GCRCs). In FY 1996, Congress gave NIH authorization to
collect third-party payments to cover the costs of clinical services provided in NIH research facilities, which includes the
GCRCs and the Clinical Center. The NIH has never had permission to recover these costs but is exploring the feasibility of doing
so. The strategies being pursued include initiating a cost accounting system, recruiting a chief financial officer, collecting
data on patients' insurance status, expanding the dialogue with insurance and managed care industries, and evaluating possible
legislative issues.
A fourth key project is the strengthening of NIH's clinical research infrastructure. Dr. Gallin described a number of activities
that are under way. For example, the NIH has established a new patient recruitment and referral center, opened a new NIH Guest
House to house families of patients, established a protocol coordination and development center as a core resource for the NIH,
placed all NIH protocols on the World Wide Web for easy access by patients and physicians, planned for a Biostatistics and
Epidemiology Service Center to serve both the intramural and extramural communities, and opened a Stem Cell Harvesting Facility
to assist investigators conducting gene transfer experiments.
In addition, the NIH continues to emphasize clinical research training. Dr. Gallin noted that a third set of students is
enrolled in NIH's core curriculum in clinical research and that 260 students have completed the training program. This course,
which is already being taped and sent electronically to the National Institute of Environmental Health Sciences in North
Carolina, will soon be available on the World Wide Web and will be complemented by the new Medical Students Clinical Research
Scholars Program referred to previously by Dr. Varmus.
New emphasis also is being given to using informatics, particularly telemedicine, to link the NIH with GCRCs and more remote
clinics to recruit and follow patients for NIH protocols. Information technology is bringing the intramural and extramural
research communities closer together and enabling NIH to make key services and databases broadly available to patients, research
scientists, and physicians. An example of this is a new local alliance formed among the NIH, Suburban Hospital, and Johns
Hopkins University to enhance clinical research training for students and senior staff and to open access to resources not
available in the Clinical Center. The NIH already collaborates with other local organizations such as the Navy Medical Center,
Walter Reed Hospital, and community hospitals, but hopes to engage in similar, more formal alliances with additional local, and
even remote, institutions.
New Governance Structure
Mr. Finan described a fifth key project, implementing the new governance structure for the Clinical Center. He noted that the
new Board of Governors assumes very specific functions and does not replace any of the relationships already existing in the
Clinical Center. The mission and role of the Board are clear and are limited to the operation of the center and not its
scientific activity. The Board acts very similar to the board of a hospital or an investor-owned organization, serving to
advise, consult, and make recommendations concerning the activities and functions of the Clinical Center. The Board also
provides oversight of the Clinical Center's Medical Executive Committee, which is responsible for reviewing quality issues,
assuring quality practice, and credentialing medical staff. The 17 members appointed to the Board are all individuals of high
caliber and represent diverse talents.
Mr. Finan conveyed the excitement of the overall effort to revitalize the Clinical Center. He complimented the Options Team and
the NIH leadership for impressive work in assessing the resource constraints that will face the Clinical Center in the future
and initiating effective processes to overcome these constraints and improve the center's capabilities. Reviewing the activities
of the Board, he reported that it held its initial meeting on October 21, 1996, for the purpose of learning about the Clinical
Center. Three outcomes of the meeting were: (1) the Board's acceptance of a budget proposal for the center; (2) endorsement of a
feasibility study for the new cost accounting system; and (3) a decision to establish subcommittees. Mr. Finan noted that a cost
accounting system is critical to ensuring an effective business or activity and that the subcommittees will assist the Clinical
Center in addressing its priorities.
Since the meeting, a proposal was made to create an executive committee of the Board. It is hoped that this committee will meet
in February 1997 and proceed to establish the working groups.
Discussion
Dr. Lederberg suggested that the term "board of governors" may be confusing because the functions of the Clinical Center Board
of Governors differ from those of a corporate board in several ways. For example, the Clinical Center board does not have
fiduciary responsibility and is not self-perpetuating. The term "regents" may be more appropriate. Dr. Horwitz agreed that the
term "board of governors" was inappropriate for the NIH and should be reconsidered. Mr. Finan noted that the appropriate
terminology was discussed by the Options Team and that the aim was to indicate a greater level of responsibility than an
advisory board but not as much as a corporate board. The term "board of governors" is on the official charter but could be
changed if an alternative is recommended.
Elaborating on the interaction of the GCRCs and the Clinical Center, Dr. Gallin stated that the NIH is consulting with
NIH-supported GCRCs concerning possible legislative issues related to NIH's authorization for reimbursement of third-party
insurers. He envisaged that expanded interaction with the GCRCs could take at least two forms: making NIH's high-technology
resources accessible to the GCRCs, and making Clinical Center patients available for collaborative studies with GCRC
investigators. The NIH is exploring specific ways of accomplishing these goals. The NIH also is exploring possible
collaborations with managed care organizations for patient recruitment and sharing of patient information. Legal and ethical
issues pertaining to the privacy of patient information will be important to address in this regard.
Dr. Fuchs commented on the education of clinical researchers, noting the need to have both an M.D. and a Ph.D.-equivalent
degree. She suggested that the NIH could take the lead in establishing a graduate program directed toward clinical research. Dr.
Gallin noted that NIH's clinical research core curriculum is one step toward this but that other programs need to be developed
to train and encourage Ph.D.s to become clinical investigators. The large pool of well-trained Ph.D.s available could be a
source for this talent.
REPORT FROM THE CLINICAL RESEARCH PANEL
Overview and Introduction
Dr. David G. Nathan, President, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues reported on the NIH
Director's Panel on Clinical Research (CRP). Dr. Nathan, who chaired the panel, was joined by three panel members: Dr. Judith L.
Swain, Chair, Department of Medicine, Stanford University, California; Dr. Guy M. McKhann, Professor of Neurology and Director,
Johns Hopkins University, Baltimore, Maryland; and Dr. William T. Friedewald, Senior Vice President and Chief Medical Director,
Metropolitan Life, New York, New York. A draft Interim Report of the panel, dated 12/6/96, was distributed to the ACD for
discussion and comment.
The CRP was convened by Dr. Varmus in spring 1995 "to review the status of clinical research in the United States and to make
recommendations to the Advisory Committee to the Director, NIH, about how to ensure its effective continuance." The panel has
met four times and has reported previously to the ACD; it will continue to meet in 1997 to complete its work.
Dr. Nathan noted that clinical research, which was endangered when the panel began its work, is now in desperate straits because
of the changes occurring in academic health centers as a result of the country's movement toward a managed health care system.
These problems, he emphasized, cannot be solved by the panel or NIH alone and will require a broader partnership of interests.
NIH Funding of Clinical Research
Dr. Swain, who chaired the panel's Subcommittee on NIH Mechanisms for Funding Patient-Oriented Research, reviewed NIH's funding
of clinical research. She prefaced her remarks by saying that the perception of a lack of funding for clinical research is
indeed a reality, but that the lack of funds is more because of the external pressures facing academic health centers than
because of NIH support. Dr. Swain noted that the coverage for and time to conduct clinical research are disappearing fast in the
medical community.
As reported previously, the subcommittee and panel defined clinical research as patient-oriented research, that is
"conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for
which an investigator (or colleague) directly interacts with human subjects." The research area includes development of new
technologies, mechanisms of human disease, therapeutic interventions, and clinical trials, as well as epidemiological and
behavioral studies, outcomes research, and health services research. It does not include in vitro studies that utilize human
tissues but do not deal directly with patients.
Dr. Swain noted that the subcommittee tested the usefulness of this definition by categorizing abstracts of NIH grants, finding
an excellent concordance among the members' designations. A review of all NIH competing awards (Type 1 and Type 2) funded in FY
1996 was then instituted to ascertain the level of NIH support for clinical research. Because FY 1996 just ended in September,
all of the awards have not yet been reviewed, but the percentages obtained from analysis of approximately 7,000 awards (out of a
total of about 8,000) are informative and are not likely to change significantly.
According to Dr. Swain, the preliminary data indicate that clinical research accounts for about 30 percent of NIH's total
support for research and for research training. Specifically, in FY 1996, 26.4 percent of the competing research awards analyzed
so far were for clinical research (n = 1,818) and 73.6 percent were for nonclinical research (n = 5,073). In terms of dollars,
36.5 percent of the awards were for clinical research (amounting to about $620 million) and 63.5 percent were for nonclinical
research (~ $1.069 billion). Among competing K (career development) awards, clinical research accounts for 31 percent of the
total number and dollars awarded. The subcommittee is analyzing the research data further to determine the level of funding for
Phase I versus Phase II or Phase III clinical trials.
Based on this study, the subcommittee will be recommending, for the full panel's consideration, the following: that the NIH
Office of Extramural Research continues to code NIH awards as clinical or nonclinical research; that the level of clinical
research funding for Phase III clinical trials be determined; and that the data obtained be made available to all ICDs for use
in developing their strategic plans. Dr. Swain also noted that the subcommittee will recommend that the panel adopt the
recommendations of the NIH Working Committee on Clinical Trial Monitoring.
Discussion
Dr. Kirschner expressed concern that categorization of research grants into clinical research and nonclinical research could
evolve into thinking about the distribution of grant monies in quota terms rather than in how best to approach a scientific
problem. Dr. Swain emphasized that the subcommittee's aim was not to prescribe a percentage distribution for the NIH as a whole
or individual ICDs, but to be able to provide ICDs with ongoing information that would help them in their strategic planning.
Dr. Kirschner agreed that the data were informative but urged that NIH make clear that the data provided are for information
only. In this regard, Dr. Varmus suggested that the Committee might find it useful to hear a presentation on how the NIH sets
research priorities. He noted that the data are tremendously valuable.
Dr. Nathan pointed out that a previous Institute of Medicine study estimated that only about 5-10 percent of the NIH budget
supports clinical research. This study, conducted about 2 years ago, included both competing and noncompeting awards. Noting
that the panel's definition of clinical research influences the data obtained, Dr. Henney asked whether the broad range of
constituent groups agrees with the definition. Dr. Swain said that the subcommittee discussed the definition at length and that
the wording adopted is fairly conservative, includes all of the activities that most persons consider clinical research, and has
been well received.
Two suggestions were made for obtaining additional data. Dr. Trelstad suggested that data on the terminal degrees of the
principal investigators of NIH grants would clarify the extent to which Ph.D.s are participating in clinical research. Dr.
Perrine suggested that a breakdown of grants into the three main categories of the definition would be informative:
patient-oriented research, epidemiological and behavioral, and outcomes research and health services research. Dr. Baldwin noted
that others have requested a breakdown by mechanism of support: investigator-initiated research project grant (R01), cooperative
agreement, contract, etc.
General Clinical Research Centers and the Clinical Center
Dr. McKhann chaired the panel's Subcommittee on GCRCs and the Clinical Center. He described the subcommittee's charge as
follows: to review the status of the GCRCs; to review the Clinical Center's intramural program, particularly its interface with
non-NIH, nongovernment research; and to address the review of clinical research grant applications by NIH study sections.
Providing background for his report of the subcommittee's findings, Dr. McKhann described the GCRCs as specialized units
dedicated to the study of specific clinical problems. Serving as a base for NIH-supported clinical research, they each have the
infrastructure necessary for conducting clinical research, including inpatient and outpatient facilities as needed. Dr. McKhann
reported that the subcommittee found that the 76 GCRCs in the United States are extraordinarily valuable in promoting and
supporting clinical research and will become increasingly valuable in the future, serving as dedicated units for clinical
research.
Because of this important, expected future role, the subcommittee is recommending that the GCRCs be made available to all
clinical researchers regardless of their source of funding. Dr. McKhann stated that the subcommittee felt that limiting the
GCRCs to NIH-funded clinical research was too narrow a role for these valuable entities, especially in light of increasing
support for clinical research from industry and other non-NIH sources.
The subcommittee's other recommendations, Dr. McKhann noted, flow from this major recommended change. For example, the
subcommittee is also recommending that the directorship of GCRCs be open to non-NIH-supported clinical investigators; that the
research program of GCRCs be made more flexible to accommodate the broad range of clinical research areas and settings; that the
GCRCs' training role be expanded; and that, within academic centers, the GCRC approaches be integrated with those of clinical
trial units, which are increasingly established to interface primarily with industry. The subcommittee's full recommendations
are stated in the draft report.
Dr. McKhann said that the subcommittee will be focusing on its second charge, the interface between the Clinical Center's
intramural programs and the GCRCs, during FY 1997.
The subcommittee is addressing its third charge, the review of clinical research grant applications in NIH study sections. This
charge emanates from the perception in the extramural community that clinical research grant applications do not fare as well as
basic research grant applications in NIH's initial review groups. Dr. McKhann reported that the subcommittee endorsed the report
and recommendations of the NIH Clinical Research Study Group, which were published in November 1994. This group found, in
general, that the perception is only partly true in that the success of clinical research grant applications in a study section
is related to the amount of clinical research reviewed by that study section. On the basis of this finding and the recognition
that clinical research is especially difficult to evaluate, the subcommittee is recommending that clinical research grant
applications be assigned to study sections that are experienced in reviewing these applications.
Discussion
Several committee members commented on the advantages and disadvantages of integrating the approaches of the GCRCs with the
clinical trial units. Dr. Kandel noted that the intellectual challenges pursued in the two types of facilities differ and that
keeping GCRCs oriented to exploring mechanisms of disease rather than a single hypothesis is desirable. Dr. McKhann suggested
that an interface between the facilities would enable closer review of a trial's goals and outcomes using the review mechanisms
that already exist in GCRCs. As a model, he envisaged a clinical research consortium that includes the GCRC and clinical trial
unit as two components. Dr. Trelstad noted that such an integration could help maximize the efficiency of both activities.
In regard to the review of clinical research applications in study sections, Dr. Kandel suggested that a closer study of the
findings by the NIH working group may be needed. Dr. McKhann agreed, noting that the working group conducted its study about 3
years ago and that Dr. Swain's committee would be addressing the issue in more detail. Dr. Fuchs commented that the differences
between the study sections underscore the need for education on the nature of clinical research.
Overall Panel Recommendations
Dr. Nathan presented the panel's draft recommendations. For perspective, he noted that, in 1995 when the panel began its work,
the working definition of clinical research at the NIH was clinical trials and human subjects research. Total support for these
activities, including both competing and noncompeting awards, in FY 1995 was $5.9 billion ($1.2 billion for clinical trials and
$4.7 billion for human subjects research). Agreeing with Dr. Swain, he suggested that the level of NIH support for clinical
research is not a problem, although the strategic distribution of this support among ICDs and research areas may merit
attention.
As noted in the draft report, the panel's recommendations represent key steps for strengthening clinical research. The panel
recommends that the NIH:
describe in detail its own contributions to and impact on clinical research, as it is defined by the panel;
extend to extramural investigators the available expertise in clinical trials design and analysis found within the ICDs,
including the Clinical Center;
broaden the scope of the GCRCs to enhance their leadership role in clinical research and in research training;
ensure fair and effective reviews of extramural grant applications for support of clinical research; panels should (a) include
experienced clinical investigators and (b) review an appreciable number of such applications;
continue to improve the quality of clinical research and strengthen research management in the Clinical Center and the
availability of its resources to extramural investigators;
improve the quality of training grants for clinical researchers by requiring grantee organizations to provide formal training
experiences and careful mentoring;
initiate new support mechanisms for young and mid-term clinical investigators, if possible in collaboration with the private
sector;
initiate a medical student training program in clinical research on the NIH campus and in academic health centers in
collaboration with the private sector;
institute a limited debt reduction program for clinical investigators;
(x) continue a productive dialogue on sustaining clinical research with its partners, the academic health centers, the
foundations, and the pharmaceutical and managed care industries; and
expand efforts to educate the public about the crucial importance of clinical research for the future health of the nation.
Dr. Nathan elaborated on the recommendations emanating from the Subcommittee on Training/Job Opportunities for Patient-Oriented
Research (recommendations vi through ix above). This subcommittee was chaired by Dr. Jean D. Wilson, Professor of Internal
Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Because clinical research is becoming more complex and
difficult to perform, the panel and subcommittee emphasize the importance of training and the need for formal training that
includes a strong didactic component. New support mechanisms for newly independent and mid-term clinical investigators are
needed as well to supplant the loss of coverage in academic health centers and to ensure that investigators who are already
trained can continue and progress in their research careers. Collaborations with the private sector, particularly pharmaceutical
agencies and foundations, could be fruitful in this regard.
Dr. Nathan noted that the recommendation for a medical student training program in clinical research is crucial and can be
expected to yield the same rewards as the medical student training program in basic research, referred to earlier by Dr. Varmus,
which is supported by the NIH and the Howard Hughes Medical Institute. He commented that his own experience as a young clinical
associate at the NIH turned him on to clinical research and engendered a lifetime career. Dr. Nathan also noted that a
particular problem for clinical investigators, and a deterrent to their pursuing a research career, is the debt they accumulate
with their education. The panel recommends an attractive solution: a limited debt forgiveness program for M.D.s who complete a
minimal time (e.g., 5 years) of full-time (at least 80 percent) clinical investigation. This program would enable M.D.s to
obtain training and a Ph.D. in a discipline relevant to clinical research, potentially yielding a greater supply of
better-trained clinical investigators. The full recommendations of the subcommittee are presented in the draft report.
In closing, Dr. Nathan said that the recommendations pertaining to training and GCRCs are mostly complete. During the next year,
the panel will refine the data on NIH funding of clinical research, assess clinical research priorities within and across ICDs,
and focus on partnership issues.
Discussion
Dr. Maupin urged that the proposed medical student training program include dental students, which Dr. Nathan noted is the
intent of the panel's recommendation. Commenting on the vital role that GCRCs have played in fostering quality research, Dr.
Carey emphasized that the quality of clinical investigation must be kept at the forefront when making the changes proposed.
Public Information and Non-NIH Funding Sources
Dr. Friedewald, who chaired the panel's Subcommittee on Funding Sources and Public Information, emphasized several items not
previously addressed by the presenters. He noted that, too often, dissemination of information to the public on the importance
and results of medical research is overlooked. Yet, surveys repeatedly show that the public is very supportive of clinical
research. More and better dissemination efforts are needed to build on this base of support. During the next year, the
subcommittee will address this need.
Most of the subcommittee's work up to now has been to understand the magnitude of non-NIH sources of funding. Dr. Friedewald
said that the subcommittee has attempted to comprehend the extent of this funding by undertaking a number of surveys (e.g., of
academic health centers) and by meeting with industry and foundation representatives. He noted that the full magnitude is not
known and that the largest unknown component, which is most threatened currently, is the funding of clinical research from
patient care services offered in academic health centers--a source of funds that is being redistributed to managed care
organizations seeking to constrain health care costs. Another component that is also threatened and even more difficult to
estimate is the in-kind contribution of research and research training time by clinical investigators who increasingly have to
dedicate more of their time to patient care and less to research and research training.
Dr. Friedewald emphasized that, even though non-NIH sources of funding appear to be very large and substantial components are
seriously threatened, "there is no pot of gold out there just waiting to be tapped." Partnerships involving the NIH, private
industry, foundations, and other nonprofit organizations are needed to sustain effective levels of funding for clinical
research. Existing partnerships should be strengthened and new partnerships (e.g., with managed care organizations) must be
forged.
Discussion
Dr. Hogan urged that more attention be given to the problems faced by academic health centers and the integrity of the entire
research enterprise which is being threatened by increased concentration of commercial managed care, reductions in Medicare and
Medicaid, cutbacks in VA hospitals, and other factors. Noting that investments in research result in new approaches to
prevention and improved treatments, Drs. Graham and Kirschner said that this message needs to be communicated widely and
particularly to managed care organizations.
Dr. Lander emphasized the need to determine the amount of dollars being lost from the research enterprise and to develop
solutions (e.g., trust funds) for replacing these lost resources. Dr. Varmus commented that the managed care organizations that
have met with the NIH already are engaged in research and also would be interested in providing resources to a common research
fund. Another partner in this effort, which NIH also is approaching, is the major employers, who pay for health insurance plans.
Dr. Varmus also noted that the Office of Science and Technology Policy is simultaneously addressing the issue of managed care
and its effects on clinical research.
Time, as well as funding, is a key issue for clinical researchers. Dr. Kirschner also emphasized the need to provide physicians
the opportunity (i.e., time) to conduct research; if given time, even without funding, clinical researchers will do research.
Dr. Lander suggested that managed care organizations could be encouraged to allow for "pro bono" research time in the same way
as the legal community does.
Dr. Beck commented that many of the research and training issues facing M.D. researchers also challenge nurse investigators and
she asked whether the panel had addressed nursing research interests in its discussions. Dr. Nathan said that the panel had not
done so yet but that it would be important to do so.
In closing, Dr. Nathan emphasized that the panel viewed its role as one of encouraging dialogue among potential research
partners and, in order to not hamper its work, has been very cautious about taking a particular stance on the issues being
discussed.
OAR IMPLEMENTATION OF LEVINE REPORT
Dr. William E. Paul, Associate Director for AIDS Research, NIH, presented an update on NIH's implementation of key
recommendations in the Levine Report. This report, issued in March 1996, was prepared by the NIH AIDS Research Program
Evaluation Working Group of the Office of AIDS Research Advisory Council, which was chaired by Dr. Arnold Levine of Princeton
University. The working group reviewed AIDS research activities sponsored and conducted by the NIH over the past several years,
evaluated their effectiveness in seizing opportunities and meeting challenges, and made recommendations for future research
activities.
In the past 2 years, during and since the working group's deliberations, remarkable advances have been made in AIDS research.
Dr. Paul noted that these advances are the fruits of investments made by the NIH and the pharmaceutical industry and that they
influence implementation of the working group's recommendations. The five major recent advances he highlighted are as follows:
Introduction of protease inhibitors, a new class of antiretroviral drugs, which when used in combination with reverse
transcriptase inhibitors, significantly lowers the amount of HIV in affected individuals for extended periods of time
Ability to measure viral load (i.e., the amount of virus in the blood), which is a substantially better predictor of the
future course of disease than any other available measurement
Increased knowledge of the dynamics of viral replication
Recognition of chemokine receptors which, together with CD4 receptors, act as coreceptors for HIV entry into cells
Demonstration of effective prevention measures in Thailand (including the use of condoms) that have diminished transmission of
HIV infection substantially in that country.
As Dr. Paul noted, these remarkable research contributions represent the work of many investigators working together and have
enormous public health significance. They are in many ways unprecedented and offer exciting ways for improving and evaluating
treatment. Despite these advances, however, the scourge of AIDS marches on. The World Health Organization now estimates that
approximately 29 million persons are infected with HIV worldwide and that 3.1 million individuals were newly infected during the
past year. The regions with the largest number of infected individuals are sub-Saharan Africa, Southeast Asia, Latin America,
and parts of South America, and substantial epidemics are projected to occur in China and the Newly Independent States of the
former Soviet Union. To combat the extent and spread of HIV infection in these countries, low-cost and broadly applicable
interventions will be needed.
Addressing the recommendations in the Levine Report, Dr. Paul outlined the implementation steps that NIH has taken. These are
summarized for each recommendation as follows:
Investigator-Initiated Research -
Increase support for and improve peer-review of investigator-initiated research
NIH anticipates an increase in the number, as well as the funding, of R01 research grants of approximately 40 percent between
FY 1994 and FY 1997. In addition, the Office of AIDS Research (OAR) will explore with the Division of Research Grants and
other NIH components ways of improving peer review within the existing peer review structure.
Vaccine Research - Establish a restructured trans-NIH vaccine research effort
NIH plans to increase funding for vaccine research by approximately 18 percent between FY 1996 and FY 1997 (from approximately
$109 million to about $129 million). As part of this increase, $6 million will be added to the budget of the National
Institute of Allergy and Infectious Diseases (NIAID) to support a restructured vaccine program. In addition, the OAR is
holding $1 million of its own budget in reserve to support new vaccine research initiatives.
Most importantly, the
NIH has persuaded Dr. David Baltimore to lead a comprehensive, trans-NIH vaccine effort. Dr. Baltimore, an eminent virologist
and leading molecular immunologist, will chair the AIDS Vaccine Research Committee that the NIH has established as recommended
by the working group. Dr. Baltimore will serve as a consultant to the NIH, working within NIAID.
Research on the Human Immune System -
Augment research efforts to better understand the human immune system
NIH anticipates an increase in R01 research grants. In addition, OAR plans to make human immunology an investment area for FY
1997 and FY 1998.
HIV Prevention Science - Develop a comprehensive NIH HIV Prevention Science Agenda
NIH has established a Prevention Science Working Group, as urged in the Levine Report. This working group is chaired by Dr.
Jim Curran, Dean, School of Public Health, Emory University, Atlanta, Georgia. The group has met and developed a plan that
will be forwarded to the ICDs. In addition, the OAR has held $6 million of its budget in reserve to transfer to ICDs to
support prevention initiatives.
Clinical Trials - Integrate all adult clinical trial programs into a single network
NIH has initiated very active discussions for creating a unified clinical trials agenda that will utilize both academic and
community clinical trial sites most effectively and promote coordination of trials for AIDS-related complications. Dr. Paul
noted that full implementation of this recommendation will take time because of the organizational complexity involved in
integrating the many independent networks for HIV and AIDS that exist.
Drug Discovery Research - Refocus and restructure the drug discovery recovery effort
The National Cancer Institute (NCI) has established an ad hoc panel to review its Developmental Therapeutics Program.
Regional Primate Centers -
Reorganize procedures to ensure that centers are available and responsive to non-center-affiliated scientists
The FY 1997 budget for the National Center for Research Resources (NCRR) includes a $2.5 million increase for expanding access
to the centers for outside investigators. In addition, NCRR has established a peer review process for NCRR-supported
collaborative research project grants involving the centers and has initiated an in-depth review of the centers' operations
and activities.
Discussion
Dr. Varmus said that the NIH is pleased with the direction provided by the Levine Report and is very enthusiastic about pursuing
the new opportunities available. Commenting on the use of the nation's resources, Dr. Trelstad noted that the $1.5 billion
proposed for HIV/AIDS research in the FY 1997 NIH budget and the $0.6 billion allocated to support GCRCs pale in comparison with
U.S. expenditures for leisure items such as microwave popcorn and sunglasses. These types of data suggest the need for education
and information to inform the public about the benefits of biomedical and behavioral research. Commenting on Dr. Baltimore's
appointment, Drs. Kirschner and Kandel commended the NIH for continuing to bring quality leadership to the campus.
VARIOUS REVIEWS OF THE INSTITUTES, CENTERS, AND DIVISIONS
Overview and Introduction
In the past 2 years, the NIH has taken a close look at its organization and functions. Part of this effort has been a continuing
series of reviews of the operations and activities of the ICDs. Extramural and intramural scientists, as well as administrative
staff, are participating in this process. Most recently, an external advisory panel reviewed international programs and
activities of the NIH and, specifically, the Fogarty International Center (FIC). This advisory panel was cochaired by Dr. Joshua
Lederberg, Rockefeller University, and Dr. Barry Bloom, Albert Einstein College of Medicine.
As an introduction to Dr. Lederberg's presentation of the panel's report, Dr. Varmus commented on the status of other reviews.
An extensive review of the NCI's intramural program was completed within the past year and a half, and a very active review of
the National Institute of Mental Health's intramural program is under way. The report from the latter review panel, which is
chaired by Dr. Herbert Pardes, is expected in January. Intramural program reviews for four additional institutes are being
organized and will probably begin in January. These institutes are: the National Institute on Aging, the National Institute of
Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the
National Institute on Drug Abuse. Each review is expected to take about 8 months and will result in a report that will be
presented to the ACD. Dr. Varmus noted that each committee includes one ACD member.
Dr. Varmus also described a second review initiative. For this activity, he is organizing small committees to review the
performance of ICD directors in order to provide feedback to the directors from their constituent groups. Each committee
includes a member of the advisory council or board for the ICD. Review committees have already been established for the National
Eye Institute; National Heart, Lung, and Blood Institute; and NIAID. Committees are being established for the National Library
of Medicine, National Institute of Child Health and Human Development, National Institute of Diabetes and Digestive and Kidney
Diseases, and NIAAA. Dr. Varmus noted that a similar review of his own performance is conducted each year by the ICD directors.
The review of NIH/FIC international programs began in March 1996. Dr. Varmus noted that he has a strong personal interest in
international science and health activities and wanted to be sure that NIH is maximizing the international dimensions of its
research efforts and that the FIC is playing an effective role in these activities. On this note, he invited Dr. Lederberg to
present the report of the External Advisory Panel to Review NIH/FIC International Programs.
NIH/FIC International Programs
Dr. Lederberg said that the panel focused on structural, rather than performance, issues of how NIH conducts international
activities. The panel met on two occasions and was advised by NIH staff, international staff from other DHHS components, and
grantees. The panel's report, dated September 16, 1996, consists of an overview of NIH international activities and the panel's
recommendations.
Dr. Lederberg summarized the panel's recommendations and conveyed some of the context of the panel's deliberations. He reported
that the panel intensely felt that the NIH could not fulfill its mission without attending carefully to global problems,
information, resources, and cooperation. The members concluded that the FIC should be retained as a separate unit of the NIH
because of its history and name recognition worldwide.
Several aspects of NIH's international programs made a particular impression on Dr. Lederberg. He emphasized, for example, that
the ICDs account for probably 90 to 95 percent of NIH's total expenditures on international programs and that the largest
component is the Visiting Program of foreign scientists and researchers in NIH's intramural laboratories. These foreign
investigators represent about one-third of the NIH's intramural science staff. Dr. Lederberg noted that this program is an
indispensable training activity for both U.S. and foreign scientists, enables the scientific community to benefit from
cross-cultural input, and links the NIH with the global research community.
The FIC provides essential administrative support for the Visiting Program, which, as Dr. Lederberg noted, the NIH staff
indicated was FIC's most important and visible activity. A modest amount of funds is administered directly by the FIC for other
international activities; however, because most of NIH's international activity is housed in the ICDs, it is very largely
discipline-oriented. The panel found that the NIH staff guiding these activities had the necessary vision and leadership for the
task. The panel also noted that the FIC could serve to focus NIH's international efforts, provide inspiration, and point to
unsatisfied opportunities. To assure still more effective coordination, the panel recommended that an Associate Director for
International Research be appointed who would report directly to the Director, NIH, and also serve as Director, FIC.
In the remaining recommendations, as noted by Dr. Lederberg, the panel strongly endorsed the concept and performance of certain
FIC programs and urged careful review and possible reduction of other FIC programs. In particular, the panel felt that the need
for a Scholars-in-Residence program had diminished. In closing, Dr. Lederberg encouraged the Committee to review the panel's
overview and recommendations.
Discussion
Dr. Fuchs commented that the panel's report, which conveys the small amount of dollars spent on much of the world's health
problems, could serve to stimulate new initiatives and resources for international research on global problems that initially
appear to be geographically restricted. One example is emerging infectious diseases. Dr. Varmus noted that the National Science
and Technology Council's Committee on International Science, Engineering, and Technology has prepared a report on emerging
infections and global health and that the report contains specific recommendations for enhanced research activities. The DHHS,
at the direction of Secretary Shalala and with input from NIAID, has suggested specific initiatives in this area for the FY 1998
budget. Dr. Lederberg emphasized that discipline-oriented research is needed to gain insight on such international health
problems and that this research should be supported through the ICDs, with the FIC providing important negotiating,
coordinating, and diplomatic skills.
The Committee focused on the rationale for retaining the FIC as a separate NIH component. Noting that most of NIH's
international activity is conducted within the ICDs, Dr. Kirschner suggested that FIC's specialized administrative functions,
such as its visa services for the Visiting Program, does not require a separate NIH center and could be handled within a smaller
NIH office. Dr. Lederberg agreed that alternative arrangements were possible. He noted, however, that the panel received
overwhelming advice to retain the FIC in name and structure and that the FIC can play an important coordinating, trans-NIH role.
Dr. Johnson asserted that the FIC has made a valuable contribution already in providing NIH an international focus for research
and research training. The panel recognized this contribution, he noted, by its endorsement of several programs, including FIC's
AIDS International Training and Research Program, which is already a model for similar international efforts to combat other
health problems. Dr. Prendergast strongly favored retaining the FIC as a separate center and expanding its activities and
resources. Dr. Fuchs suggested that the FIC needs to achieve greater visibility nationally and worldwide for its international
efforts.
Closing the discussion, Dr. Varmus said that his next step will be to consider the recommendation to recruit an associate
director for international health research.
DISCUSSION OF SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) GRANTS
Dr. Wendy Baldwin, Deputy Director for Extramural Research, NIH, summarized NIH's support of two extramural programs for small
businesses: the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. On January 22,
1997, the NIH is convening a meeting to assess the effectiveness of these programs and to identify strategies for strengthening
them. Emphasis will be given to quality issues, and potential topics include the following: outreach activities, administrative
features, composition of review groups, and streamlining applications.
Providing background on these programs, Dr. Baldwin stated that the SBIR program, which is congressionally mandated by the Small
Business Innovative Research Act, began in 1982. A defining and unusual characteristic of the SBIR/STTR programs is their
funding, which is established as a percentage of NIH's research budget. The total percentage has increased from 1.25 percent to
2.0 percent in FY 1996 and is slated to rise to 2.5 percent in FY 1997. The STTR program is a very small part of this overall
percentage (0.1 percent in FY 1996) and has been operating for only about 2 years. One advantage of the STTR is that the
principal investigator can be in a university, whereas the principal investigator for an SBIR award must spend a majority of
time (51 percent) in the small business. Both programs are transgovernmental and many of their features are set by the Small
Business Administration (SBA), not the NIH.
SBIR/STTR awards can be Phase I or Phase II awards. Phase I awards, essentially for planning a project, are made for 6 months
and do not exceed $100,000; Phase II awards, for conducting a project, cannot exceed 2 years or $500,000 in total costs.
Although most awards are grants, a few are research contracts. Dr. Baldwin noted that the review criteria for SBIR/STTR awards
are the same as for NIH's research project grants but also include the potential for technological innovation and the potential
for commercial application. Most applications are reviewed by the Division of Research Grants.
Addressing quality issues, Dr. Baldwin noted that the success rates for SBIR applications is higher than for R01s and, in the
past, has jumped even higher when funding for the program has increased. To ensure that only the best research continues to be
funded in FY 1997, the NIH has taken some preemptive steps. These include the "250 rule": Applications that an ICD
wishes to fund but that receive scores worse than 250 must be reviewed by the NIH Office of Extramural Research (OER), and
applications that an ICD cannot fund but that receive scores better than 250 can be forwarded to OER for brokering among other
ICDs.
In closing, Dr. Baldwin invited the Committee members to attend the January 22 meeting and to communicate their ideas about
these programs to her. She anticipated that abstracts of SBIR/STTR projects supported by the NIH will be online, for easy
access, by spring 1997.
Discussion
Dr. Kirschner asked about the goals and expected outcomes of the meeting and, specifically, if the participants would be
considering whether the SBIR/STTR programs are needed and deserve NIH support. Noting that the program has been successful and
is accomplishing its purposes (translating research findings into commercial products), Dr. Baldwin said that the main goal of
the meeting is to find ways to strengthen the dialogue and linkage between the basic science and small business communities. Two
evaluations, conducted separately by the Government Accounting Office and the SBA, confirm the success of the programs in terms
of rates of commercialization and value of the products sold.
Pursuing Dr. Kirschner's question, Dr. Yamamoto suggested that NIH's resources may not be needed in this area, because of
venture capital support for biotechnology development, and could be better spent on research project grants for young
investigators. Dr. Varmus noted that SBIR/STTR expenditures are legislatively mandated and therefore are not "skimmed
off" the NIH budget for research grants. Dr. Lander and others emphasized the need to develop appropriate indicators for
measuring the success of the programs and to ensure that the individuals who review SBIR/STTR applications have experience and
perspective related to the review criteria.
ADVICE ON NIDA GRANT AWARD
Introducing this agenda topic, Dr. Varmus said that he had received a letter from Public Citizen's Health Research Group in
October raising concerns about a grant that had been recently approved and funded by the National Institute on Drug Abuse
(NIDA). Because the charges were serious and the issues are of substantial public health importance, he sought independent
advice from an expert panel and asked the investigator to postpone initiation of the study until the ACD had an opportunity to
review and comment on the study. Dr. Robert J. Levine of Yale University and Dr. Ting-Kai Li of the ACD cochaired the expert
panel. Drs. Li and Levine presented the panel's final report, dated December 12, 1996, to the Committee.
Dr. Li described the proposed study. The grant, entitled "Interventions to Reduce Hepatitis B, Hepatitis C, and HIV in
Intravenous Drug Users," is 1 of 15 research projects on needle exchange and 3 on needle hygiene that have been funded by
NIDA since 1991. It is thought that needle exchange programs, by increasing the supply of sterile needles in circulation, can be
effective in preventing the spread of HIV and other blood-borne viral infections while not increasing the use of illicit drugs.
Dr. Li noted that the research literature does not fully support this thought, largely because of methodological problems in the
studies reported. Issues include selection and recruitment bias, experimental and control groups that may not be comparable,
unspecified comparison and control conditions, and crossover between the experimental groups or secondary distribution of
needles between groups.
The proposed study, a randomized controlled clinical trial of current and former users of injected drugs, will compare two
groups. Dr. Li summarized the study design and data analysis approach.
The panel that was convened by Dr. Varmus to review the study included experts in bioethics, clinical research, and substance
abuse, especially intravenous drug use. They addressed three sets of questions:
Given current knowledge, is the study design appropriate?
Are the interventions provided to the control group adequate? Are the subjects in the control intervention being treated
appropriately?
Were appropriate procedures followed in the review of the study's scientific merits and its plans for protection of human
subjects?
Dr. Levine summarized the panel's review process and presented its findings and recommendations. The members assessed the merits
of the study, addressed Dr. Varmus's questions and concerns raised about the study, and closely reviewed the extensive published
literature on needle exchange. Since the first needle-exchange program in Amsterdam in 1984, hundreds of similar programs have
been established in different areas of the world, including more than 100 programs in North America, and many studies have been
conducted of these programs.
Based on this literature, the panel found no reason to challenge the prevailing belief that needle exchange is effective in
reducing transmission of blood-borne diseases. As Dr. Li noted previously, conflicting data are reported but are apparently
attributable to methodological difficulties. Now is the time, according to Dr. Levine, to address second-generation questions
such as what is the best way of making clean, sterile needles available to individuals who need them. In 1995, a National
Academy of Sciences committee reviewing needle exchange and pharmacy access to sterile needles recommended use of both
approaches. The proposed NIH study would be the first to evaluate systematically the safety, efficacy, and effectiveness of
these two approaches.
Dr. Levine summarized the panel's findings with respect to the appropriateness of the study design, treatment of comparison
groups, and research review process and concluded:
the proposed study design is scientifically and ethically appropriate;
the interventions to be provided to both groups are adequate, and the subjects in both groups will be treated appropriately;
and
the previous reviews of this study's scientific merits and plans to protect human subjects followed appropriate procedures.
Discussion
Dr. Lander commended everyone involved in initiating, organizing, and conducting the review of the proposed study. He applauded
the process as a wonderful example of how public concerns and serious issues can be addressed and resolved expeditiously. Dr.
Lander agreed that the study should go forward because it promises to provide the scientific data needed to inform public policy
regarding needle exchange versus enhanced pharmacy access.
One serious ethical issue raised by Drs. Lander and Kirschner is whether the participants in the study will be offered
immunization against hepatitis B virus (HBV). Although this procedure has not been established as a standard of care and is not
routinely provided to participants in other studies or programs, clinical investigators have special responsibilities to the
participants in their studies. Dr. Levine stated that there is no ethical reason for providing more access to HBV vaccine than
is available in any other setting and that the participants will receive vouchers for, and educational information on, HBV
immunization. He noted further that the panel reviewed the study as proposed and did not address possible alternative research
designs, for example, to determine the effect of income and cost on the purchase of needles from a pharmacy. Dr. Dennis Fisher,
the principal investigator for the study, said that preliminary data indicate that income and cost are not predictors of drug
injection or needle sharing, but that economic data will be collected in the study.
Ms. Eisenberg agreed with Dr. Lander that the study is worthwhile. She expressed concern, however, that former intravenous drug
users may be vulnerable to relapse and inadvertently be lured back into drug use by the needle-exchange program. Dr. Levine
noted that the panel considered this possibility but found the design to be ethically justified because former intravenous drug
users are part of the same community as current intravenous drug users and are fully aware of the availability of needles and
other drug materials.
Dr. Fuchs noted that ethics is the key issue surrounding this study and that the panel has dealt with this issue effectively and
expeditiously. She strongly urged that other cases that could similarly influence public policy be handled in the same manner.
Dr. Kandel agreed, noting that the panel's report provides a clear statement of the issues involved and independently confirms
the findings of the initial review group. Dr. Needleman also agreed that the study is worthwhile because of the societal value
of its implications, but that it will probably need to be replicated in other settings because it will be conducted in Alaska, a
relatively isolated environment.
GENERAL DISCUSSION
Dr. Varmus invited the participants to suggest topics that he could relay to Secretary Shalala as possible initiatives for the
next 4 years. Referring to the Committee's previous discussion, Dr. Phillips suggested that the Department could engage in a
visible dialogue with the American public on the issues facing clinical research, managed care, and academic health centers. A
second topic is alternative medicine which, he noted, is growing in popularity while conventional medicine is facing increasing
regulation.
Dr. Kandel proposed that the Secretary consider celebrating the enormous achievements that have been made in biology over the
past 50 years and the impact of these achievements on health care. He also noted that he will be proposing to her a health
education and science education linkage that could be useful for promoting public health and recruiting individuals into science
and technology careers. Dr. Brookhouser suggested that the Secretary highlight the tremendous advances made in vaccine
technology and educate the public about the importance and availability of these vaccines.
In closing, Dr. Varmus invited the Committee members to send to him additional suggestions and agenda topics for the next
meeting.
The meeting adjourned following this discussion.
SUMMARY AND CONCLUSIONS
The Advisory Committee to the Director (ACD), NIH, joined by representatives of the National Advisory Councils and Boards of the
NIH Institutes, Centers, and Divisions, met on December 12, 1996, to consider an update on the Warren G. Magnuson Clinical
Center, a report from the NIH Director's Panel on Clinical Research, implementation of the recommendations of the NIH AIDS
Research Program Evaluation Working Group (contained in the "Levine Report"), a discussion of NIH's small business research
activities, an external advisory report on NIH/FIC international activities, and an expert panel's advice on a NIDA grant award.
The ACD provided comments, suggestions, and advice on these subjects and learned of the governmental changes being made after
the election, the status of NIH budget appropriations and various legislative bills, recent NIH activities, and significant
research accomplishments. The ACD also suggested topics that could serve as specific initiatives for DHHS during the next
several years.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Ruth L.
Kirschstein, M.D., Executive Secretary, Advisory Committee to the Director, NIH
Harold Varmus, M.D. Director,
NIH
ACRONYMS
AAU
American Association of Universities
ACD
Advisory Committee to the Director
AIDS
Acquired Immunodeficiency Syndrome
CRP
Clinical Research Panel
DHHS
U.S. Department of Health and Human Services
FIC
Fogarty International Center
FY
Fiscal year
GCRCs
General Clinical Research Centers
HBV
Hepatitis B virus
HIV
Human Immunodeficiency Virus
IC
Institute or Center
ICD
Institute, Center, and Division
IRTA
Intramural Research and Training Award
NBAC
National Bioethics Advisory Commission
NCI
National Cancer Institute
NCRR
National Center for Research Resources
NIAAA
National Institute on Alcohol Abuse and Alcoholism
NIAID
National Institute of Allergy and Infectious Diseases
NIDA
National Institute on Drug Abuse
NIH
National Institutes of Health
OAR
Office of AIDS Research
OER
Office of Extramural Research
RAC
Recombinant DNA Advisory Committee
REGO
Reinvention of Government
RM&S
Research Management and Support
SBA
Small Business Administration
SBIR
Small Business Innovation Research
STTR
Small Business Technology Transfer
VA
Department of Veterans Affairs
APPENDIX A - AGENDA
8:30 a.m.
Welcome and Opening Remarks
Dr. Harold Varmus
9:30 a.m.
Clinical Center Update
Dr. Helen Smits, Mr. John Finan, Dr. John Gallin
10:15 a.m.
Coffee Break
10:30 a.m.
Report from the Clinical Research Panel
Dr. David Nathan, Dr. William Friedewald, Dr. Guy McKhann, Dr. Judith Swain
11:30 a.m.
Discussion
11:45 a.m.
OAR Implementation of Levine Report
Dr. William Paul
12:30 p.m.
Discussion
12:45 p.m.
Lunch
1:45 p.m.
Discussion of Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Grants
Dr. Wendy Baldwin
2:15 p.m.
Various Reviews of the Institutes, Centers, and Divisions
Dr. Harold Varmus, Dr. Joshua Lederberg
2:45 p.m.
Advice on NIDA Grant Award
Dr. Ting-Kai Li, Dr. Robert Levine
3:30 p.m.
Discussion
4:00 p.m.
Adjournment
APPENDIX B - ADVISORY COMMITTEE TO THE DIRECTOR
Harold Varmus, M.D., Chairman Director, National Institutes of Health The Shannon Building, Room 126 Bethesda, MD
20892
Ezra C. Davidson, Jr., M.D. Professor and Chairman Department of Obstetrics and Gynecology King/Drew Medical
Center Los Angeles, CA 90059
Rebecca S. Eisenberg, J.D. Professor of Law University of Michigan Law School Ann Arbor, MI 48109-1215
Norman C. Francis President Xavier University of Louisiana New Orleans, LA 70125-1098
Elaine V. Fuchs, Ph.D. Amgen Professor of Basic Sciences The University of Chicago Department of Molecular
Genetics & Cell Biology Chicago, IL 60637
Ruby P. Hearn, Ph.D. Senior Vice President The Robert Wood Johnson Foundation Princeton, NJ 08543-2316
Jane E. Henney, M.D. Vice President for Health Sciences Health Sciences Center University of New Mexico Albuquerque,
NM 87131
Susan B. Horwitz, Ph.D. Professor Department of Molecular Pharmacology Albert Einstein College of Medicine Bronx,
NY 10461
Eric R. Kandel, M.D. Professor Division of Neurobiology and Behavior Columbia University New York, NY
10032-2603
Marc W. Kirschner, Ph.D. Professor and Chair Department of Cell Biology Harvard Medical School Boston,
MA 02115
Eric S. Lander, Ph.D. Professor Department of Biology Massachusetts Institute of Technology Whitehead
Institute Cambridge, MA 02139
Joshua Lederberg, Ph.D. Professor The Rockefeller University New York, NY 10021-6339
Ting-Kai Li, M.D. Distinguished Professor of Medicine and Biochemistry Indiana University School of Medicine Indianapolis,
IN 46202-5124
Jane A. Menken, Ph.D. UPS Foundation Professor in the Social Sciences Population Studies Center and Department of
Sociology University of Pennsylvania Philadelphia, PA 19104-6298
Philip Needleman, Ph.D. Senior Vice President Monsanto Company St. Louis, MO 63167
Baldomero M. Olivera, Ph.D. Professor Department of Biology University of Utah College of Science Salt
Lake City, UT 84112
Larry L. Smarr, Ph.D. Director National Center for Supercomputing Applications University of Illinois Champaign,
IL 61820
Executive Secretary Ruth L. Kirschstein, M.D. Deputy Director National Institutes of Health Bethesda,
MD 20892
APPENDIX C - ADVISORY COUNCIL AND BOARD REPRESENTATIVES
Cornelia M. Beck, Ph.D. (Member, National Advisory Council for Nursing Research) Associate Dean for Research and
Evaluation University of Arkansas for Medical Sciences Little Rock, AR 72205
Patrick E. Brookhouser, M.D. (Member, National Deafness and Other Communication Disorders Advisory Council) Director Boys
Town National Research Hospital Omaha, NE 68131
Robert M. Carey, Ph.D. (Member, National Advisory Research Resources Council) Dean University of Virginia
School of Medicine Charlottesville, VA 22908
John Donelson, Ph.D. (Member, Fogarty International Center Advisory Board) Distinguished Professor University
of Iowa School of Medicine Iowa City, IA 52242
Sid Gilman, M.D. (Member, National Advisory Neurological Disorders and Stroke Council) Professor and Chairman Department
of Neurology University of Michigan School of Medicine Ann Arbor, MI 48109-0316
Doyle G. Graham, M.D., Ph.D. (Member, National Advisory Environmental Health Sciences Council) Professor and
Chair Department of Pathology Vanderbilt University Medical Center Nashville, TN 37232-2562
Diane L. Hatchell, Ph.D. (Member, National Advisory Eye Council) Duke University Eye Center Durham, NC 27710
Michael F. Hogan, Ph.D. (Member, National Advisory Mental Health Council) Director, Ohio Department of Mental
Health Columbus, OH 43215
Warren D. Johnson, Jr., M.D. (Member, National Advisory Allergy and Infectious Diseases Council) B.H. Kean
Professor of Tropical Medicine and Infectious Diseases Department of Medicine Cornell University Medical
College New York, NY 10021
Reese T. Jones, M.D. (Member, National Advisory Council on Drug Abuse) Professor of Psychiatry University of
California, San Francisco San Francisco, CA 94143
John E. Maupin, Jr., D.D.S. (Member, National Advisory Dental Research Council) President, Meharry Medical
College Nashville, TN 37208
M. W. Perrine, Ph.D. (Member, National Advisory Council on Alcohol Abuse and Alcoholism) Director and Senior
Scientist Vermont Alcohol Research Center Colchester, VT 05466
Steven J. Phillips, M.D. (Member, Board of Regents of the National Library of Medicine) Senior Heart Surgeon Iowa
Heart Center Mercy Hospital Medical Center Des Moines, IA 50312-1946
Don W. Powell, M.D. (Member, National Diabetes and Digestive and Kidney Diseases Advisory Council) Chairman Department
of Internal Medicine The University of Texas Medical Branch Galveston, TX 77550
Franklyn G. Prendergast, M.D., Ph.D. (Member, National Advisory General Medical Sciences Council) Professor Department
of Biochemistry and Molecular Biology Mayo Clinic Rochester, MN 55905
Robert R. Recker, M.D. (Member, National Arthritis and Musculoskeletal and Skin Diseases Advisory Council) Professor,
Department of Medicine Creighton University School of Medicine Omaha, NE 68131
Barbara K. Rimer, Dr.P.H. (Member, National Cancer Advisory Board) Professor, Community and Family Medicine Director,
Cancer Prevention, Detection and Control Research Duke Comprehensive Cancer Center Durham, NC 27705
Judith L. Swain, M.D. (Member, National Heart, Lung, and Blood Advisory Council) Arthur L. Bloomfield Professor of
Medicine Chair, Department of Medicine Stanford University Stanford, CA 94305
Robert L. Trelstad, M.D. (Member, National Advisory Child Health and Human Development Council) Chairman,
Department of Pathology Robert Wood Johnson Medical School Piscataway, NJ 08854
John Q. Trojanowski, M.D., Ph.D. (Member, National Advisory Council on Aging) Professor, Department of Pathology
and Laboratory Medicine University of Pennsylvania School of Medicine Philadelphia, PA 19140-4283
David Valle, M.D. (Member, National Advisory Council for Human Genome Research) Professor of Pediatrics Johns
Hopkins University School of Medicine Baltimore, MD 21206
Keith R. Yamamoto, Ph.D. (Member, Division of Research Grants Advisory Committee) Chair, Department of
Pharmacology University of California, San Francisco School of Medicine San Francisco, CA 94143-0450
APPENDIX D - PRESENTERS
Wendy Baldwin, Ph.D. Deputy Director for Extramural Research National Institutes of Health Bethesda, MD 20892
John Finan President and CEO FMOL Health System Baton Rouge, LA 70809
William T. Friedewald, M.D. Senior Vice President & Chief Medical Director Metropolitan Life New York, NY
10010
John I. Gallin, M.D. Director, Warren Grant Magnuson Clinical Center National Institutes of Health Bethesda,
MD 20892
Joshua Lederberg, Ph.D. Professor The Rockefeller University New York, NY 10021
Robert J. Levine, M.D. Professor of Medicine Yale University New Haven, CT 06520
Ting-Kai Li, M.D. Distinguished Professor of Medicine and Biochemistry Indiana University School of Medicine Indianapolis,
IN 46202
Guy M. McKhann, M.D. Professor of Neurology and Director Zanvyl Krieger Mind/Brain Institute Johns Hopkins
University Baltimore, MD 21218
David Nathan, M.D. President Dana-Farber Cancer Center Boston, MA 02115
William E. Paul, M.D. Associate Director for AIDS Research National Institutes of Health Bethesda, MD 20892
Helen Smits, M.D. President and Medical Director HealthRight Meridan, CT 06450
Judith L. Swain, M.D. Arthur L. Bloomfield Professor of Medicine Chair, Department of Medicine Stanford
University Stanford, CA 94305
APPENDIX E - RELATED REPORTS
"Opportunity: Revitalizing the NIH Clinical Center for Tomorrow's Challenges," Report of the Reinvention of
Government (REGO) II Options Team
Interim Report of the NIH Director's Panel on Clinical Research (CRP)
Report of the NIH AIDS Research Program Evaluation Working Group of the Office of AIDS Research Advisory Council
Report of the External Advisory Panel to Review NIH/FIC International Programs
Report to the Advisory Committee to the Director of the Panel to Review the Aspects of the Study "Interventions to Reduce
HBV, HCV and HIV in IDUs"
Copies of these reports are available upon request. Call (301) 496-0959.
