The 81st meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December
7, 2000. Dr. Ruth Kirschstein, Principal Deputy Director, NIH, welcomed six new members to the committee, thanked several other
members for their recent service on subcommittees and working groups, reviewed several matters concerning personnel changes at
NIH, and acknowledged the recent receipt by NIH grantees of several prestigious awards. She provided the ACD members with an
update on the progress in developing the NIH Clinical Trials Database and on various developments involving clinical trials, the
protection of research subjects, efforts to manage or eliminate conflicts of interest, and the publication of several sets of
guidelines pertaining to such matters.
Dr. Kirschstein described to the ACD members a June 22, 2000 ceremony at the White House to celebrate the completion of a
working draft of 90 percent of the sequencing of the human genome, an international effort involving NIH leadership. Meanwhile,
in this same research field, the NIH Bioinformatics Scientific and Training Initiative (BISTI) is establishing several new
programs. Also, Congress enacted the Children's Health Act and the Public Health Improvement Act, authorizing programs in
diverse research areas. However, the status of the NIH appropriations bill for FY 2001 remained uncertain, with NIH operating at
FY 2000 budget levels under a series of continuing resolutions since October 1, 2000.
Dr. Maria Freire, Director, NIH Office of Technology Transfer (OTT), reported that policy guidelines for sharing research tools
were implemented one year ago. NIH developed and published detailed guidelines in May 1999 to advise researchers and
administrators in industry and at universities as to how to implement the guidelines. Because many researchers remain unfamiliar
with them, NIH is continuing to enhance outreach efforts and will continue to monitor how these guidelines are being
implemented.
Dr. Lana Skirboll, NIH Associate Director for Science Policy, described how NIH is fulfilling responsibilities under the
Government Performance and Results Act (GPRA) of 1993, which is intended to improve accountability and productivity by setting
performance measures, goals, and strategic plans. To assess how it is meeting overall research goals, NIH established the GPRA
Assessment Working Group, which was chaired by Dr. Ting-Kai Li of Indiana University. Dr. Li explained that working group
members reviewed some 600 items describing accomplishments of the NIH Institutes and Centers, and was guided by a set of draft
standards for assessing those items. The working group concluded that the NIH research portfolio substantially exceeded all the
goals set for FY 2000 and particularly praised NIH for surpassing milestones in sequencing the human genome and other genomes of
model animals.
Dr. Harvey Alter, Chief of the Infectious Disease Research Section and Associate Director for research, Department of
Transfusion Medicine, Clinical Center, NIH, received the 2000 Lasker Award for Clinical Research. Dr. Alter described some of
the key events in his efforts to detect and better understand several viral sources of hepatitis in the blood supply and also to
develop methods for screening blood in various ways to make it safer for clinical use. Over the course of three decades, this
research has helped bring the rate of hepatitis transmission through blood from 33 percent to near zero, bringing an enormous
benefit to public health.
Dr. Kirschstein said that President Clinton signed legislation on November 22, 2000, to establish the NIH National Center on
Minority Health and Health Disparities (NCMHD). Dr. John Ruffin, NIH Associate Director for Minority Health and
Director-Designate of the new Center, reviewed what that legislation mandates and described detailed plans developed by NIH to
implement the mandates. He said that a major responsibility of the Center is to coordinate health disparities research at NIH,
as well as to work with other Federal and local agencies. Major initiatives include:
establishing extramural centers of excellence in research training;
research endowment programs;
loan repayment programs; and
additional programs to improve extramural research facilities, particularly at institutions that serve minority or underserved
populations.
Dr. Barry Kramer, Director, Office of Medical Applications of Research (OMAR), NIH, described current efforts to implement ACD
recommendations for improving certain OMAR operations. For example, the Agency for Healthcare Research and Quality has agreed to
assist OMAR in preparing formal literature reviews and, when possible, meta-analyses on specific topics before formal consensus
development conferences are held on those subjects. In some cases, more modest, "state-of-the-evidence" conferences
will be convened instead of full-blown consensus development conferences. In addition, a discussion group is being established,
with rotating membership, to serve as a sounding board for OMAR on these and other issues. Another new activity for OMAR will be
to develop a curriculum to help members of the news media to appreciate issues such as differences between weighing solid
evidence and basing judgments on strongly held opinions.
OPENING REMARKS
The 81st meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December
7, 2000. Dr. Ruth Kirschstein, Principal Deputy Director, NIH, began by welcoming six new members to the committee and thanking
several current members for their service on several working groups of the ACD. These working groups included: clinical gene
transfer research; the Government Performance and Results Act (GPRA) Assessment; and extramural construction issues.
Dr. Kirschstein reviewed several matters concerning personnel at NIH:
Dr. Lawrence Tabak recently was appointed Director of the National Institute of Dental and Craniofacial Research, replacing
Dr. Harold Slavkin;
Dr. Raynard S. Kington was appointed Associate Director for Behavioral and Social Sciences Research;
Dr. Jack McLaughlin is serving as Acting Director, National Eye Institute, following the retirement of Dr. Carl Kupfer;
Dr. Jack Whitescarver is serving as Acting Director, NIH Office of AIDS Research, following the departure of Dr. Neal
Nathanson, who returned to the University of Pennsylvania; and
Dr. Gerald Fischbach, who was Director of the National Institute of Neurological Disorders and Stroke (NINDS) left NIH to
become Vice President and Dean of the Medical Faculty, Columbia University.
She said that Dr. Yvonne Maddox, Acting Deputy Director, NIH, is chairing a search committee for the position of Director, NIH
Office of Equal Opportunity.
Dr. Kirschstein noted that Dr. Donna Shalala, Secretary of the Department of Health and Human Services (DHHS), has been
appointed the President of the University of Miami.
Dr. Kirschstein reported that the recipients of several of the Nobel Prizes in 2000 are, or have been, NIH grantees. These
include: Dr. Eric Kandel; Dr. Paul Greengard; and Dr. Arvid Karlson, who spent several years conducting research at NIH. In
addition, the Nobel Prize in Economics recognized two NIH grantees, Dr. Daniel McFadden of the University of California,
Berkeley, and Dr. James Heckman of the University of Chicago. Dr. Harvey Alter, from NIH, received the Lasker Award in Clinical
Medicine for his contributions in helping to protect the blood supply from contamination by the hepatitis C virus. The Lasker
Award in Basic Medicine recognized several NIH grantees, including Dr. Avram Hershko at the Technion-Israel Institute of
Technology and Dr. Alexander Varshavsky at the California Institute of Technology. In addition, President Clinton named 10 NIH
grantees and two young scientists among the total of 59 recipients this year of the Annual Presidential Early Career Awards for
Scientists and Engineers.
Dr. Kirschstein presented a brief follow-up to a report on the Clinical Trials Database presented during the June 2000 meeting
by Dr. Alexa McCray of the NIH National Library of Medicine (NLM). Dr. Kirschstein said that, since February, that NLM Website
has been visited by about 5000 users per day, amounting to nearly 15 million page hits to investigate the first 4,400 (now up to
5,200) clinical trials that have been entered into the database. Efforts are under way to include clinical trials under private
sponsorship, as well as those sponsored by other Federal agencies.
Dr. Kirschstein described several recent developments involving clinical trials. She reported that Dr. Greg Koski, Director of
the recently established DHHS Office for Human Research Protections (OHRP), formerly known as the Office for Protection from
Research Risks (OPRR) while still within NIH, could not attend this ACD meeting but is scheduled to speak at the one to be held
in June 2001. Since 1979, NIH has had a policy about maintaining data and safety monitoring levels commensurate with risks on
clinical trials. Most Phase III level trials have special boards. However, since October, NIH has been asking investigators to
submit their monitoring plans for both Phase I and II clinical trials. These plans are subject to review and NIH awards are not
issued until the plans are approved. Principal investigators also are required to report to NIH within 72 hours of receiving
notices of letters, consent agreements, or clinical holds from FDA, with failure subject to enforcement action. NIH also will
require that key personnel being funded on a research grant be appropriately educated on protecting human subjects. Although NIH
leaves open the choice among several curriculum options, researchers will need to document their training before their clinical
projects are funded.
Dr. Kirschstein reminded ACD members that NIH hosted a conference focused on conflicts of interest in June 2000, during which
current rules governing individuals were reviewed. In addition, discussions were held about reviewing these issues as they may
apply at the institutional level. During the conference, the focus was on how to manage, reduce, or eliminate conflicts of
interest as a way of protecting the safety and interests of human subjects. Similar issues also are raised in articles published
in a current issue of the New England Journal of Medicine, according to Dr. Kirschstein. She said that NIH Deputy
Director for Extramural Research, Dr. Wendy Baldwin, and her staff continue to conduct information-gathering site visits to
institutions carrying out NIH-sponsored clinical research. So far, at least ten such visits have been conducted, and a report
summarizing these experiences will be provided to ACD members in the near future.
Dr. Kirschstein said that NIH is continuing to issue awards to foster the career development of clinical researchers. They
include 193 K23 awards, 77 K24 awards, both of which exceed originally anticipated levels, and 20 K30 curriculum development
awards, which is twice the number originally expected. Before issuing additional K30 awards, NIH will reevaluate this program.
Dr. Baldwin said that, because the K30 program represents a significant investment in curriculum development, it makes sense to
hear from members of the community about their sense of how successful this investment has been.
Dr. Kirschstein reported that revised draft guidelines to improve safety for participants in clinical gene transfer research
were published in the Federal Register in October 2000. Among other changes, they specify that the NIH Recombinant DNA
Advisory Committee (RAC) review novel protocols, optionally, before being reviewed by Institutional Review Boards (IRBs) but on
a mandatory basis before being reviewed by Institutional Biosafety Committees. Thus, no subjects will be enrolled in such
clinical trials before there is local oversight as well as RAC oversight, if deemed appropriate. These changes have received
broad support from researchers at universities and those in industry. Changing the time when adverse events on gene transfer
clinical trials are reported has proved less amenable to reform because of differences between NIH and FDA mandates. However,
proposals will soon be published for public comment. Meanwhile, the RAC is convening a series of symposia on safety-related
issues, with the most recent focusing on gene transfer approaches for treating cardiovascular diseases.
Dr. Kirschstein briefly described a ceremony at the White House that took place on June 22, 2000, to celebrate the completion of
a working draft of 90 percent of the sequence of the human genome. The genomic information developed by an international
consortium led by NIH is accessible through several Websites and is being brought up to date and further annotated on a regular
basis. Meanwhile, a public-private consortium is studying the mouse genome, and plans to complete a draft sequence by March
2001. Another research consortium, whose members are developing a collection of human single nucleotide polymorphisms (SNPs), is
also reporting rapid progress, having compiled two million SNPs in a database that is publicly available. Dr. Tom Cech noted
that, with all the progress being made in this field, there is still a great deal yet to learn, including the very basic issue
of more precisely estimating how many genes there are within the human genome.
Dr. Kirschstein said that the NIH Bioinformatics Scientific and Training Initiative (BISTI) that was developed following
recommendations from a working group, chaired by ACD member Dr. Larry Smarr and Dr. David Botstein of Stanford University, led
to the formation of a consortium (BISTIC). BISTIC recently released three bioinformatics program announcements. Grants are being
planned to develop national centers of excellence in biomedical computing. Meanwhile, Congress mandated the new National
Institute Biomedical Imaging and Bioengineering, for which a new director is being sought.
Dr. Kirschstein said that Congress is supposed to reauthorize NIH programs every three years but last did so in 1993. However,
recently enacted bills authorize a number of new NIH programs. One of them, the Children's Health Act, authorizes various NIH
research efforts on autism, fragile X syndrome, juvenile arthritis, asthma, and hearing loss under a Pediatric Research
Initiative within the NIH Office of Director; the same legislation also authorizes loan repayment provisions for grantees
conducting research in children's health. Another bill enacted in November, the Public Health Improvement Act, brought together
ten separate bills to address a number of diverse research areas. Because neither of these bills is directly connected to the
NIH Appropriations Bill, discussions are under way on how to meet these new mandates.
A final version of the NIH Stem Cell Research guidelines became effective on August 25, 2000, according to Dr. Kirschstein. They
specify the type of assurance documents that are required to accompany proposals requesting NIH funding to do research in this
field. A major responsibility consists of providing an assurance that cells being used were derived in accordance with the
guidelines. A recently established review group, administered under the NIH Center for Scientific Review, will review such
proposals. The members of the review group will soon be announced. In response to a question from Dr. Cech, Dr. Lana Skirboll
said that many researchers have expressed interest in this field and have sought technical assistance in preparing proposals,
but the first set of proposals is not due until April 2001.
Dr. Kirschstein noted that the first class of the NIH Academy was enrolled earlier in the year. It consisted of 10
post-baccalaureate students, many of them interested in doing research on health disparities. NIH Deputy Director for Intramural
Research, Dr. Michael Gottesman, said that, since this program began last spring, participants have expressed heightened
interest in becoming involved in such research.
Dr. Kirschstein said that NIH hosted representatives of the Heads of International Research Organizations on July 28, marking a
change from their usual venue in London where Dr. George Radda, Chief Executive of the Medical Research Council in the U.K.
hosts this group twice annually. The group also included representatives from Canada, Japan, Switzerland, the Netherlands, and
Germany, as well as Dr. Rita Colwell, Director of the National Science Foundation. Participants discussed issues such as
clinical gene transfer research, PubMed Central, and postdoctoral exchange programs.
Dr. Kirschstein described the current state of the Federal appropriation for NIH in FY 2001. President Clinton recommended a 5.6
percent increase for NIH in his budget recommendation early in the year, but both the Senate and House of Representatives
Appropriations Committees have said that they intend to provide about a 15 percent increase for NIH in this the third year of an
anticipated five-year period during which the overall NIH budget will double. The two Houses passed different versions of an
appropriations bill, and committee members have been meeting in conference to resolve differences and also to negotiate with the
President, largely over issues that relate to other DHHS agencies. With such matters still unresolved, NIH has operated under a
series of continuing resolutions since October 1, 2000, the start of the fiscal year, with budget levels during the first two
months of FY 2001 remaining at FY 2000 levels. Because NIH ordinarily does not distribute funds for major new programs during
this part of the fiscal year, these budgetary uncertainties are not yet exerting a huge impact as officials were taking steps to
manage the NIH grant portfolio by holding spending to levels consistent with FY 2000 mandates. If FY 2001 budget uncertainties
were to continue longer, it would raise serious concerns.
Meanwhile, the budget proposals for FY 2002 will not go to the Office of Management and Budget until officials in the new
Administration request them. NIH expects to be dealing not only with a new Administration, but also with new members of
Congress, since Rep. John Porter (R-IL) is retiring.
DISCUSSION
In response to a question about the NIH budget from Dr. Bettie Sue Masters, Dr. Kirschstein said that, if NIH receives
anticipated increases in the FY 2001 appropriations bill, non-competing grants will be restored to their full levels.
In response to a second question from Dr. Masters, Dr. Baldwin said that the modular grant process was intended for applications
for funding as a way of improving the alignment between requested and approved funding levels while also simplifying the budget
planning that investigators are required to incorporate into their research proposals. In addition, to reduce discrepancies
between requested and approved funding levels for grants that arose during several rounds of negotiating, NIH introduced the
modular application process, involving $25,000 increments in terms of funding requests; such grant proposals are limited to
$250,000 per year.
Although the modular concept appears to work well, attempting to evaluate the entire experiment is very difficult now because of
overriding concerns from FY 2001 appropriations-related uncertainties, according to Dr. Baldwin. Once the uncertainties have
been resolved, she will present a more detailed description of how this program is progressing. Dr. Baldwin noted that some
investigators are concerned that modular proposals make it difficult for them to defend their requests in terms of how much
funding support they are requesting.
SHARING BIOMEDICAL RESEARCH RESOURCES
In introducing Dr. Maria Freire, Director, NIH Office of Technology Transfer (OTT), Dr. Kirschstein reminded ACD members that,
in 1999, they approved a document, "Principles and Guidelines for Sharing Biomedical Research Resources," containing
policy guidelines developed by an ACD working group chaired by Ms. Rebecca Eisenberg.
Dr. Freire said that NIH policy guidelines for sharing research tools, such as monoclonal antibodies and animal models, that
enable research to move forward were implemented approximately one year ago. They were developed with two principal concerns in
mind. The first concern is short-term, having to do with NIH-funded researchers sometimes not having access to the best tools
available for conducting scientific research, in part because of protracted negotiations over terms for using those tools and
materials. The second, longer-term concern, has to do with the terms under which some of the tools may be used, with some
conditions, such as "reach-through" royalties and delays in publishing rights, imposing heavy constraints on
researchers and potentially delaying or preventing valuable products reaching the market and becoming available to improve the
public health.
To address these issues, a working group, chaired by Ms. Eisenberg of the ACD, was established in 1997, with members from
industry, universities, and other not-for-profit institutions such as the Howard Hughes Medical Institute. The working group
provided four main recommendations in its 1998 report to: (1) promote the dissemination of research tools without legal
entanglements; (2) use more widely the Uniform Material Biological Transfer Agreement; (3) develop guidelines for sharing
research tools, and (4) review and strengthen current NIH policies for sharing research tools and materials.
Dr. Freire said that NIH subsequently developed detailed guidelines, which were published in the Federal Register in
May 1999, that encourage researchers and administrators in industry and at universities to adopt several principles for sharing
such tools and materials. The draft contained sections written in language intended to satisfy the legal needs of institutions
negotiating formal agreements. NIH subsequently reconstructed the document to separate the principles intended for researchers
to follow from other more densely written sections that are intended for technology transfer specialists and attorneys to
implement. The principles stress the importance of following several practices, including: (1) maintaining academic freedom,
including the freedom to publish research findings; (2) continuing to implement the Bayh-Dole Act that mandates technology
transfer; and (3) encouraging the wide dissemination, with as little in the way of legal encumbrances as possible, of research
tools developed with the support of NIH. She later noted that a recent amendment to the Bayh-Dole Act, called the
Stevenson-Wilder Technology Transfer Commercialization Act of 1999, mandates that inventions by non-profit organizations and
small businesses "are used in a manner to promote free competition and enterprise without unduly encumbering future
research and discovery."
The overall goal of the ACD working group and the subsequent NIH detailed guidelines was to achieve a balance between protecting
intellectual property and disseminating research tools, according to Dr. Freire. Although these principles and the guidelines
developed for implementing them have been in effect for about one year, many researchers remain unfamiliar with them, leading
NIH to continue to enhance outreach efforts. Meanwhile, NIH is seen as a world leader in these efforts to develop guidelines for
ensuring that research tools may be widely disseminated. For example, OTT staff member Jack Spiegel visited Amsterdam in
December 2000 to advise the Organisation for Economic Cooperation and Development about implementing similar guidelines that it
has developed.
NIH received comments in September 2000 from researchers and technology transfer specialists regarding these guidelines. Some of
the comments indicated startling misunderstandings about the intent of NIH, according to Dr. Freire. For instance, despite some
comments to the contrary, NIH continues to encourage researchers to patent their inventions, but urges them to be strategic and
selective in these efforts. Another common misunderstanding is that NIH no longer supports exclusive licensing agreements. Here
again, because the broader goal is to support wide dissemination of research tools, NIH recognizes that exclusive licensing
agreements sometimes can favor that goal. Moreover, NIH is not undermining commercialization efforts, nor is it trying to harm
small biotechnology companies.
Other comments indicated that members of the research community appreciate the latitude that the NIH guidelines provide them,
and also appreciate that they are not regulations, according to Dr. Freire. Although some streamlining of research tools-sharing
agreements has been implemented, some still do not comport with the guidelines. Perhaps the most important problems lie in the
structuring of agreements between universities and industrial companies.
Dr. Freire said that, because one year is not sufficient for measuring their impact, NIH will continue to monitor how these
guidelines are being implemented. She also recommends that they continue as guidelines, and not be changed into regulations, and
that they be more widely adopted by other Federal agencies that support research. She also noted that representatives from the
NIH OTT are joining with members of the NIH Office of Extramural Research on their site visits to universities, using such
opportunities to monitor how, or whether, the guidelines are being implemented.
DISCUSSION
In response to a question from Ms. Eisenberg about a working group recommendation for convening a research tools forum, Dr.
Freire said that this idea is being discussed seriously but there has been no decision about how to organize such a forum or
where to place it. However, discussions have been held with three organizations that might serve as hosts to such a forum.
Ms. Eisenberg asked whether the underlying problem of barriers preventing the sharing of research tools has gotten better or
worse. She also asked whether universities were still focusing their technology transfer attentions and resources on projects
that they expect to bring them royalty revenues rather than implementing corrective measures that are recommended in the NIH
guidelines. In response, Dr. Freire said that Mr. Ted Roumel from the NIH OTT, who recently attended a meeting of the
Association of University Technology Managers, reported that members of this organization are welcoming the NIH guidelines,
which are helping them to resolve negotiating impasses between university researchers and companies. She also said that the
focus on these issues has changed over the past several years, with more attention to technology transfer coming from university
presidents and other top-level administrators, who may need to reexamine what they consider the core missions of their
institutions.
Dr. William Brody said that university administrators are being pressured by their boards and also by local or state government
officials to develop such technology transfer offices into profit centers. His response is to tell such officials that the most
effective vehicle for transferring technology still resides in fulfilling the core educational missions of such institutions.
Dr. Cecil Pickett agreed that technology transfer issues can cause difficulties and said that universities tend to over-value
technologies that their faculty members are developing. In so doing, they often seek downstream royalty agreements that are not
realistic but may tie up these technologies for months or years. He also noted that the National Cancer Policy Board of the
Institute of Medicine is addressing these issues. Dr. Freire noted that she was recently invited to speak to that board.
Dr. Freire said that she continues to work with both university and industry representatives to reexamine their differences over
evaluating the potential commercial value of research tools being developed. Because the rules are different when research is
supported with public funds compared to when it is privately funded, everyone needs to be mindful of the differences. A matrix
is being developed to help delineate the differences. Dr. Barrie Carter said that realistic evaluations of new research tools
are key to these issues, and that many universities tend to over-value technologies as they try to turn their technology
transfer offices into profit centers. Dr. Freire agreed, but said that determining such evaluations frequently becomes a
challenge.
Dr. Cech said that negotiating agreements for sharing software that is developed for use in biological research is also a
challenge, one that requires modified guidelines. In response, Dr. Freire said that software is not covered by the Bayh-Dole
Act, unless it is patented, and tends to be treated more like manuscripts. She also noted that the Stevenson-Wilder Technology
Transfer Commercialization Act of 1999 may pertain to software. Dr. Cech said that it is important to make bioinformatics
software, developed by NIH grantees, broadly available to the research community. Ms. Eisenberg later asked that if the NIH
guidelines indeed apply to bioinformatics software, are researchers choosing not to adhere to them. In response, Dr. Cech said
that the guidelines are vague on this issue, which is further complicated because of the different way in which software
typically is commercialized. He said it would help if the guidelines were more explicit and specific on this issue.
Dr. Steven Chu of Stanford University said that because many faculty members want to become entrepreneurs by starting their own
companies, some of them may leave the academic community if they find the NIH guidelines too restrictive. He also said that his
institution has conflict of interest guidelines for its faculty members to remind them that their first commitment is to the
university. Dr. Freire said that there are several examples of university-industry research agreements that NIH found to be too
extreme in terms of restricting traditional academic freedoms as they pertain to findings generated with NIH funding, notably
the Scripps-Sandoz arrangement.
Dr. Baldwin said that all institutions receiving support from NIH are expected to have a conflict of interest policy in place.
Dr. Kirschstein said that, because these issues are of deep concern and currently are receiving considerable attention, they may
be brought back for more detailed discussion at a future ACD meeting.
Mr. Arthur Ullian said that it is critical to balance individual interest in accumulating wealth against a broader interest in
stimulating good science, making it very important for NIH to continue to concern itself with conflict of interest issues.
Dr. Masters said that the behavior of academic and industry researchers is changing, with many more opportunities for members of
those once largely-separate communities to interact. She also recommended that there be a forum for continuing discussions on
research tools-sharing and related issues. Dr. Kirschstein said that the ACD has devoted a great deal of time to these issues
during the past seven years and will continue to do so. Dr. Yvonne Maddox said that, although universities may develop
guidelines on these issues for their own faculty members, it often is difficult to share such guidelines more widely as part of
on-going discussions of such matters throughout the broader community. Dr. Chu said that the discussions more often tend to
remain local among individual colleagues at an institution, who may also remain unaware of NIH guidelines. Dr. Kirschstein said
that coaxing NIH grantees to read and follow such guidelines often proves a stumbling block. She also praised Dr. Freire for her
international leadership on these issues.
REPORT ON THE GOVERNMENT PERFORMANCE AND RESULTS ACT ASSESSMENT
Dr. Lana Skirboll, NIH Associate Director for Science Policy, described NIH efforts to meet responsibilities under the 1993
Government Performance and Results Act (GPRA), which mandates Federal agencies to improve accountability and productivity by
setting performance measures, goals, and strategic plans. NIH devised an approach for developing a strategic plan and assessing
its overall programs and performance in terms of three general areas: research, training and career development, and facilities.
As part of its GPRA review, NIH specifies a series of 55 specific, mostly quantifiable "means" goals that include
communicating program results, technology transfer, leadership and administration, grants management, and peer review.
To assess how it is meeting overall research goals, NIH established the GPRA Assessment Working Group, whose members include
representatives from the ACD, COPR, NIH advisory council members, and staff, according to Dr. Skirboll. She introduced former
ACD member, Dr. Ting-Kai Li, Indiana University, who chaired that working group.
Dr. Li said that members of the working group began their task with a 500-page background document, containing 600 items
describing accomplishments of the NIH Institutes and Centers, along with a set of draft standards for assessing those items.
Working group members discussed and agreed on how to approach their task, divided those items for evaluation, and later met on
October 30, 2000, to draft a report that will be completed by January 2001. A key challenge was to decide how incremental
progress in specific research areas satisfied five criteria that apply to the entire NIH research portfolio.
Dr. Li said that the criteria included: adding to the body of knowledge about normal and abnormal biological functions by
disseminating research findings; developing new or improved instruments and technologies for use in research and medicine;
developing new or improved approaches for preventing or delaying the onset or progression of disease and disability; developing
new or improved methods for diagnosing disease and disability; and developing new or improved approaches for treating disease
and disability. The majority of the 600 items fell into the first category of adding to the body of knowledge, with the
remainder divided almost equally among the remaining four categories.
The working group praised NIH for surpassing milestones in its program for sequencing the human genome and other genomes for
model animals. It also cited broad contributions of genetic techniques to all areas of NIH-sponsored research, the essential
role played by animal models in studying disease and basic biology, and the importance of environmental factors in shaping
biological phenomena. The working group concluded that the NIH research portfolio substantially exceeded all the goals set for
FY 2000, according to Dr. Li. He thanked Ms. Robin Kawazoe, Mr. Greg Downing, Ms. Karen Goldman, and other members of the NIH
Office of Science Policy for their outstanding contributions in organizing the GPRA assessment effort and in helping to prepare
the working group report.
DISCUSSION
Ms. Eisenberg said that the GPRA Assessment proved to be an interesting, rather than an onerous, task for members of the working
group. She said that, because members of the working group have become so familiar with NIH achievements, they might be able to
contribute in other ways to the overall NIH mission, perhaps by helping to disseminate more widely some of the knowledge that
they acquire during this process.
Dr. Yank Coble commended Dr. Li proved for his leadership of the working group.
Mr. Phillip Williams said that, although a great deal of technical information was contained in the documents presented to the
working group, the documents themselves were very lucid. He also said that the documents indicate that NIH is spending Federal
funds wisely in its efforts to advance the health interests of the United States and the world.
In response to a question from Dr. Cecil Pickett about whether the GPRA report would be used for allocating resources, Dr.
Kirschstein said that the report is presented to the Office of Management and Budget and to the Congress for their use in
reviewing budget requests and setting annual appropriations. Mr. Williams said that, although research is incremental, the
report effectively highlighted what is significant as a way of best addressing the GPRA-mandated requirements. Dr. Li reminded
ACD members that a good deal of the material in the overall NIH GPRA report is not focused on qualitative descriptions of
meeting research-related goals, but represents the quantitative attainment of administrative goals.
Dr. Kirschstein thanked Dr. Li again for chairing the working group and said that his successor will be Dr. Mike Weissfeld from
Columbia University Physicians and Surgeons College of Medicine.
THE SAFETY OF THE BLOOD SUPPLY
Dr. Kirschstein introduced Dr. Harvey Alter, Chief of the Infectious Disease Research Section and associate director for
research, Department of Transfusion Medicine, Clinical Center, NIH, who received the 2000 Lasker Award for Clinical Research.
She noted that Dr. Alter has spent most of his career at NIH.
Dr. Alter described some of the events leading to his arrival at NIH following his receipt of a letter from his Selective
Service board. Had he been drafted for military service, he more likely would have pursued a career in clinical practice.
Instead, he came to NIH where Dr. Baruch Blumberg became his first research mentor, one of several chance events that led Dr.
Alter to pursuing a career in research. His first experiments involved testing of blood samples, seeking clues to what factors
other than differences in red blood cells cause transfusion reactions. Because he was using similar antibody-antigen diffusion
techniques as Dr. Blumberg, another colleague suggested that Dr. Alter meet with Dr. Blumberg to discuss mutual interests. They
immediately began to collaborate.
During the early 1960s, Dr. Blumberg was studying polymorphisms of blood serum lipoproteins and he collected samples from all
over the world, including from an Australian aborigine with hemophilia. That blood contained a previously unidentified protein
antigen that at first was referred to simply as the red antigen, later the Bethesda antigen, soon the Australia antigen to
indicate where the sample originated, and finally the hepatitis B virus surface antigen when its viral origins were recognized
several years later. The prevalence of this antigen was only 0.1 percent in healthy blood donor populations, but 10 percent
among aboriginal serum specimens and also in samples taken from patients with leukemia. Later, Dr. Alter and other researchers
learned that this antigen has nothing to do with that disease, except that such patients were immunosuppressed and had received
multiple blood transfusions.
Although Dr. Alter and Dr. Blumberg moved to different institutions, they both continued to work on the Australian antigen. Dr.
Blumberg found that the antigen appeared in 10 percent of serum samples from certain patients with Down's syndrome, but he
refined his analysis and recognized that the prevalence was 28 percent for those patients staying in large institutions but only
3 percent for those living in small institutions — the first clue to an environmentally determined, possibly infectious,
etiology of the antigen. When one of the Down's patients went from Australia antigen negative to positive, Dr. Blumberg had
another clue that an infectious agent was involved. It later proved to be the antigen for a hepatitis virus, providing yet
another example of serendipity in these efforts. Indeed, the antigen soon became a valuable marker for use by other researchers
studying hepatitis.
By 1969, Dr. Alter returned to NIH to pursue transfusion-related hepatitis studies. He began routinely to collect and retain
serum samples from heart surgery patients at the NIH Clinical Center who typically received multiple blood transfusions. By
following such patients, he learned that paid-for donor blood appeared to be the chief risk factor for those patients developing
transfusion-related hepatitis. By 1970, NIH adopted an all volunteer blood donation system, which led to a dramatic drop from 33
percent to 10 percent in the rate of post-transfusion hepatitis among its heart surgery patients. Despite this drop, cases were
still detected, due in large part to a non-B type of hepatitis virus, which was soon being called the non-A/non-B after Dr.
Steve Finestone discovered hepatitis virus A.
Dr. Alter said that other NIH efforts, studying hepatitis viruses in chimpanzees, soon paid off, in part because the ongoing
collection of blood serum samples from patients was being so carefully catalogued. This animal model proved useful first for
proving transmission of the hepatitis B virus but, later, also for tracking the behavior of (and demonstrating Koch's postulates
for) the more elusive, blood-borne hepatitis C virus. For instance, like humans, chimpanzees typically develop a persistent
hepatitis C infection, often without outward signs of disease. He cited several collaborators at NIH in these ongoing studies,
including Drs. Purcell, Hoofnagle, Yang, and Saif, and other collaborators at FDA. Dr. Purcell's group helped to establish the
approximate size of the putative virus by means of filtration-cutoff studies, while another collaborator, Dr. Finestone, used
chloroform inactivation studies to show that the virus has an essential lipid envelope. Together these findings suggested that
the hepatitis C virus belongs to the flavivirus group.
One reliable way to show that this virus persists in humans is that it causes periodic fluctuations of specific liver enzymes,
indicating intermittent inflammation of that organ, according to Dr. Alter. With special care, he and his colleagues can also
detect corresponding fluctuations in hepatitis viral RNA levels. Follow-up studies of such patients, even those who are
asymptomatic from the outset, indicate that about 70-75 percent of them develop chronic hepatitis C viral infections, and about
20 percent develop cirrhosis.
Despite progress on several fronts, efforts to develop a direct hepatitis C virus detection method and to isolate the virus were
stymied for many years, according to Dr. Alter. Hence, in the early to middle 1980s, the NIH blood bank used the ALT (alanine
aminotransferase) liver enzyme function test as a surrogate for measuring hepatitis C virus, but could not prove the efficacy of
this test, and soon switched to testing for the hepatitis B core antigen as a surrogate for detecting hepatitis C. With growing
concerns about AIDS being transmitted through contaminated blood, this analytical procedure was widely adopted in 1987. Within a
few years, the risk of contracting hepatitis C from contaminated blood fell below 4 percent, compared to 33 percent prior to
this testing and other efforts to screen blood donors had been put in place.
Another major improvement evolved at about this time when Dr. Michael Houghton and his colleagues at the Chiron Corporation used
molecular biology techniques to extract nucleic acids from large volumes of plasma from hepatitis C-infected chimpanzees. This
material was cloned into Escherichia coli and the presumptive viral gene products then were screened with serum that
was presumed to contain antibodies to some of the viral gene products that were being produced. Their efforts entailed screening
some 6 million clones before finding one containing the sought-after hepatitis C genes. Dr. Alter praised Dr. Houghton and his
collaborators for applying molecular biological techniques to identify a virus that they otherwise were unable to detect by
means of conventional techniques, including electron microscopy. With the new presumptive agent in hand, they evaluated their
new hepatitis C detection method against a panel of blood samples that Dr. Alter prepared, and their new method correctly
identified samples with a far higher degree of accuracy than did any previously evaluated test method. Since it was developed,
this new detection method has had a profound impact on the safety of the blood supply. At NIH, for instance, since the testing
method was introduced in 1992, there has not been another case of hepatitis C infection among patients at the Clinical Center.
Thus, since 1970 when this research began, the hepatitis blood transmission rate has dropped from 33 percent to near zero.
Other efforts are under way to drop this very low rate still further by means of even more sensitive molecular testing methods,
according to Dr. Alter. With such new tests, the risk of being infected by HIV through contaminated blood is estimated to be one
in one million, of developing a hepatitis C infection about one in 350,000, and the risk of hepatitis B about one in 109,000. An
additional blood supply safety measure is being evaluated clinically, namely the technique of light-activated psoralen
inactivation of nucleic acids as a way of destroying these and other viruses that may escape detection in blood samples.
After reciting a poetic homage to Dr. Houghton, Dr. Alter said that he felt privileged to have spent most of his career at NIH
where he has been free to establish collaborations and to pursue long-term studies of a problem that proved to be of major
public health importance. He also thanked past and current NIH leaders for allowing him this freedom.
DISCUSSION
Several ACD members bantered with Dr. Alter over his poems while congratulating him on receiving the Lasker Award.
In response to a question from Mr. Ullian, Dr. Alter said that it is very difficult to estimate the cost benefit in testing the
blood supply to reduce the transmission of the hepatitis C virus. However, he pointed out that some 20 percent of individuals
who are infected with this virus develop cirrhosis, a condition that is associated with huge medical costs, including those that
come with doing liver transplants to treat many of those patients. Thus, there are important savings realized from preventing
these infections despite the costs involved in screening some 15 million units of blood per year.
THE NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES
Dr. Kirschstein noted that a draft of the NIH Health Disparities Strategic Plan is available on the NIH Website. She then
outlined several NIH-sponsored, health disparities-related events held over recent months including: health awareness fair in
June 2000, in which some 600 students and family members from the Washington, D.C., area visited NIH for discussions of health
promotion and disease prevention; convening several regional roundtables to recruit Hispanics, African Americans, and Native
Americans into the health professions; and launching a computer laboratory program under the auspices of the National Library of
Medicine at a Native American museum on the Piscataway Indian Reservation in Maryland.
Dr. Kirschstein said that Congress passed legislation, which President Clinton signed into law during a White House Ceremony on
November 22, 2000, to establish the NIH National Center on Minority Health and Disparities (NCMHD). She then introduced Dr. John
Ruffin, NIH Associate Director on Minority Health, who is director-designate of the new Center.
Dr. Ruffin reviewed key features of the legislation that mandates the NIH National Center on Minority Health and Disparities as
well as plans being developed for its organization. In a sense, planning for the new Center began a decade ago with the
establishment of the NIH Office of Research on Minority Health, according to Dr. Ruffin. Senate bill 1880 authorizes the new
Center to conduct and support research and training, disseminate research-based health information, and develop other programs
that focus on the health needs of racial and ethnic minorities and other underserved population groups. The legislation also
stipulates that the director of the Center work closely with the Agency for Healthcare Research and Quality to ensure that
appropriate population groups are identified in meeting those needs.
Dr. Ruffin said the Center's Director will:
be responsible for coordinating health disparities research at NIH;
will represent NIH on such matters in relevant Executive Branch activities; and
oversee the development of a strategic plan for the Center within its first year.
The strategic plan will describe how research priorities are to be set and supported, while describing a strategy and a time
frame for meeting those objectives; it also calls for an annual review and for making budget revisions as needed. As part of its
duties, the Center will coordinate, collaborate with, but not replace relevant health disparities research activities of other
NIH Centers and Institutes. Health disparities research is to be undertaken broadly across all disciplines, including basic and
applied, behavioral and social, and cultural and linguistic areas. Moreover, the NCMHD is to establish cooperative research
programs with other Federal, state, local, and tribal agencies. An advisory council will be established to help in planning,
developing budgets, and in fulfilling several reporting responsibilities that are mandated for the Center.
The legislation calls for the Center to undertake several initiatives, such as establishing:
centers of excellence in research training;
research endowment programs;
loan repayment programs; and
programs to improve research facilities.
Dr. Ruffin said that there are several examples of research endowment programs established by other Federal departments that can
serve as models in planning the Center's versions of such programs. The mission is to bring additional institutions into the
biomedical workforce, enabling them conduct health disparities research sponsored by the Center. Similarly, there are models for
loan repayment programs that help young professionals to begin health research-oriented careers; the legislation specifies that
50 percent of the participants in this program come from health disparity populations.
Dr. Ruffin said that the NCMHD is planning to establish five-year Centers of Excellence research awards. These awards will be
made on detailed criteria laid out in the legislation, including each Center's track record and commitment to recruit and
educate health disparity population students and to hire faculty members from such population groups. The Centers may involve
partnerships or consortia with other established institutions conducting research and training but otherwise do not meet the
specific requirements making them eligible for these awards. Importantly, institutions may not use these new resources to
substitute for resources already being invested in health disparities-related research, training, or related activities. He
emphasized that resources will be provided not only for research and training but also for improving facilities and for placing
endowments with non-research-intensive institutions.
The legislation mandates several regular reporting requirements for assessing the NCMHD, including an annual report, a one-time
report on progress due in two years, and a report due after five years by the Secretary of DHHS assessing the Center's
effectiveness. The annual report will review all NIH health disparities research programs, including information on budgets and
progress in meeting health goals. These reports are to follow strict methods for tracking such expenditures, to justify any
deviations from recommendations outlined by the Institute of Medicine for this purpose, and to use FY 1999 allocations as a
baseline for describing changes in resource allocations.
Dr. Ruffin also described current plans for implementing this legislation. As with other NIH Centers and Institutes, the NCMHD
Office of the Director will report to the NIH Director. Meanwhile, this NCMHD Office of the Director will oversee several
offices with specific duties and activities, including finance and administration, extramural activities, communication and
public liaison, and research training and capacity building; each of these offices will be organized with divisions overseeing
more specific activities. For example, the division charged with administering community-based research and outreach programs
will build partnerships among Federal agencies and public health agencies at the local, tribal, regional, and state levels, with
a focus on disease prevention and the development of messages that are appropriately sensitive to the needs of racial and ethnic
minorities. As another example, the Office of Program Analysis and Data Management will build a database describing NIH health
disparities research programs. The NCMHD will have an advisory council and will also receive advice and information from a
Trans-NIH Coordinating Committee on Health Disparities Research, whose members will be individuals representing the directors of
the other NIH Centers and Institutes.
DISCUSSION
In response to several questions from Dr. William Brody about NCMHD budget levels, Dr. Ruffin said that the new legislation
authorizes $100 million in addition to current NIH outlays for health disparities research-related programs, with the NIH Office
of Research on Minority Health now budgeted for more than $90 million per year.
Dr. Kirschstein said that NIH is seeking clarification for ambiguities about budget levels for NCMHD in the legislation,
particularly in light of the FY 2000 budget for the NIH Office of Research on Minority Health, which was about $97 million, and
the FY 2001 budget request, which was for $117 million. She also said that the legislation does not provide for creating an
intramural research program. Dr. Ruffin noted that overall NIH spending for health disparities research programs exceeds these
levels. Later, in response to a request from Dr. Charles Francis for additional clarification on these budget matters, Dr.
Kirschstein said that if, and when, Congress enacts the FY 2001 appropriations bill for NIH, the Center will have an additional
$20 million in its budget, and she agreed that this additional money does not provide much in the way of new resources to meet
legislative mandates. However, she said that efforts will be made to find additional resources for NCMHD and related programs as
the FY 2002 budget request is developed.
Dr. Brody pointed out that provisions in the legislation that appear to prohibit substituting NIH funding for other sources of
funding already committed to health disparities research programs could inhibit, or prevent, the development of such programs.
This is because university administrators often use limited funds to initiate, but then transfer funds to seed other, programs.
In response, Dr. Ruffin said that the NCMHD will need to help in advising how to establish research endowments.
In response to a question from Dr. Linda Waite about research programs, Dr. Ruffin said that NCMHD will be working closely with
other NIH Institutes and Centers to seek their advice as it begins to review grant proposals and issue awards. Dr. Francis
pointed out that the NIH Office of Research on Minority Health currently supplements research programs that are being supported
by other NIH Centers and Institutes. In response to his question whether this practice would continue, Dr. Kirschstein said that
NCMHD resources will not be used to substitute for those from other Institutes and Centers now supporting health disparities
research; if anything, the other Centers and Institutes can be expected to expand their current expenditures in health
disparities research, which is considered a special area of emphasis for all of NIH and will be treated as such in the FY 2002
budget request. She also said that NCMHD and the NIH Office of the Director will monitor such spending, which is $1.3 to $1.8
billion across NIH. Dr. Ruffin said that monitoring NIH spending in this area will be a major challenge for his office.
Dr. Maddox reminded ACD members that each of the NIH Centers and Institutes has developed a strategic plan for health
disparities research and will likely be adding resources to support those plans, which are available on the NIH Website. Dr.
Kirschstein said that copies of the plans would be sent to ACD members. Dr. Ruffin added that he would appreciate receiving
comments.
In response to a question from Dr. Yank Coble about Surgeon General Satcher's initiative on health disparities involving many
medical societies, Dr. Ruffin said that new NCMHD planning efforts will entail extensive coordinating efforts with other
agencies within DHHS.
In response to a question from Dr. Cecil Pickett about how the new Center may have a unique impact on health disparities
research, Dr. Ruffin said that it should be considered as extending the efforts of all the NIH Centers and Institutes as they
address these challenges, and that the new Center can act as a partner to coordinate and otherwise help them accelerate and
improve these efforts.
In response to a question from Mr. Phillip Williams about the more intense focus of the new Center, Dr. Ruffin said that an
important emphasis will be to help in avoiding duplicative efforts under way at other NIH Centers and Institutes. In response to
a question from Mr. Arthur Ullian about going beyond research to deal with issues such as access to health care, Dr. Ruffin said
that programs under the NIH Office of Behavioral and Social Sciences Research will address some questions regarding health
outcomes. Dr. Kirschstein said that NIH is not well-suited for addressing health care access issues because its primary focus is
on research. However, recent decisions permitting Medicare patients to be supported when they participate in clinical research
may enable and encourage minority group members to gain better access to health care while also becoming involved.
Dr. David Burgess again brought up budget issues, suggesting that a 15 percent overall increase to NIH, along with a $20 million
increase for NCMHD, would not be enough to have a significant effect on health disparities research. In response, Dr. Ruffin
said that meeting the many challenges that are part of the new Center's mandate will depend on obtaining adequate resources. He
also pointed out that its predecessor, the NIH Office of Research on Minority Health, already has infrastructure and staff
members and is supporting a wide variety of health disparities-related programs in cooperation with the other NIH Centers and
Institutes, which will be called on to support the expansion of those programs. Dr. Francis said that, despite resource
limitations, Congress established the new Center in such a way to change the status of those programs and to encourage new
emphasis on such research throughout NIH. He said that endowments represent a particularly important component of the new
Center's programs inasmuch as many of the institutions it will be supporting simply do not have endowments of their own and thus
are limited in their capacity to support research.
IMPLEMENTATION OF RECOMMENDATION OF ACD ON THE OFFICE OF MEDICAL APPLICATIONS OF RESEARCH
Dr. Kirschstein introduced Dr. Barry Kramer, Director, NIH Office of Medical Applications of Research (OMAR), noting that he has
begun implementing ACD recommendations for improving certain OMAR operations.
Dr. Kramer said that the mission of OMAR is to develop formal assessments of medical applications, making decisions on solid
evidence before disseminating recommendations for making substantial changes in medical practices. He noted that introducing
expensive new medical technologies sometimes can lead to greater health disparities when certain population segments cannot
afford them. The most visible OMAR program is its consensus development conferences, each of which is sponsored by one or more
of the NIH Institutes and Centers. Topic choices are dictated by several criteria, including public health importance, whether
there is a gap between current knowledge and common medical practice, whether there is an adequate base of scientific
information, and whether there is sufficient public interest and investment of healthcare resources in a specific area.
Dr. Kramer said that the design of each consensus conference follows a similar general outline once a topic is selected. Thus,
there will be a formal literature review and, when possible, a meta-analysis before the formal consensus process begins. These
efforts will be conducted in cooperation with the Agency for Healthcare Research and Quality. Before the consensus conference
itself, smaller panels will be convened once or twice to refine critical issues, oversee the conference, frame other issues
before the scientific jury begins to develop a formal consensus statement, and meet following the conference to revise the
consensus statement as needed.
Dr. Kramer said that he thinks in general terms before each consensus conference of evidence being organized in a distinct
hierarchy, or pyramid, in terms of its credibility — with random-control clinical trials considered at the top, followed
by controlled trials without random selection, case-controlled cohort studies, ecological and descriptive studies, and opinions
of reputable experts being at the bottom of this hierarchy. Similarly, there is a hierarchy among different types of clinical
treatment trials, with mortality endpoints being the strongest and quality of life criteria being lower in that hierarchy. In
some cases, if he and institutional representatives feel that the strongest available evidence consists of opinion and clinical
judgment, they may decide to convene more modest, "state-of-the-evidence" conferences instead of full-blown consensus
development conferences.
Sometimes NIH consensus conferences can have unintended consequences, according to Dr. Kramer. Hence, OMAR is putting together a
discussion group whose rotating membership can serve as a sounding board for such issues and, more generally, to review topics
of potential interest for this office. He said that it will be useful to include, as members of this discussion group,
representatives from NIH, other agencies with health-related missions, scientists and clinicians from outside NIH, and
representatives of the general public.
Dr. Kramer said that several consensus conferences are now firmly scheduled, including one related to the management of dental
carries organized with the help of Dr. Dushanka Kleinman of the NIH National Institute of Dental and Craniofacial Research.
Other topics include an assessment of adrenocortical tumors that are imaged incidentally and of youth violence and related
behaviors.
Another new activity for OMAR will be to develop a curriculum for the news media that will help journalists appreciate some of
the differences between weighing solid evidence and basing judgments on strongly held opinions, according to Dr. Kramer. It will
also include advice on interviewing representatives of the scientific and medical communities. Ms. Anne Thomas and several other
NIH staff members are providing OMAR with advice on this undertaking, and Dr. Kramer has been speaking about these subjects with
organizations of science and medical writers.
DISCUSSION
Dr. Linda Waite asked Dr. Kramer for copies of his slides and suggested that he broaden his term, "evidence-based
medicine," to "methods-based health research." He agreed to this suggestion, and Dr. Kirschstein pointed out that
Dr. Kramer has considerably broadened OMAR's scope beyond purely medical concerns.
In response to a question from Dr. Charles Francis about improving the way in which consensus development efforts change the
behavior of physicians, Dr. Kramer said that implementing such changes remains a major challenge and he hopes that the new OMAR
discussion group can help in developing new strategies to achieve those changes. One way for consensus development conferences
to be more effective is if they can reach opinion leaders who can influence other practitioners. Dr. Kirschstein said that
summaries of OMAR-sponsored conferences are published in prominent journals for clinicians. She also said that deepening the
involvement of the news media in disseminating information from such conferences also could prove useful.
Dr. Yank Coble said that these conferences are influential, but he stated that they are not meant to represent final judgments
on specific topics. He also noted that recommendations developed through consensus development conferences often are
incorporated into clinical practice guidelines, of which some 1,000 are available through the National Guidelines Clearinghouse.
Dr. Kramer said that OMAR should not present normative statements when they are not warranted as they can discourage further
investigations to improve clinical practices. He said that the development of practice guidelines sometimes is more effective
when undertaken locally, but the consensus development process can help to inform those local undertakings. He further said that
OMAR has several ways in which it disseminates information about consensus development findings, and is developing additional
mailing lists and contacts to send that information to other recipients. In addition, OMAR is developing an online continuing
medical education (CME) examination as a learning device that also can be used to obtain CME credit.
Dr. Waite said that consensus development conferences also can lead to changes in clinical practice by reaching patients with
information, who will demand that their physicians pay heed to those evidence-based advances. Dr. Kramer agreed, noting that
both patients and physicians increasingly make use of consensus development and other relevant databases. However, he cautioned
that current direct-to-consumer medical advertising can be problematic by sending messages to consumers that may be based on
relatively weak medical evidence.
FINAL COMMENTS AND DISCUSSION
Dr. Kirschstein said that a future ACD meeting will include discussions on modular grants. She also plans to have the NIH Office
of Extramural Research and Office of Technology Transfer present information on conflict of interest issues for further
discussion at a future meeting. She then asked Dr. William Brody to sketch the progress being made by the ACD working group on
construction issues.
Dr. Brody said that members of this group have held several discussions on the subject of budgeting NIH funds for constructing
extramural research facilities, with plans for resources to go to well-established institutions and also to historically black
colleges and universities. The working group is collecting data with the intention that its recommendations be data-driven. He
plans to present a report at the next ACD meeting, scheduled for June 7, 2001.
Dr. Kirschstein said that a completed NIH appropriations bill may permit another initiative in FY 2001, one in which NIH will
make available development enhancement awards for institutions in those 24 states and Puerto Rico that consistently receive
relatively low support from NIH. As part of this new program, NIH will be urging those institutions to form partnerships to
enhance their chances of building stronger programs and then to apply for NIH funds for planning and feasibility studies. This
program, called Biomedical Research Infrastructure Networks (BRIN), is to be administered through the NIH National Center for
Research Resources, and will be used as a model in designing programs for the new NIH Center on Minority Health and Health
Disparities.
Dr. Bettie Sue Masters suggested several topics for future ACD meetings, including the development of initial review groups
within the NIH Center for Scientific Review, particularly with reference to proposals involving structural biology outside x-ray
crystallography; relative levels of NIH funding for female and male scientists; and the challenge faced by researchers in
dealing with the expanding volume of NIH rules and guidelines. In response, Dr. Kirschstein noted that the National Institute of
General Medical Sciences supports a great deal of research in structural biology including NMR. She also said that Dr. Vivian
Pinn, Director of the NIH Office of Research on Women's Health, could speak to ACD about funding support for women scientists, a
subject of long-standing interest to Dr. Kirschstein, and about a meeting being convened in conjunction with the Society on
Advancement of Research in Women's Health.
Dr. Baldwin said that there is an NIH initiative to reduce the regulatory burden of researchers, and she would be happy to
describe it at a future ACD meeting. She also said that many of the regulations now in place are necessary, but other steps are
being taken to avoid certain kinds of premature and, thus, sometimes unnecessary reviews, as reflected by the recently adopted
"Just-In-Time" IRB reviews that are postponed until a decision is made about funding a pending proposal. Dr.
Kirschstein said that stronger guidelines and other protections are sometimes needed if clinical researchers are to adhere to
the fundamental precept of doing no harm.
In response to a request from Dr. Coble, Dr. Kirschstein said that Dr. Greg Koski, Director of the DHHS Office for Human
Research Protections (OHRP) will be invited to describe patient protection measures, including plans for streamlining IRB
assurances.
SUMMARY AND CONCLUSIONS
The Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) met on December 7, 2000, to consider the
implementation of guidelines developed by the NIH Office of Technology Transfer (OTT), a working group's contributions to the FY
2000 Government Performance and Results Act assessment of NIH research programs, detailed plans for establishing the newly
mandated NIH National Center on Minority Health and Health Disparities, and current efforts to implement ACD recommendations for
improving certain NIH Office of Medical Applications Research (OMAR)programs.
The ACD acknowledged and commented on these reports, and ACD members recommended several issues for consideration at its next
meeting.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Yvonne Maddox, Ph.D. Acting Executive Secretary Advisory Committee to the Director, NIH
Ruth L. Kirschstein, M.D Acting Director, NIH
TABLE OF ACRONYMS
ACD
Advisory Committee to the Director
AIDS
Acquired Immunodeficiency Syndrome
BACs
Bacterial artificial chromosomes
BECON
Bioengineering Consortium of Institutes and Centers
BISTI
Biomedical Information Science and Technology Initiative
BRIN
Biomedical Research Infrastructure Networks
cDNAs
Copy DNAs
CDC
Centers for Disease Control and Prevention
CME
Continuing Medical Education
COPR
Council of Public Representatives
CRC
Clinical Research Center
CSR
Center for Scientific Review
DALYs
Disability adjusted life years
DHHS
U.S. Department of Health and Human Services
DOE
Department of Energy
ELSI
Educational, Legal, and Social Implications
ESTs
Expressed Sequence Tags
FDA
Food and Drug Administration
FOIA
Freedom of Information Act
FY
Fiscal Year
GPRA
Government Performance and Results Act
GROW
Genetic Resources on the Web
HIV
Human Immunodeficiency Virus
HGDP
Human Genome Diversity Project
IBC
Institutional Biosafety Committee
IOM
Institute of Medicine
IRB
Institutional Review Board
IRGs
Integrated review groups
IP
Intramural Program
IT
Information technology
NAS
National Academy of Sciences
NBAC
National Bioethics Advisory Commission
NCBI
National Center for Biotechnology Information
NCCAM
National Center for Complementary and Alternative Medicine
NCI
National Cancer Institute
NCMHD
National Center on Minority Health and Health Disparities
NCRR
National Center for Research Resources
NIAMS
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIDA
National Institute on Drug Abuse
NIDCR
National Institute of Dental and Craniofacial Research
NIDDK
National Institute of Diabetes and Digestive and Kidney Diseases
NIH
National Institutes of Health
NIMH
National Institute of Mental Health
NINDS
National Institute of Neurological Disorders and Stroke
NHGRI
National Human Genome Research Institute
NLM
National Library of Medicine
NSF
National Science Foundation
OBA
Office of Biotechnology Activities
OB3
Office of Bioengineering, Bioimaging, and Bioinformatics
OHRP
Office for Human Research Protections
OMAR
Office of Medical Applications of Research
OPRR
Office for Protection from Research Risks
ORMH
Office of Research on Minority Health
OSP
Office of Science Policy
OTT
Office of Technology Transfer
PNAS
Proceedings of the National Academy of Sciences
QALYs
Quality adjusted life years
RAC
Recombinant DNA Advisory Committee
SNP
Single Nucleotide Polymorphism
TSC
The SNPs (single nucleotide polymorphism) Consortium
William R. Brody, M.D., Ph.D. President Johns Hopkins University Baltimore, MD 21218-2688
David R. Burgess, Ph.D. Professor Department of Biology Boston College Chestnut Hill,
MA 02167
Barrie J. Carter, Ph.D. Executive Vice President and Director of Research and Development Targeted
Genetics Corporation Seattle, WA 98101-1823
Christine K. Cassel, M.D. Professor and Chairperson Department of Geriatrics and Adult
Development The Mount Sinai School of Medicine New York, NY 10029-6574
Thomas R. Cech, Ph.D. President Howard Hughes Medical Institute Chevy Chase, MD 20815
Steven Chu, Ph.D. Professor Physics Department Stanford University Stanford, CA
94305-4060
Yank D. Coble, Jr., M.D. Physician Jacksonville, FL 32205
Victor J. Dzau, M.D. Chairman Department of Medicine Brigham and Women's Hospital Boston,
MA 02115
Rebecca S. Eisenberg Professor of Law University of Michigan Law School Ann Arbor, MI
48109-1215
Charles K. Francis, M.D. President Department of Medicine Charles R. Drew University of
Medicine and Science Los Angeles, CA 90059
Eric S. Lander, Ph.D. Member, Whitehead Institute for Biomedical Research Professor of Biology Massachusetts
Institute of Technology Director, Whitehead Institute/MIT Center for Genome Research Cambridge, MA 02139-1561
Bettie Sue S. Masters, Ph.D. The Robert A. Welch Foundation Professor in Chemistry Department of
Chemistry, MSC 7760 The University of Texas Health Science San Antonio, TX 78229-3900
Cecil B. Pickett, Ph.D. Executive Vice President for Research Schering-Plough Research Center Kenilworth,
NJ 07033
Larry L. Smarr, Ph.D. School of Engineering University of California, San Diego La Jolla, CA
92093-0403
Shirley M. Tilghman, Ph.D. Lewis Thomas Laboratory Department of Molecular Biology Princeton
University Princeton, NJ 08544
Arthur D. Ullian Chairman, Task Force on Science, Health Care and The Economy Boston, MA
02110
Linda J. Waite, Ph.D. Professor National Opinion Research Center, University of Chicago Chicago,
IL 60637
Phillip L. Williams Vice Chairman (Retired) The Times Mirror Company Pacific Palisades, CA
90272
Donald E. Wilson, M.D. Vice President for Medical Affairs Dean, School of Medicine University
of Maryland, Baltimore Baltimore, MD 21201-1559
Executive Secretary Ruth L. Kirschstein, M.D. Deputy Director National Institutes
of Health
Bethesda, MD 20892
APPENDIX C - SPEAKER LIST
Harvey J. Alter, M.D. Chief, Infectious Disease Section and Associate Director of Research Department
of Transfusion Medicine Warren Magnuson Clinical Center National Institutes of Heatlh Bethesda, MD 20892
Arthur Bienenstock, Ph.D. Associate Director for Science Office of Science and Technology
Policy Washington, DC 20502
Maria Freire, Ph.D. Director Office of Technology Transfer National Institutes of Health Bethesda,
MD 20892
Barnett (Barry) Kramer, M.D. Director Office of Medical Applications of Research Office of
Disease Prevention National Institutes of Health Bethesda, MD 20892
Ting-Kai Li, M.D. Distinguished Professor Indiana University School of Medicine Indianapolis,
IN 46202-5124
John Ruffin, Ph.D. Associate Director for Research on Minority Health National Institutes of
Health Bethesda, MD 20892
Lana R. Skirboll, Ph.D. Associate Director for Science Policy National Institutes of Health Bethesda,
MD 20892
Notice of Actions Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (published in the
Federal Register, October 10, 2000)
Human Genome Sequence Data Web Sites
Human Pluripotent Stem Cell Research
National Institutes of Health Guidelines for Research Using Human Pluripotent Stem Cells
Approval Process for the Documentation of Compliance with the
NIH Guidelines On The Use of Human Pluripotent Stem Cells in NIH Research Proposed for Support Under Grants and
Cooperative Agreements
Sharing Biomedical Research Resources
Principles for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources:
Request for Comments (published in the Federal Register, May 25, 1999)
Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical
Research Resources: Final Notice (published in the Federal Register, December 23, 1999)
The Safety of the Blood Supply — Hepatitis Viruses
The Albert Lasker Medical Research Awards
Article from Nature Medicine
National Center on Minority Health and Health Disparities
Fact Sheet — Office of Medical Applications of Research
* Copies of these reports and articles are available upon request by calling (301) 496-0959.
