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.
