The 89th meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December 2 and 3, 2004. NIH Director Elias A. Zerhouni, M.D., welcomed a new committee member, Joan Reede, M.D., M.P.H., M.S., Dean, Diversity and Community Partnership, Harvard Medical School.
Dr. Zerhouni reported on meetings with committees of the U.S. Congress to discuss NIH processes and priorities, including research safety efforts, conflict-of-interest issues, and the future reauthorization of the NIH. Dr. Zerhouni announced that David A. Schwartz, M.D., would become the new Director of the National Institute of Environmental Health Sciences in April 2005.
Dr. Zerhouni expressed a deep sadness for the recent passing of John R. La Montagne, Ph.D., former Deputy Director of the National Institute of Allergy and Infectious Diseases (NIAID). Anthony Fauci, M.D., who, as Director of NIAID, worked closely with Dr. La Montagne, described him as a true hero in American medicine and an extraordinary force in the field. A memorial service was held on November 30. Dr. Zerhouni noted another tragedy in the NIH community. Mr. Ronal Alvarado Gochez, a Salvadoran immigrant who was working on an NIH construction project, was killed by the collapse of a concrete beam in a parking garage.
Dr. Zerhouni announced the retirements of five members of the Advisory Committee — David Burgess, Ph.D., Charles Francis, M.D., Bettie Sue Masters, Ph.D., Cecil Pickett, Ph.D., and Linda Waite, Ph.D. — who were participating in their final ACD meeting. This also was the final official appearance at an ACD meeting for Mr. Lawrence Sadwin, who had been serving as liaison for the Director's Council of Public Representatives (COPR).
Dushanka Kleinman, D.D.S., M.Sc.D., Assistant Director for Roadmap Coordination, provided an update on the NIH Roadmap for Medical Research. The planning of the NIH Roadmap included more than 300 stakeholders. Dr. Kleinman gave highlights of FY2004 activities and funded projects. In the area of new pathways to discovery, one initiative supported four National Centers for Biomedical Computing; additional centers will be funded in FY2005. In the area of preparing the research workforce, it funded new training programs and curriculum development programs. In the area of nanomedicine, 20 concept development awards were funded. Solicitations for Nanomedicine Development Centers in FY2005 and FY2006 are under development. Twenty-one Interdisciplinary Research Exploratory Centers were funded in FY2004. About 10 translational research centers, currently being planned with Roadmap funds, should begin operations by FY2006. Dr. Kleinman provided an overview of planned FY2006 programs such as the Interdisciplinary Technology and Methods Summit and a National Electronic Clinical Trials and Research Network.
Jeremy Berg, Ph.D., Director of the National Institute of General Medical Sciences, reported on the 2004 Director's Pioneer Awards and plans to modify the awards for 2005. Nine awards were presented in September 2004. Possible changes for the following year include allowing only self-nominations and limiting eligibility to persons who are within 15 years of receiving their terminal doctoral degree. The ACD members discussed these issues at length, considering aspects of bias, diversity, and the purposes of the awards. They voted to support a recommendation that the awards not be restricted to applicants with more recent degrees.
Mr. Sadwin presented results of the October 2004 COPR Workshop titled, Inviting Public Participation in Clinical Research: Building Trust Through Partnerships, which produced recommendations in five broad areas of interest. These were: building trust through community partnerships, building relationships with patients, building partnerships with community providers, building trust in scientists, and building trust in NIH/scientific research. Discussions within each area produced specific recommendations and action items for advancing toward the goals. A final recommendation was to document and publish best practices. The topic of building trust and partnerships also elicited a wide-ranging discussion by the ACD members, who considered issues of diversity and disparities.
Dr. Waite reported efforts by the Working Group on Research Opportunities in the Basic Behavioral and Social Sciences. She was joined by group members Robert Levenson, Ph.D., Bruce McEwen, Ph.D., and Susan Fiske, Ph.D. The working group members described applications of the basic behavioral and social sciences (BBSS) to diseases, noting in particular recent advances in matching behaviors to neural circuits and genes. A number of institutes of the NIH currently are supporting research that involves BBSS while focusing on specific diseases or life stages but much of the most basic of BBSS research has been supported at NIMH. Given recent redirection of priorities at NIMH as well as newly emerging scientific opportunities, the working group recommended establishing a stable locus within the NIH that would be dedicated to supporting non-categorical basic research in BBSS.
Dr. Reede reported progress made by the working group for outside awards for NIH employees. To address concerns that some outside awards to NIH employees have had the appearance of a quid pro quo relationship, the working group was charged with assessing current awards and developing a list of those that meet the regulatory definition of "bona fide award for meritorious public service or achievement." Dr. Reede presented a list of such awards, explaining that other awards would be added to this prescreened list when appropriate information for each was obtained.
Mr. Richard Turman, Associate Director for Budget, provided an update on the budget process. He stated that the expected 2005 NIH budget is $28 billion, but the process for the passage of a new budget is not quite complete. The NIH has been operating under a continuing resolution since October 1. President Bush had asked for an increase of about 2.6 percent over the previous year. Congress deliberated, and now appears ready to support a 2-percent increase, or about $565 million more than the previous year. As a result, the number of research project grants likely would not increase. Mr. Turman indicated he would be able to offer a clearer picture of the final dollar amounts at the next ACD meeting in June. The President's 2006 budget proposal will be released publicly in February.
Norka Ruiz Bravo, Ph.D., Deputy Director for Extramural Research at NIH, reported that the working group on training and career opportunities for postdoctoral professionals has been collecting a series of recommendations. A National Postdoctoral Association white paper released in May 2003 and an NIH postdoctoral meeting in October 2003 both recommended, among other things, that postdocs receive a uniform benefits package regardless of appointment or mechanism of support. These groups made many additional recommendations, which Dr. Ruiz Bravo reviewed. The ACD reviewed the items presented and voted to support proposed increases in paid health insurance coverage for postdocs.
Ting-Kai Li, M.D., Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), made a formal presentation of the history, scope, and work of his institute. The NIAAA joined the NIH in 1992, having been a component of the Alcohol, Drug Abuse, and Mental Health Administration. The NIAAA resides today near the middle of the list of NIH institutes and offices, as ranked by appropriation. Dr. Li reviewed essential aspects of alcohol metabolism and neuropharmacology, and noted progress in identifying genes involved in alcoholism. He described NIAAA's priority research areas and opportunities for translational research. The institute is currently realigning its focus to feature interdisciplinary research, multidisciplinary approaches among staff, and stronger career development.
Raynard Kington, M.D., Ph.D., reviewed the progress of the blue-ribbon task force, initiated by Dr. Zerhouni, for the study of conflict-of-interest issues for employees of the NIH. This task force has been working with the Office of the General Counsel, HHS, to develop policies in three areas: (1) outside activities, such as consulting by NIH employees, (2) financial interests, such as stock holdings, and (3) awards (a topic covered by Dr. Reede earlier in the meeting). The new guidelines would cover all NIH employees, including intramural researchers, and would make use of new technologies, such as online form submissions.
Mr. John Burklow, Associate Director for Communications and Public Liaison at NIH, described ongoing efforts to advance the NIH communications plan. This involves increasing media coverage of NIH news and events and developing structural consistency in NIH products, such as news releases. The announcement of the completion of the new Clinical Center has been cause for increased media attention, generating some 50 million media impressions.
John Gallin, M.D., Director of the NIH Clinical Center, presented a brief history of the NIH Clinical Center and a description of the new addition, the Mark O. Hatfield Clinical Research Center, which will begin operating soon. The new center features many state-of-the art technologies and notably includes accommodations for one-day-stays for up to 80 patients.
Dr. Ruiz Bravo reported on the progress of an initiative to increase public access to NIH research results by creating an archive of peer-reviewed publications by NIH-supported researchers. This archive also would offer the benefit of helping NIH to better manage its portfolio of research and to monitor scientific productivity. Dr. Ruiz Bravo gave details of the development, including a process of public outreach and solicitation of ideas (public meetings, notices, presentations).
The 89th meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held December 2 and 3, 2004, on the NIH campus and Webcast globally. The next meeting will be held June 2–3, 2005.
NIH Director Elias A. Zerhouni, M.D., welcomed a new committee member, Joan Reede, M.D., M.P.H., M.S., Dean, Diversity and Community Partnership, Harvard Medical School. Dr. Reede had already been serving as chair of the ACD workgroup on outside awards. Dr. Zerhouni also welcomed Mr. Lawrence Sadwin, Mr. Craig Beam, and Debra Hall, Ph.D., members of the Council of Public Representatives (COPR), and noted that U.S. Senator Connie Mack and Mr. Phillip Williams, of the Times Mirror Company, could not attend.
Dr. Zerhouni presented highlights of NIH activities since May 2004. The NIH officially opened its new Mark O. Hatfield Clinical Research Center on September 22, 2004. John Gallin, M.D., Director of the Clinical Center, oversaw the opening ceremonies after many years of shepherding the complex development process. The new center is dedicated to clinical research and represents the most significant addition to the NIH in 50 years. It offers an opportunity to perform leading-edge clinical research, and it can accomplish unique functions in comparison to other clinical centers. As the new clinical center was being built, NIH was investigating strategic plans for clinical and translational research, producing the Goldstein-Benz Blue Ribbon Panel Report.
Dr. Zerhouni announced that four former NIH grantees received Nobel Prizes in 2004. They were Richard Axel, M.D., of the Howard Hughes Medical Institute (HHMI) and Columbia University, Linda Buck, Ph.D., of HHMI and the Fred Hutchinson Cancer Research Center, Irwin Rose, Ph.D., of the University of California, Irvine, and Avram Hershko, M.D., Ph.D., of Technion–Israel Institute of Technology, Haifa, Israel.
The NIH has been studying ways to improve public access to its research, in particular, to publications of NIH-funded, peer-reviewed research. Dr. Zerhouni cited a great concern for making this information easily available. The NIH desires to establish a stable archive of its peer-reviewed research and to make it available to the public, to organizations, and to researchers. This repository also would help the NIH to review and manage its research portfolio, to monitor scientific productivity, and to link to the wider world of research databases.
A goal, explained Dr. Zerhouni, is for the repository to augment current efforts at scientific diffusion. The NIH held open meetings with publishers, scientists, patient advocates, scientific associations, and other groups, and solicited opinions from the public for this proposal. The NIH believes it heard from every group for whom this issue is relevant.
Dr. Zerhouni distributed a memorandum to the entire NIH staff in September, announcing an upcoming 1-year moratorium on consultations with pharmaceutical and biotechnology companies. The NIH would use this period to study issues of conflict of interest, to review current processes in this area, and to develop new policies, including training. One goal of new conflict-of-interest policies is to maintain the public trust. The NIH also desires to ensure that contacts between government, academia, and industry continue. It will seek policies that help to accelerate the translation of scientific research and that attract and retain the best scientists, while at the same time protecting the integrity of NIH programs and information.
Dr. Zerhouni reported that the COPR has been doing an extraordinary job. At its past few meetings, the Council discussed issues of public confidence and trust in biomedical research. Those efforts have run parallel to the NIH's Public Trust Initiative. At their October 2004 meeting, titled Inviting Public Participation in Clinical Research: Building Trust through Partnerships, the COPR produced a long list of recommendations, which will soon be released.
The U.S. House of Representatives Energy and Commerce Health Subcommittee has recently held hearings on NIH priority setting, including one in June at which Dr. Zerhouni and several NIH Institute and Center directors testified. They reviewed institute and agency processes with the aim of establishing future research priorities and eventually reauthorizing the NIH. The NIH will continue to respond to questions about priorities as this Congressional process continues.
The House Energy and Commerce Oversight and Investigations Subcommittee has held hearings on conflict-of-interest issues. In June, Dr. Zerhouni testified on the status of those issues and proposals for addressing them. Considering that the NIH is a hybrid organization (government and science/academia), he recognized the need for stronger restrictions on NIH officials who have direct granting and contracting authority. Raynard Kington, M.D., Ph.D., the ethics representative for the agency, is working with the Office of the General Counsel of the Department of Health and Human Services (HHS), to advance the discussions.
Dr. Zerhouni noted other Advisory Committee meeting agenda topics: Mr. Richard Turman, Associate Director for Budget, would provide an update on the NIH budget process. Working group presentations would stimulate discussions on training and career opportunities for postdocs, on progress by the Working Group on Research Opportunities in the Basic Behavioral and Social Sciences, and on progress by the Working Group on Outside Awards for NIH Employees.
Dr. Zerhouni announced that, on April 4, 2005, David Schwartz, M.D., M.P.H., would become the new Director of the National Institute of Environmental Health Sciences. Dr. Schwartz is the current Vice Chair of Medicine at Duke University, and his research has focused on genetic and biological determinants of environmental lung disease. His work has provided insights into the pathophysiology and biology of asbestos-induced lung disease, interstitial lung disease, environmental airway disease, and innate immunity. Kenneth Olden, Ph.D., the current Director of the NIEHS, will stay on until April, after which he will become a researcher in the institute's intramural program.
Dr. Zerhouni expressed a deep sadness for the recent passing of John R. La Montagne, Ph.D., former Deputy Director of the National Institute of Allergy and Infectious Diseases (NIAID). Dr. La Montagne died suddenly in Mexico City on November 2, 2004. Dr. Zerhouni noted that he received an outpouring of condolences immediately following the death of Dr. La Montagne, who had devoted his life to improving the health of children and adults both here and abroad. Anthony Fauci, M.D., Director of NIAID, organized a memorial service. Dr. Fauci described Dr. La Montagne as a true hero in American medicine and an extraordinary force in the field. Dr. La Montagne was selfless and never focused attention on himself as he went about his important work. When Dr. Zerhouni recently attended the World Health Forum in Mexico City, he received yet another outpouring of condolences from the international attendees.
Dr. Zerhouni noted another tragedy in the NIH community. Mr. Ronal Alvarado Gochez, a Salvadoran immigrant who was working for a steel company on an NIH construction project, was killed by the collapse of a concrete beam in a parking garage. Mr. Alvarado had come to this country to seek a new future for himself and his family. He was contributing by working in an extremely difficult job, and the NIH is doing what it can to help his family in this sad time.
Dr. Zerhouni announced that the meeting would include an update on the first year of Roadmap activities. He thanked Dushanka Kleinman, D.D.S., M.Sc.D., who has taken time from her work at the National Institute of Dental and Craniofacial Research (NIDCR) and dedicated herself to the Roadmap effort. Also, Jeremy Berg, Ph.D., Director of the National Institute of General Medical Sciences (NIGMS), would report on the Pioneer awards, and Ting-Kai Li, M.D., would make a presentation on the National Institute of Alcohol Abuse and Alcoholism (NIAAA), of which he is Director.
Dr. Zerhouni announced the retirements of the following members of the ACD: David Burgess, Ph.D., Charles Francis, M.D., Bettie Sue Masters, Ph.D., Cecil Pickett, Ph.D., and Linda Waite, Ph.D., all of whom were participating in their final ACD meeting. This also was the final official appearance at an ACD meeting for Mr. Lawrence Sadwin, who had been serving as liaison for the Director's Council of Public Representatives (COPR).
Dr. Kleinman, Assistant Director for Roadmap Coordination, provided an update on the NIH Roadmap for Medical Research. She directed the meeting participants to press releases of the past year, a list of research that has been funded, a list of FY2005 solicitations, and published articles about the NIH Roadmap for Medical Research. Nine working groups across three Roadmap themes — with representation by various institutes and centers — addressed 28 approved solicitations. More than 300 stakeholders gave input to the planning process of the NIH Roadmap, and the resulting initiatives are ones that would accelerate the conduct and application of science for public benefit. The chosen initiatives were seen as ones to benefit all Institutes and Centers.
Dr. Kleinman provided highlights of FY2004 projects leading to the development of new tools and technologies as demonstrated in the FY2004 funded projects. Four National Centers for Biomedical Computing were funded with a focus on developing software. Another four centers are to be funded next year. Seven grants funded sites for the Patient Reported Outcomes Measurement Information System (PROMIS), statistical coordinating centers that will enhance the validity and reliability of medical measurements. They will result in a publicly available data bank and an adaptable test.
In the area of preparing the research workforce, the NIH Roadmap for Medical Research funded new training programs and made solicitations for curriculum-development programs. Training is ongoing for interdisciplinary research, clinical (including multidisciplinary) research, and biomedical and behavioral research.
In the area of nanomedicine, the NIH Roadmap for Medical Research distributed 20 concept development awards that will lead to the funding of Nanomedicine Development Centers in FY2005 and FY2006. The program funded 21 Interdisciplinary Research Exploratory Centers in FY2004, which are focusing on developing teams to address complex diseases and disorders and removing institutional barriers for scientific areas such as behavioral epidemiology. The Roadmap program is funding pilot studies to learn how to build upon the backbone of clinical research networks. Another project is identifying networks and their best practices.
About 10 translational research centers, currently being planned with Roadmap funds, should begin operations by FY2006. Dr. Kleinman described additional processes that may culminate in FY2006, such as an Interdisciplinary Technology and Methods Summit and a National Electronic Clinical Trials and Research Network.
Outside the funded projects, the NIH Roadmap for Medical Research has progressed in policy and structural areas, such as changing fiscal rules that had hindered interinstitutional collaborations, enhancing guidance for performing clinical research reviews, and increasing the capacity of researchers to communicate through the Web. Senior NIH representatives have traveled around the country, offering institutions and professional organizations information about the NIH Roadmap for Medical Research and learning about the Roadmap-like initiatives of others.
Dr. Kleinman estimated that 500 to 600 individuals at NIH are working in some way on Roadmap activities. The Implementation Coordination Committee governs the process and comprises the chairs of the working groups, who are directors at the NIH. The Roadmap liaisons (individuals who speak on behalf of the directors of institutes and offices), the implementation working groups, and project teams all work together to make the initiatives happen.
Discussion
In response to a question about the involvement by extramural scientists, Dr. Kleinman cited the involvement of approximately 300 stakeholders, including scientists and healthcare providers, in the development of the Roadmap. Workshops to discuss the maturing of Roadmap initiatives have relied greatly on the input and expertise of attending extramural scientists. Extramural scientists have also participated in the review process.
Dr. Zerhouni emphasized that it is the intent of the NIH Roadmap for Medical Research to develop chemical libraries that would enrich research and act as tools. The Roadmap is not intended to develop therapeutic drugs. Using technology development, assay development, and PubChem, a Roadmap effort will develop a comprehensive, publicly available database of all known chemical interactions with biological molecules of interest.
In response to a question of whether funding of the Roadmap initiative has affected other programs, Dr. Zerhouni stated that the $37 million for the Roadmap in 2004 did not lead to a decrease in the funding of R01 grants (in fact, their funding increased). The Roadmap initiative can enrich the R01 pool in terms of capabilities and help create a balanced portfolio. Larry Smarr, Ph.D., suggested that the NIH study aggregations of researchers and areas of underinvestment and determine ways (perhaps with help of the Roadmap) to better balance the portfolio.
R. Sanders Williams, M.D., wondered whether institutions could parse-out the credit for work under large grants as an incentive to team-formation. Dr. Ruiz Bravo responded that a team within the NIH Roadmap and the National Science and Technology Council's Research Business Models initiative is studying that issue, and the program likely would move in that direction. Yet, noted Dr. Zerhouni, distributing credit satisfactorily could be very difficult. Dr. Ruiz Bravo added that this issue affects the institutions themselves, involving tenure decisions in very specific areas. The funding is complex as well. Dr. Zerhouni indicated that in some cases, increasing the distribution of funds within an institution might increase the silo effect.
Raghavendra Vijayanagar, M.D., asked how all of the institutes and centers at NIH contribute to the Roadmap initiative. Dr. Kleinman responded that the nine NIH Roadmap for Medical Research working groups feature representatives from all institutes and centers. Also, the teams working on specific projects reach out to the appropriate institutes and centers. Funding for the NIH Roadmap for Medical Research comes from each of the institutes and centers (excepting the centers that do not have appropriations), as well as the Director's discretionary fund.
Jeremy Berg, Ph.D., Director of the National Institute of General Medical Sciences (NIGMS), who, along with Nora Volkow, M.D. Director of the National Institute on Drug Abuse, chairs the High-Risk Research Work Group, presented an overview of activities surrounding the Pioneer Awards. These Awards, but one of a number of initiatives intended to encourage high-risk research, put the emphasis on supporting people rather than projects.
In the first year of the program, applicants could nominate themselves or others. This resulted in more than 1,300 nominations and, following a novel evaluation process, the distribution of 9 awards. For these FY2004 awards, 35 percent of the applicant pool was self-nominated, 33 percent of the awardees were self-nominated, and 36 percent of the nominees were women. The 9 awardees of the first year were all males, causing the current program administrators to be sensitive to any possibility of gender bias.
The program planners are considering changes to the process. One idea is to entertain self-nominations only because some first-year reviewers experienced discomfort in addressing the two types of nominations.
Another possible change is to limit eligibility to persons who are within 15 years of having attained their terminal doctoral degrees. This was proposed because some reviewers had difficulty comparing very different levels of experience. The program planners also recognized the need to address a fundamental confusion about whether the award was for past pioneers or future pioneers. The emphasis is on the latter, that is, on novel, promising science.
The announcement of the second year of the award will be made in early 2005. Dr. Berg asked the members of the ACD to help disseminate information about the program to a wide and diverse pool of potential nominees. The evaluation process would be similar to the previous year, and the ACD members would participate in the final level of review. Dr. Berg, thanked all those persons who helped launch the award program in the past year.
Discussion
The committee members discussed the proposed changes at length. By a wide margin, they felt there should be no time/age constraints on eligibility for applying for the award. The criteria should focus on the novelty and potential impact of the research idea. Annelise Barron, Ph.D., noted that a time/age limitation might allow more women to apply for and obtain the award. Dr. Waite added that such a restriction could help younger researchers — recognizing that more experienced researchers tend to have greater success when coming before study sections.
J. Michael Bishop, M.D., agreed that allowing only self-nominations is preferable. He suggested calling the process an application rather than a nomination. This would eliminate the confusion about "past pioneer" and "future pioneer" (the latter being correct).
The members decided that an initial screening of applicants should be blinded, with selection based solely on the merits of the science. They also respected the need to have a subsequent screening to look at certain issues surrounding the candidate, such as the candidate's availability, training, and work environment.
The group had mixed responses to the need for personal interviews. Some applicants interview poorly despite very promising projects, and biases can come into play. On the other hand, some applicants use the interview process to reveal important, even crucial information about the project, thereby making the process very valuable. All agreed that interviewers should be trained to eliminate bias, although some felt that it was impossible to eliminate fully.
Dr. Zerhouni stated that the NIH has been addressing the quality of the review process and hopes that the Pioneer Awards might serve as a test. The discussion in this meeting would encourage the NIH to be clearer in the language used to describe the award and application process. He asked the committee members to vote on the proposal to limit the applicants based on the number of years since attaining their doctoral degrees. The Advisory Committee moved, seconded, and passed the following recommendation: The Advisory Committee recommends to the Director that the Pioneer Award not be restricted in any way (for example, by age, sex, or time since degree) and that the review process be evaluated periodically to prevent intrinsic biases from arising.
Mr. Sadwin stated that his group would present the results and recommendations from the October 2004 COPR Workshop, "Inviting Public Participation in Clinical Research: Building Trust through Partnerships." The recommendations would be distributed to the NIH and the clinical research community. The purposes of the workshop were threefold:
To provide an overview of the current status of public participation and trust in medical research
To learn about past interrelationships and some proven strategies to build partnerships and engender trust
To explore, in highly interactive sessions, the barriers to and opportunities for building public participation and trust
Participants in the meeting represented many communities, in terms of geography, culture, and diseases. The research, health care, and medical-media communities also were represented. The workshop produced recommendations in five areas:
Building trust though community partnerships
Building relationships with patients
Building partnerships with community providers
Building trust in scientists
Building trust in NIH/scientific research
Dr. Hall, Mr. Sadwin and Mr. Beam reviewed all recommendations and possible actions within those five broad areas. The workshop recommended actions including the following:
First Area of Interest: Building Trust Through Community Partnerships
Establish grant criteria that requires community involvement
Include public trust issues in strategic planning
Identify barriers to research that engage the community
Encourage researchers to share financial support with the community
Build on NIH Clinical Research Associates Program
Partner with community sanctioned organizations
Assist communities in developing their own research projects
Reward researchers with ongoing relationships/partnerships in the community
Bridge the gap between clinical trials and additional treatment
Work with other Federal agencies to address insurance issues
Create an intergovernmental task force to study continuity of health care
Second Area of Interest: Building Relationships with Patients What do patients need, want, expect?
Be told the relevance of the study
Know that they are important and so is their health
Be treated as a person, not a case number
No conflict of interest
Ease of access
Liaison or ombudsman
Require researchers to thank participants
Require a feedback loop in study designs
Strongly encourage researchers to treat patients as partners
To hear study results
Require researchers to disclose trial outcomes
Encourage regular exchanges between researchers and participants
Train researchers to explain how research translates into community benefits
Third Area of Interest: Building Partnerships with Community Providers
Learn about the barriers to local provider participation
Engage community providers through the top 5 or 10 leading research institutions
Enlist teaching hospitals
Collaborate with professional organizations
Make participation in clinical trails easier for local physicians who could refer patients into the trials
Consider funding the development of software for local MDs
Share data with community physicians
Fourth Area of Interest: Building Trust in Scientists
Collaborate with schools, professional societies and organizations
Hold a conference for the deans of medical schools
Make presentations to professional groups
Create fellowships in public trust
Create a certification for researchers who are conducting research in the community
Enhance relationships with the media
Create pride in trial participation
Educate the public about the evolving nature of research findings
Engage elected officials and other spokespersons
Fifth Area of Interest: Building Trust in NIH/Scientific Research
Enhance relationships with the media
Create pride in trial participation
Educate the public about the evolving nature of research findings
Engage elected officials and other spokespersons
Continue and expand outreach projects
Continue to educate journalists
Continue network of health and science journalists
Host annual NIH conference
Convert consent forms into plain language documents that protect both parties equally
Educate Institutional Review Board (IRB) members about community issues vis-à-vis research
Increase public participation in IRBs
Survey researchers about IRB-related barriers
A final recommendation was to document and publish best practices. Dr. Hall directed the committee members to a matrix that proposed the application of the recommendations based on degrees of difficulty over a 10-year time period.
Discussion
Dr. Masters characterized the report as thorough. Dr. Williams asked whether the recommendation that researchers disclose trial outcomes to the community should apply to industry researchers. The workshop did not consider that idea. Dr. Williams suggested that the goal of eliminating conflicts of interest is not attainable, and presenting that expectation might be unrealistic.
Dr. Burgess stated that within the American Indian communities, trust has eroded, and the communities have created their own IRBs. He cited a need for diversity among scientists and for the scientists to resemble the people of the community. He asked if this was a potential agenda topic for a future ACD meeting. Does the NIH need a greater emphasis on disparities? Perhaps the NIH Roadmap for Medical Research could serve as a bully pulpit for this issue.
Dr. Zerhouni responded that the topic of health disparities is one of the five priorities of the Roadmap initiative. As NIH Director, he uses his bully pulpit to address these priorities. The NIH continues to have a fundamental process that addresses the issue of health disparities. The Roadmap initiative is a platform for all initiatives, and the NIH seeks to create a wider community implementation.
Diversity is a separate issue. Underrepresentation of groups continues despite great efforts through the years, including the application of large resources. The lack of diversity remains a problematic issue. Dr. Kington noted that the NIH has explored evidence-based research to develop new methods for addressing diversity problems. This is an empirical approach to reveal what efforts have failed and which programs have been successful.
Dr. Zerhouni cited a lifetime grant process study finding that no strategies were able to improve diversity. It is a large systemic issue. Dr. Francis noted that many strategies had been applied repeatedly without success. Perhaps the NIH is not the proper agent to address the diversity problem. Perhaps the answer lies within the educational system or in the political will of government. Dr. Francis suggested that a sense of science and research being open to minorities is not in the general awareness. The NIH might help by stimulating interest in the biological sciences at early ages. Community involvement is crucial. Medical schools should make better connections to communities.
Dr. Burgess noted that many pre-college diversity strategies have successfully drawn diverse populations into the sciences. However, that trend does not continue through the college years.
Dr. Zerhouni agreed that diversity should be an item on a future ACD meeting agenda. The committee could present efforts and analyses that have been done and discuss possible future actions.
Research Opportunities in the Basic Behavioral and Social Sciences Working Group Report
Dr. Waite described the charge to her working group as: "To address NIH support in basic behavioral and social sciences that was fundamental to the prevention, treatment, and cure of illness and that was not linked to specific disease." The work group studied the NIH portfolio, looking for opportunities that would benefit NIH and barriers to the funding of this research. It now was recommending improved support for basic behavioral and social sciences (BBSS) research at the NIH.
Behavioral and social processes occur within individuals, groups, organizations, and larger populations. Biopsychosocial processes are the interactions of biological factors with behavioral or social variables. Dr. Waite described BBSS research as critical to the NIH mission. We need a trans-NIH strategy for BBSS research and training. Recent changes in the priorities of the National Institute of Mental Health (NIMH) have curtailed funding for BBSS research and might cause important areas of basic research to be lost. Social and behavioral factors affect every aspect of health and illness. Behavioral and social methods, measures, and constructs will be needed to help understand the relevance to health of breakthroughs in, for example, genetics, neural activity, and biomarkers.
Robert Levenson, Ph.D., of the working group, presented a flowchart illustrating the causal areas for health and illness, including the levels of environment, social positions and processes, behavioral and psychological processes, and biological/genetic effects. Linked to those areas were broad areas of intervention. Dr. Levenson gave an example of a recent study led by BBSS researchers in developmental and personality psychology that found a gene polymorphism linked to the likelihood of developing depression. This likelihood resulted from a combination of the polymorphism and other behavioral/social factors such as stress — a complex relationship. This research (selected by Science as one of it's top five breakthrough studies of the year) demonstrated the importance of very basic BBSS for uncovering results that could lead to new interventions for prevention and treatment. BBSS researchers need to study emotions, health-promoting behaviors, cognitive styles, and much more to unravel such disorders and to develop interventions. Such sciences have been developed independently of work on genes and psychopathology. They would benefit from a stable home within the NIH.
Working group member Susan Fiske, Ph.D., reviewed opportunities in BBSS research related to health and disease. At the macro level, population changes that involve frequent moving, and changing community inter-ethnic relationships, disrupt social networks. Health suffers because people depend on each other to remain healthy and their access to health care and information changes as well. At another level, health care depends in part on interpersonal relationships, which can suffer because of issues such as stereotyping and prejudice. Also, personal emotions — positive and negative — have physiological effects and can lead to health risks.
Bruce McEwen, Ph.D., also of the work group, added the issue of gene-environment interactions and the need for cross-cutting research. For example, recent findings concerning effects of caregiver stress causing shortening of the telomeres and, hence, accelerated aging, came about through a collaboration between health psychologists and basic biological scientists. Work in this and related areas demonstrates that it is important to train researchers in multiple sciences. Such complex areas of health also require that scientists consider the entire life course, looking for pre-disease pathways as well as disease pathways.
The working group's examination of the NIH portfolio revealed BBSS research was being conducted in more than a half-dozen institutes. Yet these institutes are devoted to specific diseases or life stages. There is no home for BBSS research that is not related to a particular disease or life stage. Therefore, the working group made recommendations, including the following:
Create a new home for BBSS research that is not yet linked to specific diseases or life stages at the NIH
NIH Institutes and Centers currently supporting BBSS research should continue to do so for work relevant to their missions
OBSSR could support the following activities:
Develop research priorities and initiatives
Continue to review the NIH portfolio
Help familiarize program staff at NIH institutes with BBSS research
Help researchers to direct their proposals to appropriate institutes and centers
Discussion
Dr. Zerhouni thanked the working group for its presentation. In response to a question, Dr. Waite noted that the proposal by the working group was to create a division or program within an existing institute or center, not to create a separate institute or center.
Dr. Williams asked how needs of this research compared to other cross-cutting research that did not fit into specific diseases or life stages, for example, biophysics. Dr. Levenson responded that BBSS research was reduced when the NIMH refocused its energies on its essential mission: mental health and illness. This demonstrates how BBSS research can suffer when not tied formally to an NIH institute or center. Dr. Fiske added that historically there has been an underappreciation for social and behavioral factors in health.
Dr. Smarr expressed the concern that by placing BBSS research in one place within the NIH, the other institutes and centers would not feel obligated to pursue this research. Perhaps there could be a home for a number of basic nonapplied sciences, such as BBSS and information sciences, and a formal encouragement by the Director to spread the research among all institutes and centers where appropriate (and in the NIH Roadmap for Medical Research).
Dr. Levenson commented that the National Science Foundation has only a very small budget for BBSS research, although this research is part of the NSF mission. Dr. Zerhouni wondered why the NSF does not invest a larger fraction of its funding in such research. Other committee members emphasized the pervasive importance of BBSS research issues for diseases and disorders such as cardiovascular disease, diabetes, and obesity. Dr. Fiske stressed the need for fundamental work in BBSS research, as opposed to applied work.
Dr. Zerhouni asked the work group members whether they considered the NIH portfolio to be properly balanced with regard to fundamental undifferentiated research and basic research. Referring to an appendix of funding amounts, Dr. Waite noted that, for example, the National Cancer Institute (NCI) funds a great deal of research that is BBSS-related, yet the research focuses strictly on cancer. Much important BBSS research cannot fit into NCI's disease-based scenario or that of other institutes.
Dr. Zerhouni agreed that there was a large gap in BBSS research, yet he expressed discomfort with the prescription of large, costly structural change. He went on to suggest the possibility of an opportunity-cost analysis of the NIH portfolio. How could we balance portfolio review analysis with these issues? An important question is about scientific opportunities for new knowledge that could enhance our understanding of both biology and behavior. Dr. Zerhouni suggested that we are entering into important interface fields, such as neurobiology and behavior and the interaction with genetics. Yet, in addressing this trend, we must perform analyses on the balance of the NIH portfolio before choosing to shift funding from one area to another.
Working Group Report on Outside Awards for NIH Employees
Dr. Reede reported progress made by the working group for outside awards for NIH employees. This working group has addressed concerns that some outside awards to NIH employees have had the appearance of a quid pro quo, or employees have been paid by a sponsor to talk about official duties. Questionable activities have included:
Awards being given by an entity that has a matter pending with the recipient
Awards being given by a person or group that has broad discretion
Mislabeling lectures as awards
A two-pronged approach to the problem was developed. First, the working group created a list of pre-screened awards that would be publicly available. These were obtained by asking the institutes and centers to provide lists of prestigious awards, passing the full list to the NIH Ethics Office for review, and finally review of the list by the working group and by the full ACD. Second, the working group would continue the program of case-by-case analysis of the awards with regard to the sponsors, recipients, and the potential for conflicts of interest. Added to this would be a prohibition on the receipt of cash by senior employees in all cases except the very major awards (e.g., the Noble Prize and Lasker Award).
The working group reviewed the initial list of prestigious awards, made some subtractions, and produced a list of pre-screened awards for the ACD to consider. Dr. Reede directed the committee members to the printed list, noting that more awards would be added to it in time. Also, awards could later be removed from the list if they become inappropriate. The list would be reevaluated yearly. Dr. Reede asked the committee members to review the list and recommend a final list of "bona fide awards for meritorious public service or achievement." She provided a description of such awards — for example, the award must be given on a regular basis and the selection of a recipient made based on written standards.
The working group did not consider awards such as honors with no cash component, plaques or trophies with little intrinsic value, travel expenses to an event, and the waiver of registration fees for awards ceremonies.
In reviewing 99 awards, the working group determined that 46 met the regulatory definition. Within the list of 99 the group also identified 40 awards that met the regulatory definition and bestowed cash not exceeding $200. The remaining awards did not offer enough information to determine whether they met the criteria. More research is needed.
Discussion
Dr. Bishop questioned the need to prohibit cash awards to senior employees. Why prohibit such awards when there is no conflict of interest? Dr. Kington explained that the ethics office recognized that, by definition, senior-level employees would commonly have conflicts of interest. By senior level employees is meant the senior-most members of the Office of Director — the Director, Deputy Directors, Associate Directors, and Office Directors — and, at the institutes and centers, equivalent positions.
Dr. Zerhouni cited one case that prompted these activities. An institute director was invited to give a lecture, with a significant award, and the award was very much at the discretion of someone who was a recipient of a grant from that institute in that timeframe.
Dr. Bishop asked how the group was determining which awards are "prestigious." Dr. Zerhouni responded that this issue is contentious. The idea is to exclude awards that are not given through some sort of jury process. Dr. Kington stated that there remains a need for the NIH Ethics Office to make a judgment call at times (as in allowing senior-level employees to accept the few very major awards). The idea is to make the award process beyond reproach. Part of that is holding the most senior-level employees to a higher standard.
Dr. Kington further explained the process whereby an award not on the list could be submitted for admission and considered on an ad hoc basis. It would be reviewed by the NIH Ethics Advisory Committee and by a subgroup of the ACD. The intent of the program would be to consider any submitted award and allow it if it was found to meet the criteria, and at the same time to expedite awards that had already been vetted and were on the list of pre-screened awards.
Dr. Pickett asked whether any focus groups of intramural scientists gave input to the development of this project. What effect would such a program have on recruiting and retaining extramural researchers at the NIH? Dr. Kington responded that such focus groups were not used. Dr. Zerhouni explained that another reason to have the moratorium was to produce impact analysis and education, especially within the intramural community, which is very concerned about such restrictions. Dr. Kington reminded the group that this new policy would govern awards only, a small subset of the larger enterprise in which scientists are invited to speak at institutions and which does not have these conflict-of-interest problems. A goal is to avoid placing restrictions on any activities of researchers (speaking, teaching CME courses, etc.) other than awards that have conflicts of interest.
Dr. Smarr encouraged the working group to consider the case of the University of California, which recently developed similar rules about receiving gifts. Dr. Kington indicated that the NIH blue ribbon panel reviewed a number of university and organizational standards for conflict-of-interest management.
Dr. Vijayanagar moved that the committee vote to endorse the proposal of the working group. The motion was seconded and approved, with three abstentions.
Mr. Turman, Associate Director for Budget, NIH, described the current state of the budgetary process. The NIH budget is $28 billion, and the NIH has been operating under a continuing resolution since October 1. The process for passage of a new budget is not quite complete.
The President asked for an increase of about 2.6 percent. Congress deliberated and now appears ready to support a 2-percent increase, about $565 million more than the previous year. Mr. Turman suggested that the NIH had done as well as could be expected, considering what Congress could afford, the size of the NIH, and current priorities. In contrast, the National Science Foundation's budget was cut by more than $100 million.
Mr. Turman will be able to offer a picture of the final dollar amounts for FY2005 at the June ACD meeting. At that meeting, the ACD members also can discuss the President's 2006 budget request, which he will release in February.
Discussion
Dr. Williams wondered whether the academic community should plan for across-the-board reductions in continuation grants. And if so, should they be by institute or globally? What should researchers be told about the total pool of new R01s?
Mr. Turman responded that the NIH historically has worked hard to pay commitments in terms of the out-year cost of grants and there is every hope that this would continue. As for new and competing grants, it is hard to know.
Dr. Zerhouni noted that the budget allocations for the institutes are derived by a complex formula. Typically, each institute receives about the same increase. Exceptions occur, however, as in the case of the increased emphasis on biodefense, which caused a proportionally larger increase for the NIAID.
Mr. Sadwin asked whether the NIH had numbers that would show what could not be funded because budget levels were lower. Mr. Turman responded that his office could develop such figures. Some numbers had been printed in the Congressional Record in response to a request from Senator Specter. Mr. Sadwin stated that it might be helpful to communicate such figures.
Regarding special allocations in the new budget that went beyond the initial proposal, Dr. Zerhouni cited an extra $30 million to fund extramural construction with the National Center for Research Resources and an extra $14.5 million for phase-2 construction of the Porter Neuroscience Building.
Dr. Pickett wondered whether, given the flat budget, the NIH performed a portfolio review across all the institutes, seeking programs to eliminate. Dr. Zerhouni responded that a mechanism for this existed within each institute. He meets with the institute Directors to discuss these issues, which have become more important in this era of smaller increases.
Working Group Report on Postdocs: Training and Career Opportunities in the 21st Century
Dr. Ruiz Bravo, Deputy Director for Extramural Research, NIH, explained that the postdoc effort grew from an initial meeting in October 2003, chaired by Dr. Burgess and Ruth Kirschstein, M.D. A uniform benefits package for postdocs, regardless of appointment or mechanism of support, was proposed at that meeting. Other goals discussed in the meeting included the following: establishing postdoc offices at research institutions, creating a portable transition award that could be taken to institutions, and collecting data on postdoc fellows supported by research grants.
A National Postdoctoral Association white paper made similar proposals and went on to propose increases in stipends. A recent FASEB document also proposed increased support, especially in benefits.
The working group considered those proposals, conferred with persons at NIH who manage postdoc training programs, and developed the following list of priorities:
Health insurance for postdocs
Cost-of-living increases
Stipend adjustments to $45,000 for entry level
Additional benefits (disability, retirement, life insurance)
Transition awards (K22)
Support for postdoc offices
The group considered the first two priorities to be most important. It performed an analysis and produced the following anticipated costs (where monetary health insurance increases are offset by reductions in the number of full-time training positions (FTTP)):
A $500 increase in an F32 would cost 19 FTTPs
A $1,000 increase in an F32 would cost 38 FTTPs
A $1,500 increase in an F32 would cost 57 FTTPs
NIH currently supports more than 17,000 FTTPs (predoc and postdoc)
The National Postdoctoral Association and the NIH training managers are continuing to discuss these issues. The National Academy of Sciences plans to release a National Research Service Award personnel needs study at the beginning of 2005. The NIH is engaged in a postdoctoral evaluation study, to be completed in 2005, and it plans to evaluate the mentored career development awards (K Awards).
Discussion
Dr. Ruiz Bravo explained details of the stipends and costs to programs. For training grants, tuition and fees cover health insurance, so there is no issue. It is an issue for the F32 mechanism.
Dr. Williams made a motion, which was seconded and passed by a unanimous vote, to adopt a policy to increase the health insurance for postdocs. Dr. Burgess emphasized that the postdocs are entrusted with the future of medical science, so we must treat them well, recognizing that, in these times, they tend to be older and in need of larger stipends. Dr. Bishop cautioned that increases in benefits for the NIH intramural program could have a ripple effect, causing a need to increase pay scales for privately paid postdocs at other institutions.
Dr. Zerhouni characterized this work as a first step, and expressed concern about the issue of new investigators. He expressed hope that the ongoing efforts would yield an understanding of the potential effects of these issues on hiring and retention. Dr. Ruiz Bravo added that the NIH is developing a Web page resource for new investigators, which would include information on grantsmanship and funding issues.
Institute Director Report: Vision and Goals for the National Institute on Alcohol Abuse and Alcoholism, 2003 and Beyond
Dr. Li, Director of the NIAAA, presented a history of the institute, current work, and goals for its future, providing an example of priority setting within the NIH.
The NIAAA became an autonomous Institute of a newly created Alcohol, Drug Abuse, and Mental Health Administration in 1973. It was transferred to the NIH in 1992 as a research institute, with its service functions incorporated into the Substance Abuse and Mental Health Services Administration. Enoch Gordis, M.D., served as NIAAA Director from 1986 to 2001; Dr. Kington served as Interim Director in 2001-2002; and Dr. Li became Director in November 2002.
Dr. Li provided some statistical context. The NIAAA stands close to the middle of the range of appropriations for NIH institutes. Alcohol consumption is one of the major modifiable factors contributing to death in the United States (about 3.5 percent in 2000).
Dr. Li reviewed the pharmacokinetics of alcohol, noting that about 50 percent of the variation in its metabolism by individuals results from genetic traits. For alcohol to be psychoactive, it must be present in the body in millimolar concentrations. The neuropharmacological effect of alcohol is biphasic. At low concentrations, it acts as a stimulant; at higher concentrations, it produces a sedative, hypnotic action. It can cause death by halting respiration. All three of the metabolites — alcohol, acetaldehyde, and acetate — are psychoactive. Variation in alcohol's effects on individuals results from multiple molecular targets in the brain.
Alcoholism is regarded as a common complex disorder, with multiple genetic and environmental factors and complexities in their interactions. Researchers have made great strides in uncovering genetic bases, for example, revealing genetic variants that protect persons from drinking too much and from developing alcoholism. They also have identified nonspecific genes, that is, genes that are involved in alcoholism, mental disorders, and personality traits in complex ways.
Dr. Li stated that the NIAAA has been examining its strengths and opportunities to plan for the future. These strengths and opportunities reside in the following areas:
Alcohol pharmacogenetics (human and animal models)
Epidemiology (longitudinal population studies, high-risk studies)
Treatment (behavioral and pharmacological)
The institute crafted the following vision and mission statement:
To support and promote the best science on alcohol and health for the benefit of all. To use multidisciplinary and transdisciplinary approaches to increase understanding of normal and abnormal biological functions and behavior relating to alcohol use, to improve the diagnosis, prevention and treatment of alcohol use disorders, and to enhance the quality of health care.
The institute identified the following five areas of research emphasis: underage drinking, medications development, the etiology of risk (genes and environment), the mechanisms of alcohol action and injury, and behavioral and environmental interventions.
Dr. Li noted some opportunities for translational research. Studies of alcohol-associated increases of corticosterone (a stress hormone) may give clues to differences in the development of alcoholism in men and women. For gene-environment interactions, researchers can study rats that are bred for high-alcohol preference, and then presented with environmental factors such as alcohol deprivation and alcohol availability.
About a year ago, the NIAAA developed a matrix model to help address future challenges. The matrix links NIAAA's five areas of research emphasis to the five organizational branches of the institute:
Division of Neuroscience and Behavior
Division of Metabolism and Health Effects
Division of Treatment and Recovery Research
Division of Epidemiology and Prevention Research
Division of Intramural Clinical and Biological Research
In addition, it links to those divisions the activities of (1) technology and analysis and (2) centers and training. The purposes of this structural alignment are to reinvigorate the NIAAA and stimulate interdisciplinary research, to promote creativity and multidisciplinary approaches among the staff, and to strengthen the scientific career development of the staff. The realignment should stimulate transdisciplinary intellectual development of science and its integration into the day-to-day administration of the institute's research portfolio.
The NIAAA has begun major new research activities with the NCI, National Institute on Drug Abuse (NIDA), National Center for Complementary and Alternative Medicine (NCCAM), National Institute of Child Health and Human Development (NICHD), the Department of Justice, and the Department of Veteran's Affairs. Each is contributing to the funding of the activities. The NIAAA recently worked with the Department of Agriculture to produce a document of common definitions and measures, for example, for binge drinking and moderate drinking and for screening and treatment programs. The document is to be released in December 2004.
Dr. Li stated that the NIAAA is in the final stages of completing a formative assessment of its structures and functions. Results will be released within a few months.
Discussion
Dr. Zerhouni stated that Dr. Li has been bringing an energetic change to the NIAAA and is performing a great service for the NIH and the country.
Dr. Waite asked about the definitions of binge drinking and moderate drinking. Dr. Li responded that moderate drinking is usually defined as two drinks or less per day for men and one drink or less per day for women. Binge drinking is more difficult. Definitions range from five or more drinks per day to five or more drinks per occasion. But the occasion is not defined. Therefore, some researchers have tried to define binge drinking pharmacologically, that is, by the percentage of alcohol based on body weight.
Dr. Smarr remarked on the intersection of the NIAAA's work, including genetic and pharmacological studies, with that of the social and behavioral sciences. Dr. Li responded that animal models become valuable in this case. Animal models can illuminate social interactions, although translating results to humans is difficult. A large problem with studying alcohol in humans is the variation in pharmacokinetics, the absorption and distribution of alcohol in the body. Ultimately, we need longitudinal studies in both general populations and high-risk groups.
Dr. Smarr questioned how can the researchers study social effects in groups such as young persons. Dr. Li replied that such observational studies are conducted, although ethical concerns quickly arise. One way to address the ethical difficulties, suggested Dr. Li, would be to have health care professionals involved in designing the studies. This would allow them to intervene with the study participants when necessary, for example, if the subjects were drinking in a hazardous way. Dr. Waite noted that another problem is the lack of a good biomarker for recent alcohol consumption.
Dr. Li explained that his institute has not attempted to differentiate between applied and basic research. He commented that he believes alcohol is a good chemical probe for normal biology. To perform basic research, one must perturb the system in some way. Dr. Kington noted that because the NIAAA supports so much research in animal models, which tends to be considered basic, NIAAA is described as supporting a large amount of basic behavioral research.
Dr. Kington discussed the ongoing efforts in managing conflict of interest. In the previous year, the NIH has reviewed its ethics program, having been prompted by concerns of the Congress and journalists. Dr. Zerhouni initiated a comprehensive review of all activities and the development of recommendations by a blue ribbon task force. Since then, the NIH has been developing new policies. Dr. Zerhouni testified before the House Energy and Commerce Subcommittee on Oversight and Investigations, presenting an outline for revising the NIH's ethics program. The House subcommittee had produced a list of specific NIH activities with pharmaceutical and biotechnology companies that had not been approved.
In September, Dr. Zerhouni announced that the NIH would request that the HHS ask the Office of Government Ethics (OGE) to institute a 1-year moratorium on all activities with compensation involving NIH employees and the pharmaceutical and biotechnology industries. This would give the NIH time to develop and put into practice a new system of oversight and management of an ethics program. Dr. Zerhouni has stressed that many relationships with the industries are healthy, but we need a policy that indicates under what circumstances the activities are allowed and who may be involved.
The NIH is working with the Office of the General Counsel (OGC) to develop a policy and has requested that the OGE approve a set of supplemental regulations, allowing the NIH to operate under special rules temporarily. Policies are being developed in three areas: outside activities, awards, and financial holdings of employees.
A large group of intramural scientists asked to be allowed to give input to the process. Drs. Zerhouni and Kington met with a group of these scientists very recently and, as a result, the NIH is setting up a working group through which they can continue to give input as the process moves forward.
In the area of outside activities, one issue concerns academic pursuits, such as teaching, writing, and speaking. The NIH desires to create a policy that would allow many of those activities to occur. Long-standing government laws already regulate some of them.
In the area of financial interests, the NIH would establish limits on holdings in pharmaceutical and biotechnology companies. Such holdings would be entirely banned for some high-level employees. The goal would be to create targeted rules that address specific conflicts.
In the area of awards, again, the NIH desires to create policies that target the greatest conflicts, especially those involving high-level employees with grant-making authority.
In all cases, the NIH would increase the transparency of potential conflicts. To that end, the NIH asked the OGE to allow it to increase the number of individuals required to submit financial public disclosure statements. This number likely will increase to about 500. The request has been granted.
The NIH has investigated a list of potentially improper employee contacts with companies. The House subcommittee provided this list and the NIH and involved companies helped develop it. Some cases on the list proved to be simple mistakes. Others cases involved contacts without prior approval.
The NIH will increase the awareness of potential conflicts of interest by instituting mandatory ethics training for all employees.
Discussion
The committee asked about potential tension in hiring in the wake of these new, stricter conflict-of-interest rules. Dr. Kington explained this has been a concern from the beginning. Dr. Zerhouni has insisted that the process not harm the ability of NIH to recruit and retain first-rate scientists. Some scientists have expressed concern. In part, the 1-year moratorium will be used to measure the impact on recruitment and retention. Dr. Kington noted that most NIH scientists have not had any contacts with pharmaceutical or biotechnology companies.
Michael Gottesman, M.D., Deputy Director for Intramural Research, remarked that NIH scientists have always been restricted in many ways. The effect on morale appears to be a recent phenomenon. This process could be an opportunity to better the situation, even though a subset of scientists would always choose not to work for the Federal Government.
Dr. Smarr cited the complexity that scientists face in determining the best practices. Perhaps the NIH could develop a coaching or counseling service, setting a tone that suggests the government is there to help.
Dr. Kington noted that some steps have been taken. For cases with the highest potential for conflict, the NIH has centralized the review process. To add a level of peer review, the NIH has created an NIH Ethics Advisory Committee (including Dr. Kington, Dr. Gottesman, and senior scientists) that will review all requests and activities involving companies. The size of the Director's ethics staff is being increased, and there will be a new wave of education for officials and employees.
Dr. Pickett encouraged the NIH to focus on financial conflicts of interest and avoid being too bureaucratic. Dr. Kington responded that the planners are attempting to keep it simple. Transition periods and exception processes would be built into the new policy. The Federal Register would post the start date for the new regulations.
In response to a question about paid travel to conferences, Dr. Gottesman described efforts to ensure that NIH scientists could travel to a number of meetings each year and to allow for flexibility.
Mr. John Burklow, Associate Director for Communications and Public Liaison, NIH, provided an update on the implementation of the NIH Communications Plan. The plan employs efforts within three strategic areas: (1) infrastructure and systems, (2) proactive media, and (3) outside collaborations.
Infrastructure and systems include efforts such as creating uniform press releases. The office has produced attractive informative booklets that describe the work of the NIH. These publications contain stories of scientists and patients who represent progress throughout the NIH's history.
Recently, the office held NIH Director's Media Briefings and hard-hat tours of the new clinical center. To publicize the opening of the clinical center, the Communications Office produced radio and television spots featuring Drs. Zerhouni and Gallin, a satellite media tour, and a variety of media news releases. The activities generated about 50 million media impressions. The effort has included Spanish-language publications, Web sites, and community outreach.
For outside collaborations, the Communications Office has worked with the Association of American Medical Colleges (AAMC) to increase awareness of medical research around the nation. The office has worked with the NIH Alumni Association to increase the reach of NIH publicity. The office made strong efforts to promote the NIH Roadmap for Medical Research Anniversary and the COPR Public Trust Workshop. In a bit of serendipity, the NIH has received recognition because of a new NBC television series that uses the NIH as a dramatic fictionalized backdrop. Representatives of the NIH provided information to the television network as it created the show. The NIH and NBC cite each other on their respective Web sites. This produced a new high in NIH Web site hits in October.
Dr. Smarr suggested that the Office of Communications employ computer-Web technology to check Web trails. That is, persons coming to the NIH Web site provide evidence of their previous Web locations and can therefore reveal to the Communications Office the sites that referred them to the NIH. Dr. Smarr also suggested that the office, in its efforts to target Hispanic populations, consider collaborating with Hispanic media groups, which could lead to partnering and the sharing of ideas.
Dr. Gallin, Director, NIH Clinical Center, reported that the ribbon-cutting ceremony for the new Mark O. Hatfield Clinical Research Center occurred on September 22, 2004. The hospital will receive its first patients in early 2005.
The new research center is situated next to and connected with the original Warren Grant Magnuson Clinical Center. Together, these two facilities will now compose the NIH Clinical Center, the world's largest and most advanced clinical research facility.
Dr. Gallin hailed the original Clinical Center, with its long history of science and medicine and its unique feature of placing in-patients near the research laboratories. The Mark O. Hatfield Clinical Research Center comprises four modular units to house in-patients in 242 beds, flanked by two laboratory buildings. Patients and scientists will continue to have close proximity. The new center will feature 80 day-hospital stations, where patients may stay up to about 14 hours for complex treatments or study.
Dr. Gallin listed some of the remarkable medical breakthroughs that have occurred at the Clinical Center during the past 50 years, including the following:
The first chemotherapy and immunotherapy for cancer
The first successful artificial mitral heart valve
The first clinical research information system
The first treatment of AIDS with AZT
The first blood tests for AIDS and hepatitis
The first gene therapy
The NIH recently launched a new clinical research information system, which includes a data warehouse that eventually will partner with extramural sites.
Dr. Gallin described the population that works in the Clinical Center, including about 1,900 employees who are based there and some 4,000 institute-based employees. This includes approximately 1,200 credentialed physicians and 445 principal investigators. Nearly 83,000 patients spent time in the clinical center during 2003.
Every patient participates in a protocol. About one-third of the patients today are self-referrals. The Clinical Center has the largest group of patients with orphan/rare diseases in the world. The new clinical research center features a flexible infrastructure and unique lab equipment (e.g., cyclotrons) and will have the capacity to synthesize small amounts of candidate drugs and perform special lab tests. Dr. Gallin expressed the hope that the new clinical research center would become a national resource, drawing investigators from across the nation. It will be able to facilitate difficult and long-term studies and provide rapid response to public health emergencies (e.g., biodefense). The NIH is developing a new curriculum for clinical research training, to be used at the Clinical Center and exported to other educational institutions.
Discussion
Dr. Smarr expressed satisfaction with the plans to design information technology systems that are proactive. Dr. Gallin responded that a goal is to make these technologies available to researchers in partnerships and to export the technology to other institutions. One example is a new system, called "ProtoType," which helps researchers to write protocols, to track activities, and to coordinate with other agencies, such as in reporting adverse events to the FDA. The NIH has exported this developing program to Rockefeller University for testing and improvement.
Dr. Smarr suggested that data warehousing represents another opportunity to build and export information systems. Dr. Gallin agreed, citing the long-term goal to make the Clinical Center a national resource.
Dr. Ruiz Bravo reported on the progress of an initiative to increase public access to NIH research results by creating an archive of peer reviewed publications by NIH-supported researchers. She listed the following purposes for developing the new policy:
To ensure the preservation of these published findings in a permanent archive that is searchable with modern informatics tools
To enable the NIH to manage efficiently and better understand its research portfolio, monitor its scientific productivity, and ultimately set research priorities
To advance the NIH goal of an end-to-end grants management process
To make the peer reviewed published results of NIH-funded research readily accessible to scientists, physicians, and the public
The advancement of technologies has driven this program. Dr. Ruiz Bravo noted that about 80 percent of adult users of the Internet searched for at least one health topic in the past year.
The draft policy requests that NIH-funded investigators submit electronically to the NIH the final, peer-reviewed author's copy of their scientific manuscripts. This copy would be embargoed from release by NIH for six months after the date of publication.
The NIH held public meetings with publishers, associations, investigators, and disease advocacy groups during the summer of 2004 to discuss the new policy. The policy was announced in the NIH Guide and the Federal Register in September 2004. Dr. Ruiz Bravo showed results of comments received since the beginning of September, with a significant rise beginning in late October. Of the 6,200 responses, most were submitted electronically (Web site and e-mail). About 41 percent expressed agreement with the concept of the new policy, and about 8 percent expressed disagreement. As for the proposed implementation, about 66 percent expressed agreement, and about 22 percent expressed disagreement.
Specific opinions in favor of the new policy included the following (among many others):
Taxpayers should have access to research results in a timely manner
Enhanced access to information strengthens and expands the impact of research
The policy should improve health outcomes
The policy provides equal access for less wealthy individuals, institutions, and countries
Online access to information is less expensive and easier to obtain
Without such a policy, the government is favoring publishers at the taxpayers' expense
This policy will improve the visibility of the work of the researcher
Opinions disagreeing with the policy included the following (among many others):
The current process of development is not allowing for adequate dialogue
The policy will harm the financial stability of publishers
The policy will adversely impact peer review of research prior to publication
The policy is redundant to existing information sources and systems
The overall implementation of this plan is too costly
The proposed policy does not adequately address copyright issues
The policy may lead to an increase in cost for publications or an increase in costs for researchers to submit work
The policy will hurt learned societies and the efforts that they support financially
Frequently asked questions included the following:
Will the quality of peer review be harmed?
Will there be a negative impact on scientific publishing?
Will authors and journals be unable to copyright?
Why archive on PubMed Central?
What will this cost to implement?
Dr. Bravo stated that the NIH intends to preserve the critical role of journals and publishers in peer review, editing, and scientific quality-control processes. Only about 10 percent of all articles published in 5,000 journals are NIH-supported. The policy should have no effect on copyrighting articles. It should cost about $2 million in 2005 and slightly more in 2006. The NIH is continuing to analyze and address the comments being received.
Discussion
Dr. Masters credited the American Society for Biochemistry and Molecular Biology for pioneering this electronic publishing era by launching an online journal 10 years ago. She listed a number of recommendations, including some already expressed:
Work with the stakeholders (especially the public)
Consider the impact on professional societies and other publishers
Consider economic effects
Do not limit sources by inadvertently reducing their financial viability
Consider the political climate regarding government holding of the repository
Define what is considered to be a final manuscript
Consider copyright issues
Dr. Ruiz Bravo responded that the NIH is working with stakeholders, will build a process of evaluation into the program, will encourage other archives, will attempt to avoid redundancies, will ensure that copyrights are not affected, and will attempt to keep costs down, for example, by adding to an existing system rather than creating an entirely new one.
Dr. Barron asked whether submission of the manuscripts would continue to be voluntary. Dr. Ruiz Bravo replied that this policy is still under consideration. She explained that reasons for asking for the articles then holding them for six months include aiding in the management of the NIH portfolio and countering the fact that many manuscripts would not be submitted in a timely manner otherwise.
The committee members noted areas in which the new policy likely would have to undergo revision down the road. For example, how would the coordinates of protein structures be handled? Could the archive become an open-source environment, in which outsiders could submit comments on the articles? Could the articles link to relevant government documents written in lower-level language?
Dr. Ruiz Bravo indicated that the group would consider those questions, and she thanked the meeting participants for their input.
The Advisory Committee to the Director of the National Institutes of Health convened on December 2 and 3, 2004, to learn about progress in implementing the NIH Roadmap for Medical Research and revising the Director's Pioneer Awards Program; to hear about the progress of the new Mark O. Hatfield Clinical Research Center; to learn the results of the COPR Public Trust Workshop; to receive updates on the work of the Research Opportunities in the Basic Behavioral and Social Sciences Working Group, the Outside Awards for NIH Employees Working Group, and the Postdocs Working Group; to learn about current activities of the National Institute on Alcohol Abuse and Alcoholism; and to learn about ongoing efforts in NIH public access, communications, and ethics.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Raynard S. Kington, M.D., Ph.D. Executive Secretary, Advisory Committee to the Director Deputy Director, NIH
Elias A. Zerhouni, M.D. Chairman, Advisory Committee to the Director Director, NIH
