Director's Council of Public Representatives
Fall 2000 Meeting MinutesFourth Meeting of the Director's Council of Public Representatives The Council of Public Representatives convened its fourth meeting at 8:30 a.m., Thursday, April 6, Building 31, Conference Room 6, National Institutes of Health, Bethesda, Maryland. The meeting was open to the public. Dr. Ruth Kirschstein, Chair, Council of Public Representatives, and Acting Director, National Institutes of Health (NIH), presided. Council Members Present:
Council Members Absent:
Ad-hoc Participants:
Executive SummaryDr. Ruth Kirschstein began the Fourth Meeting of the Director's Council of Public Representatives (COPR) by briefing COPR members on uncertainties facing NIH because the Congress has not yet passed an appropriations bill and thus is funding NIH on the basis of a continuing resolution, meaning current resources are based on levels set for FY 2000. In addition, legislation is pending to establish a new NIH Institute of Bioimaging and Bioengineering. (Note: This legislation was signed into law on December 29, 2000). She also mentioned several appointments made recently at NIH as well as other appointments that are pending, reviewed many awards including recent Nobel Prizes that went to NIH grantees, and noted that a new vaccine research facility is now in operation on the NIH campus. Dr. Kirschstein said that the NIH draft strategic plan on health disparities research is posted on the NIH Web site, and will be implemented principally by the NIH Office for Research on Minority Health (Note: now the National Center for Minority Health and Health Disparities Research). In addition, the final version of the NIH Stem Cell Research Guidelines was published on August 25, 2000, but NIH has not yet funded any research projects in this area. She also summarized recommendations from an ACD working group that reviewed gene transfer clinical research, thanked the three members of COPR who participated in that review, and also expressed gratitude to other COPR members who were involved in the annual Government Performance and Results Act (GPRA) review of NIH. Several COPR members described recent COPR-related activities, including Dr. Montoya who is involved in extensive outreach activities; Ms. Quigley, Mr. Roehr, and Ms. Lappin, who participated with members of the ACD in a review of gene transfer studies; Dr. Dreher on community reactions to human genetics research; Ms. Lancaster on a site visit to Tennessee made by a delegation from NIH led by Dr. Maddox; and a future clearinghouse meeting sponsored by the NIH National Institute of Dental and Craniofacial Research that Ms. Kalabokes planned to attend. Dr. Barry Kramer, the new Director of the NIH Office of Medical Applications of Research (OMAR), reviewed how this office develops consensus reports on medical applications and practices, and outlined several reforms that are being instituted.. For instance, he said that it might be useful to include public representatives as members of a discussion group being formed to review topics of potential interest for this office. In addition, the NIH OMAR plans to develop a curriculum for the news media describing how scientific evidence is evaluated. Mary McCabe, Director of the Office of Education and Special Initiatives, NIH National Cancer Institute (NCI), described two recent clinical trials initiatives at the federal level, one involving efforts to improve informed consent procedures and the other to provide coverage to participants in clinical trials through the Medicare Program. She said that an NIH working group recently developed a prototype informed consent document to improve the understanding of potential participants in clinical trials. One special feature of this document is that it presents risks for the entire medical regimen to which a participant may be subject, according to Ms. McCabe. Meanwhile, based on a memorandum issued by President Clinton on June 7, 2000, Medicare was to begin covering expenses associated with clinical trials as of September 11, 2000, thereby widening opportunities for studying medical conditions among the elderly. Dr. Tom Murray, President of the Hastings Center and a member of the National Bioethics Advisory Commission (NBAC), said that NBAC has been methodically reviewing the system for protecting human subjects who participate in research programs. The current NBAC Oversight Project involves reviewing the adequacy of the entire regulatory framework, including the Common Rule and the Institutional Review Board (IRB) system, as well as a series of specific issues. Key recommendations under NBAC consideration include: putting all oversight, both public and private, under a single federal office or agency with a uniform set of regulations; establishing a new framework for analyzing the vulnerabilities of subjects; developing a fair system for compensating subjects who are injured during their participation in research projects; better educating IRB members and investigators; increasing the participation of non-experts and personnel who are unaffiliated with the respective host institutions in the IRB system; instituting an IRB accrediting system; and providing greater scrutiny for research protocols that entail paticularly high risks for participants. Dr. Greg Koski, Director of the HHS Office for Human Research Protections (OHRP), said that the research oversight system has limited resources with which to respond to specific incidents or to develop general policy recommendations and guidelines. Meanwhile, IRBs face a considerable challenge in trying to translate policy recommendations from OHRP and elsewhere into practice. OHRP is instituting several policy changes, including moving away from confronting IRBs, developing a certification system, and changing IRBs to be more representative of the broader community and the public. OHRP is also developing a comprehensive registry of IRBs and is asking the Institute of Medicine to help OHRP monitor its own performance as it implements various reforms. At the end of the first day, COPR members engaged in a wide-ranging discussion of measures to protect patients and conflict-of-interest issues with Dr. Koski, Dr. Murray, and Ms. McCabe. On the second day of the meeting, COPR members and NIH staff discussed a wide range of issues pertaining to the council's current and future activities. That discussion began with a review of information materials about NIH that COPR members may draw upon when they visit various communities and are asked to describe NIH programs and activities. This discussion also broached substantive issues on the agenda of the previous day, including a lengthy colloquy on the NIH initiative to support research on health disparities and the need to secure increased funding to support this expanding effort. COPR members representing five working groups summarized the current status of their activities. These discussions included brief reports from Ms. Lackritz (presented by Ms. Anne Thomas) on clinical trials, Mr. Roehr and Ms. Kalabokes on outreach efforts aimed at other public members participating in NIH groups, Dr. Montoya on health disparities and underserved populations, Ms. Kalabokes on COPR membership succession, and Ms. Lappin on protections for people participating in research. Ms. Thomas led a discussion of the draft guidebook, History, Values and Operations of COPR, that is intended to serve current and future COPR members as well as others who are interested in the council's structure and activities. She also asked COPR members to consider several options as to how they should go about decision-making, and the group concluded that, although it will strive for consensus, a simple majority vote would be sufficient for making recommendations, with allowance for members in the minority to issue dissenting opinions. Ms. Thomas said that the next set of six new COPR members will be named in January/February, and Ms. Kalabokes said that her working group plans to recommend steps for broad distribution to identify candidates for COPR membership beyond this next selection, which primarily identified candidates from among the COPR Associates. NIH Director's ReportDr. Ruth Kirschstein began the Fourth Meeting of the Director's Council of Public Representatives by briefing COPR members on uncertainties facing NIH because the Congress has not yet passed an appropriations bill for fiscal year (FY) 2001 but is funding NIH on the basis of a continuing resolution, meaning that current resources during the early part of FY 2001 are based on levels set for FY 2000. These lower spending levels remain in force despite apparent congressional plans to continue increasing the NIH budget on a course to double its budget within a five-year period. She said that the House of Representatives Appropriations Subcommittee for Labor, Health and Human Services held a hearing in September (it had been scheduled for May, but was postponed) during which several Nobel Laureates testified on behalf of NIH, calling for its continued strong support. In addition, several younger scientists also testified, including two young women investigators, and representatives of patient advocacy groups. Dr. Kirschstein reminded COPR members that NIH Acting Deputy Director Yvonne Maddox and NIH National Institute of Allergy and Infectious Diseases (NIAID) Director, Anthony Fauci, co-chaired a trans-NIH Working Group that developed a draft strategic plan on health disparities research. That draft is now posted on the NIH Web site, and it will be implemented by the NIH Office for Research on Minority Health (Note: now the National Center for Minority Health and Health Disparities Research), as well as by the individual Institutes and Centers. Dr. Kirschstein said that legislation is pending to establish a new NIH Institute of Bioimaging and Bioengineering, which would encompass the work of the current Office for such activities known as the Office of Bioimaging, Bioengineering, and Bioinformatics (OBBB). Dr. Kirschstein said that several appointments were made recently at NIH, including the appointment of Dr. Lawrence Tabak from the University of Rochester to Director, NIH National Institute of Dental and Craniofacial Research (NIDCR) and Dr. Raynard Kington from the Centers for Disease Control and Prevention (CDC) to Director, NIH Office of Behavioral and Social Sciences Research. Additional appointments are pending to Director, NIH National Eye Institute, from which Dr. Carl Kupfer recently retired; Director, NIH Office of AIDS Research, from which Dr. Neal Nathanson recently resigned; and Director, NIH Office of Equal Opportunity. Meanwhile, a new building dedicated to vaccine research recently opened on the NIH campus. Research activities in this building, directed by Dr. Gary Nabel, will focus initially on developing an AIDS vaccine within the next decade, but other projects will include research on malaria and tuberculosis vaccines. Other signs of intensified activity at NIH came during the summer when hundreds of students from the high school to the postdoctoral level were working on the Bethesda campus. Several sets of honors were recently bestowed on investigators with links to NIH, including the 2000 Nobel Prize for Physiology or Medicine to Paul Greengard and Eric Kandel, who were NIH grantees, as well as Arvid Carlson, who worked at NIH early in his career; and the Nobel Prize in economics, which went to investigators who were supported by NIH grants. This year's Lasker Award went to NIH investigator Dr. Harvey Alter for his work on hepatitis C and other efforts to safeguard the blood supply. Moreover, two investigators in the NIH Intramural Program received Presidential EarlyCareer Awards. NIH published a final version of its Stem Cell Research Guidelines on August 25, 2000, after receiving a large volume of comments, but has not yet funded any projects involving human pluripotent stem cells, according to Dr. Kirschstein. The guidelines call for establishing a special advisory process to review research proposals involving unique human stem cell lines, and to report on these activities. The Senate Committee on Appropriations, Subcommittee on Labor, Health and Human Services and Education, which is chaired by Senator Arlen Specter (R-PA), has held several hearings on this issue. In response to questions from several COPR members, Dr. Kirschstein said that the special reviews will focus on unique stem cell lines and that the guidelines apply only to research being funded by the NIH. Dr. Kirschstein said that three COPR members participated as part of a working group of the NIH Advisory Committee to the Director (ACD) that reviewed the role of NIH oversight in gene transfer research. That working group developed a series of recommendations regarding coordination of such oversight with the Food and Drug Administration (FDA), particularly in reporting adverse events. The ACD as a whole officially accepted that report on the basis of a meeting held by telephone in September. Principal recommendations include that researchers agree to provide the NIH Recombinant DNA Advisory Committee (RAC) with notification of protocol changes before enrolling patients to ensure RAC review before a clinical trial begins, that NIH attempt to harmonize its requirements for reporting adverse events with those of FDA, and that RAC establish a standing working group to review serious adverse events. The NIH Office of Biotechnology Activities, which administers RAC activities, has published these recommendations for public comment and plans to use them to amend the NIH Recombinant DNA Guidelines. Dr. Kirschstein reviewed recent activities of COPR members, including the participation by several of them in the recently completed review of NIH that was mandated by the Government Performance and Results Act (GPRA), involvement in the June NIH retreat for budget planning, participation (by Vicki Kalabokes and Melanie Dreher, Ph.D.) in performance reviews of several NIH Institute Directors, and participation (by Maurice Rabb, M.D.) as an advisor of PubMed Central and in personnel searches. COPR Members Report on COPR Activities to NIH DirectorDr. Montoya on Public Outreach Dr. Isaac Montoya described several recent occasions during which he represented COPR while participating in NIH-related activities. Thus he attended meetings, including with Elaine Baldwin of the NIH National Institute of Mental Health who directs the Outreach Partners program, which communicates science-based information on mental health to people in every part of the country, NIH advisory council meetings, a meeting devoted to conflict-of-interest issues, and a scientific meeting focused on how HIV affects elderly populations. He also visited several universities to present them with information about COPR and NIH, met with the Director of the American Society of Clinical Laboratory Science, and attended several regional meetings of community and religious groups to discuss participation by volunteers in clinical trials. Dr. Montoya said that those visits indicate to him how poorly the clinical trials process is understood, but that recently held town hall meetings are helping to correct some of those misunderstandings. He also said that he has received many inquiries about protections for subjects participating in clinical trials and about health disparities, and he has tried to refer those callers to appropriate officials at NIH. Ms. Quigley and Others on Gene Transfer, Other Clinical Trials-Related Issues Ms. Rosemary Quigley summarized some of her experiences as one of several COPR members who served on the NIH Working Group on Gene Transfer Clinical Trials. The Working Group concluded that the intense focus by the public on gene transfer research helps to set it apart from other types of clinical research, according to Ms. Quigley. She also said that it was valuable for several individuals to be representing the general public on the Working Group because even the bioethicists who serve on that body appear to bring a distinct viewpoint to its deliberations, but the public members can better represent the public at large. She said that the Working Group was trying to amend the process for reviewing research on gene transfer to improve its oversight without making the process too formal. The scope of that oversight remains limited to those research proposals involving genuinely novel activities, about ten percent of overall activities in gene transfer clinical research. Ms. Quigley said that the Working Group also recommended that RAC reviews be conducted before any patients are enrolled in a particular clinical trial and that communications improve between the NIH RAC and FDA. However, those efforts are complicated because the NIH RAC and FDA adhere to different, mandated procedures when reporting serious adverse events associated with clinical trials, making it difficult to reconcile the differences in their current practices. Mr. Robert Roehr said that, although he supports the NIH Working Group's recommendations, he would like to see data from gene transfer clinical trials treated more openly, and for the review process to be modeled after NIH rather than FDA practices. He said that he favors increased public participation, and suggested that a more open process will encourage patients to enroll in clinical trials. Subjects are more likely to protect themselves if they better understand experimental procedures through a process for informed consent that is more open. Ms. Debra Lappin said that having COPR members serve on the Working Group was valuable, and that their presence helped to demarcate important differences between the NIH and FDA. She agreed with Mr. Roehr that NIH should go further toward openly reporting serious adverse events associated with gene transfer clinical trials. Another important component of such reporting would be for NIH to present data that might indicate trends across different clinical trials. This same approach could also prove valuable in other areas of innovative clinical research, such as clinical trials involving stem cells, or wherever else sensitive issues of patient protections might arise. Discussion Dr. Kirschstein said that there is intense interest in conflict-of-interest issues as they pertain to clinical trials and protecting subjects who participate in them. Dr. Kirschstein, FDA Commissioner Jane Henney, and OHRP Director Greg Koski participated in a conference focused on these issues last August. An effort is under way to reconcile differences in FDA and NIH requirements for reporting adverse events, an effort that is made more challenging because of cultural differences between the two agencies, according to Dr. Kirschstein. Adverse event reporting is further complicated because many participants in clinical trials are ill because of their underlying diseases, meaning that many of the adverse events arise from the medical condition rather than the experimental interventions being investigated. Ms. Quigley said that data on adverse event data should be made public, even if that information discourages potential participants from taking part in clinical trials. Dr. desVignes-Kendrick agreed, noting that public trust may be eroded if participants are not fully informed about adverse events. Mr. Roehr said that such information should be made public in a timely fashion, despite technical and proprietary challenges in doing so. He said that the pharmaceutical industry, which prefers to delay the dissemination of such information, is facing a paradigm shift. Ms. Quigley said that FDA officials sometimes are put in the awkward position of being aware of studies whose results are kept proprietary even though disclosure of those results might enlighten discussions focused, for example, on adverse events arising from clinical trials under sponsorship of other, perhaps competing, companies. Dr. Dreher on Genetic Research Issues Dr. Dreher discussed a series of public meetings sponsored by the NIH involving members of ethnic and religious groups and their views on human genetics research. The tenor of these discussions varies widely, with some community members very eager to cooperate with researchers, while other groups are concerned that the results of genetic testing will be used to stigmatize their members. As these research efforts expand, additional discussions can be anticipated, according to Dr. Dreher. Although there appear to be no ready or simple answers to the many concerns now being expressed, open forums provide a valuable means to confront them. Ms. Lancaster, Dr. Maddox on Tennessee Site Visit Ms. Joan Lancaster described her recent role in initiating an NIH site visit to Eastern Tennessee. One of COPR's interests for outreach involves bringing NIH staff and resources out to states that have not previously participated fully in the research programs of the NIH. Ms. Lancaster recently coordinated a successful event in East Tennessee with Dr. Ron Geller from the NIH Office of Extramural Research. Ms. Lancaster organized an extremely impressive planning group that included medical centers, hospitals, researchers, and several local universities. Dr. Yvonne Maddox, NIH Acting Deputy Director, also attended the site visit and led a group of NIH representatives on a visit to some of these Tennessee facilities where they discussed plans for NIH research programs on health disparities with members of that community. Dr. Maddox said that the interactions between the NIH delegation and the representatives of the local community, including medical school faculty, nurses and other health care professionals, and also members of the local news media, provided valuable insights about conducting such research with the cooperation of local communities. Ms. Kalabokes on NIDCR Presentation Ms. Kalabokes said that she would shortly be talking on COPR's role and structure at a clearinghouse meeting arranged by the NIH National Institute of Dental and Craniofacial Research (NIDCR) at which members of the public and scientists were scheduled to discuss research opportunities of special interest to NIDCR. Update on the Office of Medical Applications of Research (OMAR)Dr. Kirschstein said that members of the NIH Advisory Committee to the Director recently reviewed the NIH Office of Medical Applications of Research (OMAR), recommending several changes in the way in which consensus statements are developed. She then introduced Dr. Barry Kramer, who was recently recruited to be the new Director of OMAR. Presentation by Dr. Barry Kramer, Director, OMAR Dr. Kramer said that NIH OMAR develops formal assessments of medical applications, basing decision-making on solid evidence that is carefully weighed during consensus development conferences. Over its history, the NIH OMAR has hosted some 110 such conferences, each of which is sponsored by one or more of the NIH Institutes and Centers. The choice of a topic is dictated by several criteria, including its importance to public health, whether there is a gap or controversy 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 resources for health care 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, a planning committee drafts questions to be addressed and nominates experts to participate in the formal consensus process, convenes smaller panels once or twice before the conference to refine critical issues, oversees the conference itself while allowing for broader public input before the scientific jury develops the formal consensus statement, and meets following the conference to revise the consensus statement as needed. Currently, the operations of the NIH OMAR are being adjusted and expanded, according to Dr. Kramer. For instance, OMAR is putting together a discussion group whose rotating membership can serve as a sounding board for topics of potential interest for this office. He said that it will be useful to include public representatives as members of this sounding board, such as from the NIH COPR as well as from other federal agencies with health-related missions. Another new activity for the NIH 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. He said that members of the medical community recognize several levels of evidence with a distinct hierarchy in terms of credibility, with randomized 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. Similarly, there is a hierarchy among different types of clinical treatment trials. Dr. Kramer encouraged COPR members to participate more fully in the ongoing discussions of the sounding board group, which convenes more than 3 times annually to advise the NIH OMAR. He said that he would attend future meetings of COPR and would supply additional materials to the council. Discussion Dr. Dreher said that other professionals within the health care community, such as members of the nursing community, could provide valuable contributions to the NIH OMAR as it develops evidence-based decisions. In response, Dr. Kramer welcomed her suggestion and said that other health professionals, including experts in the methodologies of public health, participate in consensus development conferences. In response to a question from Ms. Lappin about the long-term follow-up to consensus development conferences, Dr. Kramer said that it is a formidable challenge to evaluate the practical outcomes of NIH OMAR activities. Even designing a procedure for undertaking such evaluations represents a serious challenge. As a practical matter, the office tries to determine whether medical practices change following particular consensus development conferences, and it enlists the help of other federal agencies that keep track of such matters. In some specific cases, there have been follow-up efforts to redirect medical practitioners who implemented recommendations from consensus conferences in an erroneous fashion. In response to several questions about how statements issued from such consensus development conferences are put to use locally or by lawyers as part of lawsuits, Dr. Kramer said that, although such information may be misused medically or exploited as part of civil lawsuits, they are not presented as official NIH positions on medical practice. Instead, consensus development statements represent the collected views of experts and are not meant to carry the weight of law or to represent policy positions of the NIH. Making Informed Consent in Clinical Trials Understandable, as well as Other Important Updates in Clinical TrialsPresentation by Mary McCabe, R.N., M.A., Director, Office of Education and Special Initiatives, National Cancer Institute (NCI) Ms. McCabe described two recent clinical trials initiatives at the federal level, one involving important efforts to improve procedures for informed consent and the other to provide coverage to participants in clinical trials through the Medicare Program. After providing a brief account of the history of this issue, she described details of recent efforts to improve informed consent procedures, some of which was developed on the basis of feedback provided by focus groups. Fundamental to the system is the principle that each individual who considers participating in a clinical trial has the right to authorize experimental treatment (or other inquiries) by health professionals through an informed consent process that requires full disclosure on the professional's part, comprehension on the part of the individual about the procedures and risks, and a decision made on a voluntary basis. Ms. McCabe said that many of the informed consent documents now being written and used as part of consent procedures for clinical trials have grown increasingly complex, making them difficult to understand. For this and other reasons, an NIH working group was formed to develop a prototype document for informed consent in clear and simple language that could improve the understanding of potential participants in clinical trials and serve as a better tool for educating them about the experimental procedures in which they are being asked to participate. The prototype was designed to delineate—without overstating—potential benefits to participants in clinical research projects, and describes both risks and benefits of those experimental procedures in the context of standard care administered to patients with the medical condition that brought them into the clinical trial. One special feature of the prototype document is that it presents risks for the entire medical regimen to which a participant may be subject, rather than referring separately to each and every specific drug or procedure to which they may be subject, according to Ms. McCabe. Moreover, risks are ranked in terms of likelihood. The document further specifies that any risks associated with the reproductive system be described for both men and women who might participate. Other recommendations for informed consent documents include that they provide supplemental information to potential participants, be written clearly in a manner that is culturally sensitive, and that they promise to notify participants as new information related to the experimental procedure is made available. The documents also describe the likely timetable of events for participants in clinical trials. Ms. McCabe later said that a memorandum issued by President Clinton on June 7, 2000, authorized Medicare to begin covering expenses associated with clinical trials as of September 11, 2000. This new policy will widen opportunities for studying many medical conditions among the elderly because it authorizes broad coverage of their medical costs through all phases of clinical trials. She said that officials from several federal agencies are working through some of the details needed to implement this new policy. Eventually, they plan to develop a comprehensive registry of clinical trials that are covered under the aegis of Medicare. Discussion Dr. Kirschstein said that federal officials are considering ways to deal with informed consent documents for participants who may not fully understand English. In response to a question from Dr. Ted Castele about whether informed consent requires face-to-face discussions, Ms. McCabe said that such procedural decisions rest with local members of Institutional Review Boards (IRBs). Mr. Roehr said that the lines between standard medical care and research-associated care can become blurred. He also asked whether candidate participants should be routinely notified of alternative clinical trials in which they might participate. Ms. McCabe said that the development of a comprehensive clinical trials database could help to provide investigators with information about alternative clinical trials and that such information could be shared with candidate participants, and such information already is often provided. Ms. Barbara Lackritz, who has been involved as a patient in clinical trials, recommends that anyone considering participating in such trials obtain and read copies of the entire experimental protocol. In response to comments from Ms. Lydia Lewis about candidate participants whose decision-making capacities may be impaired for one reason or another, Ms. McCabe said that the NIH working group extensively discussed this issue and recognized that decision-making can be impaired for a wide variety of reasons. Dr. Montoya said that, although the prototype document is valuable, it is also important to tailor it to the specific issues that arise for any particular experimental protocol. Ms. McCabe agreed, saying that the working group did not want to present a simple check-off list of issues. In response to questions and comments from Ms. Quigley and Dr. desVignes-Kendrick about children as experimental subjects in clinical trials, Ms. McCabe said that the working group held discussions with individuals who had participated as children in clinical trials to understand some of the special issues that arose from those experiences. One result is that the working group is developing a document that takes into account some of the special needs of children, particularly adolescents, in the context of clinical trials. Dr. Montoya pointed out that NIH requires all investigators to learn about procedures for informed consent and related matters, and provides information for that purpose as part of its Web site. In response to a comment from Mr. Roehr about the managed care system, Ms. McCabe said that it is important to educate medical gatekeepers about informed consent and other issues relevant to clinical trials. In response to a question from Mr. Thomas Vaalburg about international input on informed consent, Ms. McCabe said that the NIH working group members focused on concerns in the context of U.S. clinical trials, but that they benefited from contacts with representatives of several countries in Europe. In response to a question from Ms. Lappin about potential coercion that could arise from extension of Medicare to cover clinical trials, Ms. McCabe said this possibility is not unique to Medicare, but she also said that care of a participant cannot be dropped simply because someone drops out of a clinical trial. In response to a question from Mr. Roehr whether the new Medicare policy on clinical trials would be extended to include other groups of patients besides the elderly, such as those being supported under Medicaid programs, Ms. McCabe said that discussions on such matters are under way. She also said that implementing these changes involves wonderful cooperation among several federal agencies. Dr. Kirschstein said that these changes to enable Medicare patients to participate in clinical trials are extraordinary and that they are being implemented at a rapid pace. In response to a question from Mr. Doug Yee about the cost of implementing these policy changes, Ms. McCabe said that federal officials are tabulating the projected costs but their first estimates indicate that the incremental costs for experimental procedures on a clinical trial will not be very far above the costs of standard care, indicating the new Medicare policy is fiscally responsible. Update from a Member of the National Bioethics Advisory Commission (NBAC) on NBAC's Human Research Protections ReportPresentation by Tom Murray, Ph.D., President, Hastings Center and Member of the National Bioethics Advisory Commission Dr. Murray said that there are fundamental problems with the system for protecting human subjects who participate in research programs. For instance, institutional review boards (IRBs) are overworked, under a great deal of pressure, and in a virtual state of siege. Moreover, IRBs are not particularly good at monitoring research in progress. He also said that the Common Rule, which serves as the fundamental principle for protecting subjects involved in research projects sponsored by the federal government applied to some 17 federal agencies, is unwieldy because agreement among all the parties is required to make any changes to it. In addition, there is a general concern that the informed consent process is not working properly because it is being handled in an increasingly formulaic manner. Dr. Murray said that the members of NBAC, which was established in 1995, have been methodically reviewing these matters, developing reforms that are described in a series of reports. NBAC members already have completed several reports through a transparent process that is open to the public. The reports focus on several topics, including issues of informed consent for research involving subjects who are mentally impaired, concerns revolving around the use of human tissues and other biological materials, and clinical research undertaken in developing countries. The current focus of NBAC efforts is the Oversight Project, its most ambitious undertaking to date, according to Dr. Murray. The goal is to promote good research consistent with ethical standards, while fully protecting the safety of human subjects. He said that the project involves reviewing the adequacy of the current regulatory framework including the Common Rule and the IRB system, as well as a series of specific issues such as the scope of human subject protections, the extent to which research in the private sector is covered by federal rules, a weighing of relative risks and potential benefits to research subjects, informed consent procedures, privacy and confidentiality safeguards, and measures to protect cohorts of subjects that are unusually vulnerable. In addition, NBAC is reviewing several issues related to oversight, including how to meet specific educational needs of IRB members and of researchers, how to improve the monitoring of ongoing research projects, whether reviews can be streamlined in cases of multi-institutional cooperative projects, how to institute accountability measures such as accrediting of IRBs, and how to develop adequate resources to better support IRBs. There are several key recommendations under NBAC consideration. They include: putting all oversight, both public and private, under a single federal office or agency with a uniform set of regulations; establishing a new framework for analyzing the vulnerabilities of subjects; developing a fair system for compensating subjects who are injured during their participation in research projects; better educating IRB members and investigators; increasing the participation of non-experts and personnel who are unaffiliated with the respective host institutions in the IRB system; instituting a system for accrediting IRBs; and providing greater scrutiny for research protocols that entail especially high risks for participants so that resources are directed to areas where oversight is most needed. Discussion In response to a question from Ms. Lappin about conflicts of interest, Dr. Murray said that NBAC recently drafted recommendations that focus on conflicts of interest among members of IRBs; that draft will soon be posted on the NBAC Web site for comments, along with another draft report on international research. In response to a question from Ms. Lackritz as to whether NBAC has considered the issue of solicitations over the Internet to individuals in disease groups to participate in research projects, Dr. Murray said that, although NBAC has not spent much time on this issue, the Hastings Institute is developing a code of ethics pertaining to use of the Internet for certain research purposes. In response to several questions about where in the federal government to locate an agency with comprehensive oversight and authority over IRBs, Dr. Murray said that NBAC might not make such a specific recommendation; its draft recommendation merely states that these responsibilities should be centralized. In response to questions from Dr. Rabb and Dr. Montoya about the membership of IRBs and whether individuals should be drawn from outside a particular IRB's institution, Dr. Murray said that NBAC does not have comprehensive data about the make-up of IRBs. He also said that New Zealand mandates that IRB members be unaffiliated with the institutions on whose boards they serve. Although NBAC is inclined to recommend that some members of each IRB come from outside its institution, it has not recommended what that proportion should be. Mr. Roehr asked what NBAC recommends about better informing individuals who participate in clinical trials about the experimental plans. Dr. Murray said that it is important for the public to better understand the nature of clinical trials, particularly to have a clearer picture that experimental procedures may not necessarily prove beneficial to participants in clinical trials. In response to a question from Mr. Yee about the relative merits of the U.S. IRB system compared to protections afforded individuals in other countries, Dr. Murray said that, although the United States pioneered many fundamental concepts in bioethics for protecting human subjects in research, some countries now have surpassed the U.S., particularly in terms of monitoring research projects once they are under way. New Directions for the Office for Human Research Protections (OHRP)Presentation by Greg Koski, Ph.D., M.D., Director, OHRP Dr. Koski said that investigators working with human subjects find themselves in a very different environment now compared to 30 years ago when the rules for oversight were first developed. One major difference is the enormous growth in the overall research investment compared to relatively minor changes in research oversight. Moreover, much of the research investment comes from the private sector. The system for research oversight has limited resources with which to respond to specific incidents or to develop general policy recommendations and guidelines, according to Dr. Koski. Meanwhile, investigators and IRBs need to see this system as something other than an administrative add-on, and more as an integral part of they way they operate. The IRB system has the burden of making oversight measures work effectively, and those who serve on IRBs are supposed to conduct themselves impartially, although they cannot fully divorce themselves from the research contexts in which they operate. The IRBs face a considerable challenge in trying to translate policy recommendations from OHRP and elsewhere into practice, according to Dr. Koski. One valuable measure to help them meet that challenge would be to make the system simpler and more uniform than it now is. He said that this goal can be achieved, in part, by pulling this oversight by many federal agencies involved in research involving human subjects under a single administrative umbrella. The Department of Health and Human Services took an important step in that direction by moving and changing the predecessor Office for the Protection from Research Risks (OPRR) from NIH to HHS, where it became OHRP. Even so, although 17 federal agencies have adopted the HHS-generated regulation known as the Common Rule, there is no common federal infrastructure to oversee its implementation and enforcement. He said that one of his goals is to make the Common Rule work as a common rule. FDA is among the agencies that adopted the Common Rule and mandates that it be applied to privately sponsored research that comes under its jurisdiction, mainly that research funded by industry aimed at the development of new biomedical products. Because it is housed within HHS, OHRP has an opportunity to work directly with FDA officials, and this recent administrative change, namely that involving the former NIH OPRR and the new OHRP, has led already to a great deal of cooperation and progress, according to Dr. Koski. In addition to FDA and NIH, several other HHS agencies account for more than 80 percent of federally sponsored research involving human subjects. Hence, HHS appears to be an appropriate administrative home for exercising federal-wide oversight over such research. Dr. Koski said that, although legislation is pending that would formally mandate such federal-wide oversight, there is not a great deal of enthusiasm in the Congress to fund a new federal agency for this oversight purpose. Meanwhile, OHRP is instituting several policy changes, according to Dr. Koski. One consists of moving away from confronting IRBs and instead trying to foster a broad sense of responsibility at all levels of this system for protecting human subjects. The underlying goal is that every individual within the system will come to gauge what needs to be done, what training is appropriate, and what other measures should be taken to ensure that investigators are properly trained and human subjects are fully protected when they participate in research. Part of this change will entail moving to a certification system, applying appropriate criteria to clinical investigators and to IRB members. Another change being considered is to change IRBs from having members taken exclusively from single institutions, where conflicts of interest are more prone to develop, and toward becoming unaffiliated with specific institutions and more representative of the broader community and the public. For these measures to work, it will be essential to develop a more uniform, national system that is based on meeting performance standards that are broadly recognized according to Dr. Koski. Moreover, the system needs to operate not on a post-hoc, compliance basis, but by protecting human subjects before they enroll and while they participate in research projects. To help in implementing a system of uniform accreditation, Dr. Koski has asked the Institute of Medicine (IOM) to develop accreditation standards. The IOM recommendations are expected to be ready by April 2001. Although these standards are being developed for OHRP, the eventual goal is for them to be accepted and implemented across all federal agencies and by the private sector. OHRP also is developing a comprehensive registry of IRBs, one that will provide details about the types of research that each one oversees, membership, and accreditation data-in short, a national database on the IRB system that could provide a basis for becoming a "safety monitoring board that is integrated," according to Dr. Koski. One goal is to design this system to be capable of monitoring across different clinical trials for adverse events as a way of providing alerts and very quickly preventing additional injuries to individuals who are enrolled in clinical trials. IOM will also help OHRP to monitor its own performance as it implements various reforms, according to Dr. Koski. In addition, OHRP not only will use assurances for individual institutions to help them evaluate IRB performances, but will also develop new measures to hold IRBs accountable and to help them in meeting performance standards, such as through enhanced education efforts. Efforts also will be made to educate the public about the broad benefits that come from supporting and participating in clinical research. COPR Discussion on Human Research Protectionswith Greg Koski, Ph.D., M.D., Tom Murray, Ph.D., and Mary McCabe, R.N., M.A. In response to a question from Dr. Montoya about resources for training investigators, Dr. Koski said that materials for training investigators about issues related to patient protection are available through his office and that a new handbook is being prepared. He also said that efforts are under way to heighten awareness of these issues and to use novel approaches for educating investigators about these important matters. In response to a question from Mr. Vaalburg about industry, Dr. Koski said that clinical research regulated by FDA comes under OHRP jurisdiction and is subject to its guidelines for protecting human subjects. This jurisdiction thus extends to the pharmaceutical, biotechnology, and medical device manufacturing industries, and several industry sector organizations are working directly with OHRP on these issues. Ms. Lappin praised the proposed reforms in patient protection but also questioned whether there are adequate penalties or whether patients can exert any pressure on investigators to comply with safety measures. Dr. Koski said that consumers and patient groups can do a great deal already; indeed, their willingness or reluctance to participate in clinical trials represents a potent force. He also said that OHRP's authority to enforce compliance is not being put on the back burner or being weakened, and his office is contacting IRBs about their practices and is visiting various research sites, with plans to do so more frequently than did the predecessor organization, the NIH OPRR. Ms. Lydia Lewis praised Dr. Koski for his enthusiasm but said that she was cynical about the clinical research enterprise, explaining that because researchers and industry benefit from such activities more than do patients, other measures are needed to protect patients who participate in clinical trials. Ms. Quigley added that institutions will tend to overlook guidelines to protect humans if they see those protections as not serving the institution's interests and asked whether enforcement procedures that are more potent were being contemplated. In response, Dr. Koski said that his personal experiences in Boston during the past decade provided him with a great deal of practical experience in patient protection issues and convinced him that not every injury can be prevented. Moreover, he acknowledges that industry benefits from patients who cooperate and participate in clinical trials to evaluate commercial products. With such a considerable potential for conflicts of interest, OHRP is developing points-to-consider guidelines to help in preventing such abuses. He also said that OHRP wields enormous power over academic institutions because they depend on federal funds. Mr. Yee said that the idea of using carrots rather than sticks to induce better compliance with measures to protect patients in clinical trials is a sound idea. Dr. Koski said that accreditation programs will be instituted in the future, and that providing standards of excellence for everyone to follow will be a valuable means for improving patient protections, particularly if federal enforcement undergirds that accreditation. He also pointed out that NBAC is preparing similar proposals independently, a development that helps to validate the ideas underlying these proposals. Dr. Koski also said that an advisory committee is being established to meet publicly on a quarterly basis and to provide OHRP with input from the research community and the public. Dr. Murray praised Dr. Koski for his moral passion, creativity, and energy. He said that NBAC has recommended that Congress enact legislation that will extend measures for protecting human subjects to everyone, regardless of whether the research in which they are participating is funded privately or publicly. He said that NBAC expects to release its major draft report before the end of 2000 and noted that some of the commission's recommendations to Congress and to federal agencies will be pointed. In response to Mr. Vaalburg, who recommended that focus groups be used to learn more about the views of human subjects who participate in research, Dr. Koski said that his goal is to improve the current system and to provide robust protections to human subjects participating in research. These reforms will benefit not only patients, but also the science being done. Dr. Murray said that NBAC invited several groups of human subjects to provide input to the commission. He also noted that IRBs would benefit if they included more lay representatives as members. In response to a comment from Dr. desVignes-Kendrick about the erosion of trust toward researchers among minority groups, Dr. Koski said that such populations have been approached in the wrong way and that it is essential to provide all populations with equal protection from research risks. He said that reaching out to such populations and respecting their needs represents an important challenge for the research community to meet. Dr. Kirschstein said that the NIH Women's Health Initiative has enrolled a very large number of women from minority groups and is implementing a number of special measures to develop their trust. Dr. desVignes-Kendrick agreed that such measures are needed to help in overcoming health disparities. Ms. McCabe said that training efforts are being stepped up to provide more health care professionals drawn from such communities. In response to a question from Ms. Quigley about what COPR might contribute, Dr. Murray said that some suggestions, such as developing closer contacts with human subjects, provide a good start. He said that knowing COPR's opinions on whether measures to protect human subjects should be applied to both privately and publicly funded research and whether there should be a federal office with oversight over all such research would be helpful. Dr. Koski urged COPR to share its views directly with the OHRP advisory committee that will soon begin to meet. Mr. Roehr suggested that market forces and efforts to better inform patients about clinical trials would improve protective measures and might also induce more lay individuals to participate in designing clinical trials that better meet their health needs. Ms. Lackritz praised the prototype document on informed consent described earlier by Ms. McCabe. In response to a question from Ms. Anne Thomas about how that document is being distributed, Ms. McCabe said that it has been sent to all IRBs and to cancer patient advocacy groups and to cancer research and treatment centers. She also said that other NIH Institutes are adapting the document for use in research settings where other diseases are being studied. Mr. Roehr said that he hopes that large components of the document will remain intact regardless of the settings in which it is being used. Dr. Kirschstein said that the IOM has been asked to provide advice on how to foster wide use of this prototype document. COPR Business Items, Wednesday, November 1, 2000Dr. Kirschstein acknowledged and thanked the members whose terms on the NIH COPR are ending with this meeting, including Dr. Castele, Dr. desVignes-Kendrick, Ms. Lewis, Dr. Rabb, Ms. Chin and Mr. Frohnmayer (who was unable to attend the October-November meeting). In thanking them for their contributions, she also told them that they should consider themselves permanent members of the greater NIH family and that they may be called upon for additional service. "Talking About the NIH" Packet—Anne Thomas Ms. Thomas described a packet that was presented to the members of the NIH COPR. It contains factual information about activities and budgets, key phone numbers for individuals and organizations involved in specific disease areas, a compilation of research advances since the 1950s, a brief history of NIH, a booklet called How NIH Sets Research Priorities, copies of Dr. Kirschstein's testimony presented during Congressional appropriations hearings held earlier during 2000, and two video tapes, one containing information that is available to visitors to the NIH campus and the other based on the Millennium Conference held at the White House and focused on the Genome Project and the Internet. Ms. Thomas said that additional materials can also be provided, such as detailed information about NIH research spending in a particular state. Discussion Ms. Quigley said that the video on the 8th Millennium Evening at the Whitehouse on "Informatics Meets Genomics" was excellent, both entertaining and substantive. In response to a question from Dr. Michael Anderson, Ms. Thomas said that inquiries about additional information should be directed to her or to Ms. Jennifer Gorman. In response to a question from Ms. Lewis about how COPR members might respond to inquiries about recent NIH hiring trends, Dr. Kirschstein said that NIH is almost always hiring personnel and that job openings are posted on the NIH Web site, while scientific positions typically are advertised in publications such as Nature and Science. She said that, although many NIH jobs are civil service positions and require applicants to be either U.S. citizens or permanent residents, other temporary research positions are available to scientists from abroad. She also said that there may be a temporary freeze on hiring imposed on NIH and other federal agencies during the transition to the new administration early in 2001. Ms. Thomas said that the NIH Home Page has a "careers here" link to job openings. Dr. Yvonne Maddox said that NIH recently began to do more in the way of corporate-style recruitment. She also pointed out that Mr. Steve Benowitz, Director of the NIH Office of Human Resources, produced a brochure describing career opportunities at NIH. This active recruitment approach is being used to bring more members of minority groups to NIH, as part of a campaign scheduled to begin in mid-November 2000, according to Dr. Maddox. As part of this campaign, NIH officials will hold workshops in California, Texas, and New York to encourage Hispanic Americans and members of other minority groups to join the NIH work force. In response to a question from Dr. desVignes-Kendrick about the strategic plan focused on health disparities research, Dr. Kirschstein promised to seek increased resources to support this initiative. Dr. Maddox said that 18 of the 25 NIH Centers and Institutes now have posted on the NIH Web site their final or near-final versions of their separate strategic plans for health disparities research, and she provided members of the NIH COPR with copies of one such plan, developed by the NIH National Institute of Child Health and Human Development. Each of these plans looks at such research from three perspectives: i) research, ii) infrastructure including recruitment, training, and retention of minority group researchers and health care professionals, as well as recruitment of minority group members as volunteers in clinical or other research projects involving human subjects, and iii) and community outreach and information dissemination. In regards to infrastructure, Dr. Maddox commented that the Institutional Development Awards (IdeA) Program would be expanded. She said that Congress provided additional funding in the FY 2001 budget for this NIH program, enabling the development of the NIH Biomedical Research Infrastructure Network (BRIN) and the issuance of an official request for applications (RFA) that was made public at the end of September to encourage investigators to take part in this new program. She explained that RFAs, which are a device to highlight new programs of special relevance or priority, differ from the more widely used mechanism for funding research through grants that originate as investigator-initiated proposals. The BRIN RFA is expected to stimulate applications to meet a mid-winter deadline, and successful proposals will provide funding to institutions in states that currently do not receive much NIH funding, to enhance infrastructure, conduct research, and ultimately better meet the health needs of underserved populations. These programs also emphasize community outreach and efforts in partnership development, according to Dr. Maddox. She said that the NIH efforts in Institute Director's budget retreat in June provided some of the critical planning for these activities, and these efforts are accelerating because the NIH Institutes committed nearly one-third of their requests for additional funding in these areas for community outreach activities. Dr. Kirschstein said that, once state and institutional recipients are identified, plans call for awarding each of them funding at identical or commensurate levels for three-year periods, with the option of three-year renewals if progress so indicates. Dr. Maddox said that NIH invited state and institutional representatives within the underfunded states to participate in a workshop that was held October 20, 2000. Dr. Sidney McNairy at the NIH National Center of Research Resources can be called on for guidance in developing applications in response to the BRIN RFA or for answering questions in this general area of interest. Ms. Lappin said that, in the two years since COPR was inaugurated, the NIH health disparities program has gained prominence and considerable momentum, and she credited Dr. Kirschstein and Dr. Maddox for elevating that program to the top of the NIH agenda. She also suggested that presentations describing the status of the outreach programs be part of the agenda for the next NIH COPR meeting. Dr. Kirschstein said that each of the NIH Institutes and Centers oversees active outreach programs, pointing to the example of the NIH National Cancer Institute's program providing materials and services into underserved regions such as in Appalachia. In response to Ms. Lappin's comments in praise of the NIH Record, Dr. Kirschstein promised to share those comments with its editor. Ms. Lappin also asked whether NIH would consider coordinating its outreach programs with those at the Centers for Disease Control and Prevention (CDC). Dr. Kirschstein said that NIH coordination with CDC tends to work best when conducted on an individual-to-individual basis rather than through more formal arrangements. In response to a question from Mr. Roehr about whether low levels of NIH funding levels in particular regions is associated with the absence of regional medical schools, Dr. Kirschstein said that this explanation does not appear to hold. Dr. Kirschstein said that many of the NIH-underfunded states have medical schools, and one consortium of four states, Washington, Alaska, Montana, and Idaho, was created by Senator Ted Stevens (R-AK) to encourage collaborative programs in research and health care. She said that the shortages in NIH funding have more to do with problems in putting together a critical mass of people to conduct both basic and clinical research. Dr. Kirschstein also said that the concept of outreach programs is relatively new to NIH, and it arose following lengthy discussions with various members of Congress representing those under-funded states, some of whom serve on appropriations committees. Dr. Maddox said that much of the recent growth in the NIH outreach programs also can be attributed to leadership within HHS, including from the Surgeon General and the Secretary of HHS. She said that other agencies within the department, particularly the Health Resources and Services Administration, have become important collaborators for NIH in developing community outreach programs. In response to a question from Ms. Lancaster, Dr. Maddox said that Tennessee does not qualify for the new NIH BRIN program because Vanderbilt University is a major recipient of NIH funding. Dr. Kirschstein added that the eastern region of Tennessee in Appalachia that is adjacent to parts of Kentucky, North Carolina, West Virginia, and Virginia has access to this program through the NIH NCI, where Dr. Friedel serves as liaison. She said that she would ask him to provide relevant information about the program at the next meeting of the NIH COPR. She also said that the single "have-not" state among several states that form a regional collaboration has the right to apply for funding through the NIH BRIN program. She mentioned the Vanderbilt-Meharry alliance as another example of a cooperative, infrastructure-building program that NIH has helped to fund. In response to a question from Dr. Rabb, Dr. Kirschstein said that Congress appears ready to pass legislation creating an NIH Center for Minority Health and Health Disparities Research with authority to issue funds through grants and contracts. Once the new center is created, its programs and administrative structure will need to be developed, and the current NIH Office of Research on Minority Health (ORMH) likely will help in this process by providing personnel, budget, and infrastructure. She later said that Dr. John Ruffin, Director, NIH ORMH, will be in charge of coordinating impending efforts to develop the new NIH Center, augment current outreach programs, and bring in additional experts to contribute to this process. The FY 2001 budget request called for an increase of $20 million from the previous year to an overall level of $117 million for the NIH ORMH, and additional increases will be sought in the FY 2002 budget, according to Dr. Kirschstein. Ms. Thomas said that these figures understate actual NIH spending on health disparities research that is being done by the other NIH Centers and Institutes. For example, in diabetes research, much of the NIH investment may involve projects that can benefit anyone afflicted with this disease but certainly is applicable to minority populations that suffer disproportionately from diabetes. Dr. Kirschstein said that HHS has identified six critical areas of emphasis-cardiovascular disease and hypertension, infant mortality, sudden infant death syndrome, HIV/AIDS, diabetes, cancer (particularly breast and prostate), and immunizations-throughout the Department, and NIH plays a leading role in research for five of those areas. Dr. Maddox said that the draft strategic plan for research on health disparities cites a single figure for overall NIH spending in this area, namely $1.3 billion, but if spending in related areas were included, $1.8 billion would be a better estimate of the total. However, by keeping the definition of health disparities research rather narrow for budget-tracking purposes, NIH will be better able to measure the impact of this research in the years to come, according to Dr. Maddox. She also said that research on environmental health represents another important focus of health disparities, one for NIH to follow more closely in this context in the future. Dr. Melanie Dreher, who is participating in the review of the Director of the NIH National Institute of Environmental Health Sciences (NIEHS), said that this institute deserves praise for its outreach programs because they bring attention to core health disparities issues. She said that living in particular environments can affect one's health and may lead to many different kinds of health problems. Dr. Kirschstein said that other NIH Institutes also study environmental effects on specific health problems of minority populations, such as the Asthma Project that involves a coordinated effort among the NIH NIEHS, National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases (NIAID). Dr. desVignes-Kendrick said that the National Association of County and City Health Officials (NACCHO) as well as the Houston City Health Department have designated environmental impacts and racial disparities in health outcomes a priority issue, indicating that other entities besides NIH and CDC are taking on this issue, which will require a concerted effort if progress is to be made. Ms. Lappin requested that Dr. Maddox present information at a future meeting regarding lack of subspecialty care for rare diseases of childhood. There is a growing shortage of specialists to care for sick children-for instance, one pediatric rheumatologist serves five Western states. She said that, in effect, this situation amounts to another kind of health disparity. Dr. Maddox said that there are similar shortages in other specialty areas. Dr. Kirschstein said that, despite the importance of this issue, shortfalls in the delivery of health care because of changing trends affecting the training of health professionals is not and cannot be a primary focus for NIH, which must maintain its focus on health research. Dr. Maddox added that NIH is concerned about the inclusion of children as subjects in clinical research, particularly those focusing on rare diseases, and NIH has an office devoted to such issues that helps to coordinate research related to rare diseases among the NIH Institutes and Centers. In response to a question from Dr. Anderson about clinics on indian reservations, Dr. Kirschstein said that the Bureau of Indian Affairs is within the Department of the Interior but the Indian Health Service (IHS) and its hospitals come under HHS. She said that there are more than 500 separate tribes, many with independent treaties and separate agreements with HHS on specific arrangements for health care. Although NIH had little interactions with the Indian Health Service in the past, Dr. Clifton Poodry at NIH recently developed a Native American round table to foster programs involving both NIH and IHS. Ms. Quigley, referring to issues discussed at the June NIH budget retreat, asked for a status report on industry-NIH research collaborations. In response, Dr. Kirschstein said that the NIH National Institute on Aging and the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases are working jointly with several companies on osteoarthritis research projects. She said that arranging such cooperative efforts presents challenges, particularly because NIH seeks to ensure that the results of federally sponsored research remain freely accessible. The NIH Office of Technology Transfer is in charge of negotiating agreements that attempt to do this while allowing for patenting and licensing of proprietary information. She said that an effort will be made to put this issue on the COPR agenda. In response to a comment from Mr. Roehr about the NIH NCI negotiating cooperative research agreements for research on rare diseases, Dr. Kirschstein said that, even here, problems arise when companies back away from developing products because numbers of patients with a particular disease are very low. Updates from COPR Working GroupsClinical Trials Working Group—Report prepared by Barbara Lackritz Because Ms. Lackritz could not attend the meeting, Ms. Thomas presented highlights from her working group's report. In a review of information on clinical trials provided by the Institutes on the NIH Web site, Ms. Thomas said that the working group concluded that some of the clinical trials listed on the Web site are identified clearly as to whether they are sponsored by industry or by one of the NIH Institutes. The working group did, however, report that for many of the listed clinical trials, it is unclear who is the sponsor of the trial. The group recommended that this unevenness be corrected. Similarly, patient protections and rights are not being consistently reported, and Ms. Thomas said that she would bring this discrepancy to the attention of the communications directors of the various NIH Institutes and Centers. Ms. Thomas said that the FDA Modernization Act mandates the NIH to bring all such information—including trials funded by industry and by other federal agencies—into a single database, which will be accessed through its Internet site, clinicaltrials.gov, as this system becomes more fully developed. Ms. Quigley said that, when pharmaceutical companies sponsor clinical trials, information about them needs to be disclosed in a much more forthright manner, not only in the fine print of informed consent documents. Following a discussion among several participants about how various NIH Institutes and programs handle such matters for clinical trials that they co-sponsor with industry, Ms. Thomas agreed to discuss this issue among her communications colleagues and to take steps to ensure that sponsorship of clinical trials is routinely disclosed. Dr. Kirschstein added that Ms. McCabe would welcome suggestions for making such disclosures part of the prototype informed consent document she described to the NIH COPR members. Mr. Roehr said that notice of NIH sponsorship of a clinical trial carries weight because it typically means the planning of the trial is sound and the results will not be biased, factors that encourage people to enroll in the trials. Outreach to Other Public Members Participating in NIH Groups—Working Group—Bob Roehr and Vicki Kalabokes Mr. Roehr said that he would like to see COPR members form networks with other public advisory groups at NIH. However, in meeting with NIH public liaison officers in June 2000, he learned that there are many practical obstacles to overcome before even preliminary steps toward this goal can be undertaken. Although someone at that meeting suggested that a focus group might help to identify ways to develop such networking efforts, Mr. Roehr advocated moving forward despite those many obstacles. Thus, he welcomed the availability of a partial list of public members within the NIH community that was compiled by Ms. Jennifer Gorman, the NIH Public Liaison Coordinator. He also agreed with the recommendation from one of the NIH public liaison officers that membership in the group that he envisions should not be limited to individuals who are officially public representatives but should include anyone with a genuine interest in the group's activities. He noted that he planned to meet soon with an NIH NIAMS advisory group. Ms. Kalabokes said that she planned to meet the next day with the Coordinating Council of the NIH NIDCR and, eventually, other public representatives associated with other NIH Institutes and Centers. One other current activity is to forge closer ties with the NIH COPR Associates and, with help from Ms. Gorman, efforts are under way to contact members of this group. In general, they are enthusiastic about developing deeper involvements with NIH, according to Ms. Kalabokes. One plan calls for asking them to serve on COPR working groups and, to facilitate forthcoming requests for them to do so, Ms. Gorman will provide COPR members with necessary information for contacting COPR Associates. Health Disparities/Underserved Populations Working Group—Isaac Montoya Dr. Montoya thanked Ms. Gorman for her help in coordinating the working group's efforts, which overlap extensively with those of the working group headed by Ms. Lappin that is focusing on human research protections. His working group, which has developed an outline of its plans, is considering what format of a report would be most helpful to NIH. So far, the input for this report has come mainly from communities connected to members who serve on the working group, but plans call for reaching out more broadly. One consistent comment from those who have been contacted is to try to define underserved populations not so much in terms of racial-ethnic distinctions but in terms such as geography, disabilities, and socioeconomic and educational factors. Rotation and Transition Working Group—Vicki Kalabokes Ms. Kalabokes said that the members of the working group conferred by telephone to consider how the first and subsequent rotations from membership on the NIH COPR should be handled. For the first phase, enough members identified themselves as willing to rotate off active membership, that the question of finding an equitable selection process for those who are first to retire was easily resolved. In terms of finding the first set of replacements, former NIH Director Dr. Harold Varmus had agreed that the COPR Associates would make up the primary pool of candidates for the next new group. The six new COPR candidates will primarily be selected from the COPR Associates pool. The six COPR members rotating off active membership of the council will end their terms on March 31, 2001. The six new members will be selected by February 2001 and will officially begin their terms as of April 1, 2001. However, for subsequent selection rounds, the members of this working group will work with NIH staff to make sure an open call for nominations is widely distributed every few years, in order to replenish the COPR candidate pool. Human Research Protections Working Group—Debra Lappin Ms. Lappin, who participated in deliberations conducted by an ACD working group on gene transfer research, said that those discussions in fact applied working group on more broadly to other areas of clinical research. Moreover, discussions on clinical research in other forums, including during the COPR working group sessions held on the previous day, indicate a changing landscape, particularly in terms of concerns being expressed to bolster measures to protect patients, according to Ms. Lappin. She said that COPR can provide an important, unique, and useful voice representing the public in these continuing discussions. The working group members planned to meet later on November 1, 2000, to identify specific areas of concern and to recommend additional issues for OHRP to consider, according to Ms. Lappin. Those issues include informed consent, patient confidentiality, the role of IRBs, conflicts of interest, underserved populations, patient recruitment, regulatory burden, and concerns related to behavioral research. She said that the working group plans to prepare a discussion paper. Discussion In response to Dr. Montoya about whether NIH staff members could join in working group activities, Ms. Thomas said that Dr. Wendy Baldwin and Dr. Belinda Seto would be participating in the working group's meeting. Ms. Thomas said that she and other members of her staff also will be available to the working groups. However, Dr. Kirschstein said that neither she nor Dr. Maddox should be listed as members of the COPR working groups, which may make recommendations to NIH, but that both of them would be pleased to serve as resources to the working groups. Discussion of Feedback from COPR Members on the History, Values and Operations Guide of COPR Ms. Thomas turned the discussion to the draft guidebook, History, Values and Operations of COPR, and said that, when completed, it will be helpful to address some of the many inquiries she has received about COPR, including from individuals outside the U.S. Because an additional purpose of the guidebook will be to help orient new members of COPR, the draft was distributed to the current members for their comments about a month before the October-November COPR meeting. One comment received from several members was that it should be more explicit about the time commitment required of COPR members. Dr. Montoya said that the guidebook, along with the Talking About the NIH resource kit, will provide useful tools for COPR members to interact with the public, and also for enhancing communications between NIH and the public. He said that, in interacting with the public on behalf of the NIH COPR, he spends the great majority of his time listening rather than describing NIH. Nonetheless, having these resources and tools will be helpful to COPR members as a concise means for describing NIH activities. Dr. Castele said that the guidebook should include a list of typical COPR activities outside its meetings at NIH. Dr. Dreher said that it is also important to say that COPR meetings are scheduled well in advance, enabling more of its members to attend. Mr. Roehr said that the guidebook should say COPR members are expected to participate actively in working groups. Dr. Montoya said that COPR is increasingly becoming a resource for the NIH Institutes, an activity that adds further to the time commitment of COPR members. Dr. Castele pointed out that there are typically daily e-mail messages among COPR members. Ms. Quigley said that it would be helpful to describe that the role of the NIH COPR member, although not visible every day, can present itself at any time. Mr. Vaalburg asked what the primary focus of COPR members is expected to be. In response, Ms. Thomas said that some members prefer special assignments, whereas others prefer working group assignments. He also said that many people he encounters in his work activities are surprisingly unfamiliar with NIH. Dr. Kirschstein said that other organizations are dedicated to educating the public about NIH. For example, Research America! recently commissioned a survey to determine whether it is doing enough in that regard. Because NIH is part of HHS, it is constrained in what educational and promotional activities it may conduct. Ms. Thomas asked the COPR members to consider several options as to how the group would conduct and run its decision-making process. In response, Mr. Roehr said that consensus is a prescription for paralysis and recommended that a simple majority vote would be the best general option to embrace. Dr. Castele agreed with this suggestion. Dr. Kirschstein asked whether COPR members would feel constrained in any way if their individual votes were recorded and whether that practice might lead to a sense of invasion of privacy. In response, Mr. Roehr said that holding recorded votes is not likely to be common for COPR. Moreover, because COPR serves in an advisory capacity, it seems unlikely that public pressure would be brought to bear on individual members. Dr. Kirschstein said that the minutes of the NIH ACD or other advisory groups typically do not list how each member voted on particular issues, but merely an overall vote count. Ms. Quigley said that it would be appropriate for COPR vote counts to be similarly recorded but she also noted that its members strive for consensus. Mr. Roehr said that it is important to preserve the right to present minority reports in those cases where consensus is not reached, or some members disagree with the majority viewpoint. Ms. Thomas then asked the COPR members to think about the slate of six new members to be named in January/February 2001, who are very likely to be drawn from the COPR Associates, as was indicated by former NIH Director Varmus. That group of candidates is very diverse, but some thinking is needed about how to maintain that diversity and what process to use in future rounds of identifying candidates for COPR membership. Dr. Kirschstein said that the choice of COPR members from such candidate pools is at the discretion of the NIH Director. Ms. Kalabokes said that her working group will provide recommendations for selections expected in 2002, 2003, and beyond. In response to a discussion among several COPR members whether Americans Indians are represented in the current group of COPR Associates, Ms. Thomas said that an effort to identify such candidates was made initially, and this effort would be extended, including through the Indian Health Service. Ms. Lappin said that it will be a challenge to fill this gap and to identify other appropriate candidates while rotating in new members of COPR. Part of the challenge is deciding whether to fill specific "interest" vacancies or to seek again nominations representing broad constituencies. Mr. Roehr said that adding an international component, particularly to reflect the importance of global infectious diseases should be considered. Ms. Quigley said that, although COPR members tend to be categorized according to what interest group they come from, in fact the members tend to represent amalgamations of varied interests. Dr. Castele pointed out that all three physicians now on COPR are part of the first group to rotate off active duty. Mr. Roehr said that some of those among the Associates will need to be asked again whether they continue to be interested in joining COPR. In response, Ms. Thomas said there have been efforts to contact them. Ms. Cate Timmerman said that the Associates have responded to such a survey, and most of them have registered whether they can serve or not. Mr. Roehr said that it is valuable to have good chemistry among the COPR members, but Ms. Lappin said that identifying candidates who are likely to interact well with the group is not an easy task. Dr. Kirschstein said that the final selection remains her responsibility, and that efforts were made to speak with but not interview candidates during the initial round of choices to constitute this version of COPR. Dr. Castele suggested that the COPR Guide describe potential responsibilities for COPR alumni. He also thanked COPR members and NIH staff for their collegiality during his tenure on the council. Mr. Roehr pointed to the first sentence of the draft COPR Guide and said that it might be re-phrased to better reflect the public as equal stakeholders in public input. He volunteered to rewrite that section. There was a brief discussion to set the dates for the next meetings of COPR as May 1st and October 23rd, 2001, to avoid conflicts with various holidays and other meetings. Ms. Thomas then suggested that agenda items for the April meeting be discussed in a forthcoming conference call and agreed to reserve time for working groups to meet. Dr. Kirschstein further suggested that time be reserved on October 24, 2001, for COPR members to participate in the GPRA review of NIH. As the meeting adjourned, the several departing COPR members, David Frohnmayer, Maurice Rabb, M.D., Ted Castele, M.D., Robin Chin, Mary desVignes-Kendrick, M.D., and Lydia Lewis, again thanked their colleagues and NIH staff for their cooperation and collegiality throughout their COPR undertakings. Summary and ConclusionsThe Director's Council of Public Representatives (COPR) of the National Institutes of Health (NIH) met on October 31–November 1, 2000, to consider reforms being instituted by the NIH Office of Medical Applications of Research, several matters affecting human subjects protections, and a series of activities of COPR working groups. The COPR acknowledged and commented on these presentations, made several specific recommendations about measures to protect people participating in research and on research on health disparities, agreed on procedures for how COPR will develop recommendations, and acknowledged that several working groups continue to develop specific recommendations and plans for dealing with a variety of other issues. Table of Abbreviations
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