Summary

The Food and Drug Administration (FDA), in mid-1992, had 41 standing technical advisory committees or panels that supported the work of its three centers responsible for the evaluation and regulation of human drugs, biologics, and medical devices. We refer in this report to these committees and their administrative support as the FDA's ''advisory committee system.''

In late 1991, the Institute of Medicine (IOM), in response to a request from the FDA, undertook a study of the agency's advisory committee system. This request was initiated by Commissioner David A. Kessler. He asked that the IOM examine the optimal use of FDA advisory committees in the evaluation of drugs, biologics, and medical devices and also consider such committees in relation to agency management and agency accountability. The Commissioner himself emphasized his desire to receive a report that provided operational guidance for the agency. In addition, he singled out as the most important issue the committee's examination of financial "conflict of interest" controls as they affected advisory committees.

The IOM convened a committee to conduct this study. Its members brought expertise in medical research; development of drugs, biologics, and medical devices; design and conduct of clinical trials; medicine, surgery, and nursing; regulation of drugs, biologics, devices, consumer products, and health care services; administration of medical research, health care financing, and the delivery of health care services; and health and science policy research. Three members of the IOM committee currently serve on FDA advisory committees, others have served in the past, and several were previously involved as FDA officials in the design of the current system.

In general, advisory committees are the major way by which the FDA obtains independent technical and scientific advice. Other means for obtaining such advice include workshops, symposia, consultants, and extensive, often informal, contacts between agency professionals and the scientific and medical communities. Although this report focuses on advisory



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 1
Food and Drug Administration Advisory Committees Summary The Food and Drug Administration (FDA), in mid-1992, had 41 standing technical advisory committees or panels that supported the work of its three centers responsible for the evaluation and regulation of human drugs, biologics, and medical devices. We refer in this report to these committees and their administrative support as the FDA's ''advisory committee system.'' In late 1991, the Institute of Medicine (IOM), in response to a request from the FDA, undertook a study of the agency's advisory committee system. This request was initiated by Commissioner David A. Kessler. He asked that the IOM examine the optimal use of FDA advisory committees in the evaluation of drugs, biologics, and medical devices and also consider such committees in relation to agency management and agency accountability. The Commissioner himself emphasized his desire to receive a report that provided operational guidance for the agency. In addition, he singled out as the most important issue the committee's examination of financial "conflict of interest" controls as they affected advisory committees. The IOM convened a committee to conduct this study. Its members brought expertise in medical research; development of drugs, biologics, and medical devices; design and conduct of clinical trials; medicine, surgery, and nursing; regulation of drugs, biologics, devices, consumer products, and health care services; administration of medical research, health care financing, and the delivery of health care services; and health and science policy research. Three members of the IOM committee currently serve on FDA advisory committees, others have served in the past, and several were previously involved as FDA officials in the design of the current system. In general, advisory committees are the major way by which the FDA obtains independent technical and scientific advice. Other means for obtaining such advice include workshops, symposia, consultants, and extensive, often informal, contacts between agency professionals and the scientific and medical communities. Although this report focuses on advisory

OCR for page 1
Food and Drug Administration Advisory Committees committees, the IOM committee recognizes and endorses the use of these other means of obtaining independent expert advice. The FDA advisory committee system was established at the agency's initiative to provide it with technical assistance related to the development and evaluation of drugs, biologics, and medical devices, to lend credibility to its decisions and decision-making processes, and to provide a forum for public discussion of certain controversial issues. In general, the IOM committee believes that the existing system is fundamentally sound, has served the agency well, and does not need wholesale reorganization. It should be retained and strengthened. However, the IOM committee recommends a number of administrative and procedural changes that are designed to improve the performance and usefulness of the advisory committee system. The Roles of FDA Advisory Committees The IOM committee believes that the primary role of FDA technical advisory committees is and should be to provide independent expert scientific advice to the agency in its evaluation of specific drugs, biologics, or medical devices at any stage of consideration by the agency. A related role is to advise the agency on general criteria for evaluation and on broad regulatory issues that are not related to a specific product. (A role specific to CBER, which the IOM committee recognizes, is the review of intramural research programs and personnel.) Several key terms and assumptions warrant further comment. First, "independence" refers to freedom from influence by the sponsor of the product under consideration, by any other entities or persons that could gain or lose as a result of the outcome of the process, and by the FDA itself. As a practical matter, the issue of independence of advisory committees is usually raised with respect to their relation to the FDA. The high stakes associated with FDA decisions mean that parties disappointed by its actions have strong incentives to charge that the independence of advisory committees is compromised by undue FDA influence. However, the issues of independence and undue influence may arise as a result of subtle facets of the process; for example, the recruitment of committee members; delays in distribution of advance materials; the content and tone of agenda questions; and even seating arrangements at committee meetings. The IOM committee makes recommendations on all these issues, which collectively point to greater safeguards of the independence of committees.

OCR for page 1
Food and Drug Administration Advisory Committees Second, "expert scientific advice" implies that members will be acknowledged experts in some area of science that is relevant to the purview of the specific advisory committee. Third, advisory committees advise the FDA and do not themselves have authority to make decisions that obligate the agency or any private party to a course of action. Fourth, advisory committees respond to specific questions that have been identified by the professional staff of the agency. These questions may deal with study design or methodology, adequacy of data, and assessment and interpretation of risks and effectiveness. Finally, although advisory committees have a prominent role in the product approval stage, they are sometimes used earlier in the product development cycle and sometimes invited to consider postmarketing issues. The IOM committee believes that it is proper for the FDA to use committees at any stage of review when scientific advice is needed, whether or not regulatory action on a specific product is under consideration. Practical Limits on Advisory Committees It is important to acknowledge that there are significant practical limits on the FDA's use of advisory committees. The most important limit is the time committee members are able to commit to the activity. Another limitation is the necessity that the agency be selective in choosing questions for committees from an enormous amount of material and wide range of issues under review. Still another limit is the difficulty of exercising tight control over agenda time, with the consequence that committee discussion time is often severely truncated. Finally, the use of advisory committees is limited by the resources that the FDA has available to support them. COMMITTEE MEMBERSHIP Nomination Criteria The ability of the FDA to attract and retain qualified individuals who possess "expertise in the subject matter with which the [advisory] committee is concerned" is critical to the successful operation of the advisory committee system. The "subject matter" of advisory committees pertains to (a) the evaluation of drugs, biologics, and medical devices regarding their safety and effectiveness, including indications and contraindications for use and related issues of labeling, and (b) to broader technical issues related to product evaluation, such as specific methodologies for assessing a particular class of therapeutic agents. Given the purposes of FDA advisory committees,

OCR for page 1
Food and Drug Administration Advisory Committees The IOM committee strongly endorses the criterion of scientific or technical competence as a requirement for selecting all voting members of FDA technical advisory committees. In this context, "diversity" goals of gender, race and ethnicity, and geography also guide the selection of committee members. The IOM committee believes that these goals are not incompatible with the criterion of scientific and technical competence but reflect legitimate policy objectives of a pluralistic society that are designed to ensure a range of viewpoints on what are seldom purely technical issues. However, meeting these diversity goals may necessitate special efforts by the FDA to identify women and minority group members who possess the necessary expertise. The IOM committee recommends that the FDA continue its policy of actively seeking qualified women and members of minority groups as potential candidates for advisory committee membership. Some constraints may limit the access of the Department of Health and Human Services (DHHS) to scientific and technical expertise as it seeks to meet its diversity goals. Current policy of the Department of Health and Human Services prevents an individual from serving concurrently on more than one Public Health Service advisory committee without a special departmental waiver. This policy limits the expertise that can be tapped for a particular committee and impedes meeting diversity objectives. The IOM committee recommends that the Department of Health and Human Services eliminate its policy prohibiting dual committee membership and that qualified candidates for FDA advisory committees be allowed to decide whether they wish to serve on more than one Public Health Service committee. However, it also recommends that the Department exhaust other means of recruitment before it resorts to selecting individuals who serve on other advisory committees. Although the Federal Advisory Committee Act (FACA) requires that advisory committee membership be "fairly balanced in ... the points of view represented and the functions to be performed," this criterion provides little operational guidance to agency heads in the nomination and selection of technical advisory committee members who advise on a wide and unpredictable range of issues. The IOM committee believes that "balance" for the FDA's technical advisory committees should be interpreted as a mix of relevant scientific disciplines and a diversity of scientific views. The IOM committee also believes, and court decisions now support, that it is

OCR for page 1
Food and Drug Administration Advisory Committees ultimately the Commissioner's responsibility to see that such balance is achieved. The IOM committee considered the wisdom of recommending that 'balance" be interpreted as committee membership that included representatives (or advocates) of specific constituencies, irrespective of scientific competence. The committee rejected this premise on the grounds that the primary role of advisory committees is to provide the agency with the best scientific interpretations and advice and not to represent specific constituencies.* Recruitment Procedures The FDA uses a number of procedures to generate nominees for advisory committees. The only agency-wide formal mechanism is the annual Federal Register announcement of advisory committee vacancies required by the FACA. Informal nomination-seeking practices vary across centers, within centers, and over time. The IOM committee recommends that the FDA adopt an agency-wide recruitment policy and develop a more systematic approach to seeking nominations on a continuing basis for potential advisory committee membership. The agency should actively seek nominees from many sources—academic medicine, professional societies, other government agencies, industry, and consumer and patient organizations. It should not rely solely on its own staff for such nominations. Each center should develop and periodically update a pool of qualified candidates, rather than simply seek nominations to fill vacancies. The IOM committee considers the responsibility of nominating qualified individuals for FDA advisory committees to be shared by medical and scientific societies, medical school deans and department chairs, consumer and patient organizations, and other interested parties. The IOM committee, addressing itself to these groups, urges them to accept as a continuing obligation the identification and nomination of individuals to the pool of potential FDA advisory committee members. *   The IOM committee recognized the importance of input to advisory committee deliberations from non-scientific sources such as patients, industry, and consumer groups and concluded that such input can be best achieved by testimony that relates directly to the specific agenda of a committee.

OCR for page 1
Food and Drug Administration Advisory Committees Consumer Members The IOM committee regards the expression of consumer views on FDA technical advisory committees as both valuable and necessary. For medical device advisory panels, these views are provided by nonvoting consumer representatives, as required by statute. For all drug and two biologics advisory committees, they are supplied, not by nonvoting consumer representatives, but by consumer-nominated, technically qualified voting members. The committee attaches great importance to the criterion of technical expertise for the nomination and selection of voting members of FDA advisory committees and opposes granting voting member status based on representation of specific constituencies. It considered and rejected the extension to drug and biologics advisory committees of the legally-required CDRH approach of nonvoting consumer and industry representatives but chose not to recommend modification of the law. The IOM committee believes that the concept of "consumer"—both for consumer-nominated members and consumer representatives—should be expanded to include patients or patient-nominated individuals, whose viewpoints can be valuable in the product evaluation process. The FDA should actively solicit nominations from consumer and patient organizations for technically qualified individuals to serve as voting members on all of its advisory committees. The agency should continue to solicit nominations from the consortium of consumer organizations, but it should also reach out to other interested parties. In the judgment of the IOM committee, the practice of allowing any outside organization to screen (and thus to screen out) nominees for FDA advisory committees is unsound. The IOM committee recommends that the FDA seek technically qualified nominees from consumer organizations and other interested parties to serve as voting members on all of its technical advisory committees and panels. Appointment should require the basic qualification of scientific or technical competence. The committee also recommends that the concept of "consumer" be expanded to include patient and patient-oriented organizations. Furthermore, no private individual or organization should be given the right to screen nominations from other sources on behalf of the agency. Appointment Authority Until early 1991, the Secretary of Health and Human Services appointed members of FDA technical advisory committees. This sometimes resulted in

OCR for page 1
Food and Drug Administration Advisory Committees nominees who may not have been scientifically qualified or who were selected to bring a politically preferred view on scientific and regulatory matters before the FDA. Following enactment of the Food and Drug Administration Revitalization Act of 1990, the Commissioner has appointed technical advisory committee members, but he remains under an obligation to send nomination packages to the Office of the Secretary 10 days in advance of any appointment. The IOM committee believes that vesting power to appoint committee members in the Commissioner constitutes a substantial step forward in both expediting the appointment process and ensuring that such appointments are responsive to the specific scientific and technical needs of the agency. The IOM committee commends the Office of the Secretary for its concurrence that the Revitalization Act vests formal authority to appoint advisory committee members in the Commissioner of Food and Drugs. Administrative Responsibility for Appointments The Commissioner, under his authority to appoint advisory committee members, should clearly indicate to all FDA staff that center directors, office and division directors, and executive secretaries share responsibility for recruiting qualified advisory committee members. Nominations should come to the Commissioner from the center directors. The IOM committee recommends that the job descriptions of the FDA center, office, and division directors, and executive secretaries be expanded to reflect their responsibilities for recruiting, nominating, and recommending advisory committee members. COMMITTEE INTEGRITY The IOM committee believes that it is essential that members of FDA's advisory committee be impartial and objective and not compromised by financial conflicts of interest. It is also critical that they be free of demonstrated intellectual bias. These goals are both practical conditions for the effective performance of advisory committees and an expression of deeply held democratic values. To achieve these ends, the IOM committee has addressed the FDA's standards and procedures for controlling financial conflict of interest and intellectual bias. At the outset of this study, Commissioner Kessler asked that the IOM committee provide the FDA with specific guidance on the handling of

OCR for page 1
Food and Drug Administration Advisory Committees potential financial conflicts of interest involving advisory committee members. Controversies over this issue were threatening the FDA's ability to use advisory committees. The study revealed that the "problem" identified by the Commissioner involved the interaction of new conflict of interest statutes and executive orders, the legal interpretation of what these laws required, their administrative implementation, and several highly visible committee meetings. Moreover, this interaction was occurring in a highly politicized environment and in a compressed period of time. The financial conflict of interest laws that apply to full-time federal employees also apply to advisory committee members who are appointed, as those at the FDA are, as special government employees (SGEs). As applied to advisory committee members, these laws exist to ensure that their impartiality is not compromised by their personal financial interests, or those of their spouses and immediate families, or of their employers. Advisory committee members are screened for potential conflict of interest at two different times. First, candidates for membership are evaluated at the time of nomination and, if appointed, file a statement disclosing their financial interests. This initial screen provides the basis for a set of so-called "exclusions," namely, specific companies, products, or issues that might come before a committee and that the individual may not consider. Although this stage of review is important, by far the greater number, and more difficult, conflict of interest issues arise when a member's financial interests are found to intersect with particular meeting agenda items. For each committee meeting, the FDA reviews each committee member's interests and affiliations in relation to the agenda to determine whether a potential financial conflict or the appearance of such conflict exists. The discovery of a potential conflict disqualifies a member from participating in the particular discussion of a specific agenda item unless a waiver is granted. The law allows a waiver if (1) the member's interest is not substantial, (2) if it is too remote or inconsequential to affect his or her impartial judgment, or (3) if the member's participation is so important that it outweighs the potential conflict. Any waiver must be sought and approved before the individual member may participate in the committee's discussion of the specific matter in question. Events in 1989 and 1991 raised questions about financial conflict of interest to a new prominence. In 1989, in the wake of several well-publicized instances of high-level government officials engaging in unlawful financial transactions for personal benefit, including the generic drug scandals that affected the FDA (although not with respect to any advisory committee), the executive branch took action. The President's Commission on Federal Ethics Law Reform recommended that standards of conduct be updated and that

OCR for page 1
Food and Drug Administration Advisory Committees the Office of Government Ethics (OGE) be given authority to issue uniform regulations for all executive branch agencies. Executive Order 12674, issued by President George Bush on April 12, 1989, revoked the decentralized regulatory scheme that had been established in 1965 and directed the OGE to develop "a single, comprehensive, and clear set of executive branch standards of conduct that shall be objective, reasonable, and enforceable" (56 FR 33778, July 23, 1991). The OGE, which had been part of the Office of Personnel Management, was established as a separate agency of the executive branch on October 1, 1989. Congress, unwilling to cede leadership in this arena to the executive branch, enacted the Ethics Reform Act of 1989 (Public Law 101–194) on November 30, 1989. This act included a provision [Section 208(b)(3) discussed below] intended to facilitate the use of expert advisory committees by empowering agency heads to grant waivers from the law's basic prohibition when the need for an individual member outweighed any potential conflict. Responsibility for implementing the executive order and the new statute fell primarily on the OGE and, within DHHS, on a new unit in the Office of the General Counsel. That unit, the Office of the Special Counsel for Ethics (OSCE), is responsible for DHHS-wide policies and procedures safeguarding the ethics of government employees and for coordinating departmental policy with OGE. Within the FDA, an existing unit, the Division of Ethics and Program Integrity (DEPI), retained responsibility for approving waiver requests from the centers on behalf of the Commissioner. In 1991, several FDA advisory committees convened to review high-profile products that presented particularly controversial problems of potential conflict of interest. The topics on which the agency sought advice included the controversy over the review of THA as a drug for the treatment of Alzheimer's disease; the dispute over the possible propensity of ProZac to induce suicide in September 1991; the safety of silicone gel breast implants in November 1991 and again in February 1992; and a controversy over the use of photopheresis in the treatment of scleroderma. Although each of these committee meetings originated in unique circumstances, all drew unprecedented attention to FDA's procedures for controlling potential conflicts of interest, and they arrived at FDA's doorstep in the same period of time. What did these cases reveal? First, the agency had been processing waivers under outdated standards that had not been updated to accord with the 1989 statute. Second, although waiver provisions are part of the federal criminal code, government lawyers were not involved in reviewing waivers. Consequently, the FDA's Chief Counsel, in the fall of 1991, assigned two lawyers to review waivers, and they began to question the agency's existing

OCR for page 1
Food and Drug Administration Advisory Committees procedures. Soon thereafter, OSCE became involved on behalf of the department and eventually replaced the agency's lawyers. Third, OSCE and the OGE introduced new and expansive waiver standards and procedures. Fourth, the units in the FDA still responsible for conflict of interest compliance continued to perform their roles without any high-level policy guidance. Fifth, both the agency's lawyers and those from OSCE, who felt compelled to change the rules to accord with the law and executive order, dealt with waiver issues on a case-by-case basis, and provided little general guidance to those administrators responsible for managing the advisory committee system. To make matters worse, all of these changes were occurring within a very short span of time. Not surprisingly, the conflict of interest problem was far more visible inside FDA than outside. And within the agency no one fully grasped that nature of the changes that were taking place. However, to some it appeared as though conflict of interest restrictions might cause the advisory committee system to grind to a halt because new standards had not been operationally clarified and the process had been greatly complicated. Any attempt to address the problem must deal with issues of law, of bureaucratic procedure, and of administration. The IOM committee considered reforms that would require new legislation and those that could be implemented within existing statutory authority. Options Requiring Legislation The IOM committee considered several options that would require new legislation. The first would substitute for the present disqualification system one that required committee members to publicly disclose all of their interests and affiliations, and then relied on public scrutiny to assess the objectivity of their advice. The IOM committee found this approach unacceptable, as it would allow participation of members with significant, direct financial interests that should be disqualifying and would undermine the appearance of objectivity. A second option would be a system that coupled full disclosure of all interests with a general rule barring participation by members with significant financial interests. Although this proposal may contain the core of a promising reform of the system for regulating conflict of interest, the IOM committee did not explore fully its ramifications. The committee's judgment and that of many we spoke to was that a major legislative overhaul of this magnitude was simply unlikely. Given FDA's expressed needs, our charge, and our timetable, the committee turned to solutions that were feasible within the existing statutory framework. However, this approach is clearly a candidate for further study.

OCR for page 1
Food and Drug Administration Advisory Committees Options Available within Existing Authority What can be done under existing authority? Potentially, a good deal, as the following options suggest. Although the first option below could be implemented by FDA itself, the successful implementation of the other recommendations would require the active involvement of the Commissioner and his office, the supportive collaboration of the OSCE, and at least the tolerance of the OGE. One theoretical option for FDA would be to avoid appointing advisory committee members as special government employees, thus circumventing the restrictions of the federal conflict of interest law. This solution has the notable disadvantage of attempting to define the problem away, which is hardly a way to instill confidence in the system. Moreover, new legislation would possibly be needed to allow payment of members and sharing of trade secret information. Second, the FDA itself could exercise greater care in the initial appointment of advisory committee members. It could demand even more information than is currently required to enable it to identify in advance potential members whose financial interests would clearly disqualify them for some committee meetings. Yet because the interpretation of a prohibited interest is already extremely broad, and potential conflict cannot be identified before meeting agendas are set, serious pursuit of this problematic approach might disqualify valuable members and produce no gain in integrity. Moreover, the conflicts of interest that might arise over the duration of a committee membership are unpredictable at the time of appointment. Third, the FDA, working with OSCE, could formulate and codify criteria for granting 208(b)(3) waivers. The IOM committee believes that this is essential. Codification would be a lengthy process, but some mutual understanding of the grounds for justifying a waiver is badly needed. A checklist of variables must be formulated that includes: the size of the interest; the character of the interest; the likelihood than an interest will be affected by agency action based on the committee's advice; and the actual importance of the member to the committee's deliberations. Regarding the latter point, membership alone should not be taken automatically as a decisive measure of a member's importance. Of immediate importance is the need to clarify the criteria for dealing with potential conflicts arising from institutional or employer financial interests, research grants and contracts to committee members, and member involvement with competing products and technologies. Regarding institutional financial interests, most advisory committee members are university employees; most of their employers operate medical schools,

OCR for page 1
Food and Drug Administration Advisory Committees agency informs sponsors and committee members of this stricture. This policy is designed, in general, to protect the independence of the committee from lobbying by sponsors. The IOM committee affirms the soundness of this policy. Fourth, the FDA takes the view that it is not obligated to share with sponsors, or the general public, its communications to advisory committee members before a meeting. The IOM committee, however, believes that it is appropriate for the FDA to provide sponsors with copies of all information that it sends to advisory committees. This practice would facilitate the preparation by the sponsor of its response to agency questions. The IOM committee recommends that the FDA provide sponsors of applications with the same materials that it sends to advisory committees. Questions should be sent to committees and sponsors on the same schedule. Fifth, as a general practice, the FDA releases to the public the questions that it has prepared for the advisory committee on the morning of a meeting. The IOM committee agrees with this practice and does not recommend earlier release to the public. A recent report by Kutak, Rock & Campbell, which dealt with FDA's handling of financially sensitive information, basically concurred that FDA release of the questions to the public on the morning of a committee meeting was sound practice.2 The FDA has before it the Kutak Rock & Campbell report and this IOM report on advisory committees; it must address the implications of where the two intersect and make any appropriate policy determinations. Conducting an Advisory Committee Meeting The successful conduct of an advisory committee meeting involves the conscientious efforts of the committee chair, the members, FDA officials, and the sponsors. To improve the deliberations of advisory committees and the quality of their advice to the FDA, this section recommends a number of steps to be taken regarding the interactions among these parties. Allocation and Control of Agenda Time One of the keys to an effective advisory committee meeting is the allocation and control of agenda time. Typically, the initial assignment of

OCR for page 1
Food and Drug Administration Advisory Committees time to agenda items is done by FDA professionals, sometimes in consultation with committee chairs. Once time is allocated, of course, it is important that committee meetings adhere to the established schedule. For this to occur, it is necessary that the chair exercise control over agenda time. The protection of opportunities for committee discussion is perhaps the primary reason for the chair to exercise strict adherence to the agenda schedule. Discussion time often gets squeezed because it is the last scheduled item on an agenda, sponsor and agency presentations frequently go longer than scheduled, and some committee members may leave to return home. The IOM committee recommends that the FDA routinely consult committee chairs in the allocation of time to agenda items and that this allocation try to anticipate points throughout the meeting at which committee questioning will be necessary. It further recommends that committee chairs be instructed that the control of agenda time is one of their primary responsibilities, and that they must work to protect committee discussion time, including exercising strict control on the presentations of sponsors and the FDA before the committee as well as attendant questions and discussions by committee members. Electronic Coverage of Meetings FDA advisory committee meetings often receive television coverage, which can be intrusive in committee deliberations. FDA regulations governing television or "electronic recording equipment" (21 CFR 10.200–206) vest authority in the advisory committee chair to control such coverage as necessary. The IOM committee recommends that advisory committee chairs be routinely oriented to their authorities and responsibilities in regard to the control of electronic coverage of advisory committee meetings, for the purpose of facilitating committee deliberations without compromising the public's right to know. Voting Voting by CDER and CBER advisory committees occurs at the discretion of the committee chair or according to the tradition of the reviewing division. Depending on the committee, no votes may be taken, votes may be taken only on scientific questions, or votes may be taken only on regulatory questions. All CDRH committees vote on the regulatory question only, i.e., the approvability of a device.

OCR for page 1
Food and Drug Administration Advisory Committees The IOM committee recommends that FDA adopt a policy, consistent across all advisory committees, by which committees are asked for a vote on important questions before the committee. To the extent feasible, the chair should identify in advance the issues on which votes are to be taken. Agency Neutrality As a general proposition, the IOM committee believes that FDA staff members should conduct themselves at advisory committee meetings in ways that avoid the appearance of exerting undue influence over the committee. Agency presentations to a committee should focus on the critical evaluation of data but should not withhold or disguise expressions of agency concerns with an application. The tone of agency presentations should be professional, thorough, and dispassionate, and agency staff should not dominate or appear to dominate committee discussions. Seating arrangements at advisory committee meetings should facilitate committee discussions rather than the convenience of the audience. As a general rule, the IOM committee believes that the division director should not sit next to the committee chair. Nor should other FDA personnel sit among the committee members. Custom Tailoring of Committee Membership The FDA has rechartered, or soon will recharter, all of its advisory committees. This will permit agency officials who are organizing a given meeting to draw voting members from any other FDA advisory panel or committee, or from a pool of consultants, on an as-needed basis. Although this "custom tailoring" authority is welcome in principle, it has not yet been used with any frequency, and it poses several challenges to the agency. In general, the IOM committee believes that the continuity of the standing advisory committee should be maintained and that custom tailoring should be used sparingly to augment a committee's expertise relative to a specific agenda item. On the one hand, the IOM committee recognizes that it may be necessary to add voting members in some cases in which the scientific or clinical scope of a committee may not be adequate for considering a particular class of drugs, biologics, or devices. On the other hand, the frequent use of this flexible authority by the FDA may make it vulnerable to charges of "stacking the deck" with committee members likely to favor its views.

OCR for page 1
Food and Drug Administration Advisory Committees The IOM committee recommends that in cases in which FDA must modify the composition of an advisory committee by ''custom tailoring,'' it do so judiciously and sparingly, augmenting the core committee by adding the needed expertise. The committee also recommends that FDA actively consult the committee chair in the process. It also recommends that the director of the appropriate center approve all such decisions. Meeting Follow-up Some FDA centers or divisions provide little or no follow-up to advisory committee members regarding the results of their deliberations. Failure to do so is a source of complaints. A systematic effort to provide follow-up would convey a strong positive message to advisory committee members that the agency attaches great value to their service. The IOM committee recommends that the FDA follow up each advisory committee meeting by routinely and immediately providing committee members with a copy of all press releases issued after a meeting; informing members by FAX at the time of approval or disapproval of any application that the committee has considered; routinely reporting the status of matters previously considered by the committee at the beginning of each meeting; and reporting annually the disposition of committee-related matters. ORGANIZATION AND MANAGEMENT Several prior reports on FDA that deal with advisory committees call for varying degrees of centralization of committee management functions. These reports also highlight the need to address issues of organization and management. System Management FDA's technical advisory committees are chartered by the Commissioner of Food and Drugs for the purpose of advising him on the safety and effectiveness of drugs, biologics, and medical devices. In addition, committee members are appointed by him and requests for waivers of conflict of interest are granted by him. Legally, advisory committees report to the Commissioner. In actual operation, however, the current FDA advisory committee system is highly decentralized and substantial variations exists both across and within centers. These variations have arisen as a result of historical,

OCR for page 1
Food and Drug Administration Advisory Committees organizational, and idiosyncratic influences that are not always rooted in genuine scientific or functional differences among committees. The IOM committee believes that unjustified variation in the use of advisory committees should be minimized in the interest of strengthening their role as independent advisors to the FDA. This highly decentralized system lacks any agency-wide administrative policy and management guidance. It thus appears vulnerable to controversies that might be avoided or more effectively managed, given a greater agency-wide management capability. The IOM committee recommends that a high-level official in the Office of the Commissioner of Food and Drugs be assigned primary responsibility for developing, disseminating, and enforcing administrative policy and management guidance to the advisory committees of the three centers. The directors of the three centers should have explicit responsibilities for managing the advisory committee system. Center directors should implement agency-wide policy for advisory committees; monitor the recruitment of members for technical expertise, source of nomination, and identification of qualified women and minority candidates; personally approve any "custom tailoring" of committees to avert charges that FDA staff are seeking to influence the outcome by the selection of members known to favor a particular view; help design an orientation and training program for committee members; examine issues that arise in a particular committee that may cut across several committees; and support innovation in the use of advisory committees. Office and division directors of the product review units should also have explicit responsibilities for managing the advisory committee system. They should be actively involved in recruiting advisory committee members, preparing committee agendas, and developing specific questions. Executive secretaries should report to a central unit within each center. Their responsibilities are primarily to provide administrative support to committee operations. Executive secretaries should also report to the appropriate division director to assist that individual in the program-related work of the committees. The IOM committee recognizes that CDRH executive secretaries differ from those in CDER and CBER in that they are also engaged in the technical review of applications; thus, some comments may not apply to them. The IOM committee recommends that the executive secretaries report to a central unit in their respective centers for the purpose of providing

OCR for page 1
Food and Drug Administration Advisory Committees administrative support to that center's advisory committees. It also recommends that they report to the appropriate division directors to provide program support to the committees. In general, the IOM committee believes that a clarification of the roles of all FDA officials responsible for the advisory committee system is long overdue. The objective of this role clarification should be to ensure that advisory committees provide the independent expert advice that the agency requests and needs. The IOM committee recommends that the roles and responsibilities of all FDA officials involved in the advisory committee system be clearly articulated in agency policy that is widely distributed to FDA professional staff, advisory committee members, and other interested parties. The committee further recommends that the job descriptions of all officials be changed to reflect their respective responsibilities. Compensation The authority to set the daily rate of compensation for FDA advisory committees resides with the Commissioner of Food and Drugs. He is subject to four constraints—two legal, one budgetary, and one administrative. The statutory limit on compensation for all federal government advisory committee members is the daily rate for a Senior Executive Service IV position, currently $429.50 per day. Regulations of the General Services Administration further limit the daily rate to that of a GS-15 in the General Schedule, currently $320 per day, unless the agency head personally determines that a higher rate "is justified and necessary." The budgetary limit is the obvious requirement that an agency head must have funds to cover the costs of whatever rate is adopted. Although agency heads have authority to set rates for the members of the committees that advise them, FDA's status as a Public Health Service agency also limits the exercise of that authority. As a practical matter, no single PHS agency can pay advisory committee members at rates much higher than those of the other agencies. Currently, the Centers for Disease Control pays committee members $188 per day, while the National Institutes of Health and the FDA pays $150 per day. FDA advisory committee members are paid only for those days on which they attend a meeting. The agency is barred by regulation from paying them for homework for normal meeting preparation, even though a member may spend five days or more in preparation. However, CDRH does compensate individual advisory committee members for homework if they conduct an

OCR for page 1
Food and Drug Administration Advisory Committees "agency-directed assignment" that results in a tangible end product, usually a report, that is not the end product of the advisory committee. Typically, this involves using members as primary reviewers of applications. Neither CDER nor CBER compensates committee members for homework in this way. FDA regulations also permit payment to advisory committee members at the daily rate for travel time that involves 50 percent of an additional day beyond the meeting time and that results in the loss of some regular compensation. However, no use is made of this authority. The IOM committee believes that all Public Health Service advisory committee members are underpaid, including those who advise the FDA. This is true both with respect to the maximum daily rate allowed by law and GSA regulations and with respect to the opportunity cost to members of foregone consulting fees from drug or device firms of $1,000 a day or more. Moreover, younger members in academic medicine often confront the perception that service on an FDA committee carries less academic reward than that of an NIH study section. The IOM committee believes that public service should be adequately compensated, although obviously not at the rates of the private sector. It is concerned that the current meager rate of compensation may dissuade some individuals from serving as FDA advisory committee members and may diminish the incentive to others to prepare adequately for meetings. In general, the IOM committee is concerned that these rates do not accurately reflect the value that FDA and the general public attach to the important work performed by advisory committee members. The IOM committee recommends that the Commissioner, with the Secretary of Health and Human Services, review the adequacy of compensation for Public Health Service advisory committee members, including FDA advisory committee members, and take appropriate steps to maintain daily rates in relation to increases in the federal salary schedule. It further recommends that CDER and CBER, to the extent that they use primary reviewers for applications presented to advisory committees, compensate these reviewers, as CDRH currently does, for "agency-directed" homework. The IOM committee notes that legislation enacted in October 1992 authorizes the FDA to charge user fees for product evaluation. Under this new authority, it may be appropriate for the FDA to review the compensation of advisory committee members in relation to their contribution to product evaluation.

OCR for page 1
Food and Drug Administration Advisory Committees Orientation and Training A recurring complaint from advisory committee members has been the absence of an adequate orientation and training program. Although the centers and most divisions have made a number of efforts, no systematic agency-wide or center-wide orientation program has been organized. The IOM committee believes that the need for such a program is clear; program content and organization are addressed in the body of the report. The IOM committee recommends that the FDA establish a systematic orientation and training program that is directed mainly toward new advisory committee members but that will also be useful for current members and for FDA staff who deal with committees. The Office of the Commissioner should exercise leadership in the design of this program, in cooperation with the three centers. The design should consciously search for agency-wide similarities as well as center-specific and division-specific content. The public service and public health contribution of advisory committee membership should be emphasized in this program. AGENCY MANAGEMENT AND ACCOUNTABILITY This report recommends many concrete steps for improving the use of advisory committees by the FDA in the evaluation of drugs, biologics, and medical devices. Throughout the report are general expressions of concern about agency management and accountability, which may not be captured fully by its specific recommendations. Thus, the IOM committee deems it necessary to summarize the latter in relation to these larger considerations. Agency Management In the judgment of the IOM committee, it is important to differentiate between the management of the advisory committee system and the management of the product evaluation process as affected by the advisory committee system. Regarding advisory committee system management, the IOM committee's most important recommendation is that a high-level position be established in the Office of the Commissioner to provide administrative policy and management guidance to the advisory committee system. Although the precise location of such an office is properly determined by the Commissioner, an appropriate place may be the Office of the Deputy Commissioner for Operations, to which the directors of the three relevant centers now report.

OCR for page 1
Food and Drug Administration Advisory Committees Advisory committees, the IOM committee believes, have become a permanent fixture in the FDA's evaluation of products, and their effective use should be a responsibility of FDA officials at all levels. Improvements in management would flow from clarifying the roles and responsibilities of all officials involved in the advisory committee system—from the Commissioner through the center, office, and division directors, down to the executive secretaries. Such clarification should include changing the job descriptions of these officials as necessary. The IOM committee acknowledges the important role of FDA office and division directors in the work of advisory committees; it does not recommend circumventing these officials by proposing to locate operational responsibility for committees elsewhere, but urges clarification of their responsibilities for the effective performance of the system. An orientation program for advisory committee members, which could also be used in training responsible FDA officials, would improve the performance of the entire system. Other management-related recommendations pertain to the recruitment of qualified members and establishment of a pool of potential members; greater involvement by the Office of the Commissioner in conflict of interest issues (both in developing internal FDA policies and procedures and in negotiating with the DHHS Office of the Special Counsel for Ethics and the Office of Government Ethics); and more attention to preparation for and conduct and follow-up of advisory committee meetings. Various recommendations of the IOM committee address improvement of the product evaluation process and the role of advisory committees in that process. In particular, we believe that advance scheduling of committee meetings and agendas, with attendant deadlines for the sponsor and the agency, would bring greater discipline to the product evaluation process and make more effective use of advisory committees. The IOM committee recognizes that its recommendations for improved management of the advisory committee system will require additional resources. Therefore, the report provides an estimate of the incremental costs of the IOM committee's recommendations. The IOM committee regards the recommended review of advisory committee member compensation as an important management issue that deserves attention by the Commissioner and the Secretary of Health and Human Services. The compensation of committee members should be reviewed in relation to the newly-adopted user fee system for product evaluation.

OCR for page 1
Food and Drug Administration Advisory Committees Agency Accountability The FDA as an entity, and not just its component parts, should be accountable for the effective performance of its advisory committee system. The IOM committee's recommendations lead to ways of increasing agency-wide accountability. Here, as in the recommendations above on improving management, the committee emphasizes the importance of designating a high-level official in the Office of the Commissioner who should be responsible for administrative policy and management guidance for the advisory committee system. It is also important as a component of accountability to recognize that advisory committees are advisory to the FDA, and that the authority for decisions rests with the agency. It would be unnecessary to reiterate this basic distinction were it not that some agency critics regard advisory committees as independent adjudicatory bodies that should hear sponsors' views, on the one hand, and agency views, on the other, and decide in favor of one party or the other. Acknowledging this basic authority-advisory distinction should facilitate advisory committees becoming even more effective and influential than they are at present, which the IOM committee endorses. Consequently, the IOM committee's recommendations emphasize practical ways (especially in Chapter 7) to ensure the intellectual independence of advisory committees. The rationale for this emphasis is to increase the likelihood that advisory committees will render that impartial, expert advice that the agency and the public should expect. A CONCLUDING RECOMMENDATION In the conduct of this study, the IOM committee has discovered the multifaceted complexity of the FDA advisory committee system. It has benefited from many thoughtful letters, memoranda, and communications on aspects of this complexity. As a result, the committee believes that its report could serve to increase agency accountability for the advisory committee system. The IOM committee recommends that the Commissioner circulate this report widely within the FDA, to all advisory committee members, and to other interested parties. It also recommends that the report be submitted to the Secretary of Health and Human Services and to the appropriate committees of the Congress for the purpose of seeking concurrence of goals and budgetary support for the implementation of the report's recommendations.

OCR for page 1
Food and Drug Administration Advisory Committees NOTES 1.   Memorandum from Bruce Burlington, M.D., Deputy Director for Scientific and Medical Affairs, to Carl C. Peck, M.D., Director, and Gerald F. Meyer, Deputy Director, Center for Drug Evaluation and Research, "Advisory Committees. Policy and Practices in Selection of Agenda Items to be Considered by Center for Drug Evaluation and Research Advisory Committees," September 1991. 2.   Kutak, Rock & Campbell. FDA Safeguards Against Improper Disclosure of Financially Sensitive Information. Final Report. Washington, D.C., November 14, 1991.