4
Recurring Issues

Although technical advisory committees have been an important part of Food and Drug Administration operations for more than two decades, a number of issues about their use have been the focus of recurring controversy. This chapter examines these issues through the lens of prior reports on the FDA that have dealt in some important way with advisory committees.

One cluster of issues involves the purposes, roles, and functions of advisory committees. Views on these issues appear to vary as a function of the observer—FDA leadership, FDA middle managers, academic medical scientists, industry spokesmen, and consumer representatives. A second set of issues, more prominent in the 1970s than today, reflect the suspicion of a populist Congress, which has sometimes seen scientific experts as too closely allied with the regulated industry—or at least as too inclined to endorse new technologies at the expense of risk to patients. Third, the issue of the independence of advisory committees, mainly from influence by the agency, but also from product sponsors, has long persisted as a topic.

The discussion that follows examines these major issues and more detailed questions about committee operations and management. The chapter also describes the "goldfish bowl" within which the FDA and its advisory committees operate.

MAJOR PRIOR REPORTS

The history of the FDA is a history of reports about the FDA, as Hutt has noted.1 In this section, we review several reports that have dealt with FDA advisory committees, usually in the context of reform of the drug approval process: the Fountain Committee report of 1976, the Dorsen Committee report of 1977, the McMahon Commission report of 1982, and the Lasagna Committee report of 1990. This brief historical review makes clear that many of the issues surrounding FDA advisory committees that are



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Food and Drug Administration Advisory Committees 4 Recurring Issues Although technical advisory committees have been an important part of Food and Drug Administration operations for more than two decades, a number of issues about their use have been the focus of recurring controversy. This chapter examines these issues through the lens of prior reports on the FDA that have dealt in some important way with advisory committees. One cluster of issues involves the purposes, roles, and functions of advisory committees. Views on these issues appear to vary as a function of the observer—FDA leadership, FDA middle managers, academic medical scientists, industry spokesmen, and consumer representatives. A second set of issues, more prominent in the 1970s than today, reflect the suspicion of a populist Congress, which has sometimes seen scientific experts as too closely allied with the regulated industry—or at least as too inclined to endorse new technologies at the expense of risk to patients. Third, the issue of the independence of advisory committees, mainly from influence by the agency, but also from product sponsors, has long persisted as a topic. The discussion that follows examines these major issues and more detailed questions about committee operations and management. The chapter also describes the "goldfish bowl" within which the FDA and its advisory committees operate. MAJOR PRIOR REPORTS The history of the FDA is a history of reports about the FDA, as Hutt has noted.1 In this section, we review several reports that have dealt with FDA advisory committees, usually in the context of reform of the drug approval process: the Fountain Committee report of 1976, the Dorsen Committee report of 1977, the McMahon Commission report of 1982, and the Lasagna Committee report of 1990. This brief historical review makes clear that many of the issues surrounding FDA advisory committees that are

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Food and Drug Administration Advisory Committees addressed in this report have been considered before, raising questions about what is required to maintain a system that has broad public acceptance, is well administered and adequately funded, and contributes to the public health of the country. The Fountain Committee Report (1976) In 1976, the House Committee on Government Operations issued a report, Use of Advisory Committees by the Food and Drug Administration,2 following hearings in 1974 and 1975 before its Subcommittee on Intergovernmental Relations and Human Resources. Ile subcommittee critically reviewed the use of advisory committees by the FDA's Bureau of Drugs in the light of the 1972 Federal Advisory Committee Act (FACA), over which the full committee had jurisdiction.* The FACA had imposed four requirements for establishing an advisory committee: (1) a formal process should be used to determine the need for a committee; (2) membership should be "fairly balanced" as well as technically expert; (3) meetings should be conducted according to procedures of advance notice and a quorum requirement, and should be open to the public; and (4) detailed minutes and transcripts should be maintained as the meeting record.3 The Fountain Committee report, concurring with a major goal of Congress in enacting the FACA that agencies should "limit the number of advisory committees to the minimum necessary" (p. 3), recommended that the FDA reduce the number of advisory committees to those having a clear justification, limit the frequency of their meetings, and eliminate all nonessential uses. The report emphasized improved management and compliance with the act—FDA staff and advisory committee members should adhere to its standards, and Congress should monitor the agency to prevent inadequate fiscal and management oversight of committees. It recommended that the FDA remedy a perceived lack of balance in the composition of advisory committees, that it cease to close meetings improperly, that meetings not be held in places that discouraged public attendance, that complete minutes of meetings be kept, and that verbatim transcripts not be destroyed prematurely. Several recommendations sought to strengthen advisory committees and their independence from the FDA. The report recommended that the FDA *   The subcommittee was chaired by Representative L H. Fountain (D., N.C.). Hutt indicates that Rep. Fountain held hearings (as many as three or four a year) on all aspects of the FDA from 1964 until he retired from Congress in 1982. His successor as subcommittee chairman, Rep. Theodore Weiss (D., N.Y.), continued that tradition until his death in September 1992.

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Food and Drug Administration Advisory Committees take steps "to assure that advisory committees are properly instructed and provided adequate time and information for thorough and appropriate scientific analysis and review," that committees be permitted "to arrive at independent scientific findings without further intervention by FDA to influence their judgment on the basis of non-scientific considerations," and that the FDA end the practice of "seeking recommendations from advisory committees on matters that have already been decided, or in order to bypass critical staff review of the data submitted in new drug applications." On the other hand, the subcommittee deplored undue reliance on advisory committees by the agency. It recommended that the FDA rely primarily on its own staff to carry out its responsibilities and use advisory committees only in exceptional circumstances involving difficult medical or scientific issues for which outside expertise was clearly required. The FDA was also enjoined to utilize its full-time professionals more effectively and, where necessary, to upgrade its medical, scientific, and technical personnel through advanced training, participation in scientific research, and similar professional development activities. The Fountain Committee report reveals congressional suspicion about the FDA's use of advisory committees and a suspicion that expert committees were being used to reinforce closed decision-making processes that favored industry views. Hence, its recommendation that the FDA strengthen its own professional staff and avoid becoming overly dependent on outside committees. In fact, the report emphasized the technical capabilities of the FDA staff and argued that these staff could handle some, if not most, of the agency's technical decisions. Echoes of the debate about internal staff competence versus external expertise are still heard today. Although the FDA staff, in the period immediately after the 1962 amendments, typically lacked the technical competence to evaluate drugs for effectiveness as well as safety, the agency long ago upgraded the quality of its professionals. Today, the issue of staff versus outside experts takes two forms: some observers see advisory committees as a partial counterweight to cautious, risk-averse government regulators; others see them as a necessary means by which the FDA staff stays abreast of the frontiers of science and clinical medicine. The Dorsen Committee Report (1977) In early 1975, as the Fountain Committee was holding its first hearings on FDA advisory committees, the Department of Health, Education, and Welfare (DHEW) established the DHEW Review Panel on New Drug Regulation to examine FDA policies and procedures related to the approval and disapproval of new drugs. Chaired by Norman Dorsen, professor of law

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Food and Drug Administration Advisory Committees at New York University, the panel's final report*4 declared that the system of new drug regulation was fundamentally sound but needed substantial improvement. The report identified four shortcomings that needed remedying. First, the regulatory system of the Bureau of Drugs was unnecessarily closed to public review and participation, and overly dependent on informal, unreviewable communications between the FDA and drug companies. Second, the scientific capacity of the agency was inadequate and, unless corrected, likely to deteriorate further. Third, the bureau employed unacceptably imprecise standards and unstructured, inefficient procedures for reviewing new drug applications. Fourth, the agency had not devoted enough attention to approved drugs (pp. 106–107). In the context of these criticisms, a panel of the full committee made a number of recommendations regarding the advisory committees of the Bureau of Drugs. In general, it called on the FDA to clarify its policies and procedures to ensure the uniform use and functioning of advisory committees among divisions. Regarding advisory committee members, the panel recommended that the FDA should issue written guidelines for selecting members; DHEW should abolish its policy barring concurrent membership on more than one departmental committee; should establish a "committee on committees" to recommend nomination procedures; should rescind existing regulations concerning consumer representation and provide for voting public interest members on all standing committees. On financial conflict of interest, the Dorsen committee recommended that rules and procedures should be strict enough to guarantee the integrity of advisory committees but flexible enough to allow the FDA to attract and retain qualified members; the agency should use specific rules to disqualify members with serious conflicts but apply graduated restrictions to different degrees of conflict; all committee meetings should be public, all significant potential conflicts of interest should be fully disclosed; committees should be restricted to advising on narrow scientific questions rather than broad regulatory matters; and efforts should be increased to find qualified candidates with fewer potential conflicts. Advisory committees, the report recommended, should be involved in reviewing both investigational new drugs (INDs) and new drug applications (NDAs). The FDA should provide all advisory committees a list of INDs and NDAs currently under review by their respective drug groups; the agency should use members to review significant INDs; the FDA should *   The committee had issued two interim reports in April 1977: "The Use of Standing Advisory Committees by the Bureau of Drugs of FDA" and "Conflicts of Interest on Standing Advisory Committees of the Bureau of Drugs, FDA."

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Food and Drug Administration Advisory Committees document its decision to refer an IND or NDA to a committee; and an committees should adopt the practice of assigning individual members as primary reviewers of INDs and NDAs. Recommendations dealing with committee operations included the following: the FDA should continue its efforts to send materials to advisory committee members at least three weeks before a meeting; sponsoring companies should receive the questions sent by FDA to the committee; and the Bureau of Drugs should adopt a policy against industry communicating directly to advisory committee members. In addition, the FDA should ask advisory committees precise questions about those matters on which it wished assistance and refrain from asking about evidence of safety and efficacy; FDA staff, in presentations to a committee, should refrain from stating their own views about the advice the committee should offer; draft minutes should be distributed to members as soon as they are written; and the FDA should periodically inform its committee members of the status of their recommendations. It also recommended that the FDA should limit the criteria for removal of an advisory committee member to behavior so disruptive that it significantly impedes the proper functioning of the committee; the agency should ensure that members do not discuss committee business in private; and committee members should refrain from discussing nonscientific issues such as economic or malpractice questions at meetings. The panel report recommended that the handbook under preparation for orienting advisory committee members should include the relevant FDA statutes, the regulations for new drug approval (including the standards of safety and effectiveness) and for advisory committees, a description of the matters FDA will refer to committees, and a statement of how FDA hopes to use committee members as reviewers of INDs and NDAs. Recommendations of the Dorsen Report to expand the scope of advisory committee responsibilities also find expression in the McMahon and Lasagna reports (see the later discussions). Suggestions that committees guide sponsors in the early stages of product development, especially the design and conduct of clinical trials are seldom accompanied by detailed supporting analysis. The agency has predictably resisted such expansion, noting that it would require greater agency resources and would increase committee workloads substantially. In general, the FDA prefers to focus more on using committees for product evaluation and for assessing broad issues of drug, biologic, or device evaluation. * *   As noted in prior chapters, the Center for Biologics Evaluation and Research involves itself and its advisory committees more deeply than the other centers in early stages of product development, a pattern derived from its history and regulatory responsibilities.

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Food and Drug Administration Advisory Committees The McMahon Commission Report (1982) In 1981, at the initiative of Representatives Scheuer and Gore, Congress authorized the creation of a Commission on the Federal Drug Approval Process (known as the McMahon Commission, after its chairman). The Commission reported in March 1982 on ''changes that would enhance the speed and quality of the approval process while maintaining the existing level of protection of the public health''5 (p. 2). Its report focused on four questions: the scientific evidence needed to conclude that a drug was safe and effective and who should assess the sufficiency and meaning of the evidence; the documentation needed by the FDA to support marketing or testing and the timing of its submission; the most efficient use of FDA resources to perform the agency's duties in the IND and NDA processes; and the "style of interaction" between the FDA and the pharmaceutical industry most appropriate to ensure efficiency and quality in the drug review process. The McMahon Commission proposed the following reforms: outside review boards should be used in the approval process; new indications for approved drugs should be completely exempt from IND requirements; a streamlined approval process for generic drugs should be established; and manufacturers should no longer be required to send raw data to the FDA. The report was optimistic about speeding the drug approval process, although a minority report commented that it failed to recognize the substantial progress FDA had made in this regard. Among its recommendations, the commission called for greater use of outside experts in the approval process: review procedures should be revised "to afford a more significant role" to experts from the academic and government biomedical research communities, and "due weight" should be given to the judgment of clinical investigators as to whether the standard of effectiveness had been met. It also proposed that outside experts should "become more actively involved," at the request of the FDA or a drug sponsor, in planning clinical trials, advising on INDs or new indications of an approved drug, and reviewing of NDAs. The McMahon commission further recommended that the Commissioner seek the help of "leading professional societies, universities, and other appropriate bodies" in obtaining the "most qualified experts in various fields of pharmacology and therapeutics" as consultants and advisory committee members. It agreed with the Dorsen report's proposal for a "committee on committees" to broaden the selection of advisory committee members. Regarding conflict of interest, the commission recommended that the FDA commissioner request from the Department of Justice "a less restrictive interpretation" of the federal conflict-of-interest statute than that issued in

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Food and Drug Administration Advisory Committees 1978, reflecting its belief that greater use of experts, as consultants and advisory committee members, could reduce the time needed for review (pp. 78–82). With a less conservative interpretation, it argued, "more experts could participate, and thus they could be involved earlier and more continuously in the course of developing important new drugs, [which] could . . . avert clinical studies that are not needed for NDA approval, expedite review of research data, and enhance the quality of FDA decision making" (p. 3). The McMahon Commission report reflected an optimistic view that greater use of advisory committees would shorten the drug approval process. This view, which reappears over time, assumes that advisory committees can substitute for agency personnel. Advocacy, again, draws little support from analysis. The FDA tends to respond that greater use of advisory committees requires more, not fewer, agency staff. The Lasagna Committee Report (1990) The National Committee to Review Current Procedures for Approval of New Drugs for Cancer and AIDS, chaired by Dr. Louis Lasagna, was created in late 1988 by the President's Cancer Panel, in response to a June request of then-Vice President George Bush. Its report, issued in August 1990, made a number of recommendations about the drug development and evaluation process.6 The Lasagna Committee report made several recommendations regarding advisory committees. It first recommended that a standing policy and oversight committee be established by the Secretary of Health and Human Services. This committee, which would report to the Secretary, would "monitor the Food and Drug Administration's needs and performance with regard to the regulation of drugs and biologics for human use." The report also called for "a fundamental restructuring" of the technical advisory committee system, with all committees having their independent staff located in the Office of the Commissioner. The Office of the Commissioner was to manage appointments to the committees directly, and committees were to report directly to that office. The Lasagna Committee further recommended that committees be responsible for their own agendas and "more closely monitor" the new drug approval system. The Lasagna Committee report noted a potential for increased use of advisory committees in the early stages of drug development; in evaluating INDs and NDAs, in setting priorities among drugs; in mediating between the FDA and industry; and in overseeing FDA implementation of committee recommendations. Finally, "to foster close relationships between the government agencies involved with AIDS and cancer drugs, the National

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Food and Drug Administration Advisory Committees Cancer Institute, the National Institute of Allergy and Infectious Diseases, and FDA should each have a permanent representative sitting as a voting member of the appropriate advisory committee in the other agencies" (p. v). Other Reports Two other recent reviews of FDA's performance deserve brief mention, although neither dwelled at length on advisory committees. The Department of Health and Human Services (DHHS) Advisory Committee on the Food and Drug Administration, otherwise known as the Edwards Committee, issued its report in 1991 after a year of considering the FDA's mission, structure, and responsibilities.7 Its main recommendations addressed these needs: to clarify the FDA's mission and priorities; to elevate the agency's status and authority; to strengthen its enforcement operations; to improve agency management; and to increase its resources. As part of the recommendation for increased resources, the Edwards Committee stated that "The Commissioner must be empowered, to the limits of statutory authority, to manage the FDA's scientific and technical personnel, and to improve the FDA's access to scientific expertise including advisory committee appointments" (p. v). It noted that the process for recruiting and using advisory committee members was burdensome and costly in time and effort. It cited potential conflicts of interest as a specific reason for the delays and difficulties in appointing and convening advisory committees and as a barrier to the use of "many highly qualified and respected advisors." It advocated prior disclosure of potential conflicts as preferable to premature disqualification when a conflict is anticipated and urged the agency to draw on the Augustine Commission report on the National Aeronautics and Space Administration of March 1991 and the FDA Revitalization Act to reduce the impediments introduced by the current process for managing conflict of interest (pp. 45–46). The subcommittee on human drugs and biologics of the Edwards committee noted that the FDA appeared to use advisory committees inconsistently and that service on advisory committees had to be made appealing enough to attract the appropriate experts. It recommended both expanded and earlier use of the committees to reduce delays in the approval process. Unlike the Lasagna committee, however, the Edwards committee report opposed the creation of a policy oversight board, but did recommend that the Commissioner increase the accountability and usefulness of the reporting relationship between advisory committees and the FDA. The subcommittee on devices, radiological health, and biomedical research made similar recommendations on advisory committees.

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Food and Drug Administration Advisory Committees The second report to emerge in 1991 was from the Council on Competitiveness, which responded to many of the Lasagna Committee recommendations.8 It proposed major changes in the drug approval process—such as contracting with experts outside of the federal government for reviewing drug approval applications. The overall goal of the Council report was to shorten the review and approval process. One recommendation to this end was the increased use of advisory committees for evaluating NDAs and INDs, which, citing Lasagna, meant the use of advisory committees earlier in the research and development process. THE GOLDFISH BOWL The reports discussed above indicate, as Hutt has aptly observed, that FDA operates in an environment of intense public scrutiny. Its actions are closely followed by the general public, Congress, the press, the regulated industries, and the financial community. It, as much as any federal government agency, functions in a goldfish bowl. In this section, we consider several aspects of that goldfish bowl—congressional oversight, media coverage, and attention by the financial community. Congressional Oversight The FDA interacts with the Congress in many ways. It deals with two legislative committees: the House Committee on Energy and Commerce, and its Subcommittee on Health and the Environment, and the Senate Committee on Labor, Health, and Human Resources, and its Subcommittee on Health. It deals with two other committees for its annual appropriations: the House Committee on Appropriations, Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies, and the Senate Committee on Appropriations, Subcommittee on Agriculture and Related Agencies.* In addition, the House Committee on Agriculture, Subcommittee on Domestic Marketing, Consumer Relations, and Nutrition; the House Committee on Government Operations, Subcommittee on Human Resources and Intergovernmental Relations; the House Committee on Science and Technology, Subcommittee on Oversight; the Senate Committee on Governmental Affairs; the Senate Committee on Agriculture, Nutrition and *   The FDA began as the Bureau of Chemistry of the U.S. Department of Agriculture. Its appropriations continue to be the jurisdiction of the agriculture subcommittees in both Houses of Congress.

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Food and Drug Administration Advisory Committees Forestry, Subcommittee on Nutrition and Investigations; the Senate Judiciary Committee, Subcommittee on Antitrust, Monopolies, and Business Rights; and the Senate Special Committee on Aging all deal with aspects of the FDA and its programs on a rather routine basis. In short, nearly a dozen congressional committees take an active interest in the affairs of the FDA. Controversial decisions by the agency or claims of procedural irregularities can quickly result in a hearing before one of these committees, at which the responsible agency officials are called to account. Such hearings usually receive wide media coverage, both from newspapers and television. Frequently, Members of Congress and their staff pinpoint lower echelon FDA officials who are responsible for a given action and invite them into the spotlight of the hearing room. Not surprisingly, this oversight encourages risk-averse behavior on the part of FDA officials well down on the bureaucratic ladder. Congressional interest in the FDA spans the entire range of the agency's activities. Examples include the following congressional hearings held during the 101st and 102nd Congresses (from 1989 to the present): the generic drug scandal involved 10 hearings on 19 separate days; the amendments to the Orphan Drug Act were the subject of 2 separate hearings; artificial heart valves were considered in 2 separate hearings; and the use of plentopheresis in the treatment of scleroderma was the subject of one hearing. In addition, hearings addressed the reports of the Advisory Committee on the Food and Drug Administration (the Edwards Committee) and the report of the President's Council on Competitiveness on improving the drug approval process. Media Coverage Coverage of the FDA by both newspapers and television is copious and growing. The IOM committee sampled one year's worth of articles (June 1991 to June 1992) from The New York Times, The Wall Street Journal, The Washington Post, and The Los Angeles Times on selected topics before the FDA. Consider the following examples: Even though the IOM search of these newspapers began after the FDA had publicly concluded that there was no solid evidence that Prozac, a popular antipsychotic drug, caused suicidal ideation, the four newspapers subsequently carried 11 articles on the drug (4 each in The Wall Street Journal and The New York Times, 2 in The Los Angeles Times, and 1 in The Washington Post). Similarly, when the FDA reviewed the data on the safety of Halcion, a popular sleeping pill, after its removal from several European markets

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Food and Drug Administration Advisory Committees because of concerns over its side effects, 18 articles appeared in the four papers (2 in The Wall Street Journal, and no fewer than 7 in The New York Times). Silicone gel breast implants received tremendous attention as the FDA reviewed them for safety and effectiveness in late 1991 and early 1992. The four papers published 167 articles on this topic alone, including 14 editorials. The New York Times led with 50 articles and 3 editorials; The Washington Post carried 27 articles and 3 editorials. A glimpse of this intense press and television coverage of the FDA's advisory committee meetings is provided by the item in Box 4-1, which appeared in The Washington Post on October 1, 1991. The Financial Community The financial community monitors the FDA closely, but the intensity of this scrutiny is a relatively new phenomenon. Indicative of investment community interest in FDA advisory committees was the stock market's response to the advisory committee that dealt with products made by Xoma and Centocor in September 1991, and which recommended approval of the latter firm's antiseptic biologic, and the later response to the FDA's decision in May 1992 to fail to act on this recommendation. Heightened interest in the financial community recently prompted the FDA to commission a study by Kutak Rock & Campbell, a Washington, D.C., law firm, examining the treatment of financially sensitive information by the agency. The concern of the FDA, as expressed by the November 1991 Kutak Rock & Campbell report,9 was with "the adequacy of the agency's institutional safeguards against the improper disclosure or use of information about Agency actions [that might] affect the financial markets." The Kutak Rock & Campbell report examined the FDA's handling of financially sensitive information and proposed general improvements in FDA procedures. Among its general observations, the report noted that procedural inconsistencies increased the risks of inappropriate or unauthorized actions, and specifically, the disclosure of financially sensitive information. The report concluded that "FDA's ultimate goal of adequately and reasonably protecting confidential information can be met in only two ways: by imposing appropriate safeguards or by eliminating the need for confidentially through disclosure." It recommended some new and some modified procedural safeguards and "broader and earlier disclosure" of certain categories of information, with the specific goal of reducing the effects of such disclosures on financial markets.

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Food and Drug Administration Advisory Committees Box 4-1 At an FDA Panel Hearing—Lights, Cameras, Action! When a panel of experts met recently to consider the evidence for two new drugs against sepsis, a standing-room only crowd of drug company officials, analysts, scientists and reporters packed into a conference room at the Food and Drug Administration headquarters in Rockville to observe. At stake: an estimated $1 billion market for two new genetically engineered drugs. One analyst told The Wall Street Journal the meeting was like "the gunfight at the Rockville corral." The two drug companies involved—Centocor Corp. of Malvern, Pennsylvania, and XOMA of Berkeley, California—brought their own TV crews to record the event. CNN was there. So was a row of trade journal reporters and other news media. Iley scribbled notes with one hand and held tape recorders in the other. Two photographers set up tripods in a corner and methodically clicked three shots of every data-filled slide with telephoto lenses. Men dressed in striped shirts and bow ties, their cuffs adorned with gold, reached for compact cellular phones throughout the day. They whispered the latest word decided by an 11-member advisory panel to the FDA and a panel of experts who advised the advisory panel. Drug company representatives made well-rehearsed presentations about the results of their clinical trials. Experts questioned their work. By the day's end, the FDA panel had decided that Centocor's HA-1A was safe and effective but stopped short of recommending that it be licensed. A decision on E5, the XOMA drug, was postponed for more reviews as three rows of company officials glumly looked on. But the shootout wasn't necessarily over, since as FDA spokeswoman Faye Peterson later noted, all panel decisions are recommendations only. It's up to another FDA body to decide when and if each drug goes to market. Sally Squires Washington Post "Health" section, p. 12 October 1, 1991 As mentioned above, the report devoted a chapter to FDA advisory committees and the attention they receive from the financial community. Historically, it noted, the FDA's final decisions on approving or disapproving a drug usually agree with the prior recommendations of advisory committees. As a result, the financial community pays great attention to the discussion and final recommendations at an advisory committee meeting.

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Food and Drug Administration Advisory Committees This attention is broader than a simple concern for the product being reviewed: The meetings also provide some insight into the views of FDA about the product, and thus serve as predictors of the likelihood and speed of product approval by the Agency. Indeed the [financial] analysts regard the mere scheduling of an advisory committee meeting for a product as an indication that FDA will reach a decision about a product within a relatively short time.10 Given the intense interest of the financial community and the effect the advance public release of questions prepared for the advisory committee might have on trading in the securities markets, the report basically concurred with current FDA practice of publicly releasing such questions on the morning of a committee meeting. Advisory committee members, as special government employees, the report noted, are subject to federal conflict of interest statutes. Consequently, "the regulatory prohibitions against disclosure of 'inside information' by SGEs are more stringent, more explicit, and far lengthier than the ones for actual FDA employees." But advisory committee members receive no particular training about safeguarding financially-sensitive information, and might themselves be sources of information leaks about a product's position in the approval process according to several of the FDA employees interviewed by Kutak Rock & Campbell. Among its many recommendations, therefore, the report proposed that training materials for SGEs be expanded to explain the importance of these issues. CONCLUSIONS In general, from the history of the FDA advisory committee system (chapter 2), the analysis of the current system (chapter 3), and the examination of the foregoing reports and the environment of public scrutiny in which the agency operates, the following preliminary conclusions emerge. It is worth asking why the recommendations of these prior reports have not resulted in a well-organized, efficiently functioning FDA advisory committee system. The answers are far from clear but several hypotheses may be advanced. One possibility is that financial resources have always been too scarce for the agency to give sufficient attention to the system. A second hypothesis is that recommendations about advisory committees have tended to be buried in higher priority concerns about the drug approval process. Yet a third explanation is resistance by the FDA professional staff. Equally

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Food and Drug Administration Advisory Committees plausible is the argument that the top leadership of the agency has not devoted adequate sustained attention to advisory committees, including efforts to institutionalize them with clear authority, strong management, and sufficient resources. Finally, it may be that FDA advisory committees lack a political constituency comparable to the support of academic medicine for the NIH study section system. These hypotheses cannot be tested in any scientific way and remain the bases for speculation and argument. Notwithstanding the range of possible answers to the question about the limited impact of prior reports, we optimistically hope that the reception accorded to this report will be different. A wide consensus exists that the primary purpose of the FDA's technical advisory committees is to bring independent scientific expertise to bear on agency decisions. The agency affirms this view, industry endorses it, and the medical community clearly believes in this premise. The various interested parties begin to diverge, however, in their views of their benefits of technical advisory committees. The agency sees their benefits as providing technical assistance on questions before it, adding credibility to the decisions it makes and to its decision-making procedures, and providing a public forum in which it can ventilate controversial issues and hear from directly affected interests. For the public, and especially Congress, advisory committees have helped legitimize the scientific bases for FDA decisions and have come to be seen as a counterweight to both bureaucratic overreaching and caution. Industry has become more supportive of these committees over time because it believes they have been more strongly oriented toward therapeutic innovation than the agency and that they provide some opportunity for fair review of agency decisions that would otherwise go unscrutinized. The FDA experience with advisory committees, both historically and currently, reveals that their use has usually resulted from agency initiative. Consequently, agency officials have generally determined the functional roles that advisory committees will play, what matters they will consider, when they will be asked to provide advice, what information they will be given, and—very clearly—what weight their advice will have. Technical advisory committees are seen both within FDA and by most external observers as advisers to the agency. They are not judicial bodies, save in their infrequent use as appeals bodies. Thus, their charge is not to adjudicate competing claims but to provide independent advice to the agency on the questions on which the agency decides it needs advice. A major rationale for use by the FDA of outside expert panels in the 1960s and '70s—especially in the National Academy of Sciences-National Research Council Drug Efficacy Study, the Over-the-Counter drug review

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Food and Drug Administration Advisory Committees panels, and the biologics review advisory committees—was to clear a backlog of work that the agency was not equipped to handle because it had too few professional staff and these were often lacking in the needed technical competence. This workload-clearing function of advisory committees is seldom advocated today. The proposition that advisory committees would speed the product approval process, especially for drugs, has been advanced on a number of occasions, usually without strong supporting analysis. "The IOM committee believes that the justification of advisory committees derives less from their effect on the efficiency of the product evaluation process and more from their impact on the quality of that process. In that regard, advisory committees reflect the agency's desire for expert advice, for credible decisions and decision-making processes, and for the ability to discuss controversial issues in a public arena. An underlying issue is the independence of advisory committees from sources that might wish to influence the outcomes of their deliberations. These sources include product sponsors and, in particular, agency officials. Consequently, this report takes up the matter of independence in the narrative and recommendations of the next four chapters. A continuing fact of life for the FDA is the environment of intense public scrutiny within which it operates. Consequently, any significant changes in how the agency functions require some working consensus that includes the agency, its leadership, and its large cadre of professionals; the Congress; the Executive Branch, from the White House to the Secretary of Health and Human Services and the other agencies of the Public Health Services; the regulated industries—pharmaceuticals, biotechnology, and medical devices; the academic medical science community; and organized groups representing the consumers, voluntary health organizations, and the public. The following four chapters examine analytically many of the issues that have concerned the designers, managers, and users of the advisory committee system over time. Chapter 5 deals with committee membership issues. Chapter 6 examines conflict-of-interest issues in great detail, as well as the matter of scientific bias. A cluster of issues concerned with committee operations is addressed in chapter 7. Finally, in Chapter 8, the organization and management of the advisory committee system is considered. NOTES 1.   Peter Barton Hutt, "Investigations and Reports on the Food and Drug Administration," in Food and Drug Law, Food and Drug Law Institute (Washington, D.C., 1991), p. 48.

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Food and Drug Administration Advisory Committees 2.   U.S. House, Committee on Government Operations, Use of Advisory Committees by the Food and Drug Administration, 11th report, based on a study by the Intergovernmental Relations and Human Resources Subcommittee, 94th Cong., 2nd Sess., Report No. 94-787 (January 26, 1976). 3.   Stockman, Paul K, Applicability of the Federal Advisory Committee Act to Alternative Sources of Scientific Input, report to the IOM FDA advisory committee study (July 31, 1992). 4.   Department of Health, Education, and Welfare. Review Panel on New Drug Regulation: Final Report (Washington, D.C., May 1977). 5.   Commission on the Federal Drug Approval Process, Final Report (Washington, D.C., March 31, 1982). 6.   President's Cancer Panel, National Committee to Review Current Procedures for Approval of New Drugs for Cancer and AIDS. (Washington, D.C., August 15, 1990). 7.   U.S. Department of Health and Human Services. Final Report of the Advisory Committee on the Food and Drug Administration (Washington, D.C., May 1991). 8.   Council on Competitiveness. Fact Sheet: Improving the Nation's Drug Approval Process (Washington, D.C., 1991). 9.   Kutak Rock & Campbell. FDA Safeguards Against Improper Disclosure of Financially-Sensitive Information (Washington, D.C., November 1991). 10.   Ibid., p. 69.