FDA uses advisory committees to provide expert advice and make recommendations to help the agency reach regulatory decisions, particularly concerning controversial issues or new products. FDA advisory committees are subject to the Federal Advisory Committee Act (FACA), which requires that committee memberships be fairly balanced in terms of views presented and the functions to be performed by the advisory committee. FDA advisory committees have charters that explain the purpose of the committee and specify the number of standing committee members and the expertise needed by the members. FDA advisory committee members can be medical professionals, scientists, researchers, industry leaders, consumers, and patients. At an advisory committee meeting, committee members generally meet publicly to discuss and evaluate information about a specific issue. Depending on the issues or products to be discussed at a committee meeting, a committee member may have a potential financial conflict of interest. In that event, FDA decides whether the member’s expertise is needed for discussing those issues or products, and if so, whether the member should be granted a conflict of interest determination—a waiver or an appearance authorization—to participate in the meeting. The members who do participate in the committee meeting may make recommendations to FDA—by voting or by consensus through discussions—that are nonbinding on the agency. (See app. III.) FDA Advisory Committees FDA has 31 advisory committees that are administratively attached to FDA centers or to the Office of the Commissioner. Most of the advisory committees—25—are attached to three FDA centers: CDER has 16 committees, CBER has 5, and CDRH has 4. (See app. IV.) Advisory committees usually meet as individual committees but may meet jointly to consider issues involving shared interests. Joint committee meetings may involve two advisory committees from the same center or from two different centers depending on the issue to be discussed. Advisory committees may also have subcommittees that meet to review specific information that may be presented later to the full advisory committee. FDA may permit an advisory committee member—standing or temporary—who has a conflict of interest and whose expertise is needed, to participate in a meeting under certain circumstances. There are four conflict of interest determinations—three statutory waivers and an appearance authorization as provided for in OGE regulations—that FDA can use to permit members with a conflict of interest or the appearance of a conflict of interest to participate. Federal law prohibits federal employees, including SGEs, from personally and substantially participating in an advisory committee meeting involving a particular matter that would have a direct and predictable effect on the employee’s financial interest or the interests of others specified by law. In determining whether an FDA advisory committee meeting involves a particular matter, FDA officials told us that they first consider each topic to be discussed at the meeting and determine whether it involves specific parties, a class of persons, or the interests of a large and diverse group of people. If one of the meeting topics involves specific parties or a class of persons, FDA officials then determine whether the advisory committee members who will attend the meeting have any conflicts of interest or the appearance of conflicts of interest involving that meeting topic. Officials told us if they are uncertain whether a meeting topic is a particular matter, the issue is referred to FDA’s ACOMS and EIS. EIS may refer the issue to HHS’s general counsel which may also seek advice from the OGE. The law has two waiver provisions that allow standing and temporary members to participate in an advisory committee meeting if certain criteria are met. One waiver—known as a § 208(b)(3) waiver—applies only to SGEs serving on an advisory committee subject to FACA. When granting this waiver, FDA certifies in writing in advance that the need for the SGE’s services outweighs the potential for a conflict of interest at a specific upcoming meeting. Another type of waiver—known as a § 208(b)(1) waiver— applies to federal employees generally, including SGEs and those not employed by FDA but who are members of FDA committees. When granting these waivers, FDA must determine that the interest involved is not so substantial as to be deemed likely to affect the integrity of the services which the government may expect from that individual. FDA may grant a member a full or a limited waiver—a written certification—to allow participation in the meeting. A full waiver may allow a member to participate in the discussions and to vote on recommendations. FDA may also grant a limited waiver to allow a member to discuss but not to vote on the recommendations. In addition, there are certain situations in which the member’s financial interest qualifies for an exemption from the application of the conflict of interest statutes and regulations applicable to federal employees, as provided by OGE regulations, and participation will be permitted despite the outside interest. In addition to 18 U.S.C. § 208, there was a provision in the Food and Drug Administration Modernization Act, in effect prior to October 2007, which effectively prohibited CBER and CDER advisory committee members from voting on committee meeting topics involving clinical investigations or approvals of drugs or biologics in which the member or his or her immediate family could gain financially from the committee’s advice. However, FDA could grant a waiver of this voting restriction—known as the § 355(n)(4) waiver—to a member if FDA determined that his or her participation was necessary to provide the committee with essential expertise. No waiver could be granted if the meeting involved the member’s own scientific work, such as work done by the member to develop a new drug being considered for approval by CDER. Finally, federal regulations require the consideration of the appearance of a conflict of interest for advisory committee members who will be participating in a specific-parties meeting when there are circumstances in which the member’s impartiality could be questioned. The appearance of a conflict may be created when someone in the advisory committee member’s household has a financial interest that will likely be affected by the committee’s actions or when one of the parties involved in the meeting has a close personal or professional relationship to the committee member. To grant an appearance authorization, FDA determines that the interest of the agency in the member’s participation in an advisory committee meeting’s topic outweighs the concern that a reasonable person with knowledge of the relevant facts would question the member’s impartiality in the matter before the advisory committee, which may call into question the integrity of FDA’s programs and operations. (See table 1 for a summary of the four conflict of interest determinations.) The appropriate FDA center review division and committee management staff for the advisory committee meeting decide whether a member meets the requirements for an applicable conflict of interest determination to allow him or her to participate. To assist in making conflict of interest determinations, FDA uses its Waiver Criteria 2000 guidance, which provides policies and procedures for handling conflicts of interest. On the basis of the advisory committee meeting’s topic and its designation, the center review division involved in the advisory committee meeting typically compiles a list of companies and products affected by the meeting’s topic. The advisory committee management staff then sends a memorandum with the final list of companies and products and the FDA Form 3410—the FDA financial disclosure form—to the advisory committee members. Members review the memorandum, complete the Form 3410, and report back to FDA on whether they believe they have any personal or imputed financial interests and past involvements with the affected companies and products listed for the upcoming advisory committee meeting’s topic. The FDA center advisory committee management staff for the particular advisory committee review members’ FDA financial disclosure forms and determine whether a member has a potential conflict of interest for the meeting or a part of the meeting. If a member has a conflict, FDA can accept a member’s decision to not participate because of the member’s own decision that he or she has a conflict of interest, exclude or disqualify a member from participating, seek another individual with the appropriate expertise needed to participate who has a less significant or no conflict of interest, or decide the member’s expertise is needed, and that the member meets the criteria for a conflict of interest determination to allow him or her to participate in the meeting discussion and vote. If there is a question about whether a member should be granted a determination, the center’s advisory committee management entity may seek advice from the review division. If there are further questions about whether the determination should be granted, advice may be sought from FDA’s ACOMS and EIS. ACOMS and EIS review all conflict of interest determinations before their final approval. The final decision to grant or deny a determination is made by the FDA Associate Commissioner for Policy and Planning. (See fig. 2.) Since November 2005, FDA has been subject to requirements related to public disclosure of its conflict of interest waivers on its Web site. From November 2005 until October 2007, FDA had been required by law to publicly post the nature and basis of conflict of interest waivers on its Web site. As of October 2007, the FDA Amendments Act of 2007 require FDA to publicly disclose on the agency’s Web site, prior to every advisory committee meeting, the reasons for all waivers granted as well as the type, nature, and magnitude of the financial interests being waived. In October 2007, FDA announced draft guidance to implement agencywide procedures for the public disclosure of (1) the type, nature, and magnitude of any financial conflict of interest for which an advisory committee member has been granted a waiver for a committee meeting on its Web site, and (2) conflict of interest waivers that would be written so that information protected from public disclosure would not appear in the waivers and thus would not need to be redacted. Public disclosure at an FDA advisory committee meeting can also, for example, include an announcement naming the attending members who have conflict of interest determinations. Prior to the FDA Amendments Act of 2007, FDA employed several methods to recruit candidates for advisory committees and to evaluate candidates by prescreening them for advisory committee membership. Common recruitment methods used by FDA include announcing vacancies in the Federal Register, distributing recruitment brochures at advisory committee meetings and national meetings, receiving nominations by word-of-mouth or asking current advisory committee members for nominations, and posting information about recruitment on FDA’s Web site. Candidates who are selected to serve on an FDA advisory committee either as a consumer representative, industry representative, or patient representative are recruited and nominated using a different process than candidates identified for standing advisory committee membership. To prescreen candidates, FDA reviewed candidates’ curricula vitae and usually conducted prescreening interviews. FDA officials within the three FDA centers we studied, CBER, CDER, and CDRH, prescreened each candidate to determine whether there was any financial interest or activity that might present a potential conflict of interest if the individual were to become an advisory committee member. FDA employed many of the same recruiting and prescreening methods as those employed by EPA and the National Academies, organizations we previously identified as employing certain recruitment and prescreening methods that could ensure independent and balanced advisory committees. FDA employed several recruitment methods to identify candidates for standing advisory committee membership, prior to the FDA Amendments Act of 2007. FDA officials in CBER, CDER, and CDRH told us that the methods commonly used to recruit candidates include announcing advisory committee vacancies in the Federal Register, distributing recruitment brochures at advisory committee meetings and national meetings, and receiving nominations by word-of-mouth or asking current advisory committee members for nominations. The FDA officials we interviewed stated that asking current advisory committee members for nominations was the most effective recruitment method because the members understand the advisory committee process and the commitment level required to serve as an FDA advisory committee member, and can communicate this information to the potential candidate. FDA staff in CBER and CDRH told us that posting vacancy announcements in the Federal Register was the least effective method of identifying qualified candidates because the centers received unsolicited curricula vitae from individuals seeking full-time jobs with FDA. Other recruitment methods reported include identifying possible candidates from the center’s consultant pool, which is a list of individuals whom FDA has determined have expertise that may be needed for future advisory committee meetings, and posting recruitment information on FDA’s Web site. CDRH staff reported that searching the consultant pool for a potential candidate is preferred because the executive secretary and the review division are usually familiar with the individual’s performance on an advisory committee and the individual is familiar with the advisory committee process. In February 2007, FDA posted on its Web site a link to information about advisory committees and available vacancies for individuals interested in advisory committee membership. From the Web site, the public can access information about current advisory committee vacancies, required qualifications to become an advisory committee member, and instructions on how to apply for advisory committee membership. Candidates who are selected to serve on an FDA advisory committee either as a consumer representative, industry representative, or patient representative are recruited and nominated using a different process than candidates identified for standing advisory committee membership. FDA officials work with consumer and industry organizations to identify qualified candidates to serve as representatives. Consumer and industry groups nominate the candidates and FDA indicated that it generally accepts the organizations’ recommendations for nomination. For patient representatives, FDA’s Office of Special Health Issues’ Patient Representative Program is responsible for recruiting and nominating candidates. When an advisory committee meeting topic is of particular importance to the patient population (e.g., cancer or HIV/AIDS-related topics), the advisory committee’s executive secretary will ask Patient Representative Program staff to recommend a patient representative to attend the advisory committee meeting. FDA officials in the three centers told us they prescreened advisory committee member candidates to determine whether they had any financial interests or if they were involved in any activity that might pose a potential conflict of interest, even though prior to October 1, 2007, HHS did not require its agencies to prescreen candidates at the time of their nomination to an advisory committee. To prescreen candidates, FDA reviewed the candidates’ curricula vitae and usually conducted a prescreening interview. The FDA officials told us that the interview is usually conducted by telephone using a prescreening form. The prescreening form asks candidates to provide information about their current investments, employment and consulting relationships held in the past 12 months, and current and past contracts and grants. FDA employed many of the same recruiting and prescreening methods as EPA and the National Academies, organizations found to have some promising methods that could ensure that advisory committee members are independent and advisory committees are balanced. Prior to October 1, 2007, FDA generally used the same recruitment methods as EPA and the National Academies (see table 2). One exception was FDA’s method for obtaining nominations for potential members from the public. FDA provides an e-mail address on its Web site for nominations, a method that relies on individuals submitting to the agency, via e-mail, a curriculum vitae and contact information. In contrast, EPA’s Science Advisory Board’s Web site allows the public to self-nominate or nominate an individual to be an advisory committee member by submitting information via a form on its Web site. Prior to October 1, 2007, FDA also employed many but not all of the same prescreening methods as EPA and the National Academies (see table 3). EPA and the National Academies asked candidates to complete an official financial disclosure and background form prior to being selected as a committee member. An EPA official we interviewed stated that asking candidates for detailed financial information prior to selection to an advisory committee enables EPA to identify individuals without conflicts of interest early in the advisory committee recruitment process. An FDA official told us that FDA did not ask candidates to complete a financial disclosure and background form because the form would require responses about specific products or companies or both, which may not be known at the time of the prescreening interview. EPA’s and the National Academies’ prescreening methods included obtaining input from the general public whereas FDA’s methods generally did not. For example, EPA’s Science Advisory Board used a public notice process to obtain public comments on proposed candidates. The names and biographical sketches of candidates are posted on its Web site, and EPA requests the public to provide information, analysis, or documentation that the agency should consider in evaluating the candidates. Similarly, the National Academies publicly announces the slate of provisional study committee members by posting their biographies on its Web site, and requests public comment. FDA did not post a list of potential nominees on its Web site and did not seek public comment about potential candidates. According to FDA officials, former FDA advisory committee members, and a PhRMA representative, FDA faced barriers to recruiting qualified individuals to serve on its advisory committees, particularly candidates without potential conflicts of interest, although FDA may have been able to mitigate these barriers by expanding its outreach efforts. FDA officials, former FDA advisory committee members, and a PhRMA representative identified the following barriers: FDA sought the same leading experts as industry; FDA’s most effective recruitment method—word-of-mouth—was limited in the number of potential candidates it could generate; and aspects of FDA advisory committee service deterred some potential advisory committee members. FDA already employed several recruitment methods to identify qualified FDA advisory committee candidates. However, FDA may have been able to mitigate barriers by focusing additional outreach efforts on recruiting retired experts, experts from colleges and universities, and individuals with epidemiological and statistical expertise. Under the FDA Amendments Act of 2007, FDA’s process for prescreening candidates for advisory committee membership has been modified. (See app. I.) FDA officials, former FDA advisory committee members, and a PhRMA representative identified barriers that existed to recruiting qualified FDA advisory committee candidates, particularly those without potential conflicts of interest. These barriers were that FDA sought the same experts as industry, FDA’s most effective advisory committee recruitment method was limited in the number of potential candidates it could generate, and aspects of FDA advisory committee service may have deterred some potential advisory committee members. FDA contended that it sought the same leading experts to serve on its advisory committees as industry sought to conduct its research and product trials. As a result, the experts FDA deemed most qualified to serve on its advisory committees often had industry ties, according to the agency. FDA officials, former FDA advisory committee members, and a PhRMA representative generally agreed that many individuals who have the experience necessary to participate on an advisory committee have industry ties. FDA officials told us that private industry sponsors most medical development in the United States. As a result, people in fields relevant to FDA advisory committees gain experience from working with industry. A representative from PhRMA told us if an individual has no or minimal potential conflicts of interest, he would question whether the person has the expertise needed to serve on an FDA advisory committee. Although FDA employed several methods to recruit advisory committee candidates, FDA staff generally agreed that word-of-mouth, such as informal discussions among FDA advisory committee members, agency staff, and interested parties, was most effective in generating nominations for qualified advisory committee candidates. FDA officials and former FDA advisory committee members told us that this recruitment method was effective because people familiar with the advisory committee process—FDA review division staff and FDA advisory committee members—can identify individuals who would be qualified to serve on advisory committees because they understand what advisory committee membership entails. Former members also noted that advisory committee members, who are experts in their field, know other qualified experts who could serve as advisory committee members. Similarly, former advisory committee members explained that asking FDA review division staff for recommendations was effective because these individuals are active in the scientific community and can also identify individuals qualified to serve on FDA’s advisory committees. Despite being effective in generating nominations, word-of-mouth recruitment is limited because only the colleagues of FDA advisory committee members or FDA staff learn about the opportunity to serve on committees rather than a broader pool of candidates. Two former FDA advisory committee members cautioned that, while they believe word-of- mouth is an effective recruitment method, it may lead to self-perpetuating committee membership, in which a limited group of peers continually comprise an advisory committee. An official from EPA echoed these concerns, stating that, although this is an effective method to recruit candidates for some EPA advisory committees, it also is problematic because he believes advisory committee members only nominate their colleagues. Similarly, former advisory committee members noted that FDA staff nominations may also be problematic. For example, one former member explained that it gives the appearance that FDA may pad its advisory committees, which could compromise the committees’ perceived independence. Some aspects of FDA advisory committee service may have also deterred qualified advisory committee candidates. More than half of the 12 former FDA advisory committee members we spoke with agreed that the time commitment involved in preparing for and attending FDA advisory committee meetings acted as a deterrent for some potential advisory committee members. Standing members of an FDA advisory committee are expected to participate in all meetings held by that advisory committee unless they are excluded from a meeting due to a conflict of interest. For example, CDER’s Anti-Infective Drugs Advisory Committee held three meetings in 2006. Unless excluded, a standing member of this committee would have been expected to attend all three advisory committee meetings. In addition, more than half of the 12 former advisory committee members we interviewed also agreed that FDA’s work-related activities and financial information disclosure reporting requirements dissuaded some people from becoming an advisory committee member, although some said that the public disclosure of an individual’s conflict of interest waivers was not a deterrent. As mentioned earlier, advisory committee members complete financial disclosure forms before each advisory committee meeting, and since November 2005 FDA has posted information disclosing the nature and basis of advisory committee member conflict of interest waivers on its Web site. The negative publicity surrounding certain advisory committee meetings, especially media attention to some members’ ties to industry, may have also deterred some people from serving on FDA advisory committees. An FDA advisory committee management official in CDER, the center with the most advisory committee meetings held in years 2004 and 2006 combined, explained that public scrutiny concerning advisory committee members’ conflicts of interest is the most difficult challenge FDA staff face in generating member nominations. The FDA official said people serving on FDA advisory committees “feel like they are in fishbowls” and are concerned that they are considered tainted if they receive a conflict of interest waiver. A representative from PhRMA echoed these concerns, stating that many FDA advisory committees receive public scrutiny, which may act as a disincentive for individuals to serve on committees. Some former advisory committee members we spoke with also agreed that the media attention surrounding certain advisory committee meetings can deter people from serving on FDA advisory committees, although some former members either disagreed or said that qualified candidates should be prepared to withstand media pressure. FDA may have mitigated barriers to recruiting qualified advisory committee candidates, particularly those without potential conflicts of interest, if it had expanded outreach efforts to retired experts, experts from universities and colleges, and individuals with statistical and epidemiological expertise. Former advisory committee members and representatives from entities knowledgeable about FDA advisory committee recruitment agreed that expanding outreach efforts to retired experts, experts from universities and colleges, and individuals with statistical and epidemiological expertise would be effective in recruiting qualified FDA advisory committee members, particularly those without conflicts of interest. In addition, although FDA stated that it employed several methods to recruit advisory committee members, representatives from consumer groups said that FDA should make a greater effort to recruit qualified advisory committee candidates, particularly those without conflicts of interest. Most former advisory committee members we spoke with generally agreed that FDA could have expanded outreach efforts to retired experts in fields relevant to its advisory committees in order to mitigate barriers to recruiting qualified advisory committee candidates, particularly those without potential conflicts of interest. Retired experts are no longer employed and, therefore, may be less likely to have current ties to industry. For example, a National Academies official we spoke with explained that when the type of expertise needed for a committee lends itself to inherently conflicted professionals—for example, if a committee focuses on the operations of drug manufacturers—the organization could seek an individual who is retired. However, some FDA officials noted that retired experts may not be familiar with new science and technologies or interested in committing the time necessary to serve on an advisory committee, or they may have conflicts of interest because they consult privately. One FDA official said that the center in which she is employed may recruit individuals who retired in the past 2 years to participate on an advisory committee or panel, but individuals retired longer than that are usually not familiar with current technologies and are, therefore, not qualified for the center’s advisory committee or panel participation. Although the majority of former advisory committee members we spoke with agreed that expanding outreach efforts to retired experts would improve FDA’s advisory committee process, many former members noted that FDA advisory committees require members who are active in their field. Most former FDA advisory committee members and the consumer groups we spoke with agreed that expanding outreach efforts to experts from universities and colleges would be effective in recruiting qualified advisory committee candidates. FDA noted that most of its advisory committee members are already academicians. An AAMC official suggested that FDA ask medical colleges to solicit their own staff to serve on FDA advisory committees. He also told us that AAMC does not currently assist FDA with advisory committee recruitment, but it would if asked. For example, he said AAMC would be willing to post FDA advisory committee member vacancies on its Web site at no cost. However, two former members noted that academicians may receive industry funding for research or consulting and, therefore, may have conflicts of interest. The FDA Amendments Act of 2007 modifies FDA’s process for prescreening candidates for advisory committee membership. For example, the act directs FDA to develop outreach strategies for potential members of advisory committees at universities, colleges, and other academic research centers. Most former FDA advisory committee members and consumer groups we interviewed said that expanding outreach efforts to epidemiologists and statisticians would be effective in recruiting qualified advisory committee candidates, particularly those without potential conflicts of interest. According to some former advisory committee members, epidemiologists and statisticians add expertise in data analysis to FDA advisory committees. For example, biostatisticians could provide expertise in interpreting clinical trial data. Representatives from two consumer advocacy groups told us these individuals may be less likely than clinicians to have conflicts of interest and may bring a different focus to committee deliberations. According to these consumer interest group representatives, the agency’s advisory committees are overly weighted towards clinicians and clinical trialists. One representative told us that clinicians are more likely to have potential conflicts of interest because they are more likely to have received industry funding, and another representative said that they generally have a bias towards product approval because they seek more options—that is, drugs and medical devices—to help with diagnosis and treatment of their patients. The majority of the former FDA advisory committee members we interviewed agreed that focusing outreach efforts on recruiting statisticians and epidemiologists would be an effective way for FDA to recruit qualified advisory committee candidates, particularly those without potential conflicts of interest. In The Future of Drug Safety – Promoting and Protecting the Health of the Public: FDA’s Response to the Institute of Medicine’s 2006 Report, FDA stated in 2007 that it will increase the epidemiology expertise on its drug-related advisory committees. The FDA Amendments Act of 2007 modifies FDA’s process for prescreening candidates for advisory committee membership. (See app. I.) Our analysis of the composition of FDA advisory committee meeting participants from 2 recent years indicates that most participants were standing members, but a large minority of participants were temporary members. In the 83 advisory committee meetings held by CBER, CDER, and CDRH in 2004 and 2006, standing and temporary members were 58 and 42 percent, respectively, of the 1,218 total meeting participants. An advisory committee member who has a conflict of interest and whose expertise is needed may be permitted by FDA to participate in an advisory committee meeting under certain circumstances by granting a conflict of interest determination. About 16 percent of the participants received a conflict of interest determination that allowed them to participate. In 49 of the 83 meetings, at least one participating standing or temporary member had at least one conflict of interest determination that allowed the member to participate. The 200 participants with conflict of interest determinations in those 49 meetings had a total of 234 determinations. The FDA Amendments Act of 2007 limits the number of conflict of interest determinations—statutory waivers—that FDA can grant and FDA’s conflict of interest policy revisions change the amount of the disqualifying financial interests. Standing members were the predominant participants in the 83 advisory committee meetings held by CBER, CDER, and CDRH in 2004 and 2006 that we analyzed. These 83 meetings were held before the 2007 FDA advisory committee process and statutory changes. Temporary members participated in 79 of the 83 meetings. Of the 1,218 participants in the 83 meetings, 58 percent were standing members and 42 percent were temporary. (See table 4.) The participants in CDER’s 17 meetings held in 2006 were nearly evenly split between standing and temporary members at 52 percent and 48 percent respectively. Forty-nine of the 83 advisory committee meetings we analyzed—over half of all the meetings—had at least 1 standing or temporary member with a conflict of interest determination. FDA may permit an advisory committee member who has a conflict of interest and whose expertise is needed to participate in an advisory committee meeting under certain circumstances by granting a conflict of interest determination. Two hundred standing and temporary members—about 16 percent of the 83 meetings’ 1,218 participants—had at least one conflict of interest determination. Forty-two of the 49 meetings—86 percent—had 2 or more members who received at least one conflict of interest determination. Ninety-five percent of CDER’s 2004 and 2006 meetings had 2 or more members with determinations followed by CBER (85 percent) and CDRH (73 percent). The 200 members had 234 conflict of interest determinations. (See table 5). Most members—167—had only 1 conflict of interest determination; 33 members each had 2 or more determinations. Standing members had 62 percent (nearly two-thirds) of the 234 determinations and temporary members had 38 percent (over one-third). Among the 234 conflict of interest determinations, the most often granted determination—155—was the § 208(b)(3) financial interest waiver. Standing members had 104 and temporary members had 51 of these waivers. This waiver can be granted for either specific-parties or non- specific party advisory committee meeting topics and to standing and temporary SGE members, so it should have been the conflict of interest determination most often granted to members. Nearly one-half of the 155 § 208(b)(3) waivers—72—were granted to CDER meeting members, 50 to standing, and 22 to temporary members. The remaining 79 of the 234 determinations were 36 statutory waivers—§ 355(n)(4) waivers (27) and § 208(b)(1) financial interest waivers (9)—and 43 regulatory § 2635.502 appearance authorizations. The FDA Amendments Act of 2007 limits the number of certain conflict of interest determinations—the statutory waivers—that FDA can grant and FDA’s conflict of interest policy revisions change the amount of the disqualifying financial interests. HHS reviewed a draft of this report and provided comments, which are reprinted in appendix V. HHS also provided technical comments, which we incorporated as appropriate. In its comments, HHS noted that on August 4, 2008, after we had provided the draft report for its review on July 29, 2008, FDA issued four final guidance documents concerning management of its advisory committees. The guidances include stricter limits on financial conflicts of interest for committee members, improved committee meeting voting procedures, and process improvements for disclosing information about advisory committee members’ financial interests and waivers, and for preparing and making publicly available information given to advisory committee members for specific matters considered at advisory committee meetings. These final guidance documents were available to us in draft form during the course of our work and the portions of the draft guidances that we discussed in the report did not change in the final 2008 guidances. HHS commented on several other aspects of the draft report. First, HHS asked us to note that our findings are applicable only to CBER, CDER, and CDRH advisory committee meetings, and we revised our report to clarify that we did not include all of the FDA centers. Our work focused on those three FDA centers because most of FDA’s advisory committees were affiliated with them; these centers’ advisory committee meetings represented more than 80 percent of the total FDA advisory committee meetings held in 2004 and 2006. Second, HHS commented that three groups of experts we included in the report as possible sources for expanding the agency’s recruitment outreach for advisory committee members—academic experts, epidemiologists and statisticians, and retired experts—may not be more likely to be free of conflicts of interest. These expert groups were identified by individuals we interviewed as sources they believed could be less likely to have conflicts of interest, and we attributed the statements to those individuals in the report. In addition, the FDA Amendments Act of 2007 discusses FDA’s advisory committee recruitment methods and directs FDA to develop and implement strategies on effective outreach to the academic community. Third, HHS commented that the comparison of the recruitment methods used by EPA and the National Academies to FDA’s recruitment methods did not consider additional restraints FDA may have in selecting qualified, minimally conflicted individuals to serve on an advisory committee. However, the report focuses on EPA’s and the National Academies’ methods to identify potential advisory committee members and uncover conflicts of interest that are not employed by FDA. The approaches employed by these other organizations may provide additional options that FDA could use to expand the pool of potential advisory committee members. Finally, HHS commented on our use of the term conflict of interest determinations. Throughout our report, we used the term to include both conflict of interest waivers and appearance authorizations granted to advisory committee members to allow them to participate in advisory committee meetings. Although the standards for these determinations are different, they are all made to allow members to participate in advisory committee meetings notwithstanding ethical concerns over their participation. We revised the report to clarify that the FDA Amendments Act of 2007 provisions involving the agency’s advisory committees only apply to conflict of interest waivers. As we agreed with your offices, unless you publicly announce the contents of this report earlier, we plan no further distribution of it until 30 days from its date. We will then send copies to others who are interested and make copies available to others who request them. In addition, the report will also be available at no charge on our Web site at http://www.gao.gov. If you or your staffs have any questions about this report, please contact me at (202) 512-7114 or crossem@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found on the last page of this report. GAO staff who made major contributions to this report are listed in appendix VI. In 2007, two major actions occurred that affect the Food and Drug Administration’s (FDA) processes for recruiting and prescreening individuals for advisory committee membership and for granting financial conflict of interest waivers to allow members to participate in advisory committee meetings. Those two actions were the passage of the FDA Amendments Act of 2007—an amendment of the Federal Food, Drug, and Cosmetic Act—and FDA’s draft March 2007 conflict of interest guidance. The FDA Amendments Act of 2007 modifies the agency process for prescreening candidates for advisory committee membership. The act requires FDA to develop and implement strategies to conduct outreach to potential advisory committee candidates at universities and colleges, other academic research centers, professional and medical societies, and patient and consumer groups. FDA may also develop a new committee member recruitment method, which would allow entities, such as universities and other academic research centers, receiving funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, or the Veterans Health Administration, to identify a person whom FDA could contact about the nomination of individuals to serve on advisory committees. Under the prescreening modification, a candidate for FDA advisory committee membership, as of October 1, 2007, completes the Office of Government Ethics Form 450 or FDA Form 3410—financial disclosure reports that provide information about the individual’s financial interests—prior to being appointed as an FDA advisory committee member. According to the FDA Amendments Act of 2007, this pre-appointment financial review is intended to reduce the likelihood that a candidate, if appointed as a member, would later require a statutory conflict of interest determination to participate in advisory committee meetings. Conflict of interest determinations to allow a member with a conflict to participate in an advisory committee meeting are affected by both FDA’s draft March 2007 guidance and the FDA Amendments Act of 2007. The draft guidance provides that an advisory committee member with personal financial conflicts of interest—referred to as disqualifying financial interests in the guidance—generally would not be allowed to participate in an advisory committee meeting if the combined value of those interests exceeds $50,000. FDA would not grant a waiver in those circumstances unless the FDA Commissioner determined a waiver was appropriate. Two provisions of the FDA Amendments Act of 2007 affect conflict of interest determinations. First, the law repealed 21 U.S.C. § 355(n)(4)—the § 355 (n)(4) waiver—that applied only to members voting on FDA advisory committee meeting matters related to the clinical investigations and approvals of drugs and biologics—usually Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) advisory committee meetings. The law also created a new waiver provision—the § 712(c)(2)(B) waiver—to all FDA advisory committee members. Under the new provision, an individual or a member of his or her immediate family who has a financial conflict of interest cannot participate unless FDA determines that a waiver is necessary to afford the advisory committee essential expertise. The law also limits the number of waivers that FDA can grant advisory committee members, reducing the number of waivers (per total meetings) granted annually by 5 percent for a total reduction of 25 percent over 5 years. In this report, we examined FDA’s advisory committee member recruitment, selection, and conflicts of interest prescreening and screening processes, as well as the agency’s use of temporary and standing advisory committee members. We chose to analyze three FDA centers—CBER, CDER, and CDRH—because most of FDA’s advisory committees were affiliated with them—and these three centers’ advisory committee meetings represented more than 80 percent of the total FDA advisory committee meetings held in the two years we included. We did not examine FDA’s other centers’ advisory committee meetings. Specifically, we describe (1) how FDA recruited individuals for advisory committee membership and evaluated candidates by prescreening them for potential conflicts of interest, (2) barriers that were reported to recruiting qualified individuals to serve on FDA advisory committees, particularly candidates without potential conflicts of interest, and (3) the proportion of standing and temporary members who participated in advisory committee meetings, and the frequency with which members with one or more conflict of interest determinations participated in advisory committee meetings. During the course of our work, two major actions occurred that changed FDA’s recruitment and conflict of interest policies. (See app. I.) In March 2007, FDA issued a draft advisory committee guidance that revises how FDA screens individuals to determine if they have conflicts of interest for a specific advisory committee meeting. In addition, Congress amended the Federal Food, Drug, and Cosmetic Act to include, among other provisions, a section addressing recruitment, prescreening, and conflicts of interest, which took effect on October 1, 2007. At the time of our review, it was too soon to assess the effect of the changes on FDA’s processes, consequently, this report focuses on FDA’s organization, processes, and conflict of interest determinations as documented prior to the 2007 actions. To address our objectives, we performed a literature review of studies related to FDA advisory committee member recruitment, selection, and conflict of interest prescreening and screening processes. We reviewed Office of Government Ethics and federal conflict of interest laws, and Department of Health and Human Services’ (HHS) and FDA’s written policies, guidance, reports, and forms related to advisory committee management. We interviewed individuals and groups familiar with FDA’s advisory committee member recruitment, selection, and conflict of interest screening processes including FDA staff, selected former advisory committee members, and representatives from the Association of American Medical Colleges (AAMC), Center for Science in the Public Interest, Pharmaceutical Research and Manufacturers of America (PhRMA), and Public Citizen’s Health Research Group. In addition, we reviewed FDA’s advisory committee meeting records and conflict of interest determination records for advisory committee meetings held by three FDA centers—CBER, CDER, and CDRH—in 2004 and 2006. We chose to analyze these three centers because most of FDA’s advisory committees were affiliated with them—and these centers’ advisory committee meetings represented more than 80 percent of the total FDA advisory committee meetings held in 2004 and 2006. Details on the scope of our work and methods to address each objective follow. To examine how FDA recruited individuals for advisory committee membership and prescreened candidates for potential conflicts of interest, we reviewed HHS and FDA written policies, guidances, reports, and forms related to advisory committee management. These documents include HHS’s Federal Advisory Committee Management Handbook, FDA’s Policy and Guidance Handbook for FDA Advisory Committees, and FDA’s quarterly reports to Congress on its efforts to identify and screen qualified people for appointment to FDA advisory committees. We also reviewed advisory committee information on FDA’s Web site and examined FDA forms used to prescreen candidates for advisory committee membership. In addition, we interviewed staff from FDA’s Advisory Committee Oversight and Management Staff; FDA’s Ethics and Integrity Staff; staff from CBER, CDER, and CDRH; and advocacy organizations that nominate individuals to serve on FDA’s advisory committees, including PhRMA and Public Citizen’s Health Research Group. We also interviewed officials from organizations we previously identified as employing specific recruitment and prescreening methods that could ensure independent and balanced advisory committees. These organizations are the U.S. Environmental Protection Agency (EPA) and the National Academies. To examine barriers that were reported to recruiting qualified individuals to serve on FDA advisory committees, particularly candidates with no potential conflicts of interest, we interviewed individuals and groups familiar with FDA’s advisory committee recruitment process and officials from organizations we identified in 2004 as employing specific recruitment methods that could ensure independent and balanced advisory committees. Individuals interviewed include staff from CBER, CDER, and CDRH office, review division, and advisory committee management; 12 former CBER, CDER, and CDRH advisory committee members; staff from EPA, the National Institutes of Health, and the National Academies who were involved with the advisory committee process at their organizations; and staff from AAMC, PhRMA, and consumer advocacy groups that have taken a position on FDA’s nomination and selection processes for advisory committee members. To determine the proportion of participants in FDA’s CBER, CDER, and CDRH advisory committee meetings who were standing members or temporary members, we reviewed FDA’s advisory committee meeting records for 83 meetings held by the 3 centers in 2004 and 2006. The 83 meetings did not include (1) the 10 joint advisory committee meetings— meetings involving 2 advisory committees—held in 2004 and 2006, which were analyzed separately, or (2) advisory committee subcommittee meetings, which are not covered by the Federal Advisory Committee Act. Beginning in November 2005, FDA was required to post information on its Web site about the conflict of interest waivers it granted that allowed certain members to participate in meetings. We chose to review the committee meetings held in 2004 and 2006—2 years with the most recent data when we began our work—because (1) 2004 was the last full year before FDA began to post waiver information in 2005, and (2) 2006 was the first full year in which the waiver information had to be posted. We excluded 2005 from the analysis because it was the year the Web site posting requirement began. To verify the number of standing and temporary members who attended the 83 meetings, we reviewed the 2004 and 2006 FDA advisory committee meeting records, which included meeting minutes, meeting summaries, meeting transcripts, lists of meeting attendees, and annual committee member rosters—the list of standing members—for the years 2004 and 2006. If an advisory committee meeting was conducted for more than 1 day, a standing or temporary member was included in the analysis, if the member attended at least 1 day of the meeting. To analyze the number and type of conflict of interest determinations received by standing and temporary members, we analyzed 49 of the 83 CBER, CDER, and CDRH advisory committee meetings held in 2004 and 2006. The following criteria were used to select the 49 meetings: (1) the advisory committee meetings with the designation most often used by the centers—for CDER and CDRH, specific-parties meetings and, for CBER, non-specific party meetings, and (2) advisory committee meetings that had at least one standing or temporary member who received at least one conflict of interest determination. If an advisory committee meeting involved both a specific-parties and a non-specific party meeting topic, the meeting was included if any standing or temporary member attending the meeting received a conflict of interest determination. To determine the number and type of conflict of interest determinations among the 49 advisory committee meetings’ standing and temporary members, we created a participant-level data collection instrument to retrieve information from FDA’s advisory committee meeting records and conflict of interest waiver records for each advisory committee meeting included in the project analysis. We reviewed the following records to collect the needed data: conflict of interest waivers and their conflict of interest checklists, acknowledgement and consent for disclosure of potential conflicts of interest forms, and appearance authorization memorandums. Information we collected included the advisory committee meeting participant’s status (for example, standing or temporary member) and the conflict of interest determination (for example, § 208(b)(3) waiver). When FDA issued its March 2007 Draft Guidance for the Public, FDA Advisory Committee Members, and FDA Staff on Procedures for Determining Conflict of Interest and Eligibility for Participation in FDA Advisory Committees, we narrowed the scope of our work and excluded an assessment of whether FDA adhered to its FDA Waiver Criteria Document (2000) when it made its conflict of interest determinations for the meetings we analyzed. To assess the reliability of the conflict of interest determination information we summarized, we reviewed questions from 5 percent of the data collection instruments completed for the 49 advisory committee meetings for accuracy in transferring conflict of interest determination information from the FDA records, and determined the information collected was sufficiently reliable for our report. We conducted our work from October 2006 through September 2008 in accordance with generally accepted government auditing standards. FDA may, like other federal agencies, determine its advisory committees’ meeting topics to suit its own purposes. There are many factors involved in conducting an FDA advisory committee meeting that may affect a committee’s recommendations to the agency, in addition to any possible effects from a committee member’s conflicts of interest. Also, like other federal agencies, FDA generally has the freedom to accept, reject, or modify its advisory committees’ recommendations. The following discussion of various meeting factors is limited to FDA’s CBER, CDER, and CDRH advisory committees. For each advisory committee meeting, the FDA staff involved may include individuals from the review division with subject matter expertise on the advisory committee’s meeting topics and the division director; the review team—the FDA staff working on a particular product being considered by the advisory committee; the advisory committee’s executive secretary; and the center’s advisory committee meeting management entity. Who should be selected as standing advisory committee members? The FDA advisory committee charters—the committee’s organizational document—list the expertise a committee’s standing members should have. The review division is involved in the selection of nominees for a committee’s standing members and the expertise they represent. It has been suggested that a member’s type of expertise may affect how the member analyzes the information provided at an advisory committee meeting and what recommendation decision the member makes. Who should be selected as the advisory committee chair? Review divisions determine who is selected to serve as an advisory committee’s chair rather than committee members choosing a chair from among themselves. In consultation with the review division, the chair’s responsibilities may include helping develop the meeting’s agenda and topic questions, deciding the meeting’s voting procedure, monitoring the length of meeting presentations, and approving meeting minutes. Why is an advisory committee meeting needed? Although an advisory committee may have a regular meeting schedule, the advisory committee’s review division decides when an advisory committee meeting is needed. Meetings may be held when there are controversial issues that committee advice could help the agency resolve. For example, in July 2007, two of CDER’s advisory committees met jointly to consider whether Avandia, a diabetes drug, should remain on the market given concerns that its use increased heart risks for those with diabetes. What is the advisory committee meeting’s topic and what questions are to be answered? The review division selects the topic, develops the issues FDA seeks advice on into topic questions for the advisory committee to address at the meeting, and compiles the background information for the committee to review. Other options for developing possible meeting topics: Subcommittee meetings: The review division may select a limited number of advisory committee members—including at least two standing members—and other consultants to serve as a subcommittee to discuss and develop an issue of FDA’s choosing. The subcommittee then provides this information to an advisory committee for its consideration. Homework assignments: FDA may also select advisory committee members and other experts to conduct homework assignments, again on issues of FDA’s choosing. A homework assignment may involve, for example, an in-depth review of an issue that may be considered as a potential topic at an upcoming advisory committee meeting or review of a product early in its development. Are temporary members needed, and if yes, who should be selected? The review division will determine whether the standing committee members able to attend the meeting have the needed expertise to address the topics to be discussed at the advisory committee meeting. If additional expertise is determined to be necessary, temporary members can be selected to serve on the committee for the meeting. The review division decides which individuals—usually from the center’s consultant pool—are selected to serve as temporary members. Each center maintains a consultant pool and selects the pool’s individual experts. Are guest speaker presentations needed, and if yes, who should be selected? The review division may determine that additional information needs to be presented at an advisory committee meeting. The division can select and invite guest speakers to make presentations and answer questions before the committee. Guest speakers may, for example, be members of other FDA advisory committees, individuals from a center’s consultant pool, federal employees from other agencies, or national or international experts from outside FDA. Guest speakers do not vote, and they do not participate in the committee’s discussions. Are patient representatives needed, and if yes, who should be selected? CBER, CDER, and CDRH cancer-related advisory committees are required to have patient representatives participate in all advisory committee meetings. For other advisory committees, the review division considers the topic to be discussed at a particular meeting when determining whether it is necessary for a patient representative to serve at an advisory committee meeting. Patient representatives usually serve on advisory committees that focus on disease-specific topics such as reviews of products and therapies for HIV/AIDS and cancer diagnosis and treatment. When participating in CBER and CDER advisory committees’ meetings, patient representatives usually vote, but when participating in CDRH’s committee meetings, they do not vote. Who should be selected to make FDA’s presentations at meetings? A review division’s role at an advisory committee meeting is to present the issues and data concerns the advisory committee will consider, and to pose questions to the committee throughout the meeting. For example, a review division director may introduce the committee meeting topic—for example, a new drug approval application, provide the regulatory history concerning how similar drugs were developed, describe any issues that have arisen with similar drugs, and discuss the types of clinical trials used to evaluate the previously approved drugs. The review division determines which FDA staff attend the meeting and whether they make presentations. What companies and products are determined to be affected by the meeting topic? After an advisory committee meeting’s topic is selected, the review division compiles a list of the companies and products it determines are affected by the topic. The list is then reviewed by the advisory committee’s management entity, for example, CDER’s Advisors and Consultants Staff. The more affected companies or products involved, the greater the possibility that committee members may have financial interests in an affected company or product, and the greater the possibility that members may have conflicts of interests. To which advisory committee members with conflicts of interest does FDA decide to grant conflict of interest determinations? For each advisory committee meeting, the center’s advisory committee meeting management entity reviews each member’s possible conflicts of interest based on the information the member self reports on his or her FDA financial disclosure form—3410—and determines whether they will affect the individual’s ability to participate in the meeting. If there are members that are determined to have conflicts of interest, the review division may seek individuals with similar expertise, who do not have conflicts of interest, to participate in the meeting as temporary members. Advisory committee members who have conflicts of interest, but who have expertise the review division determines is needed for the committee’s meeting topic, can be given a conflict of interest determination if the standards of the applicable statutes and regulations are met. How does the advisory committee reach its meeting’s recommendation— by voting or reaching a consensus? The review division, which determines the meeting topic and questions, can indicate whether the committee should vote or reach a consensus on the recommendations made at the committee meeting. A committee chair may also decide that an issue should be addressed by a vote of the members. Generally, committee members vote when a meeting has a specific topic, such as a new drug approval application. There may be instances when the members reach a consensus opinion without voting. What options does FDA have concerning the advisory committee meeting’s recommendation? Following an advisory committee meeting, the center’s review division evaluates the advisory committee’s recommendation to determine whether FDA should accept or reject it, have the committee discuss the meeting topic again, or hold workshops on the meeting topic subject. FDA, like other federal agencies, generally does not have to accept its advisory committees’ recommendations. Recent studies have focused on whether FDA advisory committee members with conflict of interest determinations that allow them to participate in the committee meetings may influence the committee’s recommendations. Public Citizen’s 2006 study: The Public Citizen study on FDA conflicts of interest found a “weak relationship” between an FDA advisory committee member who had a conflict of interest and who also voted in favor of the drug at issue. The study also found that excluding advisory committee members (standing members) and voting consultants (temporary members) who had conflict of interest determinations would not have altered the overall vote result—whether favorable or unfavorable toward a drug—of any advisory committee meeting studied. National Research Center for Women & Families 2006 report: The National Research Center’s report, which included information from other studies of FDA advisory committees and their members with conflicts of interest, concluded that “it is possible to understand how a few committee members with conflicts of interest can have a disproportionate impact on approval recommendations.” The report stated that because FDA has its advisory committees meet to discuss controversial or innovative products, “the public might therefore expect that many of the drugs and devices reviewed by advisory committees would not be recommended for approval.” Using 11 randomly selected CDER and CDRH advisory committees, the report found that 79 percent of the 89 products reviewed between 1998 and 2005 were recommended for approval, and that the recommendations were usually unanimous. FDA’s 2007 study: A research firm under contract with FDA assessed the relationship of FDA advisory committee members’ expertise and their financial conflicts of interest. The study concluded that (1) standing advisory committee members with higher expertise were more likely than other standing members to have been granted conflict of interest waivers, (2) alternative members—temporary members—could be found for a specific advisory committee meeting, but many of them would likely require conflict of interest waivers, and (3) the ability to create a conflict- of-interest-free advisory committee was speculative. In addition to the contact above, Martin Gahart, Assistant Director; George Bogart; Helen Desaulniers; Adrienne Griffin; Cathleen Hamann; Martha Kelly; Deitra Lee; Amanda Pusey; Daniel Ries; Opal Winebrenner; and Suzanne Worth made key contributions to this report. Federal Advisory Committee Act: Issues Related to the Independence and Balance of Advisory Committees. GAO-08-611T. Washington, D.C.: April 2, 2008. Drug Safety: Further Actions Needed to Improve FDA’s Postmarket Decision-making Process. GAO-07-856T. Washington, D.C.: May 9, 2007. NIH Conflict of Interest: Recusal Policies for Senior Employees Need Clarification. GAO-07-319. Washington, D.C.: April 30, 2007. Drug Safety: FDA Needs to Further Address Shortcomings in Its Postmarket Decision-making Process. GAO-07-599T. Washington, D.C.: March 22, 2007. Food and Drug Administration: Decision Process to Deny Initial Application for Over-the-Counter Marketing of the Emergency Contraceptive Drug Plan B Was Unusual. GAO-06-109. Washington, D.C.: November 14, 2005. Federal Research: NIH and EPA Need to Improve Conflict of Interest Reviews for Research Arrangements with Private Sector Entities. GAO-05-191. Washington, D.C.: February 25, 2005. Federal Advisory Committees: Additional Guidance Could Help Agencies Better Ensure Independence and Balance. GAO-04-328. Washington, D.C.: April 16, 2004. University Research: Most Federal Agencies Need to Better Protect against Financial Conflicts of Interest. GAO-04-31. Washington, D.C.: November 14, 2003.

Summary: The Department of Health and Human Services' (HHS) Food and Drug Administration (FDA) has been criticized about how it recruits individuals to become members of its advisory committees and how it grants some determinations that allow members with conflicts of interest to participate in committee meetings. Advisory committee meetings can include both standing and temporary members. Temporary members only serve for a particular meeting. GAO was asked to examine FDA's advisory committee processes. GAO reported on (1) how FDA recruited individuals for membership and evaluated candidates for potential conflicts of interest, (2) barriers that were reported to recruiting qualified individuals to serve on committees, and (3) the proportion of standing and temporary members, and the frequency with which members with conflict of interest determinations participated in meetings. GAO reviewed FDA advisory committee policies and analyzed meeting records for FDA's Center for Biologics Evaluation and Research (CBER), Center for Drug Evaluation and Research (CDER), and Center for Devices and Radiological Health (CDRH). GAO also interviewed individuals familiar with FDA's committee member recruiting process. GAO did not examine the effects of changes in FDA's advisory committee processes resulting from the FDA Amendments Act of 2007 and 2007 FDA policy revisions as it was too soon to assess them. Prior to the FDA Amendments Act of 2007, FDA employed several methods to recruit candidates for advisory committees and to evaluate candidates by prescreening them for potential conflicts of interest. FDA recruited candidates by announcing vacancies in the Federal Register, distributing recruitment brochures at advisory committee meetings and national meetings, word-of-mouth or asking current advisory committee members, and posting recruitment and conflict of interest information on FDA's Web site. To evaluate advisory committee candidates for conflicts of interest, FDA reviewed the candidates' curricula vitae and usually conducted a prescreening interview. FDA employed many of the same recruitment and evaluation practices used by organizations previously identified by GAO as employing methods that could ensure an independent and balanced advisory committee. FDA faced barriers to recruiting qualified advisory committee candidates, particularly those without potential conflicts of interest, according to FDA officials and former FDA advisory committee members. However, GAO found that the agency may have been able to mitigate these barriers by expanding its outreach efforts. FDA staff and former FDA advisory committee members GAO interviewed generally agreed that individuals with the expertise FDA sought for its advisory committees were the same leading experts that industry sought to conduct research. In addition, word-of-mouth--the advisory committee member recruitment method FDA officials generally agreed was most effective--was limited in the number of candidate nominations it could generate. The FDA Amendments Act of 2007 modifies FDA's process for prescreening candidates for committee membership. Standing and temporary members were 58 and 42 percent, respectively, of the 1,218 participants in the 83 advisory committee meetings held by CBER, CDER, and CDRH in 2004 and 2006 that GAO reviewed. FDA may permit an advisory committee member who has a conflict of interest, or an appearance of a conflict, and whose expertise is needed to participate in an advisory committee meeting under certain circumstances by granting a conflict of interest determination. More than half of the meetings had at least one standing or temporary member with at least one conflict of interest determination. The 200 members found to have at least one conflict of interest determination represented about 16 percent of all 83 meetings' participants. The FDA Amendments Act of 2007 limits the number of certain conflict of interest determinations that FDA can grant and FDA's conflict of interest policy revisions limit the amount of the disqualifying financial interests. In its comments on a draft of this report, HHS noted that on August 4, 2008, after GAO provided the draft report for its review, FDA issued four final guidance documents concerning management of its advisory committees. HHS also provided additional clarifications about aspects of FDA's advisory committees. GAO revised the report to cite the final guidances and to incorporate HHS's clarifications where appropriate.