FDA Advisory Committees: Process for Recruiting Members and Evaluating Potential Conflicts of Interest
Published: 2008-09-30T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: 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.
section_title: What GAO Found
paragraphs: 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.

section_title: Letter
paragraphs: The Food and Drug Administration (FDA) is responsible for ensuring the  safety and efficacy of drugs, biological products, and medical devices the  American public uses every day. FDA convenes scientific advisory  committees to provide independent expertise and technical assistance to  help the agency make decisions about the development and evaluation of  products regulated by FDA. Advisory committees include standing  members, who are appointed by FDA to serve a specified term on an  advisory committee, and may include temporary members, who are  selected by FDA to serve at only one specific meeting. Other individuals  that may contribute to the advisory committee meeting discussion include  guest speakers, such as researchers who are invited to present scientific  papers and individuals who speak on behalf of the companies whose  products are at issue. Members of the public are also allowed to speak  during an open public hearing portion of the advisory committee meeting.  The advisory committees’ recommendations are not binding on the  agency, but the agency usually follows the advisory committees’ advice.
Some advisory committee members might have financial conflicts of  interest for all or part of a committee meeting depending on the issues or  products to be discussed. Conflicts of interest, for example, might include  a member having financial investments in a drug manufacturer whose  product is under review. While some conflicts of interest could require  that a member be prohibited from participating in a meeting, FDA may  permit a member to participate in advisory committee meeting discussions  under certain circumstances by granting waivers of the statutory  prohibition on participation. FDA can also authorize a member to  participate when the statutory conflict of interest prohibition would not  have been violated, but there is the appearance of a conflict of interest,  such that the member’s impartiality involving the committee meeting’s  discussions could be questioned. For purposes of this report, both types of  decisions are called conflict of interest determinations. FDA has been  criticized about how it recruits qualified individuals for its advisory  committees and how it grants some conflict of interest determinations  allowing members with conflicts of interest to participate in committee  meetings. FDA maintains that its advisory committee members are  preeminent scientists in their field, and that it is inevitable that some of  these experts will have grants from, and contracts with, the regulated  industries, which could constitute a potential conflict of interest or  present the appearance of partiality. FDA asserts that its ability to make  conflict of interest determinations is essential to its effort to access the  most expert medical and scientific advice available. Others contend,  however, that the objectivity of the advice and recommendations given by  FDA advisory committees can be affected by the involvement of conflicted  members.
You have expressed interest in information about how FDA identified,  recruited, and prescreened qualified candidates and about FDA’s use of  standing and temporary members and the extent these members received  conflict of interest determinations. In this report 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 in advisory committee meetings, and the frequency with which  members with one or more conflict of interest determinations participated  in advisory committee meetings.
To report on these issues, we reviewed the Department of Health and  Human Services’ (HHS) and FDA’s advisory committee regulations,  policies, and guidances. We also reviewed the federal conflict of interest  statutes and the Office of Government Ethics (OGE) regulations. We  interviewed FDA’s Advisory Committee Oversight and Management Staff  (ACOMS) and Ethics and Integrity Staff (EIS). We also interviewed staff  such as executive secretaries, who manage advisory committees; review  division directors; and advisory committee management staff from the  three FDA centers that we analyzed: the Center for Biologics Evaluation  and Research (CBER), which regulates biological products such as blood  and vaccines; the Center for Drug Evaluation and Research (CDER),  which regulates drugs; and the Center for Devices and Radiological Health  (CDRH), which regulates medical devices and radiological products. 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.
To examine how FDA recruited individuals for advisory committee  membership and prescreened candidates for potential conflicts of interest,  in addition to interviews with FDA officials, we interviewed  representatives from selected advocacy organizations that participate in  nominating candidates for advisory committee membership, such as the  Pharmaceutical Research and Manufacturers of America (PhRMA) and  Public Citizen’s Health Research Group. We compared FDA’s recruitment  and prescreening methods to the methods used by the U.S. Environmental  Protection Agency (EPA) and the National Academies, organizations we  identified in 2004 as employing specific recruitment and prescreening  methods that could ensure independent and balanced advisory  committees. We updated our information on EPA’s and the National  Academies’ recruitment and prescreening methods through interviews  with agency officials.
To examine barriers that were reported to recruiting qualified individuals  to serve on FDA advisory committees, particularly candidates without  potential conflicts of interest, we interviewed individuals and groups  familiar with FDA’s advisory committee recruitment processes and  officials from organizations we identified in 2004 as employing specific  recruitment methods that could ensure independent and balanced  advisory committees. Individuals interviewed included current and former  FDA staff; former CBER, CDER, and CDRH advisory committee members;  staff involved with the advisory committee process at EPA, the National  Institutes of Health (NIH), and the National Academies; and staff from the  Association of American Medical Colleges (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 advisory committee  meetings who were standing members or temporary members and the  proportion of those members who received conflict of interest  determinations, we analyzed advisory committee meetings held by CBER,  CDER, and CDRH—the three FDA centers with both the most advisory  committees and the most committee meetings. We did not examine FDA’s  other centers’ advisory committee meetings. 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. We reviewed  FDA’s advisory committee meeting records and conflict of interest  determination records and assessed the reliability of these data by (1)  reviewing existing information about the data and (2) interviewing agency  officials knowledgeable about the data. We found that the data were  sufficiently reliable for our analysis.
During the course of our work, two major actions occurred that changed  FDA’s recruitment and conflict of interest policies. In March 2007, FDA  issued a draft advisory committee guidance that revises FDA’s policy on  how it 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. Appendix I describes these policy actions in greater  detail and we note FDA procedures that have been affected by them  throughout the report. Appendix II provides a more detailed explanation  of the scope and methodology for this report. We conducted our work  from October 2006 through September 2008 in accordance with generally  accepted government auditing standards.
subsections: section_title: Background
paragraphs: 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.
subsections: section_title: Federal Conflict of Interest Provisions May Permit Member Participation
paragraphs: 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.)
section_title: FDA Conflict of Interest Determination Process
paragraphs: 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.
section_title: FDA Used Several Methods to Recruit Candidates for Advisory Committee Membership and Prescreened Candidates for Potential Conflicts of Interest
paragraphs: 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.
subsections: section_title: FDA Employed Several Methods to Recruit Candidates for Advisory Committee Membership
paragraphs: 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.
section_title: FDA Prescreened Advisory Committee Member Candidates for Potential Conflicts of Interest
paragraphs: 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.
section_title: FDA Used Many of the Same Recruiting and Prescreening Methods as Those Employed by Organizations Identified as Having Some Promising Recruitment and Prescreening Methods
paragraphs: 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.
section_title: Barriers Existed to Recruiting Qualified FDA Advisory Committee Candidates, Particularly Those without Potential Conflicts of Interest, but FDA May Have Been Able to Mitigate Barriers by Expanding Outreach Efforts
paragraphs: 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.)
subsections: section_title: Barriers Existed to Recruiting Qualified Individuals to Serve on FDA Advisory Committees
paragraphs: 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.
subsections: section_title: The Experts FDA Sought to Serve on Its Advisory Committees Frequently Had Industry Ties
paragraphs: 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.
section_title: FDA’s Most Effective Recruitment Method Had Limitations
paragraphs: 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.
section_title: Some Aspects of FDA Advisory Committee Service May Have Deterred Potential Members
paragraphs: 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.
section_title: FDA May Have Been Able to Mitigate Barriers by Expanding Outreach Efforts
paragraphs: 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.)
section_title: Most Advisory Committee Meeting Participants Were Standing Members, and Many Members Had Conflict of Interest Determinations
paragraphs: 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.
subsections: section_title: Most Advisory Committee Meeting Participants Were Standing Members
paragraphs: 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.
section_title: At Least One Standing or Temporary Member Had a Conflict of Interest Determination in over Half of the Advisory Committee Meetings
paragraphs: 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.
section_title: Agency Comments and Our Evaluation
paragraphs: 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.
section_title: Appendix I: Major 2007 Actions Affecting FDA Recruiting and Conflict of Interest Determination Processes
paragraphs: 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.
section_title: Appendix II: Scope and Methodology
paragraphs: 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.
section_title: Appendix III: Factors That May Affect FDA Advisory Committee Meeting Recommendations
paragraphs: 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.
subsections: section_title: Pre-Advisory Committee Meeting Decisions
paragraphs: 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.
section_title: Advisory Committee Meeting Decisions
paragraphs: 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.
section_title: Advisory Committee Meeting Conflict of Interest Determinations
paragraphs: 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.
section_title: Recommendations from the Advisory Committee Meeting
paragraphs: 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.
section_title: Recent Studies on FDA Advisory Committee Meeting Recommendations
paragraphs: 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.
section_title: Appendix IV: FDA Advisory Committees for the Three Centers Analyzed
subsections: section_title: Center for Biologics Evaluation and Research
section_title: Center for Drug Evaluation and Research
section_title: Center for Devices and Radiological Health
section_title: Appendix V: Comments from the Department of Health and Human Services
section_title: Appendix VI: GAO Contact and Staff Acknowledgments
subsections: section_title: Acknowledgments
paragraphs: 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.
section_title: Related GAO Products
paragraphs: 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.