FDA Advisory Committees
Process for Recruiting Members and Evaluating Potential Conflicts of Interest
Gao ID: GAO-08-640 September 30, 2008
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.
GAO-08-640, FDA Advisory Committees: Process for Recruiting Members and Evaluating Potential Conflicts of Interest
This is the accessible text file for GAO report number GAO-08-640
entitled 'FDA Advisory Committees: Process for Recruiting Members and
Evaluating Potential Conflicts of Interest' which was released on
October 9, 2008.
This text file was formatted by the U.S. Government Accountability
Office (GAO) to be accessible to users with visual impairments, as part
of a longer term project to improve GAO products' accessibility. Every
attempt has been made to maintain the structural and data integrity of
the original printed product. Accessibility features, such as text
descriptions of tables, consecutively numbered footnotes placed at the
end of the file, and the text of agency comment letters, are provided
but may not exactly duplicate the presentation or format of the printed
version. The portable document format (PDF) file is an exact electronic
replica of the printed version. We welcome your feedback. Please E-mail
your comments regarding the contents or accessibility features of this
document to Webmaster@gao.gov.
This is a work of the U.S. government and is not subject to copyright
protection in the United States. It may be reproduced and distributed
in its entirety without further permission from GAO. Because this work
may contain copyrighted images or other material, permission from the
copyright holder may be necessary if you wish to reproduce this
material separately.
Report to Congressional Requesters:
United States Government Accountability Office:
GAO:
September 2008:
FDA Advisory Committees:
Process for Recruiting Members and Evaluating Potential Conflicts of
Interest:
GAO-08-640:
GAO Highlights:
Highlights of GAO-08-640, a report to congressional requesters.
Why GAO Did This Study:
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.
What GAO Found:
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.
To view the full product, including the scope and methodology, click on
[hyperlink, http://www.gao.gov/cgi-bin/getrpt?GAO-08-640]. For more
information, contact Marcia Crosse at (202) 512-7114 or
crossem@gao.gov.
[End of section]
Contents:
Letter:
Results in Brief:
Background:
FDA Used Several Methods to Recruit Candidates for Advisory Committee
Membership and Prescreened Candidates for Potential Conflicts of
Interest:
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:
Most Advisory Committee Meeting Participants Were Standing Members, and
Many Members Had Conflict of Interest Determinations:
Agency Comments and Our Evaluation:
Appendix I: Major 2007 Actions Affecting FDA Recruiting and Conflict of
Interest Determination Processes:
Appendix II: Scope and Methodology:
Appendix III: Factors That May Affect FDA Advisory Committee Meeting
Recommendations:
Appendix IV: FDA Advisory Committees for the Three Centers Analyzed:
Appendix V: Comments from the Department of Health and Human Services:
Appendix VI: GAO Contact and Staff Acknowledgments:
Related GAO Products:
Tables:
Table 1: Four Possible Member Conflict of Interest Determinations for
FDA Advisory Committee Meetings Prior to October 1, 2007, Changes:
Table 2: Selected Advisory Committee Recruitment Methods of FDA, EPA,
and National Academies Prior to October 1, 2007:
Table 3: Selected Advisory Committee Prescreening Methods of FDA, EPA,
and National Academies Prior to October 1, 2007:
Table 4: Standing and Temporary Member Totals for 83 FDA Advisory
Committee Meetings by Center: 2004 and 2006:
Table 5: Type and Number of Conflict of Interest Determinations for 200
Standing and Temporary Members for 49 Selected CBER, CDER, and CDRH
Advisory Committee Meetings, 2004 and 2006:
Figures:
Figure 1: FDA Organizational Structure for CBER, CDER, and CDRH
Advisory Committee Administration Prior to August 30, 2007:
Figure 2: Conflict of Interest Determination Process for FDA Advisory
Committee Members: CBER, CDER, and CDRH:
Abbreviations:
AAMC: Association of American Medical Colleges:
ACOMS: Advisory Committee Oversight and Management Staff:
ACS: Advisors and Consultants Staff:
CBER: Center for Biologics Evaluation and Research:
CDC: Centers for Disease Control and Prevention:
CDER: Center for Drug Evaluation and Research:
CDRH: Center for Devices and Radiological Health:
EIS: Ethics and Integrity Staff:
EPA: U.S. Environmental Protection Agency:
FACA: Federal Advisory Committee Act:
FDA: Food and Drug Administration:
HHS: Department of Health and Human Services:
MDAC: Medical Devices Advisory Committee:
NIH: National Institutes of Health:
OGE: Office of Government Ethics:
PhRMA: Pharmaceutical Research and Manufacturers of America:
SGE: special government employee:
[End of section]
United States Government Accountability Office:
Washington, DC 20548:
September 30, 2008:
The Honorable Edward Kennedy:
Chairman:
The Honorable Michael B. Enzi:
Ranking Member:
Committee on Health, Education, Labor, and Pensions:
United States Senate:
The Honorable Richard J. Durbin:
United States Senate:
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.[Footnote 1] 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.[Footnote 2] 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,[Footnote 3] (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)[Footnote 4] 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,[Footnote 5]
organizations we identified in 2004 as employing specific recruitment
and prescreening methods that could ensure independent and balanced
advisory committees.[Footnote 6] 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.[Footnote 7] 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.[Footnote 8] 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.[Footnote 9] 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.
Results in Brief:
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 for nominations; and posting information
about the recruitment process on FDA's Web site. To prescreen advisory
committee candidates, FDA officials reviewed the candidates' curricula
vitae and usually conducted an interview to determine whether there was
any financial interest or activity that might present a potential
conflict of interest. FDA employed many, but not all, of the
recruitment and prescreening methods used by EPA and the National
Academies, 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, we 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 generally agreed that individuals with the
expertise FDA sought for its advisory committees were the same leading
experts industry sought to conduct research. In addition, the advisory
committee member recruitment method generally agreed to be most
effective was limited in the number of candidate nominations it could
generate. Some former advisory committee members told us that other
barriers to membership related to aspects of FDA advisory committee
service, including the time commitment involved in preparing for and
attending advisory committee meetings, the financial disclosure
information reporting requirements, and the negative publicity
surrounding some advisory committee meetings. FDA employed several
recruitment methods to identify qualified FDA advisory committee
candidates. However, we found that the agency may have been able to
mitigate barriers by expanding outreach efforts to retired experts,
experts from colleges and universities, and individuals with
epidemiological and statistical expertise. The FDA Amendments Act of
2007 modifies FDA's process for prescreening candidates for advisory
committee membership.
Most FDA advisory committee meeting participants from the 2 recent
years we analyzed were standing members who served a specified term on
an advisory committee, but a large minority of participants were
temporary members who served at one specific meeting. In the 83
advisory committee meetings held by CBER, CDER, and CDRH in 2004 and
2006, 58 percent of the 1,218 meeting participants were standing
members and 42 percent were temporary members. 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. About 16 percent of the members received conflict of
interest determinations that allowed them to participate. Forty-nine of
the 83 meetings had at least one standing or temporary member with a
conflict of interest determination. Members can receive more than one
type of determination and some received both a financial conflict of
interest waiver and an appearance authorization. Two hundred
participants in these 49 meetings had 234 conflict of interest
determinations. 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
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 guidances concerning management of its advisory committees
including how it determines the eligibility of advisory committee
members with conflicts of interest to participate in meetings.[Footnote
10] The 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 guidances. 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.
Background:
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.[Footnote 11] 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.
[Footnote 12] 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.[Footnote 13] Depending on the issues or products to be
discussed at a committee meeting, a committee member may have a
potential financial conflict of interest.[Footnote 14] 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.[Footnote 15] (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:[Footnote 16] CDER
has 16 committees, CBER has 5, and CDRH has 4.[Footnote 17] (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.[Footnote 18]
Advisory Committee Management:
FDA's overall management and coordination of its advisory committees is
the responsibility of ACOMS. Each of the three centers we analyzed also
has its own advisory committee management entity--CBER's Division of
Scientific Advisors and Consultants, CDER's Advisors and Consultants
Staff (ACS), and CDRH's Integrity, Committee and Conference Management
Branch--responsible for administrative support, such as the preparation
of nomination packages for potential committee members and the review
of members' conflicts of interest. (See fig. 1.) Each FDA advisory
committee has an executive secretary who manages the committee
activities, including recruiting for advisory committee membership and
prescreening candidates for potential conflicts of interest.[Footnote
19]
Figure 1: FDA Organizational Structure for CBER, CDER, and CDRH
Advisory Committee Administration Prior to August 30, 2007:
[See PDF for image]
FDA Office of the Commissioner:
* Center for Biologics Evaluation and Research (CBER);
- Office of Management; Division of Scientific Advisors and Consultants
(DSAC)[A];
- Other CBER offices; 5 CBER advisory; committees;
* Center for Drug Evaluation and Research (CDER);
- Office of Executive Programs; Advisors and Consultants Staff
(ACS)[A];
- Other CDER offices; Other CDER divisions; 16 CDER advisory
committees;
* Center for Devices and Radiological Health (CDRH);
- Office of Management Operations; Division of Ethics and Management
Operations; Integrity, Committee and Conference Management Branch
(ICCMB)[A];
- Other CDRH offices; Other CDRH divisions; 4 CDRH advisory committees
(CDRH‘s Medical Devices Advisory Committee has 18 panels)[B];
* Office of External Relations;
- Advisory Committee Oversight and Management Staff (ACOMS);
* Office of Management; Office of Management Programs; Ethics and
Integrity Staff (EIS);
* 12 other FDA offices and centers.
Sources: Based on FDA organizational charts and GAO interviews with FDA
officials.
Notes: The chart reflects the FDA organizational structure for CBER,
CDER, and CDRH advisory committee administration prior to August 30,
2007. FDA amended its organizational structure on August 30, 2007. FDA
advisory committees can be attached to offices or divisions. A center's
advisory committees are attached to the center division or office with
subject matter responsibility for the committee's issue areas. CDER and
CDRH advisory committees are usually attached to a division--also
referred to as a review division--and CBER's committees are more
closely linked to its center's offices. For example, CDER's Anti-
Infective Drugs Advisory Committee is attached to CDER's Division of
Anti-Infective and Ophthalmologic Products and CBER's Blood Products
Advisory Committee is attached to its Office of Blood Research and
Review. ACS, ACOMS, and EIS are a part of the office they are connected
to rather than a separate group under it.
[A] Center's advisory committee management staff.
[B] For purposes of this report, the 18 panels' meetings were
considered to be individual advisory committee meetings.
[End of figure]
Advisory Committee Members:
There are two general types of FDA advisory committee members”standing
and temporary. Standing members are appointed by FDA to a specific
advisory committee, serve a specific term, and are expected to attend
all committee meetings. Temporary members are appointed by FDA to serve
for one specific advisory committee meeting.
Standing Members:
Individuals appointed to serve on an FDA advisory committee as standing
committee members generally are appointed as special government
employees (SGE),[Footnote 20] and they are subject to federal conflict
of interest statutes and regulations. Standing members are chosen for
their expertise and skills and are expected to provide advice on the
basis of their own best judgment. Federal government employees who are
not employed by FDA, such as federal employees with NIH, may also be
appointed as standing members and are also subject to these conflict of
interest statutes and regulations.[Footnote 21] FDA advisory committee
standing members serve staggered membership terms of no more than 4
years and are expected to attend all committee meetings.[Footnote 22]
CBER and CDER advisory committees‘ maximum standing committee
membership ranges from 9 to 26 members per committee, but most
committees have 11 or 13 member maximums. CDRH‘s 18 Medical Devices
Advisory Committee (MDAC) panels can have a combined maximum of 159
standing members.
Advisory committee charters may allow a committee to have members who
serve as representatives of specific interests”consumer, industry, or
patient representatives. Consumer representatives are appointed by FDA
as SGEs, are subject to federal conflict of interest statutes and
regulations, and are standing members on an advisory committee. These
individuals present the perspective of interested individual consumers
and consumer organizations, and may, for example, be consumer advocates
or consumer lawyers.[Footnote 23] Industry representatives are standing
members; however, they are not SGEs and, therefore, not subject to the
same conflict of interest laws and regulations applicable to federal
employees.[Footnote 24] Industry representatives may participate in
committee discussions to ensure that the industries affected by the
committee‘s issue jurisdiction are heard, but they are not permitted to
vote on committee recommendations. Patient representatives are
appointed as SGEs and are usually selected on a meeting-by-meeting
basis for advisory committee meetings that focus on topics specific to
a disease.[Footnote 25] For example, an advisory committee meeting
involving approval of a lung cancer drug might have as its patient
representative a caregiver or an individual with the disease who can
discuss patient concerns.
Temporary Members:
FDA may also select temporary advisory committee members to serve for a
specific advisory committee meeting given the issues or products to be
discussed to provide additional expertise or to ensure that a quorum of
members is present to conduct a meeting.[Footnote 26] Advisory
committee charters for the three centers indicate a maximum number of
temporary members who can serve for a specific meeting, usually no more
than 10 members. Temporary members are usually appointed as SGEs and
are subject to conflict of interest statutes and regulations.[Footnote
27] They may be members of the center‘s consultant pool[Footnote 28] or
members of other FDA advisory committees from the same or a different
FDA center. Federal employees from the Centers for Disease Control and
Prevention (CDC) or NIH, for example, who provide specialized expertise
for a meeting, may also serve as temporary members and are subject to
conflict of interest statutes and regulations.
Federal Conflict of Interest Provisions May Permit Member
Participation:
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[Footnote 29] that would have a
direct and predictable effect on the employee‘s financial interest or
the interests of others specified by law.[Footnote 30] 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.[Footnote 31] 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.[Footnote 32] 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.[Footnote 33] 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.[Footnote 34]
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.[Footnote 35]
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.[Footnote 36] 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.[Footnote 37]
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.
[Footnote 38] 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.[Footnote 39] 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,[Footnote 40]
which may call into question the integrity of FDA‘s programs and
operations.[Footnote 41] (See table 1 for a summary of the four
conflict of interest determinations.)
Table 1: Four Possible Member Conflict of Interest Determinations for
FDA Advisory Committee Meetings Prior to October 1, 2007, Changes:
Type of conflict of interest determination: Statutory waivers:
18 U.S.C. § 208(b)(3) waiver of the criminal financial conflict of
interest specific to SGEs serving on an advisory committee subject to
the Federal Advisory Committee Act;
Criteria for granting conflict of interest determinations to allow
attendance at a meeting or part of a meeting: A committee member‘s
service is needed and outweighs the potential conflict of interest
created by his or her personal or imputed financial interest;
Standing and temporary member types that can receive conflict of
interest determinations, SGEs: [Check];
Standing and temporary member types that can receive conflict of
interest determinations, Other federal employees: [Empty].
Type of conflict of interest determination: Statutory waivers:
18 U.S.C. § 208(b)(1) waiver of the criminal financial conflict of
interest[A];
Criteria for granting conflict of interest determinations to allow
attendance at a meeting or part of a meeting: A committee member‘s
personal or imputed financial interest is not so substantial as to be
deemed likely to affect the integrity of the services which the
government may expect from that member;
Standing and temporary member types that can receive conflict of
interest determinations, SGEs: [Empty];
Standing and temporary member types that can receive conflict of
interest determinations, Other federal employees: [Check][B].
Type of conflict of interest determination: Statutory waivers:
21 U.S.C. § 355(n)(4) waiver of financial conflict of interest
involving drugs and biologics matters[C];
Criteria for granting conflict of interest determinations to allow
attendance at a meeting or part of a meeting: A committee member”or his
or her immediate family”could gain financially from the advice given
but the member‘s voting participation is necessary to provide the
committee with essential expertise;
Standing and temporary member types that can receive conflict of
interest determinations, SGEs: [Check];
Standing and temporary member types that can receive conflict of
interest determinations, Other federal employees: [Check].
Type of conflict of interest determination: Regulatory authorization:
5 C.F.R. § 2635.502 appearance authorization to allow a committee
member to participate when his or her impartiality could be questioned;
Criteria for granting conflict of interest determinations to allow
attendance at a meeting or part of a meeting: A committee member‘s
impartiality involving specific parties meeting could be questioned by
a reasonable person with knowledge of the relevant facts, but the
interests of the government in the member‘s participation outweigh the
concern that a reasonable person may question the integrity of the
agency‘s programs and operations;
Standing and temporary member types that can receive conflict of
interest determinations, SGEs: [Check];
Standing and temporary member types that can receive conflict of
interest determinations, Other federal employees: [Check].
Sources: GAO analysis of applicable conflict of interest statutes and
regulations and FDA information.
Notes: 18 U.S.C. § 208(b)(2) provides for the OGE to exempt certain
financial interests from application of the criminal financial conflict
of interest law. When a committee member's financial interest that
gives rise to the conflict is covered by one of the Office of
Government Ethics' regulatory exemptions, the member can participate
without FDA needing to grant an individual waiver.
[A] Although 18 U.S.C. § 208(b)(1) applies to federal employees
generally, including SGEs and those not employed by FDA who are members
of FDA advisory committees because 18 U.S.C. § 208(b)(3) specifically
authorizes waivers for SGEs serving on FACA committees, FDA applied 18
U.S.C. § 208(b)(3) to SGEs in this context.
[B] The FDA's 18 U.S.C. § 208(b)(1) waivers we analyzed were granted
only to federal employees not employed by FDA.
[C] Prior to October 1, 2007, the 21 U.S.C. § 355(n)(4) waiver applied
only to allowing a committee member to vote on matters related to
clinical investigations and approvals of drugs and biologics, which
generally involved only CBER and CDER advisory committee meetings. On
October 1, 2007, the FDA Amendments Act of 2007 repealed 21 U.S.C §
355(n)(4), but at the same time also created a new provision applying a
similar waiver to all FDA advisory committee members. See Pub. L. No.
110-85, § 701, 121 Stat. 823, 900-04 (pertinent provision codified at
21 U.S.C. § 379d-1(c)(2)(B)).
FDA Conflict of Interest Determination Process:
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.[Footnote 42] 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.[Footnote 43]
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.[Footnote 44] 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,[Footnote 45]
* 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.[Footnote 46]
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.[Footnote 47] 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.[Footnote 48] (See fig.
2.)
Figure 2: Conflict of Interest Determination Process for FDA Advisory
Committee Members: CBER, CDER, and CDRH:
[See PDF for image]
Center finds a member has a conflict of interest and determines the
member‘s expertise is needed.
Center‘s advisory committee management staff prepares a conflict of
interest determination.[A]
Ethics and Integrity Staff (EIS) reviews and concurs or not with the
conflict of interest determination.
Advisory Committee Oversight and Management Staff (ACOMS) reviews the
determination.
FDA Associate Commissioner for Policy and Planning approves or denies
the determination.[B]
Source: GAO interviews with FDA officials.
[A] For our report, FDA conflict of interest determinations are
statutory § 208 and § 355(n) financial interest waivers, and appearance
authorizations as provided for in OGE regulations.
[B] The FDA Associate Commissioner title was changed in August 2007 to
the Deputy Commissioner for Policy.
[End of figure]
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.[Footnote 49] 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.[Footnote 50] In October 2007, FDA announced
draft guidance[Footnote 51] 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,
[Footnote 52] 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.
FDA Used Several Methods to Recruit Candidates for Advisory Committee
Membership and Prescreened Candidates for Potential Conflicts of
Interest:
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.
[Footnote 53] 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 Methods to Recruit Candidates for Advisory
Committee Membership:
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.[Footnote 54]
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.
[Footnote 55] 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 Prescreened Advisory Committee Member Candidates for Potential
Conflicts of Interest:
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.[Footnote 56] 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.
[Footnote 57] 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 Used Many of the Same Recruiting and Prescreening Methods as Those
Employed by Organizations Identified as Having Some Promising
Recruitment and Prescreening Methods:
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.[Footnote 58] 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.
Table 2: Selected Advisory Committee Recruitment Methods of FDA, EPA,
and National Academies Prior to October 1, 2007:
Recruitment methods: Request nominations from professional or specialty
practice societies and organizations related to the advisory
committee‘s general topic;
FDA: [Check];
EPA: [Check];
National Academies: [Check].
Recruitment methods: Ask current advisory committee members for
nominations;
FDA: [Check];
EPA: [Check];
National Academies: [Check].
Recruitment methods: Ask staff within the organization for nominations;
FDA: [Check];
EPA: [Check];
National Academies: [Check].
Recruitment methods: Publish advisory committee vacancies in the
Federal Register;
FDA: [Check];
EPA: [Check];
National Academies: [Empty].
Recruitment methods: Has brochure explaining advisory committee
membership;
FDA: [Check];
EPA: [Check];
National Academies: [Check].
Recruitment methods: Post recruitment information on organization‘s Web
site;
FDA: [Check];
EPA: [Check];
National Academies: [Check].
Recruitment methods: Enable people to nominate candidates and to self-
nominate directly through an electronic form on the organization‘s Web
site;
FDA: [Empty];
EPA: [Check];
National Academies: [Empty].
Note: Represents the recruitment methods FDA employed prior to the
implementation of the FDA Amendments Act of 2007. FDA still uses these
recruitment methods; however, the FDA Amendments Act of 2007 provides
additional recruitment methods that FDA may employ.
Sources: GAO analysis of FDA, EPA, and National Academies staff
interviews, and GAO-04-328.
[End of table]
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.[Footnote 59] 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.[Footnote 60]
Table 3: Selected Advisory Committee Prescreening Methods of FDA, EPA,
and National Academies Prior to October 1, 2007:
Prescreening methods: Review curriculum vitae or summaries of related
professional experience;
FDA: [Check];
EPA: [Check];
National Academies: [Check].
Prescreening methods: Interview candidates about financial interests
and activities;
FDA: [Check];
EPA: [Check];
National Academies: [Empty].
Prescreening methods: Post a sample financial disclosure information
form on the organization‘s Web site;
FDA: [Check];
EPA: [Check];
National Academies: [Check].
Prescreening methods: Ask candidates to complete the organization‘s
official financial disclosure form prior to being selected as a
committee member;
FDA: [Empty];
EPA: [Check];
National Academies: [Check].
Prescreening methods: Post a provisional advisory committee member list
on the organization‘s Web site for public comment on possible conflicts
of interest;
FDA: [Empty];
EPA: [Check][A];
National Academies: [Check];
Sources: GAO analysis of FDA, EPA, and National Academies staff
interviews, and [hyperlink, http://www.gao.gov/cgi-bin/getrpt?GAO-04-
328].
Notes: As of October 1, 2007, candidates for FDA advisory committees
were required to complete an official financial disclosure form that
provides information about the individual's financial interest prior to
being appointed as an advisory committee member. These methods
represent the prescreening methods FDA employed prior to the issuance
of the implementation of the FDA Amendments Act of 2007; FDA still uses
these prescreening methods.
[A] EPA's Science Advisory Board publishes the names and biographical
sketches of candidates on its Web site to obtain public comments on
proposed candidates.
[End of table]
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.
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:
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.)
Barriers Existed to Recruiting Qualified Individuals to Serve on FDA
Advisory Committees:
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.
The Experts FDA Sought to Serve on Its Advisory Committees Frequently
Had Industry Ties:
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.
FDA's Most Effective Recruitment Method Had Limitations:
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 Deterred
Potential Members:
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[Footnote 61]. 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.[Footnote 62]
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 Been Able to Mitigate Barriers by Expanding Outreach
Efforts:
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.[Footnote 63] 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.[Footnote 64] According to these
consumer interest group representatives, the agency‘s advisory
committees are overly weighted towards clinicians and clinical
trialists.[Footnote 65] 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.
[Footnote 66] 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.[Footnote 67] The FDA Amendments Act of 2007 modifies FDA‘s
process for prescreening candidates for advisory committee membership.
(See app. I.)
Most Advisory Committee Meeting Participants Were Standing Members, and
Many Members Had Conflict of Interest Determinations:
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.
[Footnote 68] 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.[Footnote 69] 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.
Most Advisory Committee Meeting Participants Were Standing Members:
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.
Table 4: Standing and Temporary Member Totals for 83 FDA Advisory
Committee Meetings by Center, 2004 and 2006:
FDA center: CBER; There were 22 advisory committee meetings; 11 in 2004
and 11 in 2006;
2004, Standing members: 58% (96);
2004, Temporary members: 42% (70);
2004, Total members[A]: 100% (166);
2006, Standing members: 70% (122);
2006, Temporary members: 30% (52);
2006, Total members[A]: 100% (174).
FDA center: CDER; There were 31 advisory committee meetings; 14 in 2004
and 17 in 2006;
2004, Standing members: 61% (137);
2004, Temporary members: 39% (86);
2004, Total members[A]: 100% (223);
2006, Standing members: 52% (137);
2006, Temporary members: 48% (125);
2006, Total members[A]: 100% (262).
FDA center: CDRH; There were 30 advisory committee meetings; 17 in 2004
and 13 in 2006;
2004, Standing members: 55% (127);
2004, Temporary members: 45% (103);
2004, Total members[A]: 100% (230);
2006, Standing members: 56% (92);
2006, Temporary members: 44% (71);
2006, Total members[A]: 100% (163).
FDA center: Total (percentage averages); There were a total of 83
advisory committee meetings; 42 in 2004 and 41 in 2006, with 1,218
members;
2004, Standing members: 58%;
2004, Temporary members: 42%;
2004, Total members[A]: 100% (619);
2006, Standing members: 59%;
2006, Temporary members: 41%;
2006, Total members[A]: 100% (599).
Source: GAO analysis of FDA's CBER, CDER, and CDRH advisory committee
meeting records for 2004 and 2006.
Note: All CBER, CDER, and CDRH advisory committee meetings held in 2004
and 2006 are included except joint advisory committee meetings and
advisory committee subcommittee meetings. CDER and CDRH held 10 joint
meetings in 2004 and 2006 and temporary members made up less than one-
third of the combined standing and temporary member total for those
meetings in both years.
[A] Represents the total number of standing and temporary members who
attended each advisory committee meeting, so individual members may be
counted more than once.
[End of table]
At Least One Standing or Temporary Member Had a Conflict of Interest
Determination in over Half of the Advisory Committee Meetings:
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.[Footnote 70] 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).
Table 5: Type and Number of Conflict of Interest Determinations for 200
Standing and Temporary Members for 49 Selected CBER, CDER, and CDRH
Advisory Committee Meetings, 2004 and 2006:
Type of conflict of interest determination: Statutory waivers:
Financial interest waiver”special government employee (§ 208(b)(3));
2004 and 2006, Standing member: 104;
2004 and 2006, Temporary member: 51;
Total determinations: 155.
Type of conflict of interest determination: Statutory waivers:
Financial interest waiver”involving drugs and biologics topics (§
355(n)(4))[A];
2004 and 2006, Standing member: 15;
2004 and 2006, Temporary member: 12;
Total determinations: 27.
Type of conflict of interest determination: Statutory waivers:
Financial interest waiver”federal government employee (§ 208(b)(1))[B];
2004 and 2006, Standing member: 4;
2004 and 2006, Temporary member: 5;
Total determinations: 9.
Type of conflict of interest determination: Statutory waivers:
2004 and 2006, Standing member:
2004 and 2006, Temporary member:
Total determinations:
Type of conflict of interest determination: Regulatory authorization:
Appearance authorization (§ 2635.502);
2004 and 2006, Standing member: 23;
2004 and 2006, Temporary member: 20;
Total determinations: 43.
Type of conflict of interest determination: Total;
2004 and 2006, Standing member: 146;
2004 and 2006, Temporary member: 88;
Total determinations: 234.
Source: GAO analysis of FDA CBER, CDER, CDRH advisory committee meeting
records for 2004 and 2006.
Notes: For all three centers, the advisory committee meetings chosen
were those with (1) the advisory committee meeting designation most
often used by the center's advisory committees--for CDER and CDRH,
specific-parties meetings and for CBER, non-specific party meetings,
and (2) at least one standing or temporary member who received a
conflict of interest determination. For all three centers, if a meeting
had 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. A participant
may have been granted more than one conflict of interest determination,
for example, an individual may have had both a § 208(b)(1) waiver and
an appearance authorization.
[A] Prior to October 1, 2007, the 21 U.S.C. § 355(n)(4) waiver applied
only to voting on topics related to clinical investigations and
approvals of drugs and biologics, which generally involved only CBER
and CDER advisory committee meetings.
[B] The FDA 18 U.S.C. § 208(b)(1) waivers we analyzed were granted only
to federal employees not employed by FDA. Although 18 U.S.C. §
208(b)(1) applies to federal employees generally including SGEs and
those not employed by FDA who are members of FDA advisory committees,
because 18 U.S.C. § 208(b)(3) specifically authorizes waivers for SGEs
serving on FACA committees, FDA applied 18 U.S.C. § 208(b)(3) to SGEs
in this context.
[End of table]
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.[Footnote 71] 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)[Footnote
72]--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.
Agency Comments and Our Evaluation:
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 [hyperlink, 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.
Signed by:
Marcia Crosse:
Director, Health Care:
[End of section]
Appendix I: Major 2007 Actions Affecting FDA Recruiting and Conflict of
Interest Determination Processes:
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[Footnote 73]--and FDA's draft March 2007 conflict of
interest guidance.[Footnote 74]
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.[Footnote 75]
[End of section]
Appendix II: Scope and Methodology:
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.[Footnote 76] 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.[Footnote 77] 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.[Footnote 78] 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,[Footnote 79] 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.[Footnote 80] 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.[Footnote 81]
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,[Footnote 82] acknowledgement and
consent for disclosure of potential conflicts of interest forms,
[Footnote 83] and appearance authorization memorandums.[Footnote 84]
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.
[End of section]
Appendix III: Factors That May Affect FDA Advisory Committee Meeting
Recommendations:
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.
[Footnote 85] 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[Footnote 86] 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.
Pre-Advisory Committee Meeting Decisions:
* 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.[Footnote 87] 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.
Advisory Committee Meeting Decisions:
* 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.[Footnote 88] 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.[Footnote 89]
* 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.[Footnote 90]
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.
[Footnote 91]
* Homework assignments: FDA may also select advisory committee members
and other experts to conduct homework assignments,[Footnote 92] 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.[Footnote 93] 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.[Footnote 94] 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.[Footnote 95] 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.
Advisory Committee Meeting Conflict of Interest Determinations:
* 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.[Footnote 96] 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.
Recommendations from the Advisory Committee Meeting:
* 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 on FDA Advisory Committee Meeting 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:[Footnote 97] 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:[Footnote
98] 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."[Footnote 99] 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."[Footnote
100] 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.[Footnote 101]
* FDA's 2007 study:[Footnote 102] 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.
[End of section]
Appendix IV: FDA Advisory Committees for the Three Centers Analyzed:
Center for Biologics Evaluation and Research:
* Allergenic Products Advisory Committee:
* Blood Products Advisory Committee:
* Cellular, Tissue and Gene Therapies Advisory Committee:
* Transmissible Spongiform Encephalopathies Advisory Committee:
* Vaccines and Related Biological Products Advisory Committee:
Center for Drug Evaluation and Research:
* Anesthetic and Life Support Drugs Advisory Committee:
* Anti-Infective Drugs Advisory Committee:
* Antiviral Drugs Advisory Committee:
* Arthritis Advisory Committee:
* Cardiovascular and Renal Drugs Advisory Committee:
* Dermatologic and Ophthalmic Drugs Advisory Committee:
* Drug Safety and Risk Management Advisory Committee:
* Endocrinologic and Metabolic Drugs Advisory Committee:
* Gastrointestinal Drugs Advisory Committee:
* Nonprescription Drugs Advisory Committee:
* Oncologic Drugs Advisory Committee:
* Peripheral and Central Nervous System Drugs Advisory Committee:
* Pharmaceutical Science and Clinical Pharmacology Advisory Committee:
* Psychopharmacologic Drugs Advisory Committee:
* Pulmonary-Allergy Drugs Advisory Committee:
* Reproductive Health Drugs Advisory Committee:
Center for Devices and Radiological Health:
* Device Good Manufacturing Practice Advisory Committee:
* Medical Devices Advisory Committee[Footnote 103]
- Anesthesiology and Respiratory Therapy Devices Panel:
- Circulatory System Devices Panel:
- Clinical Chemistry and Clinical Toxicology Devices Panel:
- Dental Products Panel:
- Ear, Nose, and Throat Devices Panel:
- Gastroenterology-Urology Devices Panel:
- General and Plastic Surgery Devices Panel:
- General Hospital and Personal Use Devices Panel:
- Hematology and Pathology Devices Panel:
- Immunology Devices Panel:
- Medical Devices Dispute Resolution Panel:
- Microbiology Devices Panel:
- Molecular and Clinical Genetics Panel:
- Neurological Devices Panel:
- Obstetrics-Gynecology Devices Panel:
- Ophthalmic Devices Panel:
- Orthopaedic and Rehabilitation Devices Panel:
- Radiological Devices Panel:
* National Mammography Quality Assurance Advisory Committee:
* Technical Electronic Product Radiation Safety Standards Committee:
[Footnote 104]
[End of section]
Appendix V: Comments from the Department of Health and Human Services:
Department Of Health and Human Services:
Office Of The Secretary:
Assistant Secretary for Legislation:
Washington, DC 20201
August 28, 2008:
Marcia Crosse:
Director, Health Care:
U.S. Government Accountability Office:
441 G Street NW:
Washington, D.C. 20548:
Dear Ms. Crosse:
Enclosed are the Department's comments on the U.S. Government
Accountability Office's (GAO) draft report entitled, "FDA Advisory
Committees: Process for Recruiting Members and Evaluating Potential
Conflicts of Interest" (GAO-08-640).
The Department appreciates the opportunity to comment on this draft
before its publication.
Sincerely,
Signed by:
Jennifer R. Luong:
for: Vincent J. Ventimiglia, Jr.
Assistant Secretary for Legislation:
Attachment:
Comments Of The Department Of Health And Human Services (HHS) On The
U.S. Government Accountability Office's (GAO) Draft Report Entitled,
"FDA Advisory Committees: Process For Recruiting Members And Evaluating
Potential Conflicts Of Interest" (GAO-08-640):
The Food and Drug Administration (FDA) appreciates the opportunity to
review and comment on the Government Accountability Office's (GAO)
draft report. As the report acknowledges, during the time period
covered by the report, FDA has issued new guidance to determine
eligibility for participation of advisory committee members with
potential conflicts of interest. The new guidance establishes a more
stringent policy to limit waivers of conflict of interest beyond the
requirements in the applicable law. We have made a number of additional
improvements to our advisory committee process that are not described
in the report -- including final guidance on public disclosure of
advisory committee members' financial information and waivers, final
guidance on voting procedures, final guidance on availability of
briefing materials, draft guidance on criteria for when to hold an
advisory committee meeting, and website improvements. These actions
occurred during the period of the report. We expect these new policies
to further strengthen public confidence in the integrity of FDA's
advisory committees.
We have a number of general comments on the report, as described below.
Scope:
The GAO report is based on data from CBER, CDER, and CDRH advisory
committee meetings held in 2004 and 2006. We suggest that the findings
in the report be clearly identified as limited in applicability to
CBER, CDER, and CDRH committees.
Recruitment efforts:
The GAO report suggests that FDA may have been able to mitigate
acknowledged bathers to recruiting qualified advisory committee
candidates without potential conflicts of interest.
1. An additional variable that is not discussed in the report is FDA's
efforts, consistent with FACA, to achieve gender, ethnic, and
geographic balance. FDA strives for members from across the United
States and for individuals who are as diverse as the United States. In
addition, we strive for diversity in points of view to facilitate
thorough discussions of all sides of the issues. These efforts may
limit the pool of experts for recruiting.
2. The GAO report suggests that FDA could have expanded its recruitment
efforts to "experts from college and universities." We note that
individuals from academia make up the bulk of the standing members and
temporary voting members that serve on our committees. These sources
are clearly not without potential conflicts of interest, as the
financial interests of the academic institution employing such experts
are imputed to the member under the laws that we must apply.
3. The GAO report suggests that FDA expand outreach to "individuals
with epidemiological and statistical expertise". We have not found that
any one particular biomedical specialty reliably yields lower conflict
of interest issues. We have found that our statisticians and
epidemiologists are as likely to have significant conflicts of
interests as other special government employees (SGEs) because they are
as likely to be involved in medical/pharmaceutical research as other
specialists.
4. The GAO report also identifies retired experts as a possible source
of conflict-free members. FDA has concerns, as noted on page 37 of the
report, that many retired individuals may not have remained current
with rapidly evolving technologies. In addition, it has been our
experience that retired experts often have large pharmaceutical stock
portfolios and, if still active in their field, may be actively
involved in pharmaceutical consulting - both of which are potential
conflicts of interest.
5. In the report, GAO compared methods used by EPA and the National
Academies to FDA methods. We believe that extrapolating findings from
experts in one industry to another should be done cautiously. Companies
that develop new drugs and devices naturally seek the best scientific
expertise to help develop such products and the experts experienced
with such product development consequently have unique insights that
can greatly benefit the FDA. As a result, many scientists with
expertise and knowledge of FDA-regulated products have financial ties
to the pharmaceutical industry. The FDA has an additional burden that
neither the EPA nor the National Academies deal with - the timelines
within the Prescription Drug User Fee Act (PDUFA) and within the
Medical Device User Fee Modernization Act. For example, PDUFA sets time
limits within which FDA must decide the fate of a particular New Drug
Application or supplement. This means that the FDA must strive to
locate not only a qualified minimally conflicted SGE within a certain
period of time, but also one that is available to serve on the
committee at the time it must meet.
Use of term "conflict of interest determinations:"
The GAO report defines the term "conflict of interest determinations"
to include both (1) waivers of the statutory conflict of interest
prohibitions and (2) determinations that the agency may make under 5
CFR 2645.502 concluding that a reasonable person with knowledge of the
relevant facts would not question the impartiality of the individual.
We believe that combining these two very different determinations in
one term is confusing and misleading. A waiver or exception is
granted only after determining that a potential conflict of interest
exists but that the statutory standard for a waiver can be met. If
there is a potential conflict of interest, FDA may not authorize the
individual's participation under the provisions of 5 CFR 2645.502 but
must instead apply the statutory criteria for waivers.
In contrast, an impartiality determination may be made when the
statutory prohibition on participation does not apply but the
individual or FDA has asked for a review of whether his participation
would create an appearance of a conflict. In those cases where FDA has
issued an impartiality determination, the agency has concluded that a
reasonable person with knowledge of the relevant facts would not
question the impartiality of the individual or has authorized the
employee to participate because the interest of the Government in the
employee's participation outweighs the concern that a reasonable person
may question the integrity of the agency's programs and operations.
We note that the report in several instances inaccurately uses the term
"conflict of interest determination" when "waiver or exception" should
be used. We have identified these instances in FDA's technical comments
that accompany these general comments.
[End of section]
Appendix VI: GAO Contact and Staff Acknowledgments:
GAO Contact:
Marcia Crosse, (202) 512-7114 or crossem@gao.gov:
Acknowledgments:
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.
[End of section]
Related GAO Products:
Federal Advisory Committee Act: Issues Related to the Independence and
Balance of Advisory Committees. [hyperlink, http://www.gao.gov/cgi-
bin/getrpt?GAO-08-611T]. Washington, D.C.: April 2, 2008.
Drug Safety: Further Actions Needed to Improve FDA's Postmarket
Decision-making Process. [hyperlink, http://www.gao.gov/cgi-
bin/getrpt?GAO-07-856T]. Washington, D.C.: May 9, 2007.
NIH Conflict of Interest: Recusal Policies for Senior Employees Need
Clarification. [hyperlink, http://www.gao.gov/cgi-bin/getrpt?GAO-07-
319]. Washington, D.C.: April 30, 2007.
Drug Safety: FDA Needs to Further Address Shortcomings in Its
Postmarket Decision-making Process. [hyperlink, http://www.gao.gov/cgi-
bin/getrpt?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. [hyperlink,
http://www.gao.gov/cgi-bin/getrpt?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.
[hyperlink, http://www.gao.gov/cgi-bin/getrpt?GAO-05-191]. Washington,
D.C.: February 25, 2005.
Federal Advisory Committees: Additional Guidance Could Help Agencies
Better Ensure Independence and Balance. [hyperlink,
http://www.gao.gov/cgi-bin/getrpt?GAO-04-328]. Washington, D.C.: April
16, 2004.
University Research: Most Federal Agencies Need to Better Protect
against Financial Conflicts of Interest. [hyperlink,
http://www.gao.gov/cgi-bin/getrpt?GAO-04-31]. Washington, D.C.:
November 14, 2003.
[End of section]
Footnotes:
[1] Standing members are individuals appointed to serve on an FDA
advisory committee and are part of the official advisory committee
roster of authorized membership. Temporary members are individuals that
FDA selects to serve for a specific advisory committee meeting to
provide additional expertise or to ensure that a quorum of members is
present to conduct a meeting.
[2] In this report, we use the term conflict of interest waivers to
refer to FDA's decision to allow an individual with a financial
conflict of interest to participate in an advisory committee meeting as
provided by statute. We use the term appearance authorization to refer
to FDA's decision to authorize an individual to participate in an
advisory committee meeting, as provided for in regulations issued by
the Office of Government Ethics (OGE), when the individual's
impartiality could be questioned.
[3] FDA uses the term prescreen to define the initial process of
evaluating an individual's financial interests to determine whether
that person has potential conflicts of interest prior to nominating him
or her for advisory committee membership. FDA uses the term screen to
define the process of evaluating advisory committee members' financial
interests prior to a committee meeting to determine whether they have
conflicts of interest based on the advisory committee meeting topic.
[4] FDA is an agency within HHS and is subject to HHS's advisory
committee regulations, policies, and guidances.
[5] The National Academies consist of four private, nonprofit
organizations that advise the federal government on scientific and
technical matters: the National Academy of Sciences, the National
Academy of Engineering, the Institute of Medicine, and the National
Research Council.
[6] In 2004, we reviewed the role of federal advisory committees in the
development of national policies. We identified EPA and the National
Academies as employing three specific recruitment and prescreening
methods that could achieve independent and balanced advisory
committees. The methods included (1) obtaining nominations for
committee members from the public, (2) using clearly defined processes
to screen for conflicts of interest, such as requesting public comment
on proposed committee membership, and (3) prescreening prospective
members using structured interviews. See GAO, Federal Advisory
Committees: Additional Guidance Could Help Agencies Better Ensure
Independence and Balance, [hyperlink, http://www.gao.gov/cgi-
bin/getrpt?GAO-04-328] (Washington, D.C.: Apr. 16, 2004).
[7] The Web site posting was required by the Agriculture, Rural
Development, Food and Drug Administration, and Related Agencies
Appropriations Act for fiscal year 2006 and continued through fiscal
year 2007. In August 2008, FDA issued a final Guidance for the Public,
FDA Advisory Committee Members, and FDA Staff: Public Availability of
Advisory Committees Members' Financial Interest Information and Waivers
(Rockville, Md.: August 2008). [hyperlink,
http://www.fda.gov/oc/advisory/GuidancePolicyRegs/ACDisclosureFINAL]
Guidance080408.pdf (accessed Aug. 5, 2008).
[8] FDA, 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 (Rockville,
Md.: March 2007) [hyperlink,
http://www.fda.gov/oc/advisory/waiver/COIguidedft.html] (accessed Mar.
18, 2007). This guidance states that it represents FDA's current
thinking on the topic and does not bind FDA or the public. FDA
finalized the draft guidance August 2008, [hyperlink,
http://www.fda.gov/oc/advisory/GuidancePolicyRegs/ACWaiverCriteriaFINALG
uidance080408.pdf] (accessed Aug. 5, 2008). Even after a guidance is
finalized, FDA staff may use an alternative approach if the approach
satisfies the requirements of the applicable statutes and regulations.
[9] See the Food and Drug Administration Amendments Act of 2007 (FDA
Amendments Act of 2007), Pub. L. No. 110-85, § 701, 121 Stat. 823, 900-
04 (adding § 712 to the Federal, Food, Drug, and Cosmetic Act)
(codified at 21 U.S.C. § 379d-1).
[10] The four final guidances are 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; Guidance for FDA Advisory Committee Members and FDA Staff:
Voting Procedures for Advisory Committee Meetings; Guidance for the
Public, FDA Advisory Committee Members, and FDA Staff: Public
Availability of Advisory Committee Members' Financial Interest
Information and Waivers; and Guidance for Industry Advisory Committee
Meetings--Preparation and Public Availability of Information Given to
Advisory Committee Members.
[11] 5 U.S.C. app. § 5(b)(2). An FDA official told us that it also
seeks to achieve gender, ethnic, and geographic balance.
[12] All federal advisory committees subject to FACA must have a
charter, although the law does not require the charter to specify the
number of committee members or their expertise. See 5 U.S.C. app. §
9(c). An FDA advisory committee charter also provides the committee's
legal authority and structure, committee meeting frequency and member
compensation, annual cost estimate and reports, and committee
termination. Under FACA, FDA advisory committees terminate every 2
years unless renewed, or the legislation authorizing an advisory
committee specifies a different period of time. See 5 U.S.C. app. § 14.
CDRH's Medical Devices Advisory Committee (MDAC) and its 18 panels is,
by statute, not subject to a renewal review. See 21 U.S.C. §
360c(b)(1).
[13] Advisory committees may meet in closed sessions to permit
discussion of trade secrets, commercial, or financial information
obtained from a person that is privileged or confidential, or
information of a personal nature where disclosure would constitute a
clearly unwarranted invasion of personal privacy. 5 U.S.C. § 552b(c).
[14] For this report, we refer to a "potential conflict of interest"
when discussing FDA's review of a member's financial interests for
possible conflicts of interest prior to granting a waiver or an
appearance authorization.
[15] In November 2007, FDA published a draft guidance that recommends
uniform voting procedures that can be used during advisory committee
meetings. See FDA, Draft Guidance for FDA Advisory Committee Members
and FDA Staff: Voting Procedures for Advisory Committee Meetings
(Rockville, Md.: November 2007), [hyperlink,
http://www.fda.gov/oc/advisory/VotingGuidance.html] (accessed Jan. 29,
2008). FDA finalized the draft guidance August 2008, [hyperlink,
http://www.fda.gov/oc/advisory/GuidancePolicyRegs/ACVotingFINALGuidance0
80408.pdf] (accessed Aug. 5, 2008).
[16] Six other FDA advisory committees are located in the Center for
Food Safety and Applied Nutrition (1), the Center for Veterinary
Medicine (1), the National Center for Toxicological Research (1), and
the Office of the Commissioner (3). The Risk Communication Advisory
Committee, established in May 2007, is one of the three advisory
committees located in the FDA Office of the Commissioner.
[17] Although CDRH has four advisory committees, its MDAC is the
umbrella title for 18 statutorily-created advisory panels whose members
are subject to the same legal and regulatory requirements as other FDA
advisory committees. FDA counts MDAC and its 18 panels as one advisory
committee. For our analysis, we treated MDAC's 18 panels' meetings as
individual advisory committee meetings.
[18] According to an FDA official, FDA does not consider subcommittee
meetings to be advisory committee meetings subject to FACA because a
subcommittee provides advice to the committee rather than to FDA. This
interpretation is in accordance with the FACA regulations issued by the
General Services Administration. See 41 C.F.R. § 102-3.35 (2006).
[19] FACA requires agencies to designate a federal officer or employee-
-the designated federal official--to chair or attend every meeting of
each advisory committee the agencies convene. Committee meetings may
not be held without the advance approval of the designated official.
See 5 U.S.C. app., § 10(e), (f).
[20] An SGE is statutorily defined as an officer or employee who is
retained, designated, appointed, or employed by the government to
perform temporary duties, with or without compensation, for not more
than 130 days during any period of 365 consecutive days. See 18 U.S.C.
§ 202(a). In general, FDA compensates advisory committee members who
are SGEs for their service, reimburses them for travel, and pays them
an amount for per diem expenses.
[21] FDA advisory committee members who are federal employees employed
by other agencies do not receive additional compensation for their
service on an FDA advisory committee.
[22] There are circumstances when a standing member may be allowed to
serve beyond their 4-year membership term including, for example, if a
member in the fourth year of his or her term is selected to serve as
the committee‘s chair and a special request is granted by HHS. A member
may also serve less than 4 years; for example, if a member resigned in
the second year of the term, the new member could serve the remaining 2
years.
[23] Consumer representative members on CDRH MDAC panels are by statute
to serve as nonvoting members. See 21 U.S.C. § 360c(b)(2).
[24] In this report, when we discuss conflict of interest for committee
members we are not including industry representatives.
[25] CBER, CDER, and CDRH are required to have a patient representative
serve on all their cancer-related advisory committees. These
representatives are voting members for CBER and CDER committees, and
nonvoting for CDRH committees.
[26] Although the general rule is that a meeting quorum consists of the
majority of current advisory committee members, FDA advisory committee
charters may allow a committee to meet with less than a majority of its
members for a specific meeting. See 21 C.F.R. § 14.22(d) (2007).
[27] Industry representatives, whether they are temporary or standing
members, are not SGEs.
[28] FDA officials told us that centers‘ consultant pools are lists of
individuals who FDA has determined have expertise that may be needed in
the future for a specific advisory committee meeting and usually have
current SGE appointments. FDA officials also told us that consultants
may be former FDA advisory committee members.
[29] A ’particular matter“ is a matter involving ’deliberation,
decision, or action that is focused upon the interest of specific
persons, or a discrete and identifiable class of persons.“ 5 C.F.R. §
2640.103(a)(1).
[30] See 18 U.S.C. § 208. According to FDA, its advisory committee
meetings generally involve either (1) particular matters involving
specific parties”typically the consideration of a specific company‘s
drug or medical device”which we refer to as a ’specific-parties“ topic;
or (2) particular matters of general applicability”consideration of
issues that affect a class of person, not specific parties, such as
clinical trials for a class of drugs”which we refer to as a ’non-
specific party“ topic. See 5 C.F.R. § 2410.102(l),(m). In addition, FDA
advisory committee meetings may have topics that are non-particular
matters”not subject to 18 U.S.C. § 208”typically involving
consideration of recommendations on broad policy options that are
directed to the interest of a large and diverse group of persons.
[31] Because FDA officials determine whether an advisory committee
meeting may create a conflict of interest by first reviewing the topic
or topics to be discussed, throughout this report we use the term topic
instead of the term particular matter as used in the statute.
[32] See 18 U.S.C. § 208(b)(3).
[33] See 18 U.S.C. § 208(b)(1).
[34] If an advisory committee meeting has more than one topic”such as
both specific-parties and non-specific party topics”FDA may issue a
conflict of interest waiver to limit the member from voting or
participating in the discussion of one, while allowing the member to
discuss and vote on the other.
[35] See 18 U.S.C. § 208(b)(2). These regulatory exemptions are based
on a determination by OGE that the interests involved are too remote or
inconsequential to affect the integrity of the government employee‘s
services. See 5 C.F.R. pt. 2640. For example, under the de minimus
exception to the application of the law, an advisory committee member
can participate in a committee meeting despite owning stock in a
company involved in the matter before the committee, if the stock has a
market value of less than $15,000. See 5 C.F.R. § 2640.202(a).
[36] See Food and Drug Administration Modernization Act of 1997, Pub.
L. No. 105-115, § 120, 111 Stat. 2296, 2318-20 (amending § 505 of the
Federal Food, Drug, and Cosmetic Act and codified at 21 U.S.C. §
355(n)). The member must publicly disclose these conflicts”the
financial interests upon which the waiver is based. FDA refers to these
waivers as § 355(n)(4) or § 505 waivers; in this report we use §
355(n)(4). Although the § 355(n)(4) waivers generally were applied to
CBER or CDER advisory committee meetings, an FDA official told us that
it is possible there were historically some issued for other centers‘
meetings, for example, if CDRH had a joint meeting that involved the
consideration of drugs or biologics. The FDA Amendments Act of 2007
repealed the § 355(n)(4) waiver provision, and added a new
provision”referred to as a § 712(c)(2)(B) waiver”which applied the
prohibition to all FDA advisory committee meetings. See Pub. L. No. 110-
85, § 701, 121 Stat. 823, 900-04 (pertinent provision codified at 21
U.S.C. § 379d-1(c)(2)(B)).
[37] In March 2007, FDA issued a draft guidance to generally not grant
committee members with financial conflicts of interest exceeding
$50,000 waivers to participate in an advisory committee meeting. The
FDA Amendments Act of 2007 also requires FDA to reduce the percentage
of waivers”§ 208 and § 712”granted by 25 percent over 5 years, starting
in fiscal year 2008.
[38] See 5 C.F.R. § 2635.502.
[39] These relationships would include a person who is a member of the
committee member‘s household and any person for whom the committee
member has served within the past year as a consultant, contractor, or
employee. See 5 C.F.R. § 2635.502(b)(1).
[40] See 5 C.F.R. § 2635.502(a).
[41] See 5 C.F.R. § 2635.502(d).
[42] The FDA Waiver Criteria 2000 guidance is titled FDA Guidance on
Conflict of Interest for Advisory Committee Members, Consultants, and
Experts (February 2000). The 2000 guidance is replaced by FDA‘s August
2008 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.
[43] We were told by an FDA official that in some cases, FDA centers
use OGE Form 450--generally used for annual confidential reporting of
financial interests by certain federal employees--in lieu of FDA Form
3410.
[44] An analysis memorandum--an internal FDA document--is prepared by
FDA staff for a specific advisory committee meeting. Among other
things, the analysis memorandum may indicate which members attending
have conflict of interest waivers, which qualify for an exemption from
the conflict of interest law, as provided for in regulations issued by
OGE, which reported interests or involvement not requiring a conflict
of interest determination, and which have been excluded from
participating in part or all of the meeting because of a conflict of
interest that FDA decides does not qualify for a conflict of interest
determination.
[45] Advisory committee members may decide they have a conflict of
interest and recuse or disqualify themselves from participating in all
or part of a meeting. We were told by CDER ACS staff that ACS began
tracking members' self recusals in 2006 because CDER is often asked why
members do not participate in some committee meetings.
[46] Conflict of interest waivers can limit a member's participation
and voting in a meeting. A member may, for example, be permitted to
participate in a meeting's discussions but not vote, or participate in
discussions involving certain topics and only vote on those topics and
vote only on certain matters.
[47] EIS typically works with the director of a center's advisory
committee management staff to provide advice on conflict of interest
determinations and to review proposed conflict of interest waivers.
[48] As of August 30, 2007, FDA changed this position title to Deputy
Commissioner for Policy.
[49] The Web site posting was required by the Agriculture, Rural
Development, Food and Drug Administration, and Related Agencies
Appropriations Act for fiscal year 2006. Pub. L. No. 109-97, § 795, 119
Stat. 2120, 2164-65. This requirement was continued through fiscal year
2007. Continuing Appropriations Resolution, 2007, Pub. L. No. 109-289,
division B, §§ 101(a) and 106(3), 120 Stat. 1257, 1311, 1313 (2006), as
amended by: Pub. L. No. 109-369, 120 Stat. 2642 (2006); Pub. L. No. 109-
383, § 1, 120 Stat. 2678 (2006); and Pub. L. No. 110-5, § 101, 121
Stat. 8 (2007). Waivers posted on the Web site may have had information
redacted; for example, the name of a drug company in which an
individual owns stock may be redacted. Appearance authorizations are
not required to be publicly disclosed. The statute--18 U.S.C. § 208(d)-
-provides for the disclosure of waiver information for § 208(b)(1) and
(b)(3) waivers upon request but allows federal agencies to redact any
information that would be exempt under the Freedom of Information Act,
such as an advisory committee member's confidential financial
information.
[50] Pub. L. No. 110-85, § 701, 121 Stat. 900-04 (pertinent provision
codified at 21 U.S.C. § 379d-1(c)(3)).
[51] FDA, Draft Guidance for the Public, FDA Advisory Committee
Members, and FDA Staff: Public Availability of Advisory Committee
Members' Financial Interest Information and Waivers [hyperlink,
http://www.fda.gov/oc/advisory/waiver/ACdisclosure1007.html] (accessed
Mar. 18, 2007). FDA finalized the draft guidance August 2008.
[52] Appearance authorizations and their grounds are not required to be
publicly disclosed.
[53] The FDA Amendments Act of 2007 allows FDA to develop a new
recruitment method through which an entity receiving funding from NIH,
the Agency for Healthcare Research and Quality, the CDC, or the
Veterans Health Administration can identify a person whom FDA can
contact regarding the nomination of individuals to serve on advisory
committees. Pub. L. No. 110-85, § 701, 121 Stat. 900-04 (pertinent
provision codified at 21 U.S.C. § 379d-1(b)(1)(B)).
[54] Most of this information was available on the Web site prior to
the revision. The revised Web site provides a link to the e-mail
address to submit individual nominations and self nominations.
[55] A group of interested consumer organizations, commonly referred to
as the consumer nominating group, assists FDA with recruiting,
interviewing, and assessing potential candidates to serve as voting and
nonvoting consumer representatives. When there is a vacancy for an
industry representative on an advisory committee, FDA publishes a
notice in the Federal Register requesting that industry organizations
send a letter stating their interest in nominating an industry
representative. FDA instructs that representatives from the interested
industry organizations consult with each other and select an industry
representative candidate for each vacancy. See 21 C.F.R. § 14.84(d)
(2007).
[56] The FDA Amendments Act of 2007 requires that an individual‘s
expertise and financial disclosure report filed in accordance with the
Ethics in Government Act of 1978 be reviewed when considering a term
appointment to an advisory committee. Pub. L. No. 110-85, § 701, 121
Stat. 900-04 (pertinent provision codified at 21 U.S.C. § 379d-
1(b)(2)).
[57] FDA‘s prescreening form is the Prospective Special Government
Employee Personal Data Sheet”Preliminary Informal Interview (FDA Form
2725a).
[58] GAO, Federal Advisory Committees: Additional Guidance Could Help
Agencies Better Ensure Independence and Balance, [hyperlink,
http://www.gao.gov/cgi-bin/getrpt?GAO-04-328] (Washington, D.C.: Apr.
16, 2004).
[59] EPA officials told us that candidates complete EPA Form 3110-48.
National Academies officials told us that provisional study committee
members fill out financial disclosure Form BI/COI (Background
Information/Conflicts of Interest) Forms 1, 2, or 3, depending upon the
type of study on which they will work.
[60] As of October 1, 2007, candidates for FDA advisory committees are
required to complete the OGE Form 450 or FDA Form 3410”financial
disclosure reports that provide information about the individual‘s
financial interest”prior to being appointed as an FDA advisory
committee member.
[61] National Academies, EPA, and NIH officials we interviewed did not
believe that their organizations‘ financial disclosure reporting
requirements acted as a significant barrier to recruiting qualified
candidates to serve on advisory committees. However, neither EPA nor
NIH is required to disclose publicly their advisory committee members‘
conflict of interest waivers like FDA is. An EPA official added that
she does not believe the agency has granted a conflict of interest
waiver to an advisory committee member in at least 5 years because the
agency typically disqualifies individuals with conflicts of interest.
[62] FDA released a draft guidance in October 2007 that would implement
new agencywide procedures for the public availability of information
about advisory committee members‘ financial interests and conflicts of
interest waivers in response to the FDA Amendments Act of 2007. FDA
finalized this draft guidance August 2008.
[63] The FDA Amendments Act of 2007 also requires FDA to develop and
implement strategies to conduct outreach to potential advisory
committee candidates at universities and colleges, among other
entities. Pub. L. No. 110-85, § 701, 121 Stat. 823, 900-04 (pertinent
provision codified at 21 U.S.C. § 379d-1(b)(1)(A)).
[64] A clinician is an individual qualified in the clinical practice of
medicine, psychiatry, or psychology as distinguished from one
specializing in laboratory or research techniques or in theory.
[65] A clinical trialist is a medical researcher in charge of carrying
out a clinical trial‘s protocol.
[66] In its comments on the draft report, HHS stated that FDA has not
found that one particular biomedical specialty yields potential
advisory committee members with less frequent conflicts of interests.
[67] HHS, FDA, The Future of Drug Safety - Promoting and Protecting the
Health of the Public: FDA‘s Response to the Institute of Medicine‘s
2006 Report (Rockville, Md.: January 2007), [hyperlink,
http://www.fda.gov/oc/reports/iom013007.html] (accessed Aug. 6, 2007).
This report was in response to an Institute of Medicine recommendation
that FDA include a pharmacoepidemiologist or individual with equivalent
public health expertise on its drug-product advisory committees. This
recommendation was included in the Institute of Medicine report, The
Future of Drug Safety - Promoting and Protecting the Health of the
Public (Washington, D.C.: 2006).
[68] For this report, advisory committee meeting participants are the
standing and temporary members who attended a respective meeting. The
participant total includes the number of standing and temporary members
who attended each advisory committee meeting, so individual members may
be counted more than once.
[69] The conflict of interest determination totals do not include the
FDA advisory committees‘ industry representatives who are not subject
to the conflict of interest statutes and regulations applicable to
federal employees.
[70] For this analysis, standing or temporary members who were industry
representatives were not included because they are not SGEs and are not
subject to the conflict of interest statutes and regulations.
[71] Some CBER advisory committee meetings used previously granted §
208(b)(3) waivers”for an earlier CBER advisory committee meeting”as
waivers for a current meeting. For example, the September 2006
Transmissible Spongiform Encephalopathies Advisory Committee meeting
records included five previously granted § 208 (b)(3) waivers dated
June 2003, September 2004, and January 2005 for members who attended
the 2006 meeting. We did not analyze whether any CBER advisory
committee meetings with § 208(b)(3) waivers may have been non-
particular matter meetings, which are not subject to § 208.
[72] The § 208(b)(1) waivers were granted to federal employees from
other agencies, such as NIH or CDC, who participated in CDER and CBER
advisory committee meetings.
[73] Pub. L. No. 110-85, § 701, 121 Stat. 823, 900-04 (codified at 21
U.S.C. § 379d-1) (adding section 712 to the Food, Drug, and Cosmetic
Act).
[74] See FDA, 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
(Rockville, Md.: March 2007), [hyperlink,
http://www.fda.gov/oc/advisory/waiver/COIguidedft.html] (accessed Mar.
18, 2007). FDA finalized the draft guidance August 2008, [hyperlink,
http://www.fda.gov/oc/advisory/guidancePolicyRegs/ACWaiverCriteriaFINALG
uidance080408.pdf] (accessed Aug. 5, 2008).
[75] Pub. L. No. 110-85, § 701, 121 Stat. 901-02 (pertinent provisions
codified at 21 U.S.C. § 379d-1(c)(2)(B) and (C)). The law provides that
fiscal year 2007 shall be the base year from which to determine the
number of waivers that cannot be exceeded to meet the yearly 5 percent
reductions.
[76] FDA advisory committees may select temporary members to serve for
a particular advisory committee meeting to provide additional
expertise, to ensure a quorum of members is present to conduct a
meeting, or both. Like standing members, temporary members who are not
industry representatives are appointed as special government employees.
They may be members of other FDA advisory committees from the same or a
different center, or may be members of a center's consultant pool.
Federal employees from, for example, the Department of Health and Human
Services, the Centers for Disease Control and Prevention, or the
National Institutes of Health may also serve as temporary members.
[77] See FDA, 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
(Rockville, MD.: March 2007) [hyperlink,
http://www.fda.gov/oc/advisory/waiver/COIguidedft.html] (accessed Mar.
18, 2007). FDA finalized the draft guidance August 2008, [hyperlink,
http://www.fda.gov/oc/advisory/GuidancePolicyRegs/ACWaiverCriteriaFINALG
uidance080408.pdf] (accessed Aug. 5, 2008).
[78] Pub. L. No. 110-85, § 701, 121 Stat. 900-04 (codified at 21 U.S.C.
§ 379d-1).
[79] We identified former CBER, CDER, and CDRH advisory committee
members to interview by determining which FDA advisory committees in
each center held the most meetings in 2006, and from these advisory
committees, which members' service ended during 2006 and 2007. Of these
former advisory committee members, we contacted those who either did
not receive a conflict of interest waiver in 2006 or who served as an
advisory committee chair. Because these criteria yielded fewer former
CBER advisory committee members than former CDER and CDRH advisory
committee members, we also contacted former CBER advisory committee
members who received conflict of interest waivers in 2006. We asked
these former members whether barriers exist to recruiting qualified
individuals to serve on FDA advisory committees, particularly those
without conflicts of interest, and how FDA could improve its
recruitment process.
[80] The Web site posting was required by the Agriculture, Rural
Development, Food and Drug Administration and Related Agencies
Appropriations Act for fiscal year 2006 and continued through fiscal
year 2007. In August 2008, FDA issued a final Guidance for the Public,
FDA Advisory Committee Members, and FDA Staff: Public Availability of
Advisory Committee Members' Financial Interest Information and Waivers
(Rockville, Md.: August 2008). [hyperlink,
http://www.fda.gov/oc/advisory/GuidancePolicyRegs/ACDisclosureFINAL
Guidance080408.pdf] (accessed Aug. 5, 2008).
[81] To determine the designation of an advisory committee meeting
(e.g., non-specific party and specific-parties), we reviewed the
meeting inventory sheets FDA provided. When the inventory sheets did
not indicate a designation, we determined the designation from records
available on FDA's advisory committee Web site [hyperlink,
http://www.fda.gov/oc/advisory] including Federal Register advisory
committee meeting notices, advisory committee meeting minutes and
summary minutes, a meeting's conflict of interest waivers, and advisory
committee meeting transcripts. If the designation could not be
determined from the meeting records, we asked FDA to provide the
designation.
[82] Conflict of interest waivers--documented in memorandums--describe
the reasons why a conflict of interest waiver is requested for a
participant, and indicate if the waiver was granted. The conflict of
interest checklists are attached to waivers and provide more detail on
why the participant's conflict of interest waiver was requested, e.g.,
the value of the stock held in a drug company affected by a new drug
application being considered by the advisory committee.
[83] An acknowledgement and consent for disclosure of potential
conflict of interest form is attached to a member's waiver and provides
a shorter summary of conflicts of interests involved. The member signs
the form to allow public disclosure of his or her conflict of interest
information for a particular advisory committee meeting. An FDA
official stated that these forms are used for specific-parties
meetings.
[84] An appearance authorization--also referred to as an appearance
determination--memorandum describes reasons why a conflict of interest
appearance determination is requested for an individual and allows him
or her to participate in the advisory committee meeting despite the
appearance concerns.
[85] The Federal Advisory Committee Act (FACA) provides that, unless
otherwise specified by statute or presidential directive, advisory
committees shall be utilized solely for advisory functions. 5 U.S.C.
app. § 9(b).
[86] CBER's advisory committees are more closely aligned with their
offices. For this appendix, the term review division is used to include
both the CDER and CDRH review divisions and CBER's offices.
[87] We were told that the committee chair is usually selected based on
FDA's observations of an individual's participation as a member of an
advisory committee. For example, whether the individual exhibits the
ability to remain focused on the meeting topic and whether the other
committee members appear to respect the individual's expertise.
[88] For example, CDRH conducts an annual closed session, approved by
the office director, with its standing advisory committee members.
During this session, the review division updates the members about
possible upcoming advisory committee meeting topics and devices in
process for approval.
[89] See FDA, [hyperlink,
http://www.fda.gov/ohrms/dockets/ac/cder07.htm#EndocrinologicMetabolic]
(accessed Oct. 18, 2007) for CDER's July 30, 2007, joint advisory
committee meeting of its Endocrinologic and Metabolic Drugs Advisory
Committee and Drug Safety and Risk Management Advisory Committee.
[90] Additional information is provided to the advisory committee by
the company at issue in the meeting. For example, a company sponsoring
a new drug for approval will provide data to support the efficacy and
safety claims for its product.
[91] A subcommittee meeting of this type is not subject to FACA because
the subcommittee is providing information to an advisory committee
rather than making recommendations to FDA. See 41 C.F.R. § 102-3.35
(2006).
[92] A homework assignment can not be given to more than three advisory
committee members or the assignment would constitute an advisory
committee meeting, according to an FDA official.
[93] Temporary members may also be selected to attend an advisory
committee meeting to ensure there is a meeting quorum.
[94] A guest speaker may be paid to attend an advisory committee
meeting. For example, if a CDER review division decides to invite a
guest speaker who is not a federal employee, the division may pay the
speaker from its division funds.
[95] An FDA official told us that patient representatives serve as ad
hoc members of the advisory committee for a particular advisory
committee meeting.
[96] The review division usually looks to the center's consultant pool
to find alternate experts, but may also go outside FDA.
[97] See P. Lurie, C. Almeida, N. Stine, A. Stine, and S. Wolfe,
’Financial Conflict of Interest Disclosure and Voting Patterns at Food
and Drug Administration Drug Advisory Committee Meetings,“ The Journal
of the American Medical Association, vol. 295, no. 16 (2006). See also
FDA‘s comment on the article at [hyperlink,
http://www.fda.gov/oc/advisory/analysis.html].
[98] See D. Zuckerman, FDA Advisory Committees: Does Approval Mean
Safety? National Research Center for Women & Families (Washington,
D.C.: 2006).
[99] Zuckerman, 3.
[100] Zuckerman, 1.
[101] The report used attributed quotations from FDA advisory committee
meeting transcripts and vote tallies to analyze voting patterns of four
types of advisory committee meeting participants (physician only,
physician plus scientific degree, doctorate only, and consumer
representative).
[102] See N. Ackerley, J. Eyraud, M. Mazzotta, Measuring Conflict of
Interest and Expertise on FDA Advisory Committees, Eastern Research
Group, Inc. (Lexington, Mass.: 2007).
[103] The Center for Devices and Radiological Health's Medical Devices
Advisory Committee (MDAC) is the umbrella title for 18 statutorily
authorized advisory panels whose members are subject to the same legal
and regulatory requirements as other FDA advisory committees. FDA
counts MDAC and its 18 panels as one advisory committee. For our
analysis, MDAC's 18 panels' meetings were treated as individual
advisory committee meetings.
[104] This committee, by law, has 5 members who represent governmental
agencies including state and federal governments, and 10 members who
represent industry and the public. See 21 U.S.C. § 360kk.
[End of section]
GAO's Mission:
The Government Accountability Office, the audit, evaluation and
investigative arm of Congress, exists to support Congress in meeting
its constitutional responsibilities and to help improve the performance
and accountability of the federal government for the American people.
GAO examines the use of public funds; evaluates federal programs and
policies; and provides analyses, recommendations, and other assistance
to help Congress make informed oversight, policy, and funding
decisions. GAO's commitment to good government is reflected in its core
values of accountability, integrity, and reliability.
Obtaining Copies of GAO Reports and Testimony:
The fastest and easiest way to obtain copies of GAO documents at no
cost is through GAO's Web site [hyperlink, http://www.gao.gov]. Each
weekday, GAO posts newly released reports, testimony, and
correspondence on its Web site. To have GAO e-mail you a list of newly
posted products every afternoon, go to [hyperlink, http://www.gao.gov]
and select "E-mail Updates."
Order by Mail or Phone:
The first copy of each printed report is free. Additional copies are $2
each. A check or money order should be made out to the Superintendent
of Documents. GAO also accepts VISA and Mastercard. Orders for 100 or
more copies mailed to a single address are discounted 25 percent.
Orders should be sent to:
U.S. Government Accountability Office:
441 G Street NW, Room LM:
Washington, D.C. 20548:
To order by Phone:
Voice: (202) 512-6000:
TDD: (202) 512-2537:
Fax: (202) 512-6061:
To Report Fraud, Waste, and Abuse in Federal Programs:
Contact:
Web site: [hyperlink, http://www.gao.gov/fraudnet/fraudnet.htm]:
E-mail: fraudnet@gao.gov:
Automated answering system: (800) 424-5454 or (202) 512-7470:
Congressional Relations:
Ralph Dawn, Managing Director, dawnr@gao.gov:
(202) 512-4400:
U.S. Government Accountability Office:
441 G Street NW, Room 7125:
Washington, D.C. 20548:
Public Affairs:
Chuck Young, Managing Director, youngc1@gao.gov:
(202) 512-4800:
U.S. Government Accountability Office:
441 G Street NW, Room 7149:
Washington, D.C. 20548: