Department of Health and Human Services
OFFICE OF 
    
IN  SPECTOR GENERAL 
 
 
 
 
 
 
 
 
T F D
HE  OOD AND  RUG 
 
A    O
DMINISTRATION S  VERSIGHT 
 
C I 
OF  LI NICAL  NVESTIGATORS  
 
F I  
INANCIAL  NFORMATION
 
 
 
 
 
Daniel R. Levinson  
Inspector General 
 
January 2009 
OEI-05-07-00730   
Office of Inspector General 
http://oig.hhs.gov 
 
The mission of the Office of Inspector General (OIG), as mandated by Public Law 95-452, as 
amended, is to protect the integrity of the Department of Health and Human Services 
(HHS) programs, as well as the health and welfare of beneficiaries served by those 
programs.  This statutory mission is carried out through a nationwide network of audits, 
investigations, and inspections conducted by the following operating components: 
Office of Audit Services 
The Office of Audit Services (OAS) provides auditing services for HHS, either by conducting 
audits with its own audit resources or by overseeing audit work done by others.  Audits 
examine the performance of HHS programs and/or its grantees and contractors in carrying 
out their respective responsibilities and are intended to provide independent assessments of 
HHS programs and operations.  These assessments help reduce waste, abuse, and 
mismanagement and promote economy and efficiency throughout HHS. 
Office of Evaluation and Inspections 
The Office of Evaluation and Inspections (OEI) conducts national evaluations to provide 
HHS, Congress, and the public with timely, useful, and reliable information on significant 
issues.  These evaluations focus on preventing fraud, waste, or abuse and promoting 
economy, efficiency, and effectiveness of departmental programs.  To promote impact, OEI 
reports also present practical recommendations for improving program operations.  
Office of Investigations 
The Office of Investigations (OI) conducts criminal, civil, and administrative investigations 
of fraud and misconduct related to HHS programs, operations, and beneficiaries.  With 
investigators working in all 50 States and the District of Columbia, OI utilizes its resources 
by actively coordinating with the Department of Justice and other Federal, State, and local 
law enforcement authorities.  The investigative efforts of OI often lead to criminal 
convictions, administrative sanctions, and/or civil monetary penalties. 
Office of Counsel to the Inspector General 
The Office of Counsel to the Inspector General (OCIG) provides general legal services to 
OIG, rendering advice and opinions on HHS programs and operations and providing all 
legal support for OIGs internal operations.  OCIG represents OIG in all civil and 
administrative fraud and abuse cases involving HHS programs, including False Claims Act, 
program exclusion, and civil monetary penalty cases.  In connection with these cases, OCIG 
also negotiates and monitors corporate integrity agreements.  OCIG renders advisory 
opinions, issues compliance program guidance, publishes fraud alerts, and provides other 
guidance to the health care industry concerning the anti-kickback statute and other OIG 
enforcement authorities.   
   
 E X E C U T I V E   S U M M A R Y  
OBJECTIVE
 
1.  To describe the extent and nature of clinical investigators disclosed 
financial interests reported to the Food and Drug Administration 
(FDA) for marketing applications approved in fiscal year (FY) 2007. 
2.  To assess FDAs oversight of clinical investigators financial 
information.   
BACKGROUND 
Most new drugs, biological products, and medical devices undergo 
clinical trials on human subjects before they are marketed in the United 
States.  Sponsors, generally pharmaceutical or device companies, 
oversee clinical trials conducted by clinical investigators.  Before clinical 
trials begin, sponsors submit a pretrial application to FDA outlining 
their study design.  After clinical trials are completed, sponsors wishing 
to market their product submit a marketing application to FDA.   
Sponsors must collect financial information from clinical investigators 
before clinical trials.  However, sponsors submit financial information to 
FDA only when they submit their marketing application after clinical 
trials end.  For each clinical investigator, sponsors submit a financial 
form either certifying that the investigator does not have a financial 
interest or disclosing the financial interest.  Federal regulations also 
allow sponsors to indicate that they acted with due diligence but were 
unable to obtain financial information from a clinical investigator.  For 
each disclosed financial interest, sponsors must attach details of the 
financial interest and a record of their actions to minimize potential 
bias toward clinical trial results. 
FDA assigns marketing applications to a multidisciplinary team for 
review.  Reviewers evaluate financial information as well as sponsors 
actions to minimize any potential bias related to clinical investigators 
disclosed financial interests.  Reviewers provide written notes that are 
used to determine whether a marketing application should be approved 
by FDA.  If reviewers suspect that disclosed financial interests 
compromised data integrity, they are required to take action to ensure 
the reliability of the data. 
We reviewed financial forms, attachments, and accompanying FDA 
review notes for all 118 marketing applications approved by FDA in    
FY 2007.  We also reviewed FDA regulations and guidance, conducted 
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structured interviews with FDA officials, and sent an electronic survey 
to FDA reviewers.   
FINDINGS 
One percent of clinical investigators disclosed a financial interest.  
Among clinical investigators listed in financial forms, 1 percent 
disclosed at least one financial interest.  This represents 206 of the 
29,691 clinical investigators listed in financial interest forms.  Of these            
206 clinical investigators, almost all disclosed only one financial 
interest, with a few disclosing two or three financial interests.   
FDA cannot determine whether sponsors have submitted financial 
information for all clinical investigators.  FDA cannot determine 
whether sponsors have submitted complete financial information for all 
clinical investigators because it does not have a complete list of clinical 
investigators.  In addition, FDA does not use onsite inspections to 
confirm that submitted financial information is complete.   
Forty-two percent of FDA-approved marketing applications were 
missing financial information.   Twenty-three percent of approved 
marketing applications were missing a certification or disclosure form 
or required attachments.  In 28 percent of marketing applications, 
sponsors used the due diligence exemption to indicate that they were 
unable to provide complete financial information.  Although allowed by 
regulation, sponsors use of the diligence exemption results in no 
financial information for FDA reviewers.  Some marketing applications 
had both missing attachments and the due diligence exemption was 
marked.    
FDA did not document a review of any financial information for                 
31 percent of marketing applications.  When FDA reviewers used a 
review template, they were more likely to document a review of 
financial information.   
Neither FDA nor sponsors took action for 20 percent of marketing 
applications with disclosed financial interests.  In 20 percent of 
marketing applications, FDA reviewers did not take action and sponsors 
did not indicate that they minimized potential bias during the clinical 
trials.  For over half of these marketing applications, reviewers did not 
document a review of financial information.  In addition, when FDA did 
take action, their actions were inconsistent.   
 
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RREECCOOMMMMEENNDDAATTIIOONNSS  
FDA should ensure that sponsors submit complete financial 
information for all clinical investigators.     
  FDA should use a complete list of clinical investigators to check 
that sponsors have submitted financial information for all 
clinical investigators. 
  FDA should check that sponsors have submitted all required 
attachments to financial forms.   
  FDA should update guidance to sponsors regarding the due 
diligence exemption. 
  FDA should add a review of financial information to the onsite 
inspection protocol. 
FDA should ensure that reviewers consistently review financial 
information and take action in response to disclosed financial 
interests. 
  FDA should require that all centers consistently use a template 
that includes a prompt to document a review of financial 
information. 
  FDA should provide additional guidance and training to 
reviewers. 
FDA should require that sponsors submit financial information for 
clinical investigators as part of the pretrial application process. 
AGENCY COMMENTS AND OFFICE OF INSPECTOR GENERAL 
RESPONSE 
FDA expressed concerns about elements of our analysis in three of our 
findings.  In response to FDAs concerns, we removed employees from 
our analysis of disclosed financial interests.  For FDAs remaining 
concerns, we maintain that our analysis is accurate.    
FDA agreed with all of our recommendations except our final 
recommendation that FDA require sponsors to submit financial 
information for clinical investigators as part of the pretrial application 
process.  FDA emphasized that collecting financial information before a 
clinical trial starts is the sponsors responsibility.  However, despite this 
important role for sponsors, FDA has no mechanism in place to ensure 
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E X E C U T I V E   S U M M A R Y  
that sponsors are in fact collecting financial information before 
beginning clinical trials. 
FDA also stated that it would take significant additional effort for both 
industry and FDA to collect and review financial information during the 
pretrial application process.  However, pursuant to regulation, FDA 
already requires sponsors to collect financial information before the 
start of clinical trials.  In addition, basic information on clinical 
investigators is submitted to FDA as they are added to clinical trials. 
Further, FDA asserted that this additional effort would not be 
worthwhile because financial interests are only one form of potential 
bias and not all clinical trials are presented in the marketing 
application.  Receiving financial information during the pretrial 
application process would allow FDA to have information on all 
potential sources of financial bias.  FDA could then work effectively with 
sponsors to identify potential bias.  In addition, receiving financial 
information related to ongoing clinical trials is in keeping with FDAs 
stated intention to improve its oversight of ongoing clinical trials.   
We continue to recommend that FDA require sponsors to submit 
financial information as part of the pretrial application process.  
Acknowledging the burden to FDAs administrative and review staff, we 
encourage FDA to develop a review of financial information that best 
balances the additional effort with the potential benefits.    
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 T A B L E   O F   C O N T E N T S  
EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i
 
 
I N T RO DUC T IO N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 
 
 
F I N D IN G S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 
  One percent of clinical investigators disclosed a financial           
  interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 
FDA cannot determine whether sponsors have submitted         
complete financial information. . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 
  FDA approved applications missing financial information. . . . . . 17 
  FDA did not always note a review of financial information . . . . . 18 
  No action taken in 20 percent of applications with disclosures  . . 20 
   
R E C O MMEN D A T ION S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 
  Agency Comments and Office of Inspector General Response . . . 26 
 
 
APPENDIXES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 
  A:  Certification of No Financial Interests, Form 3454. . . . . . . . . 30 
  B:  Disclosure of Financial Interests, Form 3455. . . . . . . . . . . . . . 31 
  C:  Financial Forms Submitted to Each Center in                           
Fiscal Year  2007. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 
  D:  Response Rates for Reviewer Survey . . . . . . . . . . . . . . . . . . . . 33 
  E:  Description of Food and Drug Administration Action . . . . . . . 34 
  F:  Agency Comments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 
 
A C K NO WL E D G M E N T S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44   
   
I N T R O D U C T I O N  
 I N T R O D U C T I O N  
OBJECTIVE 
1.  To describe the extent and nature of clinical investigators disclosed 
financial interests reported to the Food and Drug Administration 
(FDA) for marketing applications approved in fiscal year (FY) 2007. 
2.  To assess FDAs oversight of clinical investigators financial 
information.   
BACKGROUND 
Research has shown that financial relationships exist between medical 
companies and researchers, including researchers conducting clinical 
trials for the approval of new drugs, biological products, and medical 
devices.  For example, the Journal of the American Medical Association 
reported that between 23 percent and 28 percent of academic 
researchers had financial interests in medical companies.1   
Financial relationships between researchers and medical companies 
may compromise the safety of human subjects and the integrity of 
research data.  After a teenager died while undergoing experimental 
treatment in 1999, the President encouraged agencies to develop steps 
to address financial relationships.  An investigation into the case found 
that many of the clinical investigators had financial interests in the 
sponsor of that clinical trial.2  In another case, study results from a 
medical device trial may have been cast in an overly flattering light, 
potentially because researchers at about half the clinical trial sites had 
financial interests in the device company.3   
The Office of Inspector General (OIG) has worked to ensure that 
financial interests do not compromise clinical trials.  FDA developed its 
1999 regulations regarding the disclosure of clinical investigators 
financial interests after OIG officials reported that FDAs failure to 
collect information about clinical investigators financial interests could 
constitute a material weakness under the Federal Managers Financial 
 
1 Justin E. Bekelman, et al., 2003.  Scope and Impact of Financial Conflicts of Interest in 
Biomedical Research, Journal of the American Medical Association, vol. 289(4), p. 456.  
Available online at http://jama.ama-assn.org/cgi/reprint/289/4/454?ijkey= 
9e08192f3f85916bd89686c6af4713ad33b514ea.  Accessed on May 30, 2008. 
2 FDA, Human Gene Therapy:  Harsh Lessons, High Hopes.  Available online at 
http://www.fda.gov/fdac/features/2000/500_gene.html.  Accessed on May 5, 2008. 
3 Abelson, Reed, Financial Ties Cited as Issue in Spine Study.  The New York Times, 
January 30, 2008, p. 2. 
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I N T R O D U C T I O N  
Integrity Act.4  Although FDA determined that a material weakness did 
not exist, FDA concluded that there was a need to address this issue 
through rulemaking.5 
The Food and Drug Administration 
Among other activities, FDA is responsible for protecting the public 
health by ensuring the safety, efficacy, and security of human drugs, 
biological products, and medical devices (hereinafter referred to as 
investigational products).6  Within FDA, the Center for Drug 
Evaluation and Research (CDER) regulates drugs, the Center for 
Biologics Evaluation and Research (CBER) regulates biological products 
that come from living sources (such as vaccines or gene therapies), and 
the Center for Devices and Radiological Health (CDRH) regulates 
medical devices.   
Clinical Trials 
The Federal Food, Drug, and Cosmetic Act generally requires that most 
new investigational products undergo clinical trials on human subjects 
to demonstrate their safety and efficacy before they are approved for 
sale in the United States.7  Sponsors, clinical investigators, and 
institutional review boards (IRB) play a role in clinical trials. 
Sponsors.  Sponsors, often pharmaceutical or device companies, are 
responsible for developing and testing investigational products in 
clinical trials.   
Clinical investigators.  Sponsors hire clinical investigators to conduct 
clinical trials.  Clinical investigators may be researchers at academic 
institutions or practicing physicians.  Typically, there are many clinical 
investigators working in multiple clinical trial sites, including outside 
the United States, for each clinical trial.  
There are both primary investigators and subinvestigators.  Primary 
investigators recruit subjects, supervise clinical studies, collect data, 
 
4 21 CFR  54.4; FDA, Guidance Financial Disclosure by Clinical Investigators.  
Available online at http://www.fda.gov/oc/guidance/financialdis.html.  Accessed on       
March 11, 2008.   
5 63 Fed. Reg. 5233 (Feb. 2, 1998). 
6 FDA, FDAs Mission Statement.  Available online at 
http://www.fda.gov/opacom/morechoices/mission.html.  Accessed on April 3, 2008. 
7 21 U.S.C.  355; 21 CFR  812.20(b)(2); FDA, The FDAs Drug Review Process:  
Ensuring Drugs Are Safe and Effective.  Available online at 
http://www.fda.gov/fdac/features/2002/402_drug.html.  Accessed on March 11, 2008. 
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I N T R O D U C T I O N  
and report study results to the sponsor.8  Primary investigators must 
sign investigator agreements stating that they will comply with all 
relevant FDA regulations.9  Subinvestigators assist primary 
investigators with their responsibilities.   
Institutional Review Boards.  IRBs are committees that oversee clinical 
investigators research to ensure that all steps are taken to protect the 
rights and welfare of human subjects.10  IRBs must include members 
from varying backgrounds and often are composed of physicians, 
scientists, lawyers, and ethicists.11  An IRB must approve all clinical 
trials involving human subjects before clinical trials can begin.12  
During their reviews of clinical trials, IRBs are not required to review 
clinical investigators financial information.  Yet, the Department of 
Health and Human Services (HHS) strongly urges IRBs to look at 
financial information.13  It has been estimated that a quarter of IRBs 
routinely conduct such a review.14  
FDAs Oversight of Clinical Trials   
FDA requires that sponsors file a pretrial application before beginning 
clinical trials.15 16  Pretrial applications include the study protocol, the 
 
8 21 CFR  312.60 (drugs and biologics); 21 CFR  812.100 (devices).  FDA, Guidance on 
Clinical Trials, p. 18.  Available online at http://www.fda.gov/cder/guidance/959fnl.pdf.  
Accessed on May 5, 2008.    
9 Pretrial applications submitted to CDRH include investigator agreements for 
subinvestigators.  (21 CFR  312.53 (drugs and biologics); 21 CFR  812.43(c) (devices)). 
10 21 CFR  56. 
11 21 CFR  56.107. 
12 21 CFR  56.101. 
13 HHS, Financial Relationships and Interests in Research Involving Human Subjects: 
Guidance for Human Subject Protection.  May 12, 2004.  Available online at  
http://www.hhs.gov/ohrp/humansubjects/finreltn/finalguid.pdf.  Accessed on May 30, 2008.   
14 National Institutes of Health (NIH), Financial Conflicts of Interest and Research 
Objectivity:  Issues for Investigators and Institutional Review Boards.  June 5, 2000.  
Available online at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-040.html.  
Accessed on March 25, 2008. 
15 Sponsors submit an Investigational New Drug Application to CDER or CBER per            
21 CFR  312.20.  Sponsors submit an Investigational Device Exemption to CDRH per             
21 CFR  812.20.   
16 FDA uses the term sponsor and applicant at different times in the regulations.  
FDA states that generally the sponsor of the covered study, and the applicant company are 
the same party.  For the purpose of this report, we refer to sponsors and applicants 
collectively as sponsors.  Question Seven, FDA, Guidance Financial Disclosure by Clinical 
Investigators.  Available online at http://www.fda.gov/oc/guidance/financialdis.html.  
Accessed on March 11, 2008. 
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I N T R O D U C T I O N  
chosen IRB(s), and assurances that human subjects will be protected.17  
As part of the pretrial application to FDA, sponsors submit the names, 
addresses, and qualifications of all primary investigators.  They must 
also list all subinvestigators.  Pretrial applications do not include 
financial information about clinical investigators.   
Upon successful completion of clinical trials, sponsors that wish to 
market a product must submit a marketing application to FDA.18  
Marketing applications include clinical trial results, descriptions of the 
investigational products components, proposed labeling, and financial 
information about clinical investigators relationship to sponsors.   
FDA assigns the marketing application to a multidisciplinary team of 
reviewers.  Reviewers represent a variety of scientific disciplines, 
including medicine, pharmacology, statistics, and chemistry.  Reviewers 
evaluate information in the marketing application relevant to their 
expertise.19  These reviews help determine whether FDA will approve a 
marketing application. 
Onsite inspections.  During and after clinical trials, FDA performs onsite 
inspections of clinical investigators, sponsors, and IRBs through the 
Bioresearch Monitoring Program (BiMo).20  The purpose of the BiMo 
program is to ensure the protection of research subjects and the 
integrity of clinical trial data.21  BiMo officials work in each of the three 
FDA centers.   
BiMo conducts both surveillance and directed inspections to determine 
compliance with FDA regulations.  Surveillance inspections are 
typically routine inspections that occur after FDA receives a marketing 
application and target completed clinical trials.  Directed inspections 
typically target ongoing clinical trials and occur because of specific 
concerns about data integrity.  These concerns could include clinical 
investigators financial interests. 
 
17 21 CFR  312.23. 
18 21 CFR  314.50 (drugs); 21 CFR  601.2 (biologics); 21 CFR  814.20 (devices). 
19 FDA, The FDAs Drug Review Process:  Ensuring Drugs Are Safe and Effective.  
Available online at http://www.fda.gov/fdac/features/2002/402_drug.html.  Accessed on 
March 27, 2008. 
20 21 U.S.C.  355 and 360i.  FDA, Compliance Program Guidance Manual,                
Chapter 48:  Bioresearch Monitoring Background. 
21 FDA, Bioresearch Monitoring Program.  Available online at 
http://www.fda.gov/oc/gcp/compliance.html.  Accessed on October 30, 2008.  
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Sponsors Financial Disclosure Requirements 
Beginning in 1999, FDA required sponsors submitting marketing 
applications to disclose the financial interests of primary investigators 
and subinvestigators (hereinafter referred to as clinical investigators) 
who contributed data for a covered clinical study.22  In 2001, FDA 
issued guidance to sponsors providing additional details about the 
requirements.  The guidance defines terms included in the regulations 
and addresses questions from the industry.23 
Pursuant to regulations, sponsors must obtain financial information 
from clinical investigators before clinical trials.24  This is done so 
sponsors can consult with FDA early on regarding any potentially 
problematic financial interest, and take action to minimize any 
potential study bias.25  Sponsors can collect financial information from 
clinical investigators using any format or process. 
After their initial submission, clinical investigators are required to 
provide updates to sponsors with any changes in their financial status 
during clinical trials and in the year after clinical trials are complete. 26  
Sponsors must maintain complete records detailing clinical 
investigators financial information during clinical trials and for 2 years 
after FDA approves a marketing application.27   
Sponsors are required to submit financial information on clinical 
investigators to FDA only when they submit the marketing application 
after clinical trials are complete.   
FDA requires that sponsors disclose the following financial interests for 
all clinical investigators, their spouses, and their dependent children:  
(1) any financial arrangement between the sponsor whereby the value 
of the compensation could be influenced by the study outcome;  
 
22 FDA defines a covered clinical study as any study submitted in a marketing 
application relied upon to show a product is effective or any study to which a single 
investigator significantly contributes to the demonstration of safety.  For purposes of this 
report, we refer to covered clinical studies as clinical trials.  21 CFR  54.4 and 54.2(e). 
23 FDA, Guidance Financial Disclosure by Clinical Investigators.  Available online at 
http://www.fda.gov/oc/guidance/financialdis.html.  Accessed on March 11, 2008. 
24 21 CFR  312.53(c)(4) (drugs and biologics); 21 CFR  812.43(c) (devices). 
25 67 Fed. Reg. 6042 (Feb. 8, 2002); Question 6, FDA, Guidance Financial Disclosure by 
Clinical Investigators.  Available online at 
http://www.fda.gov/oc/guidance/financialdis.html.  Accessed on March 11, 2008.  
26 21 CFR  312.53 (drugs and biologics); 21 CFR  812.43(c) (devices). 
27 21 CFR  54.6. 
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(2) a sum of all significant payments exceeding $25,000 made on or 
after February 2, 1999, from the sponsor.  Payments include research 
grants, retainers for ongoing consultation, or a general honorarium.  
They do not include the payments, such as salaries, associated with 
conducting the clinical trial;  
(3) any proprietary interest in the tested product, including patents, 
trademarks, or licensing agreements; and  
(4) equity in the sponsors public company exceeding $50,000, or equity 
for which the value cannot be determined through public prices.28 
Certification:  Financial Interests and Arrangements of Clinical 
Investigators, Form 3454.  Sponsors use Form 3454 to list clinical 
investigators who have no financial interest with the sponsor.  Sponsors 
can submit a single certification form for multiple clinical investigators 
involved with clinical trials.  If sponsors cannot obtain financial 
information from a clinical investigator, they can indicate on the 
certification form that they acted with due diligence to collect the 
information.29   
FDAs 2001 guidance defines due diligence as a measure of activity 
expected from a reasonable and prudent person under a particular 
circumstance.30  In 2002, in comments to a Federal Register notice, 
FDA was asked to define what constitutes due diligence.  In response, 
FDA advised sponsors to try to locate clinical investigators through at 
least two telephone calls, and document notes of the calls.  In addition, 
FDA recommended that sponsors follow up in writing, sending at least 
two certified letters.31   
If sponsors indicate due diligence, they are expected to describe why 
they were unable to obtain the financial information and document 
 
28 21 CFR  54.2 and 54.4(a)(3); FDA, Guidance Financial Disclosure by Clinical 
Investigators.  Available online at http://www.fda.gov/oc/guidance/financialdis.html.  
Accessed on March 11, 2008.  We combined the regulations two equity disclosures in this 
list because they are combined on the form that sponsors complete when disclosing a 
clinical investigators financial interests.   
29 21 CFR  54.4. 
30 Question Three, FDA, Guidance Financial Disclosure by Clinical Investigators.  
Available online at http://www.fda.gov/oc/guidance/financialdis.html.  Accessed on             
March 11, 2008. 
31 67 Fed. Reg. 6041 (Feb. 8, 2002). 
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their attempts to obtain the information.32  Sponsors are required to 
provide the reasons why they were unable to obtain the information 
when they claim the due diligence exemption on the certification form.  
Sponsors are not required to submit documentation of their attempts to 
contact clinical investigators nor describe their attempts.  See              
Appendix A for a copy of the certification form. 
Disclosure:  Financial Interests and Arrangements of Clinical Investigators, 
Form 3455.  Sponsors use Form 3455 to disclose clinical investigators 
financial interests.  The form lists FDAs four financial disclosure 
categories.  Sponsors must submit a separate disclosure form for each 
clinical investigator with financial interests.   
Sponsors must include two attachments with each disclosure form.  The 
first must provide specific details about the financial interest.  The 
second must describe any steps taken to minimize the potential bias 
resulting from disclosed financial interests.33  FDA does not specify the 
actions sponsors must take to minimize potential bias.  See Appendix B 
for a copy of the disclosure form. 
FDAs Oversight of Financial Information 
When FDA receives a marketing application, it performs an 
administrative check to ensure that sponsors have included the required 
information, including financial forms.  If sponsors neglect to submit 
financial forms, FDA can refuse to accept a marketing application for 
review.34  When FDA accepts a marketing application for review, FDA 
reviewers evaluate the application and clinical trial data, including 
whether disclosed financial interests compromised the integrity of the 
trial data. 
Marketing application review.  Among other things, the marketing 
application review includes an evaluation of clinical investigators 
disclosed financial interests to determine their potential effect on data 
integrity.  FDA reviewers provide written notes regarding their reviews.  
 
32 FDA, Form 3455, Disclosure:  Financial Interests and Arrangements of Clinical 
Investigators.  Available online at http://www.fda.gov/opacom/morechoices/fdaforms/FDA-
3455.pdf.  Accessed on October 11, 2007.  FDA, Guidance Financial Disclosure by Clinical 
Investigators.  Available online at http://www.fda.gov/oc/guidance/financialdis.html.  
Accessed on March 11, 2008.   
33 21 CFR  54.4(a)(3)(v). 
34 21 CFR  54.4(c).  
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Division directors35 read these review notes to determine whether to 
recommend approval for a marketing application.36 
The process for reviewing financial information within the marketing 
application differs by center.  CDER has a review template that 
reviewers are required to use to review various aspects of marketing 
applications, including financial information.  CBER has a draft review 
template that reviewers may use, and that includes a review of financial 
information.  CDRH does not have a review template.   
FDA action in response to disclosed financial interests.  If FDA determines 
that clinical investigators disclosed financial interests raise a serious 
question about the integrity of the data, FDA is required to take action 
to ensure the reliability of the data.37  For example, FDA reviewers may 
take action if they discover that results from clinical trial sites managed 
by clinical investigators with disclosed financial interests were more 
favorable than average. 
Regulations do not stipulate specific actions, but offer examples of 
possible actions.38  Suggested actions include requesting an onsite 
inspection, requesting that the sponsor submit further data analyses or 
conduct additional independent studies, and refusing to review clinical 
trial results.39   
Related Reports  
An OIG report issued in 2000 found that FDAs overall oversight of 
clinical investigators was limited.40  Additionally, a 2007 OIG report 
found that FDA had limited ability to effectively manage BiMo.41  The 
 
35 Centers may refer to this position under various titles, including office director and 
team leader.  For this report, we use the term division director to indicate the FDA official 
who provides recommendations to the FDA Commissioner on whether to approve a 
marketing application. 
36 FDA, The FDAs Drug Review Process:  Ensuring Drugs Are Safe and Effective.  
Available online at http://www.fda.gov/fdac/features/2002/402_drug.html.  Accessed on 
March 27, 2008. 
37 21 CFR  54.5(c). 
38 Ibid.  
39 Ibid.  
40 OIG, FDA Oversight of Clinical Investigators, OEI-05-99-00350, June 2000. 
41 OIG, The Food and Drug Administrations Oversight of Clinical Trials,                   
OEI-01-06-00160, September 2007. 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  8   
   
  I   N T R O DD UU CC TT II OO NN   
 
eevvaalluuaattiioonn  eessttiimmaatteedd  tthhaatt  FFDDAA  iinnssppeecctteedd  11  ppeerrcceenntt  ooff  cclliinniiccaall  ttrriiaall  ssiitteess  
bbeettwweeeenn  22000000  aanndd  22000055..4422  
IInn  22000011,,  tthhee  GGoovveerrnnmmeenntt  AAccccoouunnttaabbiilliittyy  OOffffiiccee  ((GGAAOO))  iissssuueedd  aa  rreeppoorrtt  
tthhaatt  ccoommppaarreedd  ffiinnaanncciiaall  ddiisscclloossuurree  rreeqquuiirreemmeennttss  ooff  FFDDAA  aanndd  NNIIHH..    GGAAOO  
ffoouunndd  tthhaatt,,  uunnlliikkee  NNIIHH,,  FFDDAA  iiss  nnoott  nnoottiiffiieedd  ooff  cclliinniiccaall  iinnvveessttiiggaattoorrss  
ffiinnaanncciiaall  iinnffoorrmmaattiioonn  uunnttiill  aafftteerr  cclliinniiccaall  ttrriiaallss  aarree  ccoommpplleettee..    GGAAOO  
rreeccoommmmeennddeedd  tthhaatt  HHHHSS  ddeevveelloopp  ssppeecciiffiicc  gguuiiddaannccee  oorr  ppoolliiccyy  ccoonncceerrnniinngg  
ffiinnaanncciiaall  iinnffoorrmmaattiioonn..    IInn  rreessppoonnssee,,  HHHHSS  ssttaatteedd  tthhaatt  ttoo  tthhee  eexxtteenntt  
ssppeecciiffiicc  gguuiiddaannccee  oorr  ppoolliiccyy  wwaass  ddeevveellooppeedd,,  iitt  wwoouulldd  bbee  ccoooorrddiinnaatteedd  
tthhrroouugghhoouutt  tthhee  DDeeppaarrttmmeenntt..4433      
MMEETTHHOODDOOLLOOGGYY  
Scope 
To describe the extent and nature of clinical investigators financial 
interests, we reviewed disclosed financial interests from marketing 
applications approved in FY 2007.  We did not review other types of 
applications approved by FDA; for instance, applications for generic 
products.  By limiting our study to marketing applications, we focused 
on products that have been newly released to the public.   
This evaluation reviewed FDAs oversight of clinical investigators 
financial interests.  We did not review FDAs oversight of the financial 
interests of FDA employees or FDA advisory board members.    
Data Collection 
We collected financial forms and attachments from all 118 marketing 
applications approved in FY 2007.  This includes 73 marketing 
applications approved by CDER, 32 approved by CDRH, and                         
13 approved by CBER.  See Appendix C for financial forms submitted to 
each center in FY 2007.   
We also conducted six structured group interviews with FDA center 
officials and FDA BiMo officials from each of the three centers between 
January and March 2008.  We discussed FDAs process for overseeing 
financial information, guidance to sponsors and reviewers, action taken 
in response to disclosed financial interests, and BiMo reviews of 
financial information. 
 
42 Ibid. 
43 GAO, Biomedical Research:  HHS Direction Needed to Address Financial Conflicts of 
Interest, GAO-02-89, p. 39, November 2001. 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  9   
   
I     N   T R O D U C T II OO NN   
  
TToo  aasssseessss  FFDDAAss  rreevviieeww  ooff  ffiinnaanncciiaall  iinnffoorrmmaattiioonn  aanndd  aaccttiioonnss  ttaakkeenn  iinn  
rreessppoonnssee  ttoo  tthhiiss  rreevviieeww,,  wwee  ccoolllleecctteedd  FFDDAA  rreevviieewweerrss  nnootteess,,  ccoommpplleetteedd  
rreevviieeww  tteemmppllaatteess,,  aanndd  ssuummmmaarryy  rreevviieeww  ddooccuummeennttss  ((hheerreeiinnaafftteerr  rreeffeerrrreedd  
ttoo  aass  rreevviieeww  nnootteess))  ccoorrrreessppoonnddiinngg  ttoo  tthheeiirr  eevvaalluuaattiioonn  ooff  ffiinnaanncciiaall  
iinnffoorrmmaattiioonn  iinn  tthhee  mmaarrkkeettiinngg  aapppplliiccaattiioonnss..      
TToo  ffuurrtthheerr  uunnddeerrssttaanndd  FFDDAAss  rreevviieeww  pprroocceessss,,  wwee  sseenntt  aann  eelleeccttrroonniicc  
ssuurrvveeyy  ttoo  FFDDAA  rreevviieewweerrss  iinn  JJaannuuaarryy  22000088..    SSuurrvveeyy  qquueessttiioonnss  ppeerrttaaiinneedd  
ttoo  rreevviieewweerrss  pprroocceessss  ffoorr  eevvaalluuaattiinngg  ffiinnaanncciiaall  iinnffoorrmmaattiioonn,,  aannyy  
iinnssttrruuccttiioonnss  tthheeyy  rreecceeiivveedd,,  aanndd  wwhheetthheerr  tthheeyy  hhaadd  eevveerr  ttaakkeenn  aaccttiioonn  iinn  
rreessppoonnssee  ttoo  ddiisscclloosseedd  ffiinnaanncciiaall  iinntteerreessttss..      
WWee  sseenntt  tthhee  ssuurrvveeyy  ttoo  779900  ppootteennttiiaall  rreevviieewweerrss  iiddeennttiiffiieedd  bbyy  FFDDAA  cceenntteerr  
ooffffiicciiaallss..    OOff  tthhoossee,,  333377  rreevviieewweerrss  rreessppoonnddeedd  aanndd,,  ooff  tthheessee,,  116622  iinnddiiccaatteedd  
tthhaatt  tthheeyy  hhaadd  rreevviieewweedd  ffiinnaanncciiaall  iinnffoorrmmaattiioonn  iinn  tthhee  ppaasstt  33  yyeeaarrss..    WWee  ddoo  
nnoott  pprroojjeecctt  tthhee  rreessppoonnsseess  ttoo  aallll  FFDDAA  rreevviieewweerrss  aanndd  pprreesseenntt  ssuurrvveeyy  ddaattaa  
oonnllyy  ffrroomm  tthhee  116622  rreevviieewweerrss  aass  sseeccoonnddaarryy  eevviiddeennccee  iinn  oouurr  ffiinnddiinnggss..    SSeeee  
AAppppeennddiixx  DD  ffoorr  aa  bbrreeaakkddoowwnn  ooff  ssuurrvveeyy  rreessppoonnsseess  bbyy  FFDDAA  cceenntteerr..  
DDaattaa  AAnnaallyyssiiss  
DDeessccrriibbiinngg  tthhee  eexxtteenntt  aanndd  nnaattuurree  ooff  ddiisscclloosseedd  ffiinnaanncciiaall  iinntteerreessttss.  To 
describe the extent of disclosed financial interests, we reviewed all 
financial forms in marketing applications to classify each clinical 
investigator as:  (1) having no financial interest, (2) disclosing a 
financial interest, or (3) unable to provide financial information.  In 
total, sponsors listed 29,691 clinical investigators on financial forms.  
We did not include clinical investigators that the sponsor identified as 
employees because it was ambiguous whether sponsors were disclosing 
a financial arrangement for these employees.  Sponsors are exempt from 
submitting financial information for employees.44   
We also described the extent of disclosed financial interests by 
calculating the percentage of marketing applications with at least one 
disclosed financial interest.     
To describe the nature of clinical investigators disclosed financial 
interests, we categorized financial interests using FDAs four financial 
disclosure categories listed on the disclosure form.  We used disclosed 
financial interests as the unit of analysis for this assessment because 
clinical investigators could disclose multiple financial interests in a 
marketing application. 
 
44 21 CFR  54.4. 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  10   
   
 I   N T R O D UU CC TT II OO NN   
  
IInn  ffoouurr  mmaarrkkeettiinngg  aapppplliiccaattiioonnss,,  ssppoonnssoorrss  ddiisscclloosseedd  1122  ffiinnaanncciiaall  iinntteerreessttss  
tthhaatt  ffeellll  bbeellooww  tthhee  ffeeddeerraallllyy  ddeeffiinneedd  tthhrreesshhoolldd..    WWee  ssttiillll  ccaatteeggoorriizzeedd  
tthheessee  aass  ddiisscclloosseedd  ffiinnaanncciiaall  iinntteerreessttss  bbeeccaauussee  ssppoonnssoorrss  iinnffoorrmmeedd  FFDDAA  ooff  
ffiinnaanncciiaall  rreellaattiioonnsshhiippss  wwiitthh  cclliinniiccaall  iinnvveessttiiggaattoorrss..  
AAsssseessssiinngg  wwhheetthheerr  mmaarrkkeettiinngg  aapppplliiccaattiioonnss  ccoonnttaaiinneedd  ccoommpplleettee  ffiinnaanncciiaall  
information.  We assessed whether marketing applications had complete 
financial information by reviewing submitted financial forms and 
attachments.  We categorized a marketing application as having 
complete financial information if it met four criteria:  (1) included either 
a certification or disclosure form, (2) included an attachment with a 
description of steps taken to minimize potential bias with each 
disclosure form, (3) included an attachment detailing descriptions of 
disclosed financial interests with each disclosure form, and (4) did not 
claim the due diligence exemption indicating that at least one clinical 
investigator did not provide financial information.  We categorized a 
marketing application as having incomplete financial information if it 
failed to meet any of these four criteria. 
Assessing FDAs review of financial information.  To assess FDAs review 
of financial information in FY 2007, we analyzed FDAs review notes.  
We calculated the percentage of marketing applications with any 
mention of financial information in the review notes.  For this analysis, 
we excluded administrative checklists that are used to check for 
financial interests forms.  Checklists help ensure that sponsors submit 
forms, but do not indicate whether FDA reviewers read and evaluated 
the forms. 
We also calculated the percentage of marketing applications with 
disclosed financial interests that had detailed review notes.  We 
categorized review notes as detailed if they mention any of four things:  
(1) the sponsors actions to decrease potential bias, (2) aspects of the 
study design that may have minimized potential bias, (3) action taken 
to ensure data reliability, or (4) a request for additional financial 
information from sponsors.   
Assessing sponsors and FDA actions in response to disclosed financial 
interests.  To assess the extent of sponsors actions, we calculated the 
percentage of marketing applications on which sponsors indicated that 
they took action to minimize potential bias for all clinical investigators 
with disclosed financial interests.  Regulations require that sponsors 
report their actions to minimize potential bias for all disclosed financial 
interests.  Thus, we did not count two marketing applications on which 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  11   
   
 I N T R O D U C T I O N  
sponsors reported their steps for only some disclosed financial interests 
as sponsors taking actions.   
To assess the extent of FDA reviewers actions, we calculated the 
percentage of marketing applications with review notes indicating any 
action taken or requested by an FDA reviewer.  To assess the nature of 
FDA reviewers actions, we reviewed FDAs review notes.  We 
categorized FDAs actions based on the examples listed in FDA 
regulation.  Because the regulations do not provide an exhaustive list, 
we also considered reanalyzing clinical trial results from clinical 
investigators with disclosed financial interests as an action.   
Limitations 
The number of clinical investigators listed on financial forms from 
marketing applications may be slightly inflated.  Sponsors often listed 
clinical investigators without financial interests, as an attachment to 
the certification form, by their clinical trial site.  Because clinical 
investigators may work on multiple clinical trial sites, investigators 
may have been listed more than once.  We attempted to address this by 
conducting electronic searches for duplicate names.  As a result, we 
expect any potential overestimation to be minimal.   
We relied solely on review notes as an indication that FDA reviewers 
evaluated financial information.  FDA reviewers are required to 
evaluate financial information but are not required to provide written 
documentation of this review.  Therefore, FDA reviewers may have 
evaluated financial information but failed to note their review.  
Nonetheless, written notes remain the most reliable evidence of an FDA 
review.  Division directors review these written notes when determining 
whether to recommend that FDA approve a marketing application.45 
We also relied solely on review notes as an indication that FDA 
reviewers took action in response to disclosed financial interests.  FDA 
reviewers may have taken action in response to disclosed financial 
interests but failed to note their action.  Similar to assessing whether 
FDA reviewers evaluated financial information, written notes remain 
the most reliable evidence of FDA action.   
 
 
45 FDA, The FDAs Drug Review Process:  Ensuring Drugs Are Safe and Effective.  
Available online at http://www.fda.gov/fdac/features/2002/402_drug.html.  Accessed on 
March 27, 2008. 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  12   
   
I N T R O D U C T I O N  
Standards 
This study was conducted in accordance with the Quality Standards for 
Inspections issued by the Presidents Council on Integrity and 
Efficiency and the Executive Council on Integrity and Efficiency. 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  13   
   
F I N D I N G S  
 F I N D I N G S  
One percent of clinical investigators disclosed a  Among clinical investigators 
financial interest   listed in financial forms,                
1 percent disclosed at least one 
financial interest.  This represents 206 of the 29,691 clinical 
investigators.  Of the 206 clinical investigators, almost all disclosed only 
one financial interest, with a few disclosing two or three financial 
interests.  Four clinical investigators disclosed two financial interests 
and two clinical investigators disclosed three financial interests. 
Disclosed financial interests were associated with almost half of marketing 
applications 
Forty-two percent of marketing applications included at least one 
clinical investigator with a disclosed financial interest.  This represents 
49 of 118 marketing applications.   
Although most applications had few disclosed financial interests, some 
applications had numerous clinical investigators with disclosed 
financial interests.  Sixty-seven percent of the 49 marketing 
applications with disclosed financial interests had one or two clinical 
investigators with a disclosed financial interest.  On the other hand,    
12 percent of these 49 marketing applications included 10 or more 
clinical investigators with a disclosed financial interest.  The application 
with the most disclosed financial interests had 38 clinical investigators 
with financial interests.     
Most disclosed financial interests were payments from sponsors   
Seventy-seven percent of disclosed financial interests were for payments 
from sponsors.  Most payments were for consulting services or general 
honoraria.  Though not required, 53 percent of payment disclosures 
included a specific dollar amount.  The median reported payment was 
$47,252, almost twice the $25,000 minimum payment reporting 
threshold.  The highest reported payment was a sponsors payment of 
$3.9 million to a clinical investigators affiliated institution.     
Nineteen percent of disclosed financial interests were for equity 
interests, primarily stock options.  Though not required, 46 percent of 
equity disclosures included a specific dollar amount.  The median 
reported equity interest was $65,000.  This exceeds the $50,000 
minimum equity reporting threshold by $15,000.  The highest reported 
equity interest was $148,751.   
Two percent of disclosed financial interests were for proprietary 
interests.  Most of the marketing applications that included proprietary 
interests were for medical devices.   
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  14   
   
F I N D I N G S  
Lastly, 1 percent of disclosed financial interests were financial 
arrangements that could influence the study outcome.  Sponsors 
included additional descriptions of only one of these disclosed financial 
interests.  This clinical investigator was a patent owner of the product.  
See Table 1 for a list of clinical investigators disclosed financial 
interests by FDAs financial disclosure categories.   
 
Table 1:  Disclosed Financial Interests 
 
Percentage of Total 
   Number of Disclosed  Disclosed Financial 
FDA Financial Disclosure Category  Financial Interests   Interests
 
Payments from sponsors  165  77 percent 
Equ ity interests  41  19 percent 
Proprietary interests in tested product  5  2 percent 
 
Financial arrangements that could influence 
 
the study outcome  3  1 percent 
     T otal  214*  99 percent** 
* Clinical investigators can disclose more than one financial interest.  There were 206 clinical investigators with         
  214 disclosed financial interests. 
** Total does not equal 100 percent because of rounding. 
 
Source:  OIG analysis of marketing applications, 2008. 
 
FDA cannot determine whether 
FDA cannot determine whether sponsors have 
sponsors have submitted financial 
submitted financial information for all clinical 
information for all clinical 
investigators 
investigators because it does not 
have a complete list of clinical investigators.  In addition, FDA does not 
use onsite BiMo inspections as a mechanism to confirm that submitted 
financial information is complete.  These limitations could result in FDA 
being unaware of a clinical investigators financial interest and thus 
unable to gauge its potential bias on clinical trial results.  
FDA does not have a complete list of clinical investigators  
FDA cannot systematically check whether marketing applications have 
financial information for all clinical investigators because FDA does not 
maintain a complete list of clinical investigators.  FDA was able to 
provide a complete list of clinical investigators for only 7 percent of 
marketing applications approved in FY 2007.   
Although FDA maintains a database that captures demographic and 
inspection information on clinical investigators, it currently cannot be 
used to easily compile a complete list of clinical investigators per 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  15   
   
F I N D I N G S  
marketing application.  FDAs Bioresearch Monitoring Information 
System database contains information for some clinical investigators.  
However, the database does not list subinvestigators for two FDA 
centers.  In addition, the database only includes clinical investigators 
listed in pretrial applications, and does not include any clinical 
investigators who might have been recruited once the clinical trials 
were underway. 
BiMo inspections do not routinely review financial information 
BiMo inspectors are not instructed to routinely review financial 
information as part of their inspection protocol.  Currently, BiMo 
inspectors review financial information only when an FDA reviewer 
specifically requests it or when an inspector takes personal initiative.  
Although BiMo inspects only a small portion of all clinical trial sites, 
these inspections are FDAs only onsite and indepth tool for reviewing 
sponsors and clinical investigators.  
When BiMo inspectors reviewed financial information in the recent 
past, they found that sponsors had submitted incomplete financial 
information to FDA.  For instance, in 2005, an inspection found that a 
clinical investigator did not submit financial information for a 
subinvestigator.  As a result, FDA issued a letter to the clinical 
investigator suggesting areas of improvement.   
In another example, FDA reviewers, in 2006, requested an inspection of 
clinical investigators and a sponsor because of concerns about financial 
interests.  BiMo inspectors found that a clinical investigator violated 
regulations by failing to disclose financial interests to the sponsor.  
BiMo inspectors also found that the sponsor failed to disclose the 
financial interests of an additional five clinical investigators to FDA.  
FDA issued the sponsor a letter suggesting areas of improvement.   
Moreover, when BiMo inspectors reviewed a sponsor in 2005, they found 
that the sponsor collected financial information shortly before the 
submission of the marketing application and not before beginning the 
clinical trial.  According to regulation, sponsors are required to collect 
financial information from clinical investigators before beginning 
clinical trials. 
 
 
 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  16   
   
FFF III NNN DDD III NNN GGG SSS    
Forty-two percent of 
Forty-two percent of FDA-approved marketing 
approved marketing 
applications were missing financial information 
applications did not include 
complete financial 
information.  Twenty-three percent of these marketing applications 
were missing required financial forms or attachments.  Twenty-eight 
percent were missing financial information because sponsors used the 
due diligence exemption to indicate that they were unable to provide 
financial information.  Although allowed by regulation, sponsors use of 
the diligence exemption results in no financial information for FDA 
reviewers.  Some marketing applications had both missing attachments 
and the due diligence exemption marked.    
Twenty-three percent of approved marketing applications did not include 
required financial forms or attachments  
Twenty-three percent of all 118 marketing applications approved in           
FY 2007 were missing financial interest forms or required attachments 
with disclosed financial interests.  Of these, 7 percent did not include 
any certification or disclosure forms for any clinical investigators.   
Among marketing applications with disclosed financial interests,              
24 percent were missing the sponsors actions to minimize potential bias 
resulting from disclosed financial interests.  In addition, 18 percent of 
marketing applications with disclosed financial interests were missing 
detailed descriptions of the financial interests. 
Twenty-eight percent of marketing applications indicated that sponsors 
were unable to provide complete financial information 
Twenty-eight percent of marketing applications included certification 
forms on which sponsors used the due diligence exemption to claim that 
they were unable to obtain complete financial information.  As 
previously stated, Federal regulations allow sponsors to indicate that 
they acted with due diligence but were unable to obtain financial 
information from a clinical investigator.  In total, sponsors indicated 
that they were unable to provide financial information for 1,123 clinical 
investigators.  This is more than five times the 206 clinical investigators 
who disclosed financial interests.  
If sponsors use the due diligence exemption, regulations require them to 
explain why they were unable to obtain the information.  In 18 percent 
of marketing applications indicating due diligence, sponsors did not 
explain why they were unable to obtain financial information from all 
clinical investigators, as required.  When sponsors did include this 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  17   
   
F I N D I N G S  
explanation, they most often reported that clinical investigators could 
not be located or failed to return the financial form. 
 
FDA did not document a review of any financial  FDA reviewers did not document a 
review of financial information for  
information for 31 percent of marketing 
31 percent of marketing 
applications 
applications.  Over one-third of 
these marketing applications included disclosed financial interests.  If 
FDA reviewers fail to document a review, division directors may 
overlook disclosed financial interests and their potential impact on data 
integrity. 
Review templates increased the likelihood of a documented review of 
financial information 
Reviewers from CDER, the only center to consistently use a review 
template, documented a review of financial information for 95 percent of 
marketing applications.  CDER reviewers used a review template         
94 percent of the time when documenting a review of financial 
information.   
Reviewers from CBER documented a review of financial information in         
23 percent of marketing applications.  CBER is in the process of 
finalizing a review template similar to CDERs template.  When CBER 
reviewers documented a review of financial information, they always 
used a template.      
The CDER review template and CBERs draft template prompt 
reviewers to discuss whether the applicant adequately disclosed 
financial arrangements with clinical investigators and whether these 
arrangements raise questions about the integrity of the data.46  The 
review template assigns a specific member of the review team the 
responsibility of reviewing financial information. 
Reviewers from CDRH documented a review of financial information in        
28 percent of marketing applications.  CDRH reviewers do not use a 
review template.   
 
46 FDA, Manual of Policies and Procedures:  Clinical Review Template, July 9, 2004,           
p. 17.  Available online at http://www.fda.gov/cder/mapp/6010.3.pdf.  Accessed on         
March 28, 2008. 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  18   
   
FF II NN DD II NN GG SS   
See Table 2 for FDA reviewers documented reviews of financial 
information by center. 
 
 
Table 2:  FDA Reviewers Documented Reviews 
 
Percentage of Marketing 
  Applications With  Percentage of 
Documented  Reviews of  Documented Reviews 
FDA C enter  Marketing Applications  Financial Information  Found in a Template 
CDER  73  95 percent  94 percent 
 
CDRH  32  28 percent  0 percent*  
 
CBER  13  23 percent  100 percent 
 
     Total  118  69 percent  63 percent 
*  CDRH  reviewers do not use a template. 
Source:  OIG analysis of FDA review notes, 2008. 
 
Most documented reviews of marketing applications with disclosed financial 
interests were detailed  
Seventy-three percent of marketing applications with disclosed financial 
interests had documented reviews.  Among these documented reviews, 
72 percent of review notes were detailed and the remaining 28 percent 
were nondetailed.   
Detailed notes provided evidence of more complete analyses of how 
disclosed financial interests might affect clinical trial results.  For 
example, one detailed note stated that Dr. X received more than 
$25,000 in honoraria and travel expenses for educational activities.  Any 
bias was minimized by the independent data monitoring, by the use of 
multiple investigators, and by the use of double-blind placebo-controlled 
trials.   
Nondetailed notes indicated that a more cursory review may have been 
undertaken.  Most commonly, nondetailed notes either mentioned that 
financial information was included or summarized the financial 
information.  For example, one nondetailed note stated that 
Certificates of financial disclosure were submitted in compliance with 
the Final Rule on Financial Disclosure by Clinical Investigators.   
Division directors reading nondetailed notes may overlook or 
underestimate the impact of disclosed financial interests on clinical trial 
results.  On the other hand, division directors can use detailed notes to 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  19   
   
FF II  NN DD II NN GG SS   
determine financial interests potential impact on data integrity before 
recommending possible approval of a marketing application. 
 
Neither FDA nor sponsors took action for      Neither FDA reviewers nor 
20 percent of marketing applications with  sponsors noted taking action in 
response to disclosed financial 
disclosed financial interests 
interests for 20 percent of 
marketing applications with disclosed financial interests.  FDA 
reviewers did not take action on 88 percent47 of marketing applications 
with disclosed financial interests.  However, in 67 percent of marketing 
applications with disclosed financial interests, sponsors indicated that 
they acted to minimize potential bias during the clinical trials.  For 
example, sponsors hired independent observers to monitor clinical trial 
sites.  Sponsors also prevented clinical investigators with financial 
interests from knowing whether subjects were in the experimental or 
the control group.  When sponsors took action, FDA reviewers may have 
judged sponsors actions to be sufficient, and have seen no need for 
further action. 
On the other hand, FDA reviewers did not take action on 20 percent of 
marketing applications with disclosed financial interests upon which 
sponsors did not indicate taking action to minimize potential bias.  To 
protect data integrity, sponsors are required to describe their actions to 
minimize potential bias related to all disclosed financial interests.  
Although FDA reviewers may have had other reasons to believe that 
disclosed financial interests did not compromise data integrity, FDA 
reviewers did not have the assurance that sponsors acted to minimize 
potential bias during the clinical trials.   
In addition, there was no documented FDA review of financial 
information in more than half of the marketing applications upon which 
no action was taken.  Because FDA reviewers may have not reviewed 
financial information, they may not have had sufficient information to 
judge whether action to address potential bias was warranted.   
See Table 3 on the next page for sponsors and FDA reviewers action in 
response to marketing applications with disclosed financial interests. 
 
47 FDA reviewers did not review 87.7 percent of marketing applications with disclosed 
financial interests, which we have rounded to 88 percent.  
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  20   
   
FF II NN DD II NN GG SS   
 
Table 3:  Sponsors and FDA Reviewers Actions  
 
Number of Marketing  Percentage of Marketing Applications 
 
  Applications  With Disclosed Financial Interests 
No sponsor a ction; no FDA action  10  20 percent 
No sponsor action; FDA action  3  6 percent 
 
Sponsor action; no FDA action  33  67 percent 
 
Sponsor action; FDA action  3  6 percent 
     Total    49  99 percent* 
* Total does not equal 100 percent because of rounding. 
 
Source:  OIG analysis of marketing applications and FDA review notes, 2008. 
 
FDA reviewers did not consistently take action in response to disclosed 
financial interests  
Based on FDA reviewers documented notes, FDA reviewers took action 
inconsistently.  FDA reviewers took action on 12 percent of marketing 
applications with disclosed financial interests.  However, FDA reviewers 
did not take action on other marketing applications with disclosed 
financial interests.  In the cases in which FDA reviewers did not take 
action, they may have determined that other aspects of the marketing 
application mitigated the need for action, despite the disclosed financial 
interests.  However, if this was the case, FDA reviewers did not 
document this assessment in their review notes.  See Appendix E for a 
description of FDA actions taken in response to disclosed financial 
interests.   
Marketing applications upon which FDA took action had disclosed 
financial interests similar to marketing applications upon which FDA 
reviewers took no action.  In one marketing application, an FDA 
reviewer took action when sponsors failed to provide any financial 
forms.  Yet FDA approved 7 percent of marketing applications without 
any financial forms.   
In another marketing application, an FDA reviewer took action when a 
clinical investigator with disclosed financial interests enrolled a large 
number of patients.  However, a different FDA reviewer took no action 
although two clinical investigators with disclosed financial interests 
enrolled a quarter of all patients.   
In a third marketing application, an FDA reviewer took action because 
over a quarter of clinical investigators disclosed financial interests.  Yet 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  21   
   
FF II NN DD II NN GG SS   
on two other marketing applications, over a quarter of clinical 
investigators disclosed financial interests, but no FDA action was taken. 
Reviewer discretion may explain why action was taken in some 
instances and not others.  FDA states that reviewers should be given 
the flexibility to consider financial information and steps taken to 
minimize bias on a case-by-case basis.48     
Despite being given such discretion, only 10 percent of surveyed FDA 
reviewers reported receiving instruction from FDA regarding how to 
review financial information.  In addition, 70 percent of surveyed 
reviewers indicated that further instructions would be helpful.     
Most FDA action can only occur after clinical trials are complete because 
FDA receives financial information only with the marketing application 
Most FDA action to ensure that disclosed financial interests do not 
affect data integrity can occur only after clinical trials are complete 
because FDA does not receive financial information before the 
marketing application.  FDA could take action during clinical trials, 
such as conducting a BiMo inspection, if it were alerted to potential 
issues related to financial interests.  FDA encourages sponsors to 
engage in early consultation with FDA if they are concerned about their 
financial arrangements with clinical investigators.49  However, all cases 
of FDA reviewers actions in response to disclosed financial interests in 
FY 2007 took place after the clinical trials were complete.   
When sponsors submit financial information to FDA with the marketing 
application, reviewers face time constraints.  FDAs review of marketing 
applications is subject to nonbinding timelines, per Federal law.50  
Consequentially, FDA reviewers have limited time to take action to 
determine how disclosed financial interests may have affected data 
integrity.  In fact, a previous OIG report found that 58 percent of CDER 
reviewers had concerns about time constraints for approving marketing 
applications.51 
 
48 63 Fed. Reg. 5236 (Feb. 2, 1998). 
49 Ibid. 
50 The Prescription Drug User Fee Act, 21 U.S.C.  379g-h and the Medical Device User 
Fee and Modernization Act, 21 U.S.C.  379j authorize FDA to collect user fees from 
manufacturers in an effort to streamline and improve the timeliness of the review and 
approval of new drugs and medical devices. 
51 OIG, FDAs Review Process for New Drug Applications, OEI-01-01-00590,                 
March 2003.   
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 R E C O M M E N D A T I O N S  
Financial interests between clinical investigators and sponsors create a 
potential for bias that may compromise the safety of human subjects 
and the integrity of research data.  Sponsors are required to disclose all 
clinical investigators financial interests to FDA in the marketing 
application.  In FY 2007, only 1 percent of clinical investigators 
disclosed a financial interest.  By way of comparison, the Journal of the 
American Medical Association reported that between 23 percent and  
28 percent of academic researchers had financial interests in medical 
companies.52  Further, we found a number of limitations in FDAs 
oversight, leaving FDA unable to determine whether sponsors submit 
financial information for all clinical investigators.  
In addition, FDA approved 42 percent of marketing applications in           
FY 2007 that were missing financial information.  FDA did not 
document a review of financial information for 31 percent of marketing 
applications. 
Finally, neither FDA nor sponsors took action for 20 percent of 
marketing applications with disclosed financial interests.  When FDA 
did act, it did not consistently take action in response to disclosed 
financial interests.  These findings lead us to the following 
recommendations:   
FDA Should Ensure That Sponsors Submit Complete Financial Information 
for All Clinical Investigators 
To ensure that sponsors submit complete financial information for all 
clinical investigators, we recommend the following: 
FDA should use a complete list of clinical investigators to check that 
sponsors have submitted financial information for all clinical investigators.  
To check that sponsors have submitted financial information for all 
clinical investigators, FDA should create a complete list of clinical 
investigators for each marketing application.  This could be done in a 
variety of ways, including: 
  requiring that sponsors submit an updated list of clinical 
  investigators with the marketing application, 
 
 
52 Justin E. Bekelman, et al., 2003.  Scope and Impact of Financial Conflicts of Interest 
in Biomedical Research, Journal of the American Medical Association, vol. 289(4), p. 456.  
Available online at http://jama.ama-assn.org/cgi/reprint/289/4/454?ijkey= 
9e08192f3f85916bd89686c6af4713ad33b514ea.  Accessed on May 30, 2008. 
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RR EE CC OO MM MM EE NN DD AA TT II OO NN SS   
  modifying the Bioresearch Monitoring Information System to 
  identify all clinical investigators, or  
  modifying other FDA databases to capture information on clinical 
  investigators and link it to marketing applications.   
FDA should check that sponsors have submitted all required attachments to 
financial forms.  To ensure that sponsors have submitted required 
attachments to financial forms, FDA centers should use a checklist that 
includes a check for attachments to financial forms during the 
administrative filing of marketing applications.     
FDA should update guidance to sponsors regarding the due diligence 
exemption.  FDA should update guidance stressing that sponsors should 
only rarely use the due diligence exemption.  Given that sponsors are 
required to obtain financial information from clinical investigators 
before starting clinical trials, sponsors should always have the 
information they need to submit to FDA.   
In addition, FDA should update guidance to sponsors incorporating its 
2002 explanation of due diligence, which is currently provided only in 
Federal Register comments.  This would clarify that due diligence is 
making at least two telephone calls and sending two certified letters. 
This sets a higher threshold for sponsors to meet before claiming the 
due diligence exemption than the current threshold of a reasonable 
judgment made by the sponsor. 
FDA should add a review of financial information to the onsite inspection 
protocol.  To help identify previously unknown financial interests, FDA 
should add a review of financial information to sponsor and clinical 
investigator BiMo inspection protocols.   
FDA Should Ensure That Reviewers Consistently Review Financial 
Information and Take Action in Response to Disclosed Financial Interests 
To ensure that reviewers consistently review and take action in 
response to financial information, we recommend the following:   
FDA should require that all centers consistently use a template that 
includes a prompt to document a review of financial information.  To help 
ensure that reviews of financial information are completed and 
documented, CBER should finalize its draft Clinical Review Template.  
CDRH should develop a review template that includes a prompt to 
document a review of financial information.   
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  24   
   
R E C O M M E N D A T I O N S  
FDA should provide additional guidance and training to reviewers.  The 
guidance and training could address how to review financial 
information, how to identify bias, and how and when to take action to 
ensure data integrity.  
FDA Should Require That Sponsors Submit Financial Information for 
Clinical Investigators as Part of the Pretrial Application Process 
We recommend that the pretrial application process be amended to 
require that sponsors submit financial information for clinical 
investigators.  As each clinical investigator begins work on a clinical 
trial, sponsors should be required to either certify that clinical 
investigators do not have a financial interest with the sponsor or 
disclose a financial interest.  For disclosed financial interests, sponsors 
should describe the financial interest and sponsors actions to minimize 
any potential bias these financial interests may cause.   
Implementing this recommendation would require only minimal 
changes to FDAs current process.  Sponsors are already required to 
collect financial information from clinical investigators prior to 
beginning clinical trials.  Further, FDA already engages with sponsors 
during the clinical trials.  First, FDA approves the clinical trial protocol 
as part of the pretrial application.  Then, as clinical trials get underway, 
sponsors are required to submit information on each clinical 
investigator they hire.  Financial information for each clinical 
investigator could be included with these submissions.  However, we 
recognize that FDA reviewers face time and resource constraints.  Thus, 
we recommend that FDA build this review into the pretrial application 
process in the best way it sees fit, perhaps focusing most attention on 
disclosed financial interests.  
If FDA received financial information before clinical trials, FDA could 
ensure that sponsors are collecting financial information before trials 
and are taking action to ensure that disclosed financial interests do not 
threaten human subjects or compromise data integrity.  In addition, 
FDA is now devoting one-third of BiMo resources to ongoing clinical 
trials, as opposed to focusing solely on completed trials, according to 
FDA officials.  Having information about a clinical investigators 
financial interest could help FDA target which clinical trial sites are 
chosen for BiMo inspections.  Finally, FDA has acknowledged the 
importance of obtaining this information before a clinical trial.  FDA 
asserts that receiving clinical investigators financial information before 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  25   
   
R E C O M M E N D A T I O N S  
a trial allows sponsors the opportunity to consult with FDA and take 
action to minimize any potential study bias.53   
In addition to requiring that sponsors submit financial information 
during the pretrial application process, sponsors should still be required 
to submit financial information with the marketing application.  This 
ensures that FDA can review updated financial information for clinical 
investigators.  It also ensures that financial information will be 
submitted for any clinical investigators whose information was not 
submitted as part of the pretrial application process. 
AGENCY COMMENTS AND OFFICE OF INSPECTOR GENERAL 
RESPONSE 
FDA expressed concerns about elements of our analysis in three of our 
findings.  In addition, FDA agreed with all of our recommendations 
except the recommendation that FDA require sponsors to submit 
financial information for clinical investigators as part of the pretrial 
application process. 
With respect to the first finding that 1 percent of clinical investigators 
disclosed a financial interest, FDA disagreed with our decision to report           
36 disclosures for employees of the sponsor.  Based on FDAs concern, 
we removed 34 disclosures for employees from our analysis because it 
was ambiguous whether sponsors were disclosing a financial interest for 
these employees.  Two employees had clearly disclosed financial 
interests and thus were kept in our analysis.  FDA also objected to our 
decision to report 12 disclosures that fell below the defined threshold.  
We continue to include these disclosures because it was our intention to 
describe all disclosures in FY 2007, even those not required by 
regulation.  We assumed that sponsors purposefully disclosed these 
financial interests to FDA and did not question the validity of the 
disclosures.      
In our second finding, we state that FDA cannot determine whether 
sponsors have submitted financial information for all clinical 
investigators because it does not have a complete list of clinical 
investigators.  FDA took exception to our statement that FDA could 
provide complete lists of clinical investigators for only 7 percent of 
marketing applications.  FDA believed that we did not clearly ask for 
 
53 67 Fed. Reg. 6042 (Feb. 8, 2002) 
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R E C O M M E N D A T I O N S  
this information.  However, we submitted an official written request to 
FDA for a list of clinical investigators from approved marketing 
applications.  From discussions with FDA, we understood that there is 
often no list of clinical investigators in marketing applications but that 
FDA would provide us these lists when found.  In fact, subsequently 
FDA did provide us with some lists of clinical investigators, but we 
could not validate the accuracy or completeness of the lists provided. 
Finally, FDA did not agree with our decision to consider applications 
indicating due diligence as incomplete.  We acknowledge that 
regulations allow sponsors to claim the due diligence exemption, but we 
maintain that sponsors failure to submit financial information for all 
clinical investigators, whether they indicated due diligence or not, 
constitutes missing financial information.  In these cases, FDA 
reviewers have incomplete knowledge of clinical investigators financial 
information. 
In response to our recommendation that FDA ensure that sponsors 
submit complete financial information, FDA stated that it is considering 
revising its guidance to industry to instruct sponsors to provide a table 
listing all clinical investigators and indicating whether a certification 
form, a disclosure form, or the due diligence exemption is being 
provided.  FDA also stated that it is reviewing its procedures to 
determine whether modifications are needed to ensure that all required 
attachments are submitted.  In addition, FDA stated that it is 
considering providing additional advice to sponsors on the use of the due 
diligence exemption.  Finally, FDA stated that it has updated its onsite 
inspection protocol to include a closer inspection of financial 
information.       
In response to our recommendation that FDA reviewers consistently 
review financial information, FDA indicated that it is evaluating its 
review procedures and templates.  In addition, FDA is considering 
developing additional guidance and training for reviewers on the review 
of financial disclosure information. 
For many reasons, FDA did not agree with our final recommendation 
that FDA require sponsors to submit financial information for clinical 
investigators as part of the pretrial application process.   
FDA emphasized that collecting financial information before a clinical 
trial starts is the sponsors responsibility.  However, FDA has no 
mechanism to ensure that sponsors are collecting financial information 
before beginning clinical trials.  In fact, FDA commented that sponsors 
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R E C O M M E N D A T I O N S  
may find obtaining financial information difficult because there can be a 
significant amount of time between completion of a clinical trial and 
submission of the marketing application.  However, if sponsors were 
collecting financial information for all clinical investigators before they 
participated in a clinical trial as required, the lag time between when 
the clinical trial ended and when the marketing application was 
submitted would be irrelevant.  Receiving financial information during 
the pretrial application process would allow FDA to ensure that 
sponsors were collecting financial information before beginning clinical 
trials, as required. 
FDA also stated that financial interests are only one potential source of 
bias of clinical trials, emphasizing the importance of proper study 
design as a means for minimizing bias.  Although it is true that there 
are multiple sources of potential bias, FDA acknowledged that sponsors 
are required to collect financial information before beginning a clinical 
trial so that they can identify and manage all potential sources of bias to 
ensure that human subjects are protected and data are reliable.  
Similarly, FDA could use information on all potential sources of bias, 
including financial information, to help sponsors identify potential bias 
before beginning clinical trials. 
FDA also believes that for industry to collect and submit financial 
information and for FDA to review this information during the pretrial 
application process would represent significant additional work.  
However, pursuant to regulation, FDA already requires sponsors to 
collect financial information from clinical investigators before starting a 
clinical trial.  In addition, basic information on clinical investigators is 
submitted to FDA as they are added to clinical trials.  Thus, it is unclear 
how submitting financial information that is already collected, as well 
as the other information on clinical investigators that sponsors submit 
to FDA, would be a significant addition of effort on sponsors part.  
Further, FDA stated that it intends to improve its oversight of ongoing 
clinical trials.  Therefore, receiving financial information about ongoing 
clinical trials adds to an oversight initiative that is presently underway.  
FDA also pointed out that many clinical trials are ultimately not 
submitted in a marketing application, thus making a review of financial 
information in the pretrial application process a potential waste of time.  
However, FDA stated its intention to improve its oversight of ongoing 
trials.  Further, even if clinical trials do not result in a marketing 
application, the investigational products are still being tested on human 
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R E C O M M E N D A T I O N S  
subjects.  To protect human subjects, FDA should take a proactive 
approach to ensure that clinical investigators are not biased when 
recruiting and testing investigational products on human subjects.   
We continue to recommend that FDA require sponsors to submit 
financial information as part of the pretrial application process.  
Acknowledging the added burden to FDAs administrative and review 
staff, we encourage FDA to develop a review of financial information 
that best balances the additional effort with the potential benefits.       
For the full text of FDAs comments, see Appendix F.  FDAs technical 
comments are not included, but we made changes in the report where 
appropriate. 
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 A P P E N D I X   ~   A  
  
 CERTIFICATION OF NO FINANCIAL INTERESTS, FORM 3454 
 
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   A P P E N D I X   ~   B  
 
DISCLOSURE OF FINANCIAL INTERESTS, FORM 3455 
 
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   A P P E N D I X   ~   C  
 
FINANCIAL FORMS SUBMITTED TO EACH CENTER IN FISCAL 
YEAR 2007 
 
   
  Chart 1:  Financial Forms Submitted to Each Food and Drug Administration Center in FY 2007 
 
80
75
4
70
65 Does Not Include Any Financial Information
ns 60
o
plicati 55 31 Includes Forms That Disclose Financial Interests   
Ap 50
g 
n
keti 45 Includes Only Forms Certifying No Financial Interests
Mar 40
of 
er  35
umb 30 3
N
25
17
20
38
15
1
10 1
5 12 11
0
                       Center for                                                         Center for                                                      Center for                             
Drug Evaluation and Research   Device and Radiological Health  Biologics Evaluation and Research
Food and Drug Administration Center
Source:  Office of Inspector General analysis of marketing applications, 2008. 
 
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   A P P E N D I X   ~   D  
RESPONSE RATES FOR REVIEWER SURVEY 
Our goal was to survey the Food and Drug Administration (FDA) 
reviewers who evaluated financial information within the past 3 years.  
However, not all centers could identify a specific population of reviewers 
that evaluate financial information.  Therefore, for two centers, we sent 
surveys to all reviewers who reviewed a marketing application in the 
last 3 years.  Thus, we distributed our survey to a high proportion of 
reviewers who did not evaluate financial information in the past                   
3 years.  See Table 4 for survey responses by FDA center. 
 
 
Table 4:  Survey Responses by FDA Center 
 
 
 
  Respondents Who 
    Total Surveys  Total  Reported Evaluating 
Center  Survey Recipients  Sent  Respondents  Financial Information 
         
Center for Drug 
       
Evaluation and 
         
Research (CDER)* 
Medical officers  308  109  87 
  Reviewers who       
Center for Devices and 
reviewed a marketing       
Radiological He alth 
application in the last       
(CDRH)** 
3 years  305  176  61 
 
Reviewers who       
Center for Biologics 
reviewed a marketing       
Evaluation and  
application in the last       
Research (CBER)** 
3 years  177  52  14 
 
 
     Total  790  337  162 
 
* CDER identified medical officers as the discipline of reviewers who routinely evaluate financial information.   
 
** CDRH and CBER could not identify a specific discipline of reviewers who routinely evaluate financial information.  Therefore, the 
centers identified al l reviewers who reviewed a marketing application in the last 3 years, regardless of whether they evaluated 
financial information.  
 
Source:  Office of the Inspector General analysis of electronic survey respondents, 2008. 
   
 
  OEI-05-07-00730  FDAS OVERSIGHT OF CLINICAL INVESTIGATORS FINANCIAL INFORMATION  33   
   
   A P P E N D I X   ~   E  
DESCRIPTION OF FOOD AND DRUG ADMINISTRATION 
ACTION  
When the Food and Drug Administration (FDA) reviewers took action in 
response to disclosed financial interests, they most often conducted their 
own analyses to identify potential bias.  Additionally, two reviewers 
requested inspections from the Bioresearch Monitoring Program (BiMo) 
and one reviewer requested additional analysis from the sponsor.  As a 
result of their actions, FDA reviewers determined that the disclosed 
financial interests did not compromise the integrity of the data.  See 
Table 5 for details of FDA action for the six marketing applications on 
which FDA took action. 
Table 5:  Details of FDA Actions in Response to Marketing Applications 
With Disclosed Financial Interests 
 FDA Action Per Marketing Application  Reason Action Was Taken 
Compared outcomes from investigators with  Over a quarter of clinical investigators had 
financial interests against those without  disclosed financial interests  
Compared outcomes from investigators with  Some clinical investigators with disclosed 
financial interests against study mean*  financial interests had very favorable results 
Compared outcomes from investigators with 
Unspecified 
financial interests against study mean* 
Requested a BiMo inspection of an investigator  Investigator disclosed a financial interest and 
with a financial interest  had a large number of patients 
The sponsor originally did not submit any 
Requested a BiMo inspection of the sponsor 
financial forms 
Requested that the sponsor submit reanalysis 
of study outcomes excluding clinical  Unspecified 
investigators with financial interests* 
* Indicates marketing applications upon which sponsors also took action to decrease bias. 
Source:  Office of Inspector General analysis of marketing applications and FDA review notes, 2008. 
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 A P P E N D I X   ~   F  
AGENCY COMMENTS 
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A P P E N D I X   ~   F  
 
 
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AA PP PP EE NN DD II XX    ~~    FF   
 
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AA PP PP EE NN DD II XX    ~~    FF   
 
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AA PP PP EE NN DD II XX    ~~    FF   
 
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AA PP PP EE NN DD II XX    ~~    FF   
 
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AA PP PP EE NN DD II XX    ~~    FF   
 
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AA PP PP EE NN DD II XX    ~~    FF   
 
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AA PP PP EE NN DD II XX    ~~    FF   
 
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AA PP PP EE NN DD II XX    ~~    AD   
 AA CC KK NN OO WW LL EE DD GG ME ME NE NT ST  S  
This report was prepared under the direction of Ann Maxwell, Regional 
Inspector General for Evaluation and Inspections in the Chicago 
regional office, and Thomas Komaniecki, Deputy Regional Inspector 
General.   
Anne Bracken led this study and Beth McDowell served as the lead 
analyst.  Other principal Office of Evaluation and Inspections staff from 
the Chicago regional office who contributed to the report include Abby 
Lopez; central office staff who contributed include Robert Gibbons, 
Ayana Everett, Matthew McMullen, and Talisha Searcy. 
 
 
 
 
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