Guidance for Clinical 
Investigators, Industry,
  
and FDA Staff 
Financial Disclosure by Clinical 
Investigators 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice  
Center for Drug Evaluation and Research  
Center for Biologics Evaluation and Research  
Center for Devices and Radiological Health  
 
February 2013 Contains Nonbinding Recommendations 
Guidance for Clinical 
Investigators, Industry, 
and FDA Staff 
Financial Disclosure by Clinical 
Investigators  
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http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm219433.h
tm  
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice 
Center for Drug Evaluation and Research 
Center for Biologics Evaluation and Research 
Center for Devices and Radiological Health 
 
February 2013 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
  
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................1 
III.  FINANCIAL DISCLOSURE REQUIREMENTS.........................................................2 
A.  Definitions.......................................................................................................................................2 
B.   Disclosable Financial Interests and Arrangements....................................................................4 
C.  Agency Actions...............................................................................................................................4 
IV.  QUESTIONS AND ANSWERS.......................................................................................5 
A.  GENERAL......................................................................................................................................5 
B.  FORMS AND INFORMATION TO BE SUBMITTED.............................................................6 
C.  FINANCIAL INTERESTS AND ARRANGEMENTS SUBJECT TO DISCLOSURE........11 
D.  CLINICAL INVESTIGATOR...................................................................................................15 
E.  SPONSOR.....................................................................................................................................17 
F.  APPLICANT................................................................................................................................21 
G.  COVERED CLINICAL STUDY................................................................................................23 
H.  FDA REVIEW..............................................................................................................................26 
I.  RECORDKEEPING....................................................................................................................29 
J.  FDA INSPECTIONS...................................................................................................................30 
K.  CONTACTS.................................................................................................................................31 
APPENDIX..................................................................................................................................32 
  Contains Nonbinding Recommendations 
1
Guidance for Clinical Investigators, Industry, and FDA Staff  
Financial Disclosure by Clinical Investigators 
 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It 
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations.  If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.   
 
 
 
I.  INTRODUCTION  
 
This guidance is intended to assist clinical investigators, industry, and FDA staff in interpreting 
and complying with the regulations governing financial disclosure by clinical investigators, 21 
CFR part 54.  This document is a revision of the Guidance for Industry: Financial Disclosure by 
Clinical Investigators dated March 20, 2001.  In order to address issues raised by the Office of 
the Inspector General (OIG), Department of Health and Human Services, in its report, OEI-05-
07-00730, The Food and Drug Administrations Oversight of Clinical Investigators Financial 
Information2 as well as questions FDA has received from industry and the public, FDA issued a 
revised guidance in draft in May 2011 for public comment.  Comments were received from 13 
individuals and entities, which were considered in preparing this final guidance.  FDA 
encourages applicants and sponsors to contact the agency for advice concerning specific 
circumstances regarding financial disclosures that may raise concerns as early in the product 
development process as possible.   
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the agency's current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited.  The use of the word should in agency guidances means that something is suggested or 
recommended, but not required.   
 
 
II.  BACKGROUND 
 
The Financial Disclosure by Clinical Investigators regulation (21 CFR part 54) requires 
applicants who submit a marketing application for a drug, biological product or device to submit 
certain information concerning the compensation to, and financial interests and arrangements of, 
any clinical investigator conducting clinical studies covered by the regulation (see generally the 
                                                 
1 This revised guidance was prepared by the Office of the Commissioner, with input from the Center for Drug 
Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) and Center for Devices 
and Radiological Health (CDRH).  
2 The OIGs report is available at http://oig.hhs.gov/oei/reports/oei-05-07-00730.pdf.   
  1 Contains Nonbinding Recommendations 
purpose of the regulation at 21 CFR  54.1).  The regulation, which became effective on 
February 2, 1999, applies to clinical studies submitted in a marketing application, including a 
supplement or amendment to an original application, that the applicant or FDA relies on to 
establish that the product is effective, and any study in which a single investigator makes a 
significant contribution to the demonstration of safety (21 CFR  54.2(e) and 54.3).  The 
regulation requires applicants to certify the absence of certain financial interests and 
arrangements of clinical investigators that could affect the reliability of data submitted to FDA, 
or to disclose those financial interests and arrangements to the agency and identify steps taken to 
minimize the potential for bias (21 CFR  54.4(a)).  If the applicant does not include certification 
and/or disclosure, or does not certify that it was unable to obtain the information despite 
exercising due diligence, the agency may refuse to file the application (21 CFR  54.4(c)).   
 
 
III.  FINANCIAL DISCLOSURE REQUIREMENTS 
 
Under the applicable regulations,3 an applicant is required to submit to FDA a list of all clinical 
investigators who conducted covered clinical studies and to identify those who are full-time or 
part-time employees of the sponsor of each covered study (21 CFR  54.4).  For each clinical 
investigator who was not a full-time or part-time employee of a sponsor of the clinical study, the 
applicant must provide either a certification, using FORM FDA 3454, that none of the financial 
interests or arrangements described in 21 CFR  54.4(a)(3) (see Section III.B. below) exists, or 
completely and accurately disclose, using FORM FDA 3455, the nature of those interests and 
arrangements to the agency and describe any steps taken to minimize the potential for bias 
resulting from those interests and arrangements (21 CFR  54.4(a)).  If the applicant acts with 
due diligence to obtain the required information but is unable to do so, the applicant may certify 
that it acted with due diligence but was unable to obtain the information and include the reason 
the information could not be obtained (21 CFR  54.4).   
 
FDA generally expects that applicants will be able to provide this information.  Under 21 CFR 
 312.53(c), 812.20(b)(5) and 812.43(c), a sponsor is required to obtain clinical investigator 
financial information before allowing the clinical investigator to participate in a covered clinical 
study.  Under 21 CFR  54.4(b), each clinical investigator who is not a full-time or part-time 
employee of the sponsor of the covered clinical study is required to provide the sponsor with 
sufficient accurate financial information to allow for complete disclosure or certification and to 
update this information if any relevant changes occur during the study and for one year following 
its completion.   
 
A.  Definitions 
 
Clinical Investigator  For purposes of part 54, clinical investigator means a listed or 
identified investigator or subinvestigator who is directly involved in the treatment or evaluation 
of research subjects, including the spouse and each dependent child of the investigator or 
subinvestigator.  (See 21 CFR  54.2(d).)  See Section IV.D, Clinical Investigator, for additional 
information.  Clinical investigators are included in the definition even if they did not participate 
for the entire length of the study.  If a clinical investigator did not participate in the entire study, 
                                                 
3 21 CFR parts 54, 312, 314, 320, 330, 601, 807, 812, 814, and 860 
  2 Contains Nonbinding Recommendations 
information collected should be for the period of time he or she participated in the study and for 
one year following the end of his or her participation.   
 
Covered clinical study  The part 54 regulations define covered clinical study to mean any 
study of a drug or device in humans submitted in a marketing application or reclassification 
petition subject to this part that the applicant or FDA relies on to establish that the product is 
effective (including studies that show equivalence to an effective product) or any study in which 
a single investigator makes a significant contribution to the demonstration of safety.  This would, 
in general, not include phase 1 tolerance studies or pharmacokinetic studies, most clinical 
pharmacology studies (unless they are critical to an efficacy determination), large open safety 
studies conducted at multiple sites, treatment protocols and parallel track protocols.  (See 21 
CFR  54.2(e).)  This definition includes clinical studies submitted in support of new drug 
applications (NDAs) submitted under section 505(b) of the Federal Food, Drug, and Cosmetic 
Act (FD&C Act), abbreviated new drug applications (ANDAs) under section 505(j) of the 
FD&C Act, premarket notification submissions under section 510(k) of the FD&C Act, 
reclassification petitions under section 513 of the FD&C Act, premarket approval applications 
(PMAs) under section 515 of the FD&C Act, and biologics licensing applications (BLAs) 
submitted under section 351 of the Public Health Services Act (PHS Act), as well as studies 
submitted in support of amendments or supplements to any such applications.  (See 21 CFR  
54.3 and 54.4(a).)  Covered clinical studies would generally not include expanded access under 
section 561 of the FD&C Act.  If an applicant is unsure of whether a particular study is included 
in this definition, it may consult with FDA as to which clinical studies constitute covered 
clinical studies for purposes of complying with financial disclosure requirements.  (21 CFR  
54.2(e).)  See Section IV.G, Covered Clinical Study, for additional information.   
 
Applicant  Applicant means the party who submits a marketing application to FDA for 
approval of a drug, device or biologic product or who submits a reclassification petition.  The 
applicant is responsible for submitting the required certification and disclosure statements.  (See 
21 CFR  54.2(g).)  Note that for purposes of financial disclosure the term applicant includes 
submitter and the term application includes 510(k) submission.  See Section IV.F, 
Applicant, for additional information.   
 
Sponsor of the covered clinical study  For purposes of part 54, sponsor of the covered 
clinical study means a party supporting a particular study at the time it was carried out.  (See 
21 CFR  54.2(h).)  A covered clinical study may have more than one sponsor for whom 
financial information will need to be collected.  For example, if one party designed and 
conducted the covered clinical study, a second party provided funding, and a third party provided 
the test product, there would be three sponsors of the covered clinical study.  However, if the 
third party in this example was reimbursed for the test product, it would not be considered a 
sponsor of the covered clinical study and the study would be considered to have two sponsors.  
Note also that the definition of sponsor for purposes of part 54 is different than the definition 
of sponsor for purposes of investigational new drug applications (INDs) and investigational 
device exemptions applications (IDEs) (see 21 CFR  312.3(b) and 812.3(n)).  See Section 
IV.E, Sponsor, for additional information.   
 
  3 Contains Nonbinding Recommendations 
B.   Disclosable Financial Interests and Arrangements 
 
The financial interests, arrangements, and payments that must be disclosed (see 21 CFR  
54.4(a)(3), referred to herein as disclosable financial interests and arrangements) are described 
below.4  Note that the dollar amounts that trigger reporting are the combined financial interests 
of the investigator, spouse, and dependent children.   
 
1.  Any compensation made to the investigator by any sponsor of the covered clinical study in 
which the value of compensation could be affected by study outcome.   
 
2.  A proprietary interest in the tested product including, but not limited to, a patent, trademark, 
copyright or licensing agreement.   
 
3.  Any equity interest in any sponsor of the covered clinical study, i.e., any ownership interest, 
stock options, or other financial interest whose value cannot be readily determined through 
reference to public prices.  The requirement applies to interests held during the time the 
clinical investigator is carrying out the study and for one year following completion of the 
study.   
 
4.  Any equity interest in any sponsor of the covered study if the sponsor is a publicly held 
company and the interest exceeds $50,000 in value.  The requirement applies to interests 
held during the time the clinical investigator is carrying out the study and for one year 
following completion of the study.   
 
5.  Significant payments of other sorts (SPOOS) are payments that have a cumulative monetary 
value of $25,000 or more and are made by any sponsor of a covered study to the 
investigator or the investigators institution during the time the clinical investigator is 
carrying out the study and for one year following completion of the study.  This would 
include payments that support activities of the investigator (e.g., a grant to the investigator 
or to the institution to fund the investigators ongoing research or compensation in the form 
of equipment), exclusive of the costs of conducting the clinical study or other clinical 
studies, or to provide other reimbursements such as retainers for ongoing consultation or 
honoraria.  See Section IV, Questions C.4, C.5, and C.6 for additional information on 
SPOOS.  
 
C.  Agency Actions 
 
The agency may refuse to file a marketing application that does not contain the financial 
information required by 21 CFR part 54 or a certification by the applicant that the applicant has 
                                                 
4 These are the requirements for studies begun on or after the effective date of the part 54 regulations, February 2, 
1999.  For older studies, the disclosure requirements vary based on the studys status as of the effective date of the 
regulation.  For studies that were completed prior to February 2, 1999, disclosure of financial interests and 
arrangements described in paragraphs 1 through 3 is required.  For studies ongoing as of February 2, 1999, 
disclosure of financial interests and arrangements described in paragraphs 1 through 4 is required as well as 
payments as described in paragraph 5 that were made on or after February 2, 1999.  (See Federal Register, volume 
63, December 31, 1998, page 72172-3.) 
 
  4 Contains Nonbinding Recommendations 
acted with due diligence to obtain the information but was unable to do so stating a sufficient 
reason.  (21 CFR  54.4(c).) 
 
If FDA determines that the financial interests or arrangements of any clinical investigator raise a 
serious question about the integrity of the data, FDA will take any action it deems necessary to 
ensure the reliability of the data (21 CFR  54.5(c)) including:   
 
1.  Initiating agency audits of the data derived from the clinical investigator in question;  
  
2.  Requesting that the applicant submit further analyses of data, e.g., to evaluate the effect of 
the clinical investigator's data on the overall study outcome;  
 
3.  Requesting that the applicant conduct additional independent studies to confirm the results 
of the questioned study; and  
 
4.  Refusing to treat the covered clinical study as providing data that can be the basis for an 
agency action.   
 
 
IV.  QUESTIONS AND ANSWERS 
 
A.  GENERAL  
 
A.1.  Q:  Why did FDA develop the financial disclosure regulations?   
 
A:  In June 1991, the Inspector General of the Department of Health and Human Services 
submitted a management advisory report5 to FDA stating that FDA's failure to have a 
mechanism for collecting information on "financial conflicts of interest" of clinical 
investigators who study products that undergo FDA review could constitute a material 
weakness under the Federal Managers Financial Integrity Act.  As stated in the preamble 
to the final rule, although FDA determined that a material weakness did not exist, the 
agency did conclude that there was a need to address this issue through regulation.6  
During the rulemaking process, FDA also learned about potentially problematic financial 
interests and arrangements through published newspaper articles, Congressional 
inquiries, and public testimony and comments.  Based on the information gathered, FDA 
determined that it was appropriate to require the submission of certain financial 
information with marketing applications that, in part, rely on clinical data.   
 
                                                 
5 Office of the Inspector General (OIG), Department of Health and Human Services (DHHS), Management Advisory 
Report  Financial Involvement of Clinical Investigators with Sponsors of Research Leading to Food and Drug 
Administration Marketing Approval, June 1991, OI-HQ-91-003. 
6 The final rule was published in the Federal Register, Vol. 63, February 2, 1998, pages 5233-5254.  The referenced 
statement appears on page 5235. 
  5 Contains Nonbinding Recommendations 
A.2.  Q:  What is the purpose of FDAs review of clinical investigator financial disclosure 
information and how can sponsors minimize bias? 
 
A:  FDAs review of clinical investigator financial disclosure information alerts FDA 
staff to financial interests and arrangements that could lead to bias in covered clinical 
studies.  The financial disclosure process also provides FDA with information regarding 
whether and to what extent the sponsors have taken steps to minimize the risk of bias.  
An important means of minimizing the potential for bias resulting from such financial 
interests and arrangements is through proper study design (see 21 CFR  54.5(b)).  For 
example, using randomization and blinding helps to minimize the potential for bias in 
assigning subjects to receive the test article or placebo and in assessing study outcomes 
and analyzing results.  Similarly, having someone with no financial interests or 
arrangements evaluate study endpoints, especially in an unblinded study, can help 
minimize potential bias in assessing therapy outcomes.   
 
FDA staff consider the financial disclosure information and the methods the sponsor used 
to minimize bias during the review of marketing applications to assess the reliability of 
the clinical data (see 21 CFR  54.1).  Additionally, because sponsors of studies 
conducted under INDs and IDEs are required to collect financial information from 
clinical investigators prior to study initiation,7 sponsors can work with FDA to minimize 
any potential bias.  FDA strongly encourages sponsors of studies not conducted under an 
IND/IDE to collect financial information prior to study initiation for the same reasons. 
 
B.  FORMS AND INFORMATION TO BE SUBMITTED  
 
B.1.  Q:  What financial disclosure information is to be included in a marketing 
application?   
 
A:  The application must contain a list of all clinical investigators who conducted each 
covered clinical study (21 CFR  54.4).  For purposes of this list, investigators and 
subinvestigators who meet the definition of clinical investigator in 21 CFR  54.2(d) 
must be included.  Note that the term clinical investigator includes the spouse and each 
dependent child of a clinical investigator (21 CFR  54.2(d)).  This list must also identify 
those clinical investigators who are full or part-time employees of the sponsor of the 
covered study (21 CFR  54.4).  If a spouse or dependent child is an employee of a 
sponsor, that clinical investigator should be identified as an employee for purposes of 
financial disclosure.  For each clinical investigator who is not identified as an employee 
of the sponsor, one of the following must be submitted (21 CFR  54.4(a)): 
  
                                                 
7 21 CFR  312.53(c)(4), 812.20(b)(5), and 812.43(c) 
  6 Contains Nonbinding Recommendations 
1.  FORM FDA 3455, Disclosure Statement,8 for each clinical investigator who, or 
whose spouse or dependent child, had disclosable financial interests in and/or 
arrangements with any sponsor of the covered clinical study.  The form should 
include an attachment with detailed information about those financial interests and 
arrangements (for example, the nature of the contingent payment or the equity 
holdings of the investigator, or the investigator's spouse or dependent child, that 
exceeded the threshold) and a description of the steps taken to minimize the 
potential for bias resulting from the disclosed financial interests and arrangements 
(21 CFR  54.4(a)(3)).  See Section IV.C for additional information; 
 
2.  FORM FDA 3454, Certification, for any clinical investigator who has no disclosable 
financial interests in or arrangements with any sponsor of the covered clinical study 
(21 CFR  54.4(a)(1)); the applicant may append a list of investigator names to a 
single FORM FDA 3454 for those investigators with no disclosable financial 
interests or arrangements; or 
 
3.  If the applicant was unable to obtain some or all of the financial information needed 
to disclose or certify for a clinical investigator, the applicant must identify any 
disclosable financial interests or arrangements of which it is aware, certify that it 
acted with due diligence to obtain the information (listed as option 3 on FORM FDA 
3454), and include an attachment identifying the reason why any missing 
information could not be obtained (21 CFR  54.4).  FDA expects that in the vast 
majority of cases, applicants will be able to provide a complete financial 
Certification or Disclosure Statement and that the need to certify that they acted with 
due diligence will be rare.  See Question B.7 and Question F.2 for additional 
information on due diligence. 
 
FDA encourages applicants to submit financial disclosure information in a format that 
will ensure all required information is included.  For example, applicants should provide 
the total number of investigators in the study and a table indicating, for each clinical 
investigator listed who is not identified as an employee, whether they are providing a 
Certification (FORM FDA 3454), a Disclosure Statement (FORM FDA 3455) or 
certification that they acted with due diligence but were unable to obtain the information 
(option 3 on FORM FDA 3454).  Applicants should also ensure that all required 
attachments, as identified above, are included.  Applicants with questions about 
acceptable formats for submitting the financial disclosure information should contact the 
Center representatives identified in Question K.1.   
 
                                                 
8 As an alternative to a separate FORM FDA 3455 for each clinical investigator with information to disclose, 
applicants may submit a single FORM FDA 3455, with attachments clearly identifying all clinical investigators with 
information to disclose and, for each investigator, identifying the study, the specific details of their financial 
interests and arrangements and the steps taken to minimize the potential for bias.  Applicants with questions about 
alternative formats should contact the Center representatives identified in Question K.1.   
  7 Contains Nonbinding Recommendations 
B.2.  Q:  May an applicant rely upon the policies and procedures of the clinical 
investigators institution for disclosure, review and management of financial 
conflicts of interest of their employees (including spouse and dependent children)?   
 
A:  Each applicant is responsible for disclosing or certifying as required by 21 CFR part 
54.  Compliance with institutional policies or procedures by an investigator is not a 
substitute for compliance with part 54.   
 
Although a clinical investigators institution may take steps to manage a clinical 
investigators financial interests and arrangements, in order to minimize study bias, FDA 
must make its own evaluation of the clinical investigators financial interests and 
arrangements (21 CFR  54.5).  When a clinical investigator has disclosable financial 
interests and arrangements, the disclosure statement submitted to FDA is required to 
include a description of any steps taken to minimize the potential for bias resulting from 
any of the disclosed financial interests and arrangements (21 CFR 54.4(a)(3)(v)).  A 
description of the steps taken by the institution to minimize bias should be included with 
the disclosure statement, if pertinent.  See Section IV, Question D.7 for additional 
information.   
 
B.3.  Q:  Where in a marketing application for a drug or a biological product should an 
applicant include the certification or disclosure forms and attachments?   
 
A:  Applicants using the format described in FORM FDA 356h (Application to Market a 
New Drug, Biologic, or an Antibiotic Drug for Human Use) should include the clinical 
investigator list and financial certification and/or disclosure forms and attachments as 
part of item 19 (Financial Information) of the application.9  Applicants using the 
Common Technical Document (CTD) format should include this information in Module 
1.3.4.10 
 
B.4.  Q:  Where should the information be included in a device marketing application?   
 
A:  Applicants should submit the clinical investigator list and financial 
certification/disclosure forms and attachments according to the format outlined in the 
appropriate submission guidance.11   
 
                                                 
9 Application to Market a New Drug, Biologic, or an Antibiotic Drug for Human Use, available at 
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM082348.pdf. 
10 The eCTD Backbone Files Specification for Module 1, available at 
http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSub
missions/UCM163552.pdf.   
11 For premarket notification submissions, see Guidance for Industry and FDA Staff: Format for Traditional and 
Abbreviated 510(k)s, available at 
www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm084365.htm.   
For premarket approval applications, see Guidance for Industry and FDA Staff: Premarket Approval Application 
Filing Review, available at 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089430.htm. 
  8 Contains Nonbinding Recommendations 
B.5.  Q:  How should the financial information be submitted?   
 
A:  The financial information is required to be submitted using FORMS FDA 3454 
and/or 3455 (21 CFR  54.4(a)), which are available on the Web at the following Internet 
address:  http://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm 
(Forms are listed in numerical order).   
 
B.6.  Q:  Who, specifically, is responsible for signing the financial certification/disclosure 
forms?   
 
A:  The forms are to be signed and dated by the chief financial officer or other 
responsible corporate official or representative of the applicant.  FDA recommends that 
the other responsible corporate official or representative be a senior official who has 
the authority to ensure the information is collected and reported accurately.  Depending 
on company structure, such an individual could be the person in charge of regulatory or 
clinical affairs.   
 
B.7.  Q:  What does FDA mean by the term due diligence? 
 
A:  "Due diligence" is a measure of activity expected from a reasonable and prudent 
person under a particular circumstance, in this case, collecting information about 
financial interests or arrangements.  FDA expects that applicants will typically be able to 
obtain the required information because investigators are required to provide financial 
disclosure information to sponsors before participating in a clinical study.  (21 CFR  
54.4, 312.53(c), 812.43(c) and 812.20(b)(5).)  In the rare circumstance where applicants 
are unable to obtain required financial information, applicants must certify that they acted 
with due diligence and explain why the information was not obtainable (21 CFR  54.4).   
 
If all of the information required to make a complete certification or disclosure is not 
available from a sponsor, applicants should make appropriate efforts to obtain the 
information by other means.  That may mean contacting an individual investigator or 
subinvestigator directly.  If an investigators whereabouts are unknown, for example 
because the investigator left a study prior to its completion or prior to one year following 
completion of the study, FDA recommends that sponsors and/or applicants try to locate 
the clinical investigator.  Sponsors and applicants should exercise reasonable judgment 
regarding the appropriate amount of effort to expend when attempting to contact 
investigators, which may include consideration of the role of the investigator in the study 
and the importance of the investigators data contribution.   
 
In most cases, FDA suggests that more than one attempt at contacting an investigator 
would be appropriate and that more than one method of contact be attempted.  FDA also 
recommends that each attempt to contact the investigator be documented, for example, by 
maintaining copies of e-mails and letters and documenting telephone calls and 
conversation by written memoranda.  FDA also suggests that sponsors and applicants 
consider using a method of contacting investigators that allows verification of receipt, 
such as certified mail or reliable courier service that provides notice of recipients receipt 
  9 Contains Nonbinding Recommendations 
of a letter.  When such methods are used, copies of the delivery notice or undeliverable 
notice should be maintained.   
 
If an investigator is no longer at the institution where the study was conducted, FDA 
recommends that the sponsor or applicant make a reasonable attempt to locate the 
investigator, for example, by requesting contact information from the institution where 
the study was conducted or the institution with which the investigator was affiliated, 
contacting professional associations the investigator may have been affiliated with, 
and/or conducting Internet searches.   
 
If a clinical investigator cannot be located or information for some other reason cannot be 
obtained from the investigator, the sponsor should have access to certain disclosable 
financial information and arrangements, for example, payments made specifically to the 
investigator or information related to product sales that may generate royalties due to the 
investigator.  On request from an applicant, sponsors should check their records for such 
information and, subject to any privacy laws (noting that other countries laws may differ 
from United States law), the sponsor should then provide disclosable information to the 
applicant.  In addition, and as necessary, efforts should be made to obtain disclosable 
financial information from other reasonably available, reliable, public sources of 
information.  For example, information on proprietary interests in the test product, such 
as patents and trademarks, should be available from publicly available sources.12  
Another possible source of information is the clinical investigators institution, which 
may have collected financial information and, if consistent with their policies, may 
release this information to the applicant upon request.  Appropriate certifications, 
disclosures, and/or explanations should be provided to FDA on the basis of information 
obtained.  See Question F.2 for additional information.   
 
An applicant must exercise due diligence whether a covered study is conducted at foreign 
or domestic sites.  The agency expects that a reasonable and prudent applicant will take 
affirmative steps at the first opportunity to see that the financial information required for 
a complete certification or disclosure under part 54 is collected and maintained.  This is 
not only to ensure that the applicant will be able to make a complete submission but also 
to ensure that the study sponsor will take steps to protect the study against possible bias.  
See Questions E.3, E.5, and F.3 for additional information.   
 
B.8.  Q:  Is clinical investigator financial disclosure information required in IND or IDE 
applications? 
 
A:  No, IND/IDE sponsors are not required to submit information regarding clinical 
investigator financial interests or arrangements in IND or IDE applications.  They are, 
however, required to collect this information before a clinical investigator participates in 
a clinical study (see 21 CFR  312.53(c)(4), 812.20(b)(5), and 812.43(c)(5)), and 
                                                 
12 Such sources include the Patent and Trademark Office website and, once available, the federal reporting website 
proposed by the Centers for Medicare & Medicaid Services as required by Section 6002 of the Patient Protection 
and Affordable Care Act.  See the final rule, Transparency Reports and Reporting of Physician Ownership or 
Investment Interests, Federal Register, Vol. 78, February 8, 2013, page 9458.   
  10 Contains Nonbinding Recommendations 
clinical investigators are required to disclose financial information to sponsors (see 21 
CFR  312.64(d) and 812.110(d)).  The information need not be submitted to FDA until 
a marketing application is submitted containing the results of the covered clinical study 
(21 CFR  54.4). 
 
Study sponsors are encouraged to consult with FDA prior to and during clinical studies 
about the management of specific situations involving potential bias on the part of a 
clinical investigator.  During these consultations, FDA staff should focus on the 
protection of research subjects and the minimization of bias from all potential sources.   
 
C.  FINANCIAL INTERESTS AND ARRANGEMENTS SUBJECT TO 
DISCLOSURE  
 
C.1.  Q:  What information about a financial interest or arrangement should be disclosed 
to the agency?  For example, if an investigator owns more than $50,000 of stock in a 
publicly held company, can the applicant just disclose that there is an interest that 
exceeds the $50,000 threshold or is it necessary to disclose in written detail the 
interest or arrangement in question?   
 
A:  The applicant must make a complete and accurate disclosure (21 CFR  54.4(a)(3)).  
The specific details of the financial interest or arrangement, including its size and nature, 
should be disclosed as should any steps taken to minimize the potential for study bias 
resulting from the interest or arrangement.  In describing financial interests, for example, 
the applicant might list:  stock valued at $77,000, speaking fees of $7,500, consulting fees 
of $22,000, and a grant of $125,000 and include a discussion of the specific steps taken to 
minimize potential bias.  Sponsors should request that clinical investigators provide 
sufficient detail about their financial disclosure information to allow the appropriate 
disclosures to be made.   
 
C.2.  Q:  Should a clinical investigator report all fluctuations above and below the 
$50,000 level during the course of the investigation and one year after completion of 
the study?   
 
A: In light of the potential volatility of stock prices, FDA recognizes that the dollar value 
of an investigator's equity holding in a sponsoring company is likely to fluctuate during 
the course of a study.  Clinical investigators should report an equity interest when the 
investigator becomes aware that the holding has exceeded the threshold and the 
investigator should use judgment in updating and reporting on fluctuations in equity 
interests exceeding $50,000.  FDA does not expect the investigator to report when an 
equity interest fluctuates below that threshold.  See Question E.4 for additional 
information.   
 
C.3.  Q:  Are equity interests in mutual funds and 401(k)s reportable?   
 
A:  FDA expects that equity interests held in publicly traded mutual funds will not be 
reportable in the vast majority of cases.  If, however, an investigator would have control 
  11 Contains Nonbinding Recommendations 
over buying or selling stocks in a mutual fund, equity interests held in such publicly 
traded mutual funds would be reportable.   
 
If an investigator holds an equity interest in a sponsor over $50,000 in a 401(k) or 
equivalent account, and has control over whether to buy or sell the interest, the equity 
interest is reportable.   
 
C.4.  Q:  How do significant payments of other sorts (SPOOS) relate to the variety of 
payments the sponsor might make to an individual or institution for various 
activities?   
 
A:  The term "significant payments of other sorts" was intended to capture substantial 
payments or other support that has a value of more than $25,000 provided to an 
investigator or institution that could create a sense of obligation to the sponsor.   
 
These payments do not include payments for the cost of conducting the clinical study of 
the product under consideration or clinical studies of other products, under a contractual 
arrangement, but do include other payments made directly to the investigator or to an 
institution for direct support of the investigator.   
 
Significant payments of other sorts would include, for example, payments, retainers 
and honoraria from a sponsor to a clinical investigator for activities such as participating 
on committees, providing consultation, or serving as a preceptor (21 CFR  54.2(f)).  
Grants to fund ongoing research, including laboratory activities and equipment, and 
compensation in the form of actual equipment for the laboratory/clinic would also be 
considered significant payments of other sorts.  This means that if an investigator were 
given equipment or money to purchase equipment for use in the laboratory/clinic but not 
in relation to the conduct of the clinical study, payment would be considered a significant 
payment of other sorts (21 CFR  54.4(a)(3)(ii)).  If, however, the investigator were 
provided with computer software or money to buy software needed for use in the clinical 
study, that payment would not need to be reported.   
 
Payments made to the institution that are not made on behalf of the investigator and are 
not specifically targeted towards the investigator generally would not need to be reported.  
Under certain circumstances, however, a grant made to an institution would be 
considered targeted towards the investigator (and therefore considered reportable); for 
example, if the grant is worded in such a way that only the investigator could fulfill it.   
 
Finally, payments that meet the criteria for significant payments of other sorts that are 
made to other researchers at the institution, who are not part of the covered study, do not 
need to be reported.   
 
  12 Contains Nonbinding Recommendations 
C.5.  Q:  Are payments made to investigators to cover travel expenses (such as 
transportation, lodgings and meal expenses) reportable as significant payments of 
other sorts (SPOOS)?   
 
A:  Generally, reasonable payments made to investigators to cover reimbursable expenses 
such as transportation, lodgings and meals do not fall within the definition of SPOOS 
and, therefore, would not need to be reported.  Payment for other expenses that are 
generally considered outside of normal reimbursable expenditures and not expenses 
necessary to conduct the study would be considered SPOOS.  Such payments would 
include, for example, entertainment costs, travel costs associated with transporting and/or 
providing lodgings and meals for family members, and other payments that exceed 
reasonable expectations (for example, if an investigator was flown to a resort location for 
an extra week of vacation).  These types of expenses are reportable and should be tracked 
as SPOOS.  FDA understands that such payments may be limited or prohibited by 
industry ethical codes.13  To the extent such payments are made, they would be SPOOS.   
 
C.6.  Q:  Is the dollar amount that triggers reporting of significant payments of other 
sorts (SPOOS) cumulative over the course of the study or is it based on the amount 
received on an annual basis?   
 
A:  The $25,000 threshold amount for reporting SPOOS is based on the cumulative 
amount of SPOOS received by the clinical investigator (including payments made to the 
spouse and dependent children) over the course of the study and for one year following 
completion of the study.   
 
C.7.  Q:  Does FDA have expectations about how the financial information should be 
collected?  Will FDA consider it acceptable practice for a company to use a 
questionnaire to collect financial information from investigators rather than 
constructing an internal system to collect and report this information?   
 
A:  FDA regulations do not prescribe a particular method for collecting financial 
information from investigators.  Sponsors/applicants have the flexibility to collect the 
information in the most efficient and least burdensome manner that will allow for 
complete and accurate certifications and disclosures.  They may use questionnaires 
completed by the clinical investigators and/or information already available to the 
sponsor, as appropriate.  FDA does not require sponsors to establish elaborate systems to 
collect and track financial information.   
 
If sponsors intend to use a questionnaire to collect financial information from 
investigators, FDA recommends that they develop forms suited to that purpose.  FORM 
FDA 3455 was designed for applicants to use to report financial information they 
collected from clinical investigators to FDA.  It does not include the background 
                                                 
13 Examples of industry ethical codes would be the Principles on Conduct of Clinical Trials and Communication of 
Clinical Trials Results from the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Code 
of Ethics on Interactions with Health Care Professionals from the Advanced Medical Technology Association 
(AdvaMed).   
  13 Contains Nonbinding Recommendations 
information needed for clinical investigators to be aware of the financial information to 
be provided.  For example, there is no statement that the reporting requirements apply to 
the spouse and dependent children as well as to the investigator; no information as to the 
dollar amounts triggering reporting of equity interests or SPOOS; and no statement that 
the investigator must report the details of the financial interests and arrangements, not 
just a statement, for example, of equity interest greater than $50,000.  In addition, when 
there is more than one sponsor for financial disclosure purposes, the investigator should 
be apprised that the dollar amounts triggering reporting apply separately to each sponsor.  
This type of explanatory information should be provided to the clinical investigators to 
ensure that the financial disclosure information collected is as accurate and complete as 
possible.  Please see the Appendix for considerations for collecting financial disclosure 
information from clinical investigators.   
 
C.8.  Q:  The regulation requires that investigators provide information on financial 
interests and arrangements during the course of the study and for one year after 
completion of the study (see 21 CFR  54.4(b)).  What does during the course of the 
study mean?  What does "completion of the study" mean?   
 
A:  During the course of the study refers to the time from the date the clinical 
investigator entered into an agreement with the sponsor to conduct the study until the 
completion of the study.  For the purposes of financial disclosure under part 54, 
completion of the study means that all study subjects have been enrolled and follow-up of 
primary endpoint data on all subjects has been completed in accordance with the clinical 
protocol.  Many studies have more than one phase (e.g., a study could have a short-term 
endpoint and a longer term follow-up phase).  Completion of the study here refers to 
the part of the study that is being submitted in the application.  If there were a subsequent 
application based on longer term data, completion of the study would be defined using 
completion of follow-up for the longer term data.  An applicant is not required to submit 
updated financial information to FDA after submission of the application, but applicants 
must retain complete records (21 CFR  54.6).  Where there is more than one study site, 
the sponsor may consider completion of the study to occur when the last study site is 
complete, or may consider each study site individually as it is completed.   
 
C.9.  Q:  What if the sponsor changes during the course of the study or within one year of 
completion of the study, for example, through purchase or merger? 
 
A:  Agency regulations require that an IND/IDE sponsor collect financial information 
from all clinical investigators and that clinical investigators promptly update this 
information if any relevant changes occur during the course of the investigation and for 
one year following completion of the study (21 CFR  54.4, 312.53(c)(4), 312.64(d), 
812.43(c)(5) and 812.110(d)).  Therefore, if the study sponsor changes during the course 
of the study, the clinical investigators will need to update their financial disclosure 
information relevant to the new sponsor.  The new sponsor is responsible for collecting 
this information, and to ensure that the new sponsor has complete financial disclosure 
information, the new sponsor should seek this information from the original sponsor, and 
the agency encourages the original sponsor to share their records with the new sponsor.     
  14 Contains Nonbinding Recommendations 
 
With respect to covered clinical studies conducted outside the United States not pursuant 
to an IND or IDE (such as studies submitted pursuant to  312.120 or  814.15), the 
agency expects applicants to take affirmative action, at the earliest opportunity, to see 
that this information is collected and available to make a complete disclosure and/or 
certification under part 54.   
 
D.  CLINICAL INVESTIGATOR 
 
D.1.  Q:  Who is included in the definition of clinical investigator? 
 
A:  Under part 54, clinical investigator means only a listed or identified investigator or 
subinvestigator who is directly involved in the treatment or evaluation of research 
subjects (21 CFR  54.2(d)).  This definition is intended to identify the individuals for 
whom reporting under this regulation is required.  Generally, these individuals are 
considered to be the investigators and subinvestigators taking responsibility for the study 
at a given study site. The definition also includes the spouse and each dependent child of 
such an investigator or subinvestigator. 
 
It should be noted that hospital staff, including nurses, residents, fellows, and office staff 
who provide ancillary or intermittent care but who do not make direct and significant 
contribution to the data are not meant to be included under the definition of clinical 
investigator.  Additionally, individuals who only collect specimens or perform routine 
tests (such as blood pressure, EKG, x-ray) are not meant to be included under the 
definition of clinical investigator for purposes of financial disclosure.   
 
D.2.  Q:  How does the definition of clinical investigator in the financial disclosure 
regulation (21 CFR part 54) relate to the definition in the IND regulations (21 CFR 
part 312)?   
 
A:  For drugs and biological products, an investigator under 21 CFR part 312 is defined 
as an individual who actually conducts a clinical investigation (i.e., under whose 
immediate direction the drug is administered or dispensed to a subject).  In the event an 
investigation is conducted by a team of individuals, the investigator is the responsible 
leader of the team.  Subinvestigator includes any other individual member of that 
team.  (21 CFR  312.3(b).) 
 
For purposes of the financial disclosure regulation, a clinical investigator is an 
investigator or subinvestigator who is directly involved in the treatment or evaluation of 
research subjects (21 CFR  54.2(d)).  Therefore, the term clinical investigator in this 
context would generally include anyone who fits any of the following criteria:  signs the 
FORM FDA 1572 (Statement of Investigator), is identified as an investigator in initial 
submissions or protocol amendments under an IND, or is identified as an investigator in 
the marketing application.  This could include individuals identified as subinvestigators 
  15 Contains Nonbinding Recommendations 
on a FORM FDA 1572.14  For studies not conducted under an IND, the sponsor will need 
to identify the investigators and subinvestigators they consider covered by the regulation 
and provide FORMS FDA 3454 and/or 3455 as appropriate.  FDA expects that there will 
be at least one such person at each clinical site.  If other individuals are responsible for a 
study at a site, those persons should also be included as clinical investigators.   
 
D.3.  Q:  How does the definition of clinical investigator in the financial disclosure 
regulation (21 CFR part 54) relate to the definition in the medical device regulations 
(21 CFR part 812)? 
 
A:  For medical devices, investigator is defined under 21 CFR part 812 as an individual 
under whose immediate direction the subject is treated and the investigational device is 
administered, including follow-up evaluations and treatments.  Where an investigation is 
conducted by a team of individuals, the investigator is the responsible leader of the team. 
(21 CFR  812.3(i).)   
 
In general, investigators and subinvestigators sign "investigator agreements" in 
accordance with 21 CFR  812.43(c), and it is these individuals whose financial interests 
and arrangements should be reported as they would fall under the definition at 21 CFR  
54.2(d).  For studies not conducted under an FDA-approved IDE (that is, a non-
significant risk IDE or an exempt study), the sponsor would need to identify the 
investigators and subinvestigators they consider covered by the regulation and provide 
FORMS FDA 3454 and/or 3455, as appropriate.  We expect that there will be at least one 
such person at each clinical site.  
 
D.4.  Q:  Is it necessary to collect financial information on spouses and dependent 
children of clinical investigators?   
 
A:  Yes.  The definition of clinical investigator in 21 CFR part 54 includes the spouse and 
dependent children of the investigators and subinvestigators who are required to report.  
Therefore, the financial interests and arrangements of the spouse and each dependent 
child of each investigator and subinvestigator are to be included in the disclosure (21 
CFR  54.2(d)).  The dollar amount that triggers reporting is the total of the financial 
interests of the investigator, spouse, and dependent children (21 CFR  54.2(d)).  If a 
spouse or dependent child is an employee of the sponsor, the clinical investigator should 
be identified as an employee of the sponsor and no further disclosure is required.  (See 21 
CFR  54.4.) 
 
D.5.  Q:  Who is considered a dependent child? 
 
A:  For purposes of clinical investigator financial disclosure under part 54, a dependent 
child is the investigators child (whether by blood or adoption), stepchild or foster child 
who is unmarried, and for whom the investigator provides more than one-half of the 
                                                 
14 For guidance on who should be listed as an investigator or subinvestigator on Form FDA 1572, please see FDAs 
Information Sheet Guidance, Frequently Asked Questions  Statement of Investigator (Form FDA 1572) available 
at http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214282.pdf.   
  16 Contains Nonbinding Recommendations 
childs support.  This would include a child who, at any time during the course of the 
study and for one year following completion of the study, is under the age of 19, under 
the age of 24 if a full-time student, or who is permanently and totally disabled.  Such a 
child would generally have the same principal residence as the investigator.   
 
D.6.  Q:  What obligations does the clinical investigator have under the financial 
disclosure regulations? 
 
A:  Clinical investigators are to provide sponsors sufficient accurate financial information 
to allow the applicant to submit complete and accurate certification or disclosure 
statements (see 21 CFR  54.4, 312.53(c)(4), 312.64(d), 812.43(c)(5) and 812.110(d)).  
Clinical investigators must provide this information to sponsors and also promptly update 
the information if any relevant changes occur during the course of the investigation and 
for one year following the completion of the study (see 21 CFR  54.4(b), 312.53(c)(4), 
312.64(d), 812.43(c)(5) and 812.110(d)).  See also Question C.2.  
 
D.7.  Q:  May a clinical investigator rely on the information he/she provided to comply 
with his/her institutions policies and procedures pertaining to financial conflicts of 
interest to comply with the investigator obligations for financial disclosure under 
FDAs regulations? 
 
A:  The financial information a clinical investigator provides to his/her institution is 
based on the institutions requirements, which may not be sufficient to meet FDAs 
regulations.  FDAs regulations require the clinical investigator to provide sufficient and 
accurate financial information to the sponsor to allow the sponsor to submit complete and 
accurate certification or disclosure statements under FDAs clinical investigator financial 
disclosure regulations (21 CFR  54.4(b)).  However, if an investigator determines that 
the financial information he/she provided to his/her institution adequately fulfills the 
disclosure requirements in FDAs regulations, a clinical investigator could provide the 
same information to the sponsor.  The clinical investigator would still need to commit to 
promptly updating the financial information if any relevant changes occur during the 
course of the study and for one year following completion of the study (21 CFR  
54.4(b)). 
 
E.  SPONSOR  
 
E.1.  Q:  How does the definition of sponsor in the financial disclosure regulation (21 
CFR part 54) relate to the definition in the IND/IDE regulations (21 CFR parts 312 
and 812)?   
 
A:  In 21 CFR part 54, the term sponsor of the covered clinical study means the party 
supporting a particular study at the time it was carried out (21 CFR  54.2(h)).  FDA 
interprets support to include those who provide material support, for example, 
monetary support or the test product under study.  (See Question E.9 for further 
explanation of material support.)  This differs from the meaning of sponsor in other 
FDA regulations (such as 21 CFR parts 312 and 812), where the sponsor may be the 
  17 Contains Nonbinding Recommendations 
person who initiates or takes responsibility for a clinical investigation (21 CFR  
312.3(b) and 812.3(n)).  While the definition of sponsor under part 54 usually would 
include the sponsor of an IND/IDE (as defined in 21 CFR parts 312 and 812), it also 
includes any other individuals who provide material support for the study.  Therefore, a 
covered clinical study may have more than one sponsor for financial disclosure purposes.  
When there is more than one sponsor, FDA interprets the regulation to mean that the 
dollar amounts triggering reporting apply separately to each sponsor.   
 
E.2.  Q:  What obligations do IND and IDE sponsors have regarding information 
collection prior to study start?   
 
A:  The IND and IDE regulations provide that, before permitting an investigator to begin 
participation in an investigation, the IND/IDE sponsor (that is, the sponsor as defined in 
21 CFR parts 312 and 812) must obtain sufficient and accurate financial information that 
will allow an applicant to submit complete and accurate certification or disclosure 
statements as required under 21 CFR part 54 (21 CFR  312.53 and 812.43).  In order to 
fulfill these requirements and ensure complete disclosure, the IND/IDE sponsor should 
identify all sponsors of the covered clinical study (as defined in 21 CFR  54.2(h)) for 
investigators because the identity of all parties providing support may not be known to 
investigators.   
 
The sponsor is also required to obtain the investigator's commitment to promptly update 
this information if any relevant changes occur during the course of the investigation and 
for one year following the completion of the study (21 CFR  312.53 and 812.43).  By 
collecting the information prior to the study start, the sponsor will be aware of any 
potential problems, can consult with the agency early on, and can take steps to minimize 
any possibility for bias.     
 
E.3.  Q:  Why is the IND/IDE sponsor responsible for obtaining financial information 
from investigators? 
 
A:  Although reporting to the FDA is the responsibility of the applicant, the IND/IDE 
sponsor is required to collect the financial information before permitting an investigator 
to participate in a clinical study (21 CFR  312.53, 812.20(b)(5), and 812.43).  The 
purpose of this requirement is twofold:   
 
1.  to alert the IND/IDE sponsor of the study of any potentially problematic financial 
interests or arrangements as early in the product development process as possible in 
order to minimize the potential for study bias, and  
 
2.  to facilitate the accurate collection of financial information that may not be 
submitted until several years later.   
 
The IND/IDE sponsor, who is in contact with the investigator, is best placed to inquire as 
to the financial interests and arrangements of investigators, and this obligation applies to 
any IND/IDE sponsor (e.g., commercial, government, or contract research organization 
  18 Contains Nonbinding Recommendations 
(CRO)).  The IND/IDE sponsor is required to maintain complete and accurate records 
showing any financial interest in, or arrangement with, a sponsor of the covered study, as 
described in 21 CFR  54.4(a)(3)(i-iv) (21 CFR  312.57(b) and 812.140(b)(3)).  The 
IND/IDE sponsor is also best situated to ensure that required financial information is 
collected and made available to the applicant company, so that the information can be 
included in the marketing application.  (Refer to 21 CFR  54.4, 312.53, 312.57(b), 
812.43, and 812.140(b)(3).) 
 
IND/IDE sponsors conducting covered clinical studies outside the United States should 
note that the part 54 regulations do not distinguish between foreign and domestic sites.  
See Question F.3 for additional information.    
 
E.4.  Q:  Is the IND/IDE sponsor responsible for obtaining 1-year follow-up financial 
information from clinical investigators? 
 
A:  As noted in response to Question E.2 above, the IND/IDE sponsor is required to 
obtain financial information from clinical investigators before permitting the 
investigators to begin participation in an investigation and to obtain the investigators 
commitment to promptly update this information if any relevant changes occur during the 
course of the study and for one year following the completion of the study (21 CFR  
312.52 and 812.43).  The regulations do not specifically require the IND/IDE sponsor to 
obtain information from clinical investigators one year following completion of the study.  
The regulations, however, do require IND/IDE sponsors to maintain complete and 
accurate records concerning all financial interests and arrangements of clinical 
investigators subject to part 54 (see 21 CFR  312.57(b) and 812.140(b)(3)) and to 
secure investigator compliance with the regulations (see 21 CFR  312.56(b) and 
812.46(a)).  Therefore, an IND/IDE sponsor should take steps to ensure clinical 
investigator compliance, such as reminding the clinical investigators of the requirement 
to promptly update their financial information when any relevant changes occur during 
the study and for one year following completion.   
 
E.5.  Q:  What if the IND/IDE sponsor is not the party who will be submitting a 
marketing application?   
 
A:  In many cases, the IND/IDE sponsor, the part 54 sponsor, and the applicant will be 
the same party.  However, there may be times when they are not.  For example, consider 
the case when an academic institution serves as the IND/IDE sponsor and a drug 
company serves as the part 54 sponsor by providing funding or the investigational drug 
for the study.  When a marketing application is submitted, the drug company is likely to 
be the applicant.  If, however, the drug company was sold to another company, the 
applicant may be neither the IND/IDE sponsor nor a part 54 sponsor.  
 
It should be noted, however, that even if the IND/IDE sponsor will not be submitting the 
marketing application, the IND/IDE sponsor is still responsible for collecting financial 
information from the clinical investigators.  The responsibility for reporting financial 
information to FDA falls upon the applicant; that is, part 54 requires the applicant to 
  19 Contains Nonbinding Recommendations 
submit financial information when the marketing application is submitted to FDA (21 
CFR  54.4(a)).   
 
As stated above and in Question E.3, an IND/IDE sponsor is responsible for collecting 
financial information from both foreign and domestic clinical investigators.  If a sponsor 
did not collect this information, for example, because the sponsor conducted a foreign 
study that was not conducted under an IND/IDE and was not originally intended for 
submission to the FDA, the applicant is expected to contact the sponsor and/or clinical 
investigators to retrospectively obtain the financial disclosure information.  See 
Questions F.2 and F.3 for additional information.   
 
E.6.  Q:  If a contract research organization (CRO) is conducting a covered clinical study 
on behalf of another company, should the CRO collect the financial information 
from investigators?  Is it necessary to collect financial information from 
investigators who have financial interests in or arrangements with CROs? 
 
A:  If a CRO meets the definition of an IND/IDE sponsor or has contracted to collect 
financial information from clinical investigators on behalf of a sponsor, the CRO must 
collect financial information on clinical investigators interests in any sponsors of the 
covered clinical study.  See 21 CFR  312.52.  To satisfy the requirements in part 54, if 
the CRO provides material support for a covered study, financial information on clinical 
investigators' financial interests in and arrangements with the CRO is to be collected.  If 
another entity provided material support for the study, and the CRO was responsible for 
collecting the information, then the CRO also would collect financial information relative 
to that entity.   
 
E.7.  Q:  Suppose a public or academic institution conducts a covered clinical study 
without any support from a commercial sponsor, but the study is later used by an 
applicant to support its marketing application.  In that case, who is the "sponsor" of 
the study and what information should the applicant submit? 
 
A:  In this case, the part 54 sponsor of the study is the public or academic institution. 
Because such institutions are often not commercial entities, there may not be relevant 
equity interests to report.  However, if the clinical investigator is not a full-time or part-
time employee of the public or academic institution, the clinical investigator would need 
to report any relevant interests under 21 CFR  54.4, such as any proprietary interest in 
the tested product, including but not limited to a patent, trademark, copyright or licensing 
agreement, and reportable financial arrangements with the institution, such as 
compensation affected by the outcome of studies or significant payments of other sorts.  
The clinical investigators financial interests in and arrangements with the applicant 
would not need to be reported because the company was not a sponsor of the covered 
clinical study.   
 
If, however, the applicant provided material support for the study (for example, by 
providing the study product for free), then it would be considered a sponsor for financial 
disclosure purposes.  The academic institution conducting the study would need to collect 
  20 Contains Nonbinding Recommendations 
information regarding the clinical investigators financial interests and arrangements with 
the company.   
 
E.8.  Q:  If a subsidiary of a larger parent company is conducting a covered clinical 
study, are the financial interests and arrangements of the clinical investigators with 
only the subsidiary reported?  Or, are the financial interests of the investigators in 
the parent company to be reported also?   
 
A:  If the subsidiary company meets the definition of a sponsor of the covered study as 
defined in 21 CFR part 54, the IND/IDE sponsor is required to collect clinical 
investigators financial information related to the subsidiary company.  If the parent 
company is a 21 CFR part 54 sponsor of the study, the IND/IDE sponsor also must 
collect financial information related to the parent company.  If there are multiple 
companies providing material support for a covered study, the IND/IDE sponsor is 
responsible for collecting financial information from clinical investigators related to all 
companies providing that support (21 CFR  54.4, 312.53 and 812.43).  The company 
that will submit the marketing application is ultimately responsible for submitting to the 
agency the disclosable financial interests and arrangements of clinical investigators with 
respect to all the covered studys sponsors, as defined in 21 CFR part 54, at the time the 
marketing application is submitted (21 CFR  54.4).   
 
E.9.  Q:  What is considered material support when identifying sponsors of the covered 
study? 
 
A:  Parties that provide material support are considered sponsors of the covered clinical 
study.  This would include providing direct funding or other monetary support such as 
through a grant, or providing services or materials.  If a party receives reimbursement for 
the services and/or materials it is providing, then that party generally would not be 
considered a sponsor.  For example, a CRO paid by a sponsor to perform services would 
not be considered a sponsor of the covered clinical study.  Materials could include the 
product under study as well as other products and/or equipment that are needed for the 
conduct of the study, such as ancillary medication and equipment used in testing required 
by the protocol.   
 
F.  APPLICANT  
 
F.1.  Q:  Do applicant companies need to collect information for a year after completion 
of the study?  Who is responsible for collecting/providing this information?   
 
A:  The investigator must promptly provide updated financial information to the sponsor 
whenever any relevant changes occur during the course of the investigation andfor a one-
 
year period following completion of the study (21 CFR  54.4(b), 312.64(d) and 
812.110(d)).  In addition, sponsors should record SPOOS that are paid to the investigator 
or the investigator's institution to support activities of the investigator that have a 
cumulative monetary value of more than $25,000, exclusive of the costs of conducting 
the covered clinical studies, both during the study and for one year following completion 
  21 Contains Nonbinding Recommendations 
of the study (21 CFR  54.2(f) and 54.4(a)(3)(ii)).  FDA specified the one-year time 
frame because anticipation of payments or expectation of employment may be as 
influential as payments already received.  Applicants need only report these financial 
interests and arrangements when the marketing application is submitted, but sponsors and 
applicants are responsible for keeping updated financial information from the 
investigators in company files (21 CFR  54.6, 312.57 and 812.140).   
 
F.2.  Q:  Suppose an applicant has obtained the results of a clinical study conducted by 
another sponsor and that sponsor certifies it has no financial disclosure information 
in its files.  Is the applicant obligated to use due diligence in attempting to contact 
the clinical investigators directly to obtain the information?  Is the applicant 
obligated to provide any certification as to proprietary interests?  Is the sponsor 
obligated to provide the applicant with a statement as to outcome payments? 
 
A:  The applicant is required to provide financial disclosure information in a marketing 
application or certify that it acted with due diligence to obtain necessary information but 
was unable to do so and state the reason (21 CFR  54.4).  (See Question B.7 for a further 
explanation of due diligence.)  The sponsor should collect financial disclosure 
information from the clinical investigators, and, regardless of whether it collected all 
necessary financial information, should have information on any outcome payments (that 
is, payment that is dependent on the outcome of the study) and/or SPOOS made to the 
investigators.  The applicant should request this information from the sponsor.  The 
applicant should also make reasonable efforts to contact the clinical investigators to 
obtain disclosable financial information.  Information on proprietary interests, such as 
patents and trademarks, should also be available to the applicant from publicly available 
sources.   
 
F.3.  Q:  Do applicants need to provide information on investigators who participate in 
foreign studies?   
 
A:  The applicant has the same financial disclosure obligations (21 CFR part 54) with 
respect to studies conducted at foreign and domestic sites.  An applicant must include a 
certification or disclosure of information for each investigator participating in a foreign 
covered study, or, to the extent the applicant is unable to obtain sufficient information to 
certify or disclose, it must certify that it acted with due diligence but was unable to obtain 
the information and state the reason why (21 CFR  54.4).   
 
Sponsors of foreign covered studies should obtain financial disclosure information from 
clinical investigators prior to study initiation and provide this information to applicants.15    
 
The agency believes that a prudent applicant would take affirmative action at its earliest 
opportunity to collect financial information relating to a foreign covered study or to 
ensure that the information is collected by the study sponsor.  Where possible, the agency 
strongly encourages the applicant to arrange for the collection of financial information 
                                                 
15 If a foreign study is conducted pursuant to an IND or IDE, the sponsor has a legal obligation to comply with 
applicable rules, including the requirement to collect and maintain financial disclosure information. 
  22 Contains Nonbinding Recommendations 
prior to study initiation  to ensure that the information is preserved so that a complete 
submission can be made and to take any steps necessary to minimize potential bias.  
Where this is not possible, for example, because an applicant is submitting a foreign 
covered study sponsored by another entity and the applicant did not oversee, support, or 
direct the study, the applicant should take appropriate steps to obtain financial 
information from the study sponsor, investigators, or other reasonably available sources.  
See Question F.2.   
 
G.  COVERED CLINICAL STUDY  
 
G.1.  Q:  Disclosure of financial interests and arrangements is required only for covered 
clinical studies, specifically, those studies relied upon to provide support for the 
effectiveness of a product or in which a single investigator makes a significant 
contribution to the demonstration of safety (21 CFR  54.2(e) and 54.3).  An IND 
sponsor, acting much earlier, must inquire into investigator financial interests and 
arrangements before the ultimate role of a study in the application is determined (21 
CFR  312.53).  How will the IND sponsor determine which studies will ultimately 
require certification/disclosure statements?   
 
A:  The IND sponsor will need to consider the potential role of a particular study based 
on study size, design, and other considerations.  Almost any controlled effectiveness 
study could, depending on outcome, become part of a marketing application, but other 
studies might be critical too, such as a pharmacodynamic study in a population subset or 
a bioequivalence study supporting a new dosage form.  So, for many studies, it would be 
prudent to collect the information in the event that the study will ultimately require 
certification and disclosure statements.   
 
G.2.  Q: Do the reporting requirements apply to studies that include large numbers of 
investigators and multiple sites?  Will the agency consider a waiver mechanism to 
exempt applicants from collecting information from clinical investigators 
conducting these kinds of studies?   
 
A:  Large multi-center efficacy studies with many investigators are considered covered 
clinical studies within the meaning of the regulation (21 CFR  54.2(e)).  Data from 
investigators having only a small percentage of the total subject population (in a study 
with large numbers of investigators and multiple sites) could still affect the overall study 
results depending on the impact of their results on the overall study results.  Or, if a 
sponsor submitted data from a large, multi-center, double-blind study that included 
several thousand subjects, a single clinical investigator at a large site could be responsible 
for a significant number of study subjects.  In either case, if the investigator fabricated 
data or otherwise affected the integrity of the data, the results could have been influenced.   
 
By contrast, large open safety studies and treatment protocols that have large numbers of 
investigators would generally not be considered covered clinical studies.  As discussed in 
the preamble to the final rule,16 in these large open safety studies and treatment protocols, 
                                                 
16 See Federal Register, volume 63, February 2, 1998, page 5239.   
  23 Contains Nonbinding Recommendations 
the large number of investigators generally means that no single investigator has a major 
impact on the data.  In addition, important adverse events will generally be apparent 
because they lead to cessation of therapy and submission of the case report form.  
Although it is possible that a financial interest could be important in these studies, it is 
relatively unlikely.   
 
The regulations17 allow a sponsor to seek a waiver of certain requirements, including 
financial disclosure requirements.  FDA believes it is highly unlikely, however, that a 
waiver would be justified for studies begun after February 2, 1999, the effective date of 
the regulation, because the sponsor should already have begun collecting the information 
on an ongoing basis.  FDA will evaluate any request for waiver on a case-by-case basis.   
 
G.3.  Q:  The definition of a covered clinical study includes any study in which a single 
investigator makes a significant contribution to the demonstration of safety.  What 
does this mean? 
 
A:  Examples of commonly conducted studies in which a single investigator makes a 
significant contribution to the demonstration of safety would be studies that are designed 
to address a particular safety concern.  For example, an endoscopy study to evaluate a 
products effect on the stomach lining or a study in a subset of patients with a particular 
pre-existing condition or disease, such as significant cardiovascular risk factors or a 
history of poor (adverse) response to other treatments.  Such studies could have a single 
investigator, or could involve more than one clinical investigator.  If each investigator 
makes a significant contribution to the study and, therefore, to a demonstration of safety, 
such studies would be considered covered clinical studies and subject to financial 
disclosure.   
 
Studies that generally would not be covered studies are large open safety studies (where a 
large number of clinical investigators enroll subjects) that are designed to look at adverse 
events in general and do not focus on specific safety concerns.   
 
G.4.  Q:  Can a literature report be considered a covered clinical study? 
 
A:  Yes, a literature report could be considered a covered clinical study if it is being 
relied upon by the applicant or FDA to establish that the product is effective (including 
showing equivalence to an effective product) or where a single investigator makes a 
significant contribution to the demonstration of safety.18  When an applicant relies on a 
literature report in this manner, clinical investigator financial disclosure is required.  The 
author(s) and clinical investigators in the study should be contacted for this information 
to allow the applicant to submit the certification and/or disclosure forms or, if the 
applicant is unable to obtain the information, certification that the applicant acted with 
due diligence to obtain the information.  Because the financial interests and arrangements 
                                                 
17 See 21 CFR  312.10, 812.10, 314.90 and 814.20. 
18 Applicants should be aware that additional information may be needed in order for the agency to be able to use 
published literature reports in support of a marketing application.  For example, details about study methodology, 
the actual products studied, specifics about the patient population, patient accounting, etc. may be needed.   
  24 Contains Nonbinding Recommendations 
to be reported are those relating to the sponsor(s) of the covered clinical study and the 
product under study, the clinical investigators would not be required to report their 
financial interests in and arrangements with the applicant unless the applicant was a 
sponsor of the covered study.   
 
G.5.  Q:  Does the regulation include abbreviated new drug applications (ANDAs)?  Does 
the regulation include 510(k)s that include clinical data?  What about biosimilars? 
 
A:  The regulation requires an applicant whose submission relies in part on clinical data 
to disclose certain financial interest and arrangements.  A covered clinical study means 
any study of a drug (including a biological product) or device in humans submitted in a 
marketing application or reclassification petition that the applicant or FDA relies on to 
establish that the product is effective (including studies that show equivalence to an 
effective product), or any study in which a single investigator makes a significant 
contribution to the demonstration of safety.  This would, in general, not include phase 1 
tolerance studies or pharmacokinetic studies, most clinical pharmacology studies (unless 
they are critical to an efficacy determination), large open safety studies conducted at 
multiple sites, treatment protocols, and expanded access protocols.  (21 CFR  54.2 and 
54.3.)  ANDAs are subject to 21 CFR part 54 (21 CFR  314.94(a)(13)), as are 510(k)s 
(21 CFR  807.87(i)).  In addition, applications for biological products, including 
applications submitted under 351(k) of the Public Health Services Act, are also subject to 
the regulation. 
 
G.6.  Q:  Does the regulation apply to studies in support of labeling changes?   
 
A:  The regulation applies to studies submitted in a supplement when those studies meet 
the definition of a covered clinical study.  The definition includes studies to support 
safety labeling changes where individual investigators make a significant contribution to 
the safety information.  Studies to support the effectiveness of a new claimed indication 
are also included.  (21 CFR  54.2 and 54.3.)   
 
G.7.  Q:  Do actual use and labeling comprehension studies conducted to support a 
request to switch a drug product from prescription to over-the-counter (OTC) 
status fit the definition of covered clinical study?   
 
A:  Applicants who file supplements requesting that FDA approve a switch of a 
prescription drug to OTC status or who file a new drug application for OTC use often 
conduct actual use and labeling comprehension studies.  These may be intended to 
demonstrate that the product is safe and effective when used without the supervision of a 
licensed practitioner; in other cases, they may test labeling comprehension or other 
aspects of treatment by consumers.  Actual use studies performed to support these 
applications are considered covered clinical studies if they are used to demonstrate 
effectiveness in the OTC setting or if they represent a safety study where any investigator 
makes a significant contribution (21 CFR  54.2 and 54.3).  Labeling comprehension 
studies would not be considered covered studies.   
 
  25 Contains Nonbinding Recommendations 
G.8.  Q:  Are clinical investigators of in vitro diagnostics (IVDs) covered under this 
regulation?   
 
A:  Yes.  Applicants who submit marketing applications for IVDs that include covered 
clinical studies must provide the appropriate financial certification or disclosure 
information (21 CFR  54.3).  Although IVD studies may only involve specimens, under 
21 CFR  812.3(p), "subject" is defined as a "human who participates in an investigation, 
either as an individual on whom or on whose specimen an investigational device is used 
or as a control."  Under 21 CFR  812.3(h), an investigation is defined as a clinical 
investigation or research involving one or more subjects to determine the safety or 
effectiveness of a device.  Thus, if an investigation of an IVD is used to support a 
marketing application and it meets the definition of a covered clinical study, it would be 
subject to this regulation (21 CFR  54.3). 
 
H.  FDA REVIEW  
 
H.1.  Q:  Under what circumstances relating to financial disclosure would FDA refuse to 
file an application?   
 
A:  FDA may refuse to file any marketing application supported by covered clinical 
studies that does not contain, for each clinical investigator who is not an employee of the 
sponsor, a certification that no financial interest or arrangement specified in 54.4(a)(3) 
exists, a disclosure statement identifying the specified financial interests or arrangements 
and the steps taken to minimize bias, or a certification that the applicant has acted with 
due diligence to obtain the required information but was unable to do so and stating the 
reason (21 CFR  54.4(c)).  In general, if, during the filing review, an FDA reviewer 
identifies missing information, an attempt will be made to contact the applicant to obtain 
the missing information; however, applicants should take reasonable steps to ensure that 
applications are complete upon submission.  Applicants are encouraged to discuss their 
concerns on particular matters about financial information with FDA.   
 
H.2.  Q:  Who will review a disclosure of the specified financial interests and 
arrangements when such information is submitted in a marketing application?  
 
A:  FDA review staff, which may include project managers, consumer safety officers, 
medical officers, and/or others with regulatory or scientific expertise or supervisory 
authority, will evaluate financial disclosure information.  
 
H.3.  Q:  What will FDA reviewers consider when evaluating the financial disclosure 
information? 
 
A:  FDA reviewers will evaluate the information disclosed about each covered clinical 
study in an application to determine the impact of any disclosed financial interests or 
arrangements on the reliability of the data.  See 21 CFR  54.5(a).  FDA may consider 
many factors in making its evaluation (21 CFR  54.5(a) and (b)).   
 
  26 Contains Nonbinding Recommendations 
Part 54 does not categorically prohibit financial interests or arrangements, but it does 
require applicants to submit a list of clinical investigators who are full-time and part-time 
employees of the sponsor and to disclose or certify with respect to other investigators so 
that FDA can assess the possibility of bias.  The type of financial interest or arrangement 
disclosed is important because some financial interests and arrangements are of greater 
concern than others when assessing the reliability of the data.  For example, outcome 
payments (that is, payment that is dependent on the outcome of the study) elicit the 
highest concerns, followed by proprietary interests in the test article (such as patents, 
royalties, etc.).  With respect to equity interests and/or SPOOS, the amount and nature of 
the equity interests and payments may be considered.   
 
When a clinical investigator has disclosable financial interests or arrangements, the FDA 
reviewer will carefully consider the steps taken by the sponsor to minimize bias19 as 
described in the attachment to the FORM FDA 3455.  These steps may include study 
design, use of multiple clinical investigators and study sites, and replication of study 
results.  The agency also gives careful scrutiny to data from clinical investigators who are 
full-time or part-time employees of the sponsor, because of the possibility of significant 
financial interests in the outcome of studies.  (Hereafter, we refer to these investigator 
types jointly as disclosing investigators.)  Investigators for whom the applicant is not 
able to disclose or certify, despite exercising due diligence, will be considered on a case 
by case basis. 
 
The FDA reviewer may consider elements of the study design, including the method of 
randomization, the level of blinding (double-blind, single-blind), the presence or absence 
of a control group, whether placebo or active, the nature of the primary and secondary 
endpoints (objective, subjective), the method of endpoint assessment, the method of 
evaluation (including whether someone other than the disclosing investigator measured 
the endpoints), and whether many investigators, most  of whom were not disclosing 
investigators, participated in the study.  The FDA reviewer may also consider the total 
number of investigators and subjects in the study, the number and percentage of subjects 
enrolled by the disclosing investigator, information obtained from on-site inspections, 
and the data (including adverse events) of the disclosing investigator compared to other 
investigators in the study.  The reviewer may look at a re-analysis of the data performed 
either by the applicant or FDA that excludes the disclosing investigators results, other 
relevant types of reanalysis, and/or whether the results were replicated over multiple 
studies. 
 
The reviewer will make a judgment as to whether the financial interests or arrangements 
disclosed may have affected the interpretation of study results or otherwise require 
further action.  For example, if a disclosing investigator was a participant in a covered 
clinical study that (1) had randomized assignment of patients to treatment, (2) had a 
clearly objective endpoint (such as survival) or an endpoint assessed by a blinded 
observer other than the clinical investigator, (3) had multiple study sites (so that each 
investigator enrolled a small fraction of the total number of subjects), and (4) had results 
generally similar to the results of other investigators, then provided there were no other 
                                                 
19 See Question A.2 for a discussion of methods to minimize bias.   
  27 Contains Nonbinding Recommendations 
material, countervailing considerations, the reviewer might determine that a financial 
interest, employment relationship, or lack of certification or disclosure does not raise 
serious questions about the integrity of the covered study that require further action.  On 
the other hand, if the results of the disclosing investigator are clearly more favorable than 
results of the other investigators or centers and the disclosing investigators results could 
have influenced outcome, the reviewer would generally need to consider further action.  
(21 CFR  54.5(c).)   
 
FDA reviewers should consult with their management as needed to determine appropriate 
actions.   
 
H.4.  Q:  What actions may FDA take when a clinical investigator is the employee of a 
sponsor or has disclosable financial interests or arrangements? 
 
A:  If FDA determines that an investigators financial interests raise a serious question 
about the integrity of the data, FDA will take any action it deems necessary to ensure the 
reliability of the data (21 CFR  54.5(c)).  Please see Section III.C of this guidance for 
actions that may be taken.   
 
H.5.  Q:  How is the review to be documented? 
 
A:  Each FDA Center provides review templates or checklists for their review staff to use 
that include a section on financial disclosure issues.   
 
In general, the review should document that a list of clinical investigators for each 
covered clinical study was provided, and that, as applicable, there was either certification 
or documentation of disclosable financial interests and arrangements for each investigator 
on the list who is not an employee of the sponsor20 (21 CFR  54.4).   
 
When a disclosure of financial interests and arrangements is included (FORM FDA 
3455), reviewers should ensure that the details of the disclosable financial interests and 
arrangements are attached to the forms along with a description of the steps the sponsor 
has taken to minimize the potential bias of clinical study results by any of the disclosed 
interests or arrangements (21 CFR  54.4(a)(3)).  The reviewer will address the question 
of whether these interests and arrangements raise questions about the integrity of the data 
and describe any actions taken to minimize bias.  The reviewer will also describe any 
actions taken by the agency to address any questions raised by a disclosable financial 
interest or provide an explanation for why no action was indicated (21 CFR  54.5).  This 
documentation should be included in the appropriate section of the review template.   
 
When a sponsor certifies that he/she acted with due diligence to obtain information 
regarding the clinical investigators financial interests and arrangements but was unable 
to obtain it, reviewers should ensure that an explanation of the reason why the 
information could not be obtained and the efforts made to obtain the information is 
                                                 
20 If the spouse or dependent child of an investigator is an employee of the sponsor, the investigator should be 
identified as an employee and further financial disclosure under this provision is not required.   
  28 Contains Nonbinding Recommendations 
attached to the FORM FDA 3454 (21 CFR  54.4).  See Question B.7 for a discussion of 
due diligence.   
 
H.6.  Q:  Under what circumstances will FDA publicly discuss financial interests and 
arrangements disclosed to the agency?   
 
A:  As discussed in the preamble to the 1998 final rule,21 FDAs policy is that certain 
types of financial information requested under the rule, notably clinical investigators' 
equity interests, will be protected from public disclosure unless circumstances relating to 
the public interest clearly outweigh the clinical investigator's identified privacy interest.  
FDA cited the example of a financial interest or arrangement so affecting the reliability of 
a study as to warrant its public disclosure during evaluation of the study by an advisory 
panel.  FDA expects that only rarely would an investigator's privacy interest be 
outweighed by the public interest and thus warrant disclosure of the details of financial 
interest or arrangement.  The agency will carefully evaluate each circumstance on a case-
by-case basis.   
 
FDA recognizes, however, that there is increased interest in the financial arrangements 
between clinical investigators and sponsors of the clinical trials in which the investigators 
participate.  For this reason, FDA intends to provide information about the number of 
clinical investigators with disclosable financial interests or arrangements in the new 
product reviews FDA posts for an approval decision.  This information would not 
identify clinical investigators by name but likely would include information such as the 
number of clinical investigators in the study and the number of investigators, if any, with 
disclosable financial interests or arrangements.22   
 
I.  RECORDKEEPING   
 
I.1.  Q:  What are the recordkeeping requirements for financial disclosure information? 
 
A:  The recordkeeping requirements for applicants are described in 21 CFR  54.6.  
Applicants must retain certain information on clinical investigators' financial interests 
and arrangements (21 CFR  54.6(a)) and permit FDA employees to have access to the 
information and to copy the records at reasonable times (21 CFR  54.6(b)(2)).  Records 
are to be maintained for two years after the date of approval of the application (21 CFR  
54.6(b)(1)).   
 
Additionally, IND and IDE sponsors are required to maintain complete and accurate 
records of financial disclosure information as part of the records for the investigation (21 
                                                 
21 Federal Register, February 2, 1998, 63 FR 5233 
22 FDA also recognizes that subjects participating in a clinical trial may be interested in the financial 
interests/arrangements of the clinical investigator at the site where the subject is considering participation.  The 
Department of Health and Human Services Guidance Document, Financial Relationships and Interests in Research 
Involving Human Subjects: Guidance for Human Subject Protection, which is applicable to FDA regulated 
research, recommends that consideration be given to providing potential subjects with information about the 
financial interests and arrangements of the parties involved in the research.  This guidance is available at 
http://www.hhs.gov/ohrp/policy/fguid.pdf.   
  29 Contains Nonbinding Recommendations 
CFR  312.57(b) and 812.140(b)(3)) and to retain the records pursuant to the required 
retention periods identified in the IND and IDE regulations (21 CFR  312.57(c) and 
812.140(d)).   
 
I.2.  Q:  What kind of documentation is necessary for applicants to keep in case 
questions about certification and/or disclosure arise?  
 
A:  To the extent that applicants have relied on investigators as the source of information 
about potentially disclosable financial interests and arrangements, the underlying 
documentation (e.g., copies of executed questionnaires returned by investigators, 
correspondence on the subject of financial disclosure, mail receipts, etc.) should be 
retained.  Likewise, to the extent that applicants who did not sponsor a covered clinical 
study rely on information furnished by the sponsor, the underlying documentation, 
including all relevant correspondence with and reports from the sponsor, should be 
retained.  To the extent that applicants rely upon information available internally, all 
appropriate financial documentation regarding the financial interests or arrangements in 
question should be retained.  For example, in the case of significant payments of other 
sorts, applicants should keep documentation including, but not limited to, records of 
electronic financial transactions, certified mail delivery receipts, etc.  (21 CFR  54.6(a), 
312.57(b) and 812.140(b)(3).)   
 
If storage space is a concern, sponsors and applicants may use electronic storage.  For 
example, required records may be scanned as certified copies 23 of the original and stored 
electronically, as long as the records remain accessible for inspection and copying by 
FDA (see Question J.1).  If electronic records are used, you should consult guidance on 
electronic storage of clinical trial records under part 11, Computerized Systems Used in 
Clinical Investigations,24 for further information about maintaining scanned documents.    
 
J.  FDA INSPECTIONS 
 
J.1.   Q:  Will financial disclosure information be reviewed during a bioresearch 
monitoring program (BIMO) inspection of the sponsor? 
 
A:  During a sponsor inspection, it is FDAs policy to review financial disclosure 
information that clinical investigators provide to the sponsor, although FDA may request 
access to these records at other reasonable times.  FDA has the authority to access and 
copy documents supporting an applicant's certification or disclosure statement submitted 
to the agency in a marketing application (21 CFR  54.6(b)(2)).  FDAs regulations 
require sponsors to establish and maintain records of data obtained during investigational 
                                                 
23 FDAs guidance on Computerized Systems Used in Clinical Investigations defines certified copy as a copy of 
original information that has been verified, as indicated by dated signature, as an exact copy having all the same 
attributes and information as the original.   
24 This guidance may be accessed at  
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070266.pdf.   
  30 Contains Nonbinding Recommendations 
studies of drugs, biological products, and devices that will enable the agency to evaluate a 
product's safety and effectiveness.25   
 
J.2.  Q:  Will financial disclosure be part of a BIMO inspection of a clinical site? 
 
A:  It is FDAs policy that FDA investigators should ask the clinical investigator if he/she 
submitted information to the sponsor prior to initiation of the study and updated that 
information, as needed, for up to one year after completion of the study at the site. 
 
J.3.  Q:  Are there any instructions for FDAs inspectional staff with respect to reviewing 
records pertaining to financial disclosure? 
 
A:  FDA has provided instructions in the Compliance Program Guidance Manual 
(CPGM) chapters on clinical investigator inspections26 and sponsor inspections.27 
 
K.  CONTACTS 
 
K.1.  Q:  Who may be contacted in each FDA Center to answer questions regarding this 
regulation?   
 
A:  The following entities may be contacted:  Division of Drug Information in the Center 
for Drug Evaluation and Research, phone 888-463-6332 or 301-796-3400, Division of 
Small Manufacturers, International and Consumer Assistance in the Center for Devices 
and Radiological Health, phone 800-638-2041 or 301-796-7100, and the Office of 
Communication, Outreach and Development in the Center for Biologics Evaluation and 
Research, phone 800-835-4709 or 301-827-1800.   
                                                 
25 21 CFR  54.6, 312.57, 312.58, 812.140 and 812.145. 
26 http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/ucm133562.htm 
27 http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/ucm133777.htm    
  31 Contains Nonbinding Recommendations 
 
APPENDIX 
 
Considerations for Collecting  
Financial Disclosure Information  
from Clinical Investigators 
 
Suggested items to provide to clinical investigators to assist them in complying with financial 
disclosure reporting requirements:  
 
1)  Identify the sponsor(s) of the covered clinical study.  See Section IV.E. 
 
2)  Identify whose financial interests and arrangements need to be reported (e.g., clinical 
investigators, their spouses and dependent children).  See Section IV.D. 
 
3)  Identify the financial interests and arrangements that must be disclosed in detail.  See 
Section III.B and Question C.1.   
 
NOTE:  The threshold amounts apply separately for each sponsor (see Question E.1) but 
are cumulative for the investigator and his/her spouse and dependent children (see 
Section III.B).   
 
a)  Employment by any sponsor.  See Section III and Questions B.1 and D.4.  
 
b)  Any compensation by any sponsor in which the value of compensation is affected 
by study outcome.  See Section III.B.1. 
 
c)  Any proprietary interest in the tested product.  See Section III.B.2. 
 
d)  Any equity interest in any sponsor of the covered clinical study whose value cannot 
be readily determined through reference to public prices.  See Section III.B.3.   
 
e)  Any equity interest in any sponsor of the covered clinical study if that sponsor is a 
publicly held company and the interest exceeds $50,000.  See Section III.B.4 and 
Questions C.2 and C.3. 
 
f)  Significant payments of other sorts (SPOOS) that have a cumulative monetary value 
of $25,000 or more made to the investigator or the investigators institution.  See 
Section III.B.5 and Questions C.4, C.5 and C.6. 
 
4)  Remind investigators of obligation to promptly update their financial disclosure 
information when relevant changes occur during the study and for one year following 
study completion.  See Questions C.2 and D.6.   
 
 
  32