Good Clinical Practice: A Question and Answer Guide2024/2025 Edition - 305

Conflicts of Interests/Financial Disclosure
on the Form FDA-1572. By performing these significant study activities, the study coordinators should have
been listed on the form FDA 1572s as sub-investigators. "
* In a May 2008 warning letter, a clinical investigator was cited after an FDA investigation found that at least
two " physicians who had a significant role in the conduct of the investigation.... were not listed on Form FDA
1572 as sub-investigator.... "
14.3 Q. If the PI and the sub-investigator are husband and wife, is it sufficient to only collect financial
disclosure information from the investigator, since he/she will be answering for their spouse as well, or
is it still expected to have each one complete a financial disclosure?
A. In a reply to this question in January 2013, the FDA indicated that Part 54 requires the clinical investigator
(defined in Part 54 to include the investigator and sub-investigator) to provide the sponsor with financial information
(see 21 CFR 54.4(b)). Therefore, while the investigator and sub-investigator may have the same information to
disclose, the regulations could be read to require each to provide the financial information to the sponsor. The
regulations do not specify how the sponsor is to collect the information from the clinical investigator and, in
guidance, FDA has indicated that " sponsors/applicants have the flexibility to collect the information in the most
efficient and least burdensome manner that will be effective. " Therefore, the sponsor could determine that a single
disclosure is needed for the investigator and sub-investigator but, to assure clinical investigator compliance with
the regulations, could require that the disclosure be from both, for example, by having both sign it.
14.4 Q. Although the regulations at Part 54 require that financial disclosure information be collected during
clinical trials, when is this information actually submitted to FDA?
A. According to FDA regulations, the marketing application (NDA, BLA, ANDA, 510K, PMA, etc.) 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 sub-investigators 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). EMA regulations (REGULATION (EU)
No 536/2014 OF THE EUROPEAN PARLIAMENT) also require that the submitted application dossier for an
initial application include information on financial transactions and compensation paid to each investigator/site for
participating in the clinical trial.
14.5 Q. What type of information is to be provided in the marketing application regarding financial disclosure?
A. According to the regulations, 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)):
1. FORM FDA 3455, Disclosure Statement, for each clinical investigator who, or whose spouse or dependent
child, has 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));
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.
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Good Clinical Practice: A Question and Answer Guide2024/2025 Edition

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