FDA issued a final guidance on disclosure of financial interests of clinical investigators. FDA intends for the guidance to assist clinical investigators, clinical trial sponsors, and applicants in complying with 21 C.F.R. Part 54. The guidance finalized and revised a draft guidance issued May 2011 and replaces a prior guidance issued in 2001.
Under the final guidance, FDA intends to disclose, in the product reviews the agency posts for an approval decision, the number of clinical investigators in a study and the number of investigators with financial interests. FDA also reiterated that it will not publicly disclose certain types of financial information, such as investigators’ equity interests, unless the public interest in disclosure outweighs the investigator’s privacy interest. For example, FDA may disclose a financial interest that so affects the reliability of a study that it warrants public disclosure during evaluation of the study by an advisory panel. However, FDA expects that the public interest will necessitate disclosure only in rare circumstances, which the agency will evaluate on a case-by-case basis.
The public disclosure of financial interest information was a significant issue surrounding the 2011 draft guidance. In the draft guidance, FDA noted the growing interest in the public disclosure of industry financial arrangements with physicians. FDA did not specify how it planned to disclose the information; rather, the agency was considering various options and requested comments on the issue.
The final guidance also includes the following changes from the 2011 draft guidance:
- FDA explained when a party has provided “material support” and is therefore considered a “sponsor” of a clinical study for purposes of the financial disclosure requirements. “Material support” includes providing direct funding or other monetary support, or providing services without reimbursement, or providing materials (including the study product, ancillary medication, or equipment used in testing) without reimbursement. This definition of “sponsor” is therefore broader than the definition of sponsor in the Investigational New Drug and Investigational Device Exemption regulations, and a study can have more than one “sponsor.”
- FDA added that a literature report could be considered a covered clinical study if FDA or the applicant is relying on it to establish the product’s effectiveness, or if a single investigator makes a significant contribution to the demonstration of safety. In these circumstances, the authors(s) and clinical investigators in the study should be contacted for financial disclosure information.
- In the draft guidance, FDA stated that sponsors and applicants should try to locate missing clinical investigators through at least two telephone calls and send two certified letters. The final guidance clarified that sponsors and applicants should “exercise reasonable judgment regarding the appropriate amount of effort to expend,” including consideration of the role of the investigator in the study and the importance of the investigator’s data contribution. FDA suggested that, in most cases, more than one attempt to contact an investigator via more than one method of contact would be appropriate.
- FDA clarified that those individuals who only collect specimens or perform routine tests are not included in the definition of “clinical investigator.”
- FDA clarified that applicants and investigators may not rely on compliance with the investigator’s institutional policy on financial conflicts of interest.
The financial disclosure requirements apply broadly to studies conducted at both foreign and domestic study sites.
Failure to comply with the requirements can have serious consequences: FDA may refuse to file an application if the applicant does not include the required financial interest disclosure information. In addition, if FDA’s review of the sponsor’s disclosure information raises a serious question about the integrity of the trial, the agency may take a variety of steps to ensure the reliability of the data. Such steps may include auditing an investigator’s data, requesting that the applicant analyze the effect of the investigator’s data on the study outcome, requesting additional independent studies, or refusing to treat the affected study as providing data that can provide a basis for agency approval.