A guidance document released by the US Food and Drug Administration (FDA) looks to clarify the requirements associated with the disclosure of financial holdings by clinical investigators that could influence the outcome of a trial.
The guidance specifically looks at the requirements of 21 CFR 54, Financial Disclosure by Clinical Investigator. That section notes that FDA might find a study to be inadequate if it does not account for the effects of potential investigator bias.
"One potential source of bias in clinical studies is a financial interest of the clinical investigator in the outcome of the study because of the way payment is arranged (e.g., a royalty) or because the investigator has a proprietary interest in the product (e.g., a patent) or because the investigator has an equity interest in the sponsor of the covered study," FDA notes in the Code of Federal Regulations (CFR).
Thus, FDA requires applicants looking to conduct a clinical trial to submit a list of all investigators who will be working on the trial paired with a certification that either no financial arrangements exist that would cause a problem, or explaining the nature and extent of those holdings and why they do not pose a problem to the conduct of the trial. (See: 21 CFR 54.4(a))
Consequences and Clarity
FDA reserves the right to refuse to file any application that fails to disclose this information, and may also audit a company's data, request additional data or request additional independent studies to confirm the first study.
While the regulation has been in effect since 1999, and FDA has relied on a guidance document on the topic since 2001, the new document updates and clarifies some of the definitions used by FDA to implement the regulation.
For example, even a part-time investigator who did not participate in the study for its entire duration is still considered a reportable entity under the regulation.
FDA also notes that expanded access schemes, such as compassionate use, would not ordinarily be required to report to FDA as a "covered clinical study" for the purposes of financial disclosure. Rules for expanded access were only finalized in 2009.
The guidance also contains a number answers to common questions, such as methods to reduce bias, required forms and formatting, responsibilities, due diligence procedures, reportable payments and interests (including 401k investments), the definitions of various entities involved in a trial, how outsourcing a trial affects reporting requirements, and various other requirements associated with reporting financial interests.
The guidance replaces one of the same name released in March 2001, and finalizes FDA's May 2011 draft guidance.