FDA reviews data generated in clinical studies to determine whether medical device applications are approvable. Financial interest of a clinical investigator is one potential source of bias in the outcome of a clinical study. To ensure the reliability of the data, the financial interests and arrangements of clinical investigators must be disclosed to FDA.
This requirement applies to any clinical study submitted in a marketing application that the applicant or FDA relies on to establish that the product is effective or is used to show equivalence to an effective product, and any study in which a single investigator makes a significant contribution to the demonstration of safety. The requirement does not apply to studies conducted under the emergency use, compassionate use, or treatment use provisions. Financial compensation or interests information is used, in conjunction with information about the design and purpose of the study, as well as information obtained through on-site inspections, in the agency's assessment of the reliability of the data.
Anyone who submits a Premarket Approval Application (PMA) or Premarket Notification 510(k) after February 2, 1999 that contains a covered clinical study must submit certain information concerning the compensation to, and financial interests of, any clinical investigator conducting covered clinical studies in the application. Applicants must certify to the absence of certain financial interests of clinical investigators on Financial Interest Form: Certification: Financial Interests and Arrangements of Clinical Investigations FDA Form 3454 or to disclose those financial interests on Financial Interest Form: Disclosure: Financial Interests and Arrangements of Clinical Investigators FDA Form 3455.
The financial arrangements that must be disclosed include the following:
- Compensation made to the investigator in which the value of the compensation could be affected by the study outcome.
- Significant payments to the investigator or institution with a monetary value of $25,000 or more (e.g., grants, equipment, retainers for ongoing consultation, or honoraria) over the cost of conducting the trial. Any such payments to the investigator or institution during the time the investigator is conducting the study and for one year following study completion, must be reported.
- Proprietary interest in the device, such as a patent, trademark, copyright, or licensing agreement.
- Significant equity interest in the sponsor such as ownership, interest, or stock options. All such interests whose value cannot be readily determined through reference to public prices must be reported. If the sponsor is a publicly traded company, any equity interest whose value is greater than $50,000 must be reported. Any such interests held by the investigator while the investigator was conducting the study and for one year following study completion must be reported.
This requirement applies to investigators and subinvestigators including their spouses and dependent children, but does not apply to full or part-time employees of the sponsor or to hospital or office staff.
Please note that if the study was completed prior to February 2, 1999, the requirements are reduced. That is, the sponsor does not need to report equity interest in a publicly held company or significant payments of other sorts. Other reporting still applies.
Sponsors are responsible for collecting financial information from investigators and clinical investigators are responsible for providing financial disclosure information to the sponsor. The investigator's agreement with the sponsor should require the investigator to provide to the sponsor accurate financial disclosure information. (See Responsibilities). Certification or disclosure information should not be included in the IDE application.
If FDA determines that the financial interests 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 including:
- Initiating agency audits of the data derived from the clinical investigator in question
- 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
- Requesting that the applicant conduct additional independent studies to confirm the results of the questioned study
- Refusing to use the data from the covered clinical study as the primary basis for an agency action, such as PMA approval or 510(k) clearance.
Please note that FDA does NOT prohibit financial compensation to clinical investigators nor does FDA require or recommend divesture. FDA believes that divestiture could adversely affect development of new products.