The FDA's New Guidelines on Financial Disclosure by Clinical Investigators

There has been a growing number of claims in medical device and pharmaceutical product liability actions based on purported conflicts of interest of clinical investigators conducting medical device or pharmaceutical clinical studies. Financial interests of clinical investigators can be a potential source of bias in clinical study data used to support the application for FDA approval of a new drug or a new medical device. In particular, a clinical trial investigator may have a financial interest in the outcome of the study, due to payment arrangements or equity interests in the sponsors of clinical studies. While the FDA does not prohibit a clinical trial investigator from having a purported financial interest, it does regulate the disclosure of that information. The financial disclosure requirements of clinical investigators are governed by 21 Code of Federal Regulations Part 54, which came into effect in 1999. Generally, FDA regulations require that medical device and pharmaceutical manufacturers submit financial interest disclosures with their applications for a new drug or a new device. On March 20, 2001, the FDA issued its original Guidance on Financial Disclosure By Clinical Investigators to assist pharmaceutical and medical device companies, as well as clinical investigators in interpreting and complying with the federal regulations governing financial interest disclosures.

In recent years, there has been an increased public interest concerning the regulation of conflicts of interests for clinical investigators. In 2009, the Office of the Inspector General (OIG), Department of Health and Human Services published its report, The Food and Drug Administration's Oversight of Clinical Investigators' Financial Information, which raised concerns regarding the FDA's monitoring of conflict of interests to ensure the integrity of clinical research. In response, the FDA has recently updated its Guidance for Industry: Financial Disclosure of Clinical Investigators for the first time since 2001. The revised Guidance addresses issues raised in the OIG's report as well as frequently asked questions from the industry and public. This article briefly examines the key changes to the revised Guidance and the practical implications of the new guidelines in product liability cases.

Background

FDA regulations require applicants submitting a marketing application for drugs, biological products, or devices to disclose financial information relating to the compensation, financial interests and arrangements of clinical investigators conducting clinical studies. 21 C.F.R. ' 54. The regulation applies to clinical studies submitted in a marketing application that either the FDA or the applicant relies on to establish that a product is effective, and any study where a single investigator makes a significant contribution to the demonstration of safety. 21 C.F.R. ' 54.2. The applicant collects financial disclosure forms from the clinical investigators. Based upon those forms, the applicants then are required to do one of the following: certify that no financial interest exists; disclose the nature of the financial interests and steps taken to minimize any potential bias; or certify that the applicant acted in due diligence but was unable to obtain the financial information. 21 C.F.R. ' 54.4. The FDA uses this information, along with information about the design and purpose of the study and information from on-site inspections, to determine the reliability of the data from the study. If the FDA has concerns about the integrity of the data based on the financial disclosure information, the FDA can take actions, including audits, requesting further analyses of the data, requesting additional studies, and rejecting the data as support for the new drug or device marketing application.

Under the regulations, the following are considered to be disclosable financial arrangements:

• A. Compensation made to the investigator in which the value of compensation could be affected by study outcome. This requirement applies to all covered studies, whether ongoing or completed, as of Feb. 2, 1999.
• B. A proprietary interest to the tested product, including, but not limited to, a patent, trademark, copyright or licensing agreement. This requirement applies to all covered studies, whether ongoing or completed as of Feb. 2, 1999.
• C. Any equity interest in the sponsor of a covered study, i.e., any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices. This requirement applies to all covered studies, whether ongoing or completed.
• D. Any equity interest in a publicly held company that exceeds $50,000 in value. These must be disclosed only for covered clinical studies that are ongoing on or after Feb. 2, 1999. 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; and
• E. Significant payments of other sorts (SPOOS), which are payments that have a cumulative monetary value of $25,000 or more made by the sponsor of a covered study to the investigator or the investigators' institution to support activities of the investigator exclusive of the costs of conducting the clinical study or other clinical studies, (e.g., a grant to fund ongoing research, compensation in the form of equipment or retainers for ongoing consultation or honoraria) during the time the clinical investigator is carrying out the study and for one year following completion of the study. This requirement applies to payments made on or after Feb. 2, 1999.

The FDA's 2001 Financial Disclosure of Clinical Investigators Guidance provided answers to 31 questions that the FDA had received in response to the financial disclosure regulations. The questions generally related to the purpose of the financial disclosure regulations, the requirements and obligations for applicants, sponsors, and investigators, and the FDA's definitions and explanation of terms used in the regulations. The FDA also provided further clarification of the categories of disclosable financial interests.

The New Guidelines