PART 54—FINANCIAL DISCLOSURE BY CLINICAL INVESTIGATORS Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c-360j, 371, 372, 373, 374, 375, 376, 379; 42 U.S.C. 262. Source: 63 FR 5250, Feb. 2, 1998, unless otherwise noted. § 54.1 Purpose. (a) The Food and Drug Administration (FDA) evaluates clinical studies submitted in marketing applications, required by law, for new human drugs and biological products and marketing applications and reclassification petitions for medical devices. (b) The agency reviews data generated in these clinical studies to determine whether the applications are approvable under the statutory requirements. FDA may consider clinical studies inadequate and the data inadequate if, among other things, appropriate steps have not been taken in the design, conduct, reporting, and analysis of the studies to minimize 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. This section and conforming regulations require an applicant whose submission relies in part on clinical data to disclose certain financial arrangements between sponsor(s) of the covered studies and the clinical investigators and certain interests of the clinical investigators in the product under study or in the sponsor of the covered studies. FDA will use this information, 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. § 54.2 Definitions. For the purposes of this part: (a) Compensation affected by the outcome of clinical studies (b) Significant equity interest in the sponsor of a covered study (c) Proprietary interest in the tested product (d) Clinical investigator (e) Covered clinical study (f) Significant payments of other sorts (g) Applicant (h) Sponsor of the covered clinical study [63 FR 5250, Feb. 2, 1998, as amended at 63 FR 72181, Dec. 31, 1998] § 54.3 Scope. The requirements in this part apply to any applicant who submits a marketing application for a human drug, biological product, or device and who submits covered clinical studies. The applicant is responsible for making the appropriate certification or disclosure statement where the applicant either contracted with one or more clinical investigators to conduct the studies or submitted studies conducted by others not under contract to the applicant. § 54.4 Certification and disclosure requirements. For purposes of this part, an applicant must submit a list of all clinical investigators who conducted covered clinical studies to determine whether the applicant's product meets FDA's marketing requirements, identifying those clinical investigators who are full-time or part-time employees of the sponsor of each covered study. The applicant must also completely and accurately disclose or certify information concerning the financial interests of a clinical investigator who is not a full-time or part-time employee of the sponsor for each covered clinical study. Clinical investigators subject to investigational new drug or investigational device exemption regulations must provide the sponsor of the study with sufficient accurate information needed to allow subsequent disclosure or certification. The applicant is required to submit for each clinical investigator who participates in a covered study, either a certification that none of the financial arrangements described in § 54.2 exist, or disclose the nature of those arrangements to the agency. Where the applicant acts with due diligence to obtain the information required in this section but is unable to do so, the applicant shall certify that despite the applicant's due diligence in attempting to obtain the information, the applicant was unable to obtain the information and shall include the reason. (a) The applicant (of an application submitted under sections 505, 506, 510(k), 513, or 515 of the Federal Food, Drug, and Cosmetic Act, or section 351 of the Public Health Service Act) that relies in whole or in part on clinical studies shall submit, for each clinical investigator who participated in a covered clinical study, either a certification described in paragraph (a)(1) of this section or a disclosure statement described in paragraph (a)(3) of this section. (1) Certification: The applicant covered by this section shall submit for all clinical investigators (as defined in § 54.2(d)), to whom the certification applies, a completed Form FDA 3454 attesting to the absence of financial interests and arrangements described in paragraph (a)(3) of this section. The form shall be dated and signed by the chief financial officer or other responsible corporate official or representative. (2) If the certification covers less than all covered clinical data in the application, the applicant shall include in the certification a list of the studies covered by this certification. (3) Disclosure Statement: For any clinical investigator defined in § 54.2(d) for whom the applicant does not submit the certification described in paragraph (a)(1) of this section, the applicant shall submit a completed Form FDA 3455 disclosing completely and accurately the following: (i) Any financial arrangement entered into between the sponsor of the covered study and the clinical investigator involved in the conduct of a covered clinical trial, whereby the value of the compensation to the clinical investigator for conducting the study could be influenced by the outcome of the study; (ii) Any significant payments of other sorts from the sponsor of the covered study, such as a grant to fund ongoing research, compensation in the form of equipment, retainer for ongoing consultation, or honoraria; (iii) Any proprietary interest in the tested product held by any clinical investigator involved in a study; (iv) Any significant equity interest in the sponsor of the covered study held by any clinical investigator involved in any clinical study; and (v) Any steps taken to minimize the potential for bias resulting from any of the disclosed arrangements, interests, or payments. (b) The clinical investigator shall provide to the sponsor of the covered study sufficient accurate financial information to allow the sponsor to submit complete and accurate certification or disclosure statements as required in paragraph (a) of this section. The investigator shall promptly update this information if any relevant changes occur in the course of the investigation or for 1 year following completion of the study. (c) Refusal to file application. FDA may refuse to file any marketing application described in paragraph (a) of this section that does not contain the information required by this section or a certification by the applicant that the applicant has acted with due diligence to obtain the information but was unable to do so and stating the reason. [63 FR 5250, Feb. 2, 1998; 63 FR 35134, June 29, 1998, as amended at 64 FR 399, Jan. 5, 1999] § 54.5 Agency evaluation of financial interests. (a) Evaluation of disclosure statement. (b) Effect of study design. (c) Agency actions to ensure reliability of data. (1) Initiating agency audits of the data derived from the clinical investigator in question; (2) Requesting that the applicant submit further analyses of data, e.g., to evaluate the effect of the clinical investigator's data on overall study outcome; (3) Requesting that the applicant conduct additional independent studies to confirm the results of the questioned study; and (4) Refusing to treat the covered clinical study as providing data that can be the basis for an agency action. § 54.6 Recordkeeping and record retention. (a) Financial records of clinical investigators to be retained. (1) Complete records showing any financial interest or arrangement as described in § 54.4(a)(3)(i) paid to such clinical investigators by the sponsor of the covered study. (2) Complete records showing significant payments of other sorts, as described in § 54.4(a)(3)(ii), made by the sponsor of the covered clinical study to the clinical investigator. (3) Complete records showing any financial interests held by clinical investigators as set forth in § 54.4(a)(3)(iii) and (a)(3)(iv). (b) Requirements for maintenance of clinical investigators' financial records. (2) The person maintaining these records shall, upon request from any properly authorized officer or employee of FDA, at reasonable times, permit such officer or employee to have access to and copy and verify these records.