Proposed Rule Requires Sponsors to Report Suspected Falsification of Data to FDA

By David B. Clissold and Nisha P. Shah

On February 19, 2010, FDA issued a proposed rule that would require sponsors to report any person that has or may have engaged in the falsification of data in studies that involve human or animal subjects.  FDA believes the proposed rule is “intended to help ensure the validity of data that the agency receives in support of applications and petitions for FDA product approvals and authorization of certain labeling claims and to protect research subjects.”

Key definitions under the proposed rule are: 
•  “Sponsor” would broadly include sponsors of studies conducted on humans and animals; petitioners submitting food additive, color additive, nutrient content claim, and health claim petitions; and manufacturers or distributors submitting new dietary ingredient notifications.
•  “Falsification of data” would be defined as “creating, altering, recording, or omitting data in such a way that the data do not represent what actually occurred.” The proposed rule would not be intended to address “unintentional errors in recording or reporting information”, such as typographical errors or transposed numbers or characters.
•  “Data” would include, though not limited to, “individual facts, tests, specimens, samples, results, statistics, items of information, or statements made by individuals.”

The rule would require a sponsor to report information indicating that a “person has, or may have, engaged in the falsification of data in the course of reporting study results, or in the course of proposing, designing, performing, recording, supervising, or reviewing studies that involve human subjects or animal subjects conducted by or on behalf of a sponsor.”  A sponsor would not be required to determine definitively that data have been falsified, nor the intent of the person who has, or may have, falsified data.  Rather, a sponsor would be required to report information of which it is aware suggesting that a person has, or may have, engaged in the falsification of data. The reporting obligation would exist regardless of the amount of evidence, if any, the sponsor has with regard to the intent of the person who has, or may have, falsified data.  The agency emphasized that the sponsors should not wait to determine conclusively whether falsification actually occurred, or seek to determine the circumstances that led to the falsification before reporting the information with FDA. Therefore, a sponsor must report any confirmed or possible falsification of data.

The sponsor would be required to report the information to the appropriate FDA center “promptly”, but no later than 45 calendar days after the sponsor becomes aware of the information.  The reporting requirement would be ongoing and cover the periods before and after study completion.  Information in the report to FDA must include the following: 
•  The name of the person who has, or may have, falsified data, 
•  The last know address(es) and phone number(s) of that person, 
•  The specific identify of the potentially affected study, including, when applicable, application information such as the application number, investigational protocol number, study title, study site(s), and study dates, and 
•  Information suggesting that falsification occurred and describing the falsification. 

FDA commented that the agency is considering also whether additional information should be included in the report, such as the National Clinical Trial (“NCT”) number assigned to a study when the study is registered with ClinicalTrials.gov. 

FDA intends to use the reported information to determine whether further agency investigation is warranted in conjunction with other information available to the agency.  According to FDA, these investigations might form the basis of administrative or enforcement actions, such as excluding clinical trials from consideration by FDA, placing a clinical trial on hold, or initiating disqualification of investigators or criminal proceedings.  Failure to report possible falsification of data might constitute a violation of section 301(e) of the Food, Drug, and Cosmetic Act (21 U.S.C. § 331(e)) (concerning failure to make a required report) or 18 U.S.C. § 1001 (concerning the submission of a false statement to the federal government).

This proposed rule is a dramatic shift in regulatory obligations with serious implications for study sponsors and investigators alike.  Currently, if the sponsor of a clinical study under an IND determines that an investigator “is not complying” with the protocol or with FDA regulations (conduct that would include data falsification), they must discontinue the investigator’s participation in the trial and notify FDA.  Note that a mere “suspicion” of non-compliance is not enough to trigger this obligation.  In contrast, the proposed rule requires sponsors to report “possible” falsification.  FDA claims they are not interested in “errors” but as any experienced clinical trial auditor will tell you, there is a lot of gray area between an “error” and “falsification.”  As FDA noted, “falsification is more difficult for FDA to detect than errors . . . because persons who engage in the falsification process are more likely to attempt to conceal their actions.”  That is undoubtedly true, but such people are no more likely to reveal those actions to a sponsor’s representative than they are to an FDA investigator.  Moreover, data falsification is not always obvious right away, even to an auditor or monitor.  FDA generally gets to review these allegations on their own timeline with the benefit of 20:20 hindsight, yet the sponsor is expected to report suspicious activity, or apparently even unusual activity that is not resolved within 45 days, under penalty of civil penalty.  Not addressed in the proposed rule is whether FDA will expect the sponsor to continue to develop evidence for the Agency after it has reported suspected falsification.
 
Comments on the proposed rule must be submitted by May 20, 2010.