For years, the Food and Drug Administration (FDA) has acknowledged that “falsification of data can, if not detected, undermine subject protection and the underlying basis for FDA actions.” Since the agency has experienced difficulty in the reporting of such cases, and current regulations are not extensive enough for the FDA, they recently proposed a rule to amend its regulations for reporting falsification of data.
The proposed rule defines falsification of data as “creating, altering, recording, or omitting data in such a way that the data do not represent what actually occurred. FDA recommended that errors, which can include typographical errors and transposed numbers or characters, should not be reported under the proposed rule. FDA is also proposing to not include plagiarism under the proposed rule.
Specifically, the new rule will require sponsors to report information indicating that any 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 or relied on by a sponsor. FDA asserted that “this proposal is necessary because ambiguity in the current reporting scheme has caused confusion among sponsors.”
A sponsor would be required to report this information to the appropriate FDA center promptly, but no later than 45 calendar days after the sponsor becomes aware of the information. The proposed requirement for a sponsor to report information regarding falsification of data would be ongoing and cover the periods before and after study completion, including after the review, approval, or authorization of the affected product or labeling. Specifically, the proposed rule would require the sponsor to report to FDA by any means, including telephone, mail, electronic mail, or facsimile:
– The name of the person who has, or may have, falsified data;
– The last known address(es) and phone number(s) of that person;
– The specific identity 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;
– Information suggesting that falsification occurred and describing the falsification. A sponsor may provide this information; and
– FDA is considering reporting the National Clinical Trial (NCT) number assigned to a study when an applicable clinical trial is registered with ClinicalTrials.gov.
In proposing this rule, FDA noted that it is important for the agency to have confidence in any data from studies conducted by, or on behalf of, a sponsor, or relied on by a sponsor for product approvals or authorization of labeling claims. As a result, the proposed rule is intended to help ensure the integrity of data submitted to FDA because reliance on falsified data could lead to clinical testing of unsafe products, approval of ineffective or unsafe products, or marketing of products with false or misleading claims. Additionally, these reporting requirements would apply to information related to studies including, but not limited to, clinical investigations, nonclinical laboratory studies, and clinical studies in animals.
FDA also recognized the need for this rule to protect the rights, safety, and welfare of research subjects by making it less likely that persons who falsify data will continue to conduct studies, come in contact with research subjects, or jeopardize the rights, safety, and welfare of such subjects through unsound scientific practices.
After gathering such information, FDA intends to identify patterns, potential signals, or other indications of misconduct, so that the agency can conduct further investigations, which in turn, may form the basis of administrative or enforcement actions. These actions could include placing a clinical trial on hold, excluding clinical trials from consideration by FDA, or initiating disqualification of investigators or criminal proceedings. In addressing these patterns and signals, FDA hopes to:
– Lessen the magnitude and impact of the falsification in a current study;
– Reduce the potential for delays or compromise to other studies and applications (including studies and applications from other sponsors for whom such a person might also be working); and
– Protect the rights, safety, and welfare of research subjects.
What is uncertain about the proposed rule is that it would not require a sponsor to determine definitively that data have been falsified, nor would the proposed rule require that a sponsor determine the intent of the person who has, or may have, falsified data. This reporting obligation would exist regardless of the amount of evidence. Such a low threshold could cause unnecessary accusations and reporting, which will create administrative burdens for the FDA.
Accordingly, FDA would determine whether further agency investigation is warranted based on the information reported under the proposed rule in conjunction with other information available to the agency. The information would then be assessed in light of the existing legal and regulatory framework and, as appropriate, would be considered in the context of administrative or enforcement proceedings. Persons suspected of data falsification would be entitled to the legal and procedural rights that would typically apply in any such administrative or enforcement proceedings.
FDA noted that sponsors can become aware of possible falsification, including, but not limited to, monitoring the conduct of studies, reviewing and evaluating study data (e.g., noticing unusual data in case report forms and/or analytical reports), and receiving complaints from employees or former employees. Failure to report possible falsification of data might constitute a violation of section of the Federal Food, Drug, and Cosmetic Act.
It was indicated that because most firms would not generally submit more than one report of potential data falsification per year at the estimated cost of only $210 per report, FDA did not believe the proposed rule would have a significant economic impact on a substantial number of small entities.
FDA also indicated that it will take about 5 hours to prepare and report this information to the agency, and estimates that it may receive 73 reports per year in compliance with this rule, for an annual cost of about $15,330 per year.
The efforts of FDA to allow the agency to more rapidly identify persons who have falsified data and more effectively address problems is important. As long as the agency sticks to its goal, without hindering research and studies, this effort is important for the safety and security of research subjects and patients alike.
For information regarding human drugs: Leslie K. Ball, Center for Drug
Evaluation and Research, Office of Compliance, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 51, rm. 5342, Silver Spring, MD 209930002,
301-796-3150.
For information regarding biologics: Steve Ripley, Center for Biologics
Evaluation and Research (HFM17), Food and Drug Administration, 5515 Security
Lane, rm. 5130, Rockville, MD 20852, 301-827-6210.
For information regarding medical devices and radiological health: Michael E.
Marcarelli, Center for Devices and Radiological Health, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 3444, Silver Spring, MD
301-796-5490.