The Most Important Proposed FDA Rule No One Is Talking About

By James McCormack PhD

On February 19, 2010, FDA published a proposed rule [75 FR 7412] that, when finalized, will have a profound effect on sponsors and the relationship between sponsors and persons they hire to plan, design, perform, review, or report biomedical research.  The proposed rule titled, “Reporting Information Regarding Falsification of Data”, will require sponsors to report to FDA, information indicating that any person has, or may have, engaged in the falsification of data in the course of performing their duties. 

Why does FDA believe this regulation is necessary?  The answer to that question can be principally found in the disqualification of a clinical investigator, Dr. Robert A. Fiddes, in June 1999 (See FDA’s Debarment Order, Clinical Investigator Disqualification List, and the Notice of Opportunity for Hearing). Among the many acts of falsification, he created false case reports for subjects that were never enrolled or did not exist, forged signatures on informed consent forms for the respective subjects, falsified records of medical procedures that were never performed, substituted test results from subjects who met the study’s inclusion criteria and improperly substituted for other subjects who did not meet the inclusion criteria, and paid Individuals, who were not study subjects, to give specimens in place of false study subjects.  Although Dr. Fiddes conducted studies for 47 sponsors affecting over 90 applications his actions were not reported to FDA.  Out of concern for the integrity of the preclearance review process and the rights and welfare of research subjects, FDA investigated why such widespread falsification could have gone unreported.  The agency determined that there was some ambiguity in the regulatory requirements regarding what information and when sponsors were to report information on possible incidences of falsification.  Therefore, the agency has proposed this rule to clarify a sponsor’s reporting requirements for studies conducted by, or on their behalf, or a study on which a sponsor relies to support a product approval.

            What research is covered by the proposed rule?  The reporting requirements will apply to information related to studies including, clinical investigations, nonclinical laboratory studies, and clinical studies in animals.

            What products are covered?  All FDA regulated products; food, drugs (human and veterinary), biologics, and medical devices.

            What do sponsors have to report?  The proposed rule does not require sponsors to make a definitive determination of falsification or establish the intent of the person who may have committed data falsification.  A sponsor is responsible for submitting information that they are aware of that a person has, or may have, falsified data.  The agency intentionally did not propose a specific threshold of information or the form, quantity, or reliability of the evidence that a person may have falsified data.  It seems apparent that the agency intends the reporting requirement to be an intelligence gathering activity that will be subject to further investigation and evaluation before serving as the basis of administrative or enforcement actions.         

When do sponsors have to report?  Under the proposed rule sponsors are required to report information they have regarding falsification, or possible falsification, to the appropriate FDA Center, no later than 45 calendar days after becoming aware of the information.

How do sponsors distinguish falsification from unintentional errors?  This is perhaps the most intriguing question raised by the proposed rule.  The agency addressed the distinction by defining “falsification” as creating, altering, recording, or omitting data in such a way that the data do not represent what actually occurred.  The proposed rule provides examples of unintentional errors, e.g., typographical errors and transposed numbers or characters, and states that such events should not be reported under the proposed rule. 

The public comment period ended in May 2010.  It is likely that the rule be finalized soon and the biomedical research environment will change accordingly.  Sponsors will need to develop robust controls to assure that possible incidences of falsification are detected, evaluated, and reported and persons performing services for sponsors should consider implementing their own controls as sponsor scrutiny will certainly increase.    

Dr. James McCormack presently serves as the Vice President of Life Sciences Compliance, at IBM.  He previously served as the Corporate Vice President of Regulatory Affairs and Compliance at Charles River Laboratories following an 18-year career in FDA as a preclearance review scientist and as FDA’s Bioresearch Monitoring Program Coordinator. 

The views expressed in this article are those of the author and do not necessarily represent those of his employer, Life-Science Panorama, its editor or Axendia, Inc.

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