No Improvement in Expedited Safety Reports: CDER
CDER researchers writing in the journal Clinical Cancer Research say that a 9/29/10 agency final rule revising IND safety reporting regulations and guidance did not have the intended effect on the safety reporting practices of commercial sponsors of oncology drug products. More than five years since the final rule was published, they say, 86% of expedited safety reports are “uninformative.”
Sponsors of human drug and biologic products under an IND are required to distribute expedited safety reports of serious and unexpected adverse reactions to participating investigators and FDA to assure that clinical trial human subjects are protected. The final rule adopted in 2010 revised the definitions used for reporting and clarified when to submit relevant and useful information to reduce the number of uninformative reports distributed by sponsors, the report says.
The researchers say that between 1/1/06 and 12/31/14, the FDA Office of Hematology and Oncology Products received 159,174 expedited safety reports from commercial sponsors, an average of 17,686 reports per year. Their study indicates that rather than reduce the number of reports, the final rule was associated with a slight increase in the number. Also, a random audit of submitted reports found that only 14% met the criteria of serious, unexpected suspected adverse reactions, with the remainder “not providing any useful information for understanding the safety profile of the investigational drug.”
“The purpose of expedited IND safety reporting is to call attention to important safety signals of an investigational agent so that appropriate monitoring and patient management decisions are promptly instituted to ensure protection of human subjects participating in clinical trials,” the researchers say. “Reporting of uninformative adverse events is inappropriate and can consume the limited resources of investigators, institutional review boards, and FDA. Moreover, large numbers of uninformative expedited safety reports, as observed in our study, can obscure important and valid safety signals.”
The report says that barriers to the adoption of new procedures for optimal management of IND safety reporting by commercial sponsors have been examined by the Clinical Trials Transformation Initiative. Barriers include lack of international harmonization for reporting rules, liability risks, and lack of clarity of threshold rules for aggregate reporting. “The results of our study suggest little progress in overcoming these perceived barriers,” the researchers conclude, “and the number of expedited safety reports submitted to investigators. FDA is currently evaluating options for modernizing expedited IND safety reporting submissions via electronic transmission of adverse events and relevant data, including patient narratives, which can streamline reporting and monitoring activities. However, improving expedited IND safety reporting calls for sponsors to identify and address the reasons for submission of uninformative reports, independent of the mode and methods used for submission.”