Since its inception, the Clinical Trials Transformation Initiative (CTTI) has had an interest in improving the quality and efficiency of safety reporting for serious adverse events (SAE) in studies performed under investigational new drug applications (INDs). CTTI’s first project on this topic focused on expedited safety reporting of serious, unexpected and possibly related SAEs to site investigators in multi-center trials. At the project’s conclusion, CTTI recommended that sponsors decrease the volume of uninterpretable and irrelevant safety reports to investigators, and instead supply investigators with meaningful reports that would improve investigators’ understanding of a drug’s benefit-risk profile. These recommendations were developed immediately prior to the FDA issuing a new final rule on safety reporting for drugs being studied under INDs.
FDA’s new IND safety reporting rule, published in the Federal Register on September 29, 2010, became effective on March 28, 2011. The intent of the new rule is to improve the quality of safety reports by minimizing the number of uninterpretable reports that sponsors submit to FDA and investigators. This is consistent with CTTI’s recommendations described above. However, CTTI members have expressed concern that there may be some uncertainty about the best methods to implement the new rule. For this reason, CTTI formed a new project entitled “IND Safety Assessment and Communication,” with the goal of promoting responsible oversight of safety for pre-market drug products consistent with the intent of the FDA’s new IND safety rule. The project objectives are as follows:
To obtain a deeper understanding of sponsors’ current practices for assessing safety of a pre-market drug product across all trials and sources of safety information and for communicating potential safety signals
To facilitate an informed discussion of practices and challenges in assessing and communicating IND safety information
To issue recommendations for future approaches that will support the intent of the IND safety reporting rule effective March 2011
The project team first surveyed industry sponsors to obtain a deeper understanding of their current practices. CTTI then distributed anonymized survey results to a group of experts that included representatives from each sponsor organization that completed the survey, government (NIH, Department of Veterans’ Affairs, and FDA), academia, and patient advocacy. These experts participated in a meeting convened on February 28-29, 2012 in Bethesda, MD. A subgroup of attendees at this meeting were members of a biostatistics workgroup that the CTTI project team formed to advise on the methodological dilemmas related to implementing the new IND Safety Reporting rule.
Findings from the survey of sponsor practices
Companies’ strategies for implementing the new IND safety reporting rule