TL48: Blinded and Unblinded Evaluation of Aggregate Safety Data during Clinical Development
Greg Ball, AbbVie  *Bill Wang, Merck 

Keywords: Blinded, unblinded, aggregate safety, eDMC

Organizers: William Wang, Merck and Greg Ball, AbbVie

This luncheon table session will discuss recent methodological advances and practices for both blinded and unblinded evaluation of aggregate safety data. Here is a detailed abstract:

Concerns over product safety have resulted in late stage program failures and market withdrawals. This has focused more interest and attention paid to aggregate safety analyses during clinical development. The Code of Federal Regulations (CFR) requires a safety report whenever aggregate analysis indicates that “events occur more frequently in the drug treatment group than in a concurrent control group”. As stated in the FDA guidance on Safety Reporting Requirements for INDs and BA/BE Studies, safety reporting requirements of aggregate data now emphasize the importance of collecting and evaluating “safety data systematically during development, including accumulating safety data”. Any suspected adverse reactions should be evaluated relative to other events in ongoing studies as well as previous studies. The safety reporting guidance amplifies the CFR in asserting that a “systematic approach for safety surveillance … should include a process for reviewing, evaluating and managing accumulating safety data from the entire clinical trial database at appropriate intervals”. An independent group, whether an external DMC or an internal safety team, should use all of the available data, including data from outside of the clinical trials in assessing the safety of the developing product. In the end, however, any report of an aggregate analysis will require “analysis and reporting of the event rates in both the drug-treatment and placebo groups”.