The importance of cross‐disciplinary scientific engagement in the development of quantitative procedures for aggregate safety assessments

Abstract

Recent guidance on safety monitoring during drug development, issued by regulatory authorities in the United States and European Union, indicate a shift in focus towards aggregate safety monitoring and scientific evaluation of integrated safety data. The call for program-level reviews of accumulating safety data, including from ongoing studies, provides an opportunity to leverage the scientific expertise and medical judgment of safety management teams with (a) a multidisciplinary approach, (b) quantitative frameworks to measure level of evidence, and (c) assessments that are product-specific and driven by medical judgment. A multidisciplinary team, regularly reviewing aggregate safety data throughout the development program, is vital not only for early signal detection but also for generating a better understanding of the accumulating data and context needed for decreasing false alarms.

Using the Bayesian detection of potential risk using inference on blinded safety data (BDRIBS) method to support the decision to refer an event for unblinded evaluation

“…[3][4][5][6] However, the statistical methodology is only one aspect of aggregate safety data review, which is a complex endeavor that requires a multidisciplinary approach. 7,8 In this article, we show how the Bayesian detection of potential risk using inference on blinded safety data (BDRIBS) method 9 can be used to assist SMTs with the assessment of potential safety signals in ongoing blinded clinical trials. In the SMT decision-making process, this blinded quantitative assessment of the safety data is considered along with a qualitative evaluation of the available information.…”