Determining an Adaptive Exclusion Procedure following Discovery of an Association between the Whole Genome and Adverse Drug Reactions

This article concerns the identification of associations between the incidence of adverse drug reactions and features apparent from whole genome scans of patients together with the subsequent implementation of an adaptive exclusion procedure within a drug development program. Our context is not a retrospective assessment of a large and complete database: instead we are concerned with identifying such a relationship during a drug development program and the consequences for the future conduct of that program. In particular, we seek methods for identifying changes to the exclusion criteria that will prevent future patients at high risk of an adverse reaction from continuing to be recruited. We discuss the levels of evidence needed to amend an existing recruitment policy, how this can be done, and how to evaluate and revise the reformulated recruitment policy as the trials continue. The approach will be illustrated using clinical trial data to demonstrate its potential for making an immediate reduction in the incidence of adverse drug reactions.