Keywords: Phase 3 RCT, precision medicine, diagnostics, biomarkers, trial ethics, novel study designs, sufficiency of evidence
The established paradigm of a linear drug development approach represented by Phase I (safety and maximum tolerated dose), Phase II (efficacy signals), and Phase III (clinical benefit of novel therapy over standard of care) clinical trials needs to be revisited for optimality in today’s era of targeted therapeutics, which are guided by diagnostics and biomarkers. Important discussions need to be undertaken by all stakeholders in regard to trial ethics, design considerations for efficiency, and sufficiency of standards of evidence. This session will bring together an expert panel from academia, regulatory agencies, and industry to discuss whether Phase III randomized clinical trials can be foregone for targeted therapies, what would be the pros and cons of such a paradigm change, and what criteria and evidentiary needs should be required for evaluating novel precision medicines. Although the accelerated approval program of the FDA (Subpart H) continues to facilitate early access of new therapies to patients, optimal development of precision medicines will benefit from formal consensus criteria and updated study guidelines.