Replacing RCTs with real world data for regulatory decision making: a self-fulfilling prophecy?

Real world data are advocated as an alternative approach to RCTs for closing knowledge gaps on drugs, but Beate Wieseler and colleagues argue that this approach is the wrong remedy for current challenges in drug development ### Key messages Attempts to accelerate the provision of new treatments have led to evidence that is limited in quantity and quality being submitted for regulatory approval in recent years.12 Approvals based on single arm trials, for example, have become more frequent, such as for lisocabtagene maraleucel, a CAR-T cell therapy for patients with B cell lymphoma. Single arm trials are not informative enough to enable us to select the best therapy for a patient among several options. This lack of robust evidence, especially the lack of comparisons with standard care, has implications for decision making in clinical practice and health policy, as the place of new drugs in the treatment landscape remains unclear, and reimbursement and pricing decisions cannot be adequately informed.34 Current discussions of the most suitable study types for regulatory approval and the question of whether observational data instead of data from randomised controlled trials (RCTs) would suffice are relevant beyond regulatory agencies.56 The question is intertwined with the potential use of routine practice data, often referred to as real world data or real world …