How large must a dose‐optimization trial be?

Abstract

Abstract Recently promulgated Draft Guidance from the US Food and Drug Administration Oncology Center of Excellence (OCE) recommends randomized, parallel dose–response trials for “dose optimization,” but with vaguely stated aims that engage none of the statistical principles which typically attend randomization. Here, I advance a criterion for reasonable precision of such trials, and examine its implications for minimum enrollment, within a utility‐based framework that acknowledges interindividual heterogeneity simultaneously in pharmacokinetics/pharmacodynamics and in the subjective evaluation of efficacy‐toxicity trade‐offs. Even when designed and conducted under ideal circumstances, reasonably sized trials of the kind advocated by OCE may need to enroll many hundreds of participants.