How large must a dose ‐optimization trial be?

AbstractRecently promulgated Draft Guidance from the FDA Oncology Center of Excellence recommends randomized, parallel dose-response trials for ‘dose optimization’, but with vaguely stated aims that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 ac knowledges interindividual heterogeneity simultaneously in PKPD 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.
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research