A benchmark for dose finding studies with continuous outcomes

Mozgunov, Pavel and Jaki, Thomas Friedrich and Paoletti, Xavier (2020) A benchmark for dose finding studies with continuous outcomes. Biostatistics, 21 (2). 189–201. ISSN 1465-4644

Abstract

An important tool to evaluate the performance of any design is an optimal benchmark proposed by O’Quigley and others (2002. Non-parametric optimal design in dose finding studies. Biostatistics 3, 51–56) that provides an upper bound on the performance of a design under a given scenario. The original benchmark can only be applied to dose finding studies with a binary endpoint. However, there is a growing interest in dose finding studies involving continuous outcomes, but no benchmark for such studies has been developed. We show that the original benchmark and its extension by Cheung (2014. Simple benchmark for complex dose finding studies. Biometrics 70, 389–397), when looked at from a different perspective, can be generalized to various settings with several discrete and continuous outcomes. We illustrate and compare the benchmark’s performance in the setting of a dose finding Phase I clinical trial with a continuous toxicity endpoint and a Phase I/II trial with binary toxicity and continuous efficacy endpoints. We show that the proposed benchmark provides an accurate upper bound in these contexts and serves as a powerful tool for evaluating designs.