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Journal Articles Therapeutic Innovation & Regulatory Science Year : 2021

Utility-based dose selection for phase II dose-finding studies

Abstract

Dose selection is a key feature of clinical development. Poor dose selection has been recognized as a major driver of development failure in late phase. It usually involves both efficacy and safety criteria. The objective of this paper is to develop and implement a novel fully Bayesian statistical framework to optimize the dose selection process by maximizing the expected utility in phase III. The success probability is characterized by means of a utility function with two components, one for efficacy and one for safety. Each component refers to a dose-response model. Moreover, a sequential design (with futility and efficacy rules at the interim analysis) is compared to a fixed design in order to allow one to hasten the decision to perform the late phase study. Operating characteristics of this approach are extensively assessed by simulations under a wide range of dose-response scenarios.
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Dates and versions

hal-02491551 , version 1 (26-02-2020)

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Jihane Aouni, Jean Noel Bacro, Gwladys Toulemonde, Pierre Colin, Loic Darchy. Utility-based dose selection for phase II dose-finding studies. Therapeutic Innovation & Regulatory Science, 2021, 55, pp.818-840. ⟨10.1007/s43441-021-00273-0⟩. ⟨hal-02491551⟩
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