Dose optimization is a hallmark of Project Optimus for oncology drug development. The number of doses to include in a dose optimization study depends on the totality of evidence, which is often unclear in early-phase development. With equal sample sizes per dose, carrying three doses is clearly more advantageous than two for optimization. In this paper, we show that, even when the total sample size is fixed, it is still preferable to carry three unless there is very strong evidence that one can be dropped. A mathematical approximation is applied to guide the investigation, followed by a simulation study to complement the theoretical findings. Semi-quantitative guidance is provided for practitioners, addressing both randomized and non-randomized dose optimization while considering population homogeneity.

翻译：剂量优化是肿瘤药物开发中"Optimus项目"的标志性特征。剂量优化研究中应包含的剂量数量取决于证据的整体性，这在早期开发阶段往往并不明确。在每剂量样本量相等的情况下，采用三个剂量显然比两个剂量更有利于优化。本文证明，即使在总样本量固定的情况下，除非有非常强有力的证据表明可以剔除某一剂量，否则仍以采用三个剂量为优。研究采用数学近似方法指导分析，并通过模拟研究补充理论发现。本文为实践者提供了半定量指导，在考虑人群同质性的同时，涵盖了随机化和非随机化剂量优化两种情形。