Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider quantitative information available from any studies that may have been conducted previously on the same drug. A meta-analytic approach has the advantages of being able to properly account for between-study heterogeneity, and it may be readily extended to prediction or shrinkage applications. Here we propose a simple and robust two-stage approach for the estimation of maximum tolerated dose(s) (MTDs) utilizing penalized logistic regression and Bayesian random-effects meta-analysis methodology. Implementation is facilitated using standard R packages. The properties of the proposed methods are investigated in Monte-Carlo simulations. The investigations are motivated and illustrated by two examples from oncology.

翻译：早期临床研究第一阶段的早期阶段旨在调查一种药物或组合的安全及其基本剂量毒性关系,虽然对该化合物的特性可能知之甚少,但考虑从以前可能就同一药物进行的任何研究中获得的定量信息至关重要。元分析方法的好处是能够适当地说明研究之间的异质性,并且可以很容易地扩大到预测或缩小应用。这里我们提出了一个简单而稳健的两阶段办法,利用惩罚性物流回归和巴伊西亚随机效应元分析方法估计最大耐用剂量(MTDs),同时利用标准的R包件促进实施。拟议方法的特性在蒙特卡洛模拟中调查。调查的动机和由肿瘤学的两个例子来说明。