Incorporating historical information to improve phase I clinical trials |
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Authors: | Yanhong Zhou J. Jack Lee Shunguang Wang Stuart Bailey Ying Yuan |
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Affiliation: | 1. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;2. Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA |
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Abstract: | Incorporating historical data has a great potential to improve the efficiency of phase I clinical trials and to accelerate drug development. For model-based designs, such as the continuous reassessment method (CRM), this can be conveniently carried out by specifying a “skeleton,” that is, the prior estimate of dose limiting toxicity (DLT) probability at each dose. In contrast, little work has been done to incorporate historical data into model-assisted designs, such as the Bayesian optimal interval (BOIN), Keyboard, and modified toxicity probability interval (mTPI) designs. This has led to the misconception that model-assisted designs cannot incorporate prior information. In this paper, we propose a unified framework that allows for incorporating historical data into model-assisted designs. The proposed approach uses the well-established “skeleton” approach, combined with the concept of prior effective sample size, thus it is easy to understand and use. More importantly, our approach maintains the hallmark of model-assisted designs: simplicity—the dose escalation/de-escalation rule can be tabulated prior to the trial conduct. Extensive simulation studies show that the proposed method can effectively incorporate prior information to improve the operating characteristics of model-assisted designs, similarly to model-based designs. |
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Keywords: | dose finding historical data maximum tolerated dose model-assisted design real-world evidence |
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