Borrowing historical information to improve phase I clinical trials using meta-analytic-predictive priors

J Biopharm Stat. 2022 Jan 2;32(1):34-52. doi: 10.1080/10543406.2022.2058526. Epub 2022 May 20.

Abstract

Multiple phase I clinical trials may be performed to determine specific maximum tolerated doses (MTD) for specific races or cancer types. In these situations, borrowing historical information has potential to improve the accuracy of estimating toxicity rate and increase the probability of correctly targeting MTD. To utilize historical information in phase I clinical trials, we proposed using the Meta-Analytic-Predictive (MAP) priors to automatically estimate the heterogeneity between historical trials and give a relatively reasonable amount of borrowed information. We then applied MAP priors in some famous phase I trial designs, such as the continual reassessment method (CRM), Keyboard design and Bayesian optimal interval design (BOIN), to accomplish the process of dose finding. A clinical trial example and extended simulation studies show that our proposed methods have robust and efficient statistical performance, compared with those designs which do not consider borrowing information.

Keywords: Borrowing information; dose finding; maximum tolerated doses; meta-analytic-predictive prior.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Clinical Trials, Phase I as Topic
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Humans
  • Maximum Tolerated Dose
  • Neoplasms* / drug therapy
  • Research Design*