Modern Bayesian Adaptive Methods for Clinical Trials, with Application to Orphan Diseases
View Presentation View Presentation
*Brad P Carlin, University of Minnesota  Kristen Cunanan, University of Minnesota  Brian P. Hobbs, The University of Texas M.D. Anderson Cancer Center  Thomas Murray, MD Anderson Cancer Center 

Keywords: Bayesian methods, commensurate priors, meta-analysis, MCMC, orphan drugs

Bayesian methods have a long history of success in clinical trial settings where patients and other resources are scarce, where good reliable external information is available, or both. In this talk we review several real-life settings where Bayesian methods have paid such dividends. First, we describe recent Bayesian advances in the adaptive incorporation of historical information in clinical trials through what are known as commensurate priors, showing connections with traditional meta-analytic methods and illustrating their potential for improved power while maintaining acceptable Type I error. We then extend these ideas to the adaptive randomization of patients in the trial. Here the idea is to randomize fewer patients to therapies from which strength may be borrowed from historical data, in order to preserve balance among the treatment groups. Next, we describe our experiences to date using adaptive Bayesian methods in the context of recent work with the University of Minnesota Center for Orphan Drug Research. Applications to date include trials for drugs treating epilepsy and neurodegenerative diseases such as Parkinson's and adrenoleukodystrophy (ALD), in the latter case with Lorenzo's Oil. Time permitting, we will also report on a large Canadian study of the impact of device-assisted home monitoring interventions in coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), and diabetes. Here we use a Bayesian stepped wedge design that borrows of strength across similar but not identical groups (disease groups, patients within practices, etc.) and, as appropriate, incorporates external information, such as baseline utilization rates in the various practices. While like Nebraska's Platte River this talk will be "a mile wide and an inch deep," all of our success stories will be illustrated in the context of real trial settings arising in both academics and industry.