• Ananda Sen, Lili Zhao, Zora Djuric, D Kim Turgeon, Mack T Ruffin, William L Smith, Dean E Brenner, and Daniel P Normolle.
• Department of Family Medicine, University of Michigan Medical School, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan Medical School, Ann Arbor, Michigan. Electronic address: anand... more as@umich.edu. less
• Am J Prev Med. 2020 Oct 1; 59 (4): e167-e173.

IntroductionIn biomarker-driven clinical trials, translational strategies typically involve moving findings from animal experiments to human trials. Typically, the translation is static, using a fixed model derived from animal experiments for the duration of the trial. Bayesian designs, capable of incorporating information external to the experiment, provide a dynamic translational strategy. This article demonstrates an example of such a dynamic Bayesian strategy in a clinical trial.MethodsThis study explored the effect of a personalized dose of fish oil for reducing prostaglandin E2, an inflammatory marker linked to colorectal cancer. A Bayesian design was implemented for the dose-finding algorithm that adaptively updated a dose-response model derived from a previously completed animal study during the clinical trial. In the initial stages of the trial, the dose-response model parameters were estimated from the rodent data. The model was updated following a Bayesian algorithm after data on every 10‒15 subjects were obtained until the model stabilized. Subjects were enrolled in the study between 2013 and 2015, and the data analysis was carried out in 2016.ResultsThe 3 dosing models were used for groups of 16, 15, and 15 subjects. The mean target dose significantly decreased from 6.63 g/day (Model 1) to 4.06 g/day (Model 3) (p=0.001). Compared with the static strategy of dosing with a single model, the dynamic modeling reduced the dose significantly by about 1.38 g/day on average.ConclusionsA Bayesian design was effective in adaptively revising the dosing algorithm, resulting in a lower pill burden.Trial RegistrationThis study is registered at www.clinicaltrials.gov NCT01860352.Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

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