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Prior distributions for treatment effects based on previous trial results risks sample selection bias and difficulties when a proposed trial differs in terms of patient characteristics, medication adherence, or treatment doses and regimens. The aim of this study was to demonstrate the utility of using pharmacometric\u2010based clinical trial simulation (CTS) to generate prior distributions for use in Bayesian decision\u2010theoretic trial design. The methods consisted of four principal stages: a CTS to predict the distribution of treatment response for a range of trial designs; Bayesian updating for a proposed sample size; a pharmacoeconomic model to represent the perspective of a reimbursement authority in which price is contingent on trial outcome; and a model of the pharmaceutical company return on investment linking drug prices to sales revenue. We used a case study of febuxostat versus allopurinol for the treatment of hyperuricemia in patients with gout. Trial design scenarios studied included alternative treatment doses, inclusion criteria, input uncertainty, and sample size. Optimal trial sample sizes varied depending on the uncertainty of model inputs, trial inclusion criteria, and treatment doses. This interdisciplinary framework for trial design and sample size calculation may have value in supporting decisions during later phases of drug development and in identifying costly sources of uncertainty, and thus inform future research and development strategies.<\/jats:p>","DOI":"10.1002\/psp4.12579","type":"journal-article","created":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T05:50:55Z","timestamp":1607752255000},"page":"75-83","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Combining Model\u2010Based Clinical Trial Simulation, Pharmacoeconomics, and Value of Information to Optimize Trial Design"],"prefix":"10.1002","volume":"10","author":[{"given":"Daniel","family":"Hill\u2010McManus","sequence":"first","affiliation":[{"name":"Centre for Health Economics and Medicines Evaluation Bangor University Bangor UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dyfrig A.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Centre for Health Economics and Medicines Evaluation Bangor University Bangor UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"European Medicines Agency ICH Topic E 8. 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