Type: Article
Publication Date: 2009-09-03
Citations: 23
DOI: https://doi.org/10.1002/sim.3684
Abstract Proof‐of‐concept in clinical trials has traditionally focused on the identification of a maximum tolerated dose with the assumption that the higher doses provide better efficacy. However, adverse events associated with a maximum tolerated dose may have a negative effect on efficacy. We present an efficient adaptive dose‐finding strategy that concentrates patient assignments at and around the dose which has the best efficacy/tolerability profile based on a utility function. The strategy is applied within the setting of a crossover design. While the strategy may also be applied to parallel studies, a crossover design provides more power for a given sample size for comparisons between the optimal dose versus placebo and/or active control when it is reasonable to assume no carryover effects. Copyright © 2009 John Wiley & Sons, Ltd.