Clinical Trial Design as a Decision Problem

摘要

The intent of this discussion is to highlight opportunities and limitations of utility-based and decision theoretic arguments in clinical trial design. The discussion is based on a specific case study, but the arguments and principles remain valid in general. The example concerns the design of a randomized clinical trial to compare a gel sealant versus standard care for resolving air leaks after pulmonary resection. The design follows a principled approach to optimal decision making, including a probability model for the unknown distributions of time to resolution of air leaks under the two treatment arms, and an explicit utility function that quantifies clinical preferences for alternative outcomes. As is typical for any real application, the final implementation includes some compromises from the initial principled setup. In particular, we use the formal decision problem only for the final decision, but use reasonable ad-hoc decision boundaries for making interim group sequential decisions that stop the trial early. Beyond the discussion of the particular study, we review more general considerations of using a decision theoretic approach for clinical trial design and summarize some of the reasons why such approaches are not commonly used.