Identification of optimal moderators in clinical trials

Moderators and mediators can be very informative in the analysis of clinical trials to help determine what treatment should be assigned to individuals (moderators) and to determine how to improve treatments (mediators). It is well known that a treatment might not be equally beneficial to everyone and an overall effective treatment may be less effective (or even harmful) in certain groups; this highlights the importance of moderators in making treatment assignment decisions. A combined moderator, or optimal moderator, can be useful when multiple potential moderators exist, but no individual one is particularly strong. This report reviews how to assess a single moderator as well as approaches to derive an optimal moderator. An example from randomized clinical trial is presented, including the identification of an optimal moderator.