Assessing apparent treatment—covariate interactions in randomized clinical trials

In the context of clinical trials, a qualitative treatment--covariate interaction occurs when a patient's preferred treatment depends on his covariates. In this paper I review the nature and interpretation of various kinds of interactions, compare the use of overall tests for interaction to subset analysis, present some examples of apparent treatment-covariate interactions that have arisen in actual randomized clinical trials, and discuss some recent work by others related to significance testing, estimation and assessment of apparent treatment-covariate interactions.