SUBGROUPS: TIME TO GO BACK TO BASIC STATISTICAL PRINCIPLES?

Exploratory subgroup analyses are an increasing source of controversy as part of the interpretation of the results of clinical trials. In this article, we review the major challenges of multiplicity, statistical methods available to assess consistency of effect, and the part appropriate design plays in mitigating the risk of false conclusions from subgroup analyses. We discuss the problems associated with using definitions of consistency based on effect sizes in specific subgroups. We argue that what is required is a return to basic statistical principles, including more use of modeling techniques.