Subgroup analyses and pre-specification

Large clinical trials provide the opportunity to assess treatment effects in subgroups of patients, based on baseline demographic and disease-related factors, and there is always great interest in these analyses. Generally, the term “pre-specification” has major ramifications for clinical trials, particularly for adequate and well-controlled trials that are designed for formal hypothesis testing. Pre-specification is the “holy grail” of modern trials, as choosing analytical approaches with data in-hand will inflate the type I error rate. But “pre-specification” often has a different meaning with respect to subgroup analyses.