Precise definitions of some terminology for longitudinal clinical trials: subjects, patient populations, analysis sets, intention to treat, and related terms

摘要

Biostatisticians recognize the importance of precise definitions of technical terms in randomized controlled clinical trial (RCCT) protocols, statistical analysis plans, and so on, in part because definitions are a foundation for subsequent actions. Imprecise definitions can be a source of controversies about appropriate statistical methods, interpretation of results, and extrapolations to larger populations. This paper presents precise definitions of some familiar terms and definitions of some new terms, some perhaps controversial. The glossary contains definitions that can be copied into a protocol, statistical analysis plan, or similar document and customized. The definitions were motivated and illustrated in the context of a longitudinal RCCT in which some randomized enrollees are non-adherent, receive a corrupted treatment, or withdraw prematurely. The definitions can be adapted for use in a much wider set of RCCTs. New terms can be used in place of controversial terms, for example, subject. We define terms specifying a person's progress through RCCT phases and that precisely define the RCCT's phases and milestones. We define terms that distinguish between subsets of an RCCT's enrollees and a much larger patient population. The intention-to-treat (ITT) principle' has multiple interpretations that can be distilled to the definitions of the ITT analysis set of randomized enrollees'. Most differences among interpretations of the' ITT principle stem from an RCCT's primary objective (mainly efficacy versus effectiveness). Four different authoritative' definitions of ITT analysis set of randomized enrollees illustrate the variety of interpretations. We propose a separate specification of the analysis set of data that will be used in a specific analysis. Copyright (c) 2016 John Wiley & Sons, Ltd.