SeriesMultiplicity in randomised trials II: subgroup and interim analyses
Section snippets
Subgroup analyses
Indiscriminate subgroup analyses pose serious multiplicity concerns. Problems reverberate throughout the medical literature. Even after many warnings,2 some investigators doggedly persist in undertaking excessive subgroup analyses.
Investigators define subgroups of participants by characteristics at baseline. They then do analyses to assess whether treatment effects differ in these subgroups. The major problems stem from investigators undertaking statistical tests within every subgroup examined.
Interim analyses
Appropriate monitoring of trials involves more than statistical warnings for stopping. Indeed, the superiority or inferiority of the studied treatment has a major role. However, slow accrual, poor data quality, poor adherence, resource deficiencies, unacceptable adverse effects, fraud, and emerging information that make the trial irrelevant, unnecessary, or unethical, all could lead to stopping a trial. The decision process is clearly complex.12, 13 It best resides with an independent data
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