Subgroups, treatment effects, and baseline risks: some lessons from major cardiovascular trials.
BACKGROUND
The objective of this study was to determine how subgroup analyses are performed in large randomized trials of cardiovascular pharmacotherapy.


RESULTS
We reviewed 67 randomized, double-blind, controlled trials involving pharmacotherapy in at least 1000 patients with unstable angina, myocardial infarction, left ventricular dysfunction, or heart failure with clinical outcomes as primary end points, published between 1980 and 1997. Nine had no subgroup analyses but 43 reported on 5 or more subgroups and 31 reported subgroups without formal statistical tests for treatment-subgroup interactions. In most trials, a rationale for subgroup selection was missing. All but 6 focused on single-factor subgroups.


CONCLUSIONS
Trial subgroups should ideally be defined a priori on 2 bases: single-factor subgroups with a strong rationale for biological response modification and multifactorial prognostic subgroups defined from baseline risks. However, single-factor subgroup analyses are often reported without a supporting rationale or formal statistical tests for interactions. We suggest that clinicians should interpret published subgroup-specific variations in treatment effects skeptically unless there is a prespecified rationale and a significant treatment-subgroup interaction.
Parker
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AB
Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
Naylor
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CD
D000789:Angina, Unstable / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012189:Retrospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D002317:Cardiovascular Agents