Treating individuals 2. Subgroup analysis in randomised controlled trials: importance, indications, and...

Area of Science:

• Clinical Trials Methodology
• Biostatistics
• Evidence-Based Medicine

Background:

• Large pragmatic trials are essential for reliable treatment effect data.
• Effective use in routine practice necessitates proper trial design, analysis, and reporting.
• Subgroup analyses are vital for understanding treatment effects in specific patient populations.

Purpose of the Study:

• To outline principles for designing, analyzing, and reporting subgroup analyses in large pragmatic trials.
• To ensure subgroup analyses inform, rather than misinform, clinical practice and treatment decisions.
• To propose formal rules for the planning, analysis, and reporting of subgroup analyses.

Main Methods:

• Review of principles for subgroup analysis in clinical trials.
• Emphasis on predefined, justified, and limited subgroup questions.
• Discussion of statistical considerations for detecting heterogeneity of treatment effect.
• Consideration of trial power and pooled analyses for anticipated subgroup effects.

Main Results:

• Subgroup analyses are critical when potential differences in outcomes or treatment effects exist across groups.
• Post-hoc analyses require skepticism, regardless of statistical significance.
• Anticipated important subgroup effects necessitate adequate trial power or pooled analyses.
• Formal rules for planning, analysis, and reporting are proposed to enhance reliability.

Conclusions:

• Rigorous planning and justification of subgroup analyses are paramount for their valid interpretation.
• Predefined subgroup analyses enhance the utility of large pragmatic trials in routine clinical practice.
• Adherence to proposed formal rules can improve the quality and reliability of subgroup findings.