Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications

Area of Science:

• Clinical Trials
• Biostatistics
• Research Integrity

Background:

• Subgroup analyses are frequently conducted in randomized controlled trials (RCTs) but their planning and reporting can be inconsistent.
• Assessing the reliability of subgroup findings is crucial for clinical decision-making.

Purpose of the Study:

• To evaluate the extent of subgroup analysis planning in RCT protocols.
• To assess the agreement between planned subgroup analyses in protocols and reported analyses in subsequent publications.

Main Methods:

• A cohort study examined 894 RCT protocols and 515 corresponding journal publications approved by ethics committees between 2000-2003.
• Data on planned subgroup analyses, hypotheses, and statistical tests were extracted and compared.

Main Results:

• Only 28.2% of RCT protocols detailed subgroup analyses, with few specifying hypotheses (6.7%) or interaction tests (34.5%).
• Industry-sponsored trials were more likely to plan subgroup analyses than investigator-sponsored trials.
• While 47.8% of publications reported subgroup analyses, over a third of claims of prespecification lacked protocol support, and many reported subgroup effects without documented plans.

Conclusions:

• Subgroup analyses are inadequately described in RCT protocols, with rare specification of effect direction.
• Discrepancies between protocol plans and publication reports undermine the credibility of subgroup findings.
• Access to RCT protocols and analysis plans is essential for validating claimed subgroup effects.