From: Osteoarthritis subpopulations and implications for clinical trial design
Prognostic factors are not necessarily treatment effect modifiers |
Post hoc subgroup effects in trials should be regarded as unreliable unless they can be replicated in dedicated trials or meta-analyses |
When subgroup analysis is predefined in a trial, randomisation should be stratified by subgroup and the power should be adjusted to the smallest subgroup |
Testing for interaction effects in trials is more robust than subgroup analysis, but needs a well-powered study depending on the expected size of the interaction effect |
The number of subgroups should be limited to a minimum to avoid multiple testing |
Combining trials for meta-analysis has the potential to search for subgroup effects. For reliable subgroup meta-analysis, individual trials have to supply subgroup effects and use stratified treatment randomization by subgroup, or supply the distribution of prognostic variables over the treatment arms in the subgroup |
Meta-analysis using individual patient data is a powerful method and the gold standard for assessing subgroup-treatment interaction effects |