Increasing power in the analysis of responder endpoints in rheumatology: a software tutorial

BACKGROUND: Composite responder endpoints feature frequently in rheumatology due to the multifaceted nature of many of these conditions. Current analysis methods used to analyse these endpoints discard much of the data used to classify patients as responders and are therefore highly inefficient, resulting in low power. We highlight a novel augmented methodology that uses more of the information available to improve the precision of reported treatment effects. Since these methods are more challenging to implement, we developed free, user-friendly software available in a web-based interface and as R packages. The software consists of two programs: one that supports the analysis of responder endpoints; the second that facilitates sample size estimation. We demonstrate the use of the software to conduct the analysis with both the augmented and standard analysis method using the MUSE study, a phase IIb trial in patients with systemic lupus erythematosus. RESULTS: The software outputs similar point estimates with smaller confidence intervals for the odds ratio, risk ratio and risk difference estimators using the augmented approach. The sample size required in each arm for a future trial using the novel approach based on the MUSE data is 50 versus 135 for the standard method, translating to a reduction in required sample size of approximately 63%. CONCLUSIONS: We encourage trialists to use the software demonstrated to implement the augmented methodology in future studies to improve efficiency. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41927-021-00224-0.