Influence of active versus placebo control on treatment responses in randomised controlled trials in rheumatoid arthritis.

Objectives: To investigate whether treatment effects of pharmaceutical compounds compared with placebo controls are systematically different to the effects of the same compounds compared with active treatment controls in rheumatoid arthritis (RA) clinical trials.

Methods: We systematically identified randomised controlled trials (RCTs) in RA, and matched active treatment arms with comparable regimens, populations, background therapy, and outcome reporting, by the nature of their control group (active comparator or placebo). Medline, EMBASE and CENTRAL were used to identify RCTs investigating disease modifying anti-rheumatic drug therapies until December 2021.

Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology.

Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation.