Smoke and mirrors: Limited value of relative risk reductions for assessing the benefits of disease-modifying therapies for multiple sclerosis

•The value of the relative risk reduction depends on the event rate of placebo.•A high relative risk reduction in a low placebo event rate means little clinically.•A moderate relative risk reduction in a high placebo event rate is more significant.•Numbers needed to treat and absolute risk reductions clarify the above.•Cross-comparison between trials with different background risks is misleading.

A reduction in relapse rate is the main primary outcome in most clinical trials in patients with multiple sclerosis (MS), with the effect of a treatment commonly expressed as relative risk reduction for this outcome. Physicians often assume that a drug with a higher relative risk reduction demonstrated in one trial is more effective than a drug with a lower relative risk reduction in another, and may pass this idea on to younger physicians and to patients. The use of the relative risk reduction as a measure of drug efficacy can be misleading, as it depends on the nature of the population studied: a treatment effect characterized by a lower relative risk reduction may be more clinically meaningful than one with a higher relative risk reduction. This concept is especially important with regard to clinical trials in patients with MS, where relapse rates in placebo groups have been declining in recent decades. Direct, head-to-head comparisons are the only way to compare the efficacy of the different treatments for MS.