From investigational product to active reference: evolution of oral sumatriptan efficacy versus placebo for the treatment of acute migraine episodes and potential impact in comparative analyses.

: The relative efficacy and safety can vary among drugs over time. Sumatriptan, a first choice drug for acute migraine, can illustrate this phenomenon. : To assess the evolution of the relative efficacy and tolerability of oral sumatriptan against placebo between its approval in 1991 and 2006. : A systematic literature review of randomized controlled trials (RCTs) of adults suffering from acute migraine episodes was performed using Medline. Meta-analyses estimated odds ratios of the occurrence of pain-free at 2 hours and of any adverse event. : Out of the 67 RCTs identi.fied, pain-free at 2 hours and adverse events were reported in 25 and 28 studies, respectively. For pain-free, the relative effect of sumatriptan increases considerably over time, despite an increase in the absolute placebo effect. The odds ratio (95% CI) equaled 3.13 (1.67-5.86) around approval (1991-1994) and increased up to 4.14 (3.67-4.67) on the following decade. No specific variation was observed in the relative tolerability effect of sumatriptan over placebo over time. : The relative effect of sumatriptan evolved substantially over time. This phenomenon may impact the results of network meta-analysis and indirect comparisons performed to evaluate the potential of a new drug, compared to widely prescribed older drugs.