Differentiating the efficacy of 5-HT1B/1D agonists

Objective. - To examine, for a set of published clinical trials of serotoni n (5-MT1B/1D) agonists as acute treatments for migraine, whether transforma tion of efficacy data into therapeutic gain (TG) or number needed to treat (NNT) is useful. Background. - Pivotal clinical trials of 5-HT1B/1D agonists in migraine use a primary end point of change in pain score from 3 or 2 to 1 or 0. Placebo response rates among such studies are variable. Meta-analytic comparisons of 5-HT1B/1D agonists often employ TG and NNT as efficacy measures. Methods. - Data from US product labeling or published sources were converte d into TG (TG = active response rate [%] - placebo response rate [%]) and N NT (NNT = 1/TG). Pivotal clinical trial data were compared before and after transformation. Results. - Therapeutic gain ranged from 17.5% to 51%. The transformation of TG into NNT yielded no clinically significant difference in efficacy estim ate for the range of 17.5% to 47% (N = 29 clinical trials). However, NNT an d TG had a nonlinear relationship for some secondary end points. When the r elationship between the standard primary and secondary end points was compa red, the correlation of TG with clinical disability (Pearson coefficient R = 0.93) was stronger than for NNT. Placebo response rates correlated more s trongly with NNT (R = 0.66) than active response rates (R = 0.42; N = 29 cl inical trials), although both TG and NNT were sensitive to placebo response rate. Conclusions. - Transforming efficacy rates into TG or NNT adds no new infor mation to placebo-controlled trials. The variables, TG and NNT, should not be used to compare members of this class of drugs. Migraine therapies can o nly be compared using well-designed head-to-head studies and not by meta-an alysis. Broader measures of efficacy should be used to describe and compare 5-HT1B/1D efficacy.