Statistical models for the analysis of controlled trials on acute migraine

Specific efficacy criteria were defined by the International Headache Society for controlled clinical trials on acute migraine. They are derived from the pain profile and the timing of rescue medication intake. We present a methodology to improve the analysis of such trials. Instead of analysing each endpoint separately, we model the joint distribution and derive success rates in any criteria as predictions. We use cumulative regression models for each response at a time and a multivariate normal copula to model the dependence between responses. Parameters are estimated using maximum likelihood. Benefits of the method include a reduction in the number of tests performed and an increase in their power. The method is well suited to dose-response trials from which predictions can he used to select doses and optimize the design of subsequent trials. More generally, our method permits a very flexible modelling of longitudinal series of ordinal data. Copyright (C) 2003 John Wiley Sons Ltd.