Methodological considerations on the design and analysis of an equivalencestratified cluster randomization trial

The World Health Organization and collaborating institutions in four develo ping countries have conducted a multi-centre randomized controlled trial, i n which clinics were allocated at random to two antenatal care (ANC) models . These were the standard "Western" ANC model and a "new" ANC model consist ing of tests, clinical procedures and follow-up actions scientifically demo nstrated to be effective in improving maternal and newborn outcomes. The tw o models were compared using the equivalence approach. This paper discusses the implications of the equivalence approach in the sample size calculatio n, analysis and interpretation of results of this cluster randomized trial. It reviews the ethical aspects regarding informed consent, concluding that the Zelen design has a place in cluster randomization trials. It describes the estimation of the intracluster correlation coefficient (ICC) in a stra tified cluster randomized trial using two methods and reports estimates of the ICC obtained for many maternal, newborn and perinatal outcomes. Finally , it discusses analytical problems that arose: issues encountered using a c omposite index, heterogeneity of the intervention effect across sites, the choice of the method of analysis and the importance of efficacy analyses. T he choice of the clustered Woolf estimator and the generalized estimating e quations (GEE) as the methods of analysis applied is discussed. Copyright ( C) 2001 John Wiley & Sons, Ltd.