title: Methodological considerations on the design and analysis of an equivalence stratified cluster randomization trial.
abstract: The World Health Organization and collaborating institutions in four developing countries have conducted a multi-centre randomized controlled trial, in which clinics were allocated at random to two antenatal care (ANC) models. These were the standard 'Western' ANC model and a 'new' ANC model consisting of tests, clinical procedures and follow-up actions scientifically demonstrated to be effective in improving maternal and newborn outcomes. The two models were compared using the equivalence approach. This paper discusses the implications of the equivalence approach in the sample size calculation, 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 stratified 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 composite index, heterogeneity of the intervention effect across sites, the choice of the method of analysis and the importance of efficacy analyses. The choice of the clustered Woolf estimator and the generalized estimating equations (GEE) as the methods of analysis applied is discussed.
authors.affiliation: Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: G
authors.initials: G
authors.lastname: Carroli
authors.forename: J
authors.initials: J
authors.lastname: Villar
authors.forename: A
authors.initials: A
authors.lastname: Pinol
authors.forename: L
authors.initials: L
authors.lastname: Bakketeig
authors.forename: P
authors.initials: P
authors.lastname: Lumbiganon
authors.forename: P
authors.initials: P
authors.lastname: Bergsjø
authors.forename: Y
authors.initials: Y
authors.lastname: Al-Mazrou
authors.forename: H
authors.initials: H
authors.lastname: Ba'aqeel
authors.forename: J M
authors.initials: JM
authors.lastname: Belizán
authors.forename: U
authors.initials: U
authors.lastname: Farnot
authors.forename: H
authors.initials: H
authors.lastname: Berendes
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D003906:Developing Countries; D004992:Ethics, Medical; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007258:Informed Consent; D015337:Multicenter Studies as Topic / Q000379:methods; D011247:Pregnancy; D011256:Pregnancy Outcome; D011295:Prenatal Care / Q000379:methods* / Q000592:standards; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size