title: Group sequential tests for bivariate response: interim analyses of clinical trials with both efficacy and safety endpoints.
abstract: We describe group sequential tests for a bivariate response. The tests are defined in terms of the two response components jointly, rather than through a single summary statistic. Such methods are appropriate when the two responses concern different aspects of a treatment; for example, one might wish to show that a new treatment is both as effective and as safe as the current standard. We present a formulation of the bivariate testing problem, introduce group sequential tests that satisfy Type I error conditions, and show how to find the sample size guaranteeing a specified power. We describe how properties of group sequential tests for bivariate normal observations can be computed by numerical integration.
authors.affiliation: School of Mathematical Sciences, University of Bath, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Jennison
authors.forename: B W
authors.initials: BW
authors.lastname: Turnbull
mesh_terms: D001699:Biometry / Q000379:methods*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D005069:Evaluation Studies as Topic; D006801:Humans; D015233:Models, Statistical; D012449:Safety