A combined score test for binary and ordinal endpoints from clinical trials

Whitehead, J., Branson, M. and Todd, S. ORCID: https://orcid.org/0000-0002-9981-923X (2010) A combined score test for binary and ordinal endpoints from clinical trials. Statistics in Medicine, 29 (5). pp. 521-532. ISSN 0277-6715 doi: 10.1002/sim.3822

Abstract/Summary

There is growing interest, especially for trials in stroke, in combining multiple endpoints in a single clinical evaluation of an experimental treatment. The endpoints might be repeated evaluations of the same characteristic or alternative measures of progress on different scales. Often they will be binary or ordinal, and those are the cases studied here. In this paper we take a direct approach to combining the univariate score statistics for comparing treatments with respect to each endpoint. The correlations between the score statistics are derived and used to allow a valid combined score test to be applied. A sample size formula is deduced and application in sequential designs is discussed. The method is compared with an alternative approach based on generalized estimating equations in an illustrative analysis and replicated simulations, and the advantages and disadvantages of the two approaches are discussed.