Multi-arm trials with multiple primary endpoints and missing values

Stat Med. 2018 Feb 28;37(5):710-721. doi: 10.1002/sim.7542. Epub 2017 Nov 6.

Abstract

We present an extension of multiple contrast tests for multiple endpoints to the case of missing values. The endpoints are assumed to be normally distributed and correlated and to have equal covariance matrices for the different treatments. Different multivariate t distributions will be applied, differing in endpoint-specific degrees of freedom. In contrast to competing methods, the familywise error type I is maintained in the strong sense in an admissible range, and the problem of different marginal errors type I is avoided. The information of all observations is exploited, thereby enabling a gain in power compared with a complete case analysis.

Keywords: correlated endpoints; missing values; multiple contrast tests; multiplicity adjustment; multivariate t distribution.

MeSH terms

  • Bias
  • Clinical Trials as Topic / methods*
  • Computer Simulation
  • Data Interpretation, Statistical
  • Endpoint Determination / methods*
  • Humans
  • Regression Analysis