A robust method for comparing two treatments in a confirmatory clinical trial via multivariate time-to-event methods that jointly incorporate information from longitudinal and time-to-event data.

Journal Article (Journal Article)

We consider regulatory clinical trials that require a prespecified method for the comparison of two treatments for chronic diseases (e.g. Chronic Obstructive Pulmonary Disease) in which patients suffer deterioration in a longitudinal process until death occurs. We define a composite endpoint structure that encompasses both the longitudinal data for deterioration and the time-to-event data for death, and use multivariate time-to-event methods to assess treatment differences on both data structures simultaneously, without a need for parametric assumptions or modeling. Our method is straightforward to implement, and simulations show that the method has robust power in situations in which incomplete data could lead to lower than expected power for either the longitudinal or survival data. We illustrate the method on data from a study of chronic lung disease.

Full Text

Duke Authors

Cited Authors

  • Saville, BR; Herring, AH; Koch, GG

Published Date

  • January 2010

Published In

Volume / Issue

  • 29 / 1

Start / End Page

  • 75 - 85

PubMed ID

  • 19830704

Pubmed Central ID

  • PMC3146347

Electronic International Standard Serial Number (EISSN)

  • 1097-0258

International Standard Serial Number (ISSN)

  • 0277-6715

Digital Object Identifier (DOI)

  • 10.1002/sim.3740


  • eng