Interim analysis of continuous long-term endpoints in clinical trials with longitudinal outcomes

Sally Galbraith*, Ian C. Marschner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

This paper discusses interim analysis for clinical trials where the primary endpoint is observed at a specific long-term follow-up time, but where repeated measures of the same outcome are also taken at earlier times. Methods are considered for improving the efficiency with which the long-term treatment difference is estimated, making use of information from shorter-term follow-up times. This approach to interim analysis has previously been studied for binary endpoints assessed at two time points during follow-up. Here we adapt and extend this methodology to include continuous endpoints assessed at an arbitrary number of follow-up times, making use of methods for analysing multivariate normal data subject to monotone missingness and unstructured mean and covariance relationships. The magnitude of efficiency gains obtained by using short-term measurements is considered, as well as how these gains depend on the number and timing of the short-term measurements. Sequential analysis of treatment differences is discussed, including the extent to which efficiency gains translate into reductions in the expected duration of a sequentially monitored trial. The methods are illustrated on a data set involving a placebo-controlled comparison of longitudinal cholesterol measurements.

Original languageEnglish
Pages (from-to)1787-1805
Number of pages19
JournalStatistics in Medicine
Volume22
Issue number11
DOIs
Publication statusPublished - 15 Jun 2003
Externally publishedYes

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