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Interim monitoring of clinical trials based on long‐term binary endpoints
Author(s) -
Marschner Ian C.,
Becker Simone L.
Publication year - 2001
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/1097-0258(20010130)20:2<177::aid-sim653>3.0.co;2-k
Subject(s) - interim analysis , interim , clinical endpoint , term (time) , clinical trial , endpoint determination , randomized controlled trial , medicine , statistics , computer science , econometrics , mathematics , physics , archaeology , quantum mechanics , history
This paper discusses interim analysis of randomized clinical trials for which the primary endpoint is observed at a specific long‐term follow‐up time. For such trials subjects only yield direct information on the primary endpoint once they have been followed through to the long‐term follow‐up time, potentially eliminating a large proportion of the accrued sample from an interim analysis of the primary endpoint. We advocate more efficient interim analysis of long‐term endpoints by augmenting long‐term information with short‐term information on subjects who have not yet been followed through to the long‐term follow‐up time. While retaining the long‐term endpoint as the subject of the analysis, methods of jointly analysing short‐ and long‐term data are discussed for reversible binary endpoints. It is shown theoretically and by simulation that the use of short‐term information improves the efficiency with which long‐term treatment differences are assessed based on interim data. Sequential analysis of treatment differences is discussed based on spending functions, and is illustrated with a numerical example from a cholesterol treatment trial. Copyright © 2001 John Wiley & Sons, Ltd.