MULTIPLE ENDPOINTS IN CLINICAL TRIALS



Nancy L. Geller
Office of Biostatistics Research
National Heart, Lung, and Blood Institute
Bethesda, MD, U.S.A.


Abstract

This talk will focus on some approaches to multiple endpoints in clinical trials. We begin by describing some real situations in which multiple endpoints seem natural. Several approaches to multiple endpoint data will be described and some of their properties will be given. Approaches include the classical method of Bonferroni adjustment as well as more recent contributions, such as linear combinations of endpoints (1). Group sequential procedures using these statistics (2,3) and closed testing procedures to determine which endpoints differ from one another at the end of a trial (4) enhance the applicability of these methods. Recent work on closed testing in group sequential trials with multiple endpoints allows a flexible stopping time (5). An example will illustrate the methods.

References

1. O'Brien, P.C. (1984).
Procedures for Comparing Samples with Multiple Endpoints.
Biometrics 40: 1079-1087.

2. Tang, D.-I., Gnecco, C. and Geller, N.L. (1989).
Design of group sequential clinical trials with multiple endpoints.
Journal of the American Statistical Association 84: 776-779.

3. Tang, D.-I., Geller, N.L. and Pocock, S.J. (1993).
On the design and analysis of randomized clinical trials with multiple endpoints.
Biometrics 49:23-30.

4. Lehmacher, W., Wassmer, G. and Reitmeir, P. (1991).
Procedures for two-sample comparisons with multiple endpoints controlling the experimentwise error rate.
Biometrics 47: 511-521.

5. Tang, D.-I. and Geller, N.L. (1997).
Closed testing procedures for group sequential clinical trials with multiple endpoints.
(In preparation.)