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.)