TY - JOUR
T1 - Properties of multiple intersection-union tests for multiple endpoints in combination therapy trials
AU - Westfall, Peter H.
AU - Ho, Shu Yen
AU - Prillaman, Barbara A.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - We consider intersection-union tests involving multiple endpoints in a combination drug trial, for which we control the familywise error rate in the strong sense using closed testing methods. Bonferroni-Holm, Simes-Hommel, and Resampling-Based methods all are considered in this context. Familywise error rate control heuristics are developed and evaluated using a simulation study that is specifically tailored to the intersection-union setting. Both Resampling-Based and Simes-Hommel uniformly outperform the Bonferroni-Holm. Using simulations of power, the choice of Simes-Hommel versus Resampling-Based is seen to depend on the particular alternative of interest. Because it is simpler and has generally good power, we recommend the Simes-Hommel intersection-union tests. The techniques are illustrated using real data from a clinical trial to evaluate a combination asthma therapy.
AB - We consider intersection-union tests involving multiple endpoints in a combination drug trial, for which we control the familywise error rate in the strong sense using closed testing methods. Bonferroni-Holm, Simes-Hommel, and Resampling-Based methods all are considered in this context. Familywise error rate control heuristics are developed and evaluated using a simulation study that is specifically tailored to the intersection-union setting. Both Resampling-Based and Simes-Hommel uniformly outperform the Bonferroni-Holm. Using simulations of power, the choice of Simes-Hommel versus Resampling-Based is seen to depend on the particular alternative of interest. Because it is simpler and has generally good power, we recommend the Simes-Hommel intersection-union tests. The techniques are illustrated using real data from a clinical trial to evaluate a combination asthma therapy.
KW - Adjusted p-value
KW - Bonferroni inequality
KW - Closed testing
KW - Familywise error rate
KW - Multiple endpoints
KW - Resampling-based multiple testing
KW - Simes test
UR - http://www.scopus.com/inward/record.url?scp=0035157906&partnerID=8YFLogxK
U2 - 10.1081/BIP-100107653
DO - 10.1081/BIP-100107653
M3 - Article
C2 - 11725927
AN - SCOPUS:0035157906
VL - 11
SP - 125
EP - 138
JO - Journal of Biopharmaceutical Statistics
JF - Journal of Biopharmaceutical Statistics
SN - 1054-3406
IS - 3
ER -