TY - JOUR
T1 - A comparison of multiplicity adjustment strategies for correlated binary endpoints
AU - Leon, Andrew C.
AU - Heo, Moonseong
N1 - Funding Information:
This research was supported in part by grants from the National Institute of Mental Health (MH60447 and MH49762) and the National Institute of Drug Abuse (DA06534). The authors are grateful to Mauricio F. Tohen, M.D. and Richard C. Risser of Eli Lilly and Company for providing the data from the RCT of treatments for mania in bipolar disorder. The authors thank the anonymous referees for their critiques.
PY - 2005
Y1 - 2005
N2 - Several Bonferroni-type adjustments have been proposed to control for familywise type I error among multiple tests. However, many of the approaches disregard the correlation among endpoints. This can result in a conservative hypothesis testing strategy. The James procedure is an alternative approach that accounts for multiplicity among correlated continuous endpoints. Here a simulation study compares four Bonferroni-type alpha-adjustments (Bonferroni, Dunn-Sidak, Holm, and Hochberg) and the James p-value adjustment when used for multiple correlated binary variables. These procedures provided adequate protection against familywise type 1 error for correlated binary endpoints, albeit, at times, in an overly cautious manner. That is, when correlations among endpoints exceed 0.60, the result is somewhat conservative for the approaches that do not account for those correlations. Among the adjustments examined, the James approach appears to be the uniformly preferred method. Analyses of data from a randomized controlled clinical trial of treatments for mania in bipolar disorder are used to illustrate the application of the multiplicity adjustments.
AB - Several Bonferroni-type adjustments have been proposed to control for familywise type I error among multiple tests. However, many of the approaches disregard the correlation among endpoints. This can result in a conservative hypothesis testing strategy. The James procedure is an alternative approach that accounts for multiplicity among correlated continuous endpoints. Here a simulation study compares four Bonferroni-type alpha-adjustments (Bonferroni, Dunn-Sidak, Holm, and Hochberg) and the James p-value adjustment when used for multiple correlated binary variables. These procedures provided adequate protection against familywise type 1 error for correlated binary endpoints, albeit, at times, in an overly cautious manner. That is, when correlations among endpoints exceed 0.60, the result is somewhat conservative for the approaches that do not account for those correlations. Among the adjustments examined, the James approach appears to be the uniformly preferred method. Analyses of data from a randomized controlled clinical trial of treatments for mania in bipolar disorder are used to illustrate the application of the multiplicity adjustments.
KW - Bonferroni adjustment
KW - Correlated binary endpoints
KW - Multiplicity
KW - Type I error
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U2 - 10.1081/BIP-200067922
DO - 10.1081/BIP-200067922
M3 - Review article
C2 - 16080237
AN - SCOPUS:22544447055
SN - 1054-3406
VL - 15
SP - 839
EP - 855
JO - Journal of Biopharmaceutical Statistics
JF - Journal of Biopharmaceutical Statistics
IS - 5
ER -