Browse > Article
http://dx.doi.org/10.5351/KJAS.2008.21.1.035

Methods of Combining P-values for Multiple Endpoints of Various Data Types  

Kim, Su-Young (Dept. of Biostatistics, The Catholic University of Korea)
Song, Hae-Hiang (Dept. of Biostatistics, The Catholic University of Korea)
Publication Information
The Korean Journal of Applied Statistics / v.21, no.1, 2008 , pp. 35-51 More about this Journal
Abstract
Comparative studies in Phase III clinical trials quite often involve two or more equally important endpoints, and one cannot select primary endpoint from them. O'Brien(1984) proposed for continuous endpoints the OLS and GLS statistics as milti-variate test statistics. Pocock et al. (1987) mentioned the possibility of analyzing a mixture of data types, such as quantitative, binary and survival data types, with the OLS and GLS statistics, but the authors did not explore problems in combining several endpoints of different types. Furthermore, they did not perform a simulation study to assess the efficiencies of the OLS and GLS statistics for endpoints of a mixture of data types. In this paper, we propose the combining methods of correlated P-values for the analysis of multiple endpoints, and compare the efficiencies of this method with those of OLS and GLS statistics for a mixture of data types with a simulation study. Among the several methods of combining P-values that are more advantageous than combining of OLS and GLS statistics, method B maintains nominal significance levels and is more efficient, while method F and G have type I error rates that are larger than the specified significance levels, which might occasionally lead to a wrong conclusion.
Keywords
Multiple endpoints; combining independent P-values; combining correlated P-values; OLS; GLS;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Meier, P. (1975). Statistics and medical experimentation, Biometrics, 31, 511-529   DOI   ScienceOn
2 O'Brien, P. C. (1984). Procedures for comparing samples with multiple endpoints, Biometrics, 40, 1079-1087   DOI   ScienceOn
3 Wilkinson, B. (1951). A statistical consideration in psychological research, Psychological Bulletin, 48, 156-158   DOI   ScienceOn
4 Brown, M. B. (1975). 400: A method for combining non-independent, one-sided tests of significance, Biometrics, 31, 987-992   DOI   ScienceOn
5 Chow, S. C. and Liu, J. P. (2003). Design and Analysis of Clinical Trials: Concepts and Methodologies, 2nd ed., John Wiley & Sons, New Jersey
6 Fisher, R. A. (1950). Statistical Methods for Research Workers, 11th ed., Oliver and Boyd, London
7 Gehan, E. A. (1965). A generalized Wilcoxon test for comparing arbitrarily singly censored samples, Biometrika, 52, 203-223   DOI
8 Kim, J. H. (2004). Assessing Inappropriate Hospital Days with Random Coefficient Regression Models, Catholic University, Seoul, Korea
9 Gertman, P. M. and Restuccia, J. D. (1981). The appropriateness evaluation protocol: A technique for assessing unnecessary days of hospital care, Medical Care, 14, 855-871
10 Hollander, M. and Wolfe, D. A. (1999). Nonparametric Statistical Methods, 2nd ed., John Wiley & Sons, New York
11 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   DOI   ScienceOn
12 Gupta, S. S. (1963). Probability integrals of multivariate normal and multivariate t, The Annals of Mathematical Statistics, 34, 792-828   DOI
13 Littell, R. C. and Folks, J. L. (1971). Asymptotic optimality of Fisher's method of combining independent tests, Journal of the American Statistical Association, 66, 802-806   DOI
14 Littell, R. C. and Folks, J. L. (1973). Asymptotic optimality of Fisher's method of combining independent tests a, Journal of the American Statistical Association, 68, 193-194   DOI
15 Mantel, N. (1966). Evaluation of survival data and two new rank order statistics arising in its consideration, Cancer Chemotherapy Reports, 50, 163-170
16 Zaykin, D. V., Zhivotovsky, L. A., Westfall, P. H. and Weir, B. S. (2002). Truncated product method for combining P-values, Genetic Epidemiology, 22, 170-185   DOI   ScienceOn
17 Good, I. J. (1958). Significance test in parallel and in series, Journal of the American Statistical Association, 53, 799-813   DOI
18 Pocock, S. J., Geller, N. L. and Tsiatis, A. A. (1987). The analysis of multiple endpoints in clinical trials, Biometrics, 43, 487-498   DOI   ScienceOn