To minimize potential controversies in determining the need for multiplicity adjustment for multiple hypotheses, we propose a decision rule based multiplicity adjustment strategy in this paper. Resorting to a predefined decision rule of a clinical trial, one may link the different hypotheses by their logical relationships and divide them into different families. A proper multiplicity adjustment procedure can then be developed by maintaining strong control of Type I error rate within each family. The paper applies the proposed multiplicity adjustment strategy to a published raloxifene clinical trial.
Get full access to this article
View all access options for this article.
References
1.
1. CPMPPoints to consider on multiplicity issues in clinical trials. Biometrical J2001; 43: 1039–1048.
2.
2. Hochberg Y, Westfall P. On some multiplicity problems and multiple comparison procedures in biostatistics. In Sen PK and Rao CR (eds) Handbook of statistics, Vol 18: Bioenvironmental and public health statistics. The Netherlands: Elsevier, 2000: 75–113.
3.
3. Proschan M, Waclawiw M. Practical guidelines for multiplicity adjustment in clinical trials. Control Clin Trials2000; 21:527–539.
4.
4. Chi G. Multiple testings: multiple comparisons and multiple endpoints. Drug Inf J1998; 32:1347S–1362S.
5.
5. Delmas P, Bjarnason N, Mitlak B et al. Effects of Raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in post-menopausal women. New Engl J Med1997; 337: 1641–1647.
6.
6. Tamhane AC. Multiple comparisons. In Ghosh S and Rao CR (eds) Handbook of statistics, Vol 13: Design and analysis of experiments. The Netherlands: Elsevier, 1996: 587–630.
7.
7. Westfall P, Brets F. Multiplicity in clinical trials. In Shein-Chung Chow (ed.) Encyclopedia of biopharmaceutical statistics, second edition. New York, Marcel Dekker Inc., 2003: 666–673.
8.
8. Bauer P, Rohmel J, Maurer W, Hothorn L. Testing strategies in multi-dose experiments including active control. Statist Med1998; 17: 2133–2146.
9.
9. Marcus R, Peritz E, Gabriel KR. On closed testing procedure with special reference to ordered analysis of variance. Biometrika1976; 63: 655–660.
10.
10. Holm S. A simple sequentially rejective multiple test procedure. Scand J Statist1979; 6: 65–70.
11.
11. Hommel G. A stagewise rejective multiple test based on a modified Bonferroni test. Biometrika1988; 75:383–386.
12.
12. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika1988; 75: 800–802.
13.
13. Liu W. Multiple tests of a nonhierarchical finite family of hypotheses. J Roy Statist Soc Ser B1996; 58:455–461.
14.
14. Dmitrienko A, Offen W, Westfall P. Gatekeeping strategies for clinical trials that do not require all primary effects to be significant. Statist Med2003; 22:2387–2400.
15.
15. Chen X, Luo X, Capizzi T. The application of enhanced parallel gatekeeping strategies. Statist Med2005; 24: 1385–1397.
16.
16. Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J Roy Statist Soc Ser B1995; 57:289–300.
