Abstract
Treatment comparisons in clinical studies often involve several endpoints, particularly those related to quality of life of patients suffering from diseases like cancer and arthritis. We review traditional statistical methods for this problem and describe some new approaches. One approach is based on a new formulation of the null hypothesis that incorporates the essential univariate and multivariate features of the treatment effects. Another approach is based on assigning benefit scores to different regions of the toxicity-efficacy outcome space. A third approach involves patient thresholds for tolerating different treatments. Bootstrap methods are used to circumvent the analytic and computational complexities of the new approaches. We illustrate these approaches using data from patients with rheumatoid arthritis. In this setting, quality of life involves trade-offs between efficacy and toxicity of treatments.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bloch, D.A., Lai, T.L. and Tubert-Bitter, P. (2001). One-sided tests in clinical trials with multiple endpoints. Biometrics 57, 1039–1047.
Bloch, D.A. and Silverman, B.W. (1997). Monotone discriminant functions and their applications in rheumatology. Journal of the American Statistical Association 92, 144–153.
Cook, R.J. (1996). Coupled error spending functions for parallel bivariate sequential tests. Biometrics 52, 442–450.
Cook, R.J. and Farewell, V.T. (1996). Multiplicity considerations in the design and analysis of clinical trials. Journal of the Royal Statistical Society Series A 159, 93–110.
Efron, B. and Tibshirani, R.J. (1993). An Introduction to the Bootstrap. New York: Chapman and Hall.
Follmann, D. (1995). Multivariate tests for multiple endpoints in clinical trials. Statistics in Medicine 14, 1163–1175.
Fries, J.F., Williams, C.A., Ramey, D.R. and Bloch, D.A. (1993). The relative toxicity of disease-modifying antirheumatic drugs. Arthritis and Rheumatism 36, 297–306.
Jennison, C. and Turnbull, B.W. (1993). Group sequential tests for bivariate response: interim analyses of clinical trials with both efficacy and safety end-points. Biometrics 49, 741–752.
Kudo, A. (1963). A multivariate analogue of the one-sided test. Biometrika50, 403–418.
Laska, E.M., Tang, D.I. and Meisner, M.J. (1992). Testing hypotheses about an identified treatment when there are multiple endpoints. Journal of the American Statistical Association 87, 825–831.
Lin, D.Y. (1991). Nonparametric sequential testing in clinical trials with incomplete multivariate observations. Biometrika 79, 523–529.
O’Brien, P.C. (1984). Procedures for comparing samples with multiple endpoints. Biometrics 40, 1079–1087.
Perlman, M.D. (1969). One-sided testing problems in multivariate analysis. Annals of Mathematical Statistics 40, 549–567.
Perlman, M.D. and Wu, L. (1999). The emperor’s new tests (with discussion). Statistical Science 14, 355–381.
Pocock, S.J., Geller, N.S. and Tsiatis, A.A. (1987). The analysis of multiple end-points in clinical trials. Biometrics 43, 487–498.
Ramey, D.R., Raynauld, J.P. and Fries, J.F. (1992). The health assessment questionnaire 1992: status and review. Arthritis Care Research 5, 119–129.
Su, J.Q. and Lachin, J.M., (1992). Group sequential distribution-free methods for the analysis of multivariate observations. Biometrics 48, 1033–1042.
Tang, D.I., Gnecco, C. and Geller, N.L. (1989a). An approximate likelihood ratio test for a normal mean vector with nonnegative components with applications to clinical trials. Biometrics 49, 23–30.
Tang, D.I., Gnecco, C. and Geller, N.L. (1989b). Design of group sequential clinical trials with multiple endpoints. Journal of the American Statistical Association 84, 776–779.
Tang, D.I., Geller, N.L. and Pocock, S.J. (1993). On the design and analysis of clinical trials with multiple endpoints. Biometrics 49, 23–30.
Thall, P.F. and Cheng, S.C. (1999). Treatment comparison based on two-dimensional safety and efficacy alternatives in oncology trials. Biometrics 55, 746–753.
Tubert-Bitter, P., Bloch, D.A. and Raynauld, J.P. (1995). Comparing the bivariate effects of toxicity and efficacy of treatments. Statistics in Medicine 14, 1129–1141.
Wolfe, F., Hawley, D.J. and Cathey, M.A. (1991). Clinical and health status measurements over time: prognosis and outcome assessment in rheumatoid arthritis. Journal of Rheumatology 18, 1290–1297.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Tubert-Bitter, P., Bloch, D.A., Lai, T.L. (2002). Comparison of Treatments with Multiple Outcomes. In: Mesbah, M., Cole, B.F., Lee, ML.T. (eds) Statistical Methods for Quality of Life Studies. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3625-0_10
Download citation
DOI: https://doi.org/10.1007/978-1-4757-3625-0_10
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4419-5207-3
Online ISBN: 978-1-4757-3625-0
eBook Packages: Springer Book Archive