Quality-Adjusted Survival Analysis in Cancer Clinical Trials

  • Bernard F. Cole
  • Kerry L. Kilbridge


The quality of life of patients is an important component for the evaluation of therapies in clinical trials, especially in cancer. The Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST) method evaluates treatment trade-offs in clinical trials using an endpoint based on both quantity and quality of life. The methodology has been most useful for evaluating the trade-off between increased toxic side effects of treatment and improved clinical outcome. This paper provides an overview of the Q-TWiST method, brief descriptions of related statistical tools for regression analysis and meta-analysis, and examples illustrating the techniques using data from cancer clinical trials.


Eastern Cooperative Oncology Group Utility Weight Cancer Clinical Trial Threshold Line Interferon Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Glasziou, P.P., Simes, R.J. and Gelber, R.D. (1990). Quality adjusted survival analysis. Statistics in Medicine 9, 1259–1276.PubMedCrossRefGoogle Scholar
  2. 2.
    Gelber, R.D., Cole, B.F., Gelber, S. and Goldhirsch, A. (1996). The Q-TWiST method. In: Spilker, B. (ed.), Quality of Life and Pharmacoeconomics in Clinical Trials, 2nd Edition. Philadelphia: Lippincott-Raven.Google Scholar
  3. 3.
    Kaplan, E.L. and Meier, P. (1958). Nonparametric estimation from incomplete observations. Journal of the American Statistical Association 53, 457–481.CrossRefGoogle Scholar
  4. 4.
    Gelber, R.D., Gelman, R.S. and Goldhirsch, A. (1989). A quality-of-life oriented endpoint for comparing therapies. Biometrics 45, 781–795.PubMedCrossRefGoogle Scholar
  5. 5.
    Zhao, H. and Tsiatis, A.A. (1997). A consistent estimator for the distribution of quality adjusted survival time. Biometrika 84, 339–348.CrossRefGoogle Scholar
  6. 6.
    Zhao, H. and Tsiatis, A.A. (2000). Estimating mean quality adjusted lifetime with censored data. Sankhya (Series B, Part 1) 62, 175–188.Google Scholar
  7. 7.
    Murray, S. and Cole, B.F. (2000). Variance and sample size calculations in quality-of-life adjusted survival analysis (Q-TWiST). Biometrics 56, 173–182.PubMedCrossRefGoogle Scholar
  8. 8.
    Cole, B.F., Gelber, R.D. and Anderson, K.M. (1994). Parametric approaches to quality-adjusted survival analysis. Biometrics 50, 621–631.PubMedCrossRefGoogle Scholar
  9. 9.
    Cole, B.F., Gelber, R.D. and Goldhirsch, A. (1993). Cox regression models for quality adjusted survival analysis. Statistics in Medicine 12, 975–987.PubMedCrossRefGoogle Scholar
  10. 10.
    Gelber, R.D., Goldhirsch, A. and Cole, B.F. (1993). Parametric extrapolation of survival estimates with applications to quality of life evaluation of treatments. Controlled Clinical Trials 14, 485–499.PubMedCrossRefGoogle Scholar
  11. 11.
    Cole, B.F., Gelber, R.D. and Goldhirsch, A. (1995). A quality-adjusted survival meta-analysis of adjuvant chemotherapy for premenopausal breast cancer. Statistics in Medicine 14, 1771–1784.PubMedCrossRefGoogle Scholar
  12. 12.
    Glasziou, P., Cole, B.F., Gelber, R.D., Hilden, J. and Simes, R.J. (1998). Quality-adjusted survival analysis with repeated quality-of-life measures. Statistics in Medicine, 17, 1215–1229.PubMedCrossRefGoogle Scholar
  13. 13.
    Kirkwood, J.M., Strawderman, M.H., Ernstoff, M.S., Smith, T.J., Borden, E.C. and Blum, R.H. (1996). Interferon alpha-2b adjuvant therapy of high-risk resected cutaneous melanoma: The Eastern Cooperative Oncology Group Trial EST 1684. Journal of Clinical Oncology 14, 7–17.PubMedGoogle Scholar
  14. 14.
    Cole, B.F., Gelber, R.D., Kirkwood, J.M., Goldhirsch, A., Barylak, E. and Borden, E. (1996). Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: an Eastern Cooperative Oncology Group Study. Journal of Clinical Oncology 14, 2666–2673.PubMedGoogle Scholar
  15. 15.
    Kilbridge, K.L., Weeks, J.C., Haluska, F.G., Slingluff, C.L., Atkins, M.B., Sock, D.E., Kirkwood, J.M. and Nease, R.F. Patient preferences for adjuvant interferon alfa-2b treatment. Journal of Clinical Oncology 19, 812–823.Google Scholar
  16. 16.
    Kilbridge, K.L., Cole, B.F., Kirkwood, J.M., Haluska, F.G., Atkins, M.A., Ruckdeschel, J.C, Sock, D.E., Nease, R.F. and Weeks, J.C. Quality-of-life adjusted survival analysis of high-dose adjuvant interferon alfa-2b for high-risk melanoma patients using intergroup clinical trial data. Journal of Clinical Oncology 20, 1311 – 1318.Google Scholar
  17. 17.
    Early Breast Cancer Trialists’ Collaborative Group (1992). Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy: 133 randomised trials involving 31,000 relapses and 24,000 deaths among 75,000 women. Lancet 339, 1–15; 71–85.Google Scholar
  18. 18.
    Early Breast Cancer Trialists’ Collaborative Group (1998). Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352, 930–942.CrossRefGoogle Scholar
  19. 19.
    Gelber, R.D., Cole, B.F., Goldhirsch, A., Bonadonna, G., Howell, A., McArdle, C.S., Mouridsen, H.T., Rubens, R.D. and Welvaart, K. (1995). Adjuvant chemotherapy for premenopausal breast cancer: a meta-analysis using quality-adjusted survival. The Cancer Journal from Scientific American 1, 114–121.PubMedGoogle Scholar
  20. 20.
    Gelber, R.D., Cole, B.F., Goldhirsch, A., Rose, C., Fisher, B., Osborne, C.K., Boccardo, F., Gray, R., Gordon, N.H., Bengtsson, N.-O. and Sevelda, P. (1996). Adjuvant chemotherapy plus tamoxifen compared with tamoxifen alone for postmenopausal breast cancer: a meta-analysis using quality-adjusted survival. Lancet 347, 1066–1071.PubMedCrossRefGoogle Scholar
  21. 21.
    Cole, B.F., Gelber, R.D., Gelber, S., Coates, A.S. and Goldhirsch, A. (2001). Polychemotherapy for early breast cancer: an overview of the randomized trials with quality-adjusted survival analysis. Lancet 358, 277–286.PubMedCrossRefGoogle Scholar
  22. 22.
    Gelber, R.D., Goldhirsch, A., Cole, B.F., Wieand, H.S., Schroeder, G. and Krook, J.E. (1996). A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer. Journal of the National Cancer Institute 88, 1039–1045.PubMedCrossRefGoogle Scholar
  23. 23.
    Zee, B., Cole, B.F., Li, T., Browman, G., James, K., Johnston, D., Sugano D. and Pater, J. (1998). Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma. Journal of Clinical Oncology 16, 2834–2839.PubMedGoogle Scholar
  24. 24.
    Parsons, S.K., Gelber, S., Cole, B.F., Ravindranath, Y., Ogden, A., Yeager, A.M., Chung, M., Shuster, J., Weinstein, H.J. and Gelber, R.D. (1999). Quality-adjusted survival after treatment for acute myeloid leukemia in childhood: a Q-TWiST analysis of the pediatric oncology group study 8821. Journal of Clinical Oncology 17, 2144–2152.PubMedGoogle Scholar
  25. 25.
    Cole, B.F., Solal-Céligny, P., Gelber, R.D., Lepage, E., Gisselbrecht, C., Reyes, F., Sebban, C., Sugano, D., Tendier, C and Goldhirsch, A. (1998). Quality-of-life-adjusted survival analysis of interferon alfa-2b treatment for advanced follicular lymphoma: an aid to clinical decision making. Journal of Clinical Oncology 16, 2339–2344.PubMedGoogle Scholar
  26. 26.
    Rosendahl, I., Kiebert, G.M., Curran, D., Cole, B.F., Weeks, J.C, Denis, L.J. and Hall, R.R. (1999). Quality-adjusted survival (Q-TWiST) analysis of EORTC trial 30853: comparing goserelin acetate and flutamide with bilateral orchiectomy in patients with metastatic prostate cancer. The Prostate 38, 100–109.PubMedCrossRefGoogle Scholar
  27. 27.
    Gelber, R.D., Lenderking, W.R., Cotton, D.J., Cole, B.F., Fischl, M.A., Goldhirsch, A. and Testa, M.A. (1992). Quality-of-life evaluation in a clinical trial of zidovudine therapy in patients with mildly symptomatic HIV infection. Annals of Internal Medicine 116, 961–966.PubMedCrossRefGoogle Scholar
  28. 28.
    Lenderking, W.R., Gelber, R.D., Cotton, D.J., Cole, B.F., Goldhirsch, A., Volberding, P.A. and Testa, M.A. (1994). Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. New England Journal of Medicine 330, 738–743.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2002

Authors and Affiliations

  • Bernard F. Cole
    • 1
  • Kerry L. Kilbridge
    • 2
  1. 1.Dartmouth Medical SchoolUSA
  2. 2.University of VirginiaUSA

Personalised recommendations