Abstract
Generalized pairwise comparisons have been proposed to permit a comprehensive assessment of several prioritized outcomes between two groups of observations. This procedure estimates Δ, the net chance of a better outcome with treatment than with control by comparing the patients outcomes among all possible pairs taking one patient from the treatment group and one patient from the control group. For time to event outcomes, the standard procedure of generalized pairwise comparisons is analogous to the Gehan’s modification of the Mann-Whitney test which is biased in presence of censored observation and less powerful than Efron’s modification of this test. We adapt Efron’s modification to generalized pairwise comparisons. We show how a pairwise contribution to Δ can be calculated from the estimates of the survival function in the presence of right-censored data. We performed a simulation study to assess the bias, the type I error and the power of the new procedure. The estimate of Δ with the new procedure is only slightly biased even in presence of heavy censoring. We also show how this bias can be corrected when only one time-to-event outcome is analyzed. The new procedure has higher power in most cases compared to the standard procedure.
References
| 1. | Jensen, SM, Pipper, CB, Ritz, C. Evaluation of multi-outcome longitudinal studies. Stat Med 2015; 34: 1993–2003. Google Scholar | Crossref | Medline | ISI |
| 2. | Sankoh, AJ, Li, H, D’Agostino, RB. Use of composite endpoints in clinical trials. Stat Med 2014; 33: 4709–4714. Google Scholar | Crossref | Medline | ISI |
| 3. | Wittkop, L, Smith, C, Fox, Z Methodological issues in the use of composite endpoints in clinical trials: examples from the HIV field. Clin Trials 2010; 7: 19–35. Google Scholar | SAGE Journals | ISI |
| 4. | Kleist, P . Composite endpoints for clinical trials. Int J Pharm Med 2007; 21: 187–198. Google Scholar | Crossref |
| 5. | Finkelstein, DM, Schoenfeld, DA. Combining mortality and longitudinal measures in clinical trials. Stat Med 1999; 18: 1341–1354. Google Scholar | Crossref | Medline | ISI |
| 6. | Buyse, M . Generalized pairwise comparisons of prioritized outcomes in the two-sample problem. Stat Med 2010; 29: 3245–3257. Google Scholar | Crossref | Medline | ISI |
| 7. | Pocock, SJ, Ariti, CA, Collier, TJ The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur Heart J 2012; 33: 176–182. Google Scholar | Crossref | Medline | ISI |
| 8. | Luo, X, Tian, H, Mohanty, S An alternative approach to confidence interval estimation for the win ratio statistic. Biometrics 2014; 71: 139–145. Google Scholar | Crossref | Medline | ISI |
| 9. | McGlothlin, AE, Lewis, RJ. Minimal clinically important difference: defining what really matters to patients. JAMA 2014; 312: 1342–1343. Google Scholar | Crossref | Medline | ISI |
| 10. | Gehan, EA . A generalized two-sample Wilcoxon test for doubly censored data. Biometrika 1965; 52: 650–653. Google Scholar | Crossref | Medline | ISI |
| 11. | Buyse, M . Reformulating the hazard ratio to enhance communication with clinical investigators. Clin Trials 2008; 5: 641–642. Google Scholar | SAGE Journals | ISI |
| 12. | Efron, B . The two sample problem with censored data. Proc Fifth Berkeley Symp Math Stat Probab 1967; 4: 831–853. Google Scholar |
| 13. | Latta, RB . Generalized Wilcoxon statistics for the two sample problem with censored data. Biometrika 1977; 63: 633–635. Google Scholar | Crossref |
| 14. | Peto, R, Peto, J. Asymptotically efficient rank invariant test procedures. J R Stat Soc A 1972; 135: 185–198. Google Scholar | Crossref | ISI |
| 15. | Tarone, RE, Ware, JH. On distribution-free tests for equality of survival distributions. Biometrika 1977; 64: 156–160. Google Scholar | Crossref | ISI |
| 16. | Moore, MJ, Goldstein, D, Hamm, J Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960–1966. Google Scholar | Crossref | Medline | ISI |
| 17. | Peron, J, Roy, P, Ding, K Assessing the benefit–risk of new treatments using generalised pairwise comparisons: the case of erlotinib in pancreatic cancer. Br J Cancer 2015; 112: 971–976. Google Scholar | Crossref | Medline | ISI |
| 18. | Mok, TS, Wu, YL, Thongprasert, S Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957. Google Scholar | Crossref | Medline | ISI |
| 19. | Péron J, Roy P, Ozenne B, et al. The net chance of a longer survival as a patient-oriented measure of benefit in randomized clinical trials. JAMA Oncol. Epub ahead of print 2016. Google Scholar |
| 20. | Weinstein, MC, Torrance, G, McGuire, A. QALYs: the basics. Value Health 2009; 12(Suppl 1): S5–S9. Google Scholar | Crossref | Medline | ISI |
| 21. | Whitehead, SJ, Ali, S. Health outcomes in economic evaluation: the QALY and utilities. Br Med Bull 2010; 96: 5–21. Google Scholar | Crossref | Medline | ISI |
| 22. | Seymour, MT, Thompson, LC, Wasan, HS Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet 2011; 377: 1749–1759. Google Scholar | Crossref | Medline | ISI |
| 23. | Koziol, JA, Jia, Z. The concordance index C and the Mann-Whitney parameter Pr(X>Y) with randomly censored data. Biom J 2009; 51: 467–474. Google Scholar | Crossref | Medline | ISI |
| 24. | Dodgson, J, Spackman, M, Pearman, A Multi-criteria analysis: a manual, London: Department of Transport, Local Government and the Regions, 2009. Google Scholar |
