Abstract
BackgroundChemotherapy is expected to reduce cancer deaths (CD), while possibly being harmful in terms of non-cancer deaths (NCD) because of toxicity. Peto’s log-rank test is popular in the medical literature, but its operating characteristics are barely known. We compared this test to the most common ones in the statistical literature: the cause-specific hazard test and Gray’s test on the hazard of the subdistribution. We investigated for the first time the impact of reclassifications of causes of death (CoD) after recurrences, and of misclassification of CoD.MethodsWe present a simulation study in which we varied the censoring rate and the correlation between CD and NCD times, we generated recurrence times to study the role of the reclassification of CoD, and we added 20% misclassified CoD. We considered four scenarios for the treatment effect: none; none for CD and negative for NCD; positive for CD and none for NCD; positive for CD and negative for NCD. We applied the three tests to a randomized clinical trial evaluating adjuvant chemotherapy in 1,867 patients with non-small-cell lung cancer.ResultsMost often the three tests well preserved their nominal size, Gray’s test did not when the treatment had an effect on the competing CoD. With a high rate of misclassified CoD, Gray’s and the cause-specific tests lost much of their power, whereas the Peto’s test had the highest power. The cause-specific test had inflated size for NCD when the treatment was beneficial for CD with many misclassified CoD, but had the highest power for NCD when the treatment had no effect on CD, and had similar power to Peto’s test for CD when the treatment had no effect on NCD. Gray’s test performed best when the effect on the two CoD was opposite. The higher the censoring, the lower the rejection probabilities of all the tests and the smaller their differences.ConclusionsIn this first head-to-head comparison of the three tests, the cause-specific test often proved to be the most reliable. Comparing results with and without misclassification of the CoD, Peto’s test was the least influenced by the presence of such misclassification.
Highlights
Chemotherapy is expected to reduce cancer deaths (CD), while possibly being harmful in terms of non-cancer deaths (NCD) because of toxicity
Interest in the subject gained momentum in the 1990s, when two main approaches emerged: an approach based on the cause-specific hazard function and another based on the cumulative incidence function and its associated hazard of the subdistribution
The null hypothesis of no treatment effect holds in scenarios 1 and 2 for CD and in scenarios 1 and 3 for NCD
Summary
Chemotherapy is expected to reduce cancer deaths (CD), while possibly being harmful in terms of non-cancer deaths (NCD) because of toxicity. Peto’s log-rank test is popular in the medical literature, but its operating characteristics are barely known We compared this test to the most common ones in the statistical literature: the cause-specific hazard test and Gray’s test on the hazard of the subdistribution. Freidlin and Korn [27] compared the cause-specific log-rank test to Gray’s nonparametric test [14] for the CIF They concluded that the former preserves its nominal size better and has greater power than the latter, even with positively correlated event times. Ruan and Gray [29] studied Peto’s test both analytically and in simulations with independent survival times They proved that it has good properties when the rates of competing events are similar, whereas it has an inflated size and poor power otherwise
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
