Open Access 01-12-2014 | Research article
Testing the treatment effect on competing causes of death in oncology clinical trials
Published in: BMC Medical Research Methodology | Issue 1/2014
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Background
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.Methods
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.Results
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.