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Comparing treatments in the presence of crossing survival curves: an application to bone marrow transplantation.

ABSTRACT: In some clinical studies comparing treatments in terms of their survival curves, researchers may anticipate that the survival curves will cross at some point, leading to interest in a long-term survival comparison. However, simple comparison of the survival curves at a fixed point may be inefficient, and use of a weighted log-rank test may be overly sensitive to early differences in survival. We formulate the problem as one of testing for differences in survival curves after a prespecified time point, and propose a variety of techniques for testing this hypothesis. We study these methods using simulation and illustrate them on a study comparing survival for autologous and allogeneic bone marrow transplants.

SUBMITTER: Logan BR

PROVIDER: S-EPMC2754119 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Comparing treatments in the presence of crossing survival curves: an application to bone marrow transplantation.

Logan Brent R BR Klein John P JP Zhang Mei-Jie MJ

Biometrics 20080111 3

In some clinical studies comparing treatments in terms of their survival curves, researchers may anticipate that the survival curves will cross at some point, leading to interest in a long-term survival comparison. However, simple comparison of the survival curves at a fixed point may be inefficient, and use of a weighted log-rank test may be overly sensitive to early differences in survival. We formulate the problem as one of testing for differences in survival curves after a prespecified time ...[more]

PMID: 18190619

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Project description:BackgroundThe exchange of knowledge between statisticians developing new methodology and clinicians, reviewers or authors applying them is fundamental. This is specifically true for clinical trials with time-to-event endpoints. Thereby, one of the most commonly arising questions is that of equal survival distributions in two-armed trial. The log-rank test is still the gold-standard to infer this question. However, in case of non-proportional hazards, its power can become poor and multiple extensions have been developed to overcome this issue. We aim to facilitate the choice of a test for the detection of survival differences in the case of crossing hazards.MethodsWe restricted the review to the most recent two-armed clinical oncology trials with crossing survival curves. Each data set was reconstructed using a state-of-the-art reconstruction algorithm. To ensure reproduction quality, only publications with published number at risk at multiple time points, sufficient printing quality and a non-informative censoring pattern were included. This article depicts the p-values of the log-rank and Peto-Peto test as references and compares them with nine different tests developed for detection of survival differences in the presence of non-proportional or crossing hazards.ResultsWe reviewed 1400 recent phase III clinical oncology trials and selected fifteen studies that met our eligibility criteria for data reconstruction. After including further three individual patient data sets, for nine out of eighteen studies significant differences in survival were found using the investigated tests. An important point that reviewers should pay attention to is that 28% of the studies with published survival curves did not report the number at risk. This makes reconstruction and plausibility checks almost impossible.ConclusionsThe evaluation shows that inference methods constructed to detect differences in survival in presence of non-proportional hazards are beneficial and help to provide guidance in choosing a sensible alternative to the standard log-rank test.

Dataset Information

Comparing treatments in the presence of crossing survival curves: an application to bone marrow transplantation.

Publications

Comparing treatments in the presence of crossing survival curves: an application to bone marrow transplantation.

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