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Autori principali: Dormuth, Ina, Herrmann, Carolin, Konietschke, Frank, Pauly, Markus, Wirth, Matthias, Ditzhaus, Marc
Natura: Preprint
Pubblicazione: 2024
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Accesso online:https://arxiv.org/abs/2410.21098
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author Dormuth, Ina
Herrmann, Carolin
Konietschke, Frank
Pauly, Markus
Wirth, Matthias
Ditzhaus, Marc
author_facet Dormuth, Ina
Herrmann, Carolin
Konietschke, Frank
Pauly, Markus
Wirth, Matthias
Ditzhaus, Marc
contents When comparing multiple groups in clinical trials, we are not only interested in whether there is a difference between any groups but rather the location. Such research questions lead to testing multiple individual hypotheses. To control the familywise error rate (FWER), we must apply some corrections or introduce tests that control the FWER by design. In the case of time-to-event data, a Bonferroni-corrected log-rank test is commonly used. This approach has two significant drawbacks: (i) it loses power when the proportional hazards assumption is violated [1] and (ii) the correction generally leads to a lower power, especially when the test statistics are not independent [2]. We propose two new tests based on combined weighted log-rank tests. One as a simple multiple contrast test of weighted log-rank tests and one as an extension of the so-called CASANOVA test [3]. The latter was introduced for factorial designs. We propose a new multiple contrast test based on the CASANOVA approach. Our test promises to be more powerful under crossing hazards and eliminates the need for additional p-value correction. We assess the performance of our tests through extensive Monte Carlo simulation studies covering both proportional and non-proportional hazard scenarios. Finally, we apply the new and reference methods to a real-world data example. The new approaches control the FWER and show reasonable power in all scenarios. They outperform the adjusted approaches in some non-proportional settings in terms of power.
format Preprint
id arxiv_https___arxiv_org_abs_2410_21098
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Single CASANOVA? Not in multiple comparisons
Dormuth, Ina
Herrmann, Carolin
Konietschke, Frank
Pauly, Markus
Wirth, Matthias
Ditzhaus, Marc
Methodology
When comparing multiple groups in clinical trials, we are not only interested in whether there is a difference between any groups but rather the location. Such research questions lead to testing multiple individual hypotheses. To control the familywise error rate (FWER), we must apply some corrections or introduce tests that control the FWER by design. In the case of time-to-event data, a Bonferroni-corrected log-rank test is commonly used. This approach has two significant drawbacks: (i) it loses power when the proportional hazards assumption is violated [1] and (ii) the correction generally leads to a lower power, especially when the test statistics are not independent [2]. We propose two new tests based on combined weighted log-rank tests. One as a simple multiple contrast test of weighted log-rank tests and one as an extension of the so-called CASANOVA test [3]. The latter was introduced for factorial designs. We propose a new multiple contrast test based on the CASANOVA approach. Our test promises to be more powerful under crossing hazards and eliminates the need for additional p-value correction. We assess the performance of our tests through extensive Monte Carlo simulation studies covering both proportional and non-proportional hazard scenarios. Finally, we apply the new and reference methods to a real-world data example. The new approaches control the FWER and show reasonable power in all scenarios. They outperform the adjusted approaches in some non-proportional settings in terms of power.
title Single CASANOVA? Not in multiple comparisons
topic Methodology
url https://arxiv.org/abs/2410.21098