Assessing Delayed Treatment Benefits of Immunotherapy Using Long-Term Average Hazard: A Novel Test/Estimation Approach

Fuente: arXiv
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Autori principali: Horiguchi, Miki, Tian, Lu, Kehl, Kenneth L., Uno, Hajime
Natura: Preprint
Pubblicazione: 2024
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author Horiguchi, Miki
Tian, Lu
Kehl, Kenneth L.
Uno, Hajime
author_facet Horiguchi, Miki
Tian, Lu
Kehl, Kenneth L.
Uno, Hajime
contents Delayed treatment effects on time-to-event outcomes have often been observed in randomized controlled studies of cancer immunotherapies. In the case of delayed onset of treatment effect, the conventional test/estimation approach using the log-rank test for between-group comparison and Cox's hazard ratio to estimate the magnitude of treatment effect is not optimal, because the log-rank test is not the most powerful option, and the interpretation of the resulting hazard ratio is not obvious. Recently, alternative test/estimation approaches were proposed to address both the power issue and the interpretation problems of the conventional approach. One is a test/estimation approach based on long-term restricted mean survival time, and the other approach is based on average hazard with survival weight. This paper integrates these two ideas and proposes a novel test/estimation approach based on long-term average hazard (LT-AH) with survival weight. Numerical studies reveal specific scenarios where the proposed LT-AH method provides a higher power than the two alternative approaches. The proposed approach has test/estimation coherency and can provide robust estimates of the magnitude of treatment effect not dependent on study-specific censoring time distribution. Also, the proposed LT-AH approach can summarize the magnitude of the treatment effect in both absolute difference and relative terms using ``hazard'' (i.e., difference in LT-AH and ratio of LT-AH), meeting guideline recommendations and practical needs. This proposed approach can be a useful alternative to the traditional hazard-based test/estimation approach when delayed onset of survival benefit is expected.
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id arxiv_https___arxiv_org_abs_2403_10742
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Assessing Delayed Treatment Benefits of Immunotherapy Using Long-Term Average Hazard: A Novel Test/Estimation Approach
Horiguchi, Miki
Tian, Lu
Kehl, Kenneth L.
Uno, Hajime
Methodology
Delayed treatment effects on time-to-event outcomes have often been observed in randomized controlled studies of cancer immunotherapies. In the case of delayed onset of treatment effect, the conventional test/estimation approach using the log-rank test for between-group comparison and Cox's hazard ratio to estimate the magnitude of treatment effect is not optimal, because the log-rank test is not the most powerful option, and the interpretation of the resulting hazard ratio is not obvious. Recently, alternative test/estimation approaches were proposed to address both the power issue and the interpretation problems of the conventional approach. One is a test/estimation approach based on long-term restricted mean survival time, and the other approach is based on average hazard with survival weight. This paper integrates these two ideas and proposes a novel test/estimation approach based on long-term average hazard (LT-AH) with survival weight. Numerical studies reveal specific scenarios where the proposed LT-AH method provides a higher power than the two alternative approaches. The proposed approach has test/estimation coherency and can provide robust estimates of the magnitude of treatment effect not dependent on study-specific censoring time distribution. Also, the proposed LT-AH approach can summarize the magnitude of the treatment effect in both absolute difference and relative terms using ``hazard'' (i.e., difference in LT-AH and ratio of LT-AH), meeting guideline recommendations and practical needs. This proposed approach can be a useful alternative to the traditional hazard-based test/estimation approach when delayed onset of survival benefit is expected.
title Assessing Delayed Treatment Benefits of Immunotherapy Using Long-Term Average Hazard: A Novel Test/Estimation Approach
topic Methodology
url https://arxiv.org/abs/2403.10742