Weighted Hazard Ratio Estimation for Delayed and Diminishing Treatment Effect
Weighted Hazard Ratio Estimation for Delayed and Diminishing Treatment Effect
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治疗效果延迟和减弱的加权风险比估计
DOI：
10.1080/19466315.2023.2289514
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发表时间：
2024
影响因子：
1.8
通讯作者：
Kumar B
中科院分区：
文献类型：
--
作者：
Kumar B
在验证性临床试验中观察到非比例风险 (NPH) 与事件结果的时间相关。在 NPH 下，风险比不会随着时间的推移保持恒定，并且对数秩检验不再是最有力的检验。引入加权对数秩检验 (WLRT) 来处理不成比例的情况。我们将注意力集中在 Lin 和 León 提出的基于时变治疗效果的 WLRT 和补充 Cox 模型上。我们研究了所提出的加权风险比 (WHR) 方法在 WLRT 统计数据是最有力的测试的情况下是否无偏。在治疗效果递减的情况下，WLRT 统计量将是最佳的，Cox 模型估计的时变治疗效果估计的治疗效果非常接近真实效果。然而，当真实风险比很大时，所提出的模型会高估治疗效果和治疗曲线随时间的变化。在延迟治疗场景中，随着时间的推移估计的治疗效果曲线通常接近真实曲线。对于这两种情况，我们已经分析证明，在较小的治疗效果下，风险比函数大致相等。当分析中治疗效果曲线减少或延迟的速度的假设速率与真实数据生成机制中的速率不同时，WHR 方法估计的风险比曲线就会有偏差。由于实际上真实的心率时间曲线可能与腰心率分析中假设的不同，因此最好使用替代方法进行效果估计。
Nonproportional hazards (NPH) have been observed in confirmatory clinical trials with time to event outcomes. Under NPH, the hazard ratio does not stay constant over time and the log rank test is no longer the most powerful test. The weighted log rank test (WLRT) has been introduced to deal with the presence of nonproportionality. We focus our attention on the WLRT and the complementary Cox model based on time varying treatment effect proposed by Lin and León. We investigate whether the proposed weighted hazard ratio (WHR) approach is unbiased in scenarios where the WLRT statistic is the most powerful test. In the diminishing treatment effect scenario where the WLRT statistic would be most optimal, the time varying treatment effect estimated by the Cox model estimates the treatment effect very close to the true one. However, when the true hazard ratio is large the proposed model overestimates the treatment effect and the treatment profile over time. In the delayed treatment scenario, the estimated treatment effect profile over time is typically close to the true profile. For both scenarios, we have demonstrated analytically that the hazard ratio functions are approximately equal under small treatment effects. When the assumed rate of how quickly the treatment effect profile is diminishing or delaying differs in the analysis from that in the true data generating mechanism, the estimated hazard ratio profile from the WHR approach is biased. Since in practice the true HR time profile may differ from that assumed in the WHR analysis, it may be preferable to use alternative approaches for effect estimation.
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DOI：
10.1200/jco.2011.29.15_suppl.lba5006
发表时间：
2011
期刊：
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影响因子：
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DOI：
10.1097/ede.0b013e3181c1ea43
发表时间：
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期刊：
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影响因子：
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通讯作者：
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作者：
Lin RS;León LF
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