在存在不同随访时间和竞争事件的情况下估计和比较不良事件概率
Estimating and comparing adverse event probabilities in the presence of varying follow-up times and competing events
摘要：
不良事件（AE）方面的安全性分析是治疗获益-风险评估的一个重要方面。与疗效分析相比，AE分析通常相当简单。特定类型AE的概率通常通过发生率比例估计，有时提出发生率密度或卡普兰-迈耶估计量。但这些分析要么没有考虑删失，要么依赖于过于严格的参数模型，要么忽略了竞争事件。以非参数Aalen-Johansen估计量为金标准，在单样本和双样本情况下，在肿瘤学和模拟的数据示例中研究了这些潜在的偏倚来源。由于估计量在随访结束时可能具有较大的方差，因此不仅在最大事件时间处比较估计量，而且在观察时间的两个分位数处比较估计量。迄今为止，文献中几乎没有研究安全性比较的结果。使用不同估计量进行组间比较的影响尚不清楚，例如，两个低估或高估估计量的比值可能与金标准估计量的比值具有可比性，也可能不具有可比性。因此，AE概率的比率也基于不同的方法计算。通过模拟调查恒定和非恒定的危害，不同的审查机制和事件频率，我们发现，忽略竞争事件是一个问题，而不是错误地假设恒定的危害，通过使用的发病率密度和AE概率估计的选择是至关重要的组比较。
英文摘要：
Safety analyses in terms of adverse events (AEs) are an important aspect of benefit-risk assessments of therapies. Compared to efficacy analyses AE analyses are often rather simplistic. The probability of an AE of a specific type is typically estimated by the incidence proportion, sometimes the incidence density or the Kaplan-Meier estimator are proposed. But these analyses either do not account for censoring, rely on a too restrictive parametric model, or ignore competing events. With the non-parametric Aalen-Johansen estimator as the gold-standard, these potential sources of bias are investigated in a data example from oncology and in simulations, both in the one-sample and in the two-sample case. As the estimators may have large variances at the end of follow-up, the estimators are not only compared at the maximal event time but also at two quantiles of the observed times. To date, consequences for safety comparisons have hardly been investigated in the literature. The impact of using different estimators for group comparisons is unclear, as, for example, the ratio of two both underestimating or overestimating estimators may or may not be comparable to the ratio of the gold-standard estimator. Therefore, the ratio of the AE probabilities is also calculated based on different approaches. By simulations investigating constant and non-constant hazards, different censoring mechanisms and event frequencies, we show that ignoring competing events is more of a problem than falsely assuming constant hazards by use of the incidence density and that the choice of the AE probability estimator is crucial for group comparisons.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
