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为了获得稳健且准确的潜伏期分布估计,重点关注尾部概率和 SARS-CoV-2 感染。

Towards robust and accurate estimates of the incubation time distribution, with focus on upper tail probabilities and SARS-CoV-2 infection.

机构信息

Mathematical Institute, Leiden University, Leiden, Netherlands.

Biomedical Data Science, Medical Statistics Section, Leiden University Medical Center, Leiden, Netherlands.

出版信息

Stat Med. 2023 Jun 30;42(14):2341-2360. doi: 10.1002/sim.9726. Epub 2023 Apr 20.

Abstract

Quarantine length for individuals who have been at risk for infection with SARS-CoV-2 has been based on estimates of the incubation time distribution. The time of infection is often not known exactly, yielding data with an interval censored time origin. We give a detailed account of the data structure, likelihood formulation and assumptions usually made in the literature: (i) the risk of infection is assumed constant on the exposure window and (ii) the incubation time follows a specific parametric distribution. The impact of these assumptions remains unclear, especially for the right tail of the distribution which informs quarantine policy. We quantified bias in percentiles by means of simulation studies that mimic reality as close as possible. If assumption (i) is not correct, then median and upper percentiles are affected similarly, whereas misspecification of the parametric approach (ii) mainly affects upper percentiles. The latter may yield considerable bias. We suggest a semiparametric method that provides more robust estimates without the need of a parametric choice. Additionally, we used a simulation study to evaluate a method that has been suggested if all infection times are left censored. It assumes that the width of the interval from infection to latest possible exposure follows a uniform distribution. This assumption gave biased results in the exponential phase of an outbreak. Our application to open source data suggests that focus should be on the level of information in the observations, as expressed by the width of exposure windows, rather than the number of observations.

摘要

与 SARS-CoV-2 感染风险相关的个体隔离时间基于对潜伏期分布的估计。感染时间通常无法准确确定,导致数据的起始时间存在区间删失。我们详细介绍了文献中常用的数据结构、似然函数公式和假设:(i)感染风险在暴露窗口上被假设为常数,(ii)潜伏期遵循特定的参数分布。这些假设的影响仍不清楚,尤其是对通知隔离政策的分布右尾的影响。我们通过尽可能模拟现实的模拟研究来量化百分位数的偏差。如果假设(i)不正确,那么中位数和较高的百分位数会受到相似的影响,而参数方法(ii)的错误指定主要会影响较高的百分位数。后者可能会导致相当大的偏差。我们建议使用半参数方法,该方法无需参数选择即可提供更稳健的估计。此外,我们使用模拟研究来评估一种方法,如果所有感染时间都存在左删失,则可以使用该方法。它假设从感染到最晚可能暴露的时间间隔的宽度遵循均匀分布。在疫情爆发的指数阶段,这一假设给出了有偏差的结果。我们对开源数据的应用表明,应该关注观察结果的信息量,而不是观察数量。

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