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

Author:

Arntzen Vera H.1ORCID,Fiocco Marta123,Leitzinger Nils1,Geskus Ronald B.456ORCID

Affiliation:

1. Mathematical Institute Leiden University Leiden Netherlands

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

3. Trial Data Center Princess Maxima Center for Childhood Oncology Utrecht Netherlands

4. Centre for Tropical Medicine and Global Health University of Oxford Oxford UK

5. Biostatistics Oxford University Clinical Research Unit (OUCRU) Ho Chi Minh City Vietnam

6. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford Oxford UK

Abstract

AbstractQuarantine 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.

Publisher

Wiley

Subject

Statistics and Probability,Epidemiology

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