Morrison Doug, Laeyendecker Oliver, Konikoff Jacob, Brookmeyer Ron
Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
Laboratory of Immunoregulation, NIAID, NIH, Baltimore, MD, USA and The Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Stat Commun Infect Dis. 2018 Dec;10(1). doi: 10.1515/scid-2017-0003. Epub 2018 Jul 31.
Considerable progress has been made in the development of approaches for HIV incidence estimation based on a cross-sectional survey for biomarkers of recent infection. Multiple biomarkers when used in combination can increase the precision of cross-sectional HIV incidence estimates. Multi-assay algorithms (MAAs) for cross-sectional HIV incidence estimation are hierarchical stepwise algorithms for testing the biological samples with multiple biomarkers. The objective of this paper is to consider some of the statistical challenges for addressing the problem of missing biomarkers in such testing algorithms. We consider several methods for handling missing biomarkers for (1) estimating the mean window period, and (2) estimating HIV incidence from a cross sectional survey once the mean window period has been determined. We develop a conditional estimation approach for addressing the missing data challenges and compare that method with two naïve approaches. Using MAAs developed for HIV subtype B, we evaluate the methods by simulation. We show that the two naïve estimation methods lead to biased results in most of the missing data scenarios considered. The proposed conditional approach protects against bias in all of the scenarios.
在基于近期感染生物标志物横断面调查的HIV发病率估计方法开发方面已取得了显著进展。多种生物标志物联合使用可提高横断面HIV发病率估计的精度。用于横断面HIV发病率估计的多检测算法(MAA)是用于用多种生物标志物检测生物样本的分层逐步算法。本文的目的是考虑在这类检测算法中解决生物标志物缺失问题的一些统计挑战。我们考虑了几种处理生物标志物缺失的方法,用于(1)估计平均窗口期,以及(2)在确定平均窗口期后从横断面调查中估计HIV发病率。我们开发了一种用于应对缺失数据挑战的条件估计方法,并将该方法与两种简单方法进行比较。使用针对B型HIV开发的MAA,我们通过模拟对这些方法进行评估。我们表明,在大多数考虑的缺失数据情况下,这两种简单估计方法会导致有偏差的结果。所提出的条件方法在所有情况下都能防止偏差。