Coffeng Luc E, Levecke Bruno, Hattendorf Jan, Walker Martin, Denwood Matthew J
Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.
Clin Infect Dis. 2021 Jun 14;72(Suppl 3):S195-S202. doi: 10.1093/cid/ciab196.
Control of soil-transmitted helminthiasis and schistosomiasis relies heavily on regular preventive chemotherapy. Monitoring drug efficacy is crucial to provide early warning of treatment failures. The World Health Organization (WHO) recommends a survey design in which only egg-positive individuals are retested after treatment. Although this practice makes more efficient use of resources, it may lead to biased drug efficacy estimates.
We performed a simulation study to assess the potential for bias when evaluating drug efficacy using the World Health Organization-recommended survey design, and to identify alternative designs for evaluating drug efficacy that are less affected by bias. These designs were also based on selection of egg-positive individuals, but involve retesting them a second time at baseline and up to 2 times at follow-up. The utility of the different designs was compared fairly by constraining them to the same budget.
The standard procedure of selecting egg-positive individuals can introduce a substantial positive bias in drug efficacy due to regression toward the mean, particularly when infection levels or drug efficacy are low. This bias was completely eliminated by using a second baseline sample, conditionally on the first sample being excluded from analysis. Precision of estimates can be improved by increasing the number of thick smears and/or samples per person at follow-up, despite fewer individuals being tested within the same budget.
We present optimized survey designs to monitor drug efficacy in field settings, which are highly relevant for sustained control of soil-transmitted helminths and schistosomiasis, as well as onchocerciasis and lymphatic filariasis.
土壤传播的蠕虫病和血吸虫病的控制在很大程度上依赖于定期的预防性化疗。监测药物疗效对于提供治疗失败的早期预警至关重要。世界卫生组织(WHO)推荐一种调查设计,即仅对治疗后虫卵阳性的个体进行重新检测。尽管这种做法能更有效地利用资源,但可能导致药物疗效估计产生偏差。
我们进行了一项模拟研究,以评估使用世界卫生组织推荐的调查设计评估药物疗效时偏差的可能性,并确定受偏差影响较小的评估药物疗效的替代设计。这些设计同样基于对虫卵阳性个体的选择,但包括在基线时对他们进行第二次检测,并在随访时最多进行2次检测。通过将不同设计限制在相同预算内来公平比较其效用。
选择虫卵阳性个体的标准程序可能会因均值回归而在药物疗效方面引入显著的正偏差,尤其是当感染水平或药物疗效较低时。通过使用第二个基线样本(前提是将第一个样本排除在分析之外),这种偏差被完全消除。尽管在相同预算内检测的个体较少,但通过增加随访时每人的厚涂片数量和/或样本数量,可以提高估计的精度。
我们提出了优化的调查设计,以监测现场环境中的药物疗效,这对于持续控制土壤传播的蠕虫病、血吸虫病以及盘尾丝虫病和淋巴丝虫病具有高度相关性。