Disease Bundling or Specimen Bundling? Cost- and Capacity-Efficient Strategies for Multidisease Testing with Genetic Assays

D. R. Bish, E. Bish, Hussein El Hajj
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Abstract

Problem definition: Infectious disease screening can be expensive and capacity constrained. We develop cost- and capacity-efficient testing designs for multidisease screening, considering (1) multiplexing (disease bundling), where one assay detects multiple diseases using the same specimen (e.g., nasal swabs, blood), and (2) pooling (specimen bundling), where one assay is used on specimens from multiple subjects bundled in a testing pool. A testing design specifies an assay portfolio (mix of single-disease/multiplex assays) and a testing method (pooling/individual testing per assay). Methodology/results: We develop novel models for the nonlinear, combinatorial multidisease testing design problem: a deterministic model and a distribution-free, robust variation, which both generate Pareto frontiers for cost- and capacity-efficient designs. We characterize structural properties of optimal designs, formulate the deterministic counterpart of the robust model, and conduct a case study of respiratory diseases (including coronavirus disease 2019) with overlapping clinical presentation. Managerial implications: Key drivers of optimal designs include the assay cost function, the tester’s preference toward cost versus capacity efficiency, prevalence/coinfection rates, and for the robust model, prevalence uncertainty. When an optimal design uses multiple assays, it does so in conjunction with pooling, and it uses individual testing for at most one assay. Although prevalence uncertainty can be a design hurdle, especially for emerging or seasonal diseases, the integration of multiplexing and pooling, and the ordered partition property of optimal designs (under certain coinfection structures) serve to make the design more structurally robust to uncertainty. The robust model further increases robustness, and it is also practical as it needs only an uncertainty set around each disease prevalence. Our Pareto designs demonstrate the cost versus capacity trade-off and show that multiplexing-only or pooling-only designs need not be on the Pareto frontier. Our case study illustrates the benefits of optimally integrated designs over current practices and indicates a low price of robustness. Funding: This work was supported by the National Science Foundation [Grant 1761842]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.0296 .
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疾病捆绑还是标本捆绑?多疾病基因检测的成本和能力效率策略
问题定义:传染病筛查费用昂贵,能力有限。我们为多疾病筛查开发了成本和能力效率高的测试设计,考虑了(1)多路复用(疾病捆绑),其中一种检测方法使用相同的标本(例如鼻拭子、血液)检测多种疾病,以及(2)汇集(标本捆绑),其中一种检测方法用于捆绑在测试池中的多个受试者的标本。检测设计指定检测组合(单一疾病/多种检测的混合)和检测方法(每种检测的合并/单独检测)。方法/结果:我们为非线性组合多疾病测试设计问题开发了新的模型:一个确定性模型和一个无分布的鲁棒变化,它们都为成本和能力效率设计产生了帕累托边界。我们对优化设计的结构特性进行了表征,制定了稳健模型的确定性对应项,并对具有重叠临床表现的呼吸系统疾病(包括2019冠状病毒病)进行了案例研究。管理意义:优化设计的关键驱动因素包括分析成本函数、测试人员对成本与能力效率的偏好、流行/合并感染率,以及对于稳健模型,流行不确定性。当一个优化设计使用多个分析时,它与池化相结合,并且它最多使用一个分析的单个测试。尽管患病率的不确定性可能成为设计障碍,特别是对于新发疾病或季节性疾病,但多路复用和池化的集成以及优化设计的有序划分特性(在某些共感染结构下)有助于使设计在结构上对不确定性更具鲁棒性。鲁棒模型进一步增强了鲁棒性,而且它也很实用,因为它只需要每个疾病流行率的不确定性集。我们的Pareto设计展示了成本与容量的权衡,并表明仅复用或仅池的设计不需要在Pareto边界上。我们的案例研究说明了优化集成设计相对于当前实践的好处,并指出了稳健性的低代价。本研究由美国国家科学基金会资助[Grant 1761842]。补充材料:在线附录可在https://doi.org/10.1287/msom.2022.0296上获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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