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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