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arXiv · 2004.06033

The test-negative design with additional population controls: a practical approach to rapidly obtain information on the causes of the SARS-CoV-2 epidemic

Jan P Vandenbroucke·Elizabeth B Brickley·Christina M J E Vandenbroucke-Grauls·Neil Pearce
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Abstract

Testing of symptomatic persons for infection with SARS-CoV-2 is occurring worldwide. We propose two types of case-control studies that can be carried out jointly in test-settings for symptomatic persons. The first, the test-negative case-control design (TND) is the easiest to implement; it only demands collecting information about potential risk factors for COVID-19 from the tested symptomatic persons. The second, standard case-control studies with population controls, requires the collection of data on one or more population controls for each person who is tested in the test facilities, so that test-positives and test-negatives can each be compared with population controls. The TND will detect differences in risk factors between symptomatic persons who have COVID-19 (test-positives) and those who have other respiratory infections (test-negatives). However, risk factors with effect sizes of equal magnitude for both COVID-19 and other respiratory infections will not be identified by the TND. Therefore, we discuss how to add population controls to compare with the test-positives and the test-negatives, yielding two additional case-control studies. We describe two options for population control groups: one composed of accompanying persons to the test facilities, the other drawn from existing country-wide health care databases. We also describe other possibilities for population controls. Combining the TND with population controls yields a triangulation approach that distinguishes between exposures that are risk factors for both COVID-19 and other respiratory infections, and exposures that are risk factors for just COVID-19. This combined design can be applied to future epidemics, but also to study causes of non-epidemic disease.

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Jan P Vandenbroucke, Elizabeth B Brickley, Christina M J E Vandenbroucke-Grauls, Neil Pearce. 2020-04-13. The test-negative design with additional population controls: a practical approach to rapidly obtain information on the causes of the SARS-CoV-2 epidemic. https://doi.org/10.1097/ede.0000000000001251

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