ArticleInternational journal of epidemiology2026
Evaluating COVID-19 vaccine effectiveness across epidemiologic designs: test-negative case-control versus retrospective cohort analyses in a nationwide study.
Article in International journal of epidemiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundObservational studies are central to assessing vaccine effectiveness and informing public health policy. The two most common designs are test-negative case-control and cohort studies, yet direct comparisons of their performance using the same population, data sources, and analytic strategies remain rare. This study compares these two designs within a national population using harmonized analytic approaches.
methodsNationwide, matched test-negative case-control and retrospective cohort studies were conducted in Qatar between 1 January 2021 and 18 December 2021 to assess the effectiveness of the coronavirus disease (COVID-19) primary series of BNT162b2 and mRNA-1273 against any severe acute respiratory syndrome coronavirus 2 infection, symptomatic infection, and severe COVID-19.
resultsIn the test-negative design, BNT162b2 effectiveness was 71.0% [95% confidence interval (CI): 70.1-71.9] against any infection, 75.6% (95% CI: 74.2-77.0) against symptomatic infection, and 96.3% (95% CI: 95.2-97.2) against severe COVID-19. In the cohort design, after adjustment for testing rate, corresponding effectiveness was 78.0% (95% CI: 77.1-78.9), 81.2% (95% CI: 79.8-82.5), and 98.0% (95% CI: 96.6-98.8), respectively. Both designs demonstrated similar, rapid, and largely linear waning of effectiveness in both magnitude and pattern. Test-negative design estimates lay between cohort estimates with and without adjustment for testing rate. Similar results were observed for mRNA-1273.
conclusionsBoth designs yielded consistent effectiveness estimates across vaccines and clinically relevant outcomes, with only modest differences related to handling of health-seeking behavior. These findings demonstrate that, when rigorously implemented using quality data and harmonized analytic strategies, both designs produce comparable effectiveness estimates.
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