Identification and estimation of vaccine effectiveness in the test-negative design under equi-confounding
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arXiv
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| Auteurs principaux: | , , , |
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| Format: | Preprint |
| Publié: |
2025
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| _version_ | 1866911160195874816 |
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| author | Boyer, Christopher B. Li, Kendrick Qijun Shi, Xu Tchetgen, Eric J. Tchetgen |
| author_facet | Boyer, Christopher B. Li, Kendrick Qijun Shi, Xu Tchetgen, Eric J. Tchetgen |
| contents | The test-negative design (TND) is widely used to evaluate vaccine effectiveness in real-world settings. In a TND study, individuals with similar symptoms who seek care are tested, and effectiveness is estimated by comparing vaccination histories of test-positive cases and test-negative controls. The TND is often justified on the grounds that it reduces confounding due to unmeasured health-seeking behavior, although this has not been formally described using potential outcomes. At the same time, concerns persist that conditioning on test receipt can introduce selection bias. We provide a formal justification of the TND under an assumption of odds ratio equi-confounding, where unmeasured confounders affect test-positive and test-negative individuals equivalently on the odds ratio scale. Health-seeking behavior is one plausible example. We also show that these results hold under the outcome-dependent sampling used in TNDs. We discuss the design implications of the equi-confounding assumption and provide alternative estimators for the marginal risk ratio among the vaccinated under equi-confounding, including outcome modeling and inverse probability weighting estimators as well as a semiparametric estimator that is doubly robust. When equi-confounding does not hold, we suggest a straightforward sensitivity analysis that parameterizes the magnitude of the deviation on the odds ratio scale. A simulation study evaluates the empirical performance of our proposed estimators under a wide range of scenarios. Finally, we discuss broader uses of test-negative outcomes to de-bias cohort studies in which testing is triggered by symptoms. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2504_20360 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Identification and estimation of vaccine effectiveness in the test-negative design under equi-confounding Boyer, Christopher B. Li, Kendrick Qijun Shi, Xu Tchetgen, Eric J. Tchetgen Methodology The test-negative design (TND) is widely used to evaluate vaccine effectiveness in real-world settings. In a TND study, individuals with similar symptoms who seek care are tested, and effectiveness is estimated by comparing vaccination histories of test-positive cases and test-negative controls. The TND is often justified on the grounds that it reduces confounding due to unmeasured health-seeking behavior, although this has not been formally described using potential outcomes. At the same time, concerns persist that conditioning on test receipt can introduce selection bias. We provide a formal justification of the TND under an assumption of odds ratio equi-confounding, where unmeasured confounders affect test-positive and test-negative individuals equivalently on the odds ratio scale. Health-seeking behavior is one plausible example. We also show that these results hold under the outcome-dependent sampling used in TNDs. We discuss the design implications of the equi-confounding assumption and provide alternative estimators for the marginal risk ratio among the vaccinated under equi-confounding, including outcome modeling and inverse probability weighting estimators as well as a semiparametric estimator that is doubly robust. When equi-confounding does not hold, we suggest a straightforward sensitivity analysis that parameterizes the magnitude of the deviation on the odds ratio scale. A simulation study evaluates the empirical performance of our proposed estimators under a wide range of scenarios. Finally, we discuss broader uses of test-negative outcomes to de-bias cohort studies in which testing is triggered by symptoms. |
| title | Identification and estimation of vaccine effectiveness in the test-negative design under equi-confounding |
| topic | Methodology |
| url | https://arxiv.org/abs/2504.20360 |