{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:53:59Z","timestamp":1788245639459,"version":"build-2803163510"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The test-negative study design is often used to estimate vaccine effectiveness in influenza studies, but it has also been proposed in the context of other infectious diseases, such as cholera, dengue, or Ebola. It was introduced as a variation of the case-control design, in an attempt to reduce confounding bias due to health-care\u2013seeking behavior, and has quickly gained popularity because of its logistic advantages. However, examination of the directed acyclic graphs that describe the test-negative design reveals that without strong assumptions, the estimated odds ratio derived under this sampling mechanism is not collapsible over the selection variable, such that the results obtained for the sampled individuals cannot be generalized to the whole population. In this paper, we show that adjustment for severity of disease can reduce this bias and, under certain assumptions, makes it possible to unbiasedly estimate a causal odds ratio. We support our findings with extensive simulations and discuss them in the context of recently published cholera test-negative studies of the effectiveness of cholera vaccines.<\/jats:p>","DOI":"10.1093\/aje\/kwab066","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T20:10:26Z","timestamp":1615579826000},"page":"1882-1889","source":"Crossref","is-referenced-by-count":10,"title":["Adjustment for Disease Severity in the Test-Negative Study Design"],"prefix":"10.1093","volume":"190","author":[{"given":"Iuliana","family":"Cioc\u0103nea-Teodorescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Nason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvid","family":"Sj\u00f6lander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E","family":"Gabriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"issue":"12","key":"2022051715503321700_ref1","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1586\/14760584.2014.966695","article-title":"Potential of the test-negative design for measuring influenza vaccine effectiveness: a systematic review","volume":"13","author":"Sullivan","year":"2014","journal-title":"Expert Rev Vaccines"},{"issue":"1","key":"2022051715503321700_ref2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/EDE.0000000000001116","article-title":"The use of test-negative controls to monitor vaccine effectiveness: a systematic review of methodology","volume":"31","author":"Chua","year":"2020","journal-title":"Epidemiology"},{"issue":"4","key":"2022051715503321700_ref3","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.vaccine.2015.12.004","article-title":"Validity of the estimates of oral cholera vaccine effectiveness derived from the test-negative design","volume":"34","author":"Ali","year":"2016","journal-title":"Vaccine"},{"issue":"43","key":"2022051715503321700_ref4","doi-asserted-by":"crossref","first-page":"5819","DOI":"10.1016\/j.vaccine.2017.09.025","article-title":"Comparison of two control groups for estimation of oral cholera vaccine effectiveness using a case-control study design","volume":"35","author":"Franke","year":"2017","journal-title":"Vaccine"},{"issue":"39","key":"2022051715503321700_ref5","doi-asserted-by":"crossref","first-page":"5891","DOI":"10.1016\/j.vaccine.2019.07.083","article-title":"Feasibility of case-control and test-negative designs to evaluate dengue vaccine effectiveness in Malaysia","volume":"37","author":"Nealon","year":"2019","journal-title":"Vaccine"},{"key":"2022051715503321700_ref6","volume-title":"WHO R&D Blueprint\u2014Ad-Hoc Workshop on Ebola Vaccines. 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