{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:32:27Z","timestamp":1786480347948,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"10-12","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Test\u2010negative designs, a form of case\u2010cohort studies, have been commonly used to assess infectious disease interventions. Early examples of the design included the evaluation of seasonal influenza vaccines in the field. Recently, they have also been widely used to evaluate the efficacy of COVID\u201019 vaccines in preventing symptomatic disease for different variants [32]. The design hinges on individuals being tested for the disease of interest; upon recruitment, such individuals are subjected to a definitive test for the presence of the disease of interest (test\u2010positives) or not (test\u2010negatives), along with the determination of whether the individual has been exposed to the intervention under study (e.g., vaccination). In most early TND studies, individuals were tested because they were suffering from symptoms consistent with the disease in question, and the TND was a tool to reduce confounding due to healthcare\u2010seeking behavior. However, in many cases, such as COVID\u201019 and Ebola, testing results were available at healthcare facilities for individuals who presented for a variety of reasons in addition to symptoms (e.g., case contact tracing, etc.). Aggregating samples from symptomatic and asymptomatic test results leads to bias in the assessment of the efficacy of the intervention. Here we consider these issues in the context of a specific version of the \u2018\n                    <jats:italic>multiple reasons for testing problem<\/jats:italic>\n                    ,\u2019 motivated by a vaccine trial designed to assess a new Ebola viral disease vaccine (EVD) [22]. Some participants are recruited in the usual TND fashion as they present for care suffering from symptoms consistent with an Ebola diagnosis (and are thus tested); in addition, however, any test\u2010positive identified in this fashion leads to immediate testing for Ebola for all close contacts of the test\u2010positive who are likely asymptomatic at that point. We examine a simple approach to estimate the common efficacy of the vaccine intervention based on these two sources of test positives and test negatives, complemented by an assessment of whether efficacy is the same for both sources. The EVD trial was not completed for the fortunate reason that the prevailing disease outbreak ended; nevertheless, the approach here will be important if this trial is ever recommenced or similar trials are conducted in the future.\n                  <\/jats:p>","DOI":"10.1002\/sim.70525","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T11:00:07Z","timestamp":1777546807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Test\u2010Negative Designs With Multiple Testing Sources"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6818-4083","authenticated-orcid":false,"given":"Mengxin","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Statistics and Data Science, School of Art and Science, School of Public Health Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-9132","authenticated-orcid":false,"given":"Nicholas P.","family":"Jewell","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr6803a1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000000076"},{"key":"e_1_2_8_4_1","unstructured":"Icg Provisional ICG for Oral Cholera Vaccine. Report of the Annual Meeting Geneva(2017)."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.16.175166"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30993-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.02.053"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.04.026"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kww064"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dym021"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2013.18.37.20585"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2014.966695"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268814002179"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kww063"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.01.069"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199180"},{"key":"e_1_2_8_17_1","volume-title":"Causal Inference: What if","author":"Hern\u00e1n M. A.","year":"2020"},{"key":"e_1_2_8_18_1","volume-title":"Causal Inference in Statistics: A Primer","author":"Pearl J.","year":"2016"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab640"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001366"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwac203"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001438"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-055596"},{"key":"e_1_2_8_24_1","unstructured":"WHO Weekly Epidemiological Record 2019(2019) https:\/\/www.who.int\/immunization\/sage\/meetings\/2019\/april\/SAGE_April_2019_meeting_summary.pdf."},{"key":"e_1_2_8_25_1","unstructured":"SAGE Strategic Advisory Group of Experts (SAGE) on Immunization Interim Recommendations on Vaccination Against Ebola Virus Disease (EVD)(2019) https:\/\/www.who.int\/immunization\/policy\/position_papers\/interim_ebola_recommendations_may_2019.pdf."},{"key":"e_1_2_8_26_1","unstructured":"J.Johnson Johnson & Johnson Announces Donation of up to 500 000 Regimens of Janssen's Investigational Ebola Vaccine to Support Outbreak Response in Democratic Republic of the Congo (DRC)(2019) https:\/\/www.jnj.com\/johnson\u2010johnson\u2010announces\u2010donation\u2010of\u2010up\u2010to\u2010500\u2010000\u2010regimens\u2010of\u2010jansens\u2010investigational\u2010ebola\u2010vaccine\u2010to\u2010support\u2010outbreak\u2010response\u2010in\u2010democratic\u2010republic\u2010of\u2010the\u2010congo\u2010drc."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyab172"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ748"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.01.045"},{"key":"e_1_2_8_32_1","first-page":"1272","article-title":"Should Sex Be Considered an Effect Modifier in the Evaluation of Influenza Vaccine Effectiveness?","volume":"36","author":"Chambers C.","year":"2018","journal-title":"Vaccine"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2110605"}],"container-title":["Statistics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70525","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sim.70525","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70525","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:12:16Z","timestamp":1786479136000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/sim.70525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":32,"journal-issue":{"issue":"10-12","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/sim.70525"],"URL":"https:\/\/doi.org\/10.1002\/sim.70525","archive":["Portico"],"relation":{},"ISSN":["0277-6715","1097-0258"],"issn-type":[{"value":"0277-6715","type":"print"},{"value":"1097-0258","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"2024-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70525"}}