{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:23:11Z","timestamp":1787163791540,"version":"build-2736575974"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Randomized trials comparing new vaccines against tuberculosis for use in neonates and infants, for whom Bacille Calmette\u2013Gu\u00e9rin vaccination is established practice, are using tuberculosis infection as the primary endpoint in a non-inferiority design. Markers of tuberculosis infection have imperfect sensitivity and specificity. Flaws in the non-inferiority trial design typically bias towards non-inferiority, which may result in falsely declaring non-inferiority.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a statistical simulation study to assess the impact of imperfect markers of tuberculosis infection on the interpretation of tuberculosis vaccine trials testing a non-inferiority hypothesis of an infection primary outcome in a two-arm randomized comparison. Data were generated in three 2-year cumulative risk of tuberculosis infection scenarios (2%, 5%, and 8%). The specificity of tests of tuberculosis infection was assumed to range from 100% to 85%, while the sensitivity was assumed to range from 100% to 64%. Log-binomial regression was used to estimate the relative risk of tuberculosis infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>With 100% sensitivity and specificity, type I error and power were both approximately equal to the expected values (2.5% and 80%, respectively) in all three cumulative tuberculosis risk scenarios. With modest deviations from perfect sensitivity and specificity (95% for both), the risk of falsely declaring non-inferiority was 96.8%, 53.2%, and 27.8% in the 2%, 5%, and 8% cumulative tuberculosis risk infection scenarios, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Tuberculosis vaccine non-inferiority trials using an infection primary outcome must be designed and interpreted accounting for the specificity of the tools used to measure infection, otherwise they risk declaring non-inferiority by default.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ije\/dyag034","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:48:55Z","timestamp":1771418935000},"source":"Crossref","is-referenced-by-count":1,"title":["Imprecision in tuberculosis infection outcomes: implications for non-inferiority vaccine trials"],"prefix":"10.1093","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8001-6544","authenticated-orcid":false,"given":"Daniel J","family":"Grint","sequence":"first","affiliation":[{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-6635","authenticated-orcid":false,"given":"Richard G","family":"White","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-3699","authenticated-orcid":false,"given":"Gavin","family":"Churchyard","sequence":"additional","affiliation":[{"name":"Aurum Institute , Parktown, Johannesburg,","place":["South Africa"]},{"name":"School of Public Health, University of Witwatersrand , Parktown, Johannesburg,","place":["South Africa"]},{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7627-2166","authenticated-orcid":false,"given":"Andrew","family":"Fiore-Gartland","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-188X","authenticated-orcid":false,"given":"Molebogeng","family":"Rangaka","sequence":"additional","affiliation":[{"name":"Faculty of Population Health Sciences, Institute for Global Health, UCL , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto L","family":"Garcia-Basteiro","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic\u2014Universitat de Barcelona , Barcelona,","place":["Spain"]},{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Manhi\u00e7a (CISM) , Maputo,","place":["Mozambique"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC) , Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-1133","authenticated-orcid":false,"given":"Frank","family":"Cobelens","sequence":"additional","affiliation":[{"name":"Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam UMC, Location University of Amsterdam , Amsterdam,","place":["the Netherlands"]},{"name":"Amsterdam Public Health , Amsterdam,","place":["The 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