{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:03:41Z","timestamp":1790391821861,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,11,10]],"date-time":"2015-11-10T00:00:00Z","timestamp":1447113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["89857"],"award-info":[{"award-number":["89857"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["project 918.10.615"],"award-info":[{"award-number":["project 918.10.615"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["89857"],"award-info":[{"award-number":["89857"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["project 918.10.615"],"award-info":[{"award-number":["project 918.10.615"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2016,4,30]]},"abstract":"<jats:p>Composite reference standards (CRSs) have been advocated in diagnostic accuracy studies in the absence of a perfect reference standard. The rationale is that combining results of multiple imperfect tests leads to a more accurate reference than any one test in isolation. Focusing on a CRS that classifies subjects as disease positive if at least one component test is positive, we derive algebraic expressions for sensitivity and specificity of this CRS, sensitivity and specificity of a new (index) test compared with this CRS, as well as the CRS\u2010based prevalence. We use as a motivating example the problem of evaluating a new test for<jats:italic>Chlamydia trachomatis<\/jats:italic>, an asymptomatic disease for which no gold\u2010standard test exists. As the number of component tests increases, sensitivity of this CRS increases at the expense specificity, unless all tests have perfect specificity. Therefore, such a CRS can lead to significantly biased accuracy estimates of the index test. The bias depends on disease prevalence and accuracy of the CRS. Further, conditional dependence between the CRS and index test can lead to over\u2010estimation of index test accuracy estimates. This commonly\u2010used CRS combines results from multiple imperfect tests in a way that ignores information and therefore is not guaranteed to improve over a single imperfect reference unless each component test has perfect specificity, and the CRS is conditionally independent of the index test. When these conditions are not met, as in the case of<jats:italic>C. trachomatis<\/jats:italic>testing, more realistic statistical models should be researched instead of relying on such CRSs. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/sim.6803","type":"journal-article","created":{"date-parts":[[2015,11,11]],"date-time":"2015-11-11T02:24:48Z","timestamp":1447208688000},"page":"1454-1470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Bias due to composite reference standards in diagnostic accuracy studies"],"prefix":"10.1002","volume":"35","author":[{"given":"Ian","family":"Schiller","sequence":"first","affiliation":[{"name":"Division of Clinical Epidemiology McGill University Health Centre Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"van Smeden","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alula","family":"Hadgu","sequence":"additional","affiliation":[{"name":"Division of STD Prevention Centers for Disease Control Atlanta GA 30329\u20104027 U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Libman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases McGill University Health Centre Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes B.","family":"Reitsma","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care University Medical Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Dendukuri","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology McGill University Health Centre Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.02.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02595925"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2013.05.014"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(81)90059-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1128\/CMR.10.1.160","article-title":"Current methods of laboratory diagnosis of Chlamydia trachomatis infections","volume":"10","author":"Black C","year":"1997","journal-title":"Clinical Microbiological Reviews"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19991130)18:22<2987::AID-SIM205>3.0.CO;2-B"},{"issue":"12","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1128\/JCM.38.12.4382-4386.2000","article-title":"Evaluation of nucleic acid amplification tests as reference tests for chlamydia tratchomatis infections in asymptomatic men","volume":"38","author":"Johnson RE","year":"2000","journal-title":"Journal of Clinical Microbiology"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.10.3757-3763.2002"},{"key":"e_1_2_9_10_1","first-page":"1","article-title":"Screening test to detect chlamydia trachomatis and neisseria gonorrhoeae infections","volume":"51","author":"Centers for Disease Control and Prevention","year":"2002","journal-title":"Morbidity and Mortality Weekly Report"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2003.09.063"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00223-07"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00007814"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00137-13"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1128\/JCM.36.3.679-683.1998","article-title":"Evaluation of PCR for diagnosis of Bordetella pertussis and Bordetella parapertussis infections","volume":"36","author":"Lind\u2010Brandberg L","year":"1998","journal-title":"Journal of Clinical Microbiology"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f5605"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e31823b506b"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1178"},{"key":"e_1_2_9_19_1","unstructured":"US Food and Drug Administration.Draft guidance for industry and food and drug administration staff \u2013 establishing the performance characteristics of in vitro diagnostic devices for Chlamydia trachomatis and\/or Neisseria gonorrhoea: Screening and Diagnostic Testing 2011. 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