{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:04:22Z","timestamp":1789995862956,"version":"4.0.1"},"reference-count":10,"publisher":"Wiley","issue":"6-7","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS131225"],"award-info":[{"award-number":["R01NS131225"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In multi\u2010site clinical research, diagnostic assessments can vary across sites even when standardized criteria and instruments are used, leading to inconsistent disease classification. This issue is examined in settings with an anchor variable that confidently identifies disease when positive but provides no information when negative. A random effects model is introduced for site\u2010specific sensitivity, along with likelihood\u2010based methods for estimation and hypothesis testing. The approach addresses two objectives: testing whether diagnostic sensitivity varies across sites, and quantifying the magnitude of such variability. Validation data is incorporated to establish parameter identifiability. Laplace approximation and the Expectation\u2010Maximization (EM) algorithm are further engaged to address the computational challenge caused by an intractable integral in the likelihood function. Likelihood ratio and score tests are constructed to account for the boundary constraint that arises when the null hypothesis places the variance component at zero. Simulation studies demonstrate the good performance in finite samples, with accurate parameter estimates and appropriate test size and power. Application to a multi\u2010site Huntington disease cohort for diagnosing mild cognitive impairment reveals differences in diagnostic sensitivity across sites, with tests providing strong evidence of heterogeneity. This framework offers a principled approach for testing and quantifying site\u2010level variability in diagnostic sensitivity, supporting more consistent inference in multi\u2010site studies.<\/jats:p>","DOI":"10.1002\/sim.70469","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T08:26:51Z","timestamp":1773044811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Testing and Quantifying Site\u2010Level Variability in Diagnostic Sensitivity of an Anchor Variable"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9599-8410","authenticated-orcid":false,"given":"Seungchul","family":"Baek","sequence":"first","affiliation":[{"name":"Department of Mathematics and Statistics University of Maryland Baltimore County  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Statistics Penn State University  University Park PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya P.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2017.07.017"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.678652"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1198145"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jamia\/ocw028"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2008.01116.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jamia\/ocz170"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1987.10478472"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-76721-5_2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-398"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181eccfa2"}],"container-title":["Statistics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70469","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sim.70469","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sim.70469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:16:40Z","timestamp":1789993000000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/sim.70469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":10,"journal-issue":{"issue":"6-7","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/sim.70469"],"URL":"https:\/\/doi.org\/10.1002\/sim.70469","archive":["Portico"],"relation":{},"ISSN":["0277-6715","1097-0258"],"issn-type":[{"value":"0277-6715","type":"print"},{"value":"1097-0258","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70469"}}