{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:29:42Z","timestamp":1792600182121,"version":"4.5.0"},"reference-count":51,"publisher":"Becaris Publishing Limited","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Comp. Eff. Res."],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    <jats:bold>Aim:<\/jats:bold>\n                    The use of amyloid-beta (A\u03b2) clearance to support regulatory approvals of drugs in Alzheimer\u2019s disease (AD) remains controversial. We evaluate A\u03b2 as a potential trial-level surrogate endpoint for clinical function in AD.\n                    <jats:bold>Materials &amp; methods:<\/jats:bold>\n                    Data on the effectiveness of anti-A\u03b2 monoclonal antibodies (MABs) on A\u03b2 and multiple clinical outcomes were identified from randomized controlled trials through a literature review. A Bayesian bivariate meta-analysis was used to evaluate A\u03b2 as a surrogate endpoint for clinical function across all MABs and for each individual anti-A\u03b2 MAB. The analysis for individual therapies was conducted in subgroups of treatments and by applying Bayesian hierarchical models to borrow information across treatments.\n                    <jats:bold>Results:<\/jats:bold>\n                    We identified 23 randomized controlled trials with 39 treatment contrasts for seven MABs. The surrogate relationship between treatment effects on A\u03b2 and Clinical Dementia Rating-Sum of Boxes (CDR-SOB) across all MABs was strong: with a meaningful slope of 1.41 (0.60, 2.21) and small variance of 0.02 (0.00, 0.05). For individual treatments, the surrogate relationships were suboptimal, displaying large uncertainty. Sharing information across treatments considerably reduced the uncertainty, resulting in moderate surrogate relationships for aducanumab and lecanemab. No meaningful association was detected for other clinical outcomes, including Mini Mental State Examination and Alzheimer\u2019s Disease Assessment Scale-Cognitive Subscale.\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Although our results from the analysis of data across all MABs suggested that A\u03b2 was a potential surrogate endpoint for CDR-SOB, individually the surrogacy patterns varied across treatments and showed no evidence of association. Bayesian information-sharing revealed moderate surrogate relationship only for aducanumab and lecanemab.\n                  <\/jats:p>","DOI":"10.57264\/cer-2025-0095","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T10:28:09Z","timestamp":1764671289000},"source":"Crossref","is-referenced-by-count":5,"title":["Evaluating amyloid-beta as a surrogate endpoint in trials of anti-amyloid-beta drugs in Alzheimer\u2019s disease: a Bayesian meta-analysis"],"prefix":"10.57264","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9040-249X","authenticated-orcid":false,"given":"Sa","family":"Ren","sequence":"first","affiliation":[{"name":"Sheffield Centre for Health &amp; Related Research, School of Medicine &amp; Population Health, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janharpreet","family":"Singh","sequence":"additional","affiliation":[{"name":"Biostatistics Research Group, Division of Public Health &amp; Epidemiology, School of Medicine, University of Leicester, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Gsteiger","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Cogley","sequence":"additional","affiliation":[{"name":"Division of Public Health &amp; Epidemiology, School of Medicine, University of Leicester, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Reed","sequence":"additional","affiliation":[{"name":"Division of Public Health &amp; Epidemiology, School of Medicine, University of Leicester, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R","family":"Abrams","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Warwick, Coventry, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Dawoud","sequence":"additional","affiliation":[{"name":"National Institute for Health &amp; Care Excellence, London, UK"},{"name":"Faculty of Pharmacy, Cairo University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon K","family":"Owen","sequence":"additional","affiliation":[{"name":"Population Data Science, Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Tappenden","sequence":"additional","affiliation":[{"name":"Sheffield Centre for Health &amp; Related Research, School of Medicine &amp; Population Health, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrence J","family":"Quinn","sequence":"additional","affiliation":[{"name":"School of Cardiovascular &amp; Metabolic Health, University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3003-9403","authenticated-orcid":false,"given":"Sylwia","family":"Bujkiewicz","sequence":"additional","affiliation":[{"name":"Biostatistics Research Group, Division of Public Health &amp; Epidemiology, School of Medicine, University of Leicester, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"36897","reference":[{"key":"e_1_3_8_3_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature19323","article-title":"The antibody aducanumab reduces A\u03b2 plaques in Alzheimer's disease","volume":"537","author":"Sevigny J","year":"2016","unstructured":"Sevigny J, Chiao P, Bussi\u00e8re T The antibody aducanumab reduces A\u03b2 plaques in Alzheimer's disease. 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