{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:02:58Z","timestamp":1790334178462,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>A prognostic score (PS) summarizes a patient's expected disease progression and can increase the statistical efficiency of clinical trials when included as an analysis covariate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We pooled patient data from observational studies and randomized trials for early Alzheimer's disease (AD) and trained PS candidates to predict 18\u2010month changes in the Clinical Dementia Rating Scale \u2013 Sum of Boxes (CDR\u2010SB) score. The efficiency gains achieved through covariate adjustment were evaluated in a held\u2010out trial (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0650).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A machine learning PS achieved a Pearson correlation of 0.48 between predicted and observed CDR\u2010SB changes in an internal test set (\n                      <jats:italic>N\u00a0<\/jats:italic>\n                      =\u00a0398). Adjusting for this PS in the held\u2010out trial increased power from 80% to 87.9% (95% confidence interval [CI]: 85.5%\u201390.2%) with the original sample size. Alternatively, this approach could reduce the required sample size by 19.7% (95% CI: 13.7%\u201325.7%) while maintaining 80% power.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings support the use of PS adjustment for enhancing the efficiency of early AD trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71849","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:50:41Z","timestamp":1790059841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing early Alzheimer's disease clinical trials through prognostic score covariate adjustment"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-0876","authenticated-orcid":false,"given":"Bruno T.","family":"Scodari","sequence":"first","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Brown","sequence":"additional","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Shen","sequence":"additional","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Ferber","sequence":"additional","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wu","sequence":"additional","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szofia","family":"Bullain","sequence":"additional","affiliation":[{"name":"AD &amp; Dementia Clinical Development Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Millen","sequence":"additional","affiliation":[{"name":"Statistical Sciences &amp; Evidence Generation Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_8_3_1","unstructured":"Alzheimer's disease facts and figures.Alzheimer's Association. 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