{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:06:14Z","timestamp":1790190374213,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["3R33AG057806\u201005S1"],"award-info":[{"award-number":["3R33AG057806\u201005S1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Anti\u2010amyloid beta monoclonal antibodies (anti\u2010A\u03b2 mAbs) have received approval from the US Food and Drug Administration for the treatment of patients with mild cognitive impairment or mild dementia due to Alzheimer's disease (collectively known as early AD) based on evidence from clinical trials. However, whether findings from these trials are generalizable to the real world is uncertain. We need reliable evidence on the real\u2010world safety of these treatments to inform decision making for clinicians, patients, and caregivers. Using lecanemab as an exemplar, we outline the key considerations in designing and implementing an observational study on safety and utilization outcomes using established administrative healthcare claims data sources with the target trial emulation framework. The target trial emulation framework is a rigorous causal inference framework that minimizes common biases in observational studies. The approach proposed here can be applied to evaluation of additional mAbs as they become available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Little is known about real\u2010world safety of anti\u2010amyloid beta monoclonal antibodies for early Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Existing real\u2010world data can support studies of their safety and utilization outcomes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Target trial emulation can guide the design of these studies while minimizing bias.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We provide key design and analytical considerations for future studies.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70080","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:56:06Z","timestamp":1744764966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Generating real\u2010world evidence in early Alzheimer's disease: Considerations for applying the target trial emulation framework to study the safety of anti\u2010amyloid therapies"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-0846","authenticated-orcid":false,"given":"Xiaojuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Health Systems Science UMass Chan Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahareh","family":"Rasouli","sequence":"additional","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelle M.","family":"Cocoros","sequence":"additional","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Abi\u2010Elias","sequence":"additional","affiliation":[{"name":"Division of Health Systems Science UMass Chan Medical School  Worcester Massachusetts USA"},{"name":"Macon and Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University  Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry H.","family":"Gurwitz","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine UMass Chan Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12638"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2351"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.862369"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_13_7_1","unstructured":"Eisai.Eisai Receives Positive Opinion from the CHMP in the European Union for Lecanemab in Early Alzheimer's Disease.Cambridge MA;2024. 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