{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:21:17Z","timestamp":1790652077379,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG051628"],"award-info":[{"award-number":["R01AG051628"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG056102"],"award-info":[{"award-number":["R01AG056102"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K01AG088184"],"award-info":[{"award-number":["K01AG088184"]}],"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":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>With the advent of Alzheimer's disease (AD)\u2010modifying and symptomatic treatments of demonstrated efficacy, enrolling participants as concurrent placebo controls in trials can become increasingly difficult. Synthetic controls have been proposed as a viable alternative to concurrent control groups, but their feasibility and reliability remain untested in AD studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>I\u2010CONECT trial, which evaluates conversational interactions on cognition, was used to test synthetic control methods. Data from the National Alzheimer's Coordinating Center\u2010Uniform Data Set was used to create synthetic\u2010controls for I\u2010CONECT participants using two methods: 1) case mapping and 2) case modeling. Efficacy estimates were compared between original versus synthetic\u2010controlled trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In parallel\u2010group designs, treatment effect sizes for the primary outcome were closely aligned between the original trial (\u03b2\u00a0=\u00a01.67) and synthetic control analyses (\u03b2\u00a0=\u00a01.40\u20131.65). For n\u2010of\u20101 designs, the two methods showed high agreement in identifying treatment responders (Kappa\u00a0=\u00a00.75\u20130.82).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Synthetic control methods are feasible and reliable to create alternative controls in AD studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CLINICAL TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>NCT02871921.<\/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>Synthetic control methods are feasible and suitable for evaluating treatment effects in various trial designs such as n\u2010of\u20101, single\u2010arm, and parallel groups.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Synthetic control methods can help replicate early\u2010phase Alzheimer's trials, informing go\/no\u2010go decisions for larger\u2010scale studies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The choice of similarity algorithms is critical as it affects the quality of historical case mapping.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The National Alzheimer's Coordinating Center\u2010Uniform Data Set (NACC\u2010UDS) provided an ideal pool for identifying historical cases with similar demographic, biological, and social characteristics to participants in trials, enabling the creation of synthetic control groups for Alzheimer's clinical research.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70460","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T07:45:48Z","timestamp":1751874348000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthetic control methods for n\u2010of\u20101 and parallel\u2010group trials in Alzheimer's disease: A proof\u2010of\u2010concept study using the I\u2010CONECT"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-6509","authenticated-orcid":false,"given":"Chao\u2010Yi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts 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