{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:28:15Z","timestamp":1792211295765,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":34,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>With the recent approval of disease\u2010modifying treatments for mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) by the United States Food and Drug Administration (FDA), Medicines and Healthcare products Regulatory Agency (MHRA), European Medicine Agency's Committee for Medicinal Products for Human Use (EMA\/CHMP) entities, there is a growing sense of urgency and renewed efforts to reassess and understand what constitutes a clinically meaningful benefit in the context of new treatments for AD care, despite the discordance between regulatory entities in regulatory decision\u2010making. While the concept of minimal clinically important difference (MCID) was introduced many years ago, there remains an ongoing debate about how best to evaluate and define clinical benefit in the context of emerging and new therapies for dementia. In this perspective piece, we assess how MCID can be applied to common endpoints and identify areas where MCID application or generation could be useful to enable a better valuation of therapeutic innovation. We offer recommendations for greater consistency in measures used to define MCID, and encourage the prioritized use of patient\u2010reported measures in early AD to build fieldwide consensus for MCID estimation methods and application in AD.<\/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>There is no gold standard or field\u2010wide consensus on what constitutes a clinically meaningful change in Alzheimer's disease (AD) progression trajectories.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Anchor\u2010based minimal clinically important difference (MCID) may be used as a tool that can be leveraged for greater contextualization of the clinical relevance of a treatment effect.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Patient\u2010reported outcomes (PROs) should be used to define MCID, particularly within mild cognitive impairment (MCI), prodrome\/mild AD groups.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Greater consistency is needed in the outcome measures used to detect cognitive and functional change to define MCID. This will enable MCID comparisons and support replications of MCID estimates across AD populations.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Observational data can augment the clinical characterization and impact of treatment effect and help establish a \u201cground truth\u201d MCID.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MCID estimates for AD outcomes may be used in regulatory submissions to help contextualize the importance of a statistically significant treatment effect.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70138","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T06:45:26Z","timestamp":1754376326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Utilizing MCID for evaluating clinical relevance of AD therapeutic interventions"],"prefix":"10.1002","volume":"11","author":[{"given":"Jamie L.","family":"Hamilton","sequence":"first","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L. M.","family":"Fuller","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noopur","family":"Modi","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7052-9079","authenticated-orcid":false,"given":"Cristina","family":"Sampaio","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"},{"name":"Laboratoria de Farmacologia Clinica Faculdade de Medicina da Universidade de Lisboa (FMUL)  Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12694"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12328"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.41"},{"issue":"1","key":"e_1_2_7_5_1","article-title":"Composite cognitive and functional measures for early stage Alzheimer's disease trials","volume":"12","author":"Schneider LS","year":"2020","journal-title":"Alzheimers Dement"},{"issue":"3","key":"e_1_2_7_6_1","article-title":"Meaningful benefit and minimal clinically important difference (MCID) in Alzheimer's disease: open peer commentary","volume":"9","author":"Cummings J","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"7","key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/d41573-021-00099-3","article-title":"FDA approval for Biogen's aducanumab sparks Alzheimer disease firestorm","volume":"20","author":"Mullard A","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.3854"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-4-79"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(89)90005-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200817"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1081\/COPD-200050508"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2008.02122.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179521"},{"key":"e_1_2_7_15_1","unstructured":"Food and Drug Administration.Patient\u2010focused drug development: selecting developing or modifying fit\u2010for\u2010purpose clinical outcome assessments: guidance for industry food and drug administration staff and other stakeholders.Food and Drug Administration;2022."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200018050-00001"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-035980"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2024.112"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00723-1"},{"key":"e_1_2_7_20_1","volume-title":"Quality of Life\u2010Alzheimer's Disease Scale (QOL\u2010AD)","author":"Logsdon RG","year":"1999"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.12.2.233"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2018.05.010"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291798006667"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-020-01598-7"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.16-3-247"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-122308"},{"key":"e_1_2_7_27_1","article-title":"Characterizing treatment non\u2010responders vs. responders in completed Alzheimer's disease clinical trials","author":"Wang D","year":"2023","journal-title":"medRxiv"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.111.2.361"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29394"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2023.122787"},{"key":"e_1_2_7_31_1","unstructured":"United States. 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