{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:23:47Z","timestamp":1777397027691,"version":"3.51.4"},"reference-count":56,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      A theoretical endpoint staging framework was previously developed and published, aligning outcomes (i.e., memory) to the stage of Alzheimer\u2019s disease (AD) in which a given outcome is most relevant (i.e., has the greatest risk of degradation). The framework guides the selection of endpoints measuring outcomes relevant within a target AD population. Here, a proof of concept is presented via\n                      <jats:italic toggle=\"yes\">post-hoc<\/jats:italic>\n                      analyses of the Alzheimer Management by Albumin Replacement (AMBAR) Phase 2b clinical trial in patients with AD (NCT01561053, 2012).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To evaluate whether aligning endpoints measuring cognition, function, and quality of life to hypothesized \u2018target\u2019 stages of AD yields magnitudes of treatment efficacy greater than those reported in the AMBAR full analysis set (FAS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Three endpoints were tested: ADAS-Cog 12, ADCS-ADL, and QoL-AD. The magnitude of treatment efficacy was hypothesized to be maximized in the target stages of mild, mild-to-moderate, and very mild AD, respectively, compared to the full analysis set (FAS) and non-target stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      For ADAS-Cog 12, the magnitude of treatment efficacy was largest in the non-target stage (\u20134.0,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u200a=\u200a0.0760) compared to target stage and FAS. For ADCS-ADL and QoL-AD, the magnitude of treatment efficacy was largest in the target stage (14.2,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u200a=\u200a0.0003; 2.4,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u200a&lt;\u200a0.0001, respectively) compared to non-target stage and FAS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Findings indicated that evaluating endpoints in the most relevant AD stage can increase the magnitude of the observed treatment efficacy. Evidence provides preliminary proof of concept for the endpoint staging framework.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-231197","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T12:02:29Z","timestamp":1710504149000},"page":"1079-1094","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study"],"prefix":"10.1177","volume":"98","author":[{"given":"Lauren","family":"Podger","sequence":"first","affiliation":[{"name":"OPEN Health, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter F.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Medcurio Inc, Oakland, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Serrano","sequence":"additional","affiliation":[{"name":"The Psychometrics Team, Sheridan WY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard B.","family":"Lipton","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Gomez-Ulloa","sequence":"additional","affiliation":[{"name":"Grifols SA \u2013 Sant Cugat Del Vall\u00e8s, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolai D.","family":"Ayasse","sequence":"additional","affiliation":[{"name":"Formerly OPEN Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick B.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Formerly OPEN Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Anne","family":"Davis","sequence":"additional","affiliation":[{"name":"Research Triangle Park","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Chris","family":"Runken","sequence":"additional","affiliation":[{"name":"Research Triangle Park","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32399-1"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1678581"},{"key":"e_1_3_6_4_2","first-page":"22","article-title":"Outcomes assessment in clinical trials of Alzheimer\u2019s disease and its precursors: Readying for short-term and long-term clinical trial needs","volume":"14","author":"Posner H","year":"2017","unstructured":"PosnerH, CurielR, EdgarC, HendrixS, LiuE, LoewensteinDA, MorrisonG, ShinobuL, WesnesK, HarveyPD (2017) Outcomes assessment in clinical trials of Alzheimer\u2019s disease and its precursors: Readying for short-term and long-term clinical trial needs. Innov Clin Neurosci 14, 22\u201329.","journal-title":"Innov Clin Neurosci"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12213"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.12.003"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70119-8"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.204008"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.3988"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12773"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2022.2149324"},{"key":"e_1_3_6_12_2","first-page":"375","article-title":"Effect of plasma exchange with albumin replacement on cognition in Alzheimer\u2019s disease: A latent growth mixture model","volume":"29","author":"Lipton R SW","year":"2022","unstructured":"Lipton RSW, Gomez-UlloaD, RunkenM, BarceloM, AyasseN, SerranoD (2022) Effect of plasma exchange with albumin replacement on cognition in Alzheimer\u2019s disease: A latent growth mixture model. 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