Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study.
| Title: | Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study. |
|---|---|
| Authors: | Podger L; OPEN Health, London, UK.; Stewart WF; Medcurio Inc, Oakland, CA, USA.; Serrano D; The Psychometrics Team, Sheridan WY, USA.; Lipton RB; Albert Einstein College of Medicine, New York, NY, USA.; Gomez-Ulloa D; Grifols SA - Sant Cugat Del Vallès, Barcelona, Spain.; Ayasse ND; Formerly OPEN Health, Bethesda, MD, USA.; Barnes FB; Formerly OPEN Health, Bethesda, MD, USA.; Davis EA; Formerly Grifols SSNA, Research Triangle Park, NC, USA.; Runken MC; Grifols SSNA, Research Triangle Park, NC, USA. |
| Source: | Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2024; Vol. 98 (3), pp. 1079-1094. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: SAGE Publications Country of Publication: United States NLM ID: 9814863 Publication Model: Print Cited Medium: Internet ISSN: 1875-8908 (Electronic) Linking ISSN: 13872877 NLM ISO Abbreviation: J Alzheimers Dis Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : [Thousand Oaks, CA] : SAGE Publications; Original Publication: Amsterdam ; Washington : IOS Press, c1998- |
| MeSH Terms: | Quality of Life* ; Alzheimer Disease*; Humans ; Cognition |
| Abstract: | Background: A theoretical endpoint staging framework was previously developed and published, aligning outcomes (i.e., memory) to the stage of Alzheimer's 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 post-hoc analyses of the Alzheimer Management by Albumin Replacement (AMBAR) Phase 2b clinical trial in patients with AD (NCT01561053, 2012).; Objective: To evaluate whether aligning endpoints measuring cognition, function, and quality of life to hypothesized 'target' stages of AD yields magnitudes of treatment efficacy greater than those reported in the AMBAR full analysis set (FAS).; Methods: 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.; Results: For ADAS-Cog 12, the magnitude of treatment efficacy was largest in the non-target stage (-4.0, p = 0.0760) 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, p = 0.0003; 2.4, p |
| References: | Arch Neurol. 2010 Jun;67(6):746-9. (PMID: 20558394); Nat Rev Neurol. 2021 Sep;17(9):580-589. (PMID: 34239130); Lancet Neurol. 2022 Jan;21(1):66-77. (PMID: 34838239); BMJ. 2012 May 15;344:e3086. (PMID: 22589500); N Engl J Med. 2023 Jan 5;388(1):9-21. (PMID: 36449413); Innov Clin Neurosci. 2017 Feb 01;14(1-2):22-29. (PMID: 28386518); J Geriatr Psychiatry Neurol. 2022 Jan;35(1):128-134. (PMID: 33261535); Alzheimers Dement. 2022 Apr;18(4):810-823. (PMID: 34590409); Stat Med. 2000 Jun 15-30;19(11-12):1555-66. (PMID: 10844718); Alzheimers Dement (N Y). 2019 Feb 26;5:61-69. (PMID: 30859122); Alzheimers Dement. 2020 Oct;16(10):1412-1425. (PMID: 32715623); Arch Neurol. 2008 Aug;65(8):1091-5. (PMID: 18695059); Int Psychogeriatr. 2010 Feb;22(1):72-81. (PMID: 19735592); Alzheimers Dement. 2018 Apr;14(4):535-562. (PMID: 29653606); Cochrane Database Syst Rev. 2015 Mar 05;(3):CD010783. (PMID: 25740785); Alzheimers Dement. 2016 Jan;12(1):60-4. (PMID: 26710325); J Int Neuropsychol Soc. 2007 Sep;13(5):747-57. (PMID: 17521485); Lancet Neurol. 2010 Jul;9(7):702-16. (PMID: 20610346); Clin Neuropsychol. 2015;29(7):1002-9. (PMID: 26617181); Psychosom Med. 2002 May-Jun;64(3):510-9. (PMID: 12021425); Am J Geriatr Psychiatry. 2006 Feb;14(2):139-44. (PMID: 16473978); Lancet Neurol. 2021 Jun;20(6):484-496. (PMID: 33933186); J Int Neuropsychol Soc. 2008 Mar;14(2):266-78. (PMID: 18282324); J Neurol Neurosurg Psychiatry. 2010 Dec;81(12):1363-8. (PMID: 20881017); Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9. (PMID: 9236950); Lancet. 2017 Nov 25;390(10110):2327-2329. (PMID: 29185425); Semin Neurol. 2019 Apr;39(2):227-240. (PMID: 30925615); J Neurol Neurosurg Psychiatry. 2014 Apr;85(4):363-70. (PMID: 23840054); J Prev Alzheimers Dis. 2022;9(2):197-210. (PMID: 35542991); J Psychiatr Res. 2009 Jan;43(4):411-31. (PMID: 18579155); Neurology. 1984 Jul;34(7):939-44. (PMID: 6610841); Int J Geriatr Psychiatry. 2005 Mar;20(3):232-7. (PMID: 15717339); Alzheimers Res Ther. 2023 Nov 21;15(1):203. (PMID: 37990339); Alzheimers Dement. 2023 Feb;19(2):708-720. (PMID: 36086926); Am J Alzheimers Dis Other Demen. 2020 Jan-Dec;35:1533317520918719. (PMID: 32573256); Alzheimers Dement. 2017 Apr;13(4):468-492. (PMID: 27702618); Alzheimers Res Ther. 2013 Oct 07;5(5):44. (PMID: 24099236); Br J Psychiatry. 2003 Sep;183:248-54. (PMID: 12948999); J Prev Alzheimers Dis. 2018;5(4):236-244. (PMID: 30298182); JAMA Neurol. 2020 Feb 1;77(2):199-209. (PMID: 31764959); Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):285-90. (PMID: 19812472); Cell. 2020 Dec 10;183(6):1699-1713.e13. (PMID: 33188775); Psychol Assess. 2015 Dec;27(4):1234-40. (PMID: 25938338); Alzheimers Dement. 2011 May;7(3):263-9. (PMID: 21514250); Expert Rev Neurother. 2022 Oct;22(10):863-873. (PMID: 36440481); Alzheimers Dement. 2021 Apr;17(4):696-701. (PMID: 33135381); Alzheimers Dement. 2022 Jul;18(7):1314-1324. (PMID: 34726348); Alzheimers Res Ther. 2016 Feb 22;8:9. (PMID: 26899835) |
| Contributed Indexing: | Keywords: AMBAR; Alzheimer’s disease; cognition; endpoint staging framework; function; outcome measures; quality of life; trial endpoints |
| Molecular Sequence: | ClinicalTrials.gov NCT01561053 |
| Entry Date(s): | Date Created: 20240315 Date Completed: 20240408 Latest Revision: 20250429 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11091599 |
| DOI: | 10.3233/JAD-231197 |
| PMID: | 38489186 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't