Post-Hoc Assessment of Cognitive Efficacy in Alzheimer's Disease Using a Latent Growth Mixture Model in AMBAR, a Phase 2B Randomized Controlled Trial.
| Title: | Post-Hoc Assessment of Cognitive Efficacy in Alzheimer's Disease Using a Latent Growth Mixture Model in AMBAR, a Phase 2B Randomized Controlled Trial. |
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| Authors: | Ayasse ND; Department of Patient-Centered Outcomes, Statistics and Psychometrics, OPEN Health, Parsippany, NH, USA (at the time of work being conducted).; Stewart WF; Medcurio Inc, Oakland, CA, USA.; Lipton RB; Department of Neurology, Albert Einstein College of Medicine, New York, NY, USA.; Gomez-Ulloa D; Department of Health Economics and Outcomes Research, Grifols, Sant Cugat Del Vallès, Spain.; Runken MC; Department of Health Economics and Outcomes Research, Grifols, SSNA-Research Triangle Park, NC, USA. |
| Source: | Current Alzheimer research [Curr Alzheimer Res] 2024; Vol. 21 (5), pp. 353-365. |
| Publication Type: | Journal Article; Clinical Trial, Phase II; Randomized Controlled Trial |
| Language: | English |
| Journal Info: | Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101208441 Publication Model: Print Cited Medium: Internet ISSN: 1875-5828 (Electronic) Linking ISSN: 15672050 NLM ISO Abbreviation: Curr Alzheimer Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Saif Zone, Sharjah, U.A.E. ; San Francisco, CA : Bentham Science Publishers, c2004- |
| MeSH Terms: | Alzheimer Disease*/drug therapy; Cognition/drug effects ; Cognition/physiology ; Humans ; Male ; Aged ; Female ; Treatment Outcome ; Disease Progression ; Aged, 80 and over |
| Abstract: | Background: Disease progression in Alzheimer's Dementia (AD) is typically characterized by accelerated cognitive and functional decline, where heterogeneous trajectories can impact the observed treatment response.; Methods: We hypothesized that unobserved heterogeneity could obscure treatment benefits in AD. The effect of unobserved heterogeneity was empirically quantified within the Alzheimer's Management By Albumin Replacement (AMBAR) phase 2b trial data. The ADAS-Cog 12 cognition endpoint was reanalyzed in a 2-class latent growth mixture model initially fit to the treatment arm. The model with the best fit was then applied across both treatment arms to a larger (n=1000) simulated dataset that was representative of AMBAR trial cognitive data.; Results: Two classes of patients were observed: a stable cognitive trajectory class and a highly variable class. Removal of the latter (n=48, 22%) from the analysis and refitting efficacy models comparing the stable class to full placebo yielded significant treatment efficacy on cognition (p=0.007, Cohen's D=-0.4). Comparison of the stable class of each arm within the simulated dataset revealed a significant difference in treatment efficacy favoring the simulated stable treatment arm.; Conclusion: This post hoc exploratory analysis suggests that prespecified strategies for addressing unobserved heterogeneity may yield improved effect detection in AD trials. The generalizability of the analytic strategy is limited by latent stratification in only the treatment arm, a requirement given the small placebo arm in AMBAR. This limitation was partially addressed by the simulation modeling.; (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| Contributed Indexing: | Keywords: AMBAR; Alzheimer’s disease; Latent growth mixture model; cognition; exploratory analyses.; plasma exchange; unobserved heterogeneity |
| Entry Date(s): | Date Created: 20240925 Date Completed: 20241209 Latest Revision: 20250620 |
| Update Code: | 20260130 |
| DOI: | 10.2174/0115672050316936240905064215 |
| PMID: | 39318022 |
| Database: | MEDLINE |
Journal Article; Clinical Trial, Phase II; Randomized Controlled Trial