Post-Hoc Assessment of Cognitive Efficacy in Alzheimers Disease Using a Latent Growth Mixture Model in AMBAR, a Phase 2B Randomized Controlled Trial
- 作者: Ayasse N.1, Stewart W.2, Lipton R.3, Gomez-Ulloa D.4, Runken M.4
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隶属关系:
- Department of Patient-Centered Outcomes, Statistics and Psychometrics, OPEN Health
- , Medcurio Inc
- Department of Neurology, Albert Einstein College of Medicine
- Department of Health Economics and Outcomes Research, Grifols
- 期: 卷 21, 编号 5 (2024)
- 页面: 353-365
- 栏目: Medicine
- URL: https://ruspoj.com/1567-2050/article/view/643819
- DOI: https://doi.org/10.2174/0115672050316936240905064215
- ID: 643819
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Background:Disease progression in Alzheimers 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 Alzheimers 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, Cohens 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.
Clinical Trial Registration Number::NCT01561053
作者简介
Nicolai Ayasse
Department of Patient-Centered Outcomes, Statistics and Psychometrics, OPEN Health
编辑信件的主要联系方式.
Email: info@benthamscience.net
Walter Stewart
, Medcurio Inc
Email: info@benthamscience.net
Richard Lipton
Department of Neurology, Albert Einstein College of Medicine
Email: info@benthamscience.net
David Gomez-Ulloa
Department of Health Economics and Outcomes Research, Grifols
Email: info@benthamscience.net
M. Runken
Department of Health Economics and Outcomes Research, Grifols
Email: info@benthamscience.net
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