Abstract
Introduction: Clinical trials for sporadic Alzheimer's disease generally use mixed models for repeated measures (MMRM) or, to a lesser degree, constrained longitudinal data analysis models (cLDA) as the analysis model with time since baseline as a categorical variable. Inferences using MMRM/cLDA focus on the between-group contrast at the pre-determined, end-of-study assessments, thus are less efficient (eg, less power). Methods: The proportional cLDA (PcLDA) and proportional MMRM (pMMRM) with time as a categorical variable are proposed to use all the post-baseline data without the linearity assumption on disease progression. Results: Compared with the traditional cLDA/MMRM models, PcLDA or pMMRM lead to greater gain in power (up to 20% to 30%) while maintaining type I error control. Discussion: The PcLDA framework offers a variety of possibilities to model longitudinal data such as proportional MMRM (pMMRM) and two-part pMMRM which can model heterogeneous cohorts more efficiently and model co-primary endpoints simultaneously.
Original language | English |
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Article number | e12286 |
Journal | Alzheimer's and Dementia: Translational Research and Clinical Interventions |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - 2022 |
Keywords
- Alzheimer's disease
- MMRM
- proportional MMRM (pMMRM)
- proportional constrained longitudinal data analysis model (PcLDA)
- proportional treatment effect