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Proportional constrained longitudinal data analysis models for clinical trials in sporadic Alzheimer's disease
oleh: Guoqiao Wang, Lei Liu, Yan Li, Andrew J. Aschenbrenner, Randall J. Bateman, Paul Delmar, Lon S. Schneider, Richard E. Kennedy, Gary R. Cutter, Chengjie Xiong
| Format: | Article |
|---|---|
| Diterbitkan: | Wiley 2022-01-01 |
Deskripsi
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.