Journal
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
Volume 17, Issue 2, Pages -Publisher
SPRINGER
DOI: 10.1007/s11910-017-0723-4
Keywords
Generalized estimating equations; Longitudinal study; Missing data; Mixed effect models; Time-varying effects
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Funding
- National Institute Of Neurological Disorders And Stroke of the National Institutes of Health [K01NS099343]
- Huntington's Disease Society of America Human Biology Project Fellowship
- Texas A&M School of Public Health Research Enhancement and Development Initiative [REDI23-202059-36000]
- National Center for Advancing Translational Sciences [2UL1RR024156-06]
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Understanding the overall progression of neurodegenerative diseases is critical to the timing of therapeutic interventions and design of effective clinical trials. Disease progression can be assessed with longitudinal study designs in which outcomes are measured repeatedly over time and are assessed with respect to risk factors, either measured repeatedly or at baseline. Longitudinal data allows researchers to assess temporal disease aspects, but the analysis is complicated by complex correlation structures, irregularly spaced visits, missing data, and mixtures of time-varying and static covariate effects. We review modern statistical methods designed for these challenges. Among all methods, the mixed effect model most flexibly accommodates the challenges and is preferred by the FDA for observational and clinical studies. Examples from Huntington's disease studies are used for clarification, but the methods apply to neurodegenerative diseases in general, particularly as the identification of prodromal forms of neurodegenerative disease through sensitive biomarkers is increasing.
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