A Novel Method to Estimate Long‐Term Chronological Changes From Fragmented Observations in Disease Progression
Abstract
Clinical observations of patients with chronic diseases are often restricted in terms of duration. Therefore, obtaining a quantitative and comprehensive understanding of the chronology of chronic diseases is challenging, because of the inability to precisely estimate the patient's disease stage at the time point of observation. We developed a novel method to reconstitute long‐term disease progression from temporally fragmented data by extending the nonlinear mixed‐effects model to incorporate the estimation of “disease time” of each subject. Application of this method to sporadic Alzheimer's disease successfully depicted disease progression over 20 years. The covariate analysis revealed earlier onset of amyloid‐β accumulation in male and female apolipoprotein E ε4 homozygotes, whereas disease progression was remarkably slower in female ε3 homozygotes compared with female ε4 carriers and males. Simulation of a clinical trial suggests patient recruitment using the information of precise disease time of each patient will decrease the sample size required for clinical trials.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 20, 2018
- Source ID
- 10.1002/cpt.1166
Entities
People
- Akihiro Hisaka
- Hiroshi Suzuki
- Hiroyuki Takatoku
- Keita Tokuda
- Masashi Honma
- Shinichi Kijima
- Takaaki Ishida
- Takashi Moritoyo
- Takeshi Iwatsubo
- The Alzheimer’s Disease Neuroimaging Initiative*
Organizations
- AbbVie
- Alzheimer's Association
- Alzheimer's Disease Neuroimaging Initiative
- Alzheimer's Drug Discovery Foundation
- BioClinica
- Bristol-Myers Squibb
- Chiba University
- Chiron Corporation
- Eisai
- Eli Lilly and Company
- Foundation for the National Institutes of Health
- GE HealthCare
- Hoffmann-La Roche
- Innogenetics
- Johnson & Johnson
- Laboratoires Servier
- Meso Scale Diagnostics (United States)
- Ministry of Health, Labour and Welfare
- National Institute of Biomedical Imaging and Bioengineering
- National Institute on Aging
- Pfizer
- Roche (United States)
- Takeda Pharmaceutical Company
- United States Department of Defense
- University of Tokyo