Journal article
Validation of a prognostic index for Huntington's disease
Movement disorders, Vol.32(2), pp.256-263
02/2017
DOI: 10.1002/mds.26838
PMCID: PMC5318276
PMID: 27892614
Abstract
Characterizing progression in Huntington's disease is important for study the natural course and selecting appropriate participants for clinical trials.\nThe aim was to develop a prognostic index for motor diagnosis in Huntington's disease and examine its predictive performance in external observational studies.\nThe prediagnosis Neuro-biological Predictors of Huntington's Disease study (N = 945 gene-positive) was used to select a Cox regression model for computing a prognostic index. Cross-validation was used for selecting a model with good internal validity performance using the research sites as natural splits of the data set. Then, the external predictive performance was assessed using prediagnosis data from three additional observational studies, The Cooperative Huntington Observational Research Trial (N = 358), TRACK-HD (N = 118), and REGISTRY (N = 480).\nModel selection yielded a prognostic index computed as the weighted combination of the UHDRS total motor score, Symbol Digit Modalities Test, baseline age, and cytosine-adenine-guanine expansion. External predictive performance was very good for the first two of the three studies, with the third being a much more progressed cohort than the other studies. The databases were pooled and a final Cox regression model was estimated. The regression coefficients were scaled to produce the prognostic index for Huntington's disease, and a normed version, which is scaled relative to a 10-year 50% probability of motor diagnosis.\nThe positive results of this comprehensive validity analysis provide evidence that the prognostic index is generally useful for predicting Huntington's disease progression in terms of risk of future motor diagnosis. The variables for the index are routinely collected in ongoing observational studies and the index can be used to identify cohorts for clinical trial recruitment. © 2016 International Parkinson and Movement Disorder Society.
Details
- Title: Subtitle
- Validation of a prognostic index for Huntington's disease
- Creators
- Jeffrey D Long - Departments of Biostatistics, University of Iowa, Iowa City, Iowa, USADouglas R Langbehn - Departments of Biostatistics, University of Iowa, Iowa City, Iowa, USASarah J Tabrizi - Department of Neurodegenerative Disease, UCL Huntington's Disease Centre, University College London Institute of Neurology, London, United KingdomBernhard G Landwehrmeyer - Department of Neurology, University of Ulm, Ulm, GermanyJane S Paulsen - Departments of Neurology, University of Iowa, Iowa City, Iowa, USAJohn Warner - CHDI Management/CHDI Foundation, Princeton, New Jersey, USACristina Sampaio - Laboratory of Clinical Pharmacology and Therapeutics, University of Lisbon, Lisbon, Portugal
- Resource Type
- Journal article
- Publication Details
- Movement disorders, Vol.32(2), pp.256-263
- DOI
- 10.1002/mds.26838
- PMID
- 27892614
- PMCID
- PMC5318276
- NLM abbreviation
- Mov Disord
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- Publisher
- United States
- Grant note
- R01 NS040068 / NINDS NIH HHS\n200181/Z/15/Z / Wellcome Trust\nU01 NS082085 / NINDS NIH HHS\nR01 NS054893 / NINDS NIH HHS\nS10 RR023392 / NCRR NIH HHS\nR01 NS050568 / NINDS NIH HHS\nR01 AA021165 / NIAAA NIH HHS\nU01 NS082083 / NINDS NIH HHS\nUL1 TR000442 / NCATS NIH HHS
- Language
- English
- Date published
- 02/2017
- Academic Unit
- Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Biostatistics
- Record Identifier
- 9984066393002771
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