Sample enrichment for clinical trials to show delay of onset in huntington disease

Jane S Paulsen; Spencer Lourens; Karl Kieburtz; Ying Zhang

doi:10.1002/mds.27595

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Sample enrichment for clinical trials to show delay of onset in huntington disease

Journal article

Peer reviewed

Sample enrichment for clinical trials to show delay of onset in huntington disease

Jane S Paulsen, Spencer Lourens, Karl Kieburtz and Ying Zhang

Movement disorders, Vol.34(2), pp.274-280

02/2019

DOI: 10.1002/mds.27595

PMCID: PMC8121118

PMID: 30644132

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https://www.ncbi.nlm.nih.gov/pmc/articles/8121118View

Open Access

Abstract

Disease-modifying clinical trials in persons without symptoms are often limited in methods to assess the impact associated with experimental therapeutics. This study suggests sample enrichment approaches to facilitate preventive trials to delay disease onset in individuals with the dominant gene for Huntington disease. Using published onset prediction indexes, we conducted the receiver operating curve analysis for diagnosis within a 3-year clinical trial time frame. We determined optimal cut points on the indexes for participant recruitment and then conducted sample size and power calculations to detect varying effect sizes for treatment efficacy in reducing 3-year rates of disease onset (or diagnosis). Area under the curve for 3 onset prediction indexes all demonstrated excellent value in sample enrichment methodology, with the best-performing index being the multivariate risk score (MRS). This study showed that conducting an intervention trial in premanifest and prodromal individuals with the gene expansion for Huntington disease is highly feasible using sample enrichment recruitment methods. Ongoing natural history studies are highly likely to indicate additional markers of disease prior to diagnosis. Statistical modeling of identified markers can facilitate participant enrichment to increase the likelihood of detecting a difference between treatment arms in a cost-effective and efficient manner. Such variations may expedite translation of emerging therapies to persons in an earlier phase of the disease. PREDICT-HD is registered with www.clinicaltrials.gov, number NCT00051324. © 2019 International Parkinson and Movement Disorder Society.

Adult

Disease Progression

Female

Humans

Huntington Disease - genetics

Huntington Disease - physiopathology

Huntington Disease - therapy

Longitudinal Studies

Male

Middle Aged

Models, Statistical

Movement Disorders - physiopathology

Movement Disorders - therapy

Research Design

Details

Title: Subtitle: Sample enrichment for clinical trials to show delay of onset in huntington disease
Creators: Jane S Paulsen - University of Iowa, Psychological and Brain Sciences
Spencer Lourens - Department of Biostatistics, Indiana University Fairbanks School of Public Health and School of Medicine, Indianapolis, Indiana, USA
Karl Kieburtz - University of Rochester
Ying Zhang - Department of Biostatistics, Indiana University Fairbanks School of Public Health and School of Medicine, Indianapolis, Indiana, USA
Resource Type: Journal article
Publication Details: Movement disorders, Vol.34(2), pp.274-280
DOI: 10.1002/mds.27595
PMID: 30644132
PMCID: PMC8121118
NLM abbreviation: Mov Disord
ISSN: 0885-3185
eISSN: 1531-8257
Grant note: R01 NS040068 / NINDS NIH HHS CHDI Foundation, Inc. U01 NS103475 / NINDS NIH HHS NS040068 / National Institutes of Health (NIH) NS103475 / National Institutes of Health (NIH) U01 NS105509 / NINDS NIH HHS NS105509 / National Institutes of Health (NIH) R01 NS103475 / NINDS NIH HHS R01 NS105509 / NINDS NIH HHS NCATS NIH HHS
Language: English
Date published: 02/2019
Academic Unit: Psychiatry; Psychological and Brain Sciences
Record Identifier: 9984206855702771

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