Journal article
Time to Functional Loss as an Endpoint in Huntington's Disease Trials: Enrichment and Sample Size
Movement disorders, Vol.39(10), pp.1809-1816
10/2024
DOI: 10.1002/mds.29963
PMID: 39101272
Appears in UI Libraries Support Open Access
Abstract
Abstract Background Clinical trial scenarios can be modeled using data from observational studies, providing critical information for design of real‐world trials. The Huntington's Disease Integrated Staging System (HD‐ISS) characterizes disease progression over an individual's lifespan and allows for flexibility in the design of trials with the goal of delaying progression. Enrichment methods can be applied to the HD‐ISS to identify subgroups requiring smaller estimated sample sizes. Objective Investigate time to the event of functional decline (HD‐ISS Stage 3) as an endpoint for trials in HD and present sample size estimates after enrichment. Methods We classified individuals from observational studies according to the HD‐ISS. We assessed the ability of the prognostic index normed (PIN) and its components to predict time to HD‐ISS Stage 3. For enrichment, we formed groups from deciles of the baseline PIN distribution for HD‐ISS Stage 2 participants. We selected enrichment subgroups closer to Stage 3 transition and estimated sample sizes, using delay in the transition time as the effect size. Results In predicting time to HD‐ISS Stage 3, PIN outperforms its components. Survival curves for each PIN decile show that groups with PIN from 1.48 to 2.74 have median time to Stage 3 of approximately 2 years and these are combined to create enrichment subgroups. Sample size estimates are presented by enrichment subgroup. Conclusions PIN is predictive of functional decline. A delay of 9 months or more in the transition to Stage 3 for an enriched sample yields feasible sample size estimates, demonstrating that this approach can aid in planning future trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Details
- Title: Subtitle
- Time to Functional Loss as an Endpoint in Huntington's Disease Trials: Enrichment and Sample Size
- Creators
- James A. Mills - University of IowaJeffrey D. Long - University of IowaJatin G. Vaidya - University of IowaEmily C. Gantman - CHDI FoundationSwati Sathe - CHDI FoundationSarah J. Tabrizi - UK Dementia Research InstituteCristina Sampaio - CHDI Foundation
- Resource Type
- Journal article
- Publication Details
- Movement disorders, Vol.39(10), pp.1809-1816
- Publisher
- Wiley
- DOI
- 10.1002/mds.29963
- PMID
- 39101272
- ISSN
- 0885-3185
- eISSN
- 1531-8257
- Grant note
Funding agency: CHDI Foundation, Inc.
- Language
- English
- Electronic publication date
- 08/05/2024
- Date published
- 10/2024
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute; Biostatistics; University College Courses
- Record Identifier
- 9984696855802771
Metrics
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