Time to Functional Loss as an Endpoint in Huntington's Disease Trials: Enrichment and Sample Size.

Autor: Mills JA; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Long JD; Department of Psychiatry, University of Iowa, Iowa City, IA, USA.; Department of Biostatistics, University of Iowa, Iowa City, IA, USA., Vaidya JG; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Gantman EC; CHDI Management, Inc., Princeton, NJ, USA., Sathe S; CHDI Management, Inc., Princeton, NJ, USA., Tabrizi SJ; UCL Huntington's Disease Centre, UCL Queen Square Institute of Neurology, UK Dementia Research Institute, Department of Neurodegenerative Diseases, University College London, London, UK., Sampaio C; CHDI Management, Inc., Princeton, NJ, USA.
Jazyk: angličtina
Zdroj: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2024 Oct; Vol. 39 (10), pp. 1809-1816. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1002/mds.29963
Abstrakt: 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.
(© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE
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