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Time to Functional Loss as an Endpoint in Huntington's Disease Trials: Enrichment and Sample Size.
Mills, James A; Long, Jeffrey D; Vaidya, Jatin G; Gantman, Emily C; Sathe, Swati; Tabrizi, Sarah J; Sampaio, Cristina.
Afiliación
  • Mills JA; Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
  • Long JD; Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
  • Vaidya JG; Department of Biostatistics, University of Iowa, Iowa City, IA, USA.
  • Gantman EC; Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
  • Sathe S; CHDI Management, Inc., Princeton, NJ, USA.
  • Tabrizi SJ; CHDI Management, Inc., Princeton, NJ, USA.
  • Sampaio C; UCL Huntington's Disease Centre, UCL Queen Square Institute of Neurology, UK Dementia Research Institute, Department of Neurodegenerative Diseases, University College London, London, UK.
Mov Disord ; 39(10): 1809-1816, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39101272
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Progresión de la Enfermedad Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Mov Disord Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Progresión de la Enfermedad Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Mov Disord Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos