Forecasting individual progression trajectories in Huntington disease enables more powered clinical trials - Inria - Institut national de recherche en sciences et technologies du numérique Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2022

Forecasting individual progression trajectories in Huntington disease enables more powered clinical trials

Résumé

Variability in neurodegenerative disease progression poses great challenges for the evaluation of potential treatments. Identifying the persons who will experience significant progression in the short term is key for the implementation of trials with smaller sample sizes. We apply here disease course mapping to forecast biomarker progression for individual carriers of the pathological CAG repeat expansions responsible for Huntington disease. We used data from two longitudinal studies (TRACK-HD and TRACK-ON) to synchronize temporal progression of 15 clinical and imaging biomarkers from 290 participants with Huntington disease. We used then the resulting HD COURSE MAP to forecast clinical endpoints from the baseline data of 11,510 participants from ENROLL-HD, an external validation cohort. We used such forecasts to select participants at risk for progression and compute the power of trials for such an enriched population. HD COURSE MAP forecasts biomarkers 5 years after the baseline measures with a maximum mean absolute error of 10 points for the total motor score and 2.15 for the total functional capacity. This allowed reducing sample sizes in trial up to 50% including participants with a higher risk for progression ensuring a more homogeneous group of participants.
Fichier principal
Vignette du fichier
Koval_Huntington_SciRep.pdf (3.19 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03877293 , version 1 (29-11-2022)

Identifiants

Citer

Igor Koval, Thomas Dighiero-Brecht, Allan J Tobin, Sarah J Tabrizi, Rachael I Scahill, et al.. Forecasting individual progression trajectories in Huntington disease enables more powered clinical trials. Scientific Reports, 2022, 12 (1), pp.18928. ⟨10.1038/s41598-022-18848-8⟩. ⟨hal-03877293⟩
94 Consultations
27 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More