ProjectEVIDENCE-RND - Creating robust evidence for longitudinal progression changes and treatment effects in ultra- rare…

Basic data

Title:
EVIDENCE-RND - Creating robust evidence for longitudinal progression changes and treatment effects in ultra- rare neurological diseases: the case of multisystemic autosomal-recessive ataxias
Duration:
12/1/2021 to 12/31/2021
Abstract / short description:
There is a scarcity of robust trial design and analysis methods in ultra-rare neurological diseases (RND) affecting small cohorts (< 50) or even single cases. The urgency to find solutions is accelerated as disease- modifying compounds are now on the horizon for a growing number of RNDs, yet methods to generate robust evidence for treatment effects are missing. EVIDENCE-RND will develop a toolbox of innovative statistical methodologies designed to fill this gap. Our methods toolbox will deliver: (i) an optimized clinically meaningful composite endpoint for RNDs, including methods to evaluate applicability across ultra-rare RND subpopulations; (ii) robust progression models, including prediction of individual disease trajectories and quantification of their uncertainty; (iii) pharmacometrics models to analyse treatment efficacy and guide trial design and treatment decisions even in n-of-1 studies; (iv) randomization-based inference models for valid and efficient RCTs in ultra-small cohorts. As showcase, we will apply them to autosomal-recessive cerebellar ataxias, leveraging registry datasets from major transatlantic consortia (PREPARE, PROSPAX, EUROSCA, ESMI), close communication with patient organisations (Euro-Ataxia) and industry trial expertise (Novartis, AstraZeneca). Continuous interaction with EMA and C-Path will ensure that the overall goal will be readily achieved: to provide EMA with proposals for optimized outcomes, trial designs, and innovative analyses, optimized to be as informative as possible to allow robust evidence in the smallest possible populations.
Keywords:
statistics
Statistik
methods
Methoden
ataxia
Ataxie
Trial Design
Seltene Erkrankungen
Natural History Studies

Involved staff

Managers

Faculty of Medicine
University of Tübingen
University Department of Neurology
Hospitals and clinical institutes, Faculty of Medicine

Contact persons

University Department of Neurology
Hospitals and clinical institutes, Faculty of Medicine

Local organizational units

Department of Neurology with Focus on Neurodegenerative Disorders
University Department of Neurology
Hospitals and clinical institutes, Faculty of Medicine
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