Rare disease use of clinical trial simulation for the chioce and optimization of study designs/Priomedchild Call/ER

Lead Research Organisation: University of Manchester

Abstract

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Technical Summary

Background: Rare diseases are defined based on their low incidence, less than one in 2,000. Whereas randomized controlled trials (RCTs) are currently the gold standard for drug evaluation, there is still no general validated approach for the assessment of (orphan) drugs in this field.|Objectives of the CRESim (Child-Rare-Euro-Simulation) project: To develop a platform performing trial modelling and simulation in order to identify optimal trial designs in children for the evaluation of (orphan) drugs tailored to different types of rare diseases.|Methods: In silico approach using RCT modelling and Monte Carlo simulation, implemented for different categories of rare diseases in pediatrics. Several RCTs with different experimental designs will be modelled and simulated, and the different designs will be compared in terms of trial duration and precision of the estimation of the treatment effect.|Expected Outcomes: Improvement and optimization of the development of new orphan drugs.|Dissemination of results: Dissemination will target those involved in drug development (i.e pharmacologists, therapeutic specialists, methodologists and statisticians), and in drug registration (public health decision makers), and registration authorities (EMEA and national agencies).

Publications

10 25 50
 
Description IMI
Amount € 600,000 (EUR)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 06/2012 
End 04/2017
 
Description Cystic Fibrosis 
Organisation Erasmus University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution Jointly we have developed a KPD model for DNase alpha.
Collaborator Contribution They performed the literature revied and provided some data for model validation.
Impact KPD model for DNAse alpha
Start Year 2011
 
Description Dravet Syndrome 
Organisation University of Lyon
Department Department of Clinical Pharmacology
Country France 
Sector Academic/University 
PI Contribution Jointly we have developed a minimum PBPK to desribe the PK of clobazam, stiripentol and valproate
Collaborator Contribution They have reviewed the model with some imputs into the structural model
Impact A minimal PKPK model for clobazam, stiripentol and valproate.
Start Year 2011
 
Description Lymphoma 
Organisation University of Lyon
Department Department of Clinical Pharmacology
Country France 
Sector Academic/University 
PI Contribution A framework for the development of minimal PBPK model for methotrexate and mercaptopurine
Collaborator Contribution Feedback on the structural model
Impact A minimal PBPK model for Methotrexate and Mercaptopurine
Start Year 2012