Rare disease use of clinical trial simulation for the chioce and optimization of study designs/Priomedchild Call/ER
Lead Research Organisation:
University of Manchester
Department Name: UNLISTED
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).
People |
ORCID iD |
Leon Aarons (Principal Investigator) |
Publications
Cornu C
(2013)
Experimental designs for small randomised clinical trials: an algorithm for choice.
in Orphanet journal of rare diseases
Darwich AS
(2017)
IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3: Identifying gaps in system parameters by analysing In Silico performance across different compound classes.
in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Darwich AS
(2017)
Why has model-informed precision dosing not yet become common clinical reality? lessons from the past and a roadmap for the future.
in Clinical pharmacology and therapeutics
Eymard N
(2018)
Mathematical model of T-cell lymphoblastic lymphoma: disease, treatment, cure or relapse of a virtual cohort of patients.
in Mathematical medicine and biology : a journal of the IMA
Hansmann S
(2016)
Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models.
in The Journal of pharmacy and pharmacology
Lavielle M
(2016)
What do we mean by identifiability in mixed effects models?
in Journal of pharmacokinetics and pharmacodynamics
Margolskee A
(2017)
IMI - oral biopharmaceutics tools project - evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds.
in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Margolskee A
(2017)
IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results.
in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Margolskee A
(2016)
Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions.
in The AAPS journal
Martin EC
(2016)
Accounting for dropout in xenografted tumour efficacy studies: integrated endpoint analysis, reduced bias and better use of animals.
in Cancer chemotherapy and pharmacology
Ogungbenro K
(2014)
A physiologically based pharmacokinetic model for Valproic acid in adults and children.
in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Ogungbenro K
(2015)
A physiologically based pharmacokinetic model for clobazam and stiripentol in adults and children.
in Pharmaceutical research
Ogungbenro K
(2015)
Physiologically based pharmacokinetic model for 6-mercpatopurine: exploring the role of genetic polymorphism in TPMT enzyme activity.
in British journal of clinical pharmacology
Ogungbenro K
(2014)
Physiologically based pharmacokinetic modelling of methotrexate and 6-mercaptopurine in adults and children. Part 2: 6-mercaptopurine and its interaction with methotrexate.
in Journal of pharmacokinetics and pharmacodynamics
Ogungbenro K
(2015)
Empirical and semi-mechanistic modelling of double-peaked pharmacokinetic profile phenomenon due to gastric emptying.
in The AAPS journal
Ogungbenro K
(2014)
Physiologically based pharmacokinetic modelling of methotrexate and 6-mercaptopurine in adults and children. Part 1: methotrexate.
in Journal of pharmacokinetics and pharmacodynamics
Olivares-Morales A
(2015)
Analysis of the impact of controlled release formulations on oral drug absorption, gut wall metabolism and relative bioavailability of CYP3A substrates using a physiologically-based pharmacokinetic model.
in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Olivares-Morales A
(2016)
Development of a Novel Simplified PBPK Absorption Model to Explain the Higher Relative Bioavailability of the OROS® Formulation of Oxybutynin.
in The AAPS journal
Tsamandouras N
(2015)
Incorporation of stochastic variability in mechanistic population pharmacokinetic models: handling the physiological constraints using normal transformations.
in Journal of pharmacokinetics and pharmacodynamics
Tsamandouras N
(2017)
Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population.
in Pharmacogenetics and genomics
Tsamandouras N
(2015)
Development and Application of a Mechanistic Pharmacokinetic Model for Simvastatin and its Active Metabolite Simvastatin Acid Using an Integrated Population PBPK Approach.
in Pharmaceutical research
Wendling T
(2015)
Model-based evaluation of the impact of formulation and food intake on the complex oral absorption of mavoglurant in healthy subjects.
in Pharmaceutical research
Wendling T
(2016)
Reduction of a Whole-Body Physiologically Based Pharmacokinetic Model to Stabilise the Bayesian Analysis of Clinical Data.
in The AAPS journal
Wendling T
(2016)
Predicting survival of pancreatic cancer patients treated with gemcitabine using longitudinal tumour size data.
in Cancer chemotherapy and pharmacology
Description | IMI |
Amount | € 600,000 (EUR) |
Organisation | European Commission |
Department | Seventh Framework Programme (FP7) |
Sector | Public |
Country | European Union (EU) |
Start | 05/2012 |
End | 04/2017 |
Description | Cystic Fibrosis |
Organisation | Erasmus MC |
Country | Netherlands |
Sector | Hospitals |
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 |