Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines

Deliverables

DEC plan 1

Plan for dissemination and exploitation including communication activities & update

Project Risk and Quality Management Plan

Procedures for risk monitoring and evaluation throughout the project, including a risk register

DPM model for BPD

Mature DPM model is validated and ready for use in BPD

PMX models for paediatric extrapolation

Mature PMX and hybrid models are validated and ready for paediatric extrapolation

Repository

Repository of key drug development questions, related data and methods created

PMX and hybrid models for SCD and thalassemia

Mature PMX and hybrid models are validated and ready for use in SCD and thalassemia

UISS model for ataxia

Mature UISS model is validated and ready for use in AT

DEC plan 2

Plan for dissemination and exploitation including communication activities & update

Website Creation

A websitewill be created to dissiminate the result of the project

AI-based platform DRE

AI-based tools are developed to identify relevant data sources (automation of data searching, structuring and formatting) and data analysis

Publications

Unlocking the Mysteries of Rare Disease Drug Development: A Beginner's Guide for Clinical Pharmacologists

Author(s): Mariam A. Ahmed, Bilal AbuAsal, Jeffrey S. Barrett, Karim Azer, Yuen Yi Hon, Salwa Albusaysi, Elizabeth Shang, Meng Wang, Maria Burian, Noha Rayad
Published in: Clinical and Translational Science, Issue 18, 2025, ISSN 1752-8054
Publisher: Wiley
DOI: 10.1111/CTS.70215

Why Pediatric <scp>CAR</scp> ‐T Therapies Still Lag Behind: Insights from Six Treatments Centrally Approved in Europe

Author(s): Lisa Hanquet, Jean‐Michel Dogné, Flora T. Musuamba
Published in: Clinical Pharmacology & Therapeutics, Issue 120, 2026, ISSN 0009-9236
Publisher: Wiley
DOI: 10.1002/CPT.70299

Modeling and Simulation in Development and Regulatory Approval of Chimeric Antigen Receptor T‐Cell Therapies: An Analysis of European Medicines Agency Centralized Procedures From 2018 to 2024

Author(s): Lisa Hanquet, Jean‐Michel Dogné, Flora T. Musuamba
Published in: CPT: Pharmacometrics & Systems Pharmacology, Issue 15, 2026, ISSN 2163-8306
Publisher: Wiley
DOI: 10.1002/PSP4.70213

Advancing the frontier of rare disease modeling: a critical appraisal of in silico technologies

Author(s): Francesca Pistollato, Fabia Furtmann, Lindsay J. Marshall, Surat Parvatam, Jan Turner, Flora Tshinanu Musuamba, Giulia Russo, Francesco Pappalardo
Published in: npj Digital Medicine, Issue 8, 2025, ISSN 2398-6352
Publisher: Springer Science and Business Media LLC
DOI: 10.1038/S41746-025-02068-1

Assessment and Benchmarking of Model Informed Approaches in Drug Development for Hemoglobinopathies: A Review of Scientific Advices From January 2000 to December 2024

Author(s): Grace Shalom Govere, Jean‐Michel Dogné, Flora Musuamba
Published in: CPT: Pharmacometrics & Systems Pharmacology, Issue 15, 2026, ISSN 2163-8306
Publisher: Wiley
DOI: 10.1002/PSP4.70192

Model informed assessment of QT prolongation during drug development: a five-year retrospective analysis of EMA scientific advices

Author(s): Happy Phanio Djokoto, Jean-Michel Dogné, Flora T. Musuamba
Published in: Journal of Pharmacokinetics and Pharmacodynamics, Issue 53, 2026, ISSN 1567-567X
Publisher: Springer Science and Business Media LLC
DOI: 10.1007/S10928-025-10018-3

Innovations and Best Practices for Therapeutic Development in Pediatric Rare Diseases: A Model‐Informed Drug Development Perspective

Author(s): Rajesh Krishna, Satyendra Suryawanshi, Juliane Rascher, Sonja Hartmann, Bernard Sebastien, Jeffrey S. Barrett
Published in: Clinical Pharmacology & Therapeutics, 2025, ISSN 0009-9236
Publisher: Wiley
DOI: 10.1002/CPT.3683

Pharmaceutical Research

Author(s): Happy Phanio Djokoto; Lara Ernst; Jean-Michel Dogné; Flora T. Musuamba
Published in: Pharmaceutical Research, 2026, ISSN 0724-8741
Publisher: Springer Nature
DOI: 10.1007/S11095-026-04033-3

AI‐Driven Applications in Clinical Pharmacology and Translational Science: Insights From the ASCPT 2024 AI Preconference

Author(s): Mohamed H. Shahin, Prashant Desai, Nadia Terranova, Yuanfang Guan, Tomáš Helikar, Sebastian Lobentanzer, Qi Liu, James Lu, Subha Madhavan, Gary Mo, Flora T. Musuamba, Jagdeep T. Podichetty, Jie Shen, Lei Xie, Mathew Wiens, Cynthia J. Musante
Published in: Clinical and Translational Science, Issue 18, 2025, ISSN 1752-8054
Publisher: Wiley
DOI: 10.1111/CTS.70203

European Journal of Drug Metabolism and Pharmacokinetics

Author(s): Camille Massaux; Jean-Michel Dogné; Flora Tshinanu Musuamba
Published in: European Journal of Drug Metabolism and Pharmacokinetics, 2026, ISSN 0378-7966
Publisher: Springer Nature
DOI: 10.1007/S13318-026-00988-1

A review on the role of extrapolation as basis for paediatric marketing authorization applications of medicines in the EU

Author(s): Charlotte W. M. Simons, Loes C. H. Maton, Maaike van Dartel, Michiel van den Heuvel, Loes den Otter, Carolien Versantvoort, Pieter J. Colin, Jeroen V. Koomen
Published in: British Journal of Clinical Pharmacology, Issue 91, 2025, ISSN 0306-5251
Publisher: Wiley
DOI: 10.1111/BCP.16395

Use of Modeling and Simulation to Inform the Development of Monoclonal Antibodies to Treat Moderate‐to‐Severe Asthma: A Retrospective Review of <scp>EMA</scp> Centralized Procedure From 2014 to 2024

Author(s): Hélène Haguet, Jean‐Michel Dogné, Flora T Musuamba
Published in: CPT: Pharmacometrics & Systems Pharmacology, Issue 15, 2026, ISSN 2163-8306
Publisher: Wiley
DOI: 10.1002/PSP4.70222

APPLICATION OF PHARMACOKINETIC MODELING AND SIMULATION IN THE BIOEQUIVALENCE ASSESSMENT OF GENERIC DRUGS: THE CASE OF LUMEFANTRINE

Author(s): KILELA Songela Reagan ,, Helene Haguet Haguet , Lisa Hanquet , Happy Phanio Djokoto , Grace Shalom Govere , Adrien Olama , Camille Massaux , Lisa Wellin , Jean-Michel Dogné , Flora MUSUAMBA ,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Advancing sample size justifications in confirmatory paediatric exposure-matching trials submitted to regulatory authorities: a benchmarking analysis and novel methodological framework.

Author(s): Loes Maton ,, Pieter Colin ,, Jeroen Koomen ,, Douglas Eleveld , Efthymios Manolis , Roberto de Lisa
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Model-based meta-analysis of paracetamol dose-response in pediatric tonsillectomy pain

Author(s): Orestis Papatryfonos, Anna Largajolli, Li Qin, Michael Chappell Amy Cheung
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

MODEL-INFORMED APPROACHES FOR PEDIATRIC TYPE 2 DIABETES EVIDENCE GENERATION: INSIGHTS FROM A MODEL-BASED LONGITUDINAL HBA1C META-ANALYSIS FROM EMA MARKETING AUTHORIZATION APPLICATIONS

Author(s): Pieter Colin, Efthymios Manolis, Jeroen Koomen
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Population pharmacokinetics of aprocitentan and dose rationale for paediatric patients aged from 2 to less than 18 years affected by pulmonary arterial hypertension.

Author(s): Anisa Khan, Oscar Della Pasqua
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

QUANTIFYING THE IMPACT OF LLOQ AND ULOQ CENSORING ON M3 ESTIMATION PERFORMANCE IN NONMEM

Author(s): Happy Djokoto , Adrien Olama , Camille Massaux , Grace Shalom Govere , Hélène Haguet , Lisa Hanquet , Reagan Kilela Songela , Lisa Wellin , Jean-Michel Dogné ,, Flora T. Musuamba ,,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

CROSS-PRODUCT POPULATION PHARMACOKINETIC MODELING OF HAEMOGLOBIN S POLYMERIZATION INHIBITORS TO OPTIMISE PAEDIATRIC PK STUDY DESIGN USING STOCHASTIC SIMULATION-ESTIMATION

Author(s): Grace Shalom Govere ,, Jean-Michel Dogné ,, Happy Phanio Djokoto , Helene Haguet , Lisa Wellin , Adrien Olama , Lisa Hanquet , Camille Massaux , Reagan Kilela Songela , Flora T. Musuamba ,,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

The use of modeling and simulation to inform Haemoglobinopathies drug development– a review of Scientific Advices from January 2014 to December 2024

Author(s): Grace Shalom Govere, Jean-Michel Dogne, Flora Musuamba
Published in: 2025
Publisher: Population Approach Group in Europe (PAGE)

Credibility assessment of model informed drug development approaches in paediatric and rare diseases: a review of EMA submissions and assessment reports from 2014 to 2024

Author(s): Flora Musuamba Tshinanu, Ine Rusten, Helene Haguet, Lisa Hanquet, Marco Dionisi, Shalom Govere, Happy Djokoto, Camille Massaux, Jean-Michel Dogné
Published in: 2025
Publisher: Population Approach Group in Europe (PAGE)

A FIT-FOR-PURPOSE PHYSIOLOGICALLY BASED PHARMACOKINETIC APPROACH FOR INTRANASAL ANALGESICS: APPLICATION TO KETAMINE AND FENTANYL ANALOGS

Author(s): Adrien Olama , Jean-Michel Dogné ,, Happy Phanio Djokoto , Grace Shalom Govere ,, Hélène Haguet , Lisa Hanquet , Camille Massaux , Lisa Wellin , Flora Musuamba Tshinanu ,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Use of modeling and simulation to inform the development of monoclonal antibodies to treat moderate-to-severe asthma: a review of EMA centralized procedure from 2014 to 2024.

Author(s): Helene Haguet, Jean-Michel Dogne, Flora Musuamba
Publisher: Population Approach Group in Europe (PAGE)

Reconstruction of an Advanced Dissolution, Absorption, and Metabolism (ADAM) Model in R: Structural Comparison with Simcyp and PK-Sim

Author(s): Camille Massaux , Flora Musuamba ,,, Jean-Michel Dogné ,, Happy Djokoto , Lisa Hanquet , Lisa Wellin , Grace Shalom Govere
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

A Translational Multiscale Model Integrating Immune Response, Bacterial Dynamics, and Lung PBPK to Predict Tuberculosis Treatment Response

Author(s): Vasileios Chronopoulos ,, Periklis Tsiros ,, Aristeidis Dokoumetzidis ,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Development of a Population PK-PD Model for Tapentadol to Assess Postoperative Pain in Children Aged 6 to <12 using Nonlinear Mixed-Effects Modelling

Author(s): Orestis Papatryfonos, Linda Wanika, Amy Cheung, Michael Chappell
Published in: 2025
Publisher: Population Approach Group in Europe (PAGE)

MODEL-BASED META-ANALYSIS POPULATION PK MODELING OF ANTI-IL-5(RΑ) MONOCLONAL ANTIBODIES TO OPTIMIZE PEDIATRIC STUDY DESIGN USING STOCHASTIC SIMULATION-ESTIMATION

Author(s): Helene Haguet , Happy Phanio Djokoto , Jean-Michel Dogne ,, Grace Shalom Govere ,, Lisa Hanquet , Reagan Kilela Songela , Majad Mansoor , Camille Massaux , Adrien Olama , Lisa Wellin , Flora Musuamba ,,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Operationalizing the ERAMET Digital Research Environment (DRE) – Building the Ecosystem

Author(s): Ine Skottheim Rusten, Flora Musuamba, Michael Chappell, Amy Cheung, Alicia Gibson, Jeff Barrett
Publisher: Population Approach Group in Europe (PAGE)

Paediatric dosing regimen of tetrabenazine: A case study on the credibility and evaluation of paediatric and rare disease models

Author(s): Linda Wanika, Ine Skottheim Rusten, James Kermode, Amy Cheung, Mike Chappell
Published in: 2024
Publisher: PKUK

Qualification of decision tables for selecting accurate paediatric drug clearance scaling methods

Author(s): Emily Ratcliffe, Elke H.J Krekels, An Vermeulen, Catherijne A.J Knibbe, Amy Cheung, Michael Chappell
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Towards Developing a Harmonizing Framework for PK and/or PKPD Scaling for Pain Medications in the Pediatric Population

Author(s): Soumya Perinparajah, Sophie Rhodes, Yin Edwards, Anna Largajolli, Li Qin, Elke H.J. Krekels, Yu-Wei Lin, Justin Hay, Piet van der Graaf, S.Y. Amy Cheung
Published in: 2025
Publisher: Population Approach Group in Europe (PAGE)

CAR-T PERSISTENCE MODELLING: BRIDGING BIOLOGY AND DATA

Author(s): Lisa Hanquet , Happy Phanio Djokoto , Jean-Michel Dogné ,, Grace Shalom Govere ,, Hélène Haguet , Camille Massaux , Adrien Olama , Lisa Wellin , Flora Musuamba Tshinanu ,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

A review on the role of extrapolation as basis for paediatric marketing authorization applications of medicines in the EU

Author(s): Charlotte Simons, Loes Maton, Maaike van Dartel, Michiel van den Heuvel, Loes den Otter, Carolien Versantvoort, Pieter Colin, Jeroen Koomen
Published in: 2025
Publisher: Population Approach Group in Europe (PAGE)

Model informed drug development and CAR-T cells : A review of their use and credibility assessment in the context of EMA centralized procedures

Author(s): Lisa Hanquet, Jean-Michel Dogne, Flora Musuamba
Publisher: Population Approach Group in Europe (PAGE)

Credibility assessment of model informed drug development (MIDD) in pediatric pain: a review of pediatric investigation plans from 2008 to 2024

Author(s): Marco Dionisi, Jean-Michel Dogné, Flora Musuamba
Published in: 2025
Publisher: Population Approach Group in Europe (PAGE)

POPULATION PHARMACOKINETIC MODELLING TO SUPPORT BIOEQUIVALENCE ASSESSMENT OF GENERIC DRUGS: AN ILLUSTRATIVE SIMULATION STUDY USING AMODIAQUINE.

Author(s): Lisa Wellin , Happy Phanio Djokoto , Grace Shalom Govere ,, Hélène Haguet , Lisa Hanquet , Reagan Kilela Songela , Camille Massaux , Adrien Olama , Jean-Michel Dogné ,, Flora T.  Musuamba ,
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Constructing the ERAMET Digital Research Environment (DRE)

Author(s): Jeff Barrett, Flora Musuamba Tshinanu, Ine Skottheim Rusten, Scott Russell, Kara Lasater, Alicia Gibson, David Sibbald
Published in: 2024
Publisher: Population Approach Group in Europe (PAGE)

Paediatric pharmacokinetic studies could be optimized for the precision of the clinically relevant exposure endpoint instead of PK parameter precision

Author(s): Pyry Valitalo, Elke H.J. Krekels, YuWei Lin, Stephen Duffull, S.Y. Amy Cheung
Published in: 2026, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Uncertainty quantification in Mixed effects modelling

Author(s): Linda Wanika, Ine Skottheim Rusten, James Kermode, Mike Chappell
Published in: 2025, ISSN 1871-6032
Publisher: Population Approach Group in Europe (PAGE)

Deliverables

Publications

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