Regulatory Science Programme

A variety of projects are currently running within the MEB in close collaboration with academic partners and institutes. In addition, the MEB takes part in several IMI- and Horizon20/20 projects. The main projects are provided with their working titles and contact persons. Several projects refer to the PhD trajectories. Other, smaller projects are in the process of being upscaled to this end. It is the MEB’s goal to be maximally transparent in its research programme, to become visible and share views on a variety of topics.

Programme description

1.1 3R Support

1.1.1. Registry for efficacy models
Refinement of animal efficacy models towards transition to ‘animal free drug development’. A project commissioned by the Ministry of Health, Welfare and Sports and the Ministry of Economics with the objective of policy change in Europe. The project is a collaboration between UU (Prof. dr. H. Schellekens, Prof. dr. E. Moors) and the MEB and has an advisory board with stakeholders from various parties, public and private.
Contact person: Dr. P.J.K. van Meer; p.v.meer@cbg-meb.nl

1.1.2. Two species selection
Reduction and Refinement of pre-clinical regulatory requirements in the application dossier. A project in collaboration with the National Institute of Public Health (RIVM) with the objective to reduce redundancy of animal studies for reproductive toxicity testing in the registration dossier.
Contact person: Dr. J.W. van der Laan, jw.vd.laan@cbg-meb.nl

1.1.3. Predicting carcinogenicity
Reduction and Replacement of animal studies through innovative models and modelling. A project in collaboration with Leiden University (Prof. dr. B. van de Water).
Contact person: Dr. J.W. van der Laan, jw.vd.laan@cbg-meb.nl

1.1.4. In vitro vaccine models
This project is in collaboration with Utrecht University (Prof. dr. W. van Eden) and aims at building efficacy/safety models for the development of new vaccines.
Contact person: Dr. M.H.N. Hoefnagel, mh.hoefnagel@cbg-meb.nl

1.1.5. Ancillary 3R projects
1.1.5.1. Predicting dependence and abuse in psychotropic drugs.
A project investigating the need for animal and human laboratory studies during drug development.
Contact person: Dr. C.C. Gispen-de Wied, cc.gispen@cbg-meb.nl

1.1.5.2. Comparison of 1 month vs 6 month repeat dose toxicity studies in non-human primates: what duration is ideal?
Contact person: Dr. P.J.K. van Meer, p.v.meer@cbg-meb.nl

1.1.5.3. The outcome of Juvenile toxicology studies in the development of psychotropic drugs; what do they deliver?
A project in collaboration with the Safety Working Party, EMA.
Contact person: Dr. J.W. van der Laan, jw.vd.laan@cbg-meb.nl

2.1 Adaptive pathways

2.1.1. Identifying the best model registry for orphan drugs
A project in collaboration with UMC Utrecht Julius Center (Prof. dr. A. Hoes, dr. M. van den Berg) to categorise in what context regulators request registries, and to what extent data collection can be used multipurpose in the early clinical stage of drug development; an example of the Factor VIII registry.
Contact person: Drs. C. Jonker, c.jonker@cbg-meb.nl

2.1.2. Legal basis of stakeholder driven applications
This project starts in 2016 in collaboration with Utrecht University. With the patient becoming an important stakeholder in the drug development process, the project has the objective of investigating whether other parties than pharmaceutical industry can bring drugs on label or change label information based on data available in the public domain. The project builds on experience from previous research on legal aspect drug regulation.
Contact person: Drs. M.K. Polano, mk.polano@cbg-meb.nl, and Dr. A.M.G. Pasmooij, am.pasmooij@cbg-meb.nl

2.1.3. Personalized medicine and biomarkers
This project starts in 2016 and has the objective of investigating the implication of different personalised medicines issues for drug regulation. Collaborating parties are EMA and HSA Singapore.
Contact person: Dr. A.M.G. Pasmooij, am.pasmooij@cbg-meb.nl, Dr. V. Stoyanova, v.stoyanova@cbg-meb.nl , and Dr. M. Maliepaard, m.maliepaard@cbg-meb.nl

2.1.4. Levels of knowledge vs acceptable risks
The aim of this project is to understand differences in level of knowledge and uncertainties between products that follow new (adaptive) pathways vs. standard MA at time of authorisation; to describe methods used by regulators to determine the level of uncertainty and to decide upon ways to decrease uncertainties in the post-marketing phase. The project is a collaboration between Utrecht University (Prof. dr. H.G.M. Leufkens) and the MEB.
Contact person: Dr. M. de Bruin, M.L.deBruin@uu.nl

2.2 Safe (Bio)Generics

2.2.1. Interchangeability
This project investigates the validity of the generic drug principle, i.e. demonstrating bioequivalence to the innovator drug, and the potential of drifting from the innovator. The project is in collaboration with Maastricht University (Prof. dr. C. Neef), and is followed up by project 2.2.2.
Contact person: Drs. A. Yu, a.yu@cbg-meb.nl and Dr. M. Maliepaard, m.maliepaard@cbg-meb.nl

2.2.2. Personalized modelling of generic exchange
The project is a continuation of 2.2.1. and focusses on how to predict the optimal use of generics through modelling techniques. A collaboration between Maastricht UMC (Prof. dr. C. Neef), and the Radboudumc (Prof. dr. D. Burger) and the MEB.
Contact person: Dr. M. Maliepaard, m.maliepaard@cbg-meb.nl, and Drs. P. Glerum, p.glerum@cbg-meb.nl

2.3 Optimised clinical trials

2.3.1. Enriched methods
2.3.1.1. The effect of run-in on outcome
This project is part of a larger project using study- and individual patient data of clinical trials with psychotropic drugs (see also 2.3.2). It investigates how enrichment affects treatment outcome and generalizability of data in specific in psychotropic drug trials. A collaboration with the University of Groningen and the Academic Medical Center, AMC, Amsterdam.
Contact person: Dr. D. Luijendijk, h.j.luijendijk@umcg.nl, and Dr. C.C. Gispen-de Wied, cc.gispen@cbg-meb.nl

2.3.1.2. Subgroups in RCT
The project investigates statistical plausibility of defining and analyzing subgroups in clinical trials. A collaboration with the UMC Utrecht Julius Center (Prof. dr. K. Roes).
Contact person: Dr. S. Teerenstra, s.teerenstra@cbg-meb.nl

2.3.2. Trial characteristics
This project bridges with 2.3.1.1. and investigates the impact of geographic variation on trial outcome, placebo response and other factors affecting outcome in schizophrenia and bipolar disorder using IPD, in collaboration with the AMC (Prof. dr. D. Denys).
Contact person: Dr. T. Wohlfarth, t.wohlfarth@cbg-meb.nl and tk.mattila@cbg-meb.nl

2.3.3. Efficacy vs Effectiveness
Do orphan drugs deliver in clinical practice? This question is key in this project, which analyzes whether outcome measures at market access correspond to outcome in clinical practice in retrospect. A collaboration between the AMC (Prof. Dr. C. Hollak) and the MEB.
Contact person: Dr. M. Biegstraaten, m.biegstraaten@amc.uva.nl, and Dr. V. Stoyanova, v.stoyanova@cbg-meb.nl

2.3.4. Ethical bridging in the Health Chain
This project is a collaboration between the UMC Utrecht Julius Center (Prof. dr. H. van Delden), the inspectorate (IGJ), the CCMO, and the MEB with support of EMA to describe and discuss how to deal with ethical issues in clinical trials. Based on the better understanding of what should be regarded an ethical issue, solutions are proposed in the context of stakeholder responsibilities.
Contact person: Dr. N.S. Breekveldt-Postma, ns.breekveldt@cbg-meb.nl

3.1 Patient safety

3.1.1. Communicating risk
The project is a continuation of a former project on this topic in collaboration with the University of Groningen (Prof. dr. P. Denig), and investigates how risk information is perceived by health care professionals. Which indicators can be identified to improve communication?
Contact person: Dr. P. Mol, p.mol@cbg-meb.nl

3.1.2. Minimizing risk
In the context of the new Pharmacovigilance legislation (2012), the reliance on post-marketing surveillance tools is increasing. Effective tools are the core of regulatory requests and need to be feasible in clinical practice. The project is a collaboration with the Erasmus University Rotterdam, EUR (Prof. dr. M. Sturkenboom).
Contact person: Dr. S.M. Straus, sm.straus@cbg-meb.nl

3.1.3. Preventing medication errors
This project connects to the previous one 3.1.2. and aims at qualifying and quantifying the problem of medication errors and its assessment under the new Pharmacovigilance legislation. Collaborating parties are the Erasmus University Rotterdam, EUR (Prof. dr. M. Sturkenboom) and EMA.
Contact person: Dr. S.M. Straus, sm.straus@cbg-meb.nl

3.1.3. Tailored management of biologics
The project is a continuation of previous research into the safe use of biopharmaceuticals, including biosimilars. How should they be differently treated from a regulatory point of view compared to small molecules, do we always know how to trace back the product in case of ADR? These questions and more are the core of this project in collaboration with Utrecht University (Prof. dr. H.G.M. Leufkens). The project bridges with the program Safe (Bio)Generics 2.2.
Contact person: Dr. M. de Bruin, M.L.deBruin@uu.nl

3.1.4. Signal detection
The project connects 3.1.2 and investigates how safety signals can be qualified and quantified and extracted from large databases for proper safety management. Collaborating parties are the Erasmus University Rotterdam, EUR (Prof. dr. M. Sturkenboom) and EMA.
Contact person: Dr. S.M. Straus, sm.straus@cbg-meb.nl

3.1.5. Ancillary Patient safety projects
3.1.5.1. Tablet splitting

Several projects investigate the need for correct tablet splitting as quality index for medication use in special populations.
Contact person: Dr. D.A. van Riet-Nales, da.v.riet@cbg-meb.nl

3.1.5.2. Inform Elderly
The project is in collaboration with EPHOR and aims at collecting data that is less visible from the drug dossier for elderly in specific.
Contact person: Dr. P.A.F. Jansen, p.a.f.jansen@umcutrecht.nl

3.2 Fair access

3.2.1. Medicines shortages
The project is a collaboration between KNMP and MEB. Medicines shortages are a threat to society at times that medical demands are high. The various reasons for shortages as well as its consequences need thorough investigation to identify potential solution within the regulatory framework.
Contact person: Drs. D.J. Postma, D.J.Postma@knmp.nl

3.2.2. Human rights perspective
This project connects to 2.3.4. and 2.1.2. and investigates legal aspects of access to medicines over the drug life-cycle from an ethical and human rights perspective. With the empowerment of patients in a global drug development scenario, regulatory decisions and policy making are in need of these ancillary disciplines. A collaboration between Utrecht University (Prof. dr. M. Düwell) and the MEB.
Contact person: M.E.C. Gispen, LL.M, m.e.c.gispen@uu.nl and Dr. P.J.K. van Meer, p.v.meer@cbg-meb.nl

4.1 Ancillary

4.1.1. Regulatory Repository
This project aims at building a database of registered drugs for regulatory learning, connect and safeguard data from regulatory science projects for enhanced regulatory learning.
Contact person: Dr. P.J.K. van Meer, p.v.meer@cbg-meb.nl, and Dr. P. Mol, p.mol@cbg-meb.nl