In order to guide our scientific activities, the MEB has identified eight themes in the MEB regulatory science policy 2020-2024, in which we will invest in the coming years. Recently, three new PhD students have started.
- Anne Taams conducts research into identifying clinical uncertainties related to innovative medicinal products during the entire drug regulatory lifecycle, which is in line with the theme Advanced Therapy Medicinal Products (ATMPs).
- Pieter Annema investigates the impact of drug recalls on patients, clinical outcomes and societal costs, which is in line with the theme Safety and effectiveness after authorisation.
- The PhD project of Loes den Otter focuses on the extrapolation between patient subpopulations (e.g. adults to young children) and settings (e.g. isolated seizure type to epilepsy syndrome).
Below you can read more about these PhD projects.
Anne Taams was trained as a pharmaceutical scientist with specialisation in drug regulatory processes at Utrecht University. During her Master studies, she conducted research in Singapore for the Health Sciences Authority and the Medicines Evaluation Board (MEB). She joined the MEB as pharmacovigilance assessor in 2020. Anne will continue her assessment work for fifty percent of the time. In addition, she will focus on this PhD project at the Division of Pharmacoepidemiology & Clinical Pharmacology of the Utrecht Institute for Pharmaceutical Sciences (UIPS), at Utrecht University. For more information or collaboration on this topic, please contact Anne via science@cbg-meb.nl.
PhD highlight: Anne Taams
“Mapping and Managing Uncertainty for Innovative Medicinal Products in Drug Regulatory Processes”
Start: 01-07-2022. End: 30-06-2027.
Promotor: Prof. Toine Egberts (Utrecht University (UU))
Co-promotors: dr. Lourens Bloem (UU), dr. Carla Herberts (MEB)
Introduction & subject
The drug regulatory system’s main objective is to promote and protect public health by evaluating and monitoring medicines on their benefit-risk profile. Regulators do so by continuously weighing treatment effects against side effects. However, assessment of innovative medicinal products such as gene or novel immunotherapies may be complex due to uncertainties stemming from their method of manufacturing, (unknown) mechanism of action, structure or formulation.
Moreover, their efficacy and safety may be complex to establish in clinical studies considering, for example, uncertainties associated with a small study population or an uncontrolled trial design. As a result, it may be increasingly challenging for regulators to assess benefits and risks of innovative medicinal products. In order to facilitate regulatory decision-making, uncertainties of innovative medicinal products require further evaluation.
Aim
The objective of this research is to identify clinical uncertainties related to innovative medicinal products during the entire drug regulatory lifecycle, thereby assessing how regulatory bodies including trial regulators assess and address uncertainties from the early clinical (phase 1) to the post-authorisation phase. This is expected to result in increased consistency of uncertainty assessments, predictability of uncertainty management and improved communication about uncertainties to other stakeholders such as patients, healthcare professionals, but also applicants and health technology assessment bodies that are responsible for reimbursement decision-making.
Pieter Annema received his master’s degree in Pharmacy at the University of Groningen. He started his hospital pharmacy residency in 2021 at the Jeroen Bosch Hospital and Radboud University Medical Center. In the beginning of 2022 he started his PhD project alongside his residency in hospital pharmacy, combining clinical practice with research. For more information, please contact Pieter via science@cbg-meb.nl.
PhD highlight: Pieter Annema
“Impact of drug recalls on patients and healthcare providers”
Start: 01-01-2022. End: 31-12-2025
Promotors: Prof. Rob van Marum (Jeroen Bosch Hospital/Vrije Universiteit), Prof. Marcel Bouvy (UU)
Co-promotor: dr. Jeroen Derijks (Jeroen Bosch Hospital)
Introduction
The production of drugs is subject to strict quality controls to prevent that patients are exposed to defective or contaminated drugs. If a product defect is discovered in a batch of drugs that is already distributed and in use by patients, the drug may be recalled. We don't really know what the effects of communicating and initiating a drug recall are. Publicity and actions surrounding a drug recall may both positively and negatively influence patient confidence in drugs, clinical outcomes related to the drug therapies and societal costs.
An increase or decrease in drug confidence may lead to a change in medication adherence which in turn impacts clinical outcomes. In addition, a forced change of a drug therapy can also affect clinical outcomes. Moreover, a drug recall impacts healthcare providers such as pharmacists and physicians and requires a significant amount of their time and money ultimately paid for by society. The potential benefits and risks of drug recalls should therefore be carefully weighed. Research into these dilemmas is absent.
Aim
The objective of this PhD project is to clarify the impact of a drug recall on patients, clinical outcomes and societal costs. The results may give insight in how to improve decision making surrounding a recall procedure.
Loes den Otter received her master’s degree in Psychology in 2013 and research master’s degree in Cognitive and Clinical Neuroscience in 2015 from Maastricht University. She has been working as a Clinical Assessor at the Medicines Evaluation Board since 2017, specialising in human medicinal products for neurological and psychiatric disorders.
From May 2022, she will continue her work as Clinical Assessor for fifty percent of the time, the other fifty percent is dedicated to conducting her PhD project. For more information, please contact Loes via science@cbg-meb.nl.
PhD Highlight: Loes den Otter
“Exploring the possibilities to support a change in the labelling of anti-seizure medication through the use of existing data”
Start: 01-05-2022. End: 30-04-2027.
Promoters: Prof. Marian Majoie (Maastricht Universitair Medisch Centrum+/Kempenhaeghe), Prof. Kees Braun (Universitair Medisch Centrum Utrecht (UMC Utrecht))
Co-promoters: dr. André Elferink (MEB), dr. Wim Otte (UMC Utrecht)
Introduction & subject
Epilepsy is one of the most common neurological diseases worldwide. Although most epilepsy patients respond favourably to treatment, 30% will continue to have seizures despite treatment with anti-seizure medications (ASMs). In the recent years, novel ASMs have been approved within the EU for the treatment of this refractory epilepsy. Supportive evidence for approval usually comes from short-term placebo-controlled studies, which evaluate the new ASM in the add-on setting within a specific patient population. As the study population and setting determine the labelling of an ASM, any additions or changes to it usually require additional studies.
Alternatively, an extrapolation approach through the use of existing data could be envisioned. However, for ASMs, this approach has only been accepted by the European Medicines Agency in specific situations. The question is whether extrapolation can be applied more broadly, thereby reducing the amount, or even eliminating the need for controlled studies to support changes in the labelling.
Aim
This PhD project aims to evaluate in which situations extrapolation of efficacy/safety data of ASMs is possible. It will focus on the extrapolation between patient subpopulations (e.g. adults to young children) and settings (e.g. isolated seizure type to epilepsy syndrome). In addition, it will investigate what data would be necessary to support a monotherapy indication, in absence of specific studies. This project will lead to a better understanding of situations in which extrapolation could be applicable to support a change in the labelling of an ASM.
