Children are not just small adults, which is part of the reason why developing paediatric drugs is not easy. Most medicines are designed for and tested in adults, and then prescribed to children off-label. In particular, there is a lack of medicines for infants aged 0–2 years. There are a variety of reasons for this shortage — mostly relating to the ethical, regulatory and practical issues associated with testing new drugs in infants. Most parents, for instance, would not want new drugs to be tested on their children!
But infants need medicines so a solution has to be found. In Europe, the development of paediatric medicines has just been bolstered with a research grant of 1.2 million euro, which will go towards a programme called PAMPER (Pharmaceutical Accelerator Mass Spectrometry Microdose Pediatric Evaluation Research Study), which will investigate new ways of developing drugs for infants. A number of research organisation across Europe are involved in this project, including the Netherlands-based research organisation TNO, the University of Liverpool (UK), Alder Hey Children’s Hospital (UK), Tartu University Hospital (Estonia), the Pharmaceutical Research Institute (Poland), Good Clinical Practice Alliance (Belgium) and Garner Consulting (UK). The funding was awarded through the PRIOMEDCHILD ERA-NET programme.
As the programme title suggests, the focus of the study will be on microdosing. To find out more, I spoke with Wouter Vaes, who is responsible for early clinical development at the TNO.
“Children are not just small adults,” said Vaes. “Drug kinetics, metabolism and dynamics can vary substantially between adults and infants. Therefore, it is complex to derive effective but safe starting doses of drug candidates in pediatric clinical trials.”
Which is why microdosing is such an exciting development in this area. Microdosing involves administering a very small dose of a drug (defined by the European Medicines Agency as less than 1/100th of the pharmacologically active dose), which is unlikely to lead to clinically significant toxicity. Microdisng is not supposed to explore therapeutic effect; rather, it provides data about a drug’s pharmacokinetics and pharmacodynamics in humans at a very early stage of development.
“Microdosing is one of the best tools that industry can choose to obtain human data at early stage in development,” said Vaes. “We expect an increase in the use of microdosing, especially as a tool for candidate selection.”
The aim of the PAMPER study is to validate the microdoisng technology to obtain pharmacokinetic data that can, in the future, be used to study new drugs in infants.
“Eventually, we expect that microdosing will be used to derive kinetic and metabolic information for all age groups at the same time,” explained Vaes. “This information can be used to derive appropriate dosing regimes for further pediatric investigations. One of the important issues that the consortium will address is to develop methodology to determine the extremely low concentrations in tiny blood samples using the accelerator mass spectroscopy at the TNO.”
Although it’s still early days, the consortium hopes that the research will lead to safer tools that enable better, faster paediatric clinical investigations, as well as better labelling and less off-label use. The fact that the research could have such a huge impact on drug discovery and the resulting approved medicines is a testament to the value that research consortiums can bring.
“Precompetitive research is essential for the validation and subsequent application of new technologies and ideas,” said Vaes. “To increase the acceptance of new technological advancements that might lead to better drugs should be a joined effort between industry, governments, regulators and research institutes.”