Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Use of Extrapolation, Modelling & Simulation Studies in Paediatric Investigation Plans – an analysis of PIP opinions from 2007 – 2016 ***

Dr. Rita Grimm (Abschlußjahr: 2017)

Summary
Language: English
The Paediatric Regulation (EC) 1901/2006 with its mandatory demand of paediatric studies on one side and the practical constraints and ethical needs for minimizing the burden of studies in children on the other side necessitate optimal techniques in the development of safe and effective drugs of high quality in children. Extrapolation, Modelling & Simulation (E,M&S) studies are regarded as useful and promising tools which might facilitate research and drug development and alleviate regulatory burden in order to save time and costs for industry, not to delay the authorization of new medicines and to avoid to subject paediatric patients to unnecessary clinical trials. This master thesis therefore aims to systematically investigate the use of E,M&S studies in European paediatric development programs. To achieve this a comprehensive review of all opinions to paediatric investigation plans (PIP) adopted by the Paediatric Committee and archived as final versions in the database of the European Medicines Agency since the introduction of the Paediatric Regulation in 2007 until November 2016 was performed. In total 903 positive PIP opinions were analysed in regard to the bindingly agreed use of E,M&S measures. The overall frequency of E,M&S in the PIP opinions as well as the development over time was analysed and compared with former findings by Manolis et al. 2011 reflecting only the initial period of 2007-01/2010. It was investigated whether there are differences in the use of E,M&S in PIPs for orphan drugs or biological medicinal products, in different paediatric age groups or different therapeutic areas. An attempt was made to investigate which E,M&S study types were planned in detail in order to judge whether they are already used as tools to navigate through the paediatric study decision tree proposed by the FDA. An analysis was performed whether PIP applicants from different geographic regions or of different company size make different use of E,M&S models in their paediatric development programs. Encouraging examples are given how the use of E,M&S as agreed in the PIPs finally was reflected in granted marketing authorisations and their product information. Conclusions and few proposals for handling of PIP opinions, compliance check and reporting of E,M&S data for investigators and regulators were derived in order to improve and facilitate the use of Extrapolation, Modelling & Simulation in paediatric development.
Pages: 82, Annexes: pages: 6