The European Medicines Agency (EMA) has published a preliminary version of its draft reflection paper which outlines a framework for the extrapolation of clinical trialdata from adults to children to support the authorisation of new medicines for children.
Extrapolation of data aims to optimise the involvement of children in clinical studies, one of the objectives of the European Union Paediatric Regulation, by predicting how a medicine may work in children and adolescents on the basis of studies conducted in adults or other paediatric populations.
The draft reflection paper outlines a systematic approach to extrapolation of data from adults or other paediatric populations to children that is considered scientifically sound and reliable to support the authorisation of a medicine. The framework sets out when, to what extent, and how extrapolation can be applied and validated.
The principal steps of the extrapolation framework are:
- Extrapolation concept: this consists of a systematic synthesis of all available data, including the use of modelling and simulation approaches, which aims to predict the differences with regard to pharmacokinetics/pharmacodynamics, disease progression, and clinical response to treatment between adults and children;
- Extrapolation plan: this aims to propose optimal studies in the paediatric population in line with predictions identified by the extrapolation concept;
- Confirmation and extrapolation: this phase aims to confirm the extrapolation concept on the basis of the data collected in children and adults. If the extrapolation concept cannot be fully confirmed, it should be updated and the extrapolation plan revised accordingly;
- Mitigating uncertainty and risk: the limited data generated in the paediatric population may not be sufficient to resolve all uncertainties and assumptions of the extrapolation concept by the time of marketing authorisation. Additional follow-up data may be necessary to address uncertainties and to further evaluate assumptions. Measures to generate these data need to be proposed.
The draft reflection paper is the outcome of extensive work and consultation with statisticians, experts in modelling and simulation, experts in pharmacology and clinicians.
The reflection paper was developed to communicate the current status of discussions on extrapolation of data. It will provide a framework for discussion or clarification particularly in areas where scientific knowledge is fast evolving or experience is limited. EMA is organising a workshop on 17-18 May 2016 to gather the views from experts and stakeholders on the topic. These discussions will contribute to the further development of the draft refection paper which is expected to be released for public consultation by the end of July 2016. The workshop will be broadcast live on the EMA website.