On 6 July 2017, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) announced a joint proposal to promote the use of innovative approaches to paediatric drug development. The proposal focuses on paediatric Gaucher disease, but the intention is for the principles underlying the so-called “strategic collaborative approach” to be extended to other areas of development for rare paediatric diseases.

The collaborative approach was considered necessary as, given the limited number of patients with Gaucher disease, identifying multiple candidate target products, and running multiple clinical trials, may actually hinder the development of an effective treatment.

The proposal aims to optimise paediatric drug development using the following strategies:

  • Extrapolation: Clinical data from adults and other paediatric populations can be extrapolated to the relevant disease by using appropriate modelling and simulation techniques, to predict how a medicine may work in children. However, extrapolation of efficacy data can only be considered when the course of the disease and the expected response to a medicinal product is sufficiently similar in the paediatric and reference population. It is important to consider different mechanisms of action, disease modifying factors, and epigenetic factors that may result in different presentation of a disease. The EMA is expected to publish a reflection paper that will outline a systematic approach to extrapolation of data in Q4 of 2017.
  • Multi-company trials: Designing multi-arm, multi-company development programmes whereby using the same control arm to compare more than one medicine under evaluation is recommended. EMA and FDA established regulatory pathways (such as parallel scientific advice) could be used to facilitate such a study.
  • Pooled knowledge: Existing knowledge can be used to design studies with a clear description of the main inclusion criteria, age groups, efficacy end-points, and duration. For example, it is possible to use safety and risk considerations to determine whether specific mitigation, such as staggered age group enrollment, is necessary, and to identify potential issues such as differences in product quality, manufacturing, immunogenicity, and pharmacokinetics early in the paediatric development.

These techniques are intended to reduce the total number of children included in trials, thereby reducing the burden on patients and their families, while maintaining high-quality standards for medicine development. It is stated that the proposal is not meant to be exhaustive, but is intended to stimulate exploration and discussion of these new approaches to aid drug development.