This document was developed by a working group of the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA) 1 and sets out recommendations for discussions about clinical trial preparedness in paediatrics. Section 5 ‘Methodology’ provides an overview of the activity undertaken by the Enpr-EMA working group on trial preparedness as preparation of this document in collecting stakeholders’ points to consider. Enpr-EMA held a two-month public consultation on the draft document from September 2019 until November 2019, with the aim of identifying potential gaps and presenting a more comprehensive view. The feedback received during the consultation period has informed the final version of this document.
We define trial preparedness as a structured assessment of the key factors that could increase the likelihood of a smooth and timely course of a paediatric clinical trial, integrating information from multiple stakeholders on what is possible within individual studies and therefore also for the overall drug development plan within which a trial is embedded. This document focuses on preparedness for individual trials. However, as a development plan would normally constitute a number of trials, it is implicit that the same elements would also be relevant for preparation of a complete plan. Trial “feasibility” is the likelihood of completing a trial in a timely manner. This document moves beyond the definition of “feasibility” to present a global determination of all aspects of a trial that need to be prepared.
One significant factor of preparedness is the study design, but this is not the only influence on preparedness. By design, we mean the selection of methods to answer a research question (or set of questions such as biostatistics, Model Informed Drug Discovery and Development (MID3), extrapolation). When working with the paediatric population, it is essential to establish explicitly the rationale of the benefit of the research question for children. In parallel, trial design needs to take account of the specificities of neonates, infants, children and young people while maximising the use of extant data (including preclinical data such as toxicity) and minimising the burden of research in these populations. There are many sources describing details specific to the design of paediatric development programmes and trials such as ICH E8 (R1) (General considerations for clinical studies) as well as national legislations.
Trial preparation should be initiated before, and conducted in parallel to, the designing of the development plan and the individual trials, and in parallel to ‘sponsor readiness’. The latter describes a collection of measures taken by a sponsor to allow them to open and conduct a clinical trial and promote efficiency while complying with applicable laws and regulations and ethical principles.
The recommendations in this document target both sponsors as well as investigators. However, it should be noted that, whereas trial preparedness has implications for ‘sponsor readiness’ (see 3.2.4), this document does not describe all aspects of ‘sponsor readiness’, such as operational aspects within sponsors and intermediary organisations, e.g. Contract Research Organisations (CRO), or strategic factors, such as patient needs and economic opportunities (see ICH E6(R2) Guideline for good clinical practice).
Furthermore, activities relevant to development of age-appropriate formulations to pharmaceutical quality standards (including Chemistry, Manufacturing, and Controls (CMC)), as well as activities to support marketing of products using data about market size are important factors influencing paediatric trials but are out of scope of this document.
Standards to be proposed for site readiness and practical arrangements for sites and participants relating to the preparation of drug development plans and clinical trials are in progress by other initiatives.
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