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Risk-proportionate approach to paediatric clinical trials: The legal requirements, challenges, and the way forward under the European Union Clinical Trials Regulation

Research output: Contribution to journalArticlepeer-review

Mandy Wan, Elisa Alessandrini, Paul Brogan, Despina Eleftheriou, Adilia Warris, Roger Brüggemann, Mark Turner

Original languageEnglish
Pages (from-to)17407745221093812
JournalClinical Trials
E-pub ahead of print5 May 2022

Bibliographical note

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The c4c project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 777389. Publisher Copyright: © The Author(s) 2022.

King's Authors


BACKGROUND: It is now widely accepted that there is a need for safety and efficacy data on medicines used in children. In the European Union, legislation has provided the necessary framework obligating and incentivizing pharmaceutical companies to carry out appropriate paediatric research to support the development of new medicines. This change in research culture, that medicines used in children should be appropriately researched in children, has also led to the recognition of the importance of investigator-initiated clinical trials in furthering medical knowledge on the off-label use of authorized medicines for which paediatric data are often limited. However, medicines regulatory authorities of European Union countries have largely adopted a uniform approach to the regulation of both industry-sponsored and investigator-initiated trials and, in doing so, have added disproportionate burden to the conduct of paediatric clinical trials investigating authorized medicines.

CASE STUDIES: Two European multinational paediatric clinical trials funded by the conect4children consortium are presented to provide a comparative insight into past challenges and to illustrate how the new framework provided by the European Clinical Trials Regulation (No. 536/2014) addresses these barriers in practice.

CONCLUSION: The European Clinical Trials Regulation gives a strong impetus to a risk-proportionate approach and offers a path for more efficient delivery of investigator-initiated paediatric clinical trials.

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