Requirements and Special Considerations for Drug Trials with Children Across Six Jurisdictions: 2. Ethics Review in the Regulatory Approval Process

Breanne Stewart ¹ Pirkko Lepola ² Gunter Florian Egger ³ Fahimeda Ali ⁴ Albert John Allen ^5,6 Alysha Kristine Croker ⁷ Andrew Davidson ⁸ Pamela Dicks ⁹ Saul Nicholas Faust ^10,11 Dionna Jeter Green ¹² Collins Hovinga ^5,6 Agnes Victoria Klein ⁷ Robyn Langham ¹³ Hidefumi Nakamura ¹⁴ Laura Pioppo ³ Shiva Ramroop ⁴ Michiyo Sakiyama ¹⁵ Isabel Sánchez Vigil de la Villa ³ Junko Sato ¹⁶ Donna Louise Snyder ¹⁷ Mark Augustine Turner ¹⁸ Sarah Zaidi ¹² Kanecia Zimmerman ^19,20 Thierry Lacaze-Masmonteil ^1*

• ¹ MICYRN, Vancouver, Canada
• ² University of Helsinki and Helsinki University Hospital, Helsinki, Uusimaa, Finland
• ³ Pediatric Medicines Office and Data Analytics and Methods Task Force, European Medicines Agency (EMA), Amsterdam, Netherlands
• ⁴ Paediatrics – Innovative Medicines, Healthcare Quality & Access, MHRA, London, United Kingdom
• ⁵ Institute for Advances Clinical Trials for Children, Rockville, California, United States
• ⁶ Critical Path Institute, Tucson, Arizona, United States
• ⁷ Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada,, Ottawa, Ontario, Canada
• ⁸ Melbourne Children’s Trials Centre, Murdoch Children’s Research Institute, Melbourne, Australia
• ⁹ NHS Scottish Children’s Research Network, Royal Aberdeen Children’s Hospital, Scotland, United Kingdom
• ¹⁰ NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
• ¹¹ Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom
• ¹² Office of Pediatric Therapeutics, Office of the Commissioner, United States Food and Drug Administration, Silver Spring, Maryland, United States
• ¹³ Therapeutic Goods Administration, Australian Government Department of Health and Aged Care, Woden, Australia
• ¹⁴ National Centre for Child Health and Development – Department of Development Strategy, Tokyo, Japan
• ¹⁵ Pediatric Drug Working Group, Pharmaceuticals and Medical Devices Agency,, Tokyo, Japan
• ¹⁶ Pediatric Drug Working Group, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan
• ¹⁷ WCG Clinical, Princeton, New Jersey, United States
• ¹⁸ Department of Women’s and Children’s Health, University of Liverpool, Liverpool, United Kingdom
• ¹⁹ Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina, United States
• ²⁰ Department of Pediatrics, School of Medicine, Duke University, Durham, North Carolina, United States

Background: Conducting clinical drug trials (CTs) with children presents several challenges. A major challenge is the need to enrol participants at multiple sites across different jurisdictions. Recruiting the required number of children within a reasonable timeframe requires the study to be reviewed by Research Ethics Boards (REB) or Institutional Review Boards (IRB) at multiple sites across various jurisdictions. This work, undertaken by the Working Group (WG) on International Collaborations at the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA) aims to describe the research ethics review requirements including any pediatric specific requirements, as well as current or upcoming changes across six jurisdictions -the European Union (EU), United Kingdom (UK), United States of America (USA), Canada, Japan, and Australia.Methods: An open questionnaire developed by the WG and directed at both the Competent Authorities (CA) and the national pediatric clinical trial networks arranged by jurisdictions.Results: A synopsis of the current regulatory requirements covers centralized versus independent review, comparisons between investigator initiated and industry sponsored clinical trials, timelines, review board members requirements and the consenting/assent process for clinical trial (CT) applications, application submission processes and application requirements for each of the six jurisdictions. It also describes changes currently or soon to be implemented in some jurisdictions.This environmental scan highlights the differences in ethics review for CTs in pediatric medicine development across six jurisdictions. While there is a growing trend for centralized ethics review, it is not universally permitted due to institutional, state/provincial, or national policies. Even where central review is allowed, local review may still be required for vulnerable populations like children. Harmonized and centralized ethics reviews offer advantages such as expert pediatric reviewers and efficient and consistent evaluations.