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Paediatrics
Communication
Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view
  1. Laura Folgori1,2,
  2. Irja Lutsar3,
  3. Joseph F Standing1,4,
  4. A Sarah Walker5,6,
  5. Emmanuel Roilides7,
  6. Theoklis E Zaoutis8,
  7. Hasan Jafri9,
  8. Carlo Giaquinto10,
  9. Mark A Turner11,
  10. Mike Sharland1
  1. 1 Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St George's University of London, London, UK
  2. 2 Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital, University of Milan, Milan, Italy
  3. 3 Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia
  4. 4 Great Ormond Street Institute of Child Health, University College London, London, UK
  5. 5 Nuffield Department of Clinical Medicine; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
  6. 6 MRC Clinical Trials Unit at UCL, Institute of Clinical Trials Methodology, UCL, London, UK
  7. 7 Infectious Diseases Unit, 3rd Department of Paediatrics, Faculty of Medicine, Aristotle University 96 School of Health Sciences, Thessaloniki, Greece
  8. 8 Division of Infectious Diseases and the Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  9. 9 AstraZeneca, 950 Wind River Ln, Gaithersburg, MD, USA
  10. 10 Department of Woman’s and Child’s Health, University of Padova, Padua, Italy
  11. 11 Institute of Translational Medicine, Centre for Women's Health Research, Liverpool Women's Hospital, Crown Street, Liverpool, UK
  1. Correspondence to Dr Laura Folgori; lfolgori{at}sgul.ac.uk

Abstract

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS—Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators.

  • paediatrics
  • antibiotics
  • clinical trials

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2019-032592

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    Footnotes

    • Contributors LF and MS contributed to the concept and design of the work. LF, IL, JFS, SW, ER, TEZ, HJ, CG, MAT and MS, as part of the Working Group, contributed to the drafting of the suggested criteria. LF, MS, SW and IL wrote the first draft of the manuscript. All authors reviewed and contributed to subsequent drafts and approved the final version for publication.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.