Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Special Article
  • Published:

Establishing a global regulatory floor for children’s decisions about participation in clinical research

Pediatric Research volume 94, pages 462–465 (2023)Cite this article

Abstract

Background

Enrolling children in clinical trials typically requires parental or guardian permission and, when appropriate, child assent. Aligning requirements across jurisdictions would facilitate multisite pediatric trials. Guidance from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is the best candidate for a global standard but would benefit from additional specification.

Methods

Ethical analysis of ICH guidance for permission and assent for pediatric trials, with recommendations for clarification.

Results

ICH guidance regarding permission and assent would be enhanced by additional detail in the following areas: (1) what information should be provided to parents, guardians, and children considering a trial, and how that information should be provided; (2) the definition of “assent,” the criteria for when assent should be required, and the need to include children in discussions even when assent is not mandated; (3) criteria for requiring children’s signatures indicating agreement; (4) greater specificity regarding children’s right to decline or withdraw; and (5) clarification of when children’s wish to decline or withdraw from participation may be overridden and of what the overriding process should entail.

Conclusion

ICH guidance provides a global standard for decision making regarding children’s participation in trials. Several clarifications would facilitate the conduct of multinational pediatric research.

Impact

  • Enrolling children in clinical trials requires the permission of a parent/guardian ± the assent of the minor.

  • Differing global regulatory requirements for enrolling children complicate the conduct of multicenter and multinational trials.

  • The authors identify points of ambiguity and/or contradiction in the International Council for Harmonization guidelines and offer recommendations for a common ethical platform for conducting global pediatric research.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Data availability

Any data provided in this manuscript are available in the references cited.

References

  1. Nuffield Council on Bioethics. Children and Clinical Research: Ethical Issues (Nuffield Council on Bioethics, London, 2015, accessed 29 December 2022); https://www.nuffieldbioethics.org/assets/pdfs/Children-and-clinical-research.pdf.

  2. Youthpolicy.org. Youthpolicy.Org Factsheets (accessed 29 December 2022); https://www.youthpolicy.org/factsheets/.

  3. United States Centers for Disease Control and Prevention. State Laws That Enable a Minor to Provide Informed Consent to Receive HIV and STD Services (accessed 29 December 2022); https://www.cdc.gov/hiv/policies/law/states/minors.html.

  4. World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310, 2191–2194 (2013).

    Article  Google Scholar 

  5. Council for International Organizations of Medical Sciences. International Ethical Guidelines for Health-Related Research Involving Humans (Council for International Organizations of Medical Sciences, Geneva, Switzerland, 2016, accessed 29 December 2022); https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf.

  6. Blake, V., Joffe, S. & Kodish, E. Harmonization of ethics policies in pediatric research. J. Law Med Ethics 39, 70–78 (2011).

    Article  PubMed  Google Scholar 

  7. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Addendum to Ich E11: Clinical Investigation of Medicinal Products in the Pediatric Population (accessed 29 December 2022); https://database.ich.org/sites/default/files/E11_R1_Addendum.pdf (2017).

  8. United States Food and Drug Administration. Informed Consent: Draft Guidance for Irbs, Clinical Investigators, and Sponsors (accessed 29 December 2022); https://www.fda.gov/regulatory-information/search-fda-guidance-documents/informed-consent#_ftnref39 (2014).

  9. United States Food and Drug Administration. Protection of Human Subjects. 21CFR503(n)1996 (accessed 29 December 2022); https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=50.3.

  10. Pharmacy and Poisons Board, Kenya Ministry of Health. Guidelines for Conduct of Clinical Trials in Kenya (accessed 29 December 2022); https://africacheck.org/sites/default/files/media/documents/2021-03/Guidelines%20for%20Conduct%20of%20Clinical%20Trials%20in%20Kenya%202nd%20Revision.pdf (2019).

  11. Philippine Health Research Ethics Board. National Ethical Guidelines for Health and Health-Related Research 2017 (accessed 29 December 2022); http://49.231.15.21/deptw13/upload/files/hercF256312041721022781.pdf (2018).

  12. Joffe, S. et al. Involving children with cancer in decision-making about research participation. J. Pediatr. 149, 862–868 (2006).

    Article  PubMed  Google Scholar 

  13. Ungar, D., Joffe, S. & Kodish, E. Children are not small adults: documentation of assent for research involving children. J. Pediatr. 149, S31–S33 (2006).

    Article  PubMed  Google Scholar 

  14. Faden, R. R. & Beauchamp, T. L. A History and Theory of Informed Consent (Oxford University Press, 1986).

  15. Katz, A. L., Webb, S. A. & Committee on Bioethics of the American Academy of Pediatrics. Informed consent in decision-making in pediatric practice. Pediatrics 138, e20161485 (2016).

Download references

Acknowledgements

The authors are grateful to Walker Morrell, MBioethics, for research assistance and support and to Katharine Wright, MA, and Mr. Morrell for their thoughtful contributions to discussions that informed this article.

Author information

Authors and Affiliations

  1. Department of Medical Ethics and Health Policy, Perelman School of Medicine, Philadelphia, PA, USA

    Steven Joffe

  2. The Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Steven Joffe

  3. Eli Lilly and Company (retired), Indianapolis, IN, USA

    Albert J. Allen

  4. Department of Pediatrics and Tufts Clinical and Translational Research Institute, Tufts Medical Center, Boston, MA, USA

    Jonathan M. Davis

  5. Multi-Regional Clinical Trials Center, Brigham and Women’s Hospital and Harvard, Boston, MA, USA

    Elisa Koppelman & Barbara E. Bierer

  6. Clinical Research Compliance, Boston Children’s Hospital, Boston, MA, USA

    Susan Z. Kornetsky

  7. Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium

    Grace Marie V. Ku

  8. Division of Adolescent Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Victoria A. Miller

  9. National Institute for Health Research Alder Hey Clinical Research Facility, Department of Women’s and Children’s Health, Institute of Life Course and Medical Sciences, Institute in the Park, Alder Hey Children’s National Health Service Foundation Trust, Liverpool, UK

    Jennifer Preston

  10. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Lesha D. Shah

  11. Division of Global Health Equity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Barbara E. Bierer

Authors
  1. Steven Joffe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Albert J. Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan M. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elisa Koppelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susan Z. Kornetsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Grace Marie V. Ku
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Victoria A. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jennifer Preston
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lesha D. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Barbara E. Bierer
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the research and arguments presented in this article. S.J. wrote the first draft of the manuscript; all authors revised it critically for important intellectual content. All authors approved the final draft of the manuscript.

Corresponding author

Correspondence to Steven Joffe.

Ethics declarations

Competing interests

S.J. reports that he received research funding from Pfizer through the University of Pennsylvania until May 2020, and is a member of a data and safety monitoring board for CSL Behring. A.J.A. reports that he was employed by Eli Lilly and Company during the preparation of this manuscript but has since retired. J.M.D., E.K., V.A.M., S.Z.K., G.M.V.K., J.P., L.D.S., and B.E.B. have no financial relationships to report.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joffe, S., Allen, A.J., Davis, J.M. et al. Establishing a global regulatory floor for children’s decisions about participation in clinical research. Pediatr Res 94, 462–465 (2023). https://doi.org/10.1038/s41390-023-02483-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02483-8

Search

Advanced search

Quick links