Ethical aspects of clinical research with minors


Over the past decades, clinical research has increasingly been subjected to ethical requirements and legal regulation. The specific focus of ethical and legal frameworks on competent adults (which serve as the paradigmatic research subject), however, has created an ambivalent attitude towards pediatric clinical research. On one hand, minors are regarded as a vulnerable population that deserves additional protection against the risks and burdens involved in clinical research. On the other hand, the population of minors should not be denied (or not get timely) access to the benefits of clinical research. In this paper, we will explore the legal regulation and ethical guidance that currently governs pediatric clinical research in the European Union and discuss the future challenges in this field. In addition, we will discuss major ethical concerns in pediatric clinical research, with a focus on the acceptability of research risks and the informed consent process. In the discussion, we will address key concerns in both regulating pediatric clinical research and implementing ethical and legal requirement in the actual pediatric research conduct.

This is a preview of subscription content, log in to check access.


  1. 1.

    Current estimates range from 25 to 65 % of all prescriptions (e.g., depending on the condition and age group), affecting 40 to 100 % of pediatric patients in hospital settings [15].


  1. 1.

    Appelbaum PS, Lidz CW, Grisso T (2004) Therapeutic misconception in clinical research: frequency and risk factors. IRB 26:1–8

    PubMed  Article  Google Scholar 

  2. 2.

    Ballard HO, Shook LA, Desai NS, Anand KJ (2004) Neonatal research and the validity of informed consent obtained in the perinatal period. J Perinatol 24:409–415

    PubMed  Article  Google Scholar 

  3. 3.

    Chappuy H, Baruchel A, Leverger G, Oudot C, Brethon B, Haouy S, Auvrignon A, Davous D, Doz F, Tréluyer JM (2010) Parental comprehension and satisfaction in informed consent in paediatric clinical trials: a prospective study on childhood leukaemia. Arch Dis Child 95:800–804

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Chappuy H, Doz F, Blanche S, Gentet JC, Pons G, Treluyer JM (2006) Parental consent in paediatric clinical research. Arch Dis Child 91:112–116

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Council of Europe (1997) Convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine: convention on human rights and biomedicine (CETS No. 164), Oviedo

  6. 6.

    Council of Europe (2005) Additional protocol to the convention on human rights and biomedicine, concerning biomedical research (CETS No.195), Strasbourg

  7. 7.

    Cuttini M (2000) Proxy informed consent in pediatric research: a review. Early Hum Dev 60:89–100

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Durand-Zaleski IS, Alberti C, Durieux P, Duval X, Gottot S, Ravaud P, Gainotti S, Vincent-Genod C, Moreau D, Amiel P (2008) Informed consent in clinical research in France: assessment and factors associated with therapeutic misconception. J Med Ethics 34:e16

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    European Parliament and the Council of the European Union (2001) Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Off J Eur Communities L121:34–44

    Google Scholar 

  10. 10.

    European Parliament and the Council of the European Union (2006) Regulation (EC) No. 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No. 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No. 726/2004. Off J Eur Union L378:1–19

    Google Scholar 

  11. 11.

    Evans M (1994) Conflicts of interest in research on children. Camb Q Healthc Ethics 3:549–559

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Franck LS, Winter I, Oulton K (2007) The quality of parental consent for research with children: a prospective repeated measure self-report survey. Int J Nurs Stud 44:525–533

    PubMed  Article  Google Scholar 

  13. 13.

    Greenley RN, Drotar D, Zyzanski SJ, Kodish E (2006) Stability of parental understanding of random assignment in childhood leukaemia trials: an empirical examination of informed consent. J Clin Oncol 24:891–897

    PubMed  Article  Google Scholar 

  14. 14.

    Hazen RA, Drotar D, Kodish E (2007) The role of the consent document in informed consent for pediatric leukemia trials. Contemp Clin Trials 28:401–408

    PubMed  Article  Google Scholar 

  15. 15.

    Kimland E, Odlind V (2012) Off-label drug use in pediatric patients. Clin Pharmacol Ther 91:796–801

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Kodish E, Eder M, Noll RB, Ruccione K, Lange B, Angiolillo A, Pentz R, Zyzanski S, Siminoff LA, Drotar D (2004) Communication of randomization in childhood leukemia trials. JAMA 291:470–475

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Lidz CW, Appelbaum PS, Grisso T, Renaud M (2004) Therapeutic misconception and the appreciation of risks in clinical trials. Soc Sci Med 58:1689–1697

    PubMed  Article  Google Scholar 

  18. 18.

    O’Neill O (2004) Accountability, trust and informed consent in medical practice and research. Clin Med 4:269–276

    PubMed  Article  Google Scholar 

  19. 19.

    Pinxten W (2011) One size does not fit all. Integrating ethical and legal guidance into pediatric clinical research. Leuven University Press, Leuven

    Google Scholar 

  20. 20.

    Pinxten W, Dierickx K, Nys H (2009) Ethical principles and legal requirements for pediatric research in the EU: an analysis of the European normative and legal framework surrounding pediatric clinical trials. Eur J Pediatr 168:1225–1234

    PubMed  Article  Google Scholar 

  21. 21.

    Pinxten W, Dierickx K, Nys H (2011) Diversified harmony. Supranational and domestic regulation of pediatric clinical trials in the European Union. J Cyst Fibros 10 (Suppl 2):S183–S198

    PubMed  Article  Google Scholar 

  22. 22.

    Pinxten W, Nys H, Dierickx K (2008) Regulating trust in pediatric clinical trials. Med Health Care Philos 11:439–444

    PubMed  Article  Google Scholar 

  23. 23.

    Ross LF (2006) Children in medical research: access versus protection. Oxford University Press, Oxford

    Google Scholar 

  24. 24.

    Shirkey H (1968) Therapeutic orphans. J Pediatr 72:119–120

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Stultiëns L, Goffin T, Borry P, Dierickx K, Nys H (2007) Minors and informed consent: a comparative approach. Eur J Health Law 14:21–46

    PubMed  Article  Google Scholar 

  26. 26.

    Tait AR, Voepel-Lewis T, Malviya S (2003) Do they understand? (part I): parental consent for children participating in clinical anesthesia and surgery research. Anesthesiol 98:603–608

    PubMed  Article  Google Scholar 

  27. 27.

    Tait AR, Voepel-Lewis T, Malviya S (2003) Do they understand? (part II): assent of children participating in clinical anesthesia and surgery research. Anesthesiol 98:609–614

    Article  Google Scholar 

  28. 28.

    Ungar D, Joffe S, Kodish E (2006) Children are not small adults: documentation of assent for research involving children. J Pediatr 149(1 suppl):S31–S33

    PubMed  Google Scholar 

  29. 29.

    Wendler D (2008) Is it possible to protect pediatric research subjects without blocking appropriate research? J Pediatr 152:467–476

    PubMed  Article  Google Scholar 

  30. 30.

    Westra AE, De Beaufort ID (2011) The merits of procedure-level risk–benefit assessment. IRB 33:7–13

    PubMed  Google Scholar 

  31. 31.

    Wolthers OD (2006) A questionnaire on factors influencing children’s assent and dissent to non-therapeutic research. J Med Ethics 32:292–297

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Woods S, Hagger LE, McCormack P (2012) Therapeutic misconception: hope, trust and misconception in paediatric research. Health Care Anal. doi:10.1007/s10728-012-0201-8

Download references

Author information



Corresponding author

Correspondence to Wim Pinxten.

Additional information

Wendy Bos and Krista Tromp contributed equally to this paper.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bos, W., Tromp, K., Tibboel, D. et al. Ethical aspects of clinical research with minors. Eur J Pediatr 172, 859–866 (2013).

Download citation


  • Medical ethics
  • Pediatrics
  • Health law
  • Clinical research