European Journal of Pediatrics

, Volume 172, Issue 7, pp 859–866 | Cite as

Ethical aspects of clinical research with minors

  • Wendy Bos
  • Krista Tromp
  • Dick Tibboel
  • Wim PinxtenEmail author


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.


Medical ethics Pediatrics Health law Clinical research 


  1. 1.
    Appelbaum PS, Lidz CW, Grisso T (2004) Therapeutic misconception in clinical research: frequency and risk factors. IRB 26:1–8PubMedCrossRefGoogle 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 24:409–415PubMedCrossRefGoogle 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 95:800–804PubMedCrossRefGoogle 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 91:112–116PubMedCrossRefGoogle 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), OviedoGoogle Scholar
  6. 6.
    Council of Europe (2005) Additional protocol to the convention on human rights and biomedicine, concerning biomedical research (CETS No.195), StrasbourgGoogle Scholar
  7. 7.
    Cuttini M (2000) Proxy informed consent in pediatric research: a review. Early Hum Dev 60:89–100PubMedCrossRefGoogle 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:e16PubMedCrossRefGoogle 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 L121:34–44Google 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 L378:1–19Google Scholar
  11. 11.
    Evans M (1994) Conflicts of interest in research on children. Camb Q Healthc Ethics 3:549–559PubMedCrossRefGoogle 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 44:525–533PubMedCrossRefGoogle 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 24:891–897PubMedCrossRefGoogle 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 28:401–408PubMedCrossRefGoogle Scholar
  15. 15.
    Kimland E, Odlind V (2012) Off-label drug use in pediatric patients. Clin Pharmacol Ther 91:796–801PubMedCrossRefGoogle 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 291:470–475PubMedCrossRefGoogle 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 58:1689–1697PubMedCrossRefGoogle Scholar
  18. 18.
    O’Neill O (2004) Accountability, trust and informed consent in medical practice and research. Clin Med 4:269–276PubMedCrossRefGoogle Scholar
  19. 19.
    Pinxten W (2011) One size does not fit all. Integrating ethical and legal guidance into pediatric clinical research. Leuven University Press, LeuvenGoogle 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 168:1225–1234PubMedCrossRefGoogle 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–S198PubMedCrossRefGoogle Scholar
  22. 22.
    Pinxten W, Nys H, Dierickx K (2008) Regulating trust in pediatric clinical trials. Med Health Care Philos 11:439–444PubMedCrossRefGoogle Scholar
  23. 23.
    Ross LF (2006) Children in medical research: access versus protection. Oxford University Press, OxfordCrossRefGoogle Scholar
  24. 24.
    Shirkey H (1968) Therapeutic orphans. J Pediatr 72:119–120PubMedCrossRefGoogle 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 14:21–46PubMedCrossRefGoogle 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 98:603–608PubMedCrossRefGoogle 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 98:609–614CrossRefGoogle 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–S33PubMedGoogle Scholar
  29. 29.
    Wendler D (2008) Is it possible to protect pediatric research subjects without blocking appropriate research? J Pediatr 152:467–476PubMedCrossRefGoogle Scholar
  30. 30.
    Westra AE, De Beaufort ID (2011) The merits of procedure-level risk–benefit assessment. IRB 33:7–13PubMedGoogle Scholar
  31. 31.
    Wolthers OD (2006) A questionnaire on factors influencing children’s assent and dissent to non-therapeutic research. J Med Ethics 32:292–297PubMedCrossRefGoogle 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

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Wendy Bos
    • 1
  • Krista Tromp
    • 1
  • Dick Tibboel
    • 2
  • Wim Pinxten
    • 1
    Email author
  1. 1.Department of Medical Ethics and Philosophy of MedicineErasmus Medical CenterRotterdamThe Netherlands
  2. 2.Intensive Care and Department of Pediatric SurgeryErasmus Medical Center-Sophia Children’s HospitalRotterdamThe Netherlands

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