Ethical principles and legal requirements for pediatric research in the EU: an analysis of the European normative and legal framework surrounding pediatric clinical trials

Abstract

The involvement of minors in clinical research is inevitable to catch up with the lack of drugs labeled for pediatric use. To encourage the responsible conduct of pediatric clinical trials in the EU, an extensive legal framework has been developed over the past decade in which the practical, ethical, legal, social, and commercial issues in pediatric research are addressed. In this article, the European legal framework surrounding pediatric clinical trials is analyzed from the perspective of the major ethical concerns in pediatric research. The four principles of biomedical ethics will be used as a conceptual framework (1) to map the ethical issues addressed in the European legal framework, (2) to study how these issues are commonly handled in competent adults, (3) to detect workability problems of these paradigmatic approaches in the specific setting of pediatric research, and (4) to illustrate the strong urge to differentiate, specify, or adjust these paradigmatic approaches to guarantee their successful operation in pediatric research. In addition, a concise comparative analysis of the European regulation will be made. To conclude our analysis, we integrate our findings in the existing ethical discussions on issues specific to pediatric clinical research.

Developing a policy for paediatric biobanks: principles for good practice

“…Here, the principle of minimal risk is often quoted as defining a standard by which one can decide whether some proposed non-therapeutic research can be performed with children. 16, 17 Hence, minimal risk is understood as a risk that is not higher than what a child would encounter in everyday life. Moreover, the direct benefits should counterbalance the risk of a procedure.…”

“…18 For example, European normative frameworks for clinical trials (Article 4, Directive 2001/20 EC of the European parliament and of the Council of 4 April 2001) hold that research on minors should be performed out of necessity, either because there might be some direct benefit to the participant, or because the research could benefit children with the same condition. 17 The risks also need to be proportional to the potential net benefits for the child participating in the clinical trial. Another concept quoted in the context of clinical trials with minors is that of subsidiarity: such research should only be done if it cannot be done on adults.…”

The return of individual research findings in paediatric genetic research

“…They have not enrolled themselves in the research, and as such it is acknowledged that they are in need of extra protection. In the literature on clinical trials, there is often the requirement that research on children should be for the benefit of children 32. Although we admit that research on paediatric tissue samples is different from clinical trials due to the minimal physical risk involved, we think that the communication of findings of early-onset treatable and preventable diseases can be interpreted as a benefit in this context.…”

Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative

“…The benefit of participating in a research study has to outweigh the potential risk 21. The principle of minimal risk is a virtual standard for research in children 24. Minimal risk is considered a risk that is similar to the child’s risk in everyday life22 and should not be greater than the risk attached to a routine medical examination 25.…”