The European Commission has published a guideline on the ethical standards to be applied when clinical trials are conducted with children.

“The protection against the risks of research in such a vulnerable population is paramount, whilst this should not lead to denying them the benefits of research.”

Thus a new document published by the European Commission sums up the core ethical dilemma raised by clinical trials involving children. The document, Ethical Considerations for Clinical Trials on Medicinal Products Conducted with the Paediatric Population, constitutes the recommendations of the Commission’s ad hoc group for the development of implementing guidelines for the clinical trials directive, 2001/20/EC. The directive’s third recital in particular recognised the need to improve treatment options for children by involving them in clinical trials.

“Children represent a vulnerable population with developmental, physiological and psychological differences from adults, which make age- and development-related research important for their benefit,” it stated. “Medicinal products, including vaccines, for children need to be tested scientifically before widespread use. This can only be achieved by ensuring that medicinal products which are likely to be of significant clinical value for children are fully studied. The clinical trials required for this purpose should be carried out under conditions affording the best possible protection for the subjects. Criteria for the protection of children in clinical trials therefore need to be laid down.”

These were also the arguments underpinning the Community Regulation on medicinal products for use in the paediatric population (No. 1901/2006), which took effect across the member states in January 2007. As such, the Commission’s ethical guideline addresses the sharp increase in the number of trials conducted in children that will result from the EU regulation’s various requirements and incentives for paediatric testing.

Because they deserve special protection, the document notes, children should not be the subject of clinical trials when the research “can be done in legally competent subjects (i.e., adults capable of informed consent)”. If trials in children prove necessary, it adds, “the least vulnerable among them should usually be included (i.e., older children)”. Moreover, the choice of subsets for inclusion in paediatric studies should be made “on the basis of the likely target population for the medicine being tested, the possibility of extrapolation, and the scientific validity of such an approach”.

Range of topics
The recommendations cover a broad range of topics, from informed consent to the role of ethics committees, paediatric study designs, minimisation of pain, distress and fear, risk assessment and monitoring, trials with neonates, paediatric formulations, insurance issues and trials in non-EU countries.

In general, the guideline says, children are unable to provide legally binding informed consent (which must nonetheless be obtained from a parent/legal representative), but their assent should be sought using age-appropriate information. The lack of legal ability to consent has implications for the design, analysis and choice of comparators used in paediatric trials, which should only be conducted by trained investigators with paediatric experience.

The full recommendations on ethical standards for paediatric trials may be accessed online at: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-10/ethical_considerations.pdf.