SERIES: ETHICS IN PAEDIATRIC RESPIRATORY MEDICINE
Development of medicines for children in Europe: ethical implications

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Summary

Ethics of clinical trials in children have been a longstanding topic for debate. Children are vulnerable, unable to consent to participation in trials from a legal perspective and deserve to be protected. Ethical principles and the European legal framework define the safeguards that need to be put in place in any paediatric trial, be it performed in developed or in developing countries. It was considered that children should not be included in trials for ethical reasons. However, there is an ethical need to study medicines as data obtained in adults cannot be extrapolated to children. It is our collective responsibility to obtain sufficient information to be able to prescribe medicines safely whilst protecting children who are exposed in the trials. Future European paediatric regulations should encourage the development of medicines in high-quality ethical research and ensure availability of information to the public.

Section snippets

INTRODUCTION

The ethics of clinical trials in children have been a longstanding topic for debate. Children are vulnerable, unable to consent to participation in trials from a legal perspective and deserve to be protected. Ethics principles, such as those expressed in the Declaration of Helsinki1 and the Convention on Human Rights and Biomedicine (Council of Europe),2 have been established to protect trial subjects. It has been considered that paediatric clinical trials were unethical. Simultaneously, very

Medicines used in children have not been studied properly

Most of the medicines used to treat children in Europe have not been fully developed and assessed. Recent surveys have confirmed that the European situation3, 4, 5, 6, 7, 8, 9 is no different from that of the USA or other regions. Providing a full range of both old and recent medicines that are fully developed and assessed to cover the therapeutic needs of children in Europe is a major ethical and practical challenge.

Most medicines used in children have not been studied specifically for this

Differences between adults and children justify paediatric trials

Children are not small adults and weight difference is not the only difference of relevance for the use of medicines. On the basis of what we know of paediatric pharmacology in different groups of children, it is not possible to extrapolate findings and results from adults to children.18, 19 Differences can be found in disease patho(physio)logy and expression, in the influence of maturation and growth, in pharmacokinetics, pharmacodynamics and adverse drug reaction types, and in severity,

Obtaining informed consent

From a legal point of view, children cannot consent and the consent of the parents or a legal representative is necessary. The European Clinical Trial Directive27 clearly sets out that informed written consent must be obtained, and in the case of children, ‘must represent the minor's presumed will’. This provision respects the various legal systems of the Member States of parental authority as some Member States require consent from both parents simultaneously. It also respects the child's

PROTECTION OF CHILDREN WHEN STUDYING MEDICINES

Paediatric clinical trials must provide the necessary level of protection to the children participating in them.

REVIEWING PAEDIATRIC TRIALS WHEN ASSESSING MEDICINES

European authorities have several tools at hand when reviewing paediatric trials and ethical provisions. At the time of development and in particular when a company is seeking scientific advice, the European Medicines Agency (EMEA) can raise ethical questions about the proposed studies. In this respect, links with ethics committees are being developed. Should ethical issues be raised during the assessment, good clinical practice inspection of the trial sites and data can be triggered and

THE EUROPEAN PAEDIATRIC INITIATIVE

The future European paediatric regulation51 recognises in its founding principles the need for ethical research in children. The proposal aims to change the situation in line with what is happening in the USA. New medicines would have to be developed in children when there is a rationale for a potential use. Medicines without prospect of use in children would be exempted. Paediatric trials would have to be deferred until more information has been obtained for those products for which safety

CONCLUSIONS

The use of medicines that have not been studied and assessed fully in children is a common situation in Europe and the rest of the world. It has led to a number of catastrophes in the past and is still responsible for adverse drug reactions that could have been avoided or minimised. The situation is not ethical and requires action. Trials of medicines to be used in children should be performed whenever necessary but with full protection of this vulnerable population. Ethical principles and the

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