Ethics Council discusses the current status of research on medicines in children

Children have the same right as adults to appropriate and safe treatment with medicinal products. However, every day children are treated with medicines that are not approved for paediatric use, while the clinical studies necessary to put an end to this undesirable state of affairs raise ethical issues. The argument that defenceless subjects who lack the capacity to give legally valid consent are thereby instrumentalized is countered by the consideration that a blanket ban on research would specifically deprive children of the benefits of medical advances. Yet a change of paradigm seems to be emerging: instead of ruling out research in children on the grounds of protecting them from research, the emphasis now is on protecting them by research.

In his introductory address, Wolfgang Rascher, Chair of the Commission on Medicinal Products for Children and Adolescents at the Federal Institute for Drugs and Medical Devices, reported on the harm sustained by children due to the use of drugs not trialled for paediatric use. He noted that the EU’s 2002 initiative “Better medicines for children” and the latest amendments to the law governing medicinal products in Germany were already beginning to bear fruit in terms of improved provision of properly tested medicines for children. However, overall growth in the number of clinical studies involving children was very slow.

Angelika Eggert, Director of the West German Tumour Centre, reported on drug treatment in the field of paediatric oncology. She noted that the “off-label” use of medicines was a fact of life. Yet precisely in paediatric oncology very good therapeutic outcomes had been achieved in recent years, since most children underwent therapy in the context of non-commercial multi-centre treatment optimization studies. However, Professor Eggert regretted that the development of new therapies was too protracted a process. She advocated the dismantling of administrative obstacles to drug development, increased incentives for the pharmaceutical industry and the establishment of European networks for preclinical and early clinical research.

Jochen Taupitz, a member of the German Ethics Council, outlined the legal situation of research on medicines in children in Germany. Given that, in the case of children, the essential condition of informed consent by the subject to research could often be satisfied only with difficulty, if at all, the Arzneimittelgesetz (Medicinal Products Act) laid down criteria for the protection of minors. These included not only a benefit/risk assessment, prior pharmacological and toxicological trials of the drug concerned, approval by the relevant authority and a favourable opinion by an ethics committee, but also matters relating to individual rights of self-determination such as the provision of information to, and securing the consent of, the subject or the subject’s legal representatives. Other protective criteria to be applied in the case of minors were the requirement of direct individual benefit to the subject and/or the group of patients suffering from the same disorder.

Georg Marckmann, Director of the Institute of Ethics, History and Theory of Medicine at Munich’s Ludwig Maximilian University, then considered the ethics of research involving minors. In view of the risks of using untested medicines, coupled with the need to develop useful therapies, studies involving children were an indispensable prerequisite for safe and effective treatment, and the forgoing of such studies was ethically unacceptable. However, research in children raised ethical problems because children were particularly vulnerable both psychologically and physically and because their capacity to give consent was either limited or non-existent. This ultimately constituted a fundamental ethical dilemma, which could not be resolved but could only be regulated by assessment of the benefit/harm ratio, by informed or vicarious consent and by the criterion of benefit accruing primarily to the individual subject.

Claudia Wiesemann, Director of the Department for Medical Ethics and History of Medicine at Göttingen University Medical Center, amplified these considerations with empirical data from studies of the views of the children and adolescents concerned and their parents. She concluded that parents who were informed about the possibility of an individual therapeutic attempt using a drug not yet approved for the purpose were more inclined to allow their children to participate in drug trials. Furthermore, parents were capable of giving, and willing to give, consent even under conditions of stress. Children, for their part, were more discriminating in their assessment of the stresses and strains of research. Professor Wiesemann called for more studies of the attitudes of children and adolescents to research in children.

In addition to the evening’s speakers, those taking part in the ensuing panel discussion were Siegfried Throm, Managing Director of the Association of Research-Based Pharmaceutical Companies (vfa), and Dietrich Niethammer, Chair of the Board of Trustees of the Stiftung für kranke Kinder (Foundation for Sick Children), Tübingen.

According to Siegfried Throm, the question now was not whether studies involving children were permissible – that, after all, was determined by the relevant legislation – but only how they should be conducted.

In the view of Dietrich Niethammer, research on medicinal products in children was essential and demanded a careful study design directed towards the minimization of risk, together with a high level of responsibility on the part of the research workers, paediatricians and ethics committees concerned.

Other issues raised in the discussion, which was also opened to the floor, involved benefit/risk assessment, the resolution of differences of opinion between children and their parents, and the relations between research with potential benefit primarily to the subject on the one hand and group-related research on the other. Another question asked was whether subjects and their legal representatives were given appropriate and readily comprehensible information.

Audio recordings of the individual contributions can be accessed (in German) at http://www.ethikrat.org, where transcripts will also be available in due course.