The Ethics of Drug Research in Children

Abstract

The obligation of society to improve the welfare of its members requires the conduct of paediatric drug trials. Nevertheless, research activities must satisfy obligations to individual participants. The obligation to protect the welfare of children requires that nontherapeutic research procedures generally involve no more than minimal risk. It also requires that randomisation occurs only when the relative merits of therapeutic procedures remain unsettled among the relevant community of experts. The duty to respect the developing autonomy of children requires that they be included in decision-making about research participation in a manner consistent with the level of their decision-making capacity. However, when children lack mature decision-making capacities, the duty of parents to protect their welfare may properly constrain their choices. Justice requires that the benefits and burdens of research be distributed in a manner that assures equal opportunity for all children. Vulnerable children should receive special protection against the burdens of nontherapeutic research procedures. The benefits of participating in clinical trials should be available to all children with serious illnesses for which current treatment is unsatisfactory. Justice also requires that initiatives be undertaken to rectify current shortcomings in the scope of paediatric drug research. Striking an appropriate balance between obligations to conduct research and to protect the interests of participants is essential to the moral integrity of paediatric drug research.

Clinical trials in children

“…For example, faster metabolism of cyclosporin in children could lead to subtherapeutic concentrations because of under-dosing [26]. Prescribing tetracycline in children during the period of mineralization of developing teeth results in severe enamel dysplasia [27]. Children may experience paradoxical hyperactivity with phenobarbital which is not experienced in adults due to differences in pharmacodynamics [26].…”

“…There is a dilemma in finding a balance between the obligation to conduct trials to protect children from the risk of using untested medicines and to protect children against unknown risks and harms which may occur with trial participation [27,39,108,109]. The ethical principles of respect for persons, beneficence, non-maleficence and justice in trials involving children are the same as for adults.…”

“…The most frequently cited suggestions from interviews and focus groups for improving informed consent related to allowing parents more time to make their decision, the amount and type of information provided, organization of the consent meeting, communication style and providing additional materials [115]. Although consent by parents or guardians is a legal requirement for trials, the autonomy of children should be respected and investigators also need to include them in decision making as much as they are capable [27,87,116]. Children's dissent should also be respected, particularly if their dissent is different from their usual response to the same procedure in normal clinical care.…”

The Newborn Drug Development Initiative

“…Ethical principles in the neonatal population are evolving as newer approaches to study design are developed and as newer therapies, drug-delivery systems, and diagnostic imaging (eg, positron emission tomography scanning) are applied to newborn studies. 35,36 The ethics group will continue to serve as a resource to the other work groups. The large number of drugs that require study, coupled with limited resources, dictates the need to prioritize the drugs for study in neonatal populations.…”

Pharmacoeconomic analysis of therapies for pediatric patients

“…Yet, 67% of new drugs with potential applications in pediatrics do not have labeling for such use [2]. Furthermore, up to 80% of drugs used in pediatrics do not have approval for use in children [2].…”