Children involved in drug research: how to optimally protect them in practice?

Doing drug research with children is ethically complex. On the one hand it is unacceptable that many drugs prescribed to children are not proven to be safe and effective for them. On the other hand children cannot be included in research unless under strict conditions, because they deserve special protection. Thus, although it is imperative that we do more research into developing therapies for children, there are constraints and limits. Now that paediatric drug research is expected to expand it is even more important that the protection of children who will be involved in these studies will be executed optimally. The protection of research subjects in general relies on two pillars: 1) before executing research, review boards have to judge whether protocols fulfil all the requirements for ethical research (e.g., a favourable risk-benefit ratio), and 2) the research may not be conducted without the subject’s informed consent. The main extra requirement for research with children is that the risks and burdens of so-called ‘nontherapeutic’ research may not be more than ‘minimal’, regardless of the expected benefits to future children. Furthermore, instead of informed consent, parents must provide proxy consent. Additionally, those children who are capable to make their own decisions must give their ‘assent’, and any ‘dissent’ has to be respected. Clearly, children involved in research can only be optimally protected when sound protective measures have not merely been written down in paper documents but also function well in practice. Regulation by law does not automatically imply that all conceptual, ethical and practical issues have been solved. For example, the distinction between ‘therapeutic’ and ‘nontherapeutic’ research is not as sharp as often suggested, and therefore it is not always clear whether a protocol should comply with the added requirements of minimal risk and minimal burden. Furthermore, ‘minimal risk’ and ‘minimal burden’ are rather vague concepts. And the code that expresses respect for the child’s dissent (‘code of conduct related to expressions of objection’) seems difficult to implement in practice. The proposed project aims to analyse these three issues, and where possible, to provide solutions. To do this we will combine our ethical analysis with several empirical studies: if we know the facts, and understand them, we can use these in our ethical analysis. The expected results of the project are: 1) recommendations for review boards on the use of an alternative approach to risk-benefit assessment called ‘component analysis’, 2) a practical list with empirical data on the risks and burdens children experience with several common research procedures, which can be used by review boards and researchers when assessing whether a protocol can be considered to involve ‘minimal risk’ and ‘minimal burden’, and 3) an improved ‘code of conduct related to expressions of objection’, including recommendations for researchers on how to use this code in practice. The research group involves close cooperation between ethicists, members of review boards and those who are experienced in conducting drug studies with children. This multidisciplinary group has been working together for several years now, which has resulted in interesting results and publications.