Pediatrics International | 2021
Ethical considerations in pediatric clinical research
Abstract
Safety and efficacy should be investigated when a drug is likely to be used in children. However, a significant number of commonly prescribed pediatric drugs are still used off-label or unlicensed in Japan. Children were once excluded from clinical trials as they were considered a vulnerable population and were overprotected. Nowadays, it is common practice for the efficacy and safety of drugs to be studied in children if they are intended for pediatric use. Drug evaluation in children was recently mandated by law in both the EU and the USA, highlighting the importance of a robust ethical framework to protect children. Although there are no regulations mandating pediatric drug development in Japan, an ethical framework remains essential for good practice in pediatric clinical research. The complete republication of the “Principles of Ethical Consideration Required for Clinical Research Involving Children” that Matsui et al. initially published in Japanese in the Journal of the Japan Pediatric Society in 2016, appears in this issue of Pediatrics International. These principles were written with the leading research ethicists in Japan and were originally published as an outcome of the Regulatory Science for Promoting Pediatric Drug Development Project (RS Research Project) funded by the Ministry of Health, Labour and Welfare (2013 and 2014) and the Japan Agency for Medical Research and Development (2015). Until this paper was published, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Topic E-11 (Clinical Investigation of Medicinal Products in the Pediatric Population) was the only guideline for the conduct of pediatric clinical trials in Japan, and reliance was placed on the guidance and guidelines in the EU or USA to further examine the ethical principles. The ICH guidelines are practical, and there were no specific Japanese guidelines focusing on the ethical principles for clinical research in children. The concept of informed assent in drug trials was first widely recognized when ICH Topic E-11 was implemented in Japan in 2000, and discussion on comprehensive ethical principles for pediatric clinical research did not occur in a coordinated fashion. This paper is the first attempt of its kind by Japanese scholars and is written in a similar style as the Council for International Organizations of Medical Sciences guidelines, with a commentary on each guideline so that readers can understand the background philosophy, including current evidence and relevant international discussions and arguments, rather than merely describing practical procedures. The paper was finalized after seeking advice and opinions from pediatric specialists with various subspecialties involved in the RS Research Project mentioned above, clinical research coordinators specializing in pediatric research, relevant members of the Pharmaceutical and Medical Devices Agency, and legal specialists from the Japan Association for Bioethics. As pediatric drug development becomes increasingly global, international discussion on ethical considerations in pediatric clinical research should be initiated. Scientific validity and ethical robustness must go hand in hand, and we should also take into account regional and religious differences in ethical considerations in children. I believe that these principles will provide a good guide for those involved in pediatric clinical research in Japan and will also become a useful reference for international discussion.