LEADING ARTICLE Ethics Review of Pediatric Multi-Center Drug Trials Allison C. Needham • Mufiza Z. Kapadia • Martin Offringa Published online: 30 October 2014 Ó Springer International Publishing Switzerland 2014 Abstract The assessment of safety and efficacy of ther- apeutics for children and adolescents requires the use of multi-centered designs. However, the need to obtain ethical approval from multiple independent research ethics boards (REBs) presents as a challenge to investigators and spon- sors who must consider local requirements while ensuring that the protection of human subjects is consistent across sites. In pediatrics, this requirement is complicated by pediatric-specific ethical concerns such as the acquisition of assent and consent and the need for pediatric expertise to assess the scholarly merit of the proposed research. Efforts to tackle these challenges have focused on the process of ethics review, which will improve efficiency. In addition to improving process, we suggest further research to fill gaps in the evidence base for recommendations and decisions made by REBs, specifically their effectiveness to protect human subjects. Evidence gathered will contribute to the successful development, adoption and implementation of harmonized guidance to apply ethics principles in order to protect children through research rather than from research. Key Points Assessment of the safety and efficacy of therapeutics for children requires multi-centered designs. Ethics review of multi-center trial protocols presents challenges to research ethics boards, investigators, and sponsors who must consider both general and local institutional regulations and requirements for human subjects’ protection. Although streamlining ethics review processes may improve efficiency, there is an urgent need for the development, adoption and implementation of ethics guidance to protect children through research rather than from research. 1 Introduction Pediatric clinical research is essential in order to assess the safety and efficacy of new treatments for children. His- torically, children have been regarded as vulnerable sub- jects who should be protected from the risks of research. Unfortunately, concern about protecting children has resulted in reluctance to involve them in research [1, 2]. Such views have led to an environment where most med- icines currently prescribed to children have not undergone formal studies evaluating safety and effectiveness [3, 4]. A lack of research in children has caused harm. Children are at increased risk of adverse effects when administered off- label medicines that were prescribed according to extrap- olations of adult data [5–8]. These observations are well supported by research demonstrating that children are not This article is part of the topical collection on Ethics of Pediatric Drug Research. A. C. Needham (&) Á M. Z. Kapadia Á M. Offringa Child Health Evaluative Sciences CHES, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON M5G 1X8, Canada e-mail: allison.needham@sickkids.ca M. Z. Kapadia e-mail: Mufiza.kapadia@sickkids.ca M. Offringa e-mail: martin.offringa@sickkids.ca Pediatr Drugs (2015) 17:23–30 DOI 10.1007/s40272-014-0098-9