Case studies and decision tree for determining the need of juvenile animal studies for pediatric drug development

Abstract

In the development of pediatric drugs, juvenile animal studies (JAS) are important to support clinical trials in the pediatric population. However, JAS are not always needed depending on factors such as pediatric patient age, dosing duration, and available existing data. The need for JAS should be decided on case-by-case basis considering animal welfare and technical feasibility in addition to the aforementioned factors. The guideline on nonclinical safety testing for pediatric pharmaceutical developments (ICH S11) issued in 2020 states the criteria for determining the need of JAS, which were insufficient in the guidelines previously issued by regulatory authorities in various countries. The guideline describes the factors to be considered and the consideration on evaluating each factor and recommends the weight of evidence (WoE) approach through which multiple factors are evaluated together. As supportive tools, a conceptual diagram and 4 case studies are included. Approximately 2 years have passed since the guideline was issued. However, it remains complicated to decide whether JAS are necessary even after referring to the guidelines. We prepared a collection of case studies as training material to better understand the WoE approach. Throughout this work, as the efficient flow for deciding the need of JAS based on the importance and relationship of each factor became clear, we tried to create a decision tree. In this presentation, we will introduce case studies in which the currently generated decision tree was used for making complicated decisions.