i. With the goal of reducing or eliminating placebo burden on pediatric patients while maintaining FDA's high standards for the development of safe and effective medicines, it is recommended that FDA conduct analyses of placebo and natural history data from both successful and unsuccessful clinical trials in pediatric rare diseases. The aims of the research should be to: 1) consider published, peer-reviewed literature and complete an assessment of consistency or gaps between FDA's own analysis and published analysis; 2) provide recommendations regarding the contexts in which placebo may be reduced or eliminated based on pooling of existing data sources; 3) collaborate with disease area Consortia efforts that seek to provide both clinical and RWE evidence that could enhance FDA analyses of natural history data to support drug development in pediatric rare disease;4) provide recommendations to the scientific community regarding future research that is needed to further reduce use of placebo in pediatric clinical trials
ii. Given the DMD community's position on placebo-controlled trials, the considerable number of clinical trials in DMD (both successful and unsuccessful), and the on-going drug development activity in DMD, we recommend DMD as an initial disease area for this research. Once a framework for the research is established, we encourage FDA to look to other areas of unmet need where the pooling of placebo data have the potential to reduce placebo burden on pediatric patients.