Real-World Evidence (RWE) Generation for Rare Disease Drug Development and Orphan Drug Approvals

Course Outline
This course presents four topics related to generation of real-world evidence to support rare ‎disease drug development and orphan drug approvals.‎

Course Introduction and Session QnA will be led by Emily Bratton. ‎

‎1.‎ ‎‘Natural History of Disease Studies for Rare Disease Drug Development’
The speaker will introduce Natural History of Disease Studies (NHODs) and outline the key ‎differences and similarities with disease registries. Key uses for NHODs for rare disease drug ‎development will be presented and discussed, along with rationale for NHOD, approaches in ‎study design, execution, and methods. Methodological strategies for using natural history ‎studies for external comparator arms (ECAs) will be described with relevant case studies and ‎examples throughout her talk. ‎
‎2.‎ ‎‘Leveraging real-world data in rare-disease study design and analysis’
The speaker will outline the opportunities for studying rare diseases using secondary databases, ‎which include studying the epidemiology and clinical prodrome/natural history of the disease, ‎using prediction to identify patients with rare diseases earlier and applying novel methods from ‎clinical trials to observational research for answering causal questions. For each opportunity, the ‎methodological challenges and potential solution(s) will be discussed. Case studies will be ‎presented for each topic.‎
‎3.‎ ‎‘Applied methods of casual inference in rare disease research’
The speaker will address the following:‎
• Review of the target trial emulation framework
• Identify aspects of target trial emulation of special interest for rare disease research
• Case examples illustrating such aspects
• Discuss how the target trial emulation framework can help identify and tackle some of ‎the challenges of using external comparators
‎4.‎ ‎[Currently Tentative] ‘RWE for Rare Disease Treatment – Regulatory Perspectives’,
The speaker will introduce FDA’s RWE Program and RWE Framework which direct the evaluation ‎of RWE to support regulatory decision making. There will be discussions on RWE-related Draft ‎Guidance’s for industry, as well as the FDA Guidance specific to rare diseases. The instructor will ‎present key considerations for evaluating RWE in data sources, study designs, and study ‎conducts, in the context of rare diseases to intersect with above lecturer examples. Case studies ‎will demonstrate the quality of RWE required in support of regulatory approval for ‎pharmacological treatments for rare diseases. ‎