SC-13 - Real-World Evidence Generation for Rare Disease Drug Development

Course Outline: This pre-conference course presents topics related to generation of real-world evidence to support rare disease drug development and orphan drug approvals. There are 4 experienced faculty that will spend the session presenting on integrated themes for pharmacoepidemiologist interested in rare disease research methods, inclusive of a classroom activity to illustrate core concepts.

1. Natural History of Disease Studies for Rare Disease Drug Development, E. Bratton
Emily 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 regulatory decisions.

2. Optimizing data sources for rare disease research, D. Rosenberg
Daniel will dive more deeply into finding and selecting existing data and data partners for rare disease research. Fit for use assessment RWD for rare disease including topics such as patient identification challenges and opportunities, challenges with general federated data network (FDN)s and opportunity for disease specific FDNs in rare disease, including meta-analytic approaches will be discussed. Case studies will be included.

3. Rare diseases analyses in secondary databases, L. Hester
Laura will outline opportunities and methodological approaches for exploring rare diseases using secondary data, including studying the epidemiology and clinical prodrome/natural history of the disease, developing prediction models for earlier identification of rare disease patients, and conducting comparative studies using strategies that address small sample sizes. For each opportunity, the methodological challenges and potential solution(s) will be discussed. Case studies will be presented for each topic.

4. Applied methods of casual inference in rare disease research, X. Garcia de Albeniz Martinez
Xabi will address the following, while using case examples illustrating core concepts:
• Review of the target trial emulation framework
• Identify aspects of target trial emulation of special interest for rare disease research
• External Control Arms studies: review of regulatory feedback, study design and methods of recent submissions to a regulator.
• Discussion of a methodological framework.