Bratton E, Izem R, Garcia de Albeniz X, Li J. Real-World Evidence (RWE) generation for rare disease drug development and orphan drug approvals. Presentation to be given at the 2022 ICPE Conference; August 25, 2022. Copenhagen, Denmark.


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

1. ‘Natural History of Disease Studies for Rare Disease Drug Development’, E. Bratton The speaker will introduce Natural History of Disease Studies and outline the key differences and similarities with disease registries and relevant regulatory guidance. The benefits of conducting Natural History Studies for RD drug development will be presented and discussed, along with epidemiology considerations for natural history studies including study design, execution, and methods. Methodological strategies for using natural history studies for external comparators will be described.

2. [Currently Tentative] ‘Real World Evidence for the Treatments of Rare Diseases – Regulatory Perspectives’, J. Li The speak 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 Guidances 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. Case studies will demonstrate the quality of RWE required in support of regulatory considerations for pharmacological treatments for rare diseases.

3. ‘Leveraging longitudinal data in rare-disease study design and analysis’, R. Izem The speaker will review study designs exploiting repeated measures on the same subject. She will draw a parallel between some new and existing randomized studies in rare diseases and their less well-known controlled observational study designs. She will illustrate considerations, feasibility, and added values of these longitudinal designs with examples of analyses in multiple rare disorders, including urea cycle disorder and cystic fibrosis.

4. ‘Emulating a Target Trial in Case-Control Designs’, X. Garcia de Albeniz Martinez Textbooks refer to Case-Control studies as “particularly useful when one is studying a relatively rare disease” (Strom BL (2020). Pharmacoepidemiology. John Wiley & Sons Ltd). At the same time, conventional wisdom is that they do not yield estimates of effect that are as valid as those obtained from cohort studies, the same way as cohort studies are not considered as valid as randomized trials. The target trial emulation framework has helped close the gap between cohort studies and randomized trials. In this session we will explain how to apply the target trial emulation framework to the design and analysis of case-control studies.

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