Rare disease is a rapidly expanding area of research and clinical development. Advancements in genetic understanding and other scientific breakthroughs have led to improved identification of rare diseases and possible pathways for improving rare disease diagnosis, prognosis and treatment, as well as stratifying relatively common diseases into many rarer ones. Rare disease research challenges are diverse, interrelated, and can be either unique to or especially severe or burdensome. Rare diseases, inherently characterized by their low frequency, make disease recognition and diagnosis, evaluation of treatment effect, and patient recruitment problematic. These research challenges impact HTA, reimbursement, and market access. The lack of clinical data, disease natural history, validated endpoints and assessment instruments, and established comparator treatments lead to uncertainty for health care payers and other stakeholders, consequently impacting equity of access. This Rare Disease Special Interest Group will present an in depth discussion of their findings and answer audience questions.