ISSUE: Innovative medicines for rare diseases are often transformative for patients, especially when they are the first medicines designed to treat the underlying cause of disease. They may offer significant value to patients, caregivers and society. However, the ability to demonstrate clinical benefit and cost effectiveness at the time of regulatory approval using existing methodologies can be challenging. Paul Hodgkins (moderator) will introduce this issue and the panel. Ron Akehurst will present the case for largely adhering to current methods and evidence standards. Maarten Postma will consider alternative methodological approaches and data sources that have been and can be used. Alastair Kent will focus on patient engagement and the justification for adaptation of existing HTA processes to better evaluate innovative medicines. OVERVIEW: Evolution of the regulatory pathways for transformative therapies is enabling access to medicines at an earlier stage than ever before. To benefit from advances in clinical research in rare diseases and to take advantage of this evolving regulatory framework, an appropriately timed and conducted value assessment of these therapies is required. A balance is needed between early access, evidence of clinical benefit, acceptable cost effectiveness and the application of integrative and iterative methodologies for assessment. The issues faced in rare diseases are exemplified when a therapy may primarily offer survival benefits that are many years in the future and potentially subject to relevant uncertainty but costs accrue immediately. Can faster patient access to medicines be achieved whilst satisfying the need for demonstration of clinical and economic value of transformative medicines at time of approval? What can be learned from recent HTAs of rare diseases? Does this require decision makers to accept higher degrees of uncertainty within a broader context of benefits? This panel will review the opportunities and challenges for assessment of innovative medicines for rare diseases.