The Challenge for Orphan Drugs Remains: Three Case Studies Demonstrating the Impact of Changes to NICE Methods and Processes and Alternative Mechanisms to Value Orphan Products.

Background: The National Institute for Health and Care Excellence (NICE) is responsible for ensuring that patients in England and Wales can access clinically and cost-effective treatments. However, NICE's processes pose significant reimbursement challenges for treatments for rare diseases. While some orphan medicines have been appraised via the highly specialised technology route, most are appraised via the single technology appraisal programme, a route that is expected to be increasingly used given new more restrictive highly specialised technology criteria. This often results in delays to access owing to differences in applicable thresholds and the single technology appraisal approach being ill-equipped to deal with the inevitable decision uncertainty. NICE recently published their updated methods and process manual, which includes a new severity-of-disease modifier and an instruction to be more flexible when considering uncertainty in rare diseases. However, as the threshold gap between the single technology appraisal and highly specialised technology programmes remains, it is unlikely that these changes alone will address the problem.

Objective: We explored the potential impact of quality-adjusted life-year weights in decision making.

Methods: We explored the impact of NICE's new severity-of-disease modifier weighting and two alternative methods (the use of alternative quality-adjusted life-year weights and the fair rate of return), using three recent single technology appraisals of orphan medicines (caplacizumab, teduglutide and pirfenidone for mild idiopathic pulmonary fibrosis).

Results: Our results suggest NICE's severity-of-disease modifier would not have affected the recommendations. Using alternative methods, based upon achievement of an incremental cost-effectiveness ratio below standard thresholds, patients could have received access to caplacizumab approximately 5 months earlier, and the appraisals for teduglutide and pirfenidone would have resulted in a positive recommendation following appraisal consultation meeting 1 when neither of these products was available over 5 years from the initial submission.

Conclusion: Ultimately, moving from a restrictive end-of-life modifier to one based on disease severity is a more equitable approach likely to benefit many therapies, including orphan products. However, NICE's single technology appraisal updates are unlikely to result in faster reimbursement of orphan medicines, nor will they address concerns around market access for orphan medicines in the UK.