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.

Survival after acute episodes of immune-mediated thrombotic thrombocytopenic purpura (iTTP) - cognitive functioning and health-related quality of life impact: a descriptive cross-sectional survey of adults living with iTTP in the United Kingdom.

OBJECTIVES: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare life-threatening thrombotic microangiopathy affecting adults with unpredictable disease onset and acute presentation. This study aimed to describe the health-related quality of life (HRQoL), cognitive functioning and work productivity of survivors following acute episode(s) of iTTP in the United Kingdom (UK). METHODS: An online survey was developed in collaboration with the TTP Network. Descriptive statistics were calculated for the health questionnaire Short Form Survey-36 Version 2 (SF-36v2), the Hospital Anxiety and Depression Score (HADS), the PROMIS Cognitive Function Abilities Subset - Short Form 6a (PROMIS CFAS - SF6a), and the Work Productivity and Activity Index: Specific Health Problem (WPAI-SHP), along with several iTTP-specific bespoke questions. RESULTS: Fifty participants were recruited between July-November 2019. The mean (standard deviation [SD]) standardized SF-36v2 physical and mental component scores were 42.16 (9.59) and 33.61 (12.34), lower than population norms. The mean (SD) standardized PROMIS CFAS - SF6a score was 39.69 (7.86), lower than population norms. HADS mean (SD) scores of 12.18 (3.14) and 11.78 (2.36) indicated moderate levels of anxiety and depression, respectively. Of those employed (58%), approximately 42.73% of participants reported work productivity loss due to their iTTP. Participants also reported experiencing flashbacks, fatigue interference in family, social and intimate life, and fears of relapse. DISCUSSION AND CONCLUSION: Regardless of recency of the last acute episode, participant scores signified impairments in all domains. Remission from an acute episode of disease does not signify the conclusion of care, but rather the requirement for long-term healthcare particularly focused on psychological support.

Development of a New Quality of Life Measure for Duchenne Muscular Dystrophy Using Mixed Methods: The DMD-QoL.

OBJECTIVE: Based on concerns about existing patient-reported outcome measures (PROMs) for assessing quality of life (QoL) in Duchenne muscular dystrophy (DMD), we describe the mixed methods development of a new QoL PROM for use in boys and men with DMD: the DMD-QoL. METHODS: The DMD-QoL was developed in 3 stages. First, draft items were generated from 18 semistructured qualitative interviews with boys and men with DMD, analyzed using framework analysis. Second, cognitive debriefing interviews with patients (n = 10), clinicians (n = 8), and patients' parents (n = 10) were undertaken, and a reduced item set was selected and refined. Third, psychometric data on the draft items from a cross-sectional online survey (n = 102) and stakeholder input from patients and patients' parents were used to produce the final questionnaire. Patient and public involvement and engagement was embedded throughout the process. RESULTS: From an initial draft of 47 items, a revised set of 27 items was produced at stage 2, and this set was further refined at stage 3 to generate the DMD-QoL, a 14-item QoL PROM. The DMD-QoL is designed for use from 7 years of age by proxy report and from 10 years of age by self-report or proxy report. The final measure showed good psychometric properties. CONCLUSION: The DMD-QoL is a new 14-item QoL PROM for boys and men with DMD, with demonstrable content and face validity.