Issues, Challenges and Opportunities for Economic Evaluations of Orphan Drugs in Rare Diseases: An Umbrella Review.

BACKGROUND AND OBJECTIVES: There are significant challenges when obtaining clinical and economic evidence for health technology assessments of rare diseases. Many of them have been highlighted in previous systematic reviews but they have not been summarised in a comprehensive manner. For all stakeholders working with rare diseases, it is important to be aware and understand these issues. The objective of this review is to identify the main challenges for the economic evaluation of orphan drugs in rare diseases. METHODS: An umbrella review of systematic reviews of economic studies concerned with orphan and ultra-orphan drugs was conducted. Studies that were not systematic reviews, or on advanced therapeutic medicinal products, personalised medicines or other interventions that were not considered orphan drugs were excluded. The database searches included publications from 2010 to 2023, and were conducted in MEDLINE, EMBASE and the Cochrane library using filters for systematic reviews, and economic evaluations and models. These filters were combined with search terms for rare diseases and orphan drugs. A hand search supplemented the literature searches. The findings were reported by a compliant Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. RESULTS: Two hundred and eighty-two records were identified from the literature searches, of which 64 were duplicates, whereas five reviews were identified from the hand search. A total of 36 reviews were included after screening against inclusion/exclusion criteria, 35 from literature searches and one from hand searching. Of those studies 1, 27 and 8 were low, moderate and high quality, respectively. The reviews highlight the scarcity of evidence for health economic parameters, for example, clinical effectiveness, costs, quality of life and the natural history of disease. Health economic evaluations such as cost-effectiveness and budget-impact analyses were scarce, and generally low-to-moderate quality. The causes were limited health economic parameters, together with publications bias, especially for cost-effectiveness analyses. CONCLUSIONS: The results highlighted issues around a considerable paucity of evidence for economic evaluations and few cost-effectiveness analyses, supporting the notion that a paucity of evidence makes economic evaluations of rare diseases more challenging compared with more prevalent diseases. Furthermore, we provide recommendations for more sustainable approaches in economic evaluations of rare diseases.

A Cost-Utility Analysis of SQ® Tree SLIT-Tablet versus Placebo in the Treatment of Birch Pollen Allergic Rhinitis from a Swedish Societal Perspective.

Background and Aims: Allergic rhinitis (AR) is an immunoglobulin E antibody-mediated inflammatory condition that arises in response to inhaled allergens such as pollen. Pollens from trees in the birch homologous group are the most common allergenic tree pollens in Northern and Central Europe and North America. SQ® Tree SLIT-Tablet (ITULAZAX®) is a sublingual immunotherapy tablet indicated for moderate-to-severe AR and/or conjunctivitis induced by pollen from the birch homologous group. The present analysis evaluated the cost-utility of treating adults with AR with SQ Tree SLIT-Tablet versus placebo, both in combination with symptom-relieving medications, from a Swedish societal perspective. Methods: A model was developed to evaluate changes in cost and quality of life associated with using SQ Tree SLIT-Tablet relative to placebo in an adult population of individuals with AR. The model captured costs associated with symptom-relieving medications, healthcare professional interactions, SQ Tree SLIT-Tablet, and indirect costs arising from absenteeism and reduced workplace productivity. The analysis was conducted over 10 years with costs captured in 2021 Swedish Krona (SEK) and future costs and effects discounted at 3% per annum. One-way and probabilistic sensitivity analyses were conducted. Results: Treatment with SQ Tree SLIT-Tablet resulted in an improvement of 0.041 quality-adjusted life years (QALYs) over 10 years versus placebo. From a Swedish societal perspective, costs increased by SEK 9077 over the same period, resulting in an incremental cost-utility ratio of SEK 223,445 per QALY gained. One-way sensitivity analysis showed that the model was most sensitive to assumptions around the disease-modifying effect of SQ Tree SLIT-Tablet. Conclusion: SQ Tree SLIT-Tablet improved quality of life in moderate-to-severe AR and/or conjunctivitis induced by pollen from the birch homologous group in Sweden, with only a modest increase in societal costs over a medium-term time horizon, representing good value for money at a willingness-to-pay threshold of SEK 700,000 per QALY.

ITULAZAX® versus Alutard SQ® in the treatment of allergic rhinitis induced by pollen from the birch homologous group: A cost-minimization modeling analysis from the Danish societal perspective.

BACKGROUND AND AIMS: Allergic rhinitis (AR) is an inflammatory disorder triggered by an allergic immune response to inhaled allergens. Birch pollen is the major allergenic tree pollen in parts of Europe. ITULAZAX® is a sublingual immunotherapy tablet for the treatment of adults with moderate-to-severe AR and/or conjunctivitis induced by pollen from the birch homologous group. The aim was to compare the costs of treating AR with ITULAZAX® versus subcutaneous ALUTARD SQ® Betula verrucosa (ALUTARD SQ®) from a Danish societal perspective. METHODS: A cost-minimization model was developed to capture costs of allergy immunotherapy (AIT), interactions with healthcare professionals (HCPs) in three different care settings (general practice, allergy specialist, and hospital), and indirect costs arising from absenteeism and presenteeism. The cost-minimization analysis was conducted over a 3-year time horizon with costs reported in 2021 Danish Kroner (DKK) and Euros (EUR) based on the European Central Bank 365-day average exchange rate. One-way sensitivity analyses were performed. RESULTS: The base case analysis showed that the total cost of treatment over 3 years was estimated to be DKK 49,117 (EUR 6598) per patient with ALUTARD SQ®, compared with DKK 30,996 (EUR 4164) with ITULAZAX®, reflecting a cost saving of DKK 18,121 (EUR 2434) per patient with ITULAZAX® over 3 years. Over the 3-year time horizon, costs of AIT were predicted to increase by DKK 17,928 (EUR 2408) with ITULAZAX®, while costs of interactions with HCPs were predicted to decrease by DKK 22,528 (EUR 3027) versus ALUTARD SQ®, more than offsetting the increased cost of ITULAZAX®. CONCLUSIONS: Given the equivalent effectiveness of the two AIT products, and the cost savings with ITULAZAX® versus ALUTARD SQ® from a Danish societal perspective, ITULAZAX® should be considered as a cost-saving alternative to ALUTARD SQ® for the treatment of birch pollen-induced moderate-to-severe AR in adults.

The cost-effectiveness of oral contraceptives compared to 'no hormonal treatment' for endometriosis-related pain: An economic evaluation.

OBJECTIVE: To develop a preliminary cost-effectiveness model that compares oral contraceptives and 'no hormonal treatment' for the treatment of endometriosis-related pain. METHODS: A de novo preliminary state transition (Markov) model was developed. The model was informed by systematic literature review and expert opinion. The uncertainty around the results was assessed both by deterministic and probabilistic sensitivity analyses. The economic evaluation was conducted from National Health Service (NHS) England perspective. The main outcome measure was incremental cost per quality-adjusted life year (QALY), with cost-effectiveness plane and cost-effectiveness acceptability curves presented for alternative willingness-to-pay thresholds. RESULTS: Oral contraceptives dominated 'no hormonal treatment' and provided more QALYs at a lower cost than 'no hormonal treatment', with a cost-effectiveness probability of 98%. A one-way sensitivity analysis excluding general practitioner consultations showed that oral contraceptives were still cost-effective. CONCLUSIONS: The analyses showed that oral contraceptives could be an effective option for the treatment of endometriosis, as this treatment was shown to provide a higher level of QALYs at a lower cost, compared to 'no hormonal treatment'. The results are subject to considerable parameter uncertainty as a range of assumptions were required as part of the modelling process.

Utility elicitation in adults and children for allergic rhinoconjunctivitis and associated health states.

PURPOSE: Allergic rhinitis and asthma symptoms are detrimental to health-related quality of life (HRQoL). Health technology appraisal agencies often require cost-utility analysis when assessing new interventions. Appropriate utility estimates, which quantify the value of different conditions in cost-utility analyses, are scarce for allergic rhinitis and asthma health states. This study aimed to generate utilities for allergic rhinitis and asthma health states from a European general population sample of adults and children. METHODS: Health state descriptions incorporating symptoms, impact of symptoms on daily life and symptom treatment were developed using clinical guidelines. Descriptions were amended with clinician and patient input, and incorporated into a survey in which each health state was followed by a standard gamble (adults) or visual analogue scale (children) item. The survey was distributed to samples of adults and children aged 8 to 11 from four European countries that were stratified to represent the general population within that country. RESULTS: 1454 adults and 1082 children completed the survey. Mean health utilities ranged from 0.635 to 0.880 and those elicited in children were lower (0.635 to 0.705) than those elicited in adults (0.812 to 0.880). Disutilities assessing the impact of increased allergic rhinitis severity and comorbidities were also greater in children than in adults. CONCLUSIONS: Symptoms of allergic rhinitis and asthma were valued as having a clinically meaningful impact on HRQoL. Children valued health states as poorer than adults, and further research should investigate whether this reflects true preferential differences or results from methodological and/or comprehension differences between the two groups.