{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:57:04Z","timestamp":1789016224398,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gene therapies are poised to become a new therapeutic option for persons with haemophilia (PwH), having begun to show durable efficacy and safety in clinical trials to date. However, value assessment of gene therapies faces challenges from small populations that preclude randomized clinical trials (RCT), ethical considerations when treating a serious genetic disorder with lifelong consequences, and appropriate endpoint selection that captures the full scope of the disorder and its lifelong complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary<\/jats:title><jats:p>Health technology assessment (HTA) for new haemophilia therapies may require greater flexibility in evidence requirements and recognition of factors that vary across patient populations and health systems, including current standard\u2010of\u2010care, gains in survival and health\u2010related quality\u2010of\u2010life (HRQoL), and reduced replacement factor utilization. It will be important for HTAs to consider limitations of RCTs for gene therapy and to consider intra\u2010patient data as evidence of clinical effectiveness. Despite long\u2010term clinical trials with up to 8 years of follow\u2010up, ongoing uncertainties about durability of effect may be informed by extrapolating clinical data out \u223c10 years, using different projections of durability. Beyond objective endpoints, such as Petersson scores or annualized bleed rates, health utilities that accompany gene therapy (e.g., mental health, freedom of choice, peace of mind) should be considered in HTA evaluations, particularly for comparisons with low dose or no prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HTAs of gene therapies in haemophilia are encouraged to rise to the challenge of filling evidence gaps and conducting assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>KEY POINTS OF CONSIDERATION<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>It is important for HTA bodies to consider the limitations to conduct randomized controlled trials for gene therapy and to consider intrapatient data as evidence of comparative effectiveness.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Given the uncertainties around the long\u2010term gene therapy use, clinical trial data should be extrapolated \u223c10 years, using scenarios that consider different durations of effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The major value drivers in a model, in addition to drug pricing itself, will be based on assumptions about duration of effect and savings\/cost offsets from reduced use of replacement therapy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Assessment methodologies and modelling configurations need to evolve to fully capture the value of gene therapy, including patient meaningful outcomes, in a validated and quantitative fashion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Regardless of payment system archetype, the intersection between NGOs, the clinical community's voice, HTA willingness to collaborate, and alignment with regulatory acceptance of benefit is critical.<\/jats:p>\n<jats:p>[Correction added on 21 February 2022, after first online publication: the \u2018Key Points of Consideration\u2019 have been added in this version.]<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14413","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T09:29:23Z","timestamp":1643102963000},"page":"19-26","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Health technology assessment for gene therapies in haemophilia"],"prefix":"10.1111","volume":"28","author":[{"given":"Jamie","family":"O'Hara","sequence":"first","affiliation":[{"name":"HCD Economics  Daresbury UK"},{"name":"University of Chester  Chester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Center for the Evaluation of Value and Risk in Health Institute for Clinical Research and Health Policy Studies, Tufts Medical Centre  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the International Haemophilia Access Strategy Council","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01123-X"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01882.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12288-015-0562-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-528414"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2020.069"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-018-0610-0"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708483"},{"key":"e_1_2_11_10_1","unstructured":"U.S. Centers for Disease Control and Prevention. 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