A Transferable Health Economic Evaluation Framework for Alzheimer’s Disease-Modifying Therapies

A Transferable Health Economic Evaluation Framework for Alzheimer’s Disease-Modifying Therapies | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Transferable Health Economic Evaluation Framework for Alzheimer’s Disease-Modifying Therapies Sevinc Elif Sen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9602832/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Disease-modifying therapies (DMTs) for Alzheimer’s disease, including lecanemab and donanemab, have secured regulatory approval in multiple jurisdictions, yet health technology assessment (HTA) bodies in small and medium healthcare systems face unique challenges in evaluating these therapies. Existing economic evaluation frameworks have been developed predominantly within large-market HTA contexts (e.g., NICE, ICER), leaving a critical methodological gap for smaller systems with constrained diagnostic infrastructure, limited specialist workforce capacity, and distinct epidemiological profiles. This study presents a transferable health economic evaluation framework and accompanying interactive decision-support platform designed to address this gap. Methods: A decision-analytic modelling framework was developed incorporating three interconnected components: (1) a five-state Markov cohort model for cost-effectiveness analysis (CEA) of lecanemab and donanemab versus standard of care; (2) a multi-treatment budget impact analysis (BIA) engine with seven cost layers, country-specific population cascades, and adjustable market share trajectories; and (3) a discrete choice experiment (DCE) module for eliciting stakeholder preferences regarding DMT implementation attributes. The framework was parameterised and validated for Ireland as the index country, representing a tax-funded EU small market with emerging DMT readiness challenges. An interactive R Shiny platform was developed and publicly deployed to enable real-time scenario analysis and threshold exploration. The modular architecture is designed for transferability to additional healthcare systems. Model validation included comparison against published HTA assessments from NICE, ICER, CADTH, and PBAC. Results: Base-case incremental cost-effectiveness ratios (ICERs) for lecanemab versus standard of care were €296,506 per QALY gained, and €371,299 per QALY for donanemab, from the HSE payer perspective under HIQA guidelines. Neither treatment met the €45,000/QALY willingness-to-pay threshold at current list prices. Five-year budget impact under the base-case uptake scenario was estimated at €48.7 million, with drug acquisition costs representing the largest cost category (42–58%) followed by diagnostic infrastructure (18%). The DCE module identified monitoring burden, out-of-pocket costs, and treatment location as dominant preference attributes. Probabilistic sensitivity analysis demonstrated that cost-effectiveness conclusions were most sensitive to drug price, treatment discontinuation rates, and the time horizon adopted. The R Shiny platform enabled identification of threshold drug prices at which DMTs become cost-effective, providing actionable evidence for pricing negotiations. Conclusions: This study provides a transferable health economic evaluation framework specifically designed for DMT assessment in small and medium healthcare systems, demonstrated through application to Ireland. The integrated CEA-BIA-DCE architecture, combined with the publicly accessible interactive platform, offers a replicable methodology that can be adapted to additional country contexts as DMTs progress through regulatory and reimbursement pathways. The framework directly addresses calls from recent service-readiness analyses for quantitative decision-support tools to complement qualitative implementation planning. Health Economics & Outcomes Research Alzheimer’s disease disease-modifying therapies cost-effectiveness analysis budget impact analysis discrete choice experiment health technology assessment decision-analytic modelling Full Text Additional Declarations The authors declare no competing interests. Figure 1 is not available with this version. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9602832","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":633744871,"identity":"7b8e6e47-82a6-4235-b5a7-eff055bf9f1a","order_by":0,"name":"Sevinc Elif Sen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIie3PsWrDMBAGYBWDsqidCynWExTOBDIVP0ZnBYO9JOCxgwdBIVlC5hQPeYWYQmeJA09+gEI7OEtmQ6FjW8lkjI27FaofNOi4j18ixMXlj0aZc0M9daElIX47qQcQRqkglkzaiRjQxMiJzKS99hG+WgeYZnfsinq13mbvye4eD6Yl9G/leQJVBbgtY/MwCnpfHhfFWwyGRJOp6iDXscBLiYxyCbqmuChyYYmavXQQvjta8m1aRo2uvzAJ8qTpJeTVU4YoQxjoYomCj+f9LVBFClkZWZLqpw0G+/E8VQK6/8JX+vGDZaHPl6PisP5EzvPkuWkeQr+LnOltN2Hoetsrf7Pt4uLi8h/yAzBbZ3hwRqLvAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0008-5982-5812","institution":"Independent","correspondingAuthor":true,"prefix":"","firstName":"Sevinc","middleName":"Elif","lastName":"Sen","suffix":""}],"badges":[],"createdAt":"2026-05-03 22:54:12","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9602832/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9602832/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108976667,"identity":"df0792df-1b71-4e39-8be9-559359ae52cf","added_by":"auto","created_at":"2026-05-11 11:27:34","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":219558,"visible":true,"origin":"","legend":"","description":"","filename":"senaddmtIRELAND.docx.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9602832/v1_covered_f6d55a5e-10c0-4ea8-bfa5-8bc58e1d48fd.pdf"}],"financialInterests":"\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eFigure 1 is not available with this version.\u003c/p\u003e","formattedTitle":"\u003cp\u003e\u003cstrong\u003eA Transferable Health Economic Evaluation Framework for Alzheimer’s Disease-Modifying Therapies\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Alzheimer’s disease, disease-modifying therapies, cost-effectiveness analysis, budget impact analysis, discrete choice experiment, health technology assessment, decision-analytic modelling","lastPublishedDoi":"10.21203/rs.3.rs-9602832/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9602832/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eDisease-modifying therapies (DMTs) for Alzheimer’s disease, including lecanemab and donanemab, have secured regulatory approval in multiple jurisdictions, yet health technology assessment (HTA) bodies in small and medium healthcare systems face unique challenges in evaluating these therapies. Existing economic evaluation frameworks have been developed predominantly within large-market HTA contexts (e.g., NICE, ICER), leaving a critical methodological gap for smaller systems with constrained diagnostic infrastructure, limited specialist workforce capacity, and distinct epidemiological profiles. This study presents a transferable health economic evaluation framework and accompanying interactive decision-support platform designed to address this gap.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA decision-analytic modelling framework was developed incorporating three interconnected components: (1) a five-state Markov cohort model for cost-effectiveness analysis (CEA) of lecanemab and donanemab versus standard of care; (2) a multi-treatment budget impact analysis (BIA) engine with seven cost layers, country-specific population cascades, and adjustable market share trajectories; and (3) a discrete choice experiment (DCE) module for eliciting stakeholder preferences regarding DMT implementation attributes. The framework was parameterised and validated for Ireland as the index country, representing a tax-funded EU small market with emerging DMT readiness challenges. An interactive R Shiny platform was developed and publicly deployed to enable real-time scenario analysis and threshold exploration. The modular architecture is designed for transferability to additional healthcare systems. Model validation included comparison against published HTA assessments from NICE, ICER, CADTH, and PBAC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eBase-case incremental cost-effectiveness ratios (ICERs) for lecanemab versus standard of care were €296,506 per QALY gained, and €371,299 per QALY for donanemab, from the HSE payer perspective under HIQA guidelines. Neither treatment met the €45,000/QALY willingness-to-pay threshold at current list prices. Five-year budget impact under the base-case uptake scenario was estimated at €48.7 million, with drug acquisition costs representing the largest cost category (42–58%) followed by diagnostic infrastructure (18%). The DCE module identified monitoring burden, out-of-pocket costs, and treatment location as dominant preference attributes. Probabilistic sensitivity analysis demonstrated that cost-effectiveness conclusions were most sensitive to drug price, treatment discontinuation rates, and the time horizon adopted. The R Shiny platform enabled identification of threshold drug prices at which DMTs become cost-effective, providing actionable evidence for pricing negotiations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis study provides a transferable health economic evaluation framework specifically designed for DMT assessment in small and medium healthcare systems, demonstrated through application to Ireland. The integrated CEA-BIA-DCE architecture, combined with the publicly accessible interactive platform, offers a replicable methodology that can be adapted to additional country contexts as DMTs progress through regulatory and reimbursement pathways. 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