{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:00:36Z","timestamp":1790938836041,"version":"4.1.0"},"reference-count":23,"publisher":"Becaris Publishing Limited","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Comp. Eff. Res."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>On 30 April 2026, the Member State Coordination Group on Health Technology Assessment endorsed Europe\u2019s first joint clinical assessment (JCA) under Regulation (EU) 2021\/2282, evaluating tovorafenib (Ojemda) for pediatric low-grade glioma harboring BRAF alterations. This perspective analyses the inaugural JCA report as a diagnostic of the European Health Technology Assessment framework under conditions of structural evidentiary constraint. The assessment revealed two structural points. First, between evidentiary rigor and feasibility: seven of eight predefined PICO (Population, Intervention, Comparator, Outcome) questions could not be answered comparatively, reflecting both the unavoidable limits of single-arm trial design in ultra-rare pediatric oncology and addressable failures in submission quality. Second, a temporal: the JCA is a one-time assessment, yet the report repeatedly identifies uncertainties that future evidence could reduce, with no regulatory mechanism to update the record. Our perspective further examines how comparator selection risks encoding access inequality as a scientific requirement, how the framework\u2019s legislative scope renders caregiver and family burden invisible to assessment, and how the absence of explicit certainty grading limits the actionability of JCA outputs for national payers. We suggest some improvements organized across three tiers: better use of existing mechanisms, guidance development within the current framework and legislative revision where structural change is required.<\/jats:p>","DOI":"10.57264\/cer-2026-0141","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:59:43Z","timestamp":1789642783000},"source":"Crossref","is-referenced-by-count":0,"title":["Rigorous, transparent and inconclusive: what Europe\u2019s first joint clinical assessment reveals about a framework trying to serve everyone"],"prefix":"10.57264","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-7729","authenticated-orcid":false,"given":"Ramiro","family":"Gilardino","sequence":"first","affiliation":[{"name":"Insights &amp; Impact, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3685-1512","authenticated-orcid":false,"given":"Antonella","family":"Cardone","sequence":"additional","affiliation":[{"name":"Cancer Patients Europe, Bruselles, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6004-9488","authenticated-orcid":false,"given":"Carlos M","family":"Cossio","sequence":"additional","affiliation":[{"name":"University of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"36897","reference":[{"key":"e_1_3_6_2_2","first-page":"1","article-title":"Regulation (EU) 2021\/2282 of the European Parliament and of the Council of 15 December 2021 on health technology assessment and amending Directive 2011\/24\/EU","volume":"458","author":"European Parliament, Council of the European Union","year":"2021","unstructured":"European Parliament, Council of the European Union. Regulation (EU) 2021\/2282 of the European Parliament and of the Council of 15 December 2021 on health technology assessment and amending Directive 2011\/24\/EU. Off. J. Eur. Union. L458, 1\u201332 (2021).","journal-title":"Off. J. Eur. Union."},{"key":"e_1_3_6_3_2","unstructured":"Member State Coordination Group on Health Technology Assessment. Joint Clinical Assessment Report of a Medicinal Product: Tovorafenib Version 1.0 (2026). Directorate-General for Health and Food Safety European Commission Brussels. Version 1.0. (2026). https:\/\/health.ec.europa.eu\/publications\/joint-clinical-assessment-report-tovorafenib-ojemda_en"},{"key":"e_1_3_6_4_2","unstructured":"European Commission. Implementation of the regulation on health technology assessment [rolling plan webpage]. Directorate-General for Health and Food Safety. https:\/\/health.ec.europa.eu\/health-technology-assessment\/implementation-regulation-health-technology-assessment_en"},{"key":"e_1_3_6_5_2","unstructured":"European Commission Directorate-General for Health and Food Safety. Guidance on filling in the Joint Clinical Assessment (JCA) dossier template \u2013 Medicinal products. (2024). https:\/\/health.ec.europa.eu\/document\/download\/3943ae6a-1bca-4afd-b05c-fd9a54a252d7_en?filename=hta_jca_mp_dossier-template_guidance_en.pdf"},{"key":"e_1_3_6_6_2","unstructured":"European Medicines Agency. Ojemda (tovorafenib): summary of positive opinion. Reference number EMA\/CHMP\/43372\/2026. Amsterdam: EMA; (2026). https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/ojemda"},{"issue":"1","key":"e_1_3_6_7_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41591-023-02668-y","article-title":"The type II RAF inhibitor tovorafenib in relapsed\/refractory pediatric low-grade glioma: the Phase II FIREFLY-1 trial","volume":"30","author":"Kilburn LB","year":"2024","unstructured":"Kilburn LB, Khuong-Quang DA, Hansford JR The type II RAF inhibitor tovorafenib in relapsed\/refractory pediatric low-grade glioma: the Phase II FIREFLY-1 trial. Nat. Med. 30(1), 207\u2013217 (2024).","journal-title":"Nat. Med."},{"issue":"1","key":"e_1_3_6_8_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s12885-024-11820-x","article-title":"LOGGIC\/FIREFLY-2: a Phase III, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration","volume":"24","author":"van Tilburg CM","year":"2024","unstructured":"van Tilburg CM, Kilburn LB, Perreault S LOGGIC\/FIREFLY-2: a Phase III, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer 24(1), 147 (2024).","journal-title":"BMC Cancer"},{"key":"e_1_3_6_9_2","first-page":"L1381","article-title":"Commission Implementing Regulation (EU) 2024\/1381 of 23 May 2024 laying down, pursuant to Regulation (EU) 2021\/2282 on health technology assessment, procedural rules for the interaction during, exchange of information on, and participation in, the preparation and update of Joint Clinical Assessments of medicinal products for human use at Union level, as well as templates for those Joint Clinical Assessments","author":"European Commission","year":"2024","unstructured":"European Commission. 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Health Econ. 23(6), 913\u2013915 (2022).","journal-title":"Eur. J. Health Econ."},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/jmahp13030032"},{"key":"e_1_3_6_12_2","unstructured":"Member State Coordination Group on Health Technology Assessment (HTACG). Methodological guideline for quantitative evidence synthesis: direct and indirect comparisons. (2024). 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Commission Implementing Regulation (EU) 2024\/2699 laying down procedural rules on cooperation and exchange of information between the coordination group and the EMA with the facilitation of the HTA secretariat in relation to JCAs and JSCs. https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=OJ:L_202402699"},{"key":"e_1_3_6_15_2","unstructured":"European Commission Directorate-General for Health and Food Safety. Patients carers and clinical experts involvement \u2013 FAQ. https:\/\/health.ec.europa.eu\/health-technology-assessment\/implementation-regulation-health-technology-assessment\/opportunities-patients-carers-and-clinicians\/patients-carers-clinical-experts-involvement-faq_en"},{"key":"e_1_3_6_16_2","unstructured":"European Commission. Commission Implementing Regulation (EU) 2024\/2745 laying down rules on the management of conflicts of interest in the joint work of the coordination group and its subgroups. https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=OJ:L_202402745"},{"issue":"3","key":"e_1_3_6_17_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3390\/jmahp13030038","article-title":"Patient involvement in health technology assessments: lessons for EU Joint Clinical Assessments","volume":"13","author":"Pickaert A-P","year":"2025","unstructured":"Pickaert A-P, Acute Leukemia Advocates Network. Patient involvement in health technology assessments: lessons for EU Joint Clinical Assessments. J. Mark. Access Health Policy 13(3), 38 (2025).","journal-title":"J. Mark. Access Health Policy"},{"issue":"3","key":"e_1_3_6_18_2","doi-asserted-by":"crossref","first-page":"e240239","DOI":"10.57264\/cer-2024-0239","article-title":"Access in all areas? 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