{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:51:20Z","timestamp":1791910280558,"version":"4.3.4"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>In the EU, conditional marketing authorization is a pragmatic tool for early approval of a medicine that fulfills an unmet medical need. In the pharmaceutical legislation, an unmet medical need means that a condition lacks a satisfactory method for diagnosis, prevention, or treatment. If such satisfactory methods exist, the new medicinal product must hold a major therapeutic advantage for those affected, meaning that it must demonstrate an improvement in efficacy or safety over existing methods or, in exceptional cases, a major improvement in patient care. This review evaluates the approaches taken to justify a major therapeutic advantage in oncology and hematology products recommended for approval between 2006 and 2023. The review confirmed an increase in the number of conditional marketing authorizations over time. Out of a total of 65 CMAs, a satisfactory treatment method was available for 40 cases (61.5%), thereby requiring a demonstration of major therapeutic advantage to fulfill the unmet medical need requirement. Satisfactory treatments existed more often for the more recently approved medicinal products. Qualitative arguments and quantitative comparisons were common to demonstrate meaningful improvement in efficacy or safety. In the absence of head\u2010to\u2010head trials, indirect comparisons were often used. Most quantitative comparisons used na\u00efve side\u2010by\u2010side comparisons, lacking adjustments for trial differences or quantification of uncertainty. Regulatory guidance on indirect comparisons and data requirements may be helpful to support applicants and assessors in making available promising medicines early that fulfill an unmet medical need and continue to meet rigorous efficacy and safety standards pending availability of comprehensive data post\u2010approval.<\/jats:p>","DOI":"10.1002\/cpt.3554","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T05:51:16Z","timestamp":1736229076000},"page":"1098-1105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Demonstration of Major Therapeutic Advantage From a Review of <scp>EU<\/scp> Conditional Marketing Authorizations in Oncology and Hematology"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-0212","authenticated-orcid":false,"given":"Florian","family":"Lasch","sequence":"first","affiliation":[{"name":"European Medicines Agency  Amsterdam The Netherlands"},{"name":"Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9404-1043","authenticated-orcid":false,"given":"Joana R. B.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"European Medicines Agency  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4989-4792","authenticated-orcid":false,"given":"Caroline","family":"Pothet","sequence":"additional","affiliation":[{"name":"European Medicines Agency  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123193"},{"key":"e_1_2_10_2_1","unstructured":"European Medicines Agency.Annual report 2023<https:\/\/www.ema.europa.eu\/en\/annual\u2010report\/2023\/homepage.html> (2024)."},{"key":"e_1_2_10_3_1","unstructured":"European Commission.Commission Regulation (EC) No 507\/2006 of 29 March 2006 on the Conditional Marketing Authorisation for Medicinal Products for Human Use Falling within the Scope of Regulation (EC) No 726\/2004 of the European Parliament and of the Council(2006)."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00592-2"},{"key":"e_1_2_10_5_1","unstructured":"European Commission.Regulation (EC) No 726\/2004 of the European Parliament and of the Council of 31 March 2004 Laying down Union Procedures for the Authorisation and Supervision of Medicinal Products for Human and Veterinary Use and Establishing a European Medicines Agency(2004)."},{"key":"e_1_2_10_6_1","unstructured":"European Medicines Agency.Guideline on the Scientific Application and the Practical Arrangements Necessary to Implement Commission Regulation (EC) No 507\/2006 on the Conditional Marketing Authorisation for Medicinal Products for Human Use Falling within the Scope of Regulation (EC) No 726\/2004(2016)."},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2906"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2021.01.015"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2012.05.004"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(97)00049-8"},{"key":"e_1_2_10_11_1","unstructured":"Health Technology Assessment Coordination Group.Methodological guideline for quantitative evidence synthesis: direct and indirect comparisons(2024)."},{"key":"e_1_2_10_12_1","unstructured":"Phillippo D.M.et al.Nice DSU Technical Support Document 18: Methods for Population\u2010Adjusted Indirect Comparisons in Submissions to Nice S. Decision Support Unit University of Sheffield Editor.2016."},{"key":"e_1_2_10_13_1","unstructured":"European Commission.Proposal for a Directive of the European Parliament and of the Council on the Union Code Relating to Medicinal Products for Human Use and Repealing Directive 2001\/83\/EC and Directive 2009\/35\/EC(2023)."},{"key":"e_1_2_10_14_1","unstructured":"European Commission.Proposal for a Regulation of the European Parliament and of the Council Laying down Union Procedures for the Authorisation and Supervision of Medicinal Products for Human Use and Establishing Rules Governing the European Medicines Agency Amending Regulation (EC) No 1394\/2007 and Regulation (EU) No 536\/2014 and Repealing Regulation (EC) No 726\/2004 Regulation (EC) No 141\/2000 and Regulation (EC) No 1901\/2006(2023)."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3554","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:21:31Z","timestamp":1754904091000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/cpt.3554"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3554","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"assertion":[{"value":"2024-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}