Stefanov Rumen, Raycheva Ralitsa, Kostadinov Kostadin, Stefanov Georgi, Zdravkova-Aneva Iva, Dzhambazova Elizabet, Iskrov Georgi
Department of Social Medicine and Public Health, Faculty of Public Health, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
Institute for Rare Diseases, 4017 Plovdiv, Bulgaria.
Healthcare (Basel). 2025 Sep 9;13(18):2258. doi: 10.3390/healthcare13182258.
: Orphan medicinal products offer essential treatments for rare diseases, but patient access varies across European Union countries despite a common regulatory framework. In Bulgaria, access is primarily through inclusion in the positive drug list following health technology assessment or via individual access schemes under Ordinance No. 2/2019, which allows for ad hoc reimbursement. This study evaluates the timeliness and extent of Bulgarian patient access to orphan-designated drugs authorized by the European Medicines Agency. : We analyzed European Medicines Agency-authorized orphan drugs between July 2006 and September 2023 using data from the European Medicines Agency, Bulgarian health technology assessment bodies, positive drug list records, and individual access scheme reports. Medians, interquartile ranges, stratified analyses, and permutation/bootstrapping methods were applied. Of the 142 European Medicines Agency-approved orphan drugs, only 41 (28.9%) were included in the Bulgarian positive drug list. The median time to positive drug list inclusion was 828 days, with pre-health technology assessment delays (median 570 days) as the main bottleneck. Health technology assessment evaluations had a median duration of 204 days. Cancer and accelerated-assessment drugs reached health technology assessment faster, while conditional approvals faced longer delays. Twenty-four drugs were accessed through individual schemes; twenty remained outside the positive drug list. Overall, 43.0% of orphan drugs reached Bulgarian patients via either mechanism. : Access to orphan drugs in Bulgaria is limited and delayed, mainly due to pre-health technology assessment lags. In light of the forthcoming European Union health technology assessment regulation, Bulgaria must ensure that national processes are capable of rapidly translating centralized assessments into meaningful patient access.
孤儿药为罕见病提供了必要的治疗方法，但尽管有共同的监管框架，欧盟各国患者获得孤儿药的情况仍存在差异。在保加利亚，患者主要通过卫生技术评估后被列入药品报销清单，或根据第2/2019号法令的个人获取计划获得孤儿药，该法令允许临时报销。本研究评估了保加利亚患者获取欧洲药品管理局授权的孤儿药的及时性和程度。
我们利用欧洲药品管理局、保加利亚卫生技术评估机构、药品报销清单记录和个人获取计划报告的数据，分析了2006年7月至2023年9月期间欧洲药品管理局授权的孤儿药。应用了中位数、四分位距、分层分析以及排列/自抽样法。在欧洲药品管理局批准的142种孤儿药中，只有41种（28.9%）被列入保加利亚药品报销清单。被列入药品报销清单的中位时间为828天，卫生技术评估前的延误（中位时间570天）是主要瓶颈。卫生技术评估的中位时长为204天。癌症药物和加速评估药物进入卫生技术评估的速度更快，而有条件批准的药物面临更长的延误。24种药物通过个人计划获得；20种仍未被列入药品报销清单。总体而言，43.0%的孤儿药通过这两种机制之一提供给了保加利亚患者。
保加利亚患者获取孤儿药的机会有限且存在延误，主要原因是卫生技术评估前的滞后。鉴于即将出台的欧盟卫生技术评估法规，保加利亚必须确保国家程序能够迅速将集中评估转化为切实可行的患者获取途径。
