Kranz Philip, McGauran Natalie, Ünal Can, Kaiser Thomas
Researcher, Drug Assessment Department, Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, Germany.
Researcher, Communications Department, IQWiG, Cologne, Germany.
Int J Technol Assess Health Care. 2024 Dec 3;40(1):e68. doi: 10.1017/S026646232400062X.
The number of orphan drug (OD) approvals has increased sharply in Europe. In Germany, all ODs are initially subject to a limited assessment after market access. Their added benefit over the standard of care is accepted as established upon EU approval; a regular health technology assessment (HTA) is performed only in certain cases.
We assessed whether the increase in OD approvals has led to improvements in patient-relevant outcomes as supported by the evidence submitted by market authorization holders (MAHs) for HTA in Germany. We also examined the extent to which these ODs address unmet medical needs.
The results of limited assessments and regular HTAs of ODs in Germany (January 2011-September 2021, plus January-December 2023) were analyzed to determine their added benefit based on MAH-submitted dossiers. Added benefit was reported separately for each research question generated from the EU-approved therapeutic indications and any sub-indications (e.g., different subpopulations or control interventions) specified for HTA in Germany.
Eighty-nine ODs (limited assessments: sixty-nine; regular HTAs: twenty) were evaluated in 175 research questions (limited assessments: ninety-seven; regular HTAs: seventy-eight). The added benefit granted in limited assessments was non-quantifiable in nearly eighty percent of the ninety-seven questions. In regular HTAs, no proof of added benefit was shown in fifty-four percent of the seventy-eight questions, mainly due to insufficient comparative data with the standard of care. Established treatments were available for fifty-eight percent of the seventy-eight questions; more than half of which addressed oncology indications (although these account for only eight percent of rare diseases).
Due to evidence gaps in post-approval HTA, many ODs approved in the EU lack proof of added benefit in terms of improving patient-relevant outcomes. Moreover, most approved ODs are indicated for diseases with established treatments and oncology indications, while many unmet medical needs remain. Incentives are required to encourage research in areas of unmet medical need and to generate comparative data with the standard of care.
欧洲孤儿药（OD）的获批数量急剧增加。在德国，所有孤儿药在上市后最初都要接受有限评估。其相对于标准治疗的额外获益在欧盟获批后被视为已确立；仅在某些情况下进行常规卫生技术评估（HTA）。
我们评估了孤儿药获批数量的增加是否如德国上市许可持有人（MAH）提交给卫生技术评估的证据所支持的那样，带来了与患者相关结局的改善。我们还研究了这些孤儿药满足未满足医疗需求的程度。
分析了德国孤儿药有限评估和常规卫生技术评估的结果（2011年1月至2021年9月，以及2023年1月至12月），以根据上市许可持有人提交的档案确定其额外获益。针对从欧盟批准的治疗适应症以及德国卫生技术评估指定的任何亚适应症（例如，不同亚组或对照干预措施）产生的每个研究问题，分别报告额外获益情况。
在175个研究问题（有限评估：97个；常规卫生技术评估：78个）中评估了89种孤儿药（有限评估：69种；常规卫生技术评估：20种）。在97个问题中，近80%的问题在有限评估中给予的额外获益无法量化。在常规卫生技术评估中，78个问题中有54%未显示额外获益的证据，主要原因是与标准治疗的比较数据不足。78个问题中有58%有既定治疗方法；其中一半以上涉及肿瘤学适应症（尽管这些仅占罕见病的8%）。
由于批准后卫生技术评估中的证据空白，许多在欧盟获批的孤儿药在改善与患者相关结局方面缺乏额外获益的证据。此外，大多数获批的孤儿药适用于有既定治疗方法的疾病和肿瘤学适应症，而许多未满足的医疗需求仍然存在。需要激励措施来鼓励在未满足医疗需求领域开展研究，并生成与标准治疗的比较数据。
