Making decisions based on uncertain evidence: Exploring uncertainty in health technology assessment for rare diseases in England and Germany

在获得营销授权后，包括罕见病治疗(RDT)在内的健康技术在不同的司法管辖区接受健康技术评估(HTA)，目的是向支付者提供有关技术覆盖和/或报销的决策信息和建议。然而，由于与疾病和治疗相关的挑战，RDTs通常与有限和不确定的证据基础有关，这使得与其他替代品相比，对其益处的判断变得复杂。此外，创新的RDT的持续增长导致了大量的RDT报销申请，HTA系统需要及时做出反应。这给HTA评估员带来了相当大的挑战，他们试图决定在公共资助的医疗系统内支付什么费用。他们将不得不平衡RDT的不确定证据，同时努力在有限资源的背景下满足大量和多样化的罕见疾病患者的医疗需求。广泛的研究表明，HTA机构倾向于使用类似的方法来评估卫生技术提交的证据，但各国的报销建议有所不同。此外，深入分析了区域技术援助在区域技术援助进程中面临的挑战，以及通过通常不那么可靠的证据被接受的定制方案来解决区域技术援助的不确定性的办法。偶尔，研究会探索不同国家的HTA机构是如何考虑或评估不确定性的。然而，特别关注如何在HTA中评估RDT的不确定性的研究很少。虽然HTA中的不确定性总是在一定程度上存在，但HTA机构如何考虑不确定性是根据具体情况和背景而定的。因此，这项拟议的研究试图了解英国和德国的HTA流程如何解决这些困难并评估RDT的不确定性，并探索已用于克服这些挑战的方法。定量方法将包括对从HTA报告中提取的数据进行统计分析，定性方法将包括采访来自HTA机构、制药制造商和患者组织的关键信息者。我选择英国和德国作为分析的国家，因为这两个司法管辖区都有强大的制药业存在，因此经历了新的和创新的治疗方法的快速引入。此外，在这两个司法管辖区，HTA机构的作用、HTA实践和医疗保健系统的类型都不同，但对于定价和报销目的同样至关重要。最后，两个司法管辖区都将其HTA报告在网上公开提供，并且司法管辖区的语言不会对分析构成障碍。鉴于医疗保健部门可用资源有限，这项研究有助于制定证据，为罕见疾病的资源分配决策提供信息。更好地了解RTT的HTA中的不确定性可以提供重要的见解，以确保患者及时、负担得起和公平地获得创新治疗，更好地协调RDT的决策，并改善罕见疾病患者的健康结果，最终有助于改善整体健康和福祉。学员如何满足ESRC的技能优先事项：-应用定量和定性研究方法-开发和执行协作的跨学科研究设计-发展卫生技术评估、卫生经济学和政策联系方面的专门知识，与研究用户接触并建立网络，包括来自HTA机构、政策、学术界和罕见疾病患者组织的利益相关者-提高可转换性和领导力技能

After having received marketing authorisation, health technologies, including rare disease treatments (RDTs), undergo health technology assessment (HTA) in different jurisdictions, with the purpose to inform and advise payers in their decision-making about coverage and/or reimbursement of the technology. However, due to disease- and treatment-related challenges, RDTs are typically associated with a limited and uncertain evidence base, which complicates judgements about their benefits in comparison to other alternatives. Additionally, the continuous growth in innovative RDTs is resulting in a high volume of RDT reimbursement applications to which HTA systems need to respond timely. This poses considerable challenges for HTA assessors seeking to make decisions about what to pay for within publicly funded health systems. They will have to balance the uncertain evidence for RDTs, while striving to meet the healthcare needs of a large and diverse rare disease patient population in the context of finite resources. Extensive research demonstrated that HTA bodies tend to draw on similar methodologies for evaluating the submitted evidence for health technologies, but reimbursement recommendations diverge across countries. Moreover, challenges of RDTs in HTA processes and approaches to addressing uncertainty around RDTs through bespoke programmes in which often less robust evidence is accepted have been analysed thoroughly. Occasionally, studies have explored how uncertainties are considered or assessed by HTA agencies in different countries. However, studies focusing particularly on how uncertainty is assessed in HTA for RDTs are scarce. While uncertainties are always present at some level in HTA, how uncertainty is considered by HTA agencies is situation- and context-specific. Therefore, the proposed research seeks to understand how HTA processes in England and Germany address these difficulties and evaluate uncertainty for RDTs, and explore approaches that have been used to overcome these challenges.Quantitative methods will include statistical analyses of extracted data from HTA reports, and qualitative methods will include interviews with key informants from HTA agencies, pharmaceutical manufacturers and patient organisations. I chose England and Germany as countries for analysis as both jurisdictions have a strong pharmaceutical industry presence and thus experience a rapid introduction of new and innovative treatments. In addition, the role of the HTA agencies, HTA practises, and the type of healthcare system are different in both jurisdictions but equally crucial for pricing and reimbursement purposes. Lastly, both jurisdictions make their HTA reports publicly available online and the languages of the jurisdictions for not pose a barrier for analysis.In light of limited available resources in the healthcare sector, this research contributes to the development of evidence that can inform resource allocation decisions for rare diseases. A better understanding about uncertainties in HTA for RDTs can provide important insights towards ensuring timely, affordable, and equitable patient access to innovative treatments, better consistency in decision-making for RDTs, and improve health outcomes of rare disease patients, ultimately contributing to better health and wellbeing overall.How the studentship meets ESRC skill priorities:- Applying quantitative and qualitative research methods- Developing and executing a collaborative, interdisciplinary research design- Developing specialized expertise in health technology assessment, and health economics and policy- Connecting, engaging and establishing a network with research users, including stakeholders from HTA agencies, policy, academia, and rare disease patient organizations- Improving transferable and leadership skills