Making decisions using uncertain evidence: An exploration of health technology assessment (HTA) and subsequent decision-making processes for rare dise

在获得上市许可后，包括罕见病治疗在内的卫生技术在不同的司法管辖区进行卫生技术评估，目的是在付款人就技术的覆盖范围和/或报销作出决策时向付款人提供信息和建议。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相关，这使得对其与其他替代方案相比的益处的判断变得复杂。此外，创新RDT的持续增长导致了大量的RDT报销申请，HTA系统需要及时响应。这对试图决定在公共资助的卫生系统内支付哪些费用的卫生评估人员构成了相当大的挑战。他们必须平衡RDTs的不确定证据，同时在资源有限的情况下努力满足大量不同罕见病患者的卫生保健需求。广泛的研究表明，卫生技术审查机构倾向于采用类似的方法来评估提交的卫生技术证据，但各国的报销建议不同。此外，在HTA过程中，RDTs面临的挑战以及通过定制方案解决RDTs不确定性的方法已经得到了彻底的分析，在定制方案中，通常不太可靠的证据被接受。偶尔也有研究探讨不同国家的HTA机构如何考虑或评估不确定性。然而，特别关注如何评估rdt的HTA不确定性的研究很少。虽然HTA在某种程度上总是存在不确定性，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，本研究旨在了解英国和德国的HTA流程如何解决这些困难，评估RDTs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HTA报告中提取的数据进行统计分析，定性方法将包括对HTA机构、制药商和患者组织的关键线人的访谈。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，因此经历了快速引入新的和创新的治疗方法。此外，HTA机构的作用、HTA实践和医疗保健系统的类型在两个司法管辖区是不同的，但对于定价和报销目的同样至关重要。最后，两个司法管辖区都在网上公开提供其HTA报告，并且司法管辖区的语言不会对分析构成障碍。鉴于医疗保健部门的可用资源有限，本研究有助于证据的发展，可以为罕见病的资源分配决策提供信息。更好地了解RDTs的HTA不确定性可以为确保患者及时、负担得起和公平地获得创新治疗提供重要见解，提高RDTs决策的一致性，并改善罕见病患者的健康结果，最终促进整体健康和福祉。学生如何满足ESRC技能重点：应用定量和定性研究方法开发和执行协作性跨学科研究设计开发卫生技术评估，卫生经济学和政策方面的专业知识与研究用户（包括HTA机构，政策，学术界和罕见疾病患者组织的利益相关者）建立联系，参与和建立网络提高可转移和领导技能

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 methodsDeveloping and executing a collaborative, interdisciplinary research designDeveloping specialized expertise in health technology assessment, and health economics and policyConnecting, engaging and establishing a network with research users, including stakeholders from HTA agencies, policy, academia, and rare disease patient organizationsImproving transferable and leadership skills