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

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