Where Might HTA Be Heading?
Cross-Border Collaboration
The theme of ISPOR Europe 2022 was ‘Collaborating Across Borders: Building & Using Evidence to Enable Access’ with a number of sessions, including the plenary sessions, focusing on cross-border collaboration and its role in evidence generation, health technology assessment (HTA) and enabling access to new medicines. Two particular contexts in which cross-border collaboration was discussed were that of Joint Clinical Assessments (JCAs) and the Data Analysis and Real-World Interrogation Network (DARWIN) EU project.
Joint Clinical Assessments
The upcoming introduction of Regulation on Health Technology Assessment (HTAR) and the associated JCA for the European Union (EU) was a key topic of many sessions, in particular the plenary in which representatives from both the European Medicines Agency (EMA) and EUnetHTA discussed the future for collaboration between their respective organisations.1 This regulation will replace the current EUnetHTA system and aims to enhance transparency, reduce access gaps and avoid redundancies in the current process.2
The JCA will examine the health problem, the proposed technology and its relative safety and efficacy, whilst pricing and reimbursement decisions will remain the responsibility of the member countries. The scheme is currently in its pilot phase and will become introduced using a staggered approach, initially applied for oncology drugs in 2025 and orphan drugs in 2028 before becoming mandatory for all drugs in 2030.
Discussions were held on the potential advantages of the scheme as well as the practical challenges of implementing this process.3,4 A key challenge raised by stakeholders was how differences in healthcare systems and treatment pathways between member countries would be addressed within the JCA to ensure that the JCA was generalisable across populations. In an attempt to ensure generalisability, each member state will be required to take part in a PICOS survey which will then be consolidated for use within the assessment. Whilst this may help to identify some country-specific clinical context, it will be interesting to see whether differences in how a manufacturer might be positioning their product in different regions, for example with regards to targeting of specific clinical subpopulations based on expectations of cost-effectiveness, will also be accounted for within the JCA. Another challenge is the differing requirements for data throughout the member states; for example, the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany does not accept any form of indirect treatment comparisons within HTA submissions. Finally, given the increasing focus on the use of real-world data (RWD) to support decision-making, the use and role of country-specific RWD in informing the JCA will need to be considered.
DARWIN EU
As with ISPOR International 2022, the role of RWD in regulatory and reimbursement decision-making was a key focus of ISPOR Europe 2022, as discussed in separate commentaries here (‘Innovations in the Generation of High-Quality Real-World Evidence’) and here (‘Collaboration Is Key – Real-World Evidence for Decision-Making’). Combining this with the theme of cross-border collaboration, the importance of cross-border RWD collection was frequently discussed at ISPOR this year, with a particular emphasis on the DARWIN EU.5,6
DARWIN EU was established by the EMA earlier this year with the aim of providing timely and reliable pan-European RWD on the use, safety and effectiveness of medicines in real-world settings. More specifically, the aim of DARWIN EU is to provide a coordination centre for the collection and delivery of reliable European RWE to aid regulatory decision-making by: establishing a catalogue of observational data sources; providing a source of high-quality and validated RWE; and carrying out high-quality, non-interventional studies.7 By doing so, DARWIN EU intends to help provide quicker access for patients to new medicines, particularly innovative medicines. Although launched in early-2022, DARWIN EU will be fully operational in 2024.
Although primarily developed with an aim to aid regulatory decision-making, DARWIN EU can also contribute to reimbursement decision-making and HTA by providing a high-quality source of RWE from European countries. With the drive for cross-European HTA via JCA, DARWIN EU may prove to be a valuable resource to provide RWD on new technologies for HTA.
Figure 1: Overview of Joint Clinical Assessment and DARWIN EU timelines
Abbreviations: ATMPs: advanced therapy medicinal products; DARWIN: Data Analysis and Real-World Interrogation Network
A ‘Living’ Approach to HTA
A number of sessions and posters focused on the concept of ‘living HTA’ and the role that it may have in the future of HTA and reimbursement decision-making, including an Issue Panel titled ‘Innovate or Continuously be Outdated: The Need for a “Living” Approach to HTAs’.8-10 With growing pressure to provide patients with earlier access to new technologies and growing financial pressure on healthcare systems, this Issue Panel discussed whether a new approach to HTA is required: a ’living’ approach in which the clinical- and cost-effectiveness of treatments is constantly (re-)evaluated as part of an ever-evolving treatment and evidence landscape.
The Issue Panel explored this concept from a research, industry and technological perspective. It highlighted the importance of a ‘living’ approach in the context of the COVID-19 pandemic, during which a responsive and innovative approach was necessary, and also explored the potential for automated software to efficiently develop the required evidence to allow a ‘living’ approach to HTA. Specifically, the role of machine-based learning in systematic literature reviews (SLRs) was highlighted as a novel technique to constantly re-review an increasing evidence base efficiently.9, 10 Furthermore, there may be potential for machine-based network meta-analysis (NMA) software to allow NMAs to be subsequently updated, as required. These software could theoretically help produce some of the evidence needed for HTA bodies to implement a ‘living’ approach.
Despite this, a number of methodological and operational challenges of a ‘living’ approach were highlighted; who benefits from a ‘living’ approach to HTA; who pays for the continuous assessment by HTA bodies; can a ‘living’ approach to HTA be implemented without a significant increase in resource required? Based on our experience, HTA bodies are facing growing pressure and strain on capacity globally. As such, unless feasible with a substantial reduction in resource required, ‘living’ HTA is unlikely to become a reality in the near future. If an approach that is sustainable from a resourcing perspective can be found, the robustness and accuracy of the data generated for decision-making should be carefully considered; otherwise there is a risk that ‘living’ HTA generates more decisions but not necessarily better ones.
Although not discussed during the Issue Panel, in addition to the methodological challenges highlighted above, it is important to consider what a ‘living’ HTA process would actually look like in terms of influence on reimbursement decisions, and the downstream impact of this on patients, clinicians and the healthcare system. Disinvestment in currently available technologies has implications for many stakeholders and it is unclear whether HTA bodies would be willing to make these decisions in line with emerging evidence.
In theory, ‘living’ HTA may alleviate some of the challenges HTA bodies can face in having to make important one-off decisions on new technologies based on limited and uncertain data, but solutions to the operational challenges will need to be established first.
