The Future Trajectory for RWE in European Healthcare Decision-Making

The European Health Data Space (EHDS) is a proposed regulation unveiled by the European Commission in 2022, which represents the first common EU data space to emerge from the European Strategy for Data initiative.^1-3 At its core, the proposed EHDS is a health specific ecosystem comprised of rules, common standards and practices, infrastructures, and a governance framework.² The proposal aims to support individuals in taking greater ownership of their health data; facilitate the use of health data for better healthcare delivery, research, and policy making; and to enable the EU to fully capitalise on the availability of health data.²

This EHDS has the potential to induce a step-change in the use of European electronic health data (EHD); however, as the legislative process continues, logistical details pertaining to how researchers and industry stakeholders will be permitted to access and use data, as well as the associated timelines for data access, remain key. To this end, a two-year pilot programme (HealthData@EU) was launched in October 2022, which seeks to establish how the EHDS could be utilised for secondary use of health data. The project connects data platforms in a network infrastructure and is developing services to support research projects using health data from various EU Member States. It will also establish guidelines for data standards, data quality, data security and data transfer to support this cross-border infrastructure.⁴

Issues surrounding public consent to the secondary use of data also remain a challenging hurdle, with the merits of opt-in and opt-out approaches an ongoing debate within European Parliament.⁵ Additionally, it remains to be seen how much access to the EHDS will be granted to researchers in countries outside of the EU, such as the United Kingdom. The level of access permitted is likely to have profound implications for the real-world data landscape in these countries.

The EHDS aims to facilitate the sharing of EHD across member states, which will reduce data siloing and allow researchers access to a much larger pool of data than previously possible. In this new environment, identifying and mitigating sources of confounding becomes ever more crucial when considering the important differences in the health systems and populations of member states. Furthermore, in the rush for greater data linkage and standardisation, it is important to give due consideration to ensuring that common data models offer sufficient specificity to answer complex research questions. This is particularly the case in fields such as orphan diseases, where highly specialised outcomes are often required. As such, existing health data infrastructures should be leveraged by the EHDS, to allow continuity and build on existing expertise.

Despite industry calling for improved access to secondary health data, reservations are still held regarding the potential impact of the EHDS, due to key logistical challenges. Inconsistencies in the level of health record digitisation and the format of patient information systems pose key challenges which could threaten the target of having the EHDS fully operational by 2025. As the pilot programme continues, we should seek to learn from prior experiences with other European-wide health initiatives, such as the implementation of European Reference Networks for rare diseases, which have encountered political, data sharing, and funding model challenges.⁶ Energy should be focused on areas where alignment between Member States is both possible and productive, and the EHDS should aim to avoid ‘over alignment’ which is neither feasible or desirable due to differing national landscapes. The success of the EHDS will ultimately be determined on the basis of its ability to unlock the European health data economy, and the extent to which it is able to foster a genuine single market for healthcare data which meets the needs of patients, clinicians, and researchers.

RWE in HTA Decision Making – Has the Dial Moved on Payer Acceptance?

The use of RWE has rapidly increased in recent years; RWE is now accepted by health technology assessment (HTA) bodies when utilised as supportive evidence for epidemiological inputs, treatment patterns, health-care resource use, and patient-reported outcomes.⁷ However, HTA bodies still remain sceptical about the use of RWE in demonstrating comparative effectiveness, where ‘gold-standard’ randomised controlled trials (RCTs) remain the very strong preference.

In the regulatory space, it is a different story. There is now a growing acceptance from regulatory agencies for RWE that can be used as substantial evidence of effectiveness, provided that the scenarios for flexible evidentiary standards are met. These standards generally state that the intervention must be for a life-threatening or debilitating condition where conducting an RCT is infeasible, and that the RWE presented offers a compelling result. ⁸ The difference in RWE perception between regulatory and HTA stakeholders is mainly due to their differing remits; whilst the former are solely concerned with establishing the safety and efficacy of an intervention, the latter must also consider additional factors such as the geographic relevance and timing of data collection.⁹ These additional considerations add another layer of complexity to the suitability of RWE for comparative effectiveness.

Several sessions at ISPOR Europe emphasised the importance of early preparedness when manufacturers anticipate a heavy reliance on RWE.^{8, 9} Recommended actions for industry include initiating the collection of RWE at the earliest opportunity to maximise the follow-up period, and seeking early scientific advice from HTA experts so that RWE studies can be designed in the most appropriate manner for HTA purposes.^{8, 9} Echoing this was the perceived importance of adopting a robust ‘target trial’ approach when designing real-world studies, thus ensuring the final study aligns as closely as possible to an ‘ideal RCT’.⁸ Despite this advice, HTA bodies need to take steps to practically demonstrate a greater willingness to accept high-quality RWE which appropriately address the decision problem, in order for manufacturers to trust the advice offered.

In response to the surge in RWE usage, there have been several guidance documents published by HTA bodies over recent years (e.g. NICE and CADTH).^{10, 11} These documents purposefully do not provide minimum acceptable standards for RWE, however, industry stakeholders desire greater clarity on the HTA acceptance of RWE; HTA bodies should be bolder with their position on standards for electronic health record (EHR) data, and implement data qualification procedures.¹² To obtain an insight into HTA acceptance of RWE, manufacturers should consider conducting a review of previous HTA appraisals to better understand prior precedence in acceptable RWE before designing their study.^{9, 12}

At ISPOR Europe, the preliminary recommendations from the ISPOR Good Practices Taskforce on the use and interpretation of EHR-derived RWD for HTA were presented, and the ISPOR Suitability of EHR Data (SUITED) Checklist for HTA Evidence Developers was unveiled. The SUITED checklist provides a framework for understanding the suitability of EHR data to answer HTA questions and a checklist for developers using EHR data in their analyses.¹³ If endorsed by HTA bodies, this could provide a valuable tool for assessing the quality of RWE for decision making.

In conclusion, whilst there is clearly a lot of noise being made about RWE for HTA, the use of RWE for comparative effectiveness still faces substantial scepticism from HTA bodies. To maximise the likelihood of RWE being deemed acceptable by HTA bodies, manufacturers should endeavour to produce high-quality and strategically relevant RWE which addresses the decision problem of interest. Whilst the absence of minimum acceptable standards for RWE is a challenge for industry, HTA guidance documents and tools such the recent ISPOR SUITED Checklist may offer some clarity.