GetReal Conference 2024: insights from Day 2

Session 6 – Keynote: A Vision for The Future: What If We Accelerate The Convergence of Regulatory & HTA?

Shahid Hanif welcomed Patrice Verpillat (European Medicines Agency’s [EMA], The Netherlands), who also spoke on Day 1, and Niklas Hedberg (Dental and Pharmaceuticals Benefits Agency [TLV], Sweden) to provide their perspectives on the convergence of regulatory and HTA. In his presentation, Verpillat highlighted the distinct evidence requirements of regulators and HTA bodies: regulators determine efficacy through randomized controlled trials (RCTs) versus placebo, while HTA bodies evaluate comparative effectiveness through RCTs against the standard of care or active comparators. Both entities, he stressed, must develop strategies to manage uncertainty.

Verpillat elaborated on DARWIN EU, a key initiative for delivering RWE in the EU, and identified three main areas where RWD analyses support EMA decision-making: understanding clinical context, supporting planning and validity, and investigating associations and impacts, which align with HTA needs. He referred the audience to an October 2022 workshop that examined DARWIN EU’s potential to support HTA decision-making and shared an example of natural history study in multiple myeloma from this initiative, which can be used by payers and HTA bodies in their decision-making.

Verpillat emphasized the long-standing collaboration between the EMA and HTA bodies through various EMA committees and noted opportunities through parallel joint scientific consultations under Regulation (EU) 2021/2282EN on health technology assessment (HTAR) would further accelerate convergence. HTAR also offered other avenues for convergence; for example, by enabling prospective planning of post-licensing/launch evidence generation that addresses evidence needs by HTAs and regulators. He concluded by underscoring shared principles for the use of RWE between HTA bodies and regulators to enhance transparency and manage uncertainty.

In the following presentation, Hedberg discussed the ongoing challenge between external and internal validity in research, highlighting the ideal scenario where both types of validity are combined, although this remains unlikely at present. He aligned with Verpillat’s point on the varying evidence requirements for regulatory and HTA bodies, emphasizing the distinct needs of demonstrating efficacy (“does it work?”) versus demonstrating superiority (“does it work better?”) Hedberg expressed a desire for HTA and regulatory bodies to work complementarily rather than duplicating efforts, stressing the importance of innovation in this collaborative process.

Hedberg underscored the necessity for collaborative advancements in scientific methods, infrastructure development and the initiation of pilot projects to drive progress. With the increase in RWD, he noted a significant shift in the balance of power within the research landscape. He cautioned that formulating the right research questions requires careful consideration, as organizations with access to RWD datasets hold considerable influence.

Hedberg suggested that resistance to utilizing RWE often stems from companies developing new products, who may be apprehensive about the outcomes of studies based on RWD. He stressed the importance of fair comparisons in evidence generation and warned against practices such as data mining and phishing, which can lead to confusion due to an overabundance of studies. Despite the potential benefits of RWD, Hedberg acknowledged that it will not address underlying ethical challenges. He concluded by criticizing the duplication of efforts in research as a waste of time and resources, advocating for a more streamlined and cooperative approach to evidence generation across HTA and regulatory bodies.

Session 7 – Closing Discussion: Regulatory & HTA Town Hall

In a dynamic multi-stakeholder panel moderated by Niklas Hedberg, participants shared their insights from the discussions held over the past 2 days of the conference and highlighted what they believe should be the top priorities for the field.

Patrice Verpillat began by addressing the significant progress made in the HTA and regulatory landscape, emphasizing the importance of evidence generation and collaboration. He praised the open discussions facilitated by the GetReal Institute and described DARWIN EU as a ‘game-changer’. Verpillat expressed optimism about the ongoing journey and shift in mindset towards collaborative efforts, drawing parallels to the collaborative model seen during the COVID-19 pandemic, which acted as a catalyst for integrating RWE into decision-making processes.

Donna Rivera (FDA, USA), joining the discussion virtually, continued the regulatory perspective and echoed the sentiments of collaborative working. She emphasized the collective effort to determine the success of RWE in regulatory decision-making and noted the importance of discussing the next steps to advance the field. Donna highlighted the necessity of leveraging the conference’s outcomes to push the field forward.

Iñaki Gutiérrez-Ibarluzea (BIOEF, Spain) focused on the robustness of innovative methods to reduce uncertainty around the use of RWD. He raised critical questions about which methods to adopt, given the varying requirements of regulators, HTA bodies and assessors. Gutiérrez-Ibarluzea stressed the need for including the voices of payers, citizens, and policymakers in the conversation, calling for greater transparency.

Elena Petelos (University of Crete/HTAi, Greece), also presenting virtually, underscored the significance of the European Health Data Space (EHDS) and the explicit mention of RWD/E within this context. She highlighted the cultural and methodological shifts required within organizations and the efforts towards harmonizing data standards and hospital data. Petelos welcomed discussions on methodologies and data quality for HTA and called for broader, more transparent dialogues involving regulators, payers and global stakeholders.

Wim Goettsch (University of Utrecht, The Netherlands) noted the political aspects of RWE, acknowledging the inherent uncertainties and the need to leverage ongoing European efforts, for example through the EU-funded SUSTAIN HTA project. He appreciated the openness between HTA bodies and regulators but recognized the need to move beyond the ‘RWE bubble’. Wim suggested fostering more dialogues with other HTA bodies and collaborating with groups like ISPOR, ISPE, and HTAi to enhance awareness and use of RWD.

Bettina Ryll (Melanoma Patient Network Europe, Sweden) shared her thoughts on the value of exchange at the GetReal Conference. She called for increased awareness around data sources and the ethical use of RWD, particularly regarding consent. Ryll emphasized the need to involve more clinicians in the discussions, as their perspectives can provide valuable insights into the datasets that regulators and HTA bodies use. She cautioned against oversimplifying complex systems and advocated for learning opportunities from pilot projects and investing in innovative capacities. Drawing on the COVID-19 experience, Bettina encouraged more exploration and a push to expand the boundaries of RWE, noting that the current approach is too cautious.

Following these reflections, Hedberg moderated an interactive discussion between the panelists and audience, exploring some of the themes raised. This included ways to ‘break the RWE bubble’ to include more stakeholders, appropriate ways to incentivize clinicians for better primary data collection, and democratization in research with RWD. The session closed with each of the speakers making their own recommendations to advance the field.