The action under this topic is expected to achieve the following impacts:

• Improved access to innovations that meet the increasingly diverse needs of patients and those of the healthcare systems.
• Better informed decision-making at different levels of the healthcare system (authorities, organisations) using RWD/RWE that will in turn contribute to a better allocation of resources towards cost-effective innovations as well as representation of different patient populations and needs.
• Faster entry to the market of cost-effective medicinal products and devices (including combinations) developed by industry or public not-for-profit developers, which could translate to a positive effect on their R&I investments.

• Industry, sponsors, and other stakeholders have access to structured, evidence-based and practical guidance and recommendations on the use of real-world data / real world evidence (RWD/RWE)¹ that could be followed to support the development, and regulatory, health technologies assessment (HTA), and payer decision-making of innovative medicines and health technologies with a focus on medicinal products, medical devices, and therapeutic products that combine a medicinal product with a medical device (drug-device combinations).
• Regulators, HTA bodies and payers will receive more structured and consistent RWD/RWE submissions to inform their decision making.

¹ _{Real World Data (RWD) are defined as “routinely collected data relating to a patient's health status or the delivery of health care from a variety of sources other than traditional clinical trials.” Real-world evidence (RWE) is defined as the information derived from analysis of RWD. https://doi.org/10.1002/cpt.1426}

The use of real-world evidence to support decision making on the safety of medicinal products is already well established. More recently, RWE has also been used to complement evidence and support marketing authorisation, conformity assessments and HTA submissions. While high-level guidance on the use of RWD/RWE exists, the practical implementation is left up to individual sponsors. Currently, RWD/RWE submissions are usually custom-made to a specific use-case and require significant expertise and effort from the sponsor to prepare, and from the healthcare decision-maker to assess. Much knowledge exists within individual sponsors on these use-cases, but, to date, this has not been leveraged to develop practical guidance which could act as a baseline for future submissions.

To leverage the learning from individual use cases and facilitate the efficient use of RWD/RWE for regulatory, HTA, and payer submissions and to inform healthcare decision-making, structured, evidence-based, and practical guidance is needed.

To address this challenge, the action funded under this topic should:

• Map relevant RWD/RWE initiatives across Europe and their (expected) outcomes. Where relevant, build on, align, and complement these initiatives, including the European Medicines Agency’s vision to establish the value of RWE across the spectrum of regulatory use cases by 2025 ¹.
• Identify the main challenges faced by industry, sponsors, non-commercial sponsors, health professionals, prescribers, and other stakeholders in the routine use of RWD/RWE for regulatory and HTA decision-making. This is to be done by also taking into account the differences in the regulatory frameworks of medicinal products and medical devices and how stakeholders’ experiences, needs, and situations are reflected in these.
• In collaboration with the relevant stakeholders, identify, review, and evaluate existing methodologies, guidelines, and practices for the use of RWD/RWE in healthcare decision-making.
• Focus on an in-depth study of a broad range of use cases where RWD/RWE has been previously assessed for decision-making for medicinal products, medical devices, and combinations. This should include an analysis of methods, designs, and defining variables that enable the grouping and thereafter the utilisation of RWD/RWE sources. Particular attention should be paid to the features that enable efficient assessments.
• Using the results of the study as a foundation, develop a draft of the practical guidance document and recommendations on the use of RWD/RWE to support submissions and decision-making processes, taking into consideration the specific needs of medicinal products and medical devices. Considerations on how RWD/RWE can be used within an ethical framework and respects EU values should be included. In addition, ensure that the guidance respects the EU data quality framework and the relevant RWD specialisation (which is currently under development).
• Test the draft guidance in several pilots to ensure validity and broad acceptability.The precise scope of these pilots should be selected by the full consortium during preparation of the full proposal and should address multiple contexts and areas that are not already being addressed, including but not limited to: chronic serious diseases, oncology, and auto-immune diseases. They should also cover clinical development and the regulatory, HTA, and payer assessment of medicinal products and medical devices including combinations.
• Based on the learnings from the pilots, finalise the practical guidance document and recommendations on the use of RWD/RWE to support clinical development, regulatory, HTA and payer submissions and inform decision-making processes.
• Broadly disseminate the guidance and recommendations to the stakeholder community. Create training plans to enable dissemination.

Applicants should develop a strategy and plan for generating appropriate evidence as well as for engaging and formally consulting with regulators, HTA agencies and payers in a timely manner, in particular on the draft guidance (e.g. through national competent authorities, the EMA Innovation Task Force, qualification advice).

In addition, while the project will focus on supporting the development of a recommendation for a structured, practical and evidence based guidance, the funded project is also expected to explore synergies with complementary initiatives to advance RWD/RWD in Europe such as the GetReal Institute, REDDIE, More-EUROPA, Oncovalue, Real4Reg, RWE4Decisions, TEHDAS, QUANTUM, CORE-MD, REALM² and projects under the ongoing call for proposals HORIZON-HLTH-2024-IND-06-08. It should also be aligned with the ambitions and guidelines set out for the European Health Data Space (EHDS)³.

¹ _{Arlett P. et al. Real-World Evidence in EU Medicines Regulation: Enabling Use and Establishing Value. Clinical Pharmacology & Therapeutics 2021 https://doi.org/10.1002/cpt.2479}

² _{www.getreal-institute.org, www.reddie-diabetes.eu, cordis.europa.eu/project/id/101095479, oncovalue.org, www.real4reg.eu, realm-ai.eu}

³ _{health.ec.europa.eu/ehealth-digital-health-and-care/european-health-data-space_en}