he European Union has been at the forefront of fostering innovative research projects aimed at harnessing real-world evidence (RWE) and cutting-edge data analytics to enhance healthcare decision-making.

With the rapid pace of clinical innovation, an increasing number of medicines are gaining marketing approval for specific patient subsets and at earlier disease stages. However, this trend presents a challenge in the realm of clinical evidence gathering, as the pool of eligible patients for recruitment diminishes and achieving conclusive outcomes becomes time-consuming.

RWE emerges as a promising solution to bridge this gap, offering a complementary perspective to traditional clinical trial data. The main goal of randomized clinical trials (RCTs) is to produce evidence regarding the efficacy and safety of a new treatment within a tightly controlled environment featuring a relatively uniform population. By incorporating RWE, uncertainties faced by Health Technology Assessment (HTA) bodies, which often lead to delays in reimbursement decisions, can be alleviated as RWE can demonstrate the effectiveness of a treatment across diverse real-world scenarios. Other factors must also be taken into consideration when designing a trial; however, the growing utilization of RWE showcases instances where it has influenced positive reimbursement outcomes, facilitating patient access to cutting-edge treatments. Nonetheless, and despite its potential benefits, the acceptance of RWE within regulatory decision-making and/or HTA evaluations varies significantly across countries, posing limitations to its widespread impact.

While the pharmacovigilance mandate has resulted in routine collection of real-world data (RWD) for post-approval safety studies, the analysis of huge data sets to identify safety signals is still challenging today. In addition, structured collection of RWD for efficacy studies of pre-approval products remains a challenge.

The extremely high volumes of data being produced, commonly referred to as Big Data, along with the heterogeneity of data sources and the lack of data standardization and interoperability, are some of the reasons why it’s so difficult to create RWE of sufficient robustness to be used for regulatory decision-making.

Here is where the following five projects come in.

MetReal Cluster

On 6 October 2021, the European Commission (EC) issued a call titled New methods for the effective use of real-world data and/or synthetic data in regulatory decision-making and/or in health technology assessment under the Horizon Europe program, the key EC funding program for research and innovation.

Horizon Europe consists of three pillars, and the second pillar—Global Challenges and European Industrial Competitiveness—has six clusters:

• Culture, Creativity, and Inclusive Society
• Civil Security for Society
• Digital, Industry, and Space
• Climate, Energy, and Mobility
• Food, Bioeconomy, Natural Resources, Agriculture and Environment
• Finally, the one which this topic falls under: Health.

The “Health” cluster has six main areas of intervention or six destinations; the topic of the above-mentioned call focuses on supporting activities that enable or contribute to achieving one or more expected impacts outlined in destination 5 of the Health cluster: Unlocking the full potential of new tools, technologies, and digital solutions for a healthy society. Under this program, five projects were selected by the European Commission to support its mission: for health regulatory and HTA bodies to adopt optimized data-driven methodologies, including real-world and synthetic data, for evaluating medicinal products and digital health innovations.

Representatives of the MetReal Cluster (the name representing the five projects funded under the same Horizon Europe call) shared project updates to the DIA Innovating Clinical Trials in Europe conference held virtually in November 2023. This cluster, established approximately one year ago, outlined its future objectives and emphasized the promotion of synergies between projects through shared experiences and collaborative activities.

These five projects are listed below.

Real4Reg: Unlocking Real-World Data with Artificial Intelligence (AI)

This Horizon Europe initiative focuses on the development, optimization, and implementation of AI-based methods for analyzing RWD in regulatory decision-making and HTA. The four-year Real4Reg project involves a consortium of 10 partners, spanning regulatory bodies, academic institutions, and patient organizations, from six EU countries. According to Britta Hänisch (Federal Institute for Drugs and Medical Devices in Germany [BfArM]), the aim would be to ultimately “increase acceptance and the impact of real-world data and synthetic data along the whole product lifecycle.”

More-EUROPA Project: Rethinking Drug Development with Real-World Insights

More-EUROPA, which stands for “More Effectively Using Registries to support Patient-centered Regulatory and HTA decision-making,” was introduced by Peter Mol, the project coordinator representing a consortium of more than 10 partners, including regulators, academia, and industry, who highlighted “the potential of registry based RCTs” and its overarching objective to “seamlessly integrate evidence from both RCTs and RWD, contributing to more efficient and cost-effective development processes.”

The REDDIE Project: Revolutionizing Diabetes Care

The project manager for REDDIE (Real-World Evidence for Decisions in Diabetes), Martina Radanovic, outlined the key objectives and structure of their diabetes-focused initiative. With a consortium of 15 partners, ranging from industry to ethics committees, REDDIE aims to bridge the gap between RCTs and RWE, incorporating machine learning techniques for data analysis, establishing standards for RWE, and ultimately augmenting their data.

REALM Project: Shaping the Future of Medical Devices Software

Gökhan Ertaylan (VITO) shared insights about the RWD-enabled assessment for health regulatory decision-making (REALM) project, which shifts the focus to medical device software evaluation. Spanning eight countries, REALM seeks to streamline the evaluation process in Europe by “simplifying the challenging task of locating medical data and standardizing the evaluation of innovative software solutions for notified bodies and HTA agencies.”

The ONCOVALUE Project: Pioneering in Evaluation of Novel Cancer Therapies through RWD

Coordinator of the ONCOVALUE project Pekka Kahri (Helsinki University Hospital) sheds light on their initiative: “The focus is really on cancer as a disease and then in hospital data, in terms of RWD.” A consortium of six cancer centers and strategic partnerships with technology leaders, ONCOVALUE is pioneering advancements in real-world evidence generation by building methods to evaluate the effectiveness of novel cancer therapies with RWD, combining hospital data on clinical outcomes, patient-reported quality of life, and costs. By harmonizing clinical variables, employing AI tools for unstructured data analysis, and engaging with HTA bodies, the project is propelling the use of hospital data for impactful decision-making in cancer treatment.

Interconnected Pursuits and Shared Objectives

As these projects unfold, they collectively address challenges in RWD quality, completeness, and biases. They transcend individual focuses to create a rich tapestry of advancements that could redefine healthcare practices globally.

The interconnected nature of these projects reveals a shared vision: To harness the potential of RWE (defined as “data that are collected outside the constraints of conventional randomized clinical trials” and are dependent on the collection of RWD) for more informed, effective, and personalized healthcare decisions.

A panel discussion led by Jesper Kjaer, at the time co-chair of the Big Data Steering Group (a joint effort of the Heads of Medicines Agencies [HMA] and European Medicines Agency [EMA]), highlighted additional key points regarding the intersection of RWE, clinical trials, and innovative technologies within the healthcare landscape:

• Collaboration Across Stakeholders: The convergence of regulators, industry experts, academics, hospitals, and patients is evident in the development of initiatives aimed at harnessing RWE. This collaborative approach is critical to emphasize the importance of a multistakeholder environment to address the complexities of healthcare data.
• Innovative Initiatives in the EU: Five innovative initiatives illustrate ongoing efforts to enhance the use of RWE and are anticipated to play a crucial role in shaping the future of healthcare research and regulatory processes.
• Diverse Applications Across Medical Fields: This discussion underscored the breadth of applications for real-world evidence, from clinical settings to medical devices; the variety of applications underscores the dynamic landscape of healthcare research and the necessity for thorough evidence generation.
• Embracing Future Technologies: Integration of AI and other advanced technologies is a key component in unlocking the potential of RWE. Enabling the extraction of meaningful insights from RWE through analysis of large and complex data sets highlights the significance of exploring AI to enhance accessibility and the impact of RWE.
• Patient-Centric Approaches: The patient remains at the core of healthcare initiatives, from the early stages of clinical trial design through collaboration with patient representatives and patient organizations in various aspects of research.

As we consider the journey ahead, the optimism lies in the valuable insights derived from EU initiatives propelling innovation and where real-world evidence and data analytics converge to redefine decision-making and enhance patient outcomes.

All projects are expected to achieve their objectives by the end of 2026. So far, More-EUROPA published their first articles looking for outcomes in important vulnerable subgroups, such as patients with heart failure. REDDIE has scheduled their first face-to-face progress meeting in April 2024 and looks forward to possible developments, such as validation of the RWE against evidence from RCTs, and to publications from other projects in the coming months.

These initiatives are positioned to have a significant impact beyond European borders! Ongoing dialogue regarding international harmonization related to RWE and regulatory decision-making has gained special attention following an ICMRA statement on international collaboration to enable real-world evidence (RWE) for regulatory decision-making.