How Real-World Evidence Is Changing the Way European Payers Value New Medicines

There is one question that sits at the heart of every pricing and reimbursement negotiation in Europe and has not changed in thirty years: Does this medicine really work, in real patients, in the real world? What has changed, dramatically and in a very short time, is the evidence payers demand to answer that question, the infrastructure being built to generate that evidence, and the commercial consequences for pharmaceutical companies that come to the negotiating table without it.

Real-world evidence is not a new concept. The tension between the controlled conditions of a randomized controlled trial and the complexity of everyday clinical practice has been documented in the research literature for decades. What is new is the speed and ambition with which European regulators, health technology assessment bodies, and national payers are building the frameworks, infrastructure, and regulatory requirements that are turning real-world evidence from a supplementary consideration into a central one. For market access directors and health economics and outcomes research teams thinking about long-term evidence strategies, understanding what is being built and why is enormously important, because the decisions made today about how and when real-world evidence is generated will determine commercial outcomes in every major European market for years to come.

Why randomized controlled trials have never been enough

Before examining what is changing, it is worth defining precisely why this change is happening, because the limitations of randomized controlled trial evidence for payer decisions are structural rather than incidental.

Randomized controlled trials are designed to answer a specific scientific question with maximum internal validity: Does this intervention cause this outcome under controlled conditions? To achieve that internal validity, trials set strict inclusion criteria that exclude patients with comorbidities, polypharmacy, and the complex social and clinical circumstances that characterize most real-world patients. They standardize treatment settings in ways that do not reflect routine clinical practice. They follow patients over defined periods that often fail to capture the long-term course of chronic diseases. And they measure outcomes selected for scientific precision that may not correspond to the outcomes that matter most to patients, clinicians, and payers.

A systematic scoping review published in 2025 in the International Journal of Technology Assessment in Health Care confirmed what market access teams have long known empirically: payers are cautious about which technologies they fund when they are forced to make decisions based on limited or single-arm trial evidence, and randomized controlled trials rarely reflect real-world conditions because of strict inclusion and exclusion criteria, a lack of external validity, the use of intermediate outcomes, and short follow-up periods. The same review found that comparative effectiveness, cost analyses, treatment adherence, and patient-reported outcomes were highlighted as critical to payer decisions but were consistently inadequately covered by clinical trial evidence alone.

Payers have always known this. What they historically lacked was a reliable, standardized, credible alternative to fill the gap. That alternative is now being built at the European level with an ambition and a pace that the industry is only beginning to fully grasp.

The infrastructure being built: DARWIN EU and the European Health Data Space

Two initiatives are reshaping the real-world evidence landscape in Europe in ways that directly affect how payers will assess the value of new medicines over the next decade.

The first is DARWIN EU, the Data Analysis and Real World Interrogation Network, established by the European Medicines Agency (EMA) and the European medicines regulatory network. DARWIN EU provides a federated network for generating real-world evidence from healthcare databases across Europe, covering data from around 180 million patients in 16 European countries. The network now works with 30 data partners and delivered 59 studies in the period from February 2024 to February 2025 alone, an increase of 47.5 percent compared with the previous reporting year. DARWIN EU's stated goal is to deliver more than 140 real-world data studies per year on an ongoing basis, supporting regulatory, HTA, and payer decisions across the entire lifecycle of medicines.

Crucially, DARWIN EU does not operate in isolation from HTA bodies and payers. The EMA has explicitly positioned the network to serve health technology assessment bodies and payer organizations alongside regulators, and pilot studies have already been conducted to test the use of DARWIN EU-generated real-world data for HTA decisions. One completed study examined patient characteristics, treatment patterns, and survival in multiple myeloma in more than 30,000 European patients and was explicitly described as piloting the use of real-world data generated through DARWIN EU for decision-making by health technology assessment bodies and payers.

The second initiative is the European Health Data Space, formally Regulation (EU) 2025/327, which entered into force on March 26, 2025. The EHDS creates a new governance and technical framework for how health data is accessed and reused across EU member states, both for primary healthcare purposes and for secondary purposes, including research, evidence-based policymaking, and regulatory activities. The secondary-use infrastructure, which is the component most directly relevant to real-world evidence generation, is being built gradually through 2026 and beyond, with the cross-border data exchange infrastructure expected to be operational by March 2029. The EHDS represents one of the most ambitious digital health data initiatives in the world, and once it is in operation, it will give HTA bodies access to extensive datasets from electronic health records, registries, and clinical databases from all 27 member states in a standardized, governed, and interoperable form.

Together, DARWIN EU and the EHDS are building the evidence infrastructure that will enable European payers and HTA bodies to systematically access, analyze, and apply real-world evidence in a way that was previously impossible at the European level. The direction of travel is clear, and the pace of construction is accelerating.

What payers are actually demanding and why randomized controlled trials cannot deliver it

The shift toward real-world evidence in European payer decision-making is not driven by regulatory ambition alone. It reflects a genuine and well-documented evidence gap that payers regularly encounter when assessing new medicines.

Research published in PharmacoEconomics Open, which conducted a broad literature review to understand payers' experiences with real-world evidence, found that payers valued real-world evidence specifically for filling evidence gaps that randomized controlled trials do not address. The types of evidence that payers consistently identified as most important and least adequately covered by clinical trials included high-quality, long-term effectiveness and safety data in real-world patient populations, head-to-head drug comparisons in conditions where trials did not include active comparators, cost analyses to support formulary decisions, and medication adherence and persistence data that reflect actual treatment behavior rather than protocol behavior in trials.

This last category is particularly significant. Adherence and persistence data from clinical trials, in which patients are closely monitored, supported, and encouraged to stay on protocol, bear little resemblance to what happens when the same medicine is used in routine clinical practice. A therapy that achieves 85 percent adherence in a trial setting may achieve 50 percent in the real world, and that gap matters enormously for payer assessments of cost-effectiveness, which depend fundamentally on how consistently and for how long patients actually take the medicine prescribed to them.

A study published in 2025 in the Actions for Stakeholders journal, produced by a multi-stakeholder initiative on behalf of the Belgian payer, explicitly called on pharmaceutical companies to invest in prospective real-world evidence generation earlier in the product lifecycle. It pointed out that the evidence most valued by HTA bodies and payers, namely long-term effectiveness, safety profiles in broader populations, and patient-reported quality-of-life outcomes, requires longitudinal data collection that cannot be created retroactively at the time of HTA submission.

The rise of outcomes-based managed entry agreements

One of the most concrete expressions of how payer attitudes toward real-world evidence are changing is the growing use of outcomes-based managed entry agreements, sometimes also referred to as performance-based risk-sharing arrangements, in European markets.

Managed entry agreements are arrangements between manufacturers and payers that allow provisional reimbursement of a medicine at launch, subject to ongoing evidence generation and reassessment. Finance-based agreements, which are essentially confidential discounts and rebates, have historically dominated the managed entry agreement landscape because they are simpler to implement and do not require complex data collection infrastructure. But outcomes-based agreements, which link reimbursement to a medicine's observed performance in real-world clinical practice, are increasing in number and complexity across Europe, as payers are becoming both more dissatisfied with clinical trial evidence alone and increasingly able to collect and analyze real-world data.

A study published in 2025 that examined managed entry agreements for rare disease therapies in Belgium found that the Belgian payer had implemented outcomes-based managed entry agreements for 57 orphan drugs, all under a coverage with evidence development scheme. The average duration of these agreements was 24 months, with some extended or renewed up to five times. This finding reflects a broader European reality: payers are increasingly willing to grant innovative therapies conditional access at launch in exchange for a commitment to generate the real-world evidence that justifies the price paid, but they are also becoming increasingly serious about enforcing those evidence commitments and reassessing reimbursement based on the evidence demonstrated.

The same study found that real-world evidence was frequently rejected at reassessment because of concerns about validity and incomplete registries, which underscores the critical importance of designing evidence generation programs that meet the methodological standards payers demand from the outset, rather than the data quality standards achievable with whatever infrastructure happens to be in place.

The evidence quality problem market access teams need to solve

The shift toward real-world evidence in European payer decision-making does not simply create an opportunity for pharmaceutical companies to generate more data. It creates a specific and demanding quality requirement that most current approaches to real-world evidence generation do not yet fully meet.

Research published in PMC that examined the use of real-world evidence to support HTA and payer decisions found that payers have consistent and well-documented concerns about real-world studies: data quality, poor internal validity, potential bias, and a lack of meaningful endpoints are the most frequently cited limitations. A multi-stakeholder report published in 2025 as part of the RWE4Decisions initiative stated explicitly that the acceptance of real-world evidence by HTA agencies and payers in the assessment of medicines is currently suboptimal and varies between jurisdictions, and that improving it requires systematic changes in how evidence is generated, governed, and presented.

Experts who wrote an analysis in 2026 of what counts as high-value real-world data summed up the current state of play concisely: in 2026, real-world evidence requires more than just data. Evidence must be built around a clear decision question, with transparent methods, appropriate comparators, and results that stand up to critical scrutiny. Dataset size or novelty alone is no longer enough.

This has direct implications for how pharmaceutical companies should think about the design of their patient support and engagement infrastructure. Real-world evidence that will be credible to European payers and HTA bodies in 2026 and beyond must be generated through platforms and programs that have prespecified collection methods, validated outcome instruments aligned with payer-relevant endpoints, transparent governance, and longitudinal follow-up that matches the time frames payers need to assess long-term effectiveness. Evidence gathered through informal channels, unstructured data collection, or programs designed primarily for patient engagement rather than evidence generation will not clear the bar that payers are setting and that regulators are reinforcing through frameworks such as DARWIN EU and the EHDS.

The link between patient engagement and market access

This is where the strategic narrative running through this blog series converges on a single conclusion that market access and HEOR leaders need to take seriously.

The evidence that European payers are increasingly demanding, namely longitudinal real-world data on effectiveness, adherence, quality of life, and patient-reported outcomes, is precisely the evidence that well-designed, structured digital patient engagement platforms are able to generate as a natural by-product of supporting patients on their treatment journey.

A patient who continuously interacts with a digital platform that captures their treatment experience over months and years in a structured, validated, and GDPR-compliant format generates the longitudinal patient-reported evidence that payers need for HTA submissions, reassessments of outcomes-based managed entry agreements, and pricing negotiations. This data is not generated by clinical trials, because clinical trials end. It is not generated by pharmacy claims data, because pharmacy data captures dispensing but not experience. It is not generated by ad hoc patient surveys, because retrospective surveys capture memories rather than lived experience. It is generated through continuous, structured engagement with patients in their daily lives, which is exactly what integrated digital health platforms are designed for.

The link between investment in patient support and market access outcomes is real, but it only materializes if the patient support infrastructure is designed from the outset with the evidence quality requirements of European payers in mind. A platform that collects engagement metrics but no structured clinical insights, that captures patient experiences in unstructured formats but not in validated outcome measures, and that supports patients effectively but generates data that cannot withstand HTA scrutiny delivers patient value without the market access value that the same investment could create with better design.

What the next five years look like for European market access

Looking at the trajectory of the initiatives described in this article together, the direction of European market access strategy becomes clear, and it has significant implications for how pharmaceutical companies should allocate their investments in evidence generation and patient engagement today.

From 2027 onward, the EHDS will make vast quantities of standardized, interoperable European health data available for secondary use by HTA bodies and researchers, fundamentally broadening the evidence base against which individual products are assessed. DARWIN EU will continue to expand its real-world data study capacity toward 140 or more studies per year, providing HTA bodies and payers with independent real-world evidence on diseases, populations, and drug performance. The EU Joint Clinical Assessment will continue to generate pan-European clinical assessment reports that drive national HTA processes in all 27 member states simultaneously. And outcomes-based managed entry agreements will continue to grow as payers use conditional access arrangements to manage the uncertainty that inevitably comes with launching innovative therapies with limited long-term data.

In this environment, the pharmaceutical companies that achieve the strongest pricing and access outcomes will not necessarily be those with the best clinical trial programs, although those will remain indispensable. They will be the companies that come to national reimbursement negotiations with the most credible, longitudinal, patient-generated evidence of real-world effectiveness, the companies whose patient support programs have generated structured, validated, payer-relevant data from the very first moment of prescription, and the companies whose market access teams have built cross-functional evidence strategies that connect patient engagement infrastructure with HEOR outputs and HTA dossiers in a single coherent system.

This coherence does not happen by itself. It requires deliberate decisions about platform design, data governance, the selection of outcome instruments, and cross-functional collaboration between patient support, market access, HEOR, and regulatory teams, decisions that most organizations have not yet made systematically.

The window to make these decisions ahead of the curve is open now. The infrastructure being built at the European level will reward companies that started generating credible real-world evidence early. It will make the position of those that did not considerably harder to defend.

Find out at britehealth.com/en-de/partner/pharma how brite helps pharmaceutical companies build patient relationships that generate the real-world evidence European payers demand