Evidence by Design: Toward Coherent, Decision-Ready Data Across Europe’s Regulatory, HTA, and Payer Systems

Julia Chamova, Senior Director, Global Development, ISPOR

Europe’s healthcare innovation pipeline rests on a deceptively simple promise: Once a treatment is judged safe and effective, eligible patients should be able to access it. In practice, access timelines remain uneven, and evidence requirements fragment after marketing authorization. The result is not merely slower uptake—it is a structural misallocation of research effort, repeated evidence translation costs, and recurring uncertainty that delays or limits reimbursement decisions.

The central challenge for the European Economic Area (EEA) is coherence. Regulatory approval, health technology assessment (HTA), and payer pricing and reimbursement are distinct decision domains with separate mandates defined by legislation. Yet their processes remain largely sequential and inward-looking. Evidence is generated once but interpreted multiple times—through benefit–risk, comparative/relative effectiveness, and affordability lenses—without a shared upstream evidence roadmap. The system repeatedly asks stakeholders to answer new questions with incomplete information, often after pivotal trials are already complete.

The recent evolution of EEA/European Union (EU) policy—with the EU pharmaceutical legislation update, Critical Medicines Act, and Biotech Act among the most relevant examples—creates a timely opportunity. The EU HTA Regulation (EU HTAR) introduces joint clinical assessments and proactive evidence scoping, shifting Europe from reactive dossier assessment to product-specific evidence planning. Meanwhile, the European Health Data Space (EHDS) and distributed real-world evidence (RWE) networks (including the Data Analysis and Real World Interrogation Network [DARWIN] EU) offer infrastructure that can make decision-grade RWE feasible at scale, if HTA and payer needs inform data requirements early enough. These reforms create genuine “windows of alignment” for facilitating not just better bilateral communication but also a coherent, multistakeholder evidence ecosystem spanning the full technology life cycle.

In 2025, ISPOR launched its Strategic Dialogues Initiative, beginning with a pilot focused on the EU/EEA. The first Dialogue convened in late 2025 in Amsterdam, bringing together experts from regulatory, HTA, payer, and wider health policy fields. The primary aim of this initial pilot project has been to enhance the understanding and identification of needs, challenges, and alignment opportunities in the regulator–HTA body–payer decision-making process.

Recent reforms in Europe create genuine “windows of alignment” for facilitating a coherent, multistakeholder evidence ecosystem spanning the full technology life cycle.

Areas of focus include evidence generation and other pertinent issues for improving the relevance and application of health economics and outcomes research (HEOR) methods and practices. In particular, because patients are the ultimate users—or “customers”—of the healthcare system, integrating patient preferences and engaging patients early, regularly, and consistently in assessment or decision-making processes is essential.

Building on that premise and momentum, ISPOR plans to continue the dialogue, while incorporating perspectives from more stakeholders (including patients), in October 2026 in Brussels.

The white paper resulting from the ISPOR Dialogue 2025, summarized below, reflects on the 2025 conversation and extends an invitation for evidence generation practitioners, decision makers, researchers, industry partners, and other relevant stakeholders to engage with the white paper’s proposals.

Why Misalignment Persists: Different Mandates, Shared Consequences

More than an issue of poor communication, misalignment reflects institutional realities. Regulatory bodies assess benefit–risk and grant legal authorization. HTA organizations assess clinical value and comparative effectiveness. Payers decide coverage under constraints shaped by affordability, budget impact, and implementation feasibility.

Because these mandates are legitimate and distinct, coherence does not mean forcing identical value criteria across systems. It means designing evidence generation so that answers produced for one stage do not create avoidable new questions for the next. Three structural factors keep misalignment in place: 

• Siloed evidence planning. Even when early dialogues exist between manufacturers and regulators or HTA bodies, payer priorities (affordability, pathway fit, budget impact) often enter too late. What looks complete from a marketing authorization standpoint may still be incomplete for comparative effectiveness or health-economic modeling.

• Translation effort increases uncertainty. Differences in comparators, outcome definitions, and trial populations force stakeholders to interpret evidence through assumptions that may not match local decision frameworks. Rather than reducing uncertainty, this shifts it from the evidence-generation stage to the decision stage, causing delays.

• RWE potential is not consistently realized. Data may exist but are not always structured, standardized, or governed in ways that enable comparative conclusions with confidence. Without fit-for-purpose RWE, postlaunch decision making becomes slow and duplicative rather than cumulative.

From Sequential Decisions to Life Cycle Evidence Planning

Europe is now positioned to move from sequential decision making toward life cycle evidence planning. EU HTAR’s joint clinical assessments and structured scoping processes create incentives to embed payer- and implementation-relevant questions earlier, so evidence is not only regulatory-persuasive but also decision-ready across stages.

Joint scoping should evolve beyond defining dossier requirements. It should become an exercise about structured mapping of uncertainty: identifying which uncertainties are critical for valuation and which directly affect affordability and access conditions. Once those uncertainties are clearly articulated, evidence generation can be designed prospectively to address the most consequential gaps.

Adaptive approaches are particularly relevant in areas (oncology, orphan drugs, and transformational innovation) where a product’s high uncertainty profile at launch is structurally misaligned with its premarket assessment. Adaptive pathways, conditional approaches, and living HTA models can align access decisions with evidence maturation, as long as governance is explicit about what evidence will be generated, when and how it will be appraised, and what decisions it will update.

Joint scoping should become an exercise about structured mapping of uncertainty: identifying which uncertainties are critical for valuation and which directly affect affordability and access.

Making RWE Truly Decision-Grade

Distributed RWE initiatives and broader European health data infrastructure can reduce the gap between data reflecting “what happened in practice” and “data decision makers can use.” But RWE is valuable only when it is comparable, interpretable, and fit for scrutiny.

Fit-for-scrutiny RWE requires:

• Clarity on core data elements, endpoint definitions, and potential comparators

• Transparency on methodology, bias handling, and uncertainty quantification

• Inputs on resource use and costs that are suitable for health-economic and budget-impact reasoning

Decision makers must trust not just the statistical output, but also the inferential credibility of the methods and the governance behind data quality.

Cross-border RWE is especially valuable for smaller populations. For rare diseases with limited national sample sizes, pooled evidence generation can improve the robustness of comparative conclusions—but only when definitions and key variables are harmonized.

Payers as Strategic Buyers: Incentives Tied to Uncertainty Resolution

One of the most consequential reframes in evidence coherence is treating payers not as final arbiters in access pathways, but as strategic buyers who actively shape evidence priorities. The challenge is that evidence-generation incentives are not always aligned with what payers need most to reduce decision risk.

A coherent model would connect better evidence generation with pricing and reimbursement through:

• Prospective, uncertainty-informed evidence plans established prior to market entry

• Mechanisms for adjustments in price or access conditions when identified uncertainties are resolved—or when evidence fails to confirm expected value

This shifts the incentive landscape: It replaces ad hoc postlaunch data requests with a planned, decision-driven evidence roadmap, reducing uncertainty management costs and shortening the path from authorization to stable patient access.

Governance: The Mechanism Matters

Coherence requires more than aligned intent. It needs a governance mechanism for durable information exchange, scoping discipline, and life cycle evidence planning, while appropriately maintaining confidentiality and respecting institutional independence.

Structural heterogeneity among European nations should not be treated as a barrier but as a baseline feature that informs how evidence must be planned and packaged across stages.

Stakeholders must go beyond stating general evidence needs. They should explicitly articulate context-specific uncertainties and the rationale for value judgments, priority-setting logic, and budgetary constraints. When those elements are communicated early and consistently, health technology developers can design studies and RWE strategies that directly address decision questions rather than optimizing for a single assessment stage.

To this end, the white paper calls for sustainable financing and training to enable meaningful patient engagement across the full evidence life cycle, and for patient-reported outcomes, performance outcomes, and patient experience data to be systematically integrated—from real-world settings in addition to clinical trials—so the evidence base genuinely reflects what matters to those living with the conditions being assessed.

Coherence as a Competitiveness Strategy

Systemic coherence in evidence generation is ultimately a competitiveness and sustainability strategy. When evidence is misaligned across regulatory, HTA, and payer systems, delays become structural and patient access becomes uneven. When coherence is built upstream—through life cycle evidence planning, decision-grade RWE, uncertainty-resolution incentives, and durable governance—innovation becomes more predictable, reimbursement can progress more smoothly, and health systems can sustain access to therapies that deliver true value.

A critical framing point is that the EU/EEA is not a single pricing and reimbursement market. It comprises 30 member states, each with distinct pricing rules, reimbursement processes, affordability constraints, and value assessment traditions. This structural heterogeneity should not be treated as a barrier but as a baseline feature—one that informs how evidence must be planned and packaged across stages. Alignment does not mean a single shared decision outcome across nations; it means reducing avoidable duplication and translation loss while respecting national realities.

Europe’s reforms (eg, EU HTAR, EHDS, and growing RWE capabilities) create favorable conditions for this shift toward systemic coherence. The remaining task is to build the mechanism that turns reforms into consistent practice.

ISPOR welcomes a wider stakeholder dialogue that will be critical to strengthen what comes next. We invite feedback on the associated white paper with its intent to contribute to realizing a patient-centered, adaptive evidence ecosystem in Europe.