From gatekeeper to system shaper

Adigens Health was at HTAi 2026 in Istanbul. We help pharmaceutical and rare disease companies design real-world evidence strategies built around the target trial framework: from early development planning through HTA submission. Get in touch at info@adigenshealth.com.

HTAi 2026 in Istanbul settled a long-running debate: real-world evidence is no longer supplementary to health technology assessment. It is central to it. Three themes from the conference explain what that means in practice.

HTAi’s 2026 annual meeting in Istanbul did not introduce new ideas so much as formalise existing ones. The debate over whether real-world evidence belongs in health technology assessment has, for practical purposes, been resolved. The questions that occupied the three days at the Lütfi Kırdar congress centre were harder and more practical: what kind of real-world evidence, designed how, and assessed against what standard? The answers that emerged carry direct implications for every company building an HTA evidence strategy.

The end of the gatekeeper

The meeting’s theme was ‘HTA as a system shaper’, reflecting a substantive shift in how the field defines its own role. For much of its history, HTA has operated as a gatekeeper: a technical process that evaluates completed evidence packages and advises payers whether to fund or reject a new medicine. That model is under pressure.

The acceleration of regulatory approvals (for advanced therapies, cell and gene treatments and AI-enabled diagnostics) means that products increasingly reach the market before their evidence base is mature. Single-arm trials, surrogate endpoints and accelerated pathways are now commonplace. The HTA body that waits for long-term, head-to-head comparative data before reaching a decision faces a difficult choice: accept evidence it knows is incomplete, or deny access indefinitely. Neither is a workable position.

System shaping means something different. It means HTA bodies engaging earlier in the development cycle by setting expectations about what evidence will be generated. It means the early value assessment consultations that EU JCA has formalised becoming standard practice beyond Europe’s borders. And it means building the analytical capacity to evaluate evidence that continues to accumulate after approval. Under this model, real-world evidence is not a contingency plan for when trial data falls short. It is part of the planned evidence strategy from the start.

Borrowing evidence across borders

A second prominent theme at Istanbul was analytical transportability. Many health systems, particularly in smaller or lower-income countries, cannot generate sufficient local real-world data to support rigorous comparative effectiveness analyses. The standard response has been to rely on indirect comparisons of uncertain quality or to wait for local data to accumulate. Transportability frameworks offer a more rigorous alternative.

Real-world data from large registries can be formally adjusted to reflect the baseline mortality rates, standard-of-care patterns and demographic profiles of a different health system. Rather than treating external data as inapplicable, transportability methods make the necessary adjustments explicit and auditable. Countries without established registry infrastructure can draw on data from those that have it, provided the adjustments are pre-specified and defensible.

Where this matters most is rare diseases.  Rare disease registries are small by definition. A transportability framework that allows an HTA body to use well-characterised external natural history data (adjusted for local context) expands the usable evidence base substantially. It does not resolve the data-scarcity problem. But it makes existing data more useful, particularly when developed in a robust and pre-specified way (see our earlier post on the role of a target trial framework in the pre-specification of external comparison). 

When contracts depend on data

The third theme at Istanbul was the most commercially direct. Outcomes-based contracts (i.e., arrangements in which a manufacturer’s payment is tied to a therapy’s real-world performance) have been discussed in HTA circles for years. What is changing is their practical feasibility.

For an outcomes-based contract to work, outcomes must be measured reliably. Historically that has required separate research programmes running alongside routine clinical care: slow, expensive and often contested. The integration of automated real-world data collection into electronic health records and hospital billing systems changes that equation. When performance metrics are monitored continuously, the data needed to trigger payment adjustments is generated as part of routine care rather than through a dedicated study.

The consequence is significant. If outcomes-based agreements are to become a standard mechanism for managing uncertainty around cell and gene therapies, the quality of the underlying data matters directly. A risk-sharing contract is only as reliable as the evidence it depends on. Real-world data collected without pre-specified endpoints, or analysed without the causal rigour that target trial emulation provides, cannot serve as a credible basis for substantial payment adjustments. The methodological standards required at submission and the data infrastructure required for post-approval monitoring are, increasingly, the same standards.

What Istanbul confirmed

The themes of HTAi 2026 point in a consistent direction. Real-world evidence now has a structural role in health technology assessment. The methods to generate it rigorously—target trial emulation, transportability frameworks, pre-specified data collection built into clinical operations—will be becoming requirements rather than recommendations. And the commercial arrangements that depend on it, outcomes-based contracts in particular, are moving towards operational use.

The shift is global: HTA bodies are building the capacity to demand better-designed evidence, at an earlier stage, focused on the comparative effectiveness questions they are already asking.

For companies planning market access across multiple markets, the practical question is not whether real-world evidence will be evaluated rigorously. It will. The question is whether the infrastructure to produce it (pre-specified, causally grounded, built before the data arrive) is already in place.