EU JCA is here. Rare diseases are next. Your RWD strategy can’t wait.

Europe has begun standardising the clinical questions that sit behind reimbursement. The EU Joint Clinical Assessment (JCA) has been in force since 2025 for new cancer medicines and ATMPs, and it will expand to orphan medicines in 2028, then all centrally authorised medicines by 2030.

For rare disease sponsors, the timing is useful though creating some challenges. Those challenges are because many pipelines were built for national HTA variation: different comparators, different outcomes, different tolerances for uncertainty. Useful because the new regime clarifies what to do: comparative value will be examined earlier, more consistently, and with less patience for vague claims.

A single assessment, multiple consequences

The EU’s aim is straightforward: a joint clinical assessment that Member States can reuse, reducing duplication while leaving national pricing and reimbursement decisions where they already sit. In practice, that still changes sponsor behaviour, because it shifts the “hard questions” forward in time.

The JCA will reliably pull on the same threads:

• Comparator realism: what is “standard of care” across countries, not just on paper?

• Outcome relevance: are endpoints meaningful beyond specialist centres and trial protocols?

• Generalisation: do results hold for routine practice and broader patient mixes?

• Residual uncertainty: what bias remains, and how is it bounded?

In rare diseases, these questions are not easy to answer.  And yet, the answers are needed to help define a path towards future reimbursement, something that is not straightforward in rare conditions.

RWD: either scaffolding or sand

Real-world data (RWD) has become the default solution to rare disease evidence gaps. That is both sensible and dangerous. Sensible, because trials are small, follow-up is limited, and comparators are frequently contested. RWD can ground a programme in clinical reality: natural history, treatment pathways, switching patterns, durability, and outcomes that matter to patients and systems.

Dangerous, because most “early RWD” is not fully ‘baked’ by default. At that stage, the risk of initiating expensive and long term data collection projects, across many jurisdictions is very high.  Any review of existing RWD too often begins with the dataset rather than the decision, and treats observational comparison as an analysis rather than a design problem. Under JCA scrutiny, “we used RWD” won’t help if the basics are weak: unclear time zero, mismatched eligibility, unconvincing outcome definitions, and bias handled with a paragraph instead of a plan.

The discipline that works is familiar to anyone who has dealt with sceptical regulators or payers: specify the trial you wish you could run, then emulate it. That target-trial framing forces clarity on population, treatment strategies, follow-up, outcomes, estimand, and the bias you cannot wish away.

What to do before 2028

January 2028 is not far away in evidence-generation terms. Sponsors with orphan ambitions should move now on four practical steps:

1. Treat PICO as a design constraint.

   Lock the comparator too late and you end up defending the indefensible. 

2. Write the target-trial specification early.

   If you may need external comparisons, even as supportive evidence, make the design explicit before habits harden.

3. Maintain a “bias register”, not a limitations paragraph.

   Decision-makers expect competence: confounding, misclassification, missingness, informative censoring, and country-level practice variation should be named, assessed, and mitigated.

4. Build the patient journey first.

   Rare disease reimbursement is won on credible trajectories and meaningful outcomes.  Help patients and clinicians be informed.

The inevitable conclusion

The EU JCA is already shaping oncology and ATMP evidence packages. Rare diseases are next.  In rare diseases, you need to start even earlier because timely and quality data are even more difficult to come by.  The focus is not “data access”. It is decision-ready cohorts that support the questions the JCA will ask and those can come from multiple sources as long as you understand their provenance.  Think of rAIre(TM) as a way of generating evidence to support EU JCA quickly and cost efficiently.

Sponsors who treat RWD as an add-on will spend 2027 trying to retrofit credibility into a locked programme. Sponsors who treat RWD as design infrastructure with target-trial discipline, fit-for-purpose data, explicit uncertainty management, will enter the orphan JCA era with fewer surprises.