GAVIN OUTTERIDGE

Reducing uncertainty in the EU HTA Regulation

Reducing uncertainty in the EU HTA Regulation

Reducing uncertainty in the EU HTA Regulation

Reducing uncertainty in the EU HTA Regulation

Why it makes sense to opt for a Joint Scientific Consultation

Reducing uncertainty in the EU HTA Regulation

GAVIN OUTTERIDGE & CATHERINE CHAMOUX

Reducing uncertainty in the EU HTA Regulation

Reducing uncertainty in the EU HTA Regulation

“Even though there are no ways of knowing for sure, there are ways of knowing for pretty sure.” - Lemony Snicket

The new EU HTA regulation¹ is introducing a major change to market access in Europe, by establishing a central appraisal of a new, comprehensive clinical data dossier² that should serve as a basis for national price and reimbursement decisions. This multi-national clinical appraisal is set to be based on a list of PICOs³ developed by the new EU HTA Co-ordination Group and sent to the company applicant (or “health technology developer”, HTD) approximately 2 months before the required Joint Clinical Assessment (JCA) dossier submission date.

The list of PICOs should cover the requirements of all 27 member states but may differ from the clinical evidence base prepared by the HTD and/or those submitted to the EMA (as the existing EU regulatory approval process and the new EU HTA process are set to run in parallel, not in sequence).

In the case of ATMPs⁴ and some forms of cancer, it is common to have a lack of clinical data as the disease may be ultra-rare and its natural history not studied in detail, constraining the ability of the HTD to answer the PICO questions. Another case would be the necessity to run new statistical analyses & reports e.g. indirect treatment comparisons, such tasks taking time and effort, not compatible with a 2-month deadline.

Many surprises can come from the list of PICOs, adding a lot of pressure on the HTD at the last minute, further complicated by the risk of the final EMA label not being known at the time of the JCA dossier submission.

In the context of such uncertainty arising from the draft JCA process, companies with oncology or gene and cell therapies due to be submitted for EMA approval after 13th January 2025 (and thus in scope of the EU HTAR) need to start work soon to reduce the uncertainty around which PICOs will be specified for their forthcoming JCA.

One way to help with predicting PICOs is to take advantage of new EU consultation process, the Joint Scientific Consultation or JSC, which has been formally established by the EU HTA . While this JSC is officially not binding for the Co-ordination Group, industry experience with the EMA suggests that it is unlikely that the JCA process will totally ignore the conclusions of a JSC.

Although no JSC has yet been conducted under the EU HTAR, there are also lessons we can draw from an examination of the closest analogue. EUnetHTA conducted multiple so-called Early Dialogues

between 2017 and 2020¹ with multi-national HTA, joint EMA-HTA and formats. The joint EMA-HTA Early Dialogues save precious time for HTDs. Such authority interactions allowed HTDs to propose major changes to their evidence plans, like the addition of a study, changes of comparator, design adaptation and primary endpoint choice as well as population criteria and other outcome selection. EUneHTA, which is creating the first version of processes and guidelines for the EU HTAR implementation, considers the results of the prior Early Dialogues to be a good signal of better evidence for future HTA.

At the beginning of this new HTA process, there is a lot of uncertainty in the outcomes and HTDs fear the results of the JCA, especially in terms of how they will influence price, reimbursement and access in the 27 EU countries. AESARA recommends that HTDs should consider opting for a JSC, as doing so would allow them to better predict the PICOs and create the opportunity to gather new evidence, and more time to prepare a targeted JCA submission. A joint EMA-HTA JSC would be the best option so both regulators and HTA bodies can hear each other’s concerns and achieve some convergence on evidence requirements.

In summary, biotech and pharma companies with oncology, gene or cell therapy products in scope of the EU HTAR should consider:

  1. Going for a JSC to forecast likely PICOs, ideally jointly with the EMA
  2. Aligning HTA strategy with European Regulatory strategy
  3. Engaging cross-functionally and cross-countries as they do so.

Taking these preparatory steps will reduce the risk of last-minute, non-strategic adjustments to the JCA submission and, ultimately, improve the chances of positive HTA across the EU.

References

[1] https://eur-lex.europa.eu/legal-content/FR/TXT/PDF/?uri=CELEX:32021R2282&from=EN

[2] https://www.eunethta.eu/wp-content/uploads/2022/12/EUnetHTA-21-D5.1-Submission-Dossier-Guidance-v1.0.pdf

[3] PICO is a mnemonic used in evidence-based medicine to frame a research question. In health technology assessment practice the four letters typically stand for: Population, Intervention, Comparator and Outcome(s) (e.g. “progression-free survival” or “Change From Baseline in Hammersmith Functional Motor Scale” ).

[4] ATMP: “Advanced therapy medicinal products” as defined by the EMA i.e. gene and cell therapies and some other innovative treatment modalities. Cf: https://www.ema.europa.eu/en/human-regulatory/overview/advanced-therapy-medicinal-products-overview

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