Treatment of evidence is key for the new EU HTA system’s workability

The overhaul of EU Health Technology Assessment, or EU HTA, is a significant policy milestone. From January, Member States will be able to use common HTA tools, methodologies and procedures across the EU. Medicines for cancer and advanced therapeutic medicinal products, or ATMPs, will be included first in the new system.

Policymakers’ goal, supported by Bristol Myers Squibb, is to make clinical assessments more integrated and efficient. There is significant room for improvement in how the new system will operate. This is especially true when it comes to the definition of the assessment scope for clinical evidence.

Complexity

In December, the HTA Coordination Group will publish guidance for the scoping processⁱ, one of the final and most important pieces in the architecture of the new system. The scoping process will define the range of evidence required for the assessment by each Member State. This will be based on PICOs - patient, intervention, comparison and outcomes. The PICO framework is a common model in evidence-based medicine. It sets the framework for the evaluation of a medicine and the data requirements for the health technology developer by outlining all the comparisons and outcomes for the new technology.

The PICOs proposed in the scoping process for the new EU HTA system would include variations in standards of care between, and within, Member States for the assessment of each new medicine. These variations in clinical options available and used in each country mean that indirect treatment comparisons will become a standard component of joint clinical assessments.

Scoping process

With wide variation in clinical practice, the number of alternative treatments in a therapy area can be very highⁱⁱ. Some of these will only be used in very few patientsⁱⁱⁱ. These low-incidence comparators would add disproportionate complexity to the new system. This would compromise the workability of the EU HTA system.

The system’s architects should forecast all possible and probable scenarios so that the eventual design works well. By considering these scenarios, they can anticipate where certain rules might need attention.

Let’s take this scenario which the current draft rules make likely.

It is possible that during a scoping exercise for a new medicine, five alternative standards of care will be used in most Member States. But in 10 Member States there will be a specific variation in clinical practice where a treatment option is used but it is not shared with any other country.

This means that the number of comparators for assessment would be 15, with five countries sharing data and 10 relying on their own evidence^iv. The joint clinical assessment dossier would include analyses of all outcomes requested by all Member States for 10 comparators that are each relevant to only one Member State. This would disproportionately increase the complexity of the joint clinical assessment process and potentially result in redundant analyses for most Member States.

A health technology developer would submit data relevant for only one country to the joint clinical assessment dossier and then country teams - both at the developer and at the HTA body - would extract data from the 14 other comparators and join it to their national processes.

This level of complexity is unnecessary. It would make work at national level much harder.

Improvements

There is a better way.

The data needed for the assessment of a medicine used in just one country should only be submitted once at the national level where it is relevant. This should be done in the local language. The HTA scoping consolidation process should automatically remove comparators if the request comes from only one country.

Comparators relevant for a very small proportion of European patients need careful consideration in the consolidation process. In common disease areas, there would likely be a long ‘tail’ of treatment options used in low single-digit percentages of patients.

With wide variation in clinical practice, some medicines would be used to treat only very small numbers of patients. Including these medicines as comparators would cause disproportionate complexity and, ultimately, generate redundant analyses because they would not be used in national decision-making.

Policymakers should introduce an explicit and verifiable threshold of use across EU Member States so that country evidence is consolidated consistently.

Opportunity

Joint clinical assessment under the EU HTA is an opportunity to make the flow of new medicines to patients more efficient. Now is the time to get the operation of the new system right.

We are pleased that the methodological guidelines emphasize independent national decision-making, with the appraisal of evidence and methodology, as well as value judgements, belonging to Member States.

As waves of science approach with more speed and regularity, the EU’s policy architecture will need to adapt so that patients can take full advantage. Regulatory pathways should evolve to reflect epidemiology and product complexity. Clinical trial designs are reflecting changing research and development patterns.

The future of healthcare will make more use of digital technologies and artificial intelligence, as well as combinations of diagnostics, biologics and advanced therapeutic medicinal products.

All this makes the task of assessing the scientific, clinical and economic value of medicines more challenging. It is up to all of us to work together on smoothing the transition to a new era of science.

References:
ⁱ Implementation of the Regulation on EU HTA
ⁱⁱ Value in Health
ⁱⁱⁱ BMC Cancer
^iv European Network for HTA