The EU HTA Regulation

The Regulation on Health Technology Assessment (Regulation (EU) 2021/2282) Regulation (EU) 2021/2282) provides a permanent framework for joint clinical assessment (JCA) in the European Union and is aimed at reducing the burden on the industry and EU Member States and increasing the quality of health technology assessment (HTA). In the following piece, we will explore key concerns voiced by pharmaceutical industry representatives about the implementation and implications of JCA and will also highlight some responses offered by European HTA bodies.

Industry concerns

While regulators promise to optimize the number of decision problems (PICOs), uncertainty around the consolidation process remains

According to the regulation, JCA will review the analyses within the PICOs (patient, intervention, comparator, outcomes) framework, but Member States’ HTA bodies may still request complementary analyses following the joint work. Importantly, the JCA must be inclusive, meaning that all Member States’ needs will be taken into account via a survey, but will be converted into as few PICOs as possible. However, it is currently unclear how optimization of PICOs will take place to ensure the most meaningful impact across the EU while capturing all individual Member States’ requirements. The following questions remain:

• How will prioritization of Member States’ needs and requirements be done in a fair and transparent way?
• Will the ‘biggest impact across the EU’ for an intervention be defined as the largest number of patients or the majority of Member States?
• Will the list of comparators be based on the best available alternative, or will it also include later-generation therapies in countries that do not yet use novel treatments as their standard of care?

Manufacturers are worried about complexity, short timeframes and no opportunity to contribute to the scoping process

Another of the industry’s concerns is that JCA will add another level of complexity to EU market access. PICO scoping may result in a multitude of comparators, including off-label ones, thus requiring a large number of indirect treatment comparisons (ITCs) and adding to the size of the dossier. This could particularly be the case for larger indications, such as oncology, which in turn could be especially challenging for small and mid-size pharmaceutical companies with limited resources. In addition, there is no opportunity for companies to contribute to PICO scoping or respond to the JCA’s conclusions.

Since the appraisal decision remains with the Member States, there is a risk of duplication of work at a national level

Member States are required to give ‘due consideration’ to the JCA. It remains to be seen whether they will commit to using the JCAs or continue using their own guidelines that request additional analyses on the national level. The latter might especially be likely for larger national HTA bodies with well-established HTA practice (for example, safety data typically requested by Germany’s Institute for Quality and Efficiency in Health Care [IQWIG]). The level of alignment from all Member States remains to be seen. 

The methodological level of the dossier is hard to predict due to large differences in standards and requirements between Member States

Regulatory agencies have reaffirmed that the JCA will aim to produce a state-of-the-art quality dossier. However, it should be acknowledged that methodological requirements vary per Member State. Since HTA is not implemented by some, the industry is concerned that a consolidated pan-EU assessment process is a difficult goal to accomplish. Larger Member States involved in multiple implementation working groups might be driving the dossier standards and advocating for the addition of specific analyses. A particular concern is an alignment by national HTA bodies on ITCs, surrogate endpoints and real-world evidence (RWE). There will be a need for smaller Member States’ HTA bodies to master advanced statistical methods (network meta-analyses, matching-adjusted indirect comparisons, etc.) and RWE application to have their voices heard during PICOs scoping.

Stakeholders would like to see a monitoring process in place, continuously assessing and improving the JCA process 

Different stakeholders (pharmaceutical companies, including small and mid-sized, the European Federation of Pharmaceutical Industries and Associations [EFPIA], and patient organizations [EUCOPA]) have spoken about the need to regularly monitor the implementation of the regulation so that the new JCA process delivers on its goals while continuously improving.

In addition to their concerns regarding JCA processes, many industry representatives feel concerned about unpreparedness for the new assessment process. This will require shifting the evidence generation and synthesis strategy to a much earlier point; the future assessment should be kept in mind from the clinical program development stage. Connecting different departments at different steps of the product pipeline and raising awareness of the evidence generation objectives will become an important task for global pharmaceutical companies.

HTA representative statements

In response to the concerns of industry representatives, members of the European Medicines Agency (EMA), the Directorate-General for Health and Food Safety, the European Network for Health Technology Assessment (EUnetHTA), the Swedish Dental and Pharmaceutical Benefits Agency (TVA), the National Health Institute (ZiN) in The Netherlands, and the Norwegian Medicines Agency (NoMA) have offered the following statements communicating their vision of the new regulation:

Value judgments are not allowed in JCA

The JCA will report the consensus view on relative clinical benefits but not provide recommendations on added value/reimbursement. As is outlined in the Regulation, these decisions will remain at the Member State level. The EMA and EUnetHTA additionally stress that the Regulation is about assessment, not appraisal meaning that sponsors should see the dossier as highly technical and data-driven and thus be prepared to supplement all the statements with robust evidence based on statistical analyses.

PICO will be driven by policy, not data

The Committee will ensure that all Member States’ needs will be accounted for; relevant comparators will be based on the local standards of care and are non-negotiable. Further, according to NoMA and ZiN, if companies are worried about short timelines, they can define the comparator list in advance (e.g. through a landscaping exercise) and start conducting ITCs in time.

More patient and clinical expert engagement will be sought

Member States will be encouraged (but not required) to seek clinicians’ and patient advocate groups’ engagement for scoping and assessment. In addition, external experts, including clinical and patient communities, will be able to provide input on methodological matters and data collection. The industry is advised to proactively consult these groups early, at the evidence generation stage.

The industry needs to be more proactive in generating the necessary evidence

HTA bodies wish to emphasize that the responsibility lies with the industry to reduce uncertainty around scoping by collecting data, reaching out to stakeholders and conducting relevant analyses in advance.

How can industry get ready for the new process?

Overall, there is plenty of enthusiasm for the harmonization initiative, its potential to improve the quality of HTA and ensure timely access to novel therapies across all EU countries despite widely acknowledged uncertainty. As crucial as the open dialogue with HTA bodies is, there is a lot that pharmaceutical companies can do already.

As stakeholders have indicated, there is a large, shared concern for the unpreparedness that pharmaceutical companies will face around the new assessment process, a concern that is further corroborated by a survey that Lumanity conducted during ISPOR Europe in Vienna last November. However, the concern for unpreparedness has led to the growing understanding that better early internal interaction is needed to effectively map the evidence generation strategy. This will involve engaging, training and coordinating all functions, from medical departments to regulatory and health economics and outcomes research, to ensure a smooth transition to the new assessment process.

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