By Anke van Engen, senior principal, EMEA value & payer evidence, IQVIA, and Dima Samaha, senior principal, EMEA value & payer evidence, IQVIA
The European Union (EU) comprises 27 member states (MS) with varying laws, processes and regulatory standards. This variation has led to a complex data landscape for health technologies and drug therapeutics developers, including duplication of assessment efforts.
With the aim of addressing historical complexities, the European Health Technology Assessment Regulation (EU HTAR) was adopted in 2021 to enable the development of a joint perspective on clinical aspects of medicines, in vitro diagnostics, and high-risk medical devices.
The main goal of the HTA regulation (HTAR) is to accelerate patient access to treatments across Europe by increasing transparency and reducing duplication of assessment efforts. Formalizing regular collaboration among stakeholders will promote increased patient and clinician involvement, ensuring their unique needs are addressed. Harmonization of efforts will be especially beneficial for smaller European countries with less established HTA bodies. It is also essential to note within these geographies, pharmaceutical firms will have longer drug launch times as noted in the EFPIA Patient W.A.I.T Indicator 2022 Study.
While there are many benefits, the mandatory shift brings some uncertainty for stakeholders, including the complexity of the documentation needed for a joint clinical assessments (JCAs) submission, the accelerated timeline to produce a comprehensive submission, the lack of input from stakeholders during the drafting process guidance, and the lack of cohesion among the different components of the regulation, namely joint scientific consultations (JSCs) and JCAs.
Key terms in the EU HTA regulation guidelines
To fully understand the guidance, it’s essential to understand its terminology, including: JCAs are health technology assessments that cover the health problem and current use of the technology, description of the technical characteristics of technology, safety, and clinical effectiveness.
JSCs allow industry to consult with the European Medicine Agency (EMA) and multiple EU HTA bodies to obtain guidance on the information, data, analyses and other evidence that are likely to be required from clinical studies.
Population, Intervention, Comparator(s), Outcomes (PICO) is the framework used to define the scope of the JCA. Within the framework, a research question to be addressed is defined by patients or population(s) of interest, the intervention being addressed, the relevant comparator(s), the intervention under assessment it should be compared to, and the outcomes of interest.
European Network of Health Technology Assessment 21 (EUnetHTA 21) is the consortium of 13 HTA bodies tasked with supporting the implementation of the HTA regulation between September 2021 and September 2023.
Coordination Groups (CG) are comprised of representatives from HTA authorities who oversee the implementation of JCAs and other joint work related to this regulation.
What challenges do stakeholders face with the HTA regulation?
As industry prepares for the 2025 implementation deadline for the HTAR, it is essential to understand the broad impacts early. Some of the critical areas for stakeholders to keep in mind as they develop their compliance approach include:
The JCA process is triggered shortly after regulatory filing is completed, which begins with the CG sending a survey to collect PICO information determined by each MS.
Currently, the recommendation for scoping processes is more an amalgamation of country-specific PICOs than a streamlining of evidence requirements. For example, if a company is launching a new lung cancer drug, they could be required to develop evidence to support at least 10 different PICOs.
As the HTAR is currently drafted, the short timeframe for developing robust evidence adds additional analytical complexity. When a submission is filed, the EMA notifies the HTA coordination group secretariat and shares details on the drug, its regulatory details and the claimed indications.
Additionally, as this triggers the JCA start, the sponsor must wait upwards of three months to receive the final PICO, thus only leaving another three months to complete the dossier. Since timelines often take four to five months to complete, the constrained timelines create added pressure for sponsors.
With the goal of inclusivity, the HTAR was drafted with the involvement of all 27 member states, including the review of methods and outputs and the input of patients and clinicians. The European Community (EC) has also initiated training processes for patient and clinical experts who are contributing to joint HTA activities, such as validation of the PICO and draft JCA report.
However, due to the limited resources available to both MS and the patients and clinicians, there are questions about how input collection will be achieved.
Surprisingly, under the HTA, there is a lack of communication with sponsors during the JCA process which poses concern. Due to the differences in the PICO between MS, pharmaceutical companies need to contribute to the scoping process, although this is a digression from the JA3.
This will assist in the factual accuracy check and review meeting for the draft report with the assessment team and relevant stakeholders.
How to prepare for the HTA regulation implementation deadline?
Although there are challenges when implementing a new, wide-reaching regulation, there are steps industry can take between now and 2025 to best prepare for the HTAR implementation deadline.
Engage with key stakeholders early
Industry will need to remain up to date on the guidance released by EUnetHTA 21 as well as the implementation acts from the EC. They will also need to engage with the CG, HTA bodies and national decision-makers.
There is still time before the 2025 deadline for stakeholder input, so it is essential to provide feedback on the requirements before the implementation acts are finalized. This input can be provided alone or as part of an industry association.
Adapting internal processes
Pharmaceutical companies should map out future EU JCA processes and governance to prepare for HTAR implementation, including processes for HTA submissions. An operating model should align with the EU JCA process and define governance to ensure each organizational function is united. To meet evidence-generation requirements and timelines, literature reviews should include EU epidemiological data for the past five years that describes clinical management and internal validity assessments to address variations in MS.
PICOs need to be anticipated and it will be fundamental to generate (indirect) evidence to account for all populations, comparators, and outcomes against those PICOs.
As is currently done with EMA and the U.S. Food and Drug Administration (FDA), sponsors should also begin embedding early dialogues such as JSC into their processes. To do so, close collaboration should be established between different departments, including HEOR, market access, biostatistics, regulatory, and clinical development.
Anticipate relevant PICOs
Advance planning is critical to allow for the generation of robust comparative evidence needed to meet JCA requirements. Sponsors should have a clear picture of what PICOs to expect prior to the start of the JCA. This will need to include an understanding of the payer-relevant populations and comparators in each market, which can be supported by input from local affiliates as well as local clinicians and patients.
If comparative data cannot be generated, an indirect treatment comparison (ITC) feasibility assessment will need to be conducted to evaluate available options carefully.
What the future holds
The HTA regulation is a large-scale shift in industry processes that will have broad-reaching impacts, which inherently introduces challenges in the initial implementation. Between now and the 2025 deadline, the EU HTA will undoubtedly evolve as stakeholder concerns are addressed throughout the implementation process. There are steps that industry can take now to best prepare for the upcoming changes, including engagement with HTA bodies and other stakeholders, anticipating PICOs based on the available information, and adapting internal processes to make later adjustments easier to implement.
Once the requirements and processes are better established, the long-term benefits will shape the future of therapeutic development and innovation. Less time will be spent on duplication efforts and the accessibility of treatments will increase across the EU, leading to more equitable access for patient communities.