Key Takeaways
- Joint Clinical Assessment is now a parallel requirement under HTAR.
Health technology developers must prepare for a JCA alongside EMA or notified body submissions, reflecting a major shift toward centralized, comparative effectiveness evaluations in the EU drug and device approval process. - Strategic trial design and early HTA engagement are critical. Developers must align pivotal trial designs with JCA evidence needs, favoring active comparators and broader populations. Engaging in joint scientific consultation with both EMA and HTA bodies early in development is increasingly important.
- Cross-functional coordination and global planning must evolve. HTAR demands tighter collaboration between regulatory and market access teams and may complicate global dossier harmonization. Adapting to JCA processes can ultimately improve access and efficiency but requires proactive, strategic planning.
Since Regulation (EU) 2021/2282, also known as the Health Technology Assessment Regulation (HTAR) has come into effect, health technology developers (HTDs) now need to plan for a joint clinical assessment (JCA) in addition to submitting their drug common technical document to the European Medicines Agency (EMA) or medical device technical file to their chosen notified body. The HTDs, with new drugs eligible for the centralized procedures, must run the JCA process in parallel to their submissions.
The HTAR is designed to reduce duplicated assessment of new health technologies at the member state level—representing the near completion of the European Commission and Council’s HTA process improvement, which began 20 years ago. The implementation of the new regulation has also ended the pilot phase under Directive 2011/24/EU on patient rights in cross-border healthcare, which brought us EUnetHTA Joint Action 2 and the frameworks for the new processes.
Why is this important? HTA authorities are responsible for negotiating the price of drugs for each EU member state, meaning the commercial imperative to return a profit must also be considered and accounted for earlier in development. While there are extensive reviews of HTAR, its procedural implications and requirements, there is often less focus on the implications that are of immediate relevance to HTDs.
In this article, we have outlined some initial points for sponsors when making decisions around “what should we prioritize now?”
Consider classifications
It is necessary to understand where your medicine or medical device fits within the new framework. For drugs, determine whether you fall under the mandatory scope of the centralized procedure or if you will request consideration on the basis of the applicable optional scope criteria. For devices and in vitro diagnostics, confirm whether you are Class IIb or III or Class D, respectively. Once determined, the next stage is to understand where your application will fall in relation to the implementation schedule:
Jan. 12, 2025, onwards:
- Medicinal products that contain a new active substance for which the therapeutic indication is the treatment of cancer and advanced therapy medicinal products.
- Medical devices that are subject to review and input from an expert panel.
Jan. 13, 2028, onwards:
- Medicinal products that are designated orphan products.
Jan. 13, 2030, onwards:
- The medicinal products not previously included.
This phased implementation leaves a small window for drugs where the marketing authorization application (MAA) will be filed before the implementation date to still follow established processes for market access after approval—rather than preparing for it in parallel. But the window is closing. Now is the time to adapt.
Aim, adapt, achieve
For those looking to adapt, it’s necessary to understand what the JCA hopes to achieve. JCAs focus on the relative effectiveness of new or existing technologies, emphasizing added value compared to established technologies.
The assessments are based on scientific evidence, including confidence intervals and an analysis of the strengths and limitations of the evidence. This approach aims to improve the use of scientific evidence, inform clinical decision-making, and support patient access.
The JCA dossier will be based around PICOs: patient, intervention, comparator, and outcomes. Beyond the usual concerns involving Phase III clinical trial design, including sample sizes, duration, and patient populations, JCA is likely to lead to increased demands on developers for directly comparative studies.
Ideally these studies will use active comparators rather than placebos and include broader patient populations to achieve the evidence standards necessary for JCA.
Collating and collaborating with joint scientific consultation
Collating this feedback and incorporating it into the pivotal trial designs is also a key recommendation. Prior to the new regulation, end-of-Phase II interactions with HTAs to discuss the pivotal trial designs with regulators was likely already a key milestone in most development plans, especially for larger pharma. Now, it is an important consideration for all sponsor organizations. Opting for the refined “joint scientific consultation” under the new HTAR, where EMA and HTA advice can be sought in parallel, may be a more efficient approach.
The involvement of so many regulatory and HTA authorities will inevitably lead to divergent advice, as witnessed during the pilot scientific advice between the EMA and EUnetHTA. It may also lead to scenarios where EU protocol requirements cannot be aligned with US FDA or Japanese Pharmaceuticals and Medical Devices Agency expectations. This may lead to more pivotal trials with regional adaptations. Study teams may need to conduct advanced planning to avoid unnecessary duplication.
Opportunities for JSC may be restricted during the phased implementation of the JCAs; if a JSC is not available, a mix of EMA advice and national HTA meetings may be the alternative. At the time of this writing, the EMA website suggests that there will be around 10 slots per year for JSC.
Additional factors to consider
Now with the JCA, the submitting team will need to coordinate the optimal submission deadline around the availability of results, in addition to collaborating more closely with the market access team, as their applications will be in parallel to the MAA with timelines pegged to its progress. Market access teams will be more closely involved in authoring the Summary of Product Characteristics and the Clinical Overview (Module 2.5), given that both documents will be included in the JSC.
This is also an example of how the new HTAR presents challenges to the global marketing dossier if European Module 2.5 departs significantly from that used in the rest of the world. Shortened timelines also apply for the JCA procedures during an accelerated assessment procedure. Thus, if pursuing this pathway, it becomes ever more important to involve market access team members in the planning discussions. The HTAR may also cool aggressive conditional marketing authorization strategies, given the reduced clinical data package they are based on. Yet another factor to consider.
HTAR and the benefits beyond
The JCA regulation has highlighted the HTA aspects of drug development and made it a central pillar of the development plan for all health technology developers. While the regulation presents new challenges, strategies exist to adapt successfully, and most of them will benefit from deeper collaboration.
Adapting to the HTAR will bring additional benefits, including faster patient access, resource sharing for authorities that will reduce bottlenecks, and more consistency in HTA assessments. These benefits, which help bring drugs to market in a timelier manner, are worth celebrating.
Graham Bell is Director, Global Regulatory Strategy, ICON plc
