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
