In the realm of healthcare regulation, the proposed methods for conducting EU-level joint clinical assessments (JCAs) have stirred significant debate and concern within the pharmaceutical industry. A recent report commissioned by the European Federation of Pharmaceutical Industries and Associations (EFPIA) sheds light on the potential pitfalls and challenges companies may face under the forthcoming Health Technology Assessment Regulation ((EU) 2021/2282).
The guidelines put forth for implementing these JCAs, as highlighted by EFPIA, lack the requisite flexibility and pragmatism necessary to navigate the complexities of rapidly evolving disease areas, particularly oncology. A recent study, published on March 28, scrutinized the methodology proposed by EUnetHTA21 by applying it to three anonymized oncology products with EU regulatory approval.
One of the key findings of the report reveals that the scoping process outlined in the proposed methodology results in an overwhelming number of Population, Intervention, Comparator, and Outcome (PICO) elements that companies must address. For instance, one drug subjected to analysis had a staggering 57 PICOs initially, even after consolidation, the number remained at 23. This imposes a significant burden on companies to gather and present data for each PICO, often necessitating complex analytical methods or real-world evidence from disparate sources.
Furthermore, the report underscores the challenge posed by the wide range of comparator therapies mandated by the proposed guidelines. In the context of oncology, where treatment options vary widely across EU member states, identifying appropriate comparators becomes particularly daunting. This issue is compounded by the inclusion of off-label drug use as comparators, a practice that diverges from regulatory standards and complicates the assessment process.
JCA is not the cause of differing and partly even conflicting evidence requirements across Europe. These differences existed for decades. So far, industry coped with these requirements by planning their trials for key countries (most notably the US and Japan) and then trying to meet the evidence requirements of all other countries one after another according to their position in the (European) launch sequence. What JCA changes, is that all EU requirements have to be accounted for at once within a very restricted timeframe. This puts the timeline of life-saving innovations in jeopardy and should raise serious concerns among industry, patients, physicians, regulators as well as politicians. Doing this in oncology – a field of extreme unmet need where lives of patients are at stake and where treatment options as well as evidence requirements differ strongly across the EU – seems to be a questionable choice.
Another critical concern raised by EFPIA relates to the requirement for mature Overall Survival (OS) data, which may not be available at the time of regulatory approval for many oncology submissions. The report suggests a reconsideration of this requirement, advocating for the inclusion of intermediate outcomes such as Progression-Free Survival (PFS) in JCAs. Additionally, it highlights discrepancies between the proposed guidelines and the endpoints commonly used in national HTA assessments, further complicating the evaluation process.
EFPIA’s apprehensions regarding the JCA process echo broader industry concerns, with organizations like the Alliance for Regenerative Medicine (ARM) also cautioning against potential impediments to the implementation of the HTA regulation at a national level.
As discussions surrounding the implementation of EU-level JCAs continue, it is evident that addressing the outlined challenges and refining the proposed guidelines will be crucial to ensuring a streamlined and effective assessment process that aligns with the diverse needs of stakeholders across the European healthcare landscape.
