Why early preparation is essential for new health product regime

New regulatory regime promises significant benefits for patients and opportunities for manufacturers but only if the industry is properly prepared.

The European Union's Regulation on Health Technology Assessment (HTAR) is set to revolutionise patients’ access to medicines by introducing common clinical effectiveness assessments, or Joint Clinical Assessments (JCAs) of new health technologies.

The introduction of JCAs represents one of the most significant changes in the European healthcare landscape in recent years. In short, JCAs are centralised EU-level submissions of clinical data demonstrating relative effectiveness and relative safety with the aim of accelerating patients’ access to new health technologies. Individual Member States will retain power over evidence requirements, however.

The regulation will be applied to oncology medicines and advanced therapy medicinal products (ATMPs) from January 2025, with orphan medicinal products and other new medicines following in 2028 and 2030, respectively. While the regulation offers the opportunity to streamline submissions and more rapidly reach a wider patient group, to realise the full potential benefits, manufacturers need to begin planning immediately for the operational and strategic challenges that will accompany its introduction.

The diversity of evidence requirements, complexities of the PICO (Population, Intervention, Comparison, and Outcome) research framework, potential access delays and resource constraints created by the HTAR, will require strategic organisational adaptation by manufacturers.

Large pharmaceutical companies and small to medium-sized enterprises (SMEs) will face different challenges. Large companies have the advantage of resources and presence across Member States, while SMEs may struggle with the additional workload as well as limited local knowledge and past experience. Both, however, must reassess their existing HTA preparation process and foster cross-functional synergies to successfully navigate the new JCA-centric approach.

While the JCA signifies a milestone in advancing patient access to innovative therapies, manufacturers will be required to navigate several strategic and organisational challenges:

1. Diverse evidence mandates: With Member States retaining power over evidence requirements, manufacturers may be faced with additional data requests, increasing the burden at the national level.
2. PICO framework complexities: Adoption of the PICO process introduces nuances in clinical trial design which may sideline relevant clinical outcomes and not fully align with real-world applicability. Moreover, the PICO preferences may vary across EU member states leading to a large number of PICOs being required for the assessment of a single treatment. In the European Federation of Pharmaceutical Industries and Associations (EFPIA) study based on a simulation of the impact of proposed EUnetHTA21 methodology for three oncology products, a large number of potential PICOs were identified for each product, ranging from 16 for product X to 22 for product Y, and up to 57 for product Z ^{EU HTA Regulation}
3. Resource constraints: Time-sensitive JCA submissions may overextend manufacturers' capacities, presenting additional administrative hurdles and potentially delaying the evaluation process in certain jurisdictions.
4. Potential access delays: Integration of JCA reports into national evaluations remains ambiguous and could potentially stall market access timelines if national assessments await JCA recommendations. This is especially relevant for early access countries such as Germany and France.

Figure1: Challenges posed by EU HTAR and its implications for manufacturers

Securing successful product launches: Key areas for manufacturers to focus on for optimal readiness

In response to the many intricacies and uncertainties related to the JCA, organisations must pivot their focus to a number of essential strategic domains to ensure seamless integration of the new requirements with existing processes, ways of working and culture.

Figure 2: Key strategic domains for EU HTAR preparation

1. PICO Simulation preparation: Organisations need to engage in PICO simulations earlier and more proactively to grasp the breadth of variations and differing requirements across the European landscape. An increase in PICO diversity is expected to increase analytic complexities, straining internal capabilities. Additionally, increased proficiency in the assessment of Patient-Reported Outcomes (PRO) will be fundamental for fulfilling JCA criteria.
2. Timelines assessment: It is imperative to reassess pre-launch timelines to accommodate JCA dossier deliveries and local submissions. Preparatory activities such as value proposition development, early stakeholder engagement, systematic literature reviews (SLRs), indirect treatment comparison models development and so on, will need to commence earlier, and timelines may have to extend to account for the increased complexity of multi-market PICOs and analysis requirements.

Figure 3: Interdependency among EMA assessment, JCA, and national HTA submission timelines

3. Leveraging AI enabled technologies: Given the varied standards of care and the difference in availability of medicines throughout Europe, multiple PICOs can be demanded.  AI powered technologies can be used to leverage stakeholder insights to predict the probable spectrum of PICO requirements including during the JCA scoping phase.

4. Capacity and capability forecasting: Anticipating peak workloads associated with the JCA will be crucial. This includes forecasting the need for technical expertise, particularly across biostatistics teams, to manage additional demands such as the analysis of numerous PICOs, subgroups, as well as any supplementary data required during national submissions. Through process simulation, early retro-planning and robust forecasting, organisations can determine additional time and resource needs with greater accuracy.

5. Adaptive governance: The EU HTA has prompted a realignment of roles within companies, transitioning the task of developing national HTA submissions from national entities to global teams responsible for assembling the EU JCA dossier. This shift will alter organisational dynamics, necessitating tighter cooperation between local and Global teams throughout the process to align with the evolving JCA landscape. Both global and regional teams will need to adapt their operational modalities, implementing new strategic decisions and updating current operating procedures.

6. Stakeholder engagement: Effective JCA integration will depend on intensified internal and external coordination. Internally, cross-functional collaboration will be vital for PICO drafting, innovative trial design, and JCA dossier completion. Externally, it is crucial to engage in JCA dialogue with national HTA bodies early on to optimise the potential for report adoption at the local level. Moreover, the Implementation Act mandates that the HTA Secretariat, in collaboration with the JCA Subgroup, must incorporate inputs from pertinent stakeholders, including patients, clinical specialists, and, when required, additional experts. Engagement with patient organisations, which had previously been underrepresented in national HTA preparations, represents a significant additional activity. The development of a streamlined and early stakeholder engagement strategy will therefore be imperative for guiding manufacturers strategic market access activities.

Figure 4: Roles of various stakeholder groups on JCA strategy

7. Real-World-Evidence (RWE) generation plan adapted to EU HTAR: The scope of RWE generation must expand to incorporate the needs of both larger EU markets and smaller territories into comprehensive evidence plans. Supporting and unifying PICO simulation results will guide evidence accumulation, assist in identifying gaps for both JCA and national HTA filings, and facilitate risk assessments.

By focusing on these vital areas, organisations can prepare for the imminent JCA landscape, enhancing adaptability and improving the prospect of sustained success in the rapidly evolving European health technology assessment environment.

Big Pharma vs. SMEs: Charting the JCA ocean with the power of tankers and the agility of speedboats

The impact of JCAs on large pharmaceutical companies, which launch multiple products annually, and small and medium-sized enterprises (SMEs) that generally introduce one asset at a time, varies significantly. The former can capitalise on their established presence across various Member States and, as a result, are better positioned to pre-empt PICO requirements. Moreover, they can marshal a wealth of resources to form specialised, cross-functional groups proficient in drafting high-calibre submissions.

In contrast, SMEs often struggle as they may lack local presence in the Member State. This hinders their ability to gather specific local knowledge on clinical practices and epidemiology. Additionally, SMEs have smaller teams that may find it challenging to take on the extra work imposed by HTAR obligations. Nevertheless, SMEs can adopt a nimbler approach by collaborating with industry associations such as the EFPIA and the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE) to stay abreast of regulatory developments and bridge any internal gaps in expertise and resources.

Regardless of company scale, the dynamic nature of HTAR demands that businesses reassess their current processes for HTA preparation. A focus on enhancing the scalability and robustness of workflows for multiple product submissions in parallel and across diverse therapeutic areas will be key. Establishing a comprehensive JCA-centric approach will be essential for fostering synergies between market access, regulatory affairs, medical, clinical development, and biostatistics departments to ensure streamlined dossier development, and workflow continuity. As organisations venture into this redefined landscape, they must not only adapt, but also adopt a forward-thinking strategy that accommodates agility, flexibility, and innovation in organisational practices and processes.

In conclusion, manufacturers are at a critical juncture where they must either adapt or face the consequences. While HTAR presents a promising commercial opportunity and the prospect of wider and quicker patient access, the stakes are high. There is a significant risk of revenue loss and market leadership erosion for organisations that are unprepared or unable to effectively implement JCA.