How should health technology developers prepare for future market access activities in Europe?

Numerous discussions have already taken place in various forms and on various platforms around the upcoming implementation of the EU Joint Clinical Assessments (JCA); it’s a hot topic and keeps many of us in our industry occupied. Despite the European Commission’s active efforts in developing draft regulation and related materials to support the transition to JCA, to date, some questions remain unanswered. As the EU JCA aims to harmonize and accelerate evaluation processes in Europe, all stakeholders, including health technology developers, national health technology assessment (HTA) authorities, and EU JCA assessors and patients, are facing substantial changes with this new process on European-level HTA.

A step toward timely and robust evaluation of medicinal products

With the upcoming implementation of the European Regulation 2021/2282 on Health Technology Assessment, the assessment and access to novel therapies in the EU is on the brink of a transformative shift. This shift is anchored by the new EU JCA, a game-changer in how the relative clinical effectiveness of new medicines is evaluated. The new process, effective starting January 12, 2025, will initially apply to oncology and advanced therapeutic medicinal products, followed by orphan drugs in 2028 and all novel interventions in 2030.¹ The EU JCA regulation represents a step forward towards a timely and robust evaluation of medicinal products, ultimately benefiting patients and healthcare systems across Europe.

A cornerstone of the EU JCA pathway is its scoping process, driven by a population-intervention-comparator-outcome (PICO) survey for the targeted product under assessment involving all EU Member States. This approach aims to cater to all local requirements from each Member State while applying a centralized, standardized European relative effectiveness assessment process. Although the PICO consolidation process is still to be finalized (the draft implementing act was published on March 5, 2024, by the European Commission),² there are some potential hurdles for health technology developers. This may include how the large numbers of PICOs driven by the Member States‚ input will be handled and streamlined, short timelines to develop and evaluate the dossier of new technology under assessment, and the current focus of the clinical relative assessment as an output of an academic exercise rather than informing decision-making regarding balancing benefits and harms of new technology.

The role of indirect treatment comparisons in evaluating the relative effectiveness

Building upon the pioneering efforts of the European Network for Health Technology Assessment (EU-HTA) during the last years, which has laid the groundwork for cross-border collaboration on joint relative effectiveness assessments within Europe, several lessons can be learned. Between 2006 and 2021, EU-HTA conducted 23 relative effectiveness assessments of pharmaceutical products, which provide insights into how relative efficacy data of novel therapies were evaluated, what sources and analytical methods were provided to inform comparative evidence, and how well this was accepted by the EU-HTA assessors.

One key aspect highlighted by EU-HTA’s work is the role of indirect treatment comparisons (ITCs) in evaluating the relative effectiveness of interventions. By comparing treatments that may not have been directly studied against each other, ITCs offer insights into relative effectiveness of novel therapies versus standard clinical care.

Traditional ITC methods include Bucher ITCs, network meta-analyses, or patient-adjusted methods such as matching-adjusted indirect comparison or simulated trial comparisons. Novel ITC methods have been developed to overcome specific challenges of traditional ITC methods, for example, related to time-varying treatment effects or imbalances in prognostic or effect-modifying variables within a network of trials.

In preparation for the JCA, the HTA Coordination Group recently adopted practical and methodological guidelines on quantitative evidence synthesis for both direct and indirect evidence, elaborating on multiple of these traditional and novel ITC methods.³ Interestingly, to meet the EU-HTA PICO scope, ITCs were employed in over half of all EU-HTA’s relative effectiveness assessments. Guided by the numerous critiques, the ITC acceptance remains unclear and value judgments on the relative effectiveness evidence are mostly missing.

Notes

1 European Commission. (2023). Implementing the EU Health Technology Assessment Regulation.

2 European Commission. (2024). Public Consultation on Implementing the EU Health Technology Assessment Regulation.

3 European Commission. (2024). Methodological Guideline for Quantitative Evidence Synthesis: Direct and Indirect Comparisons.

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