EU adopts new guidance on clinical study validity for joint clinical assessments

The Member State Coordination Group on Health Technology Assessment adopted a new scientific guidance on the validity of clinical studies for joint clinical assessments during its tenth meeting on September 19, 2024.

The 44-page guidance titled, “Guidance on Validity of Clinical Studies for Joint Clinical Assessments,” aims to objectively and transparently define, classify, and assess the certainty of clinical study results for an intervention, including medicinal products, medical devices, and procedures.

This guidance focuses on single clinical studies, providing a clear framework for interpreting results and determining the reliability and applicability of data in assessing relative effectiveness. It builds upon previous guidance documents adopted by the Member State Coordination Group for joint clinical assessment (JCA), including the published guidance discussing the methodological and practical approaches to quantitative evidence synthesis for direct and indirect comparisons, and reporting requirements for issues such as multiplicity, subgroup analysis, and sensitivity analysis.

Set to take effect on January 12, 2025, the new guidance supports the EU Health Technology Assessment Regulation (HTAR) by providing practical guidelines to ensure that clinical studies used in JCAs meet rigorous standards for internal and external validity, as well as statistical precision. These criteria are crucial for evaluating the relative effectiveness of health interventions compared to their alternatives – a key consideration in decision-making processes across EU member states. As the guidance notes:

“… valid scientific principles are still required, not only to guide the development of JCAs at the European level, but also to support the understandability and usability of these results for national decision-making.”

The guidance provides detailed recommendations on the classification and labelling of study design for use in JCA. Clinical studies are categorized as either interventional or observational, with specific reporting requirements outlined for various designs. These include randomized controlled trials (RCTs), considered the ‘gold standard,’ as well as single-arm trials, cohort studies, and case-control studies. The guidance highlights the strengths and limitations of each design, offering a structured approach to assessing their applicability to the specific research question. It also emphasizes the use of standard, study design-specific tools to assess the risk of bias.

Additionally, the guidance addresses studies that fall outside traditional trial design frameworks but are increasingly relevant for HTA. These include studies utilizing master protocols, such as platform, basket, and umbrella trials, as well as clinical registries. Real-world data (RWD) and the generation of real-world evidence (RWE) are also discussed in this context. For studies that rely on RWD, the guidance emphasizes the importance of assessing the validity and reliability of the data, particularly when using proxy variables, mitigating attrition bias, and ensuring adequate measurement of outcomes.