Mapping methods gaps between EU joint clinical assessments and local health technology assessment decision-making: an environmental scan of guidance in select EU markets and harmonization challenges

Abstract

Aim: Under the newly instituted health technology assessment (HTA) regulation (HTAR), health technology developers must build evidence packages that meet the needs for both the upcoming EU joint clinical assessment (JCA) and national decision-making. In-depth knowledge of local methodological requirements as well as preparedness for effective strategic development is crucial. This study aimed to review methodological guidance documents to map similarities/misalignments between the EU HTAR and select HTA agencies. Materials & methods: An environmental scan was performed in March 2024 and updated in December 2024 of the websites for European Network for HTA, the European Commission and HTA agencies in France, Germany, The Netherlands and Spain. The search aimed to systematically identify and summarize methodological guidance documents from the respective organizations on scoping considerations, evidence identification and synthesis. Results: Overall, published EU HTAR methods guidelines are detailed, prescriptive and make reference to a preference (or lack thereof) for specific analytical methods. There was consensus among EU JCA and local HTA guidelines that clinical comparative assessments should be based on a systematically identified, unbiased selected evidence base derived from various sources. However, agencies differed on guidance related to evidence derived from indirect treatment comparisons. Conclusion: An environmental scan of methods documents revealed that it will likely be challenging for health technology developers to build strong evidence packages that can support both EU JCA and local reimbursement decision-making. A greater understanding of the similarities and differences between EU and local HTA requirements will be needed, including a greater capacity to demonstrate value through advanced analytics.

Keywords: European Union; comparative effectiveness; data; health technology assessment; joint clinical assessment; methods; uncertainty.

Figure 1.. Sources: EU versus French, German, Dutch and Spanish guidance.

AEMPS: Spanish Agency of Medicines and Medical Devices; AQuAS: Agency for Health Quality and Assessment of Catalonia; G-BA: Germany’s Federal Joint Committee; HAS: Haute Autorité de Santé; HTAR: Health technology assessment regulation; IQWiG: Institute for Quality and Efficiency in Health Care.

Figure 2.. Recommended tools: EU versus French, German, Dutch and Spanish guidance.

CONSORT: CONsolidated Standards of Reporting Trials; EUnetHTA: European Network for Health Technology Assessment; GRADE: Grading of Recommendations Assessment, Development, and Evaluation; HTAR: Health technology assessment regulation; PASKWIL: Palliative, adjuvant, specific side effects, quality of life, impact of treatment and level of evidence; PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses; QUADAS: Quality Assessment of Diagnostic Accuracy Studies; RCT: Randomized controlled trial; REQueST: Registry Evaluation and Quality Standards Tool; RoB: Risk of bias; ROBINS-I: Risk Of Bias In Non-randomised Studies - of Interventions; STARD: Standards for Reporting of Diagnostic Accuracy; STROBE: Strengthening the Reporting of Observational Studies in Epidemiology; TREND: Transparent Reporting of Evaluations with Nonrandomized Designs.

Figure 3.. Flowchart evidence synthesis methods as constructed based on EU health technology assessment regulation guidelines.

*Informative priors should only be used for the heterogeneity parameter. HTAR: Health technology assessment regulation; IPD: Individual patient data; ITC: Indirect treatment comparison; MA: Meta-analysis; MAIC: Matching-adjusted indirect comparison; ML-NMR: Multilevel, network meta-analysis; RCT: Randomized controlled trial; STC: Simulated treatment comparison.