Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Real-world evidence in the German HTA process – acceptance by G-BA in the European regulatory and HTA context ***

Dr. Verena Schipper (Abschlußjahr: 2023)

Summary
Language: English
Real-world data (RWD) are an emerging topic in the regulatory and health technology assessment (HTA) context as an alternative source for clinical evidence, because more and more medicinal products are approved in (very) rare conditions in which large, randomised pivotal trials may be unfeasible and/or unethical.
This work focuses on the role of RWD in the German HTA assessment and systematically analyses acceptance or rejection of RWD in past early benefit assessments by the federal joint committee (Gemeinsamer Bundesausschuss, G ¬BA). By comparison to the approach of the European Medicines Agency (EMA) and the English National Institute for Health and Care Excellence (NICE), G BA policies are considered in the European regulatory and HTA context. Furthermore, in 2019 novel RWD-based procedures, which may change the impact of RWD on the German HTA process, were introduced (e. g. the obligation for routine practice data collection). This work also provides an early overview of these instruments.
Proceedings in which RWD played any role as clinical evidence were identified from all justifications of resolutions by G BA from 2011 (start of early benefit assessment in Germany) until end of January 2023 in a systematic search and relevant proceedings were analysed in detail. For all questions addressed (e. g. systematic analysis of G BA proceedings in which RWD were relevant, comparative analysis to EMA and NICE, proceedings for routine practice data collection), detailed information on the reasons for each decision was derived, extracted and analysed from relevant, open-access documents of the respective institutions (e. g. justifications of resolutions by G BA, assessment reports by EMA, guidance by NICE).   
RWD were most relevant in orphan indications, for medicinal products with expedited forms of approval and for advanced therapy medicinal products (ATMPs); most commonly RWD were presented as external control for indirect treatment comparison (ITC). The rate of acceptance of RWD was particularly high in severe ultra-orphan metabolic diseases affecting young children. Despite acceptance of RWD, in many cases the resulting additional benefit was still non-quantifiable (due to the remaining risk of bias); in two cases, however, a major additional benefit was based on real-world evidence (RWE).
G BA was generally more critical towards RWD/RWE than EMA and NICE, but this work also reflects on the different natures of their assessments as a potential contributor to this finding.
A trend for RWD to be likely to become more relevant within the German HTA system could be established. For example, the proportion of proceedings with RWD relevance increased over time. Furthermore, from 2026 onwards the first benefit assessments based on routine practice data collection are going to commence.
This work found that routine practice data collection will introduce comparative assessments based on registry data in orphan indications with established therapeutic options (e. g. spinal muscular atrophy, SMA). In the standard early benefit assessment, no comparative assessments would be conducted for most of the respective medicinal products. How well this novel, potentially powerful tool in the German HTA system will work and provide data suitable for benefit assessment remains to be seen.
In summary, RWD/RWE are a highly dynamic topic with growing impact on the German HTA system. Harmonisation of European HTA assessments from 2025 onwards may add further momentum to the role of RWD/RWE in the German benefit assessment.     
Pages: 87
Annexes: 1, Pages: 4