Real World Evidence in German HTA: The Challenges of Comparative Routine Practice Data Collection (ABD) for Early Benefit Assessment (AMNOG)

OBJECTIVES: Increasingly, active substances are being approved for which randomized controlled trials are neither feasible nor ethical, particularly orphan drugs and ATMPs. To address the resulting evidence gap, the German Federal Joint Committee (G-BA) may require manufacturers to conduct a routine practice data collection (AbD) for health technology assessment (HTA). However, the strict methodological requirements of HTA pose challenges, especially for manufacturers and patient registries tasked with data collection. We aim to address main challenges of realizing AbD within strictly defined timelines.

METHODS: We systematically reviewed the publicly available documents of all AbD procedures initiated by the G-BA. By combining publication dates with G-BA’s set deadlines, a process roadmap was derived. Methodological requirements for AbD were obtained from G-BA publications and compared with the decisions of AbD procedures to identify challenges and requirements of the process.

RESULTS: As of June 2023, the G-BA has initiated 8 AbD procedures, with publicly available methodological information for 6 of them. The challenges in realizing an AbD under the G-BA’s requirements primarily resulted from the population, intervention, comparator and outcome (PICO) criteria. In 3 out of 6 procedures, limitations of the registries arose from insufficient inclusion of patients treated with the appropriate comparative therapy as determined by the G-BA. Moreover, in all 6 procedures, the registries deemed most suitable for AbD were not equipped to collect data on quality-of-life measures, such as patient-reported outcomes. In the 2 procedures where protocol and statistical analysis plan (SAP) are available, significant adaptations to the data collection process of the registries were implemented.

CONCLUSIONS: With AbD, the G-BA imposes strict requirements on generating real-world evidence (RWE) for HTA that necessitate extensive adjustments to existing registries. Going forward, the quality and quantity of real-world data, and their relevance for HTA, are likely to improve, thereby enhancing the overall evidence base for healthcare decision-making.