Indirect Comparisons in German AMNOG-Assessments: Keep the Faith

OBJECTIVES: In Germany, pharmaceutical companies are required to demonstrate the benefit of newly approved drugs in their respective therapeutic areas compared to an appropriate comparator therapy (ACT) as defined by the Federal Joint Committee (G-BA) at the time of market launch. Although direct evidence via randomized controlled trials (RCT) is considered the gold standard, in certain circumstances, indirect comparisons (ICs) are the best available alternative evidence. Thus, our objective was to identify benefit assessments incorporating indirect comparisons and to critically evaluate the key parameters influencing these indirect comparisons within the context of the benefit assessments.

METHODS: A systematic search for ICs was performed using a database containing all benefit assessments published on the G-BA website until April 2024.

RESULTS: ICs were present in 222 concluded benefit assessments, encompassing 334 subpopulations. The predominant therapeutic fields were oncology (51.2%), metabolic (15.0%) and infectious diseases (11.4%). In 22.5% of the cases, the IC was accepted, with an added benefit granted in 1.8% of all assessed subpopulations. Methodological deficiencies and insufficient similarity of the compared studies were identified as main reasons for rejection of an IC by the G-BA. Among the accepted ICs, only adjusted and unadjusted comparisons were identified, while other methods such as network meta-analyses or propensity score matching were not considered to be methodologically appropriate. Furthermore, most non-adjusted ICs accepted by the G-BA were considered under additional exceptional circumstances.

CONCLUSIONS: Overall, the acceptance criteria for ICs are stringent, with success often hinging on special circumstances. However, in rapidly evolving therapeutic fields like oncology, in which frequent changes in the definition of the ACT occur, or among highly vulnerable patient populations (e. g. pediatric populations), ICs will continue to provide critical evidence.