Establishing efficacy based on single-arm trials submitted as pivotal evidence in a marketing authorisation
Human
Scientific advice
Scientific guidelines
Following a public consultation, the Methodology Working Party (MWP) has finalised the Reflection paper on establishing efficacy based on single-arm trials submitted as pivotal evidence in a marketing authorisation.
The reflection paper discusses key issues and requirements for single-arm clinical trials that are submitted as pivotal evidence in support of marketing authorisation applications for medicines in the European Union (EU).
During the public consultation phase comments from 45 stakeholders were received. The comments were taken into careful consideration and have resulted in the following major changes compared to the draft version:
The final version adapts a more targeted implementation of ICH E9(R1) with respective changes implemented in section 3. It expresses more clearly that regulatory assessment of efficacy of an investigational treatment conceptually requires comparative information and that single-arm trials only allow to observe outcomes under the investigational treatment. A previously drafted subsection on “internal validity” was removed and a new section on the “target of estimation” was introduced which outlines estimand attributes such as treatment condition, intercurrent events and population summary measures.
In addition, it is emphasized that the results from clinical trials usually are intended to address several objectives, and a single-arm-trial intended to address a primary question to elucidate a treatment effect, may still not be capable to serve other objectives or decisions.
The reflection paper has been adopted by EMA’s human medicines committee (CHMP) with contributions from the Committee for Advanced Therapies (CAT), the Methodology Working Party (MWP) and the Oncology Working Party (ONCWP).
Keywords: Single-arm trials, non-randomised trials, regulatory decision making