EMA issues Reflection Paper on Demonstrating Efficacy for Advanced Therapies

The European Medicines Agency (EMA) has opened a public consultation on a reflection paper that discusses key concepts for single-arm clinical trials for new therapies. According to the agency, this is the first guidance issued by an international medicine regulator articulating the considerations and challenges associated with this type of clinical trials. Stakeholders are invited to send their comments until 30 September 2023.


Typically, regulatory agencies favor randomized controlled clinical trials (RCTs) in which subjects receive either the test drug or a comparator drug or placebo. This is considered the so-called "gold standard" for demonstrating efficacy. It is foreseeable that the next generation of medicines will be increasingly personalized and targeted at very small patient populations. For this reason, European regulatory authorities are increasingly forced to address the approval of drugs that have only undergone single-arm trials (SATs). In SATs, all subjects entering the trial are planned to receive the experimental treatment and to be followed prospectively for a period of time. SATs can have specific design features, such as a monitoring period to obtain baseline data of the subjects before the start of treatment.

The reflection paper outlines practical considerations for SATs that can be submitted as key evidence to demonstrate efficacy in a marketing authorization application. The goal is to stimulate scientific discussion about key concepts and challenges associated with SATs and to improve their design and conduct.

More information is provided on the EMA website under Single-arm trials as pivotal evidence for the authorisation of medicines in the EU.

Go back

GMP Conferences by Topics