This reflection paper is intended to reflect the current thinking of EMA’s Committee for Medicinal Products for Human Use (CHMP) on single-arm trials (SATs) that are submitted as pivotal evidence for establishing efficacy in a marketing authorisation application. The reflection paper discusses considerations in relation to the design, planning, conduct, analysis and interpretation of results derived from single-arm trials. It is applicable across different therapeutic areas, including for rare diseases.


The purpose of this reflection paper is to outline the current thinking about SATs that are submitted as  pivotal evidence for establishing efficacy in marketing authorisation applications. Defining general  conditions under which SATs may be considered acceptable as pivotal evidence for marketing  authorisation is outside the scope of this reflection paper. Such considerations strongly depend on the  clinical context and other things such as the drug treatment modality. It is the responsibility of the
applicant to adequately justify to regulators why a SAT, which deviates from the standard approach of  providing pivotal evidence on efficacy through RCTs, can provide clear pivotal evidence of efficacy.

Obtaining scientific advice is therefore strongly recommended to discuss whether pivotal evidence from  SATs may be considered acceptable for seeking marketing authorisation for a specific development  programme.