EMA Issues Draft Paper on Single-Arm Trials as Pivotal Evidence for Approval

Rare Daily Staff

The European Medicines Agency has issued a draft paper on the use of single-arm trials as pivotal evidence for a marketing approval.

Though randomized controlled trials are the standard for providing confirmatory evidence of the efficacy of an experimental therapy, the EMA said the paper was intended to outline the general conditions under which a single arm trial may be considered acceptable for providing pivotal evidence of efficacy. The EMA noted that these trials have shortcomings, not only with regards to establishing efficacy, but safety as well.

The EMA said it is the responsibility of drug developers to justify to regulators why a single-arm trial can provide clear evidence of efficacy.

Single-arm trials lack a control arm, randomized allocation to treatment, and blinding to participants, investigators, and outcome accessors as to which patients received treatment. These features are intended to avoid bias.

“If results derived from [single-arm trials] are to be used as pivotal evidence for approval, it is essential that their adequacy is systematically addressed in terms of their characteristics, limitations, and remaining uncertainties,” the paper said.

The EMA said there are important considerations about the selection of endpoints, target and trial population, and the use of external data in the analysis and interpretation of the study results.

The EMA said it will be accepting public comments on the paper until September 30, 2023.