What if all participants get the same treatment? An ethical perspective on single arm trials

Randomised controlled trials have traditionally been considered the gold standard for evidence on the efficacy of new treatments. However, applications to marketing authorisation are increasingly based on data stemming from single arm trials (SATs), which do not randomise to a control arm and in which all patients receive the treatment under study. This has generated debate over the characteristics and methodological limitations of SATs and the appropriateness of SATs’ data to inform marketing authorisations. This paper discusses SATs from an ethical perspective by exploring (1) The ethical concerns raised by SATs’ methodological limitations; (2) SATs’ risk–benefit assessment; and (3) How to address ethical concerns raised by SATs with a favourable risk–benefit ratio. Given the ethical quandaries associated with SATs’ methodological limitations, this analysis will highlight the relevance of (1) An independent and design-specific review from both scientific and ethical perspectives, and (2) An adequate informed consent process for prospective participants.