Uncertainty and novel clinical trial designs in oncology – when should equipoise matter?

Equipoise is usually considered a requirement for the ethical conduct of phase III randomised controlled trials. Notwithstanding theoretical critiques since the concept's initial proposal, equipoise has remained an important moral consideration. In oncology, many research questions are now pursued via clinical trial designs that diverge in various ways from conventional, fixed-design, two-arm randomised controlled trials. In this article, we outline the challenges that these new designs pose for implementing equipoise. Specifically, we consider challenges posed by trials incorporating seamless designs, 'immortal' trials, and trials incorporating adaptive techniques. While we note that equipoise retains a central role in the ethical evaluation of conventional randomised controlled trials, we contend that its utility as a moral construct is challenged by more recent, 'novel randomised controlled trial' designs. Consequently, other ethical tools become important in considering the different types of risk that trial participants are exposed to in modern clinical trial designs.