The ‘power of 1’: the ethics and epistemology of ‘N-of-1 trials’ in oncology

Conduct of clinical research involving single patient subjects has a relatively long history. The notion of ‘N-of-1 trials’ first emerged in the 1980s, introducing a method for evaluating the impact of alternately exposing individuals ‘on’ and ‘off’ a particular treatment. In the years since, interest in conventional, randomised, ‘N-of-1 trials’ has fluctuated, though recent advancements in data science, remote monitoring technologies and, more broadly, the ‘personalised’ medicine era has seen renewed engagement with the methodology. Amongst patient cohorts with cancer conduct of such trials has, for the most part, been uncommon, given the methodology is best suited to study of chronic, stable conditions. In recent years however, there has been growing attention within oncology research communities to the idea of ‘N-of-1 trials’. In part, this has been driven by the need to accommodate increasingly granular levels of molecular heterogeneity in cancer research. However, use of the label ‘N-of-1 trial’ has been applied to a variety of research endeavours involving single participants, with varying resemblance to conventional definitions of an ‘N-of-1 trial’. In this paper we review recent cases in which the term ‘N-of-1 trial’ has been operationalised in relation to clinical research amongst adult cancer populations. We then consider both the epistemic and ethical implications of individual-patient research endeavours in oncology. We conclude by noting the phenomenon represents a new frontier for those engaged in ethical oversight, as well as other stake-holders in cancer clinical research, including clinicians, researchers and health-care consumers.