Abstract

Methods for investigating interventions to influence clinical practice are dominated by large phase III randomised controlled trials comparing experimental treatments with standard of care. Regulatory bodies and research funders acknowledge that trials in rare diseases are challenging and indicate that less conventional methodological approaches may be acceptable. Strategies that maximise recruitment, minimise sample size or maximise the utility of the evidence may enable the application of conventional clinical trial design to rare cancer populations. Alternative designs that address specific challenges for rare cancers with the aim to potentially influence clinical practice include Bayesian designs, uncontrolled n-of-1 trials and umbrella and basket trials. Rare cancers fall on a sliding scale of rarity and different methods may be appropriate at different points on the scale. This presentation will review the methods, illustrated with real world examples and highlight approaches that have been implemented by the International Rare Cancers Initiative.