Table 1 Three examples of late-phase platform protocols

PLATO (ISRCTN88455282) is a platform protocol, labelled as an “umbrella” trial, in anal cancer, a rare tumour with 1000 UK diagnoses per year [13]. Platform approaches help to address recruitment challenges posed by rare diseases, allowing trials to be performed that would not be viable on their own. PLATO comprises three individually powered sub-trials: the three-arm ACT5 for high-risk disease, the most common presentation; the smaller two-arm ACT4 for intermediate risk disease; and the non-randomised ACT3 for low-risk disease which would likely never have run on its own. Combination in a single platform allowed evaluation of a broader set of clinical and translational objectives (see Additional file 1 for flow diagram)

Add Aspirin (ISRCTN74358648) is a basket trial assessing the use-and-duration of aspirin in four tumour-specific randomisations. Each is individually powered with a primary outcome measure relevant to the disease setting. The overarching platform allowed a cohesive and consistent approach to complementary studies, with the potential to increase impact of the results. Overall survival will be assessed across the tumour-specific cohorts and increased power for secondary research questions (such as assessing the effect of different aspirin doses) will also be achieved by combining the cohorts. Release of primary results (which will be available at different times for different cohorts) will need to be carefully managed, considering the impact on ongoing cohorts. Efficiencies are derived from having a single protocol requiring only a single approval at both the global and local (site) level; however, protocol amendments can take longer to implement due to the need to consult multiple groups/stakeholders and ensure the impact of any changes are considered for each tumour-specific cohort. Whilst there is only one DSMC and one TMG, the latter functions mostly as a number of separate subgroups (each the size of a more traditional TMG) (see Additional file 1 for flow diagram)

CompARE (NCT04116047) is a phase III multi-arm multi-stage (MAMS) trial assessing treatments for patients with high-risk oropharyngeal cancer. The trial started with four arms, three research, and one control. During the trial, one further research treatment was added before assessment and recruitment to three of the research arms has been completed (see Additional file 1 for flow diagram)