Early stopping of a randomised trial for efficacy: a medical, ethical and regulatory challenge

[...]just before discontinuing combination therapy and switching to non-study aspirin, patients from the combination arm were at lower risk of event, but the event rate afterwards was similar. [...]the benefit gained by patients under combination therapy was not lost but rather diminished by discontinuing low-dose rivaroxaban. Overall, patients previously randomised to the combination therapy had a significant excess risk of all-cause stroke when discontinuing low-dose rivaroxaban, but a similar risk of ischaemic or uncertain stroke (39 vs 24, HR 1.62 (0.97 to 2.69)), although close to statistical significance. [...]the excess risk of stroke seems to be weighted by three haemorrhagic strokes, all occurring in the group of patients previously randomised to low-dose rivaroxaban. When not anticipated, the ending of a clinical trial may be a challenging period, both for medical staff and for patients, the former caught between ethical, financial8 and regulatory issues,9 and the latter sometimes expressing anxiety and distress while potentially being withdrawn from a beneficial treatment.10 Moreover, theses considerations could lead to various decisions from the research staff varying across countries or sites, increasing the disparity and inequality in post-trial access to medication. [...]the majority of countries who have adopted obligations for post-trial access are located in South America.