Author's comment: we address these issues with an emphasis on binary outcomes, and discuss how authors of randomized trials should address issues of both noncompliance and missing data.
The frequency of VLEs followed by a large trial is vanishingly small, and where they occur they do not appear to be a reliable marker for a benefit that is reproducible and directly actionable. An empirical rule using a VLE in a randomised controlled trial as a marker that further trials are unnecessary would be neither practical nor useful. Caution should be taken when interpreting small studies with very large treatment effects.
*VLE denotes "very large effect (VLE; defined as a relative risk of ≤0.2 or ≥5)".