Assessing the risk of complications or adverse events following an intervention presents challenges when they have not yet occurred. Suppose, for instance, a chronic shortage of cardiac telemetry beds has prompted a hospital to implement a new policy that places low-risk patients admitted to ‘rule out myocardial infarction’ in regular ward beds (ie, with no telemetry). After 6 months and the admission of 100 such patients, no cardiac arrests or other untoward events have occurred. This absence of harm (ie, zero adverse events) indicates a low risk, but clearly we cannot infer a risk of zero on the basis of only 100 patients. But, what can we say about the true underlying risk?

The Rule of Three (Ro3), first proposed by Hanley and Hand,1 provides an estimate for the upper bound of the underlying risk when zero events of interest have occurred through considering the lack of occurrences as moderately rare. The Ro3 estimates the risk as no greater than 3/n, where n is the number of opportunities or exposures to the risk. Technically, 3/n is obtained through assigning the probability 0.95 to measure the likelihood of realising more events than those observed. Note that the Ro3 estimate applies only when one has at least 30 observations. In the above example, the Ro3 would estimate the upper limit for the risk of adverse events associated with the new policy as 3/100 or 3%.

This estimate does not sound as reassuring …