In this week's JAMA, Freund et al report the results of the PROPER randomized controlled trial of the PERC (pulmonary embolism rule -out criteria) rule for safely excluding pulmonary embolism (PE) in the emergency department (ED) among patients with a "low clinical gestalt" of having PE. All things pulmonary and all things noninferiority being pet topics of mine, I had to delve deeper into this article because frankly the abstract confused me.
This was a cluster randomized noninferiority trial, but for most purposes, the cluster part can be ignored when looking at the data. Each of 14 EDs in France was randomized such that during the "PERC period" PE was excluded in patients with a "low gestalt clinical probability" (not yet defined in the abstract) if all of the 8 items of the PERC rule were excluded. In the "control period" usual procedures for exclusion of PE were followed. The primary end point was occurrence of a [venous] thromboembolic event (VTE) during 3 months of follow-up. The delta (pre-specified margin of noninferiority) for the endpoint was 1.5%. This is a pleasingly low number. In our meta-research study of 163 noninferiority trials including those in JAMA from 2010-1016, we found that the average delta for those using an absolute risk difference (n=137) was 8.7%, almost 6 times higher! This is laudable, but was aided by a low estimated event rate in the control group which means that the sample size of ~1900 was feasible given what I assume were relatively low costs of the study. Kudos to the authors too, for concretely justifying delta in the methods section.