To determine the beneficial effect of a protective intervention, each group should have equal exposure to potential harms. The experimental group should deploy the intervention with perfect adherence, and deploy the intervention in all settings for which an exposure event may occur. In doing so, any adverse outcome would solely result from lack of intervention efficacy.

Among the trials of mask wearing included in this Cochrane Review, none remotely resemble this standard. For example, an included trial examined mask use while in tents used by pilgrims during the Hajj.³ In the intervention group, self-reported daily mask use was a mere 25 percent, while the control group reported daily mask use of 14 percent. Another trial recruited students in a University of Michigan residence hall, from which staff observed an average of 0.0007 participants properly wearing a mask for each hour of observation.⁴ Three other trials described use of masks within households of patients with influenza-like illness, with adherence to mask use measured in a handful of hours per day, if at all.

Similarly problematic issues arise with respect to trials comparing the effectiveness of medical masks and N95 respirators in health care settings. A few of these trials, performed primarily in Chinese hospitals during influenza seasons, showed dose-dependent positive effects favoring N95 respiratory use when comparing continuous, intermittent, and no respiratory use in hospitals.^5,6 In contrast, a more prominently published trial failed to show any advantage.⁷ In the trial failing to demonstrate any difference, however, N95 masks were worn solely when caring for patients with febrile respiratory illness. The remaining time, whether in staff stations, with other patients, or in the community, trial participants were unmasked. Clearly, an intervention is not reliably tested if exposure events occur outside the time in which the intervention is deployed.

However, the pooled results cannot reflect anything other than the included trials, and it becomes inevitable the authors of this Cochrane Review report a failure to demonstrate advantages to mask use. The vast majority of the amplification of this review focuses on this finding, including by the lead author to the lay media.⁸ This runs in stark contrast to the actual conclusions of the review, which lead off with a very sensible: “The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions.”

In most cases where RCT evidence is too weak upon which to draw any firm conclusions, the prudent course of action is to incorporate evidence from further down the evidence pyramid. Retrospective cohorts, case-control studies, before-and-after reports, and other quasi-experimental designs may have additional susceptibilities to bias, but frequently remain the best option to inform medical and policy decision-making when the RCT evidence is unhelpful.