Those connections are seldom made as clear as they have been in the BioNTech-Pfizer and Moderna vaccine trials, though. The one other big Western vaccine trial for which results have been released found the vaccine developed at the University of Oxford and produced by AstraZeneca Plc to be 70.4% effective. Subjects who were erroneously given a half-dose on their first shot seemed to be better protected than that, but that result may necessitate new trials to determine that it’s not a fluke.

Meanwhile, the large-scale Randomised Evaluation of Covid-19 Therapy (known by the portmanteau “Recovery”) trials in the U.K. have so far found three of the four treatments studied, azithromycin, hydroxychloroquine and lopinavir-ritonavir, to deliver “no clinical benefit” and the fourth, dexamethasone, to reduce deaths by about one-third among patients already on ventilators. Trial results of new antibody therapies from Regeneron Pharmaceuticals Inc. and Eli Lilly and Co. seem to indicate improvements in outcomes of 50% or more, but the trials have been small and there are still lots of questions about how to maximize the effectiveness of the treatments.

Go from pharmaceuticals to the so-called “non-pharmaceutical interventions” — such as masks and distancing — used to slow the pandemic, and things rapidly get more complicated and muddled. In many cases RCTs just aren’t practical, and even when they are they face obstacles that trials of shots and pills generally don’t.

Norwegian public-health researcher Atle Freheim tried to set up an RCT last spring on the effect of school closures on the spread of Covid, for example, but the country’s health minister, while agreeing that it was a good idea, said (in Freheim’s paraphrase) “it would be too difficult to get popular support for it.”

In Denmark, a large group of researchers did succeed in conducting an RCT on the protective benefits of face masks this April through June, but it was tough to draw any conclusions from it. Just 46% of those who were given disposable surgical masks and instructed to wear them outside the home reported following those instructions every week, with another 47% saying they did so most weeks — making the trial a test perhaps more of adherence to mask mandates than of mask effectiveness. Low incidence of the disease in Denmark during the study period also made it hard to produce meaningful results, as did the fact that the study wasn’t even testing what is generally represented to be masks’ main benefit: keeping mask wearers from infecting others.

“Statistical insignificance and/or too-small effect measured are the most likely outcome as an artifact of the study’s design, regardless of the true effect of masks,” three public-health researchers argued in a letter posted online well before the results were published. Sure enough, the study’s authors ended up reporting that while members of the mask group were less likely to test positive for SARS-CoV-2 infections or antibodies than those in the non-mask control group, the difference (1.8% versus 2.1%) wasn’t statistically significant.

Most evidence on masks thus comes not from RCTs but from simple observation of how masks affect air flow, as well as studies that compare real-world Covid-19 outcomes where and when masks are widely used with those where and when they aren’t. The latter approach has great limitations, though, compared to an RCT where every variable but one can be held constant. One early study that made big claims for the effectiveness of masks by comparing the spread of Covid-19 in different parts of the U.S., published in June in the prestigious Proceedings of the National Academy of Sciences, “ignores other clear differences in disease control policy between these areas,” wrote the same three researchers cited above, along with several dozen others, in a letter requesting retraction of the article (it hasn’t been retracted).

Still, I would guess that all the signatories of that letter also believe that masks are effective in the fight against Covid-19. Noah Haber, a postdoctoral fellow at Stanford University’s Meta-Research Innovation Center and a ring-leader of both letter-writing efforts, certainly does. Which begs the question of why. As Haber said last month when I sought him out for advice on weighing Covid evidence, “One of the things that I get asked a lot, especially with masks, is ‘Okay, these studies are bad. What’s a good one that you’re basing all of your opinions on?’”

While there are definitely better mask studies than the one discussed above, there is none that delivers results anywhere near as convincing as the BioNTech-Pfizer and Moderna vaccine trials. Instead, as Haber said in an article for Wired, there is “a collection of evidentiary bits and pieces; and when these are taken all together they say that masks are certainly somewhat effective — maybe even very effective — at slowing the spread of SARS-CoV-2.”

Also key, in my opinion, is that the cost-benefit analysis for masks is a bit like Pascal’s wager on the existence of God. If they do in fact work the gains are huge, while if they don’t the cost of having worn them for nine or 12 months is relatively modest.