To clarify, I’m not implying anything nefarious when I say “off” (poor word choice). The study was clearly a huge undertaking, which is commendable, especially under very difficult conditions. And since the numbers in the trial look favourable for fluvoxamine, it’s important that the results be clearly understood by clinicians. I think what I’m trying to articulate is that even after reading the study a couple of times, I’m not quite sure, clinically, what to do with the results.

Maybe the problem is that I’m just not experienced in reading Bayesian analyses (most likely). But if that’s the case, then I’m probably not the only MD who will struggle. Or maybe part of the problem is the choice of the primary endpoint (see below) (?)

Here are a few study excerpts with questions below each:

*“We applied a Bayesian framework for our primary outcome analysis and a frequentist approach for all sensitivity analyses and secondary outcomes.”*

Q: Is this a common approach? Are there any potential problems that arise from using mixed methods?

*“Posterior efficacy of fluvoxamine for the primary outcome is calculated using the beta-binomial model for event rates assuming informed priors based on the observational data for both placebo and fluvoxamine…”*

Q: Under the heading “Comparison with Prior Evidence,” the authors mention a previous small US RCT which recorded few outcomes of interest, as well as an observational study from France. I can’t figure out how/whether they used the results of these trials to demonstrate “informed” priors or what “informed” priors even means in this trial (?) And if they did use results of such a small RCT to inform their prior, was this a good idea?

*“Based on the beta binomial model, there was evidence of a benefit of fluvoxamine reducing hospitalization or observation in an emergency room for greater than six hours due to COVID-19 (Relative Risk [RR]: 0.71; 95% Bayesian Credible Interval {BCI}: 0.54-0.93)…The probability that the event rate was lower in the fluvoxamine group compared to placebo was 99.4% for the ITT population…”*

Q: How would I present this finding to a patient if the overall “positive” trial result is partly being driven by a reduction in how long they might have to spend in an ER rather than the chance that fluvoxamine will help them to avoid hospitalization or death? What phrasing would I use when talking to the patient? Ideally, I’d like to be able to say: “If I treat you (an ostensibly “high risk” patient) with fluvoxamine early in your infection course, the chance that I will be able to reduce your risk of death or hospitalization by more than “X” percent is “Y”. Does the current study presentation permit such an interpretation?

Q: Re Table 3- to what extent is the “ER visit for at least 6 hours” component of the composite primary outcome driving the overall trial result? If ER visit >6 hours is driving the result, what is the clinical significance of this finding?