Does taking ivermectin reduce the risk of COVID-19 infection by 83%?

Question

I came across a study that makes the following claim (emphasis mine):

Two doses (300 μg/kg/dose in a gap of 72 hours) of ivermectin chemoprophylaxis reduced COVID-19 infection by 83% among HCWs for one month. Ivermectin is a safe and effective strategy to prevent COVID-19, in the containment of pandemic alongside vaccine. Further research is required to guide the frequency of chemoprevention, acceptability, and cost-effectiveness in the community setting.

Is this a robust study and are the conclusions supported by the data?

Answer 1

Summary: The conclusions are not generally applicable because the study did not isolate the role of ivermectin in the outcomes, and the process was not a randomized controlled trial.

First, this August 2021 report of a September-to-November 2020 study the sort of study that suggests "this may be promising, more research is needed." As the authors note, "Further research is required to guide the frequency of chemoprevention, acceptability, and cost-effectiveness in the community setting." (Result so far have been dubious: see Meta-Analyses Do Not Establish Improved Mortality With Ivermectin Use in COVID-19 in the Jan.-Feb. 2022 issue of American Journal of Therapeutics)

This study of 3,532 doctors, nurses, students, administrators and other staff at All India Institute of Medical Sciences (AIIMS) Bhubaneswar has some shortcomings that undercut its conclusiveness, some as noted in the comments above:

• Administration of the ivermectin was not double-blind and was not randomized. Drug studies typically compare the results of two randomly-assigned populations, one taking the drug, the other taking a placebo or other control, with neither the researchers nor the participants knowing which they were getting. In this case, not only did the participants know they were taking the drug, they were also the people who chose to take the drug. For example, the authors note that "Ivermectin prophylaxis uptake was better with increasing age and among males."
• We don't know how the behavior of the subject group differed from the general population given that they were people who chose to take ivermectin, or how their behavior might have changed knowing they were taking ivermectin or by participating in the study. They may have taken more or fewer risks to avoid infection, or otherwise altered their activities, their diet, or their other medication. The authors suggest "we had a strong institutional policy in place related to COVID-19-appropriate behavior in the workplace, which may have avoided the possible bias," but we don't know if that policy was enforced; there have been many studies about doctors misestimating how often they wash their hands, for example. There were also reports of ivermectin side effects such as nausea and headache among 42 participants; while side effects are commonly over-reported, we don't know if those drug-takers were so sick they missed work and had reduced exposure, for example.
• We don't have conclusive evidence about how many health care workers (HCWs) in the overall study were infected. The authors note: "The major limitation is that we only tested HCWs who either developed symptoms or who were direct or high-risk contacts of positive patients. This was done in keeping with the Government strategy for COVID-19 testing in India. However, this precludes us from including the HCWs who may have been asymptomatic or mildly symptomatic and chose not to get tested."
• Some unknown number of the hospital employees had already contracted covid in September 2020, which is what prompted the study. "We noticed an increasing number of HCWs getting infected with SARS-CoV-2 infection in early September 2020 at our hospital, which was negatively impacting the healthcare services we had to provide." We don't know how many of those employees were back at the hospital or how their participation in the study, other behavior, or chance of getting reinfected might have been affected by their personal experiences.

Answer 2

This recent Cochrane review did consider the Behera study mentioned by the OP, but rejected it on the grounds that it wasn't an RCT (randomised controlled trial), along with eight other studies for the same reason.

Out of interest, there are other reviews of ivermectin for covid. This one is from last year, and this one is very recent. Both found significant issues in some of the studies they considered.

The first two reviews I linked to were mentioned by @jeffronicus in their excellent answer. However, the third wasn't, and maybe the most relevant finding in that review was how strongly the effect of ivermectin decreased as more problematic studies were excluded from the meta-analysis.

See Figure 1 here, which I've also posted below. The effect of ivermectin is strong when all studies are included, but the p-value is very low (0.01). However, when studies with any degree of concern are excluded, the effect of ivermectin is marginal (a 4% increase in terms of improvement in survival, i.e. 1.04, 95% CI, 0.56–1.66; p = 0.90).

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Edit: there is also the PRINCIPLE trial, run by the University of Oxford. They are currently investigating ivermectin for covid treatment. For context, they're also testing favipiravir and the "usual standard of NHS care". They've already looked at inhaled budesonide, azithromycin, doxycycline and colchicine, of which only budesonide showed any benefit ("shortens recovery time by a median of three days in patients with COVID-19 who are at higher risk of more severe illness and are treated in the community").

Mentioning this as ivermectin results will presumably be released in the near future.

Answer 3

I cannot fully explain why, but I am not sceptical of the massive amount of reproducible work that has gone into the collation of evidence for the efficacy of Ivermectin (and other treatments in linked pages) done by the analysts at the c19ivm.org live meta analysis. As I write this they have analysed 98 studies relating to Ivermectin. The good the bad and the ugly.

The 17 relevant studies included in the Prophylaxis results, with almost 20'000 patients, combined, offer an improvement of 85%. That seems to match the claim of the OP better than could be expected.

EDIT:
Response to popular criticism-
1: Wikipedia knows better, they choose to use a failed policy over the health of humanity. They have chosen to promote variable public policy instead of research results even though ephemeral data does not belong in an encyclopedia.
2: The lady and her dog have the following populist agendas that they promote without basis, Understand that using propaganda to support a narrative is not very scientific, much has transpired since the video was made to further weaken her case.
2A: A RCT is not the only way medicine is practised. The lady says "which is the only type of clinical trial that is able to determine if our treatment is effective" Yet the regulators know that is not true. Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999–2014. The contested site includes all trials but the results of the RCTs are available separately for those that are not able to see past the RCT myth. However he results are similar but statistical weight is achieved later, other trials show the same benefit 5 months earlier.
2B: The lady also says "need to remove any studies where the drug you are interested in is combined with another drug or therapy" which is also nonsensical, this would preclude many therapies, some that have been meta-analysed by her champion "The Lancet". Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis
2C: She states "need to remove studies where there is no placebo or standard of care arm". This is not an absolute and standard of care differs in different locations. Some researchers will accept some treatments as standard of care but not others while eliminating studies that use a treatment they say has no efficacy. Insisting on standard of care that does not allow other treatments prevents the development of multidrug remedies. This limitation is sidestepped by patent drugs that are combinations of single remedies. Many of the patent remedies were combination treatments and did not have isolated meta-analysees before approval.
2D: ROB fails to consider conflict of interest for some reason yet this is known to be a massive driver of bias in drug trials. Industry bias is real but not included in the ROB analysis. Industry sponsorship and research outcome, Why the Cochrane Risk of Bias Tool Should Include Funding Source as a Standard Item
2E: The Authors at IVMMeta are anonymous to limit cancel culture destroying their lives, if this was not a risk I expect they would be glad to unblind their identities. Note also that the editors at Wikipedia that black list the site are also anonymous.
2F: The Galan study she thought was important to add is included on the site but of limited value because there was no control arm due to ethical reasons. So no placebo that the lady was very concerned about earlier. It compared 3 working remedies that showed benefit compared to population statistics which are a proxy for Standard of care.
2G: The missing i² value has been added to the forest plots for those that care.
2H: I do believe it would be impossible for the lady and her dog to use the same claims to dispute the evidence base as it now stands. Also if she applied her critical reasoning to other patent treatments we might find that they also show no evidence of efficacy, almost certainly at the time they were authorised for use. 2I: There are many results with exclusions of poor studies, RCTs only, Peer-reviewed only, etc., etc. Almost all show some or significant benefit.

For a sceptics stack there is a surprising amount of credulity for a random YouTube lady and her dog that she claims is her assistant. Why is it that the commentary and analysis at the offered site appear so much more credible than the casual criticism from the lady and her dog that look like something you would expect from a pharmaceutical industry advocate. Why do the results from the other sister sites show credible results using consistent methods for 51 treatments, some efficacious and some not. If I was a sceptic the Cost per life saved chart would trigger me big time even if there was an error or two included the differences are HUGE. It would be prudent to read the comments for each study and see if the conflicts of interest and failures are enough to change minds.