Dr Tess Lawrie Ivermectin Meta-Analysis: UK-based Meta Analysis Suggests Ivermectin A Key Weapon in the War Against COVID-19 (Updated)

By Dr. Frank Yap, MD - January 01, 2022

Just published in the peer-reviewed American Journal of Therapeutics, Dr. Tess Lawrie, an expert in medicinal evidence, along with other experts in population health and gastroenterology out of the United Kingdom (UK), conducted a comprehensive meta-analysis involving the certainty of evidence using an approach known as GRADE, which led to the focus on twenty-four ivermectin-centered randomized controlled trials involving 3,406 participants. The authors concluded based on this extensive review that ivermectin actually reduced the risk of death compared with no ivermectin (average risk ratio 0.38, 95% CI 0.19-0.73; n = 2438; I2 = 49%; moderate-certainty evidence). This result, posits Dr. Lawrie and team, confirmed via trial sequential analysis employing what was the same DerSimonian-Laird method behind the unadjusted analysis. The authors also ran their findings against a trial sequential analysis employing the Biggerstaff-Tweedie method. They found low-certainty evidence that ivermectin prophylaxis (as a preventive method) actually lowered infection association with SARS-CoV-2, the virus behind COVID-19, by an average of 86% (95% CI 79-91%). Also, the team’s findings reveal that the evidence for secondary outcomes, such as efficacy associated with “need for mechanical ventilation” is less compelling; however, effective estimates for “improvement” and “deterioration” point to the positive impact of ivermectin use. The authors found little safety risk as reports of severe adverse events were rare among the reviewed studies.

This article has been updated with new information.

This study published in the peer-reviewed American Journal of Therapeutics suggests a “moderate-certainty evidence” indicating a substantial reduction in COVID-19 related deaths would be a feasible outcome with the use of ivermectin. The study results mirror what TrialSite’s observed in study after study from Bangladesh and India to Peru and Argentina; from Israel and Nigeria to the ICON study in South Florida and population-wide public health initiatives using ivermectin from Mexico City to Uttar Pradesh, India, that there’s now overwhelming data that this generic drug used as an antiparasitic treatment should be considered on at least an emergency basis as another tool in the medical tool chest to fight SARS-CoV-2.

Dr. Lawrie shared with the TrialSite:

“We are overjoyed to have the product of months of hard work finally published! And what a wonderful author team – it’s been an honour to work with people of such high integrity, who maintained a spirit of hope and optimism in spite of all the difficulties with which we have been confronted. Thank you for not giving up! Now the authorities have all the evidence they need to approve ivermectin immediately.”

The preprint of this review received no funding. This updated version was funded by the crowdfunding initiative.

TrialSite’s Coverage of Ivermectin

TrialSite’s been one of the few, if not the only, media platforms to consistently chronicle ivermectin-based research since the initial findings of a group of scientists last April at Monash University that the generic drug absolutely destroys the SARS-CoV-2 pathogen in a lab setting. TrialSite chronicled the organization, conduct, and conclusion of dozens of studies since then. The platform’s only been rivaled by the anonymously owned platform that tracks every ivermectin study, now at 60. One of the key authors here, Dr. Tess Lawrie, has been a guest on the TrialSite podcast and is a frequent contributor.

Lead Research/Investigator

Andrew Bryant, MSc, Division of Gastroenterology, Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom
Theresa A. Lawrie, MBBCh, PhD, Division of Gastroenterology, Evidence-based Medicine Consultancy, Bath, United Kingdom
Therese Dowswell, PhD, Division of Gastroenterology, Evidence-based Medicine Consultancy, Bath, United Kingdom
Edmund J. Fordham, PhD, Division of Gastroenterology, Evidence-based Medicine Consultancy, Bath, United Kingdom
Scott Mitchell, MBChB, MRCS, Emergency Department, Princess Elizabeth Hospital, Guernsey, United Kingdom
Sarah R. Hill, PhD, Division of Gastroenterology, Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom
Tony C. Tham, MD, FRCP, Division of Gastroenterology, Ulster Hospital, Dundonald, Belfast, Northern Ireland, United Kingdom

Frequently Asked Questions

Independent scientists that have looked into the evidence say some of these studies are highly flawed or contain fabricated data?

I am aware of a journalist and an epidemiologist in Australia who hold a very vocal position against ivermectin; however, most independent scientists who have looked at the evidence on ivermectin agree that the big picture supports its use for covid-19. Whether or not the Elgazzar study is discredited remains to be determined but it may well be. We have rerun removing the disputed trial from the relevant analysis and have reported the findings here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415517/

Whilst the quantitative result inevitably changes with the removal of the Elgazzar study, the mortality outcome remains clear, demonstrating an average reduction in deaths of 49% in favour of ivermectin. The effect on reducing covid-19 infections when used for covid prevention remains virtually unchanged.

It is important to remember that systematic reviews, which restrict studies to randomised control trials only, are just one type of evidence on ivermectin. There is also a vast amount of real-world evidence from patient, doctors and countries that are successfully using ivermectin. Please visit the www.worldivermectinday.org and also see the proceedings of the International Ivermectin for Covid Conference held in April https://bird-group.org/conference-post-event/ for more information.

The Together trial found no benefit from the drug and the Cochrane review said there was no evidence of benefit?

The Together trial is one of many and will be added to our meta-analysis in due course. Trials are often flawed and single trials are not as robust as systematic reviews, which are the best way to understand the effects of treatments because they consider all the relevant trials. In addition, particularly during a health emergency, it is important to consider all data, including observational and real-world data, which is what the British Ivermectin Recommendation Development meeting on 20th February 2021 was about. This meeting was conducted in accordance with the WHO Handbook for Guideline Development. As required, the evidence-to-decision document took into account people’s preferences, acceptability, feasibility, equity and cost of ivermectin use in the context of covid-19.

The Together trial is a medium size, non-peer reviewed study and adds to the bank of knowledge that suggests that given late and for only 3 days, ivermectin may have little effect on covid-19 hospitalisation rates. This is not too surprising, as this would be the case for most medicines. Had the investigators followed a dosing-regime from well-documented expert protocols on early treatment, this study could have shown better results. A late-stage intervention will have less-positive outcomes. Ivermectin is widely available in Brazil, but the researchers did not check to see if participants in the placebo group had access to it or were using it. This could have skewed the results against ivermectin. In addition, the authors state that their study was under-powered to detect a difference between the two groups. These potential flaws were pointed out to them in the early stage by experts in the field. There are therefore many doctors who feel this study was designed to fail.

The Cochrane study has some concerning problems and I invite you to take this opportunity to investigate them. Out of 24 available RCT’s the authors chose only 4 to include in their mortality analysis, a small subset of those available. The Cochrane authors split these up further into two separate analyses. This dilutes their findings to the extent that meta-analysis was not possible in most instances, as there were no trials to pool. Instead of utilising all available evidence and presenting appropriate caveats around such wider evidence, they present an empty review with bulk but little analysis. We have written a letter to the BMJ regarding the limitations of their approach. You can find the pre-print here https://osf.io/peqcj/.

We’ve spoken to an expert who has been critical of the quality of the metaanalysis you co-authored and the claims it followed the Cochrane method. They said you and the group have muddled up advocacy and scientific process and didn’t examine your own conflicting interests. How do you respond?

The authors of Bryant et al have over 120 Cochrane systematic reviews under our belt. I think you can safely say that we know what we are doing. The review team included three highly experienced systematic reviewers; two of them are guideline methodologists. The meta-analysis was peerreviewed and conducted according to PRISMA methods (the base of Cochrane reviews), using GRADE and WHO guidance. Our findings are robust to the exclusion of the questionable study by Elgazzar and others and are supported by an independent team from Queen Mary’s University in London https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415515/

Please explain on what my conflicts of interest are? Does my Hippocratic Oath constitute a conflict of interest? Personally, I have more to lose than to gain. As a doctor, advocating for a safe and effective medicine in a pandemic is not a conflict of interest, it is being a good doctor. That I champion a medicine known to work in an environment hostile to its existence is my duty. I am the Director of an independent not for profit company with no paymasters to please. I have absolutely no commercial interest in any medicine nor pharmaceutical company. My aim is to save lives and alleviate suffering.

In a pandemic context, the benefits of Ivermectin almost certainly outweigh any risks, given its outstanding safety profile, negligible base cost, and the existing large body of evidence showing that ivermectin provides benefit in a variety of important clinical outcomes.

As someone who has remained a promoter of ivermectin, have such issues with the evidence base weakened your belief in ivermectin?

I am not a promoter of ivermectin – I am a mother, medical doctor and scientist trying to help families survive covid-19. The only issues with the evidence base are the relentless efforts to undermine it. There are over 100 scientific papers on the use of human ivermectin that are relevant to covid-19. The majority suggest benefit, none show harm. I do not have a belief; I have knowledge that I would like to share.

You said on a panel that: "Ivermectin works. There's nothing that will persuade me". Do you stand by that statement?

Yes. We are beyond the point of whether or not ivermectin works, with ivermectin now being used widely by doctors around the world to treat covid-19 in combination with other effective medicines and supplements. Ivermectin is included in covid treatment protocols as evidenced at the recent International Covid Summit in Rome. Please refer your readers to www.earlycovidcare.org for expert guidance on how to treat covid.

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