Ivermectin is good at killing parasites, but it's still not clear it can do much for COVID-19.
Some of the most popular studies people use to tout its benefits against the coronavirus are deeply flawed.
Better answers are on the way.
Ivermectin has revolutionized our ability to kill parasites, and it is widely available around the world.
Japanese chemist Satoshi Omura and Irish biologist William C. Campbell shared half of the 2015 Nobel Prize in Physiology or Medicine for discovering ivermectin.
Chinese chemist Tu Youyou (wearing the yellow scarf) won the other half of that prize for discovering new malaria drugs.
"Parasitic diseases affect the world's poorest populations and represent a huge barrier to improving human health and wellbeing," the Nobel committee said in a release at the time. "This year's Nobel Laureates have developed therapies that have revolutionized the treatment of some of the most devastating parasitic diseases."
The World Health Organization lists ivermectin as an essential medicine because it can treat life-threatening diseases, including hookworm infections and river blindness (onchocerciasis).
"I'm used to prescribing [it] here in Brazil," Dr. Ana Carolina Antonio, who works in intensive care at a government hospital in Porto Alegre, recently told Insider.
She said ivermectin is "necessary to deworm patients," including some of those who develop COVID-19 symptoms.
Ivermectin can clear out roundworm infections, which is critical to do before people are given immunosuppressing steroids for coronavirus treatment. Left untreated, it's possible those roundworms could invade the lungs.
"In the context of COVID-19, it can worsen your respiratory failure," Antonio said. "It's a concern for low-income countries."
But lately, there's been an unusual rush on ivermectin in the US. People are scrambling for both the human and animal formulations of the drug, propelled by the belief that it can treat or prevent COVID-19, and that vaccines aren't needed.
One of the main sources of information for ivermectin fans in the US has been the Front Line COVID-19 Critical Care Alliance, which not only provides links to reputable-looking studies of ivermectin from around the world, but also publishes many of its own analyses of the drug.
The FLCCC is frequently cited by America's Frontline Doctors, a top destination among people searching the internet for ivermectin tablets, and their work is included in various internet roundups of ivermectin research which proclaim the drug is not only safe, but extremely effective against COVID-19.
At first blush, it may look like all this evidence stacks up to provide an impressive track record, demonstrating ivermectin's supreme usefulness in fighting COVID-19. But the truth is far murkier than that.
One of the earliest signs that ivermectin could be useful against COVID-19 came from a laboratory study of monkey kidney cells, published in June 2020 by researchers at Monash University in Australia.
The study in question, published in the peer-reviewed journal Antiviral Research, is what researchers sometimes refer to as "hypothesis-generating" research.
"It doesn't say that this drug is effective in real life clinical practice, but it gives you the hint that it needs to be studied further," Dr. Zain Chagla, an infectious-disease physician at St. Joe's Hamilton and associate professor at McMaster University in Canada, said.
In other words, just because something works in a petri dish doesn't mean it'll do the same thing in humans.
Chagla, and many other experts, have also pointed out that the ivermectin dosage used in the study is far higher than anything that could safely be given to us.
"There's effective ways to kill viruses in a lab that don't translate into what we could safely do in people," Dr. Kevan Akrami, an infectious-disease and critical-care physician working in Salvador, Brazil, recently told Insider.
Even the study authors from Monash say their work does not "provide a definitive answer to whether or not ivermectin is a potential treatment for COVID-19."
(They are committed to conducting further research on the drug to better answer that question.)
Two months after the Monash lab study came out, a study from Egypt suggested that ivermectin could be used to prevent people who had contact with a COVID-19 case from getting sick, but "the study is fake," one expert said.
In order for a study like this to truly be randomized, patients "should be divided into equally sized-groups," based on their conditions and comorbidities, professor Ben Mol of Monash University, who independently reviewed the study and complained to the journal that published it, said.
That's not what happened here. Patients were ferried into different groups in seemingly haphazard ways, making it impossible to draw firm conclusions about what effect the medicine might've had on their outcomes.
For example, there is a far greater percentage of patients in the non-ivermectin group with hypertension (12.9%, compared to 7.9% in the ivermectin group). That could be one reason why they didn't fare as well in the trial, which has nothing to do with the ivermectin.
"You have to read about research in a critical way," Susanna Priest, editor in chief of the peer-reviewed journal Science Communication, previously told Insider. "What we have here is a conflict between our commitment to freedom of speech, and a clash with the nature of scientific truth."
(The Journal of Clinical and Diagnostic Research, where this study was published, did not respond to Insider's questions about whether this study was being investigated and/or retracted.)
Another ivermectin study from Egypt, released in November of 2020, has been withdrawn.
The study was pulled after independent researchers, and one master's degree student doing an assignment for class, raised concerns that the data was potentially fabricated, and large sections of the study were plagiarized.
"Amazingly, the study found that people treated with ivermectin were 90% less likely to die than people who got the placebo, which if true would make ivermectin the most incredibly effective treatment ever to be discovered in modern medicine," epidemiologist Gideon Meyerowitz-Katz from the University of Wollongong wrote in a blog post combing through the study's various errors.
The introduction has been plagiarized, many of the data are near-identical from patient to patient (raising questions about whether they were fabricated), and some of the participants included in the study were already dead when this research began.
A day after the study from Egypt came out, another ivermectin study of hundreds of healthcare workers in Argentina was released, suggesting the drug prevented all who took it from getting COVID-19. The study might not have happened at all, at least in some of the hospitals originally included.
According to an investigation published in Buzzfeed News in September, local authorities in Buenos Aires have no record of the study ever receiving formal approval, and one of the hospitals where it supposedly took place said it had no record of the study ever happening.
Dr. Alkis Psaltis, an Australian author on the paper who was not involved in collecting the data for it (but lent his expertise to the writing and editing stage), later grew so alarmed at all the red flags that he asked to have his authorship withdrawn.
"I trusted the information provided to me," the head and neck surgeon at The Queen Elizabeth Hospital told BuzzFeed.
Medical Press, which is a pay-to-publish journal, did not respond to Insider's questions about whether it was investigating and/or retracting this study.
Pay to publish scientific journals don't charge readers, but instead charge the scientists who publish in them hundreds to thousands of dollars to have a single study printed. Not all pay-to-publish journals are bad, but there is often a monetary incentive for them to push out lots of studies quickly, even if the quality of that work is not up to par, and there is little incentive to retract inaccurate work.
By February 2021, ivermectin was being widely tried out as a COVID-19 treatment. An observational study of healthcare workers in India suggested those who'd taken it reduced their odds of developing a coronavirus infection by 73%, but the authors only controlled for a few factors, making it difficult to know the true impact of the drug on the study outcome.
This is the challenge with all observational research, Meyerowitz-Katz said.
"It doesn't matter how many studies there are, ultimately we still haven't answered the question," he said.
That's because the study wasn't designed to parse out what role ivermectin is playing in patient outcomes, versus all the other factors in people's lives that might affect how they fare.
Large, well-designed randomized controlled trials (RCT), the gold standard for all drug research, are needed.
None so far have surfaced for ivermectin that stand up to scrutiny.
"The quantity of evidence is meaningless, it's the quality of evidence that we care about," Meyerowitz-Katz added.
In April, the FLCCC drew up this meta-analysis of ivermectin. Some of the largest studies it cites have been withdrawn, and the conclusions are dubious.
A meta-analysis is essentially a big research review. Meta-analyses round up lots of different studies on the same topic, aiming to identify trends and common themes, to say something more conclusive than a single study could.
But "a review that includes research that's been retracted is not very useful," Meyerowitz-Katz said.
In addition to relying heavily on flawed research, this meta-analysis also points to "natural experiments" with ivermectin in Brazil as proof the drug can combat COVID-19. But doctors working in that country have told Insider that Brazil's experience with ivermectin should be a warning to anyone who thinks the drug could be useful to treat COVID, or replace vaccines.
"Whether somebody was taking it or not didn't seem to have any impact on whether or not they got hospitalized or ended up dying from their COVID infection," Akrami told Insider. "At this point in the pandemic, we really don't have any reason to continue prescribing ineffective medications for prophylaxis or treatment."
In May 2020, a supposed randomized controlled trial of ivermectin was conducted in Lebanon. But the patient data looks like a huge copy-paste job.
Meyerowitz-Katz dissected the study in a recent blog post.
"People will find poor quality studies to justify prescribing, and that would almost be equal to malpractice," Dr Akrami said, adding that there's "a lot more faith than evidence behind some of these practices."
There are a few large, well-controlled trials of ivermectin going on now, which aim to better answer whether ivermectin might help with COVID-19. Early indications don't look promising.
The Together Trial, which is studying all kinds of potential repurposed drugs for COVID-19 treatment around the world, has yet to publish any official results on ivermectin. But Together did share a glimpse at some results in an August presentation.
According to the slide shown here, the researchers found no meaningful difference in the outcomes of patients who were treated early on in their COVID-19 infection with ivermectin, versus those who had recieved a placebo pill.
That's quite similar to what researchers found in a March RCT of 476 COVID-19 patients in Colombia. Their research was published in the peer-reviewed journal JAMA, which does not make authors pay to have their studies printed.
More definitive answers may come soon from Oxford's Principle trial, the world's largest study of at-home treatment for COVID-19.
"Once we have findings from our study about ivermectin that have been validated, I would be delighted to comment," Principle investigator Christopher Butler told Insider.
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