Watchdog scientists are sounding the alarm over covid-19 studies involving ivermectin, a long-used antiparasitic that some claim can be effective at treating or preventing the viral illness. In a new article this week, they argue that the research into ivermectin has been plagued by widespread fraud and lax oversight by other researchers. The best way to prevent similar issues moving forward, they say, is to impose stricter standards in general on how data is collected and re-analysed by scientists conducting reviews of the evidence.
Ivermectin has emerged as an unexpected cultural totem of the pandemic. Some people, who often also distrust vaccines or have downplayed the pandemic, believe that ivermectin is a highly effective covid-19 drug that has been kept away from the public at the behest of Big Pharma. Many people have been rightly sceptical of these claims, though some have been fooled by reports claiming that overdoses of ivermectin have overwhelmed emergency rooms or that it’s causing a mass epidemic of infertility in users.
In truth, ivermectin is an immensely valuable drug that’s very safe and effective when taken as an antiparasitic. But despite some early studies in animals or in the lab suggesting that it could also help kill the coronavirus, the bulk of the evidence does not point to a major benefit from the drug for actual covid-19 patients, at least to date. The largest and seemingly highest-quality studies have found no real effect on mortality or prevention of infection. Meanwhile, the findings of some studies that seemed to show a tremendous effect have since been thrown into question.
In a new article published this week in Nature Medicine, scientists from the UK, Australia, Sweden, and the U.S. highlight two of these suspect studies that they’ve brought attention to in the past: a purported clinical trial in Egypt that has now been pulled from the preprint server where it was released amid allegations of plagiarism and suspect data, and another in Iran that found a benefit in reducing mortality among hospitalized patients. The Iran study may have failed to properly randomize participants to the treatment and control groups, an important step for obtaining valid results, the authors say.
But they say these examples are just the tip of the iceberg. There are numerous other ivermectin studies they’ve found where even a cursory look at the data reveals glaring errors, conflicting details, and numbers so impossible that they were likely faked, the group argues. Not only are these studies bad science, they add, they’ve actively harming people.
Hundreds of thousands of people, often in poorer countries with little access to expensive antivirals or experimental drugs that have shown some promise in treating covid-19, have been given ivermectin for covid-19, despite very little good evidence that it does anything for them. In the U.S., some people have gotten hurt from taking ivermectin without medical supervision. Just today, New Mexico health officials reported that at least two residents were killed as a result of ivermectin toxicity, while others have developed seizures and hallucinations.
“Relying on low-quality or questionable studies in the current global climate presents severe and immediate harms,” the authors wrote. “The enormous impact covid-19 and the consequent urgent need to demonstrate the clinical efficacy of new therapeutic options provides fertile ground for even poorly evidenced claims of efficacy to be amplified, both in the scientific literature and on social media.”
One key way these studies are amplified is through something called a meta-analysis, which is when scientists take a bunch of relevant studies on a topic and try to summarize the state of the evidence. Though meta-analyses are an important part of science, they have to be done carefully to weed out poorly conducted or suspect research, or their results can become tainted. The authors note that at least two meta-analyses have claimed to find a net benefit for ivermectin, thanks largely to the inclusion of the Egyptian study. Following that study’s withdrawal, the authors of one meta-analysis have retracted their paper and have said they would reanalyze and republish their work without either the study from Egypt or Iran.
Scientific research is an imperfect process in the best of times. But scientists and institutions like academic journals and media outlets are especially vulnerable to fraud, because the basic assumption is that everyone’s making a good faith effort to conduct science ethically. Without rigorous checks and balances, even studies so flimsy that they fall apart with a brief glance can get media attention or be published. The newfound popularity of ivermectin adds even more incentive for some to not check the maths, since many fans will and have turned a blind eye to dodgy studies that claim to have found huge benefits for the drug.
Throughout this year and last, for instance, proponents of ivermectin have touted a study from Argentina that appeared to show ivermectin could prevent 100% of infections in health care workers. Yet an investigation by Buzzfeed News published earlier this month unearthed evidence that parts of the study’s claimed methods and results simply don’t make sense and may have been fabricated, while some of the authors of this new paper have criticised it as well.
While scientific fraud can be hard to root out, the authors say a lot more could be done to prevent it from hijacking clinical research, not just for covid-19 but in general. They’re calling for scientists to adopt a new standard for meta-analyses, where individual patient data, not just a summary of that data, is provided by scientists who conducted the original trials and subsequently collected for analysis. Though this would mean more work for scientists (among other things, the data has to be properly anonymised to protect people’s privacy), having access to this kind of raw data would make it much easier for researchers to detect potential fraud or fatally flawed studies. Studies whose authors don’t provide this information should be earmarked as having a high risk of bias or outright excluded from a meta-analysis, they add.
“We recognise that this is a change to long-accepted practice and is substantially more rigorous than the standards that are typically currently applied, but we believe that what has happened in the case of ivermectin justifies our proposal,” the authors wrote.
Notably, the authors of the Brazilian and Iranian studies have so far refused to make their patient data available to anyone else.
There are still ongoing clinical trials of ivermectin, in the U.S. and elsewhere, and it’s not inconceivable that the drug could yet have a modest benefit for covid-19. But as things stand now, the state of ivermectin research is shameful. “This research has created undue confidence in the use of ivermectin as a prophylactic or treatment for covid-19, has usurped other research agendas, and probably resulted in inappropriate treatment or substandard care of patients,” the authors wrote.