Back in January 2021, TrialSite reported that the University of Oxford was “considering” ivermectin for its PRINCIPLE clinical trial or the “Platform Randomized Trial of Treatments in the Community for Epidemic and Pandemic Illnesses.” Backed by the UK government via the Department of Health and Social Care as well as Oxford Nuffield Department of Primary Care Health Sciences, the importance and stature of this study was, and is, promising. However, given the pervasive “regulatory capture” problem, TrialSite’s suggested that the generic drug triggered worldwide controversy and pressure, and for months, it wasn’t clear if the University of Oxford was moving forward or not with ivermectin. Now there’s confirmation in the popular press that the ivermectin study arm is in fact moving forward. Of course, one challenge is timing – much like in the U.S., where the National Institutes of Health (NIH) via its Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, ACTIV-6 also included ivermectin recently – ivermectin proponents argue this occurred a year too late given the death toll of the pandemic. These proponents posit that there’s compelling evidence now that the drug can inhibit COVID-19 severity and progression if administered to early-onset, mild-to-moderate cases. While The BBC’s Rachel Schraer confirms that the PRINCIPLE study now includes ivermectin, the health reporter, unfortunately, provides a fairly one-sided view of the growing ivermectin controversy. The study is led by joint chief investigator Prof. Richard Hobbs, a prominent, well-respected British principal investigator.
The Conflicting POVs
There are two conflicting points of view out there when it comes to ivermectin. The first could be called the pro-ivermectin camp. That is, a group of front-line physicians and a selection of investigators and public health professionals and advocates that believe that the 60 completed ivermectin studies evidence sufficient safety and efficacy. To date, these 60 studies involve 18,931 patients and 549 investigators/scientists and represent stunning results: 85% improvement across 14 prophylaxis studies; 76% improvement in 25 early treatment trials; and 46% improvement in 21 late treatment trials along with 70% improvement in 22 mortality results. Of 31 randomized controlled trials, 64% show improvement. A prominent meta-analysis from the UK, published in the peer-review American Journal of Therapeutics, reveals that across 3,406 COVID-19 patients, ivermectin led to a reduced risk of death, lowered infection, and even prophylactic benefits.
Moreover, as TrialSite’s reported, a number of observational and population-wide public health studies evidence significant positive benefit. TrialSite’s reported on these efforts from the Mexico City population health initiative during the pandemic to Uttar Pradesh’s statewide initiative. The proponents remind all that the drug is economical, widely available, and that several nations have authorized the use of the drug off-label during the pandemic, including Slovakia.
On the other side are the more traditional-minded individuals that for whatever reason do not yet see enough sufficient evidence in the 60 existing trials (including 31 randomized trials). Representing the overwhelming majority of academia, government and, of course, industry, this camp critiques these studies, with the argument ranging from lack of sufficient size to deficient in design to other critiques. TrialSite suggests an underlying bias from the U.S. and European academy thinking may also be at work as well as the concept of regulatory capture, showcased recently by Merck’s aggressive anti-ivermectin stance (it’s their product) while purportedly neutral, unbiased agencies, such as the World Health Organization (WHO), U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and to some extent the NIH evidence lock-step alignment.
Ms. Schraer unfortunately mixes some misinformation-leading material in with legitimate reporting, serving to mix up and ultimately confuse the ivermectin discussion at this stage. TrialSite suggests the mainstream media’s one-sided, biased reporting and coverage of the ivermectin debate represents evidence of the phenomena of regulatory capture. Note that BBC consciously sets out to do this but because of the entanglement of interests, the presentation of information is distorted, morphed, and shaped to achieve a particular agenda. In this case, that’s ultimately to help industry develop, market, and sell more expensive pills on the market addressing COVID therapeutic care.
The BBC journalist pointed to limitations of existing research, such as mentioning that some of the studies are observational, but she fails to mention that there have been 60 ivermectin studies, including 31 randomized controlled trials extending across over 18,00 patients! Even when critiquing some of the studies for being observational, she fails to convey that the U.S. FDA embraces real-world evidence, that is, data from observational studies and other care sources for purposes of developing medicinal evidence. But in all seriousness, how could a legitimate investigative journalist not report on 60 total studies, 31 of them randomized controlled trials?
Additionally, when the journalist declares that “Despite the lack of good evidence so far, Ivermectin has been taken up by doctors or by individuals self-medicating in countries including Brazil, Bolivia, Peru, South Africa and the U.S.,” she fails to mention that some of these country’s (or states within these nations) governments have actually authorized the use of the drug for COVID-19, such as South Africa. Or for that matter, that the U.S. NIH doesn’t recommend against the drug off-label either. Aren’t these facts material to the story?
While she quotes a Dr. Stephen Griffin from the University of Leeds comparing the ivermectin situation to hydroxychloroquine in a clear attempt to establish controversy or “guilt by association,” the lack of balanced reporting here, in the middle of a pandemic, raises considerable concern about BBCs’ reporting standards, or objectivity.
Why can’t the BBC write the truth? That the drug was approved for use in COVID-19 in places such as Slovakia, South Africa, India, and major municipalities such as Mexico City? Isn’t this relevant for background?
Rather, the reporter writes about the negative point of view, serving to taint the reader toward that direction. When addressing the use of the drug off-label, she shares, “The danger with such off-label use is that…the use of the drug becomes driven by specific interest groups or proponents of non-conventional treatments and becomes politicized.”
But what about the fact that despite all the evidence to the contrary, Merck went into attack mode on their own ivermectin-based product, declaring there’s absolutely no evidence in any of the 60 studies, shockingly even calling into question the safety of ivermectin. So did the FDA with no data. Why didn’t Schraer connect Merck’s attack to the fact that they received $356 million in taxpayer money from the U.S. government, along with a recent $1.2 billion commitment for a branded experimental study drug that will be a lot more expensive than ivermectin?
Why did the Oxford Principle team select ivermectin?
With six study drugs, the BBC reports that only one of the PRINCIPLE drugs was proven effective thus far—inhaled steroid budesonide. The bias in this BBC piece continued when the writer offered a description of why ivermectin was selected by the PRINCIPLE trial in the first place. Noting that the Oxford study team picked ivermectin due to 1) its status “as readily available globally” and 2) “known to be relatively safe,” she then inserts “although, like most things, it can be toxic at very high doses.” Isn’t there more to the story? A major university just doesn’t select a drug because it’s available and safe. Why would PRINCIPLE actually select ivermectin? Why wouldn’t a BBC reporter live up to the journalistic standards of that great news organization, bringing a more balanced, objective, and critical point of view?
The PRINCIPLE Trial
Of note, the majority of studies to date lead to the use of the study drug at the early onset of the COVID-19 disease lifecycle. Up to 14 days into the disease could deviate from that understanding.
The trial’s main objective centers on the quest to find safe and effective treatments to help patients suffering with SARS-Cov-2 at home and in the community improve and heal faster without the need for hospitalization. The study team has been testing well-known treatments, many of them used for decades.
Inclusion criteria include either aged 65 and above or aged 18-64 coupled with shortness of breath associated with SARS-CoV-2 infection or this age range in association with any of the following underlying health conditions, including “a) Known weakened immune system due to a serious illness or medication (e.g. chemotherapy); b) Known heart disease and/or a diagnosis of high blood pressure; c) Known chronic lung disease (e.g. asthma); d) Known diabetes; e) Known mild hepatic impairment; f) Known stroke or neurological problem; and g) Self-report obesity or body mass index ≥35 kg/m2.”
Prof. Richard Hobbs, Head of Department and Nuffield Professor of Primary Care Health Sciences, Director, NIHR English School for Primary Care Research, Director, NIHR Applied Research Collaboration (NIHR ARC) Oxford
Call to Action: Check out the study site if interested here.