Cochrane has developed a brand as a prestigious, independent and unbiased medical research non-profit pursuing evidence-based choices involving healthy interventions of health professionals, patients, and policy makers. With 53 review groups based at research institutes around the globe, the well-respected organization includes 30,000 volunteer experts. Long a reliable player in this field of evidence-based medicine, it was some activity in the German-speaking world that prompted TrialSite’s attention recently. Recently, Cochrane Austria opted to evaluate ivermectin in a document titled “Ivermectin against corona: probably ineffective.” Now an organization that prides itself on objective, unbiased and systematic reviews might look more carefully at the over 50 clinical trials that demonstrate positive outcomes. There is a growing list of dedicated, committed biomedical researchers that have made a case via meta-analyses that ivermectin should be considered for some form of emergency use authorization. For example, medical evidence expert Dr. Tess Lawrie, not on any industry payroll, has performed a comprehensive meta-analysis showcasing what she and many others argue is compelling evidence for safety and efficacy. So has the Front Line COVID-19 Critical Care Alliance (FLCCC), which just had its physicians’ ivermectin meta-analysis research published in the American Journal of Therapeutics. But Cochrane reviewers ignore all of this. Moreover, out of ten studies, the only one they rank as “low bias” is perhaps the most controversial study, the Lopez Medina et al. (2021 JAMA)study performed in Cali, Colombia.
Authored by Dr. Jana Meixner and supported by medical editor Julia Harlfinger, the Cochrane ivermectin position caught the attention of a number of respected researchers in both Austria and Germany. They expressed considerable concern as to the unfortunate potential for bias from what has been a truly important independent organization. With their high ranking of the Colombian study—which is a theme among other pharmaceutical industry players from regulators to industry and the mainstream media, TrialSite had to dedicate some space to address.
TrialSite has reported about the severe faults of the Lopez Medina et al. study. For example, frequent TrialSite contributor Peter Yim has demonstrated that the investigator openly deceived subjects in a blatant ethical violation. Yim also points out a number of issues involving the self-reporting of a modification to the endpoint, to an acknowledgment that the study wasn’t “designed to detect a difference in the hazard ratio between the intervention and the control arms of less than 1.4.” Yim also points out there was no virological assessment and other issues. Moreover, an open letter with hundreds of physicians and scientists asked for a retraction due to scientific fraud—again, citing a host of mistakes and errors from bad study design, blinding errors, different taste of placebo and ivermectin, etc.
Moreover, the Lopez-Median et al. (2021) study was purely based on self-reporting and conducted at home, after supplied with ivermectin and placebo for the whole study period. Control of ivermectin/placebo consumption was purely based on counting the empty bottles after the study period.
Beside erroneous supply of placebo and ivermectin by the study personnel, and the different taste, there was no analysis of the serum level of ivermectin. Also, other essential clinical data, such as the dynamics of the viral load, was not performed.
In addition, ivermectin was freely distributed and advertised by the mayor of Cali before the study period, and ivermectin was sold over the counter in Cali. Self-reported symptoms and adverse effects were equal for the placebo arm and the ivermectin arm. Probands of both arms reported the typical, non-severe symptoms of too high a dose of ivermectin, such as blurred vision and digestion problems, at a comparable extent.
Also, Cochrane only presents a limited selection of ivermectin studies. A far better overview on ivermectin studies is given by Kory et al. (2021) and an excellent statistical evaluation of RCTs is provided by Bryant et al. (2021). A well updated overview on the finalized ivermectin studies, actually a total of 53 studies, is presented on the website of FLCCC (https://covid19criticalcare.com/).
Why and how this faulty study by Lopez-Medina et al. (2021) was at all selected as a study indicating the effect of ivermectin for treatment of Covid-19 by Cochrane should be clarified. If this error is not corrected and explained, we have to carefully observe and eventually re-assess the value of Cochrane in the world of evidence-based medicine.
Finally, the study does not provide any criteria that allow readers to differentiate the placebo from the ivermectin group. If the study participants used additional ivermectin by themselves or if the erroneous distribution of ivermectin by the nurses that distributed the bottles in the home of the study participants contribute to the observation that both arms showed comparable ivermectin side effects could not be assessed retrospectively (ivermectin serum analysis would have been very helpful but was not achieved). However, the performed study does not allow a reliable distinction between which probands consumed ivermectin and who did not, thus it does not provide any reliable information about the effect of ivermectin against Covid-19. And finally, a wrong informed consent was provided that leaves the study without ethical clearance, according to the Helsinki Declaration.
Rumblings from Germania
TrialSite reports that some prominent researchers from various disciplines were shocked by this analysis and, unfortunately, now question the ethics and independence of Cochrane itself. For example, two well-respected microbiologists from Germany recently communicated to TrialSite’s editorial board that to some extent the judgment of WHO and European EMA against the use of ivermectin for therapy of COVID-19 relies to some extent on this incorrect Cochrane assessment—that is, the whole point of view is premised on a faulty ivermectin study from Cali, Columbia. Others have communicated concern from individuals in academia to the clinic setting in Europe.
The physicians, researchers and healthcare professionals that have participated in the ivermectin-based studies or have successfully administered ivermectin as part of an off-label regimen suggest that these biased and narrow views based on a faulty study prevent the possibility of saving thousands of COVID-19 patients every day worldwide.
TrialSite notes that Cochrane Austria isn’t alone. The New York Times, CNN, and others ignored the dozens of ivermectin-based clinical trials reported on by TrialSite for many months. Once a study with neutral results surfaced, the mainstream media pounced like lions on prey.
Positioning themselves as independent and transparent, Cochrane continues to grow its revenue with a combination of proceeds from the Cochrane Library and other “Cochrane products.” They maintain a global network of Groups supported by national governments, NGOs, universities, foundations, hospitals, and more. They position that “Cochrane is able to generate authoritative and reliable information because we never accept commercial or conflicting funding.” Hence they declare to the reader, don’t worry, they can “work freely,” and hence “unconstrained by commercial or financial interests.” But what about systemic interests?
In their “Strategy to 2020,” the organization seeks to “Put Cochrane evidence at the heart of health decision-making all over the world.”
As shared in their annual report, the organization has ambitious aspirations. With skyrocketing web traffic and ubiquitous mention in mainstream media, their goals of becoming the “home of evidence” can be further dissected by various strategy pieces.
Cochrane has played a key role, given its brand as independent, objective and impartial, in the systematic rebuttal of the considerable positive data associated with ivermectin—and its potential as a low cost, available and seemingly safe and efficacious potential option for adjuvant therapy. Should there be COVID-19 investigations into the need for systemic reform of health systems and the process of establishing medical product evidence, Cochrane will be a target of inquiry.
- López-Medina, Eduardo, et al. “Effect of Ivermectin on Time to Resolution of Symptoms Among Adults with Mild COVID-19.” JAMA, March 4, 2021. Doi:10.1001/jama.2021.3071.
- Scheim, David, et al. “Protocol violations in López-Medina et al.: 38 switched ivermectin (IVM) and placebo doses, failure of blinding, widespread IVM sales OTC in Cali, and nearly identical AEs for the IVM and control groups.” Preprint, March 8, 2021. Doi:10.31219/osf.io/u7ewz.
- Bryant et al. 2021. Ivermectin for prevention and treatment of COVID-19 infection: a systematic review and meta-analysis Research Square, doi:10.21203/rs.3.rs-317485/v1 Research Square Preprint, https://www.researchsquare.com/article/rs-317485/v1
- Kory et al. 2021 Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 American Journal of Therapeutics: Volume 28 – Issue 3 – p e299-e318 doi: 10.1097/MJT.0000000000001377https://journals.lww.com/americantherapeutics/Fulltext/2021/00000/Review_of_the_Emerging_Evidence_Demonstrating_the.4.aspx
Call to Action: To review the Cochrane Austrian analysis, follow the link.