Dear Editor,
Ivermectin is a drug approved to treat parasitic infections (e.g., fleas, lice and intestinal worms) in both animals and humans. To date, it is not approved by the US FDA, Health Canada, Public Health England, the WHO and others for the treatment of COVID-19 but has significantly shaped the pandemic response of Latin America. Over the past year it was included in Peru’s national therapeutic guidelines for COVID-19. It was mass administered to 350, 000 people in Bolivia for the treatment and prevention of COVID-19. Colombians are advocating to have a national Ivermectin policy and Paraguay restricted its sale as it was in such high demand. Why is this happening in Latin America?
Of course, high infection rates and despairing times can cause people to turn to whatever potential solution presents itself but why are health professionals approving this? Many believe that policy decisions in Latin America were largely based on a high impact pre-print publication (downloaded over 15000 times and abstract viewed over 80000). Note pre-prints are not taken as established evidence because they have not undergone peer-review or scrutinised by experts. Decisions were also based on an Australian study (Caly et al. Antiviral Res. 2020, 178: 104787.) conducted in vitro (in the lab). They showed that in monkey cells, Ivermectin was able to stop SARS-CoV-2 from growing, however, the minimum amount of drug needed to do this is 10 times that approved for human use by the FDA. Further, lab studies don’t necessarily translate to human efficacy and
safety and this is the reason why there are human clinical trials. The authors themselves wrote that before the drug is used there should be proper clinical trials, “Well-conducted clinical trials informed by robust pharmacokinetic models should be considered to validate the impact before the use of Ivermectin to treat SARS-CoV-2 is implemented.” Small clinical trials conducted after and to date, at best, are not conclusive (the WHO does a good review on this); larger trials comprising more control experiments were recommended and ongoing.
An article in the Kaieteur News on June 8th points to a meta-analysis (data pulled from many research studies) which include several pre-prints and lauds it as evidence that this drug is effective. Meta-analysis or ‘data analysis of data’ is not evidence that a drug is effective. Meta-analysis itself has significant bias as it does not take into account variations in individual studies; it’s very problematic when study design does not include proper controls. A simple google search will bring up scientific reviews on existing biases with using this type of approach such as the inclusion of mediocre and low-quality studies. Direct evidence comes from assessment of direct experimental data not data analysis of data. I think the Scientistic Advisory Board for Alberta Health Services in Canada, from their review of existing publications on the subject, puts it best, “Existing evidence on this topic is inconclusive due to low quality of the literature and mixed findings of the primary studies and meta-analyses. There is considerable uncertainty due to the shortcomings in study design and execution. Further research is necessary to confirm the role of Ivermectin as an effective, clinically useful treatment for COVID-19.”
The US FDA’s position is that it’s not approved for COVID-19 and a look at their guidance shows a section on “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19” and includes, “Taking large doses of this drug is dangerous and can cause serious harm.” This is a very important warning since ‘in vitro’ experiments (mentioned earlier) show that quite a large amount is required to stop the virus from growing in monkey cells (at least 10 times that approved for safe use by the FDA); drug dosage is usually worked out in clinical trials and clearly this is vital information prior to usage since large amounts of it are toxic to humans (even small doses are toxic to some breeds of dogs). The European Medicines Agency and the WHO have the same position – current data does not support its use “outside well-designed clinical trials” in a control setting where people being treated have given their permission (voluntarily) for it to be used. Further, India recently removed it (along with other unproven drugs) from its approved COVID treatment list in accordance with the WHO warnings and many Indian scientists’ protests against the use of unproven drugs.
The drug manufacturer (Merck) they state (https://www.merck.com/news/merck-statement-on-ivermectin-use-during-the-covid-19-pandemic/) that their analysis shows:
– No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies;
– No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and;
– A concerning lack of safety data in the majority of studies.
As it stands now, the drug is still being investigated in controlled clinical trials to determine whether it is truly effective or whether the alleviation in COVID-19 symptoms observed does not have complicating factors – anecdotal (observational) evidence is not acceptable for drug use. If this is a satisfactory standard, why go through the rigor of clinical trials then? This is not trivial. We don’t want another case of hydroxychloroquine. It is concerning that some health professionals are touting Ivermectin as a wonder drug based on personal anecdotal evidence; at best, to date, the data from trials is inconclusive. We are living in a pandemic and high COVID-19 infection rates may render us desperate to protect ourselves. However, it is my view that this does not justify the use of an unproven drug. All approved vaccines have undergone rigorous testing in clinical trials completing large scale phase 3 clinical trials prior to authorisation for use; post authorisation these vaccines are continuously monitored to accumulate long term safety data so that best decisions can be made for their continued use. The same process is used for drugs and therapeutics which must be held to the same standard of rigorous testing prior to use. We have approved and proven vaccines, get vaccinated and keep cooperating with public health measures to protect yourself and others.
Sincerely,
Jacquelyn Jhingree, PhD.