"Generous" Contract Research Organization in Colombia claims it worked for free to sink ivermectin. JAMA played along with the charade

Finally, after dozens of positive studies, one got published in which the authors claim ivermectin does not help Covid patients.  But it actually did help them, although the benefit missed statistical significance.

Let's drill down.  First off, Covid19Crusher has written a good summary of some of the methodological problems of the study. I won't repeat them.

Let me give you the background.  The study was performed at the Center for the Study of Pediatric Infectious Disease (CEIP) in Cali, Colombia, and supposedly CEIP paid the costs.  That in itself is surprising.  A pediatric research center doing unfunded adult research?  But then, the researchers disclose other funding from GSK, Janssen (J and J), Sanofi and one author disclosed payments from Gilead.

When I went to the website of CEIP, it looked like a contract research organization: a healthcare company that does clinical research for pharma companies.  The home page opens with a come-on seeking subjects for a Covid-19 vaccine trial.

On another page (below), you see the pale logos of the Center's clients, which include Bristol Myers Squibb, GlaxoSmithKline and Novartis. This is not the kind of business that performs unfunded research.  

This study also enrolled patients late, and slowly.  It involved first a physician phone call to ascertain eligibility and then a nurse visit to draw blood.  Patients were finally enrolled and given their medication only when a third contact was made by another nurse visit to their home.  Unnecessary delays appear to have been built into the protocol.

The study protocol was considerably changed in the middle of the study, which is normally unacceptable.

The placebo changed in the middle of the study.  The medicine came as a liquid, and the first placebo was sugar water, so there was would have been unblinding of subjects based on the taste of the medication. The content of the second placebo was not described in the text.

The study pharmacist is said to have given all enrollees (during a 16 day period) ivermectin, during which none received the placebo, in error.  These subjects were pulled from the study.  Was this done to reduce the study's power so it did not achieve statistical significance?

Finally, there might have been an effort to overdose patients.  The normal dose of ivermectin is 150-200 mcg/kg.  Patients may get this dose on alternate days or daily for up to 5 days to treat Covid.  Although the subjects in this study were all outpatients with reportedly mild disease at onset, they received an ivermectin dose of 300 mcg/kg daily for 5 days.  While ivermectin is considered a very safe drug, it is normally given as a single dose or only two doses for its pre-Covid indications.  It is here being used at a higher dose than ever approved for any indication, for 5 days (a prolonged dosing duration, which has only been in use a few months) and so this study seems like a high dose experiment.  In any event, there was no reported harm to the patients. And a few other ivermectin studies have tested the 300 mcg/kg dose.

UPDATE March 13:  Dr. David Scheim has posted a preprint that also criticizes this study. He notes that ivermectin was an over-the-counter drug in Colombia, and that up to 50,000 blister packs and bottles of ivermectin liquid were sold per month in the state of Valle del Cauca, where the trial was conducted, during the trial period.

While ivermectin can have clinical effects lasting a month or more, the trial only required that subjects had not received ivermectin during the preceding 5 days.  Might some of those who received the sugar water placebo purchased their own OTC ivermectin?

Supporting this notion is the fact that the adverse event rates in the drug vs placebo group were almost identical.

The takeaway message is that this is simply a dreadfully conducted study, from which no conclusions can be drawn.

Some hidden entity had this study done, and managed to get it published in the JAMA despite its obvious failings. It definitely lacks the caliber of a paper published by the JAMA. Whoever was working behind the scenes to fund and publish this study has not been disclosed by the authors or by the JAMA.  JAMA seems to have been remarkably incurious about the study's provenance, especially after the NEJM and Lancet were exposed for publishing fabricated studies on Covid drugs last year.

This looks like another crude attempt to sink a drug that has shown phenomenal efficacy in the fight against Covid. 

UPDATE March 6:  Apparently right on cue, one day after the above study was published, FDA warned against the use of ivermectin for Covid.  How much information do you need before you figure out that our public health agencies are in fact working to harm us and keep the pandemic going?

UPDATE March 11: A local pharmacist refused to fill a prescription I wrote for ivermectin for Covid, citing the FDA warning above.  Despite the fact the FDA web posting lacked any force of law or regulation. The pharmacist did inform me that for the past year she has been instructed to evaluate the prescribing of the chloroquines and azithromycin to be sure they are not being used for Covid. Is this public health turned upside down, or not? Are your public health agencies working for or against you?