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Hi JAMA, I think your bias is showing? February 4, 2023

Full disclosure, I have no financial interest in the Journal of American Medical Association, pharmaceutical companies, or anything else for that matter. I’m a doctor who sees real, live patients every day, and I try my best to practice evidence-based medicine. 

I was perusing the latest study regarding ivermectin and COVID outcomes in the October 21, 2022 edition of The Journal of the American Medical Association (JAMA) the other day. I usually lazily read the conclusions first (don’t we all do this?) The conclusion reads like this: “Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19”. How shocking!  Another COVID study finding no benefit from ivermectin. This time from JAMA which had already published another negative ivermectin trial in 2021. Who would have predicted it? Call me a cynic or a psychic, either one will do. 

I was about to move on to the next article, but something inside me urged me to dig deeper on this one. So I did. It turns out, problems stuck out from the very beginning. People were recruited who had tested positive for COVID and had been symptomatic for the past 7 days.  7 days? Really? Truly? They can’t be serious, can they? 7 days is an eternity when studying the efficacy of antiviral drugs. 

For example, the flu drug Tamiflu (oseltamivir) MUST be prescribed within 48 hours of symptom onset, and Valtrex (valacyclovir) for shingles MUST be prescribed in the first 48-72 hours of symptom onset. 72 hours is only 3 days.  These are both antiviral drugs. Why is this so important? Well, both of these drugs (that I prescribe very often) fare no better than placebo after about 5-6 days of waiting to start treatment. Meaning, almost all of the benefits derived from these very commonly prescribed drugs are found by taking them within the first 3 days of symptoms. Indeed that’s why they must be prescribed by a doctor within the first 3 days of symptoms! 

But for ivermectin, it was supposedly ok to wait 2.5-3.5 times longer than Tamiflu or Valtrex to start treatment? And the authors were ok with this? 

The authors did acknowledge this obvious confounding problem and responded with, “There was no evidence of a differential treatment effect based on the median time of symptom onset to receipt of study drug.” My response? “OK, I trust you, but I’m going to need some verification as I don’t see the data you used to make this conclusion.”  I have emailed the authors and am awaiting their response. 

The second thing that struck me as odd, is that the primary outcome measure of assessing the time of recovery was just barely non significant (the posterior P value must be 0.95 or greater, in this case it was 0.91). Technically, a non significant finding. Ok, fine. However, one of the secondary outcomes, the difference in time spent feeling unwell, was indeed significantly in favor of ivermectin, with a posterior P value of 0.99 (yes, it greater than 0.95, meaning it is significant finding). In addition, those taking ivermectin experienced one day less (12 days) of COVID symptoms than those taking placebo (13 days). Yet no mention of this significant finding  was made in the conclusion! Also amazingly, no reference was made of the (yet again, barely squeak through-the-door insignificant finding) 2 day difference in symptoms found in the 2021 JAMA study! 

Now you may say that one day doesn’t make a lot of difference. Why all the fuss about a one day difference in time to feeling better? I say, “Au contraire!” Let’s look at the Tamiflu study published by the same journal, JAMA, back in 2000 when Tamiflu was being rolled out. Keep in mind, you better believe these folks got their Tamiflu dose no later than 36 hours of symptom onset. The drug-maker Roche made sure of that. And even with that head start, they found that Tamiflu reduced the “time unwell” by only 1.3 days. Think of it–Tamiflu got on average over a 100 hour head start on ivermectin. And Tamiflu is handed out like candy during flu season. Trust me, I do a lot of it. 

So let me get this straight:  Tamiflu–with a 100+ hour head start, gets handed out like candy, and shortens flu symptoms by 1.3 days. Ivermectin–with a 100+ hour late start, is astonishingly still able to eek out shortening of symptoms by 1 day, and does so with statistical significance printed in black and white for all to see in JAMA–and STILL gets kicked to the curb to be yet again, crucified by the “experts”.  

All I can say is, I’m glad I don’t practice in California–where I can actually lose my license for prescribing a drug that shows a statistically significant positive effect in a study published by one of the most prestigious medical journals in the world.

Where is the serious scientific discussion on this? I will now politely excuse myself from the political warfare on ivermectin, which is basically stupidity on brilliant display by both sides of the political aisle. If you don’t have anything scientific to add, don’t say it. Ad hominem attacks are pathetic. I applaud the authors and JAMA for publishing this article. It must have taken a lot of work, and I appreciate their efforts. I really do. As I have said countless times in the past, I have no skin in this game, nobody pays me, I’m just a primary care doctor who sees patients every day of the week. I’m not married to any idea or political slant, including ivermectin. But these are serious questions that need serious answers if I am going to remain neutral on this. Hi JAMA, I think your bias is showing?

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