Ivermectin: Much More Than You Wanted To Know
By Scott Alexander, Astral Codex Ten.
The linked article is an exhaustive review of Ivermectin studies for laypersons. It’s pretty damned long but can be a real treat for those with the capacity and inclination to get deep into the weeds on the studies---good, bad, meh, and outright fraudulent. Also, his analysis is liberally seasoned with levity and wit, which makes wading through the daunting content less onerous for those of us less inclined to venturing through weedy thickets of data and complex logic.
There is a finding and a hypothesis toward the end of the piece to which I feel it well worth drawing attention. It has to do with immunosuppression, parasitic worms, and Ivermectin. First, we now know that the timing of which class of drugs to administer during which phase of Covid-19 infection is key to outcomes. Rule of thumb: first, administer antivirals early to suppress the virus and limit the damage it does; administer immune response inhibitors days later when, not the virus, but the body’s own overly enthusiastic inflammatory response causes tissue damage and death. Getting this wrong kills patients.
Once the studies Ivermectin studies discussed in the article are well winnowed, the few that remain display an intriguing geo-epidemiological feature, which could turn out to be a principal source of both the confusion and strife surrounding the use of Ivermectin in treating Covid-19.
The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive.
Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias...
If nothing else there are indications that there exists evidence for a hypothesis that deserves more investigation :
An element of parasitic worms’ survival strategy is the suppression of the host’s immune system. Covid-19 or any pathogen will generally do more harm to those with weakened immune systems. Parasitic worms weaken the immune system. Ivermectin prevents parasitic worms from weakening the immune system. Therefore, it is plausible that Ivermectin is effective in concert with other proven treatments against Covid-19 in patients with the comorbidity of parasitic worm infection.
Like I said, this article is long and exhaustive. The author goes on to delve into problems with scientific publishing, such as the “replication crisis” and ways to correct for it when evaluating studies and performing metanalyses.
There follows discussion on the sociology and politics of the Ivermectin controversy. An excerpt:
Ivermectin supporters were really wrong. I enjoy the idea of a cosmic joke where ivermectin sort of works in some senses in some areas. But the things people were claiming - that ivermectin has a 100% success rate, that you don’t need to take the vaccine because you can just take ivermectin instead, etc - have been untenable not just since the big negative trials came out this summer, but even by the standards of the early positive trials. Mahmud et al was big and positive and exciting, but it showed that ivermectin patients recovered in about 7 days on average instead of 9. I think the conventional wisdom - that the most extreme ivermectin supporters were mostly gullible rubes who were bamboozled by pseudoscience - was basically accurate.
Mainstream medicine has reacted with slogans like “believe Science”. I don’t know if those kinds of slogans ever help, but they’re especially unhelpful here. A quick look at ivermectin supporters shows their problem is they believed Science too much.
[Remember, certain areas are producing good pro-ivermectin studies, while other areas are producing good anti-ivermectin studies]
They have a very reasonable-sounding belief, which is that if dozens of studies all say a drug works really well, then it probably works really well. When they see dozens of studies saying a drug works really well, and the elites saying “no don’t take it!”, their extremely natural conclusion is that it works really well but the elites are covering it up.
This “extremely natural conclusion” that elites mislead us is prevalent across the political spectrum and not without just cause. My living memory of of elite official deception goes back to the Gulf of Tonkin incident. Examples before and since producing horrendous consequences are, to put it mildly, not unheard of.
Ivermectin doesn’t reduce mortality in COVID a significant amount (let’s say d > 0.3) in the absence of comorbid parasites: 85-90% confidence
Parasitic worms are a significant confounder in some ivermectin studies, such that they made them get a positive result even when honest and methodologically sound: 50% confidence
Fraud and data processing errors are of similar magnitude to p-hacking and methodological problems in explaining bad studies (95% confidence interval for fraud: between >1% and 5% as important as methodological problems; 95% confidence interval for data processing errors: between 5% and 100% as important)
Probably “Trust Science” is not the right way to reach proponents of pseudoscientific medicine: ???% confidence
For the bits I left out, many of them both amusing and informative, see the original.