Thread by @awgaffney

Notable that one of the leading physician advocates for using ivermectin for COVID-19, Paul Marik, was once also convinced that he had cured sepsis with a combination of vitamins and steroids — a finding not replicated once a randomized trial was actually performed.

/Thread

His words: "We haven't seen a patient die of sepsis since we began using the combination therapy a year ago. We have completely changed the natural history of sepsis."

nbc12.com/story/34986689…

He's a member of the FLCCC Alliance, along with Pierre Kory, who testified in the Senate for Ron Johnson that Ivermectin is "effectively a 'miracle drug' against COVID-19."

Ivermectin is not the only FLCCC Alliance's recommendation that is not evidenced-based.

For instance, here's their "Long COVID" protocol, which calls for treatment (on the basis of little to no evidence) with:
-Ivermectin
-Steroids
-"Treatment of Suspected Mast Cell Activation" (various agents)
-"Macrophage/Monocyte Repolarization Therapy"
(various agents)

One can disagree about role that social media companies should (or shouldn't) play in censoring misinformation — I fall more on the ACLU end of the spectrum — but the push by @BretWeinstein & others to cast ivermectin as a suppressed miracle cure is goofy, and indeed harmful.

A large, high-quality trial can be conducted. If benefit is demonstrated (and a priori that's improbable with such a re-purposed drug), that would be wonderful! But based on where things stand now, these individuals, including critical care doctors, are making extraordinary, ...

... indeed grandiose claims that is simply not backed by adequate evidence, both for ivermectin and their "protocols" more broadly. It's grossly irresponsible.

It's not at all surprising that this happened- earlier with hydroxychloroquine and now with ivermectin. The "allure of the miracle cure" exerts such a strong pull - both patients and physicians are potentially prone to perceive such a cure based on narrow reading, or experience

... even if motives are the best (they aren't always).

One takeaway is that we need a broader public understanding of why we need high-quality, randomized clinical trials with hard endpoints before approving / using the vast majority of drugs...

There's a general sense that the direct observations of physicians ("My patients got better!") or patients ("I felt better!") is powerful evidence of efficacy. That's understandable, but it isn't: frequently such observations suggest efficacy for drugs that are useless or harmful

The reality is that we are all prone to excessive belief in what our own observations and experiences reveal about cause-and-effect relationships — it's not a sign of an intellectual deficit but just the fundamental, invariable limitations of one particular mode of human inquiry.

Similarly, we can be excessively credulous about physiologic explanations for efficacy, e.g. a molecular hypothesis for why drug X helps disease Y. At issue here is a biased assessment of how fully we understand real-world biological drug effects, which are profoundly complex.

We also inappropriately accept "surrogate outcomes" - lab values or imaging findings that we can track, versus hard outcomes (e.g. death). If Alzheimer's is associated with more amyloid in the brain, and amyloid is bad, and a new drug reduces amyloid levels — isn't that good?

Not necessarily — regardless of the overall correctness of the biological hypothesis. If the drug doesn't also improve either the length or quality of life, who cares what "the levels" do?

Yet the FDA is using such surrogate outcomes for approvals more and more.

Some of these issues didn't matter nearly as much say 100 years ago, except to scientists and physicians perhaps, but with the tremendous rise of medicine as a presence and force in our daily lives — and a major issue in politics and policy — I think that teaching of ...

... these and related issues should perhaps be a part of our basic primary education.