Wednesday, April 29, 2020

The Trouble with "Evidence Based" Medicine

Is this loose, informal transmission of anecdotal findings--call it chatter, call it rumor--part of medicine?  It isn't what anyone taught in medical school; it doesn't fit in with the professional's image as a purveyor of rigorously tested interventions. But continuous, iterative clinical knowledge--the kind that can be updated minute by minute--is invaluable during this tumult, when time is of the essence and there's scant research to fall back on."
--Siddhartha Mukherjee, MD (Columbia P&S)




Daniel Griffin, MD is one of my favorite doctors and his appearances on This Week in Virology are a highlight.

But I have to dissent regarding one point he tried to make about "Evidence Based Medicine" on TWIV #606. And this is no quibble, but an essence.

Trying to analyze how we come to agree on a course of therapy for patients in the real world, whether the ICU or the ward, Griffin analyzed the way medical therapies get established--and in this he did something I have never heard but I thrilled to his observations because they were  so spot on.
Daniel Griffin, MD, a prince among physicians

It was when he tried to suggest an alternative, we parted ways.

First, we should listen to his observations, and understand it comes in the backdrop of President Trump shouting from his podium we should be using hydroxychloroquine on all COVID 19 patients because Mr. Trump had heard, IT'S JUST AMAZING. 
Most doctors hear that sort of testimonial, Hallelujah & Praise the Lord, and recoil, appropriately. 

Griffin also recounts cases of doctors who feel helpless and desperate to "just do something" to save their patients.

But, as he said this, I thought of Franklin Roosevelt saying, about the Depression, another pestilence which we did not understand, it was important to simply try something, anything, and if it did not work, try something else.  Better than the do nothing impotence of Herbert Hoover. It's fine to define the ideal, but we do not live in an ideal world, on the wards. 

Griffin says when he went to medical school there was no effort to base therapeutic practices on prospective, double blind studies and he says, "I still remember one senior physician saying 'You're telling me one well controlled prospective study of a thousand patients is better than my years of experience' and we said, 'Yes, that's what we're saying.'"

And I thought, I went to medical school a decade earlier, and just 30 blocks up the street from where Dr. Griffin went to medical school and we tried, as did our faculty, to base our therapies on the literature, but the literature was often changing and contradictory. We were constantly citing  articles to each other, and we had only a small fraction of the information available to us we have today with the internet and with podcasts and streamed conferences.

Griffin goes on to outline the types of persuasion used on the ward or the ICU to get a particular approach accepted:
1/ The "In my experience"  mode:  where you're asked to listen to  someone "who has been making the same mistakes with increasing confidence over an impressive number of years," as Griffin describes it. The 3 most dangerous words on the ward. "In my experience."  But are we to discount experience on the ward? Is "proning" the patient  from lying on his back to front not "in my experience"? 
2/ "Vehemence based medicine": Someone with a loud aggressive confident voice "confidence based" drives care by force of intimidation. This is the sort of bullying, which hurls overt or implied accusations of ignorance, fecklessness at those who might oppose it. 
3/ "Eloquence based  medicine" by which Griffin sees doctors beguiled into accepting an approach because that approach seems to make sense, to be based on solid theory in the absence of rigorously tested medicine. If we believe, in theory, the 1st week of COVID is when the viral replicates and the 2nd week is when all hell breaks loose because of an over reaction of the immune system, which causes cellular damage, endothelial cell injury and the unleashing of an avalanche of clotting, a consumptive coagulation cascade and widespread embolic bombs to cut off oxygen to brain, lung, liver and kidneys, then we should be focusing anti viral medications like remdesivir in the 1st week and glucocorticoids and anti IL6 drugs thereafter, but where are the prospective, double blind placebo controlled studies? 
4/ "Diffidence based medicine" when the doctor says, "No good evidence here."
And here Griffin is most puzzling, "There may be no good answer but there are certainly a lot of bad answers" 
5/ "Nervousness based medicine" Which Griffin describes as the attitude,  "the only bad therapy is the one you forgot to do," as in,  "I'm going to do everything because maybe one of those things is good." So "when the family calls you on the phone and asks did you try A, B and C, I say we didn't do that because we tried what we tried what we actually thought what would make your loved one better." 
But he has, implicitly admitted, we really don't know what will make your love one better; we are simply afraid of doing something to make him worse: Primum non nocere. 



So what Griffin proclaims as his approach is "Careful observational based medicine where we are trying things" So he puts a patient in anticoagulation. "We're seeing a lot of people clotting and so we anticoagulated and the numbers went from 8 a day to much lower."  
But how is that different from "eloquence based medicine" or "diffidence based medicine' or "nervousness based medicine," except when Dr. Griffin tries it he thinks he looks more critically or carefully for the response than others do?

When he discusses clinical trials and how some studies deviate from the golden standard,  he describes Paul Merek's observation of treating septic patients with vitamin C plus steroids where he did a clinical trial and saw mortality rates from sepsis drop 70% . But there was non control group.   Then a prospective controlled trial was done and found no benefit. So what Griffin is saying is some observational/retrospective trials are misleading. 

Then Griffin describes an observational trial he did using steroids + Tosi (an IL6 receptor inhibitor) to treat cytokine storm which showed a survival rate of patients rise from 3% to 21% but it was not a controlled trial, nor was it a blinded trial which is meant to correct for physician bias. 

When he describes his own recommendations, based on his own experience in treating patients, it's hard to see how much more objective and scientific he is than doctors who he criticizes as practicing diffidence medicine. 

He mentions patients who are afraid to go to the hospital so they stay home and let their appendices burst at home.  He decries denying an appendicitis an appendectomy. But there are plenty of studies where patients are treated with antibiotics rather than surgery and seem to do as well at least in the short term. So he has bought into an experienced based therapy himself, namely, appendectomy.

Griffin is the sort of physician I admire: He is confident enough in what he knows to be humble; the really good doctors are almost always humble, more impressed by what they do not know than by what they do know. 

But he is clearly offended by the "cowboys" and bullies he has to deal with on the wards whose egos ascend over the best interests of their patients.

To hold out evidence based medicine as the true holy grail however, is to deny the impossibility of limiting therapy to  evidence from double blind prospective controlled studies. There simply are not enough of those to apply to every clinical problem, or to the complexity of multiple problems at once. 

As one of the TWiV crew asked (I think it was Rich Condit, a PhD self proclaimed "lab nerd"): You are doing so many things to the patient, how do you figure out which part of the magic sauce was important?  Condit is not a clinician, but he had the experience of learning how to do lab science and he knew he had slowly accrued experience which helped him work more efficiently.

Ward medicine is something like the problem of developing a car which drives itself, as opposed to being driven by a experience driven driver who takes in multiple cues at once and without doing a study when he sees a ball bounce along the grass toward the road, hits the brakes because he knows (even if his intelligent car never notices the ball) that balls rolling down to the road are often followed by children in pursuit.


Semmelweiss observed that women who delivered their babies  in the hospital in Hungary  got infections after delivery, but women who delivered at home almost never did. He also observed physicians going from autopsy room to bedside and examining the vaginas of post partum women without washing their hands or using gloves. (Rubber gloves came much later.) He may not have had double blind controlled prospective studies but he had observation. He did not even have solid germ theory, but he had the ability to make connections and he advocated for washing hands between examining patients. He died in 1865, well before microbiology and germ theory had taken hold in medical practice, but he saved lives by cleaving to an observing, in his experience. 


Daniel Griffin notes he's stopped using hydroxychloroquine, tosilisimab, remdesivir and azithromycin which were therapies without proper studies, but his reason for stopping them was his own observation they didn't work.  So he acts based on his observations, while he awaits better studies; he used them for a while, which is what other doctors have done. Try something until you lose faith. 

Putting patients prone, which he's observed increased oxygenation of his patients, has no evidence based studies, but as he says, "It seems to work." 

So, having stated what amounts to a practice of purity, he quickly diverges toward what seems practical. 

Still, he is trying for an ideal; you can't criticize him for trying for exalting an ideal,  and if your mother got sick with COVID19, you'd want him taking care of her. 




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