the battle between the ivory tower academics vs. the rogue cowboys
An internecine war is brewing about the treatment of COVID-19. You can hardly open up a journal or look at social media without getting caught in the cross-fire.
The cause of the schism is pretty simple. There are no proven treatments for COVID-19. Based on personal philosophy towards risk, this has divided practitioners along an ideological axis:
At one end are the Ivory Tower Academics, who argue:
- Any treatment which hasn’t been proven in a double-blind, randomized controlled trial among COVID-19 patients is experimental.
- Experimental treatments should be restricted to randomized controlled trials.
- Outside of a randomized controlled trial, patients should be treated with basic supportive care only.
At the other end of the spectrum are the Rogue Cowboys, who argue:
- Nearly all hospitals lack access to randomized controlled trials. So, while it sounds nice to recommend that treatments be provided within randomized controlled trials, this is unrealistic.
- Patients are doing poorly with basic supportive care only.
- Based on indirect evidence, it’s sensible to use some interventions which haven’t been proven to be effective in COVID-19.
You can’t run away from this ideological axis. Everyone will fall somewhere along it. The Ivory Tower Academics and the Rogue Cowboys merely represent two extremes – most of us will fall somewhere in-between.
There’s no “right” answer to this. Smart, well-intentioned people will disagree. In fact, medical societies are in active disagreement! For example, the SCCM guidelines recommended using steroid for intubated COVID patients with ARDS. Meanwhile, the IDSA guidelines recommend that steroid is experimental therapy which should be provided only within an RCT. War!
On paper, the Ivory Tower Academics will always look better. Their arguments are technically impeccable. It’s easy for them to paint themselves as the paragon of scientific virtue, while shaming others as irresponsible dilettantes. However, the closer one gets to the bedside struggle against COVID-19, the less compelling these intellectual arguments become. Thus, I daresay that among frontline providers actually caring for patients with COVID-19, the rogue cowboy mentality often has greater appeal.
One example of this is, yet again, the Infectious Disease Society of America guidelines for COVID-19. These guidelines recommend against any unproven therapies for COVID-19. However, at least one co-author of these guidelines works at a hospital which was publicly recommending hydroxychloroquine (at the time that the IDSA guidelines were published). Thus, there was a blatant schism between academic guidelines and actual bedside care.
this battle ignores the larger issue at stake: Failure of the American research infrastructure
Everyone loves a nice ideological battle! It’s intellectually satisfying to fling insults and arguments at the other side, while high-fiving your comrades. So this battle continues to rage on with increasing fury.
Unfortunately, this battle steals our attention from a more important issue, which is that American research infrastructure has failed us horribly. Indeed, this failure is the main reason that we are waging this ideological battle at all.
To date, over a million people in the United States have contracted COVID-19 and over 50,000 have died. Those numbers are mind-boggling. To add insult to injury, we have failed to learn much from this experience.
An epidemic should present an easy opportunity to perform clinical research. Literally thousands of patients were pouring into hospitals with a single disease process. It should have been simple to design several pragmatic, multi-center studies which could have each recruited thousands of patients. Pragmatic studies could have investigated simple interventions (e.g. heparin anticoagulation or steroid). These studies wouldn’t have been fancy (e.g. blinding would be impossible) – but they could have provided vital information.
Instead, relatively few patients were included in randomized controlled trials. The dust is settling now and different hospitals are publishing their experiences with COVID-19 – which are generally ambiguous. A few industry-funded studies will likely emerge soon. Overall, this represents a tragically missed opportunity. As we re-tool for the next wave of COVID-19, we remain in a weak position.
Why did we allow this opportunity to slip through our fingers? Several reasons, but one main one is the delay required for any trial to gain approval of institutional review boards (IRBs). By the time RCTs gained IRB approval, the surge had already passed by. The difficulty of obtaining IRB approval alone may have deterred investigators who were busy managing patients. IRBs are designed to protect patients, but in a time of pandemic they prevented us from properly investigating this disease – thereby placing the remaining populace at risk.
Research is difficult, but it can be done promptly. For example, a lab at the University of Vermont devised a new way to perform PCR on nasal swabs which omits RNA extraction, perfected it, validated it, and published it – in under a week! Innovative, energetic people are available, and they can make great progress rapidly if allowed to do so.
We’ve grown so accustomed to the chronic failure of our research infrastructure, that nobody seems to even recognize this as a problem. Clinicians take it for granted that RCTs are only available at a few, selected centers. It’s widely understood that only a few RCTs will be performed – usually the ones with industry sponsors who have the time and funding to push them through. Fifty years ago we put a man on the moon, but today it seems like an insurmountable challenge to organize an open-label randomized trial of prednisone.
Instead of endless philosophical arguments over the use of experimental therapies, we should be arguing about the most effective and ethical ways to perform research during a pandemic. If we could devise a nimble system to perform large-scale pragmatic trials, then perhaps we could bring the cowboys and the academics together to serve the greater good.
conclusion
We’re nearing the end of the first chapter on COVID-19. In reflecting on the past few months, our failure to rapidly organize pragmatic trials has prevented us from learning very much. This failure of RCTs has led to ideological trench warfare between the Ivory Tower Academics and the Rogue Cowboys. As intellectually satisfying as it might be to partake in this battle, the battle itself is a dangerous distraction from the larger problem – failure of our clinical research infrastructure.
(Image credits: Ivory Tower & Rogue Cowboys)
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Thanks Josh. I appreciate your editorial comments. I’ll be transparent and tell you that I’m no where near an academic, research oriented physician. I just battle day-to-day trying to keep up with what’s new, relearn my basics, and expand my understanding of how I can be a better doctor to my patients. In so doing, the Ivory Tower research facilities and faculty seem very far off and untouchable. So much so that the very idea of performing simple research to find answers, though appealing, is a complete joke. I have read about the battles required to get research dollars and… Read more »
Is ANZICS the model we should be using? They seem to have their crap together and can move agilely on a multi-national level
Yes, I think so. I don’t know the exact organization of ANZICS, but they seem extremely awesome. Having a pre-established research network *before* a pandemic strikes is probably essential (otherwise you’re playing catch-up).
What do you do when the evidence is that evidence based medicine is failing. There is a reason it is called a novel virus. Is anecdotal and observational evidence such a bad thing when it is coming from respected doctors?
“Respected doctors” – Oh dear!
You mean like Peter Piot, who helped discover Ebola, and David Heymann, who is now an expert advisor to the World Health Organization, and all of Médecins Sans Frontières (MSF) arguing against randomization in the ZMapp trial during EBOLA? They even wrote a rather vehement letter to the LANCET – https://doi.org/10.1016/S0140-6736(14)61734-7 expressing shock and horror at the prospect of withholding potentially life saving treatment to the control group, if one conducted a methodologically robust trial
We all know what happened to ZMapp later on, when a proper study was conducted – don’t we?
Other smarter people (Vinay Prasad) state it: Rare is a treatment that has a truly golden saving effect and lacks harm. It’s usually a modest treatment effect and more than understood.
But
I’ve been doing this long enough to remember when virtually all resuscitation research was put on hold because of the requirement for informed consent.
IRBs wouldn’t approve the research without informed consent from the patient in cardiac arrest.
Unfortunately this is probably the consequence of a fractured healthcare system as a whole. There are few unifying process to speak of. I am not optimistic that this can be fixed any time soon.
thank you for calling attention to this josh. I have never felt so helpless and disappointed as trying to navigate everyone’s opinions on how to treat coronavirus. when we started our COVID ICU at the start of the surge in NYC, I looked around for ways to get our–and everyone else in the city’s–data out immediately, so others not yet affected could learn from what we were doing. what I encountered was a research infrastructure that is focused on slowly, methodically churning out publications. the main american data registry for COVID is designed to start producing publications some months from… Read more »
LEt’s not forget CV bloat. There was a NEJM article that had like 12 people describing how they created an ICU in their OR rooms. They were from elite NYC hospital so it gets in…but come on…it’s not like other places were not figuring that out.
Josh, As a ‘burnt out’ critical care physician (I am retired now), I can clearly recognize the angst in your sentiment. I am also old enough and ugly enough to call a spade a fucking spade. There are four kinds of people in the world – the helpless, the stupid, the bandit and the intelligent. One should never under-estimate the power of collective stupidity. From being driven mostly by GREED (for name, fame and wealth – the three are siblings), the world has shifted to being driven by FEAR and GREED and that, is a dangerous place to be because… Read more »
I would like to subscribe to your newsletter. I’m worried about all the recklessness that I’m seeing on a daily basis, and the justification is often that we simply want to do “something.” It’s absolutely the Wild West out there, and some of the “respected doctors” are really advocating that we just shoot from the hip based on extremely limited and flawed evidence. I worry that overly aggressive anticoagulation may be our second big mistake after the hydroxychloroquine mess. On a call yesterday with a large academic medical center discussing anticoag for COVID, a nephrologist repeatedly called for full anticoagulation… Read more »
Fully echo your anguish, Andrew! Isn’t it ironic that the best of our training in critical thinking seems to desert us completely in a crisis, and the guys (“respected doctors”) who are supposed to be our ‘pillars of strength’ run around like headless chicken without a fucking clue? We have been in this situation before, during the EBOLA outbreak in the first half of this decade. If you haven’t come across this article already, this here is a link that you might want to look up – https://www.businessinsider.in/science/news/were-repeating-one-of-the-worst-mistakes-of-the-ebola-outbreak-in-the-hunt-for-a-coronavirus-cure/articleshow/75434954.cms. I may have mentioned the same in response to a comment elsewhere… Read more »
“All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.” In general, key opinion leaders in medicine have always believed, that they are practicing in the most sound way. That includes their process, methods etc. It happens in every field, but in medicine, it generally stymies advances. History, continuously proves that the evidence and the methods aren’t accurate. Just think about what doctors were doing 50 years ago. Thats how what we do today will be observed by future doctors. However, in a circumstance where you are dealing… Read more »
I wonder if a solution might be to have third party research groups (contracted, mandated or voluntary) that help hospitals without research infrastructure sift through data and run trials while the providers continue to work on the front lines and provide input to the groups. Your totally right that a few institutions are known as the RCT castle. Maybe we adopt the national health model of providing national research support to your everyday hospital.
Hi Josh, Have you seen what the UK did by developing trials in hibernation after swine flu? We set trials up on a national scale which were in hibernation and ready to go when the next pandemic. When coronavirus hit these were rapidly converted into corona trials and we now have several trials, including RCTs of Azithromycin, Tocilzamab, HCQ, Dex and Lopinovir/Ritonavir running. These already have thousands of patients enrolled and will likely report in June. NIHR set these up and it’s a great example of how a national research structure, embedded into a national health service can function at… Read more »
Exciting! The NHS is going to save more lives than their own citizens it seems.
I will take the rogue cowboy if I’m struggling to breath. HCQ, antivirals whatever….., in vitro, observational, level 6, anecdotal…I will take it! Because I know that when you guys get out your laryngoscope…..I am fucked!
1) yes, total travesty that US wasn’t engaged in more covid trials over last 2mo 2) yes, it’s an basically an infrastructure problem 3) fixing that will require nationalized healthcare system where all hospitals are under one umbrella, driven to serve the interests of the public at large above all else 4) this has been called “politically untenable” 5) maybe an economic and moral depression will make it tenable 6) articles like this help start that discussion and some well thought out published estimates of excess deaths and $ lost due to this lack of infrastructure would help too #noamchomsky… Read more »
I will take the rogue cowboy if I’m struggling to breath. HCQ, antivirals whatever, in vitro, observational, level 6, anecdotal…I will take it! Because I know that when you guys get out your laryngoscope…I am fucked!
Excellent post as usual. When reading the Zhou/APRV paper one point is just how much ARDS a single center was able to see to generate a study relatively quick. But, that’s China’s medical system and population base. And, we have a similar opportunity here and we missed it completely. Like so completely. I’m at a community hospital in the NYC suburbs and we have seen about 200 covids admitted, intubated about 75 max at one point. Intensivist shifts come and go. The variation in care flat out astonishing. I can supportive care up the wazoo for a week and then… Read more »
Thanks Josh. I suspect you are closer to the Cowboy. & it is heroic to stand up. I think like many other things many academics on the opposite extreme are fine with their perspective until its a family member at the other end. There opinions tend to then change rapidly when they move from the theroetical towards reality.
@drmikeny
Thank you for the analysis. We can extrapolate this analysis for all clinical research, not only during the covid crisis.
Thanks josh, I really appreciate this article.