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.
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.