There's no doubt about it. When people are scared, when they're stressed, when they're tired, they're not at their best. The same thing that's true for an intern at the end of a 30-hour shift is true for an anxious person in year three of the pandemic. But ultimately, the best medical and public health decisions are the ones based on the best available evidence, and the most deliberate thinking. That’s what I hope to do in these pages.
I joined my colleagues in writing Sensible Medicine for a few reasons.
First, I believe we need to hear a range of opinions to make sense of current events and medical practice. No one person has the monopoly on truth. And often many people are right, to some degree. Sensible medicine is a place that will feature a range of views. Even some that I may disagree with!
Second, Medicine has always captured many dimensions of life. It ranges from the molecular to the poetic. Doctors have to interpret clinical trials and have hard conversations. It's the breadth of the profession that makes it constantly challenging and eternally validating. I'm thrilled that Sensible Medicine will be a place that features stories from the trenches of medical practice, as well as takedowns of research articles.
Third, I'm a student and scholar of evidence-based medicine. That means something to me. It means that when we have really good evidence, we follow it. And we don't prioritize anecdotes and opinion above the best available evidence.
It also means that when you don't have great evidence, you're honest about that. You don't lie or oversell the truth. It's okay to tell people this is my best guess, but it's not okay to embellish or falsify. During the pandemic, we ran into a lot of situations where people outright lied about the evidence instead of acknowledging its deep limitations.
Evidence-based medicine means that, as much as humanly possible, you conduct studies to reduce uncertainty. You don't live mired and ignorance for the rest of your life. Again, during the pandemic I saw many people create excuses for why we are not generating evidence. Those excuses were almost always vapid. Recently, we published a study debunking many of the misconceptions about randomized control trials.
But if we're perfectly honest. All of these deficiencies existed before Covid-19, and all will persist thereafter. We have often adopted costly, toxic, invasive medical practices on the basis of limited evidence. Brave investigators have called for randomized control trials. Rarely they have been performed. And when they have, as often as they validate practice, they contradict it. Trials testing unproven established medical care frequently result in medical reversals. Adam and I detailed this in our book: Ending Medical Reversal.
Someday COVID-19 will be over. And the New York Times will return to its hard-hitting coverage on the pros and cons of eating blueberries or drinking coffee. Sensible Medicine will be a place to discuss the latest medical news, health policy bills on the docket, or Supreme Court rulings that affect the practice of medicine.
We will still need to re-learn the principles of evidence-based medicine for years to come. I hope Sensible Medicine is one place where I can remind you of that. If you appreciate our project, share this post.
Vinay Prasad is a hematologist-oncologist and Associate Professor of Epidemiology and Biostatistics, and also writes the substack Vinay Prasad’s Observations and Thoughts
It is "common knowledge" in medicine that HCQ doesn't work. I don't think that the evidence supports this belief in _one particular case_--when treatment with a clinical dose of HCQ begins within 72 hours of symptom onset.
There have been various trials of HCQ--many showing no benefit--in hospitalized patients when treatment is started late. This is mostly uncontroversial among HCQ adherents, because the working hypothesis is that HCQ is an antiviral which is best given before viral load achieves a maximum, which, in mild cases of healthy people, has been found to be close to 72 hours after symptom onset. We would expect that in high risk people, treatment should likewise be started within 72 hours for best prognosis, even if the viral load doesn't reach a maximum until later than 72 hours because likely the viral load in high risk people is much higher than in the healthy group and viral replication is best stopped early.
What is the evidence for the 72 hour optimal treatment window? Not a lot, because the working hypothesis has barely been tested. Accinelli found that there were no fatalities in his treatment population when treatment began within 72 hours of symptom onset in his retrospective study of 1265 patients treated with HCQ.
"Hydroxychloroquine / azithromycin in COVID-19: The association between time to treatment and case fatality rate"
"Results
A total of 1265 COVID-19 patients with an average age of 44.5 years were studied. Women represented 50.1% of patients, with an overall 5.9 symptom days, SpO2 97%, temperature of 37.3 °C, 41% with at least one comorbidity and 96.1% one symptom or sign. No patient treated within the first 72 h of illness died."
https://www.sciencedirect.com/science/article/pii/S1477893921002040
Accinelli suffers from studying a young population. There was a fair amount of control of the patient population, which we see in the methods. Accinelli is promising--that is the best that we can say.
You can find many "early treatment" studies at c19hcq.com/ . Unfortunately, in these studies, the median time to treatment often begins after the 72 hour treatment window post symptom onset (PSO). When you look at the median time to treatment in these studies, the further that the median value is from 72 hours, the less benefit from HCQ we see.
So the 72 hour PSO covid treatment hypothesis (which should really be attributed to one of the authors in the Accinelli study) suffers from a lack of adequate testing. (This hypothesis would apply to all proposed antivirals against covid.) However, Accinelli's data is promising and suggests that the 72H-PSO hypothesis should be tested by RCTs with various antivirals, including remdesivir, HCQ, molnupravir, ivermectin, paxlovid, the various MAB treatments, etc.
Thank you for saying exactly what I have been thinking! Unfortunately, when you quote the evidence you often get the smackdown from those who don't want to hear it. I'm exhausted from dealing with this and looking forward to reading posts that are actually informed and intelligent. The best part of the pandemic has been finding you and Zubin and your candid posts and podcasts.