Wednesday, August 17, 2022

Stop ignoring the evidence on Covid-19 treatments

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Thanks to Twitter, now you can watch a doctor’s heart break in real time. Like everyone else, we have often expressed our feelings during the pandemic – our discouragement at all deaths, our anger at avoiding them – but there is another kind of public display that is more unique to our discipline. I like to call it post humiliation. It shows up when you realize that the published data on preferred treatment is just not on your side.

There was a lot of humiliation in the publications a few years ago, when studies began to oppose the magical healing powers of vitamin D. Researchers had noticed that people with low vitamin D seemed have a greater chance of developing a range of problem drugs, and many serious doctors have directly joined. Recent data from well-designed clinical trials suggest otherwise. Could taking vitamin D prevent cancer or heart disease? Good, no. What about diabetes and depression? No, and no again. But grief, as it often is, played out like denial. It wasn’t the treatment that was bad; that was the science used to study it. If randomized controlled trials have opposed the use of vitamin D, it is because they were not performed correctly. Maybe the the doses were too low to have an effect; or, if the doses were high enough, then the timing was not right. “If you are already too sick or have an illness, it is too late for vitamin D”, a doctor tweeted when a major trial found that the treatment did not save any life. (Never mind that prevention trials are also insufficient.)

While some physicians like to turn a blind eye in grief, others are looking for answers deeper in the data. A “subgroup analysis” – where you may end up selecting only the parts of a data set that support your theory – is a useful tool in this regard. Doctors who weren’t deterred by the 26,000-person study of vitamin D supplements and cancer got to work quickly publication drawing the same results. This one suggested that the vitamin could, at least, prevent more serious cancers… as long as you only looked at skinny patients. (If that hadn’t happened, they might have tried to divide patients by eye color or by favorite Seinfeld episode.)

Latest source of post humiliation is convalescent plasma, alleged Covid-19 miracle drug pulled through a needle of people who have recovered from an infection. Former Food and Drug Administration chief Stephen Hahn last summer promised that beneficiaries would see a “35% improvement in survival”. Experts quickly highlighted that he was only looking at the tiny subset of data that was most favorable to plasma. Subgroup analysis strikes again! But still, doctors jumped at every opportunity to help their patients. In December alone, more than 100,000 units of convalescent plasma were delivered in the USA.

Our enthusiasm was not entirely unfounded. It’s reasonable to think that giving sick patients someone else’s natural antibodies could help them recover or even save their lives, and doctors have tried convalescent plasma to at least treat viral illnesses. so far back like the Spanish Flu of 1918. Here’s the problem, though: the evidence for its benefit has never been very good. I can forgive those old doctors of 1918, but a Systematic review of the work published in 2013 was based on “mostly low-quality and uncontrolled studies”. Then this month, the biggest medical study in the pandemic – the UK Recovery trial – turn off her preliminary results on plasma, and they are not promising at all. Eighteen percent of Covid hospital patients who received treatment died within 28 days, compared to 18 percent of patients who did not receive plasma. You don’t have to be a scientist to understand the implication: plasma didn’t help.

You might think that would be enough to change your mind. After all, Recovery’s simple, haphazard design has been final for other drugs. By recruiting tens of thousands of participants, he was able to answer our most important question about a number of potential Covid treatments: is it actually keeping you from dying? For hydroxychloroquine or the antibiotic azithromycin, the answer was no. For the steroid dexamethasone, it was yes. Now for the convalescent plasma, it looks like we have another no.


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