If I get intubated, give me dexamethasone!

A really big deal for severe COVID

COVID news so far has been super depressing.

The number of infections. The deaths. The social isolation. The unemployment numbers. The economic standstill.

We’ve been grasping for positive news anywhere we can find it. So when the ACTT trial came out showing a real benefit in COVID from remdesivir treatment, it was big news!

But now the RECOVERY data on dexamethasone has blown remdesivir out of the water. To understand why, I think it’s worth spending a few minutes thinking about how we quantify effectiveness of a medication.

How do we measure the effectiveness of a medical intervention?

I’m sure you’ve seen articles in the newspaper about how a new class of cholesterol medications reduces risk of a heart attack by 20% or that a purified drug derived from fish oil reduces heart attacks by 25%.

What do these numbers actually mean?

Whenever the effect of a medication is reported in the media, the number that’s reported is generally the relative risk reduction. But relative risk reduction only gives a small part of the story.

In order to understand this better, you need to know the absolute numbers, not just the relative ones.

Let’s look at an example

Hypothetical medication A reduces your risk of dying by 20%.

If your risk of dying to begin with was only 1%, a 20% relative risk reduction only lowers your risk to 0.8%.

Yes, it’s a 20% reduction, but in practice it’s only a 0.2% change.

Understanding the absolute risk rather than the relative risk is crucial to interpreting how “effective” medication A is.

The story changes as your risk increases - if your chance of death is 50%, then that same 20% reduction means your risk of death drops down to 40%.

Now we’re talking about an effect that’s worthwhile.

Talking about just the relative effects of a treatment is profoundly misleading!

Once we understand absolute risk, we can figure out how many people need to be treated

We generally measure the effectiveness of a medication with something called the number needed to treat (NNT).

The NNT is the number of patients who need to be treated to prevent one additional bad outcome.

The NNT is calculated by dividing 100 by the absolute percentage difference between the intervention and a control. So in our hypothetical example of a 20% relative reduction dropping your chance of dying from 50% to 40% means there is a 10% absolute reduction.

100/10 = 10. This means our NNT is 10 - so we need to treat 10 people with the medication to prevent one death.

The majority of the medications you take have an NNT of waaaaaaay more than 10. Many are probably over 50 or 100. I’m sure this is almost never explained when a doctor prescribes a medicine for you! An NNT of 10 is considered a pretty fantastic medication effect.

The fact that this type of information isn’t generally transparent is a real problem in medicine. Many of our most prescribed medications have a really shitty NNT.

Now, NNT isn’t the only thing that matters when you’re deciding whether to take/prescribe a medication. But it does matter and it’s the best way we have of quantifying effectiveness.

So tell me about the RECOVERY trial and dexamethasone.

This was a gigantic study - over 6000 patients - looking at some really sick patients with COVID. The risk of death was high: more than 1 in 5 patients in this trial died. The majority of patients were under 70, but patients over 70 were represented as well.

About 2/3 of the patients were male, and they started treatment with dexamethasone more than a week after the onset of symptoms.

In patients who were intubated and received dexamethasone, the risk of dying dropped from 40.7% to 29%. This is an absolute reduction of over 11% and an NNT of 8.5.

You almost never see a treatment effect this big with medical interventions in critically ill patients!

The effect wasn’t as big in non-intubated patients requiring oxygen therapy, but it was still there. NNT in this group was closer to 25.

Patients who didn’t need extra oxygen didn’t seem to benefit from dexamethasone.

What’s the bottom line?

The RECOVERY trial is huge news and dexamethasone should now be considered part of the standard of care of treatment for COVID patients who are sick enough to require extra oxygen or need to be intubated.

Every day, we learn more about how to treat this disease. Seeing this magnitude of benefit from dexamethasone in the sickest COVID patients is fantastic news.

In other words, it’s a big fucking deal.

P.S. The original version of this article had a typo and said “dexamethasone should not be considered part of the standard of care” instead of “dexamethasone should now be considered part of the standard of care.” This mistake has been corrected.