Hydroxychloroquine, Parachutes And How to Understand 'The Evidence'

Abstract

It is deliberately misleading to make general claims that hydroxychloroquine doesn’t work for CoViD-19. It is even more misleading to claim that “the evidence” proves that hydroxychloroquine doesn’t work.

To understand this, consider the use of parachutes. Consider someone who claimed that parachutes don’t work to stop death or serious injury when jumping out of a plane. What if they further claimed that “the evidence” proves that parachutes don’t work? Now consider if this same person advocated that because parachutes “don’t work”, we should ban their use and demanded that conscientious pilots who give a parachute to someone jumping out of a plane should lose their pilot’s license. Surely, such claims would be considered false and misleading.

Two classic parodies, published in the British Medical Journal, showed that the above statements about parachutes are technically true. In 2003, a straight-faced literature search found no high quality, randomized, placebo-controlled trials of parachutes. The fact that people usually get squashed to smithereens when they hit the ground without a parachute was just epidemiological data. There’s no proof the parachute makes any difference. It could be due to confounding factors or bias.

Subsequently, in 2018, a group of researchers actually did a randomized, placebo-controlled trial of the use of parachutes when jumping from a plane. There was no difference in death or serious injury in those who wore a parachute and those who didn’t. However, the participants jumped out of a plane 60cm off the ground while it was stationary.

So, it would, or course, be misleading to make the claim that the “evidence says that parachutes don’t work.” That is, the general claim that parachutes “don’t work” cannot be derived from studies where they are not used in the situation where they can provide benefit. Of course, everyone is going to survive whether you give them a parachute or not when jumping from 60 cm. It is egregiously misleading, and it would be lethal, to deprive someone of a parachute when jumping from 10,000 feet based on a study that tested a parachute at 60 cm.

Now let’s look at hydroxychloroquine. CoViD-19 is a disease with very different stages. And the vast majority of people, especially young people, are not going to die from CoViD-19.

The suggestion from a significant amount of epidemiological data is that, if given early in the course of the disease, HCQ might prevent progression to critical illness or death in at-risk population groups.

However, the randomized controlled trials (RCTs) performed to test the effect of hydroxychloroquine have been the equivalent of testing the effect of parachutes in the following circumstances: after a 60 cm jump; or pulling the rip-cord 2 feet above the ground after free-falling; or putting the parachute on someone after they hit the ground.

Different RCTs on hydroxychloroquine have had variable characteristics including the following: control groups with average ages in the 30s and 40s; a cohort with 99% of patients with mild to moderate disease; a cohort with death rates of 0.4%; a cohort with zero incidence of death or mechanical ventilation; patients already on ventilators or even ECMO; patients having symptoms up to 14 days before being commenced on hydroxychloroquine; patients having symptoms an average of 16 days before commencement of hydroxychloroquine.

Note: Funding: None to declare

Declaration of Interest: None to declare

Keywords: CoViD-19, coronavirus, hydroxychloroquine, randomized controlled trials