Trump’s miracle cure is no such thing – probably
Is hydroxychloroquine – the drug Donald Trump’s been taking – of use in the prevention or treatment of COVID-19?
One might have thought, or hoped, that seemingly simple questions such as this would find a swift and definitive answer. After all, there have been millions of cases worldwide, hydroxychloroquine is a widely available drug and there have been untold numbers of dedicated researchers into precisely these questions.
And yet, six months into the epidemic, there is still uncertainty. This is partly because there has been no co-ordination of efforts and partly because the questions are much more complex than might at first sight appear.
Hydroxychloroquine has been shown in the laboratory to be bad for the virus; moreover, the drug is used in autoimmune conditions such as lupus. The fulminating immune reaction to the virus is what is most dangerous. So it seems to stand to reason that hydroxychloroquine, alone or in conjunction with antibiotics, might be of value in the treatment of the disease.
A paper in the Lancet, however, appeared to show that the drug was not only of no value, but positively harmful. The authors analysed the results of 96,000 cases from around the world, comparing those who were treated with the drug and those who weren’t, controlling for a large number of factors such as BMI (body mass index). This is important because it has emerged indisputably that the obese are more likely to die from COVID-19 than the lean.
The BMI is calculated as a person’s weight in kilograms divided by his or her height in metres squared. The paper, purportedly demonstrating the inefficacy of the drug, implied that the BMI was known in all 96,000 cases and therefore could be adequately controlled for. But the chances that 96,000 patients with COVID-19 had their BMI calculated are nil.
In other words, the authors must have, at best, extrapolated from the data they had to produce data they hadn’t, which is scientifically illegitimate. The authors, unable to justify their data, were forced to retract their paper.
None of this means that the drug actually is effective; it means only that we still can’t be sure.
But even if it were ineffective as treatment, it might still be effective as prophylaxis. A paper in the New England Journal of Medicine tried to answer this question. Just over 800 people who had had contact with proven COVID-19 patients were assigned to receive either placebo or hydroxychloroquine as prophylaxis against developing the disease themselves. Neither their doctors nor they themselves knew which they received.
In brief, the results showed that hydroxychloroquine had no statistically significant protective effect against COVID-19, and more people suffered side-effects than those receiving placebo (though the side-effects were not serious).
However, the trial was severely limited in its implications, even if reproducible. It was too small to detect any serious side-effects of the drug that occurred in fewer that one in 150 cases. But a fatal side-effect that occurred in, say, one in 300 cases would be very significant in a drug given to billions of people, especially if the efficacy of the drug were slight or minimal.
Moreover, the results applied only to people similar in all characteristics to those enrolled on the trial and given the same dosages of the drug. As a guide to doctors, it was almost useless.
This illustrates a problem of pharmacological or pharmaceutical research, namely the infinitude in number of possible hypotheses. It can always be argued that the reason a drug did not work is because it was given in the wrong dosage, by the wrong route and at the wrong time. An Italian study once showed that anti-hypertensives work better when taken at night.
All one can say at present is that there is no satisfactory evidence that hydroxychloroquine is of value in either the treatment or the prophylaxis of COVID-19.
Uncertainty remains, therefore. In the words of the song of Flanders and Swann, it all makes work for the working man to do.