UPDATES: The discussion of this paper has gone back and forth, and the cause is that neither Alex nor I read the paper carefully. I just skimmed it, and Alex read it quickly but paid most of his attention to the tables. That led to this first update in which he concluded (and I agreed) that the study wasn’t very useful at all:
In two comments below, my own physician, Dr. Alex Lickerman, who carefully read the study I describe below (see his first comment and his second), noted that the sickest patients were the ones more likely to be given the chloroquine drugs, and were also the patients with the highest comorbidities—factors like heart disease that would tend to make them sicker. In other words, as Alex notes,
So–was it the drugs that were responsible for their increased likelihood of death or the risk factors already known to increase the likelihood of death? We simply can’t tell from this study. This is the problem with the observational study design. We CAN almost certainly say that hydroxychloroquine and its ilk don’t improve survival in COVID-19, but whether or not they increase mortality in COVID-19 we don’t yet know.
This is only part of his analysis; read the whole thing in comment 1. He also notes in his second comment that there is no evidence that using hydroxychloroquine as a preventive has any benefit.
I am guilty of not having detected the flaws in the study, which are, I found, not even clearly pointed out by its authors in the traditional “here-are-some-weaknesses-in-this-study” part of the paper, and I thank Alex for the clarification. But even more culpable are the reviewers of that study, who did not insist on a clear outline of its limitations, as well as the medical/science journalists, who touted the study uncritically (like me!) Alex has helped me learn that many medical studies, even in journals as reputable as The Lancet, are pitifully weak or even fatally flawed.
UPDATE 2: In a very useful comment, reader BillyJoe noted that the paper does indeed say that the paper controlled to some extent for comorbidities, so its conclusions are stronger than we thought: we can have more confidence in its conclusions that hydroxychloroquine and chloroquine are positively dangerous when given to people sick with Covid-19. Alex then said yes, he was wrong about the study not taking into account comorbidities, and has posted this comment in the thread:
Yikes! I’m guilty of the same criticism I made of others: not reading the trial carefully. You are absolutely correct that the authors made good-faith attempts to control for the inequalities/confounding variables between treatment groups. This is still a statistical adjustment, not a direct measurement as would be done in a randomized trial, so must be taken with a grain of salt, but to the authors’ credit, they address that.
The problem does remain that when you do the randomized trials, results are often different because of confounding variables the authors didn’t know about and therefore weren’t able to statistically adjust for—but also because sometimes their multivariate analysis (meant to adjust for known confounding variables)–also wasn’t adequate. So we still need a randomized trial to really know the answer definitively.
Nevertheless, I withdraw my criticism of the authors and the Lancet reviewers. I guess this is a good example of why science and statistics should always be done by more than one person! I’m quite embarrassed to have made this mistake. I apologize to readers and to our host, who must now fall on his sword with me.
Well, it’s official (I mean, of course, “provisional”): a new and large study published in the medical journal The Lancet (second link below; click screenshots to go to both articles) confirms that hydroxychloroquine and chloroquine not only don’t help patients seriously ill with Covid -19, but increases their mortality (in other words, kills them). Below is the CNN report, with a more layperson-y summary (my emphasis):
Researchers analyzed data from more than 96,000 patients with confirmed Covid-19 from 671 hospitals. All were hospitalized from late December to mid-April, and had died or been discharged by April 21.
Just below 15,000 patients were treated with the antimalarial drugs hydroxychloroquine or chloroquine, or one of those drugs combined with an antibiotic.
All four of those treatments were linked with a higher risk of dying in the hospital. About 1 in 11 patients in the control group died in the hospital. About 1 in 6 patients treated with chloroquine or hydroxychloroquine alone died in the hospital. About 1 in 5 treated with chloroquine and an antibiotic died and almost 1 in 4 treated with hydroxychloroquine and an antibiotic died.
Researchers also found that serious cardiac arrhythmias were more common among patients receiving any of the four treatments. The largest increase was among the group treated with hydroxychloroquine and an antibiotic; 8% of those patients developed a heart arrhythmia, compared with 0.3% of patients in the control group.
Note that the mortality in the control group was about 9%, rising to about 16% with chloroquine or hydroxychloroquine alone, and 20-25% when either of the chloroquine drugs was supplemented with an antibiotic (remember, antibiotics kill bacteria, not viruses like Covid-19. Clearly, refraining from using these drugs is the wisest course of action.
Here’s The Lancet study that went online today, and the findings and summary, while more comprehensive, are the same (“macrolides”, as is meant here, refers to a class of antibiotics that includes erythromycin). If you can’t access the paper, a judicious inquiry will yield it.
96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.
We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.
What Trump is doing is not only injurious to himself (I suspect his heart is a ticking time bomb given his weight and penchant for McDonald’s food), but sets a terrible example to the public. It’s a President flaunting quackery, and of course his supporters are more likely to dose themselves or ask for the drug if they get the virus. The saving grace is that no decent doctor will give an infected patient hydroxychloroquine.
But remember, Trump’s osteopath official physician, Sean Conley, in consultation with Trump, decided that the potential benefits outweighed the risks when prescribing Trump the drug as a preventive. That’s doubly shameful: a faux President being treated by a quack physician with a useless drug, and the President bragging about it and lying about the drug’s “benefits.” No wonder other countries look upon the U.S. with pity!