Chloroquine trial exaggerations
Q: Did you see hydroxychloroquine is back?
A: No
Q: In the Herald (blamed on news.com.au) ‘Hydroxychloroquine: Divisive drug may hold secrets to stopping Covid-19‘ and ‘Covid 19 coronavirus: Hydroxychloroquine: The drug that could be our saviour‘. What’s the news?
A: There’s a new Australian trial in healthcare workers, to see if taking the drug before you get exposed will protect you from infection — previously there had only been evidence that it doesn’t help if you take it when you’re already sick.
Q: And what were the results?
A: There aren’t any results. There won’t be any results for quite a while.
Q: When?
A: The entry at the Clinical Trials Registry says they plan to finish taking measurements at the end of the year, and the story says the results will be in by January. Though the Trials Registry also says they plan to recruit 2250 people and follow them for four months, and the story says they have ‘roughly 200’ people now. So it’s not completely clear.
Q: Will it work?
A: We don’t know. That’s the point of the trial. We know it’s nowhere near 100% effective, because people taking hydroxychloroquine for auto-immune diseases have ended up with COVID, but it’s possible that it provides some useful level of protection. It’s also very possible that it doesn’t.
Q: And healthcare workers are at high risk, so it would be most useful for them?
A: Yes, and healthcare workers are already trying to do all the other protective things, and they are still at high risk, so the drug might be a useful addition even if it’s only moderately effective
Q: And for the rest of us?
A: It’s unlikely to be as safe or effective as masks.
Q: If it does work, it will be pity that the politicisation has slowed it down
A: Well and the fact that it doesn’t work after you get sick. But yes, that’s one of the points the story makes, quoting both the lead researcher and a study participant
Q: This is the story that’s illustrated with a picture of Donald Trump?
A: <sigh>
Q: Apart from the headline and picture, the story is ok?
A: Well, later on, one of the researchers says
“For example if there was a case in a meatworks or an aged care, you’d go there and give the drug to all the residents or workers to try to prevent them getting Covid-19,” he said.
Q: But how is that before they’re exposed? If there’s a diagnosed case, they’ve already exposed people and they will be isolated in the future and not expose anyone else. It’s the people who are already exposed that are the problem.
A: I hope he’s just saying there’s a potential for using it as post-exposure prophylaxis in the future, after a different trial
Q: That … could have been clearer.
A: And the biggest problems for healthcare workers in the current Australian outbreak seem to have been a shortage of protective equipment or poor ventilation, so you’d hope irresponsible news headlines about a miracle cure wouldn’t distract from that.
Thomas Lumley (@tslumley) is Professor of Biostatistics at the University of Auckland. His research interests include semiparametric models, survey sampling, statistical computing, foundations of statistics, and whatever methodological problems his medical collaborators come up with. He also blogs at Biased and Inefficient See all posts by Thomas Lumley »
The story says that there is a 50:50 chance the person in the story is taking the drug, or it could be a placebo.
Is that the usual case, the placebo is given randomly to half the people in the study. If you assumed the placebo wasnt going to work could you then reduce the % taking it ( within limits). So far they have 200 in the study.
Maybe that study the other day about
covid testing via serology of over 2000 Australian elective surgery patients should test their blood samples for Chloroquine, as I understand usage had shot up and many people , with access, were taking it anyway.
4 years ago
It turns out that 1:1 randomisation gives you the smallest total sample size. If you went 2:1 you would have fewer people taking the placebo, but more people in total
4 years ago
I have followed Dr John Campbell UK on Youtube re covid.
A week or so ago he spoke about this Belgium trial published in NCBI journal on 24 August 2020.
Titled:
Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants
In his presentation Campbell praised the trial for its methodology and handling of the data. The significant decrease in mortality as stated in the paper was reported by Campbell to be in the order of 30%.
The upshot is as quoted from the paper:
In conclusion, in this large nationwide observational study of patients hospitalised with COVID-19, HCQ monotherapy administered at a dosage of 2400 mg over 5 days was independently associated with a significant decrease in mortality compared with patients not treated with HCQ. This impact was observed both in the early and late treatment groups.
Worthy of consideration?
4 years ago
The UK RECOVERY trial was a bit larger than that, and more importantly was *randomised* rather than just observational It showed no evidence of benefit and ruled out any benefit larger than about 5%. A US randomised trial run by the National Institutes of Health was stopped early because the treatment was showing no benefit. And there are other smaller trials. This is a good example of what we often see: that treatments with some scientific rationale look very promising either in observational studies or in very small trials, but are revealed as ineffective when evaluated more reliably in randomised trials. Historically, about 50% of treatments that go into large randomised trials will turn out to be ineffective.
4 years ago
Campbell argues that the UK RECOVERY trial used significantly higher doses than the recommended dose of hydroxy. He says the key is the lower correct dosage and is convinced by the Belgium trial, even though it is not ideal as an observational trial but that the large numbers and the significant statistical outcome of lower death rate is fairly convincing.
I can only refer you to Campbell’s presentation. He covers a number of trials.
This is the link:
4 years ago
The key thing is how did they choose the patients to give hydroxychloroquine to. Campbell gives the impression that they did it before hand in a balanced way but it’s clearly accounted for afterwards in the modelling.
There is also something going on as obesity was found to be protective (although non-significant) when obesity is not protective for covid-19. When that happens then it’s usually something odd going on with age – obesity is a competing risk for cardiovascular disease so very few older people are fat – but older people are most at risk from covid-19. So, when obesity is seen to be protective then it’s usually being middle-aged that is protective.
Anyway, here is the table of age from the article
HCQ non-HCQ
Age (years)
16–30 1.4% 2.0%
31–44 8.2% 5.0%
45–64 36.5% 19.7%
65–79 30.7% 28.8%
≥80 23.3% 44.6%
Clearly there are more middle aged people and fewer very old people in the HCQ group. The difference in the median ages is 11 years.
And then in their model, it looks like they treated age as a linear predictor of covid-19 mortality when the risk is highly non-linear.
But as a check … if Belgium had found the secret sauce for treating very ill covid-19 patients then they should have a low death rate compared to their case rate. On the covidometer, Belgium is currently 37th for the number of cases per million pop at (9070 per million) but they are number 3 for the death rate (858 per million) – where a higher ranking is worse. Even if they are screwing up how they count their cases or get their cases to hospital, it’s still a pretty big discrepancy in the wrong direction.
4 years ago