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Do any Covid-19 ‘cures’ actually work? There has been a huge increase in scientific papers aimed at a desperate public — and many of them are garbage

When will the magic pills arrive? Photo Illustration by Rafael Henrique/SOPA Images/LightRocket via Getty Images

When will the magic pills arrive? Photo Illustration by Rafael Henrique/SOPA Images/LightRocket via Getty Images


May 26, 2020   6 mins

A couple of things happened in the past week that will have been of huge interest to a lot of people, for obvious reasons. One, a study on the impact of hydroxychloroquine, an antimalarial drug, on Covid-19, was retracted. Two, another study, looking at the effect of the Ebola drug remdesivir on the virus was shown to have an extremely basic statistical error.

Those two drugs and their potential for treating the Covid-19 have been in the news a lot recently. Hydroxychloroquine in particular has received a lot of attention, because one Donald J Trump has apparently been taking it. The US president had tweeted in March about a different study, headed by the French scientist and Asterix character lookalike Didier Raoult, stating (capitalisation his):

“HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine 
 Hopefully they will BOTH (H works better with A, International Journal of Antimicrobial Agents) be put in use IMMEDIATELY. PEOPLE ARE DYING, MOVE FAST, and GOD BLESS EVERYONE!”

That study, by the way, contained the same basic statistical error as the remdesivir one. That error, for those interested: they divided people into two groups, one who’d taken the drug and one control group. Then they looked at whether people’s conditions improved after a certain time. 

But for some reason, both studies took people who’d died out of their results: one in the hydroxychloroquine study (and three people who ended up in the ICU); seven in the remdesivir one. “Dying” is pretty obviously “not improving” — but because those deaths were removed (and because the deaths fell disproportionately among the treatment group rather than the control), it made the drugs’ results look better than they were.

That wasn’t the only problem with the two. They were also tiny (remdesivir study, 61 subjects; hydroxychloroquine study, 42 subjects, 16 of whom were controls) and, in the case of the latter, not randomised — the control group was some people in another hospital, and some patients who’d refused to be given the drug. This is all on top of an earlier remdesivir study that seems to have changed what it was looking for half-way through, a tried and tested way of making unsuccessful drug trials look successful.

We’re living in a strange and frightening time, and we’re relying heavily on medical science to save us from it. Vaccine trials, drug trials; antibody testing to discover how many people have had it and therefore how deadly it is; studies on whether children are likely to get or pass on the disease, to see if it’s safe to reopen schools. We desperately need good science done quickly.

And science has changed, as a result. Studies are coming out faster. “Preprint” papers, studies which have been carried out and posted by the authors to an open-access server like ArXiv, PsyArXiv or MedRxiv, have been around for years, and had been becoming more popular even before Covid-19. They’re a good idea, in many ways: they allow other scientists to examine studies and check them for problems ahead of official publication, in a way that the standard peer-review system doesn’t.

But they are, as that implies, not peer-reviewed. Peer review is certainly far from perfect — the remdesivir study I mentioned in the first paragraph was peer-reviewed and still the statistical error got through; and there are major systemic problems with it which are too complex to go into here. But it does act as a basic sense check. Preprints are a useful system, but they can’t replace peer-review entirely.

I’m used to seeing press releases and expert comments appear in my inbox about new scientific papers. Usually, the bulk of them are embargoed: big red letters at the top of the email saying “please do not publish before 08:00 BST 24 May” or whatever. Now, the large majority of them are preprints, available immediately. Everything is happening faster.

That is fine, and as it should be — and as a science writer, it’s hard to resist. I love a preprint as much as the next deadline-pressed journalist with no institutional journal access. (See?) But, in the end, as XKCD reminds us, an un-peer-reviewed study could also be described as “a PDF”. Some contain a vital contribution to scientific knowledge; some are worse-than-useless garbage. (That is also true of peer-reviewed studies, I should admit; but slightly less so.) It requires some skill to tell which is which, or who to trust.

Since peer-reviewed papers are being rushed through, too, it means that there is a lot more noise in the system than there usually is; a lot more garbage. That’s not anyone’s fault, it’s inherent in trying to do things quickly. (“Cheap, fast, good. Choose two.”)

And over the last few months, we’ve seen an awful lot of things catch people’s attention: the apparent link between a country’s Covid-19 outcomes and BCG vaccination; the use of plasma from recovered patients’ blood as a treatment; the idea that smoking offers protection (or very much doesn’t). Zinc, vitamin D. Many, perhaps most, of these will turn out to be nonsense.

You might — and some do — say: so what? People are dying in hospitals; who cares whether the remdesivir trials are imperfect, let’s throw it at people and see what happens. We’re in a burning building, we might as well use this bedsheet as a parachute and see what happens.

But we’re not in a burning building. Covid-19 is terrible and frightening, but it’s not a death sentence for most people; in London, it seems that 17% of people have had the disease, which works out as an infection fatality rate of about 0.5% — one person in every 200 dying. It could be higher in reality; it’s a complicated thing to measure. But that’s probably not too far off. Most people who get it will get better.

And drugs are not harmless. According to the FDA, remdesivir’s side effects include liver damage; hydroxychloroquine has  this list of possible unwanted outcomes. Some drugs actively worsen people’s chances of survival. If we start giving these drugs to people, there’s a strong possibility that we’ll end up killing a few of them.

More than that: there’s this thing that the psychologist and serial debunker of bad science Nick Brown, calls “scientific hysteresis”. Hysteresis is when something gets pushed out of shape by something and then doesn’t fully reform to its original position.

The idea of scientific hysteresis is that when a scientific idea — vaccines cause autism, say, or power-posing makes you confident — gains traction, it changes the shape of public opinion. Now, more people believe that thing than previously did.

If those ideas are debunked,  as both those examples essentially have been, there is no reason to believe them any more. The original reason has been removed. But often, public opinion does not reshape properly; still, there’s a lingering deformation. People still believe that vaccines cause autism or that standing with your legs apart will get you a pay rise; some of them might not believe it as strongly, but there’s a lingering “wasn’t there
” feeling. This phenomenon, under the name “canonisation of false facts”, appears to be real, and it’s a real problem in psychology and other disciplines where many purported facts are being overturned by the replication crisis.

This is the danger of we in the media, or the public, or any presidents who happen to be passing, leaping on studies into hydroxychloroquine or remdesivir or convalescent plasma and holding them up as saviours. Most of them probably won’t be, but there will still be thousands of people who think they are, and pressure on doctors and regulators to provide them.

I can’t see a way of getting science done quickly without lots of these sorts of mistakes being made; I suppose the only thing I can do is call for the media to be extra careful about reporting on interesting new treatments, and to really stress the uncertainties and possible mistakes. 

If you want a salutary lesson in all this, last week, a huge and much better study — 96,000 patients, almost 15,000 of whom received hydroxychloroquine or chloroquine — was published by the Lancet. It wasn’t a full randomised controlled trial, but it used the 81,000 subjects who received other treatments as a control.

(For the record, that means there were pre-existing differences between the intervention group and the control, making the results harder to be confident in, although the researchers did their best to account for those differences statistically.)

The study found that the subjects given the drug not only did no better than those who weren’t — if I’m reading the study right, they were several times more likely to suffer from cardiac arrhythmia — and, more importantly, about 30% more likely to die. 

Fast science is happening. It has to happen. But the rest of us (especially those of us who make science public and well-known) need to be extra careful to make it clear that fast science is not the same thing as good science, because sometimes people will die.

 

ADDENDUM: I said a few posts ago that I was going to try to make more falsifiable predictions, but I haven’t managed it since, so I’m going to get back on the horse.

  • By 20 May 2021, at least one systematic review published in a top-50 impact factor journal looking at randomised controlled trials into remdesivir for Covid-19 will have found some benefit of mortality (55% confidence)
  • By 20 May 2021, no systematic reviews of randomised controlled trials into hydroxychloroquine published in top-50 impact factor journals will have found any benefit of mortality (60% confidence)

I gather from a superforecaster friend that the time you put into forecasting is one of the strongest predictors for how well you do, so having bashed these out in two minutes, I expect them to be dreadful. Hence the low confidence.

 


Tom Chivers is a science writer. His second book, How to Read Numbers, is out now.

TomChivers

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John H Abeles
John H Abeles
4 years ago

The negative studies mentioned in this article using hydroxychloroquine (HCQ) are all in serious, later stage, hospitalised Covid19 patients

No known oral antiviral for outpatients works unless given early in disease eg oseltamivir/Tamiflu influenza; valacyclovir/Valtrex in herpes

Even remdesivir – a potent IV antiviral – didn’t achieve hoped for results in hospitalised patients

Later stage Covid19 patients are mostly suffering from the effects of hyperinflammation ( cytokine storm) and when viral titres are well beyond their peaks. Hyperinflammation can cause myocarditis which can certainly predispose to further cardiac toxicity

HCQ was also used in the negative studies without added zinc which could be a design for failure, as one of the main, but certainly not only, antiviral actions of HCQ is as a zinc ionophore ie it gets zinc to enter cells much more easily where it can exert its added and established antiviral actions

For early Covid19 the usually prescribed course is for 5 to 7 days which would not invoke the long term side effects mentioned so often by the politically correct – and very few toxicities are reported even in long term therapy for autoimmune disorders. Any arrhythmia concerns can be allayed by making sure of normal potassium blood levels

In the several thousands of outpatient Covid19 case reports published up to now , when used in early disease, there have been few if any major side effects noted.

HCQ is a cheap, easily made generically available drug – main manufacturers, like Novartis and Teva have donated billions of doses worldwide since the event of Covid19, so shortages for those taking it for malaria ( preventions or treatment) or for autoimmune diseases, like lupus or rheumatoid arthritis etc are highly unlikely

Here are some pertinent references for further reading on the question of HCQ plus zinc plus either doxycycline ( my preferred choice because it isn’t associated with further cardiac risk) or azithromycin

https://aapsonline.org/hcq-

https://www.medrxiv.org/con

https://www.preprints.org/m

https://www.evms.edu/media/

https://pjmedia.com/news-an

https://www.medrxiv.org/con

https://www.medrxiv.org/con

Russell Hamilton
Russell Hamilton
4 years ago

“it seems that 17% of people have had the disease, which works out as an infection fatality rate of about 0.5% ” one person in every 200 dying.” Wouldn’t it be helpful to say here that (I’m not sure of the statistics) 90% of those 200 people who died were over the age of 65? Otherwise someone reading that who is aged 25 will think “I have a one in 200 chance of dying if I get it”, which isn’t the case.

Fraser Bailey
Fraser Bailey
4 years ago

There are lies, damned lies and Covid-19 statistics…

Mike Smith
Mike Smith
4 years ago
Reply to  Fraser Bailey

And rather slapdash so called ‘science journalists’.

Mike Smith
Mike Smith
4 years ago

For the author – not Russel!

The ‘17% of people’ and ‘fatality rate of 0.5%’ – neither fact connects to the other. As far as I know, no-one really knows how many people in London have caught Covid. I think the 17% might be right based on the number of people who caught Covid on the Diamond Princess (20% of the passengers and crew), but so far virtually no-one seems to have used the evidence from that ship. It implies a large immunity in the general population.

Would have been nice where you got your figures from for clarity.

Paul Wright
Paul Wright
4 years ago
Reply to  Mike Smith

The underlining in Tom’s text means it is a link. If you click the link on the 17% figure, you’ll find that the source is Matt Hancock’s daily briefing. Hancock was reporting initial results of the UK serology survey. This has nothing to do with the Diamond Princess, not sure where you got that from. 17% is nowhere near enough for herd immunity.

0.5% connects to 17% percent because about 6000 people have died in hospital in London (https://www.london.gov.uk/c… ). The population is about 9 million (Google it). 17% of 9 million is the number of people who’ve had it, divide that 6000 by that and you get about 0.4% IFR. Possibly Tom got a better estimate from somewhere, hospital deaths will be an underestimate.

Richard Lustemberg
Richard Lustemberg
4 years ago

Another superficial article debunking some claim without doing a thorough homework.

john.mchugh02
john.mchugh02
4 years ago

Correct. Hydrochloriquine + zinc is being used on the frontline by many doctors. If taken early there is a 93% positive outcome.
A NY doctor prescribes this to his elderly patients and has had a 100% positive rating.
The issue with big pharma is that this is 10 cents a tablet so no money in it. No wonder that 12 big pharma companies signed up to do a hatchet job on Hydrochloroquine – and the media take it as gospel! It doesnt take rocket science to find this out. Unfortunately, people that pass as journalists do very little research and do not use any logic.

Journalists : ask the doctors on the frontline who do not necessarily have a financial and political interest.

Richard Lustemberg
Richard Lustemberg
4 years ago
Reply to  john.mchugh02

Besides, any laymen can read the papers disavowing hydroxychloroquine and notice that their methodology is even worse that what they are criticising. Basically just meta-analysis from big data

Robert Forde
Robert Forde
4 years ago
Reply to  john.mchugh02

But what does a “positive outcome” mean in this context? Do you mean they recover? Far more than that recover without medication at all. If that’s not what you mean, please define the terms you are using. And what does “early” mean? Sorry to be picky but proper science IS picky. That’s how it avoids error. When it does.

Robert Harneis
Robert Harneis
4 years ago

‘…last week, a huge and much better study ” 96,000 patients, almost 15,000 of whom received hydroxychloroquine or chloroquine ” was published by the Lancet.’
A much better studty!?! Hardly – it in no way produces a reasonable comparison with the recommended treatment. It is a typical hatchet job in the anti hydroxychloroquine campaing and has been severely criticised as the writer would know if he was paying attention.

David Bell
David Bell
4 years ago

I stopped reading this about half way for one simple reason. The chances are we will not see a vaccine or anti viral for Covid 19 for some time and we need to learn to live with that basic premise. Holding on to lonkdown while we wait for trail results is not a workable solution.

runfred
runfred
4 years ago

While drugs and vaccines occupy pharmaceutical and vaccine manufacturers and the academic scientific community, I suggest we study low cost, less risky, non-pharmacological interventions (NPIs). Over a decade ago I proposed a simple, three-step maneuver to decrease the risk of small and large droplets emanating from coughs, sneezes or speech from impacting on the face and being inhaled (1). Simply put, if you hear or sees a person cough, sneeze or speak loudly within 6 feet, you should:
1) EXHALE to minimize inhalation of droplets into the upper and lower airways; and
2) TURN YOUR HEAD away to minimize larger droplets from impacting on your face; and
3) WALK AWAY to minimize the inhalation of smaller droplets that have remained airborne.
While these three maneuvers have not been tested in sequence or individually, I believe scientific experiments could be constructed to study them. For example, a mannequin with a primitive upper and lower airway could be programmed to exhale, rotate and move laterally when faced with droplet particles of a human sneeze, cough or loudly spoken phrase (2). Subsequently, the facial surface of the mannequin and the upper and lower airways could be assessed for various size droplets or other markers. We need to study these maneuvers so we can expand our social distancing toolbox while we search for effective drugs and vaccines with minimal adverse side effects.

(1) Sherman FT. Learning to exhale: don’t catch the flu this season. Geriatrics 2008;63,10,2-3(October)
(2) https://doi.org/10.5281/zen

Go Away Please
Go Away Please
4 years ago
Reply to  runfred

Which is?
Thank you.

john.mchugh02
john.mchugh02
3 years ago
Reply to  runfred

All these years and I didn’t know my immune system doesn’t work so that nice man, Bill Gates, has kindly come along to ‘fix’ it ……… every year.
This reminds me of when you get a new computer (human body) and you load up Microsoft version? (chipping jab) and it needs regular updates (annual booster jabs) to keep up with technology.

Derek M
Derek M
4 years ago

I’m not sure describing a scientist you disagree with as an “Asterix character lookalike” really gives your piece the air of gravitas and seriousness you would presumably aspire to as a “science writer”

Robert Forde
Robert Forde
4 years ago

Unfortunately, as I pointed out in my book “Bad Psychology”, the peer-review system has many faults, and many peer-reviewed articles are published which should not be. There are now some “open” journals online which will publish without peer-review, but invite comments from professional peers. If the original author refuses to answer the comments, the article is taken down. Time will tell whether this is a better system, but editors still allow inadequately peer-reviewed studies to be published which prove nothing but contribute to the hysteresis effect even so. Chief culprits, IMO, are inadequately controlled experiments and
meta-analyses of studies which themselves are poor (“garbage in, garbage
out” as our IT colleagues say).

I used to be a peer-reviewer on the editorial board of an academic journal, and found that articles which I had panned mercilessly for basic errors still got published, presumably because they had been more gently reviewed by others. This doesn’t help the reputation of science. But in academia the rule is publish OR be damned, so there is great pressure to churn ’em out.

susienevis
susienevis
4 years ago

HOSPITAL RESTRICTS PROMINENT DOCTOR FROM TREATING COVID WITH HYDROXYCHLOROQUINE
The infectious-disease specialist who briefed President Trump last month on the safety and effectiveness of hydroxychloroquine will no longer be allowed to prescribe the drug to patients at the New York City-area hospital where he has admitting privileges unless it’s done in a clinical trial. Now, he said, the hospital is inhibiting the use of a protocol he and many physicians have found to be effective and is backed by controlled studies worldwide, including a French study. Conflicting studies cited by media, he argues, vary widely in dosage and many other factors, making comparisons impossible. It’s never happened before,” he said of the new hospital policy. “It’s a bad sign for medicine going forward. People have doubled down on the toxicity of a drug that is not toxic,” he said. They’ve gone around and told everybody it’s killing people. It’s not. There’s just a craziness out there, and I don’t know how to correct it, Smith said. The truth doesn’t matter any more. It’s a game-changer. An absolute game-changer.” But resistance has only intensified”Š” Art Moore
https://www.wnd.com/2020/05

Robert Forde
Robert Forde
4 years ago
Reply to  susienevis

“Which he has found to be effective”? Snuff was once “found to be effective” for respiratory disorders (they didn’t find it caused cancer) and radioactive drinks once recommended as health-promoting (ditto). Personal opinion based on clinical experience is rarely worth a damn. That’s why so many dud therapies proliferate in psychology (my own field). Science doesn’t progress by personal opinion.

john.mchugh02
john.mchugh02
4 years ago

The best scenario would be to go to the world’s top person on immunity and microbiology. That would be Professor Dolores Cahill, an Irish lady that has the ear of the EU, the White House, etc. etc?
It seems that she is shunned by the main stream media on this occasion. Now why would that be?

matthewcfrost
matthewcfrost
4 years ago

HCQ has to be taken with zinc to be effective – apparently. Did the 96,000 study do that ?

Mike Hughes
Mike Hughes
4 years ago

“We’re living in a strange and frightening time, and we’re relying heavily on medical science to save us from it.”

UTTER GARBAGE. Over hundreds of millions of years we, and most of creation, have developed superb immune systems that have protected us from millions of viruses. The present one is no different.

Robert Harneis
Robert Harneis
4 years ago

“a huge and much better study ” 96,000 patients, almost 15,000 of whom received hydroxychloroquine or chloroquine ” was published by the Lancet.”
Is it not time to withdraw this article with its embarrassing statement about the disgraceful Lancet study?

olivps
olivps
4 years ago

Great article. So far to my knowledge only one human viral disease (Hepatitis C) has proved to be controlled or even cured with direct anti-viral drugs. For all others everything else is as good as tap water!

Mike Smith
Mike Smith
4 years ago
Reply to  olivps

I had shingles once and that was very well handled by an antiviral drug (Zovirax I think). Shingles gone in a week. So that makes 2 viruses that can be controlled by an antivirus drug. And what about AIDS – that’s 3.

Not being an expert, it looks like lots of viruses are controlled by antivirus drugs. Otherwise, why do antivirus drugs exist?

olivps
olivps
4 years ago
Reply to  Mike Smith

Three different aspects: one is eradication of the vírus (that has been achieved for Hepatitis C); the second is the use of antiviral agents that have so far not been validated to be truly beneficial like Zovirax and Tamiflu that one can take but probably will not interfere with the evolution of the disease (your own immune system do it); the third is the drugs for AIDS that allow you to have almost a normal life span in spite still having the virus. One thing that we need to have in mind is that around 10% of our genome has integration of genetic material from virus. This mean that our species have found a way to live for longtime with virus.

Robert Forde
Robert Forde
4 years ago
Reply to  Mike Smith

If you had taken aspirin for it, would you have assumed it was that? Or if you had taken vitamn C, or maybe Coca-Cola? Just curious.

Alex Sneddon
Alex Sneddon
4 years ago
henk korbee
henk korbee
4 years ago

Please stop writing about statistics, about R0, prevalence, incidence and risk. In corona time it started with counting the deaths caused by corona. Hence it is determined that one died of corona or exclusively not. Even that can’t be done quite well. It seems to be easy, but it isn’t.

runfred
runfred
4 years ago

While drugs and vaccines occupy pharmaceutical and vaccine manufacturers and the academic scientific community, I suggest we study low cost, less risky, non-pharmacological interventions (NPIs). Over a decade ago I proposed a simple, three-step maneuver to decrease the risk of small and large droplets emanating from coughs, sneezes or speech from impacting on the face and being inhaled. (1) Simply put, if you hear or sees a person cough, sneeze or speak loudly within 6 feet, you should:
1) Exhale to minimize inhalation of droplets into the upper and lower airways;
2) Turn your head away to minimize larger droplets from impacting on your face; and
3) Walk away to minimize the inhalation of smaller droplets that have remained airborne.
While these three maneuvers have not been tested in sequence or individually, I believe scientific experiments could be constructed to study them. For example, a mannequin with a primitive upper and lower airway, could be programmed to exhale, rotate and move laterally when faced with droplet particles of a human sneeze, cough or loudly spoken phrase (2). Subsequently, the facial surface of the mannequin and the upper and lower airways could be sampled for various size droplets or other markers. We need to study this low cost, low risk three-step maneuver so we can expand our social distancing toolbox while we search for effective drugs and vaccines with minimal adverse side effects.
1) Sherman FT. Learning to exhale: don’t catch the flu this season. Geriatrics 2008;63,10,2-3(October)
(2) https://doi.org/10.5281/zen

roslynross3
roslynross3
4 years ago

If vaccines categorically cannot trigger Autism then why have some kids with Autism received compensation for vaccines as the cause?

And since no independent study has ever been done looking at Autism rates in fully, partially and non-vaccinated children, how on earth is it possible to make the claim that vaccines can never cause Autism?

Robert Forde
Robert Forde
4 years ago
Reply to  roslynross3

Under the US court system, awards are decided by juries. These tend to make awards to people like themselves, regardless of the facts (I assume that your report of successful cases is correct). That’s pretty much it. Don’t forget that Wakefield’s original scaremongering was based on 8 cases with no control group. And he was struck off. Studies since than have not found any such effect, nor a mechanism by which it could operate. The latter is crucial: people can always cherry-pick data, but science needs to do more than just find statistical effects. It also needs to elucidate HOW things happen. If it can’t, that does suggest a spurious effect.

jpmrwb9
jpmrwb9
4 years ago

All I want to see is a picture of the virus Corvid-19.

jpmrwb9
jpmrwb9
4 years ago

I am from the old school and I look at scientifically-sound evidence and this evidence has never been provided, even though it’s as easy as taking a sample of patient blood and isolating one of these viruses, in a purified form with its complete genetic material (genome) and virus shell, directly from it, and then imaging it with an electron microscope. Have these critical steps been done with Corvid-19? Have they been done with H5N1(avian flu), the so-called hepatitis C virus, HIV, and numerous other particles that are officially called viruses and depicted as attack-crazy beasts.
I wonder how it can be continually claimed that this or that virus exists and has potential to trigger diseases through contagion. An important aspect in this context is that some time ago, mainstream virus-science left the road of direct observation of nature, and decided to go with so-called indirect “proof” with procedures such as antibody and PCR tests. These methods lead to results which have little or no meaning.
So to accept this, the existence of this so-called “killer virus” CORVID-19 must first be proven based on the scientifically sound evidence as indicated above.

michaelbish
michaelbish
4 years ago

Though Chivers offered some qualifications at publication time, I think he would want to revise his coverage of The Lancet study, which has come under extreme scrutiny. https://www.tctmd.com/news/

Russ Littler
Russ Littler
4 years ago

.and this guy’s a science writer?…really? This article is a mass of misinformation, half truths, and just plain damn lies. I can only question his allegiances. It certainly isn’t truth, that’s for sure.

Paul Wright
Paul Wright
4 years ago
Reply to  Russ Littler

The article provides evidence. You do not. Why should we believe you?