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:
UPDATE 1:
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.
Findings:
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.
Interpretation:
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!
sub
Here’s my estimate of the probabilities.
33% That Trump is actually taking the pills.
33% That he claims he is, but is not.
33% That he thinks he is, but the doctors are giving him sugar-pill placebos.
You decide which is worst/scariest of the 3.
I had thought his doctor was giving him a placebo. Shut the baby up while not being hugely unethical.
A doctor? I thought he was a chiropractor or something. Osteopath?
Osteopaths are doctors. There can be good ones.
Only in the US of A.
In the rest of the world Chiropraxy and Osteopathy are considered quackery.
(Note, I did not say that US trained osteopaths are necessarily bad doctors, they do appear to get some serious training in the US)
My probability on the second possibility is much higher. tRump is a habitual liar.
Agreed!
I think Trump is the worst President in history, and I think the country will be immensely better off if he loses in November. That said, I certainly don’t wish him to die due to either his doctor being an idiot or a pushover.
So if he’s taking the pills, I hope as this publication gets more press, he stops.
They’re all bad in terms of the implication for public health.
I would put money on the middle option.
tRump may be lying about taking this drug, since he can use this to justify his stupid recommendation for people to take a poorly studied drug.
With tRump you can’t tell the difference between a) “He’s lying”, and b) “He’s stupid enough to actually do this”.
There must be some corollary of Poe’s Law that covers this conundrum.
Now I don’t know the answer… but there is some debate about using hydroxychloroquine along with an antibiotic and a zinc supplement as a preventative and their use as a cure or palliative for those ill enough to be in hospital.
The research paper doesn’t seem to address this and shouldn’t be used to make the general case for or against all uses of hydroxychloroquine.
Do you think maybe there is a general case against use before there is some some proven benefit from using it? Instead of using it because there is “some debate” about it.
Where did AC Harper say we should start using it without studying it first? All AC Harper said is that research needs to be done on its use as a preventative, not that it should be used as one immediately. The whole point of a study is to prove (or disprove) its usefulness.
But tomh, that is the point of clinical trials – you don’t want people, like Trump’s Dr, just using unproven therapies willy nilly. You test them first. There is reason to think this drug might work as a prophylactic therapy – there are anecdotal accounts as well as some biological grounding to think it may work for certain kinds of infections. It’s worth testing.
Oh wait. Sorry, tom. That’s actually what YOU said. We’re in violent agreement.
My apologies.
Two trials (NCT04370782 & NCT04377646) are not fully enrolled yet and won’t be completed until at September (former) and July (later). They are both MUCH smaller trials (under 1000 patients).
Details on these can be found at clinicaltrials.gov, a website maintained by the NIH.
Yes, it’s a shame this drug has become politicized. We need research done on people who haven’t yet contracted the virus and those who have only just contracted it but for whom it hasn’t replicated nearly as much.
That’s my take as well. This study was for use of the drug (w/ or w/o antibiotics) as a treatment or “cure” of confirmed, serious cases, not as a “preventive” for the not-yet-infected or treatment of those with mild symptoms. For Trump, the case for prevention is not proven.
What IS proven is that it’s either useless or too dangerous to use for seriously infected patients. (And don’t use antibiotics – yikes!)
In wingnut-ville this is fake news, and so is the virus itself, and both of those conspiracies happily live together simultaneously.
And of course wingnut-ville is where half the population of US lives.
At least it would be a great name for a hardware store. I will give them that much.
Here’s today’s report of mass graves being dug for cornoavirus victims in Brazil. It is from Murdoch’s News Corps tabloid, The Sun. More fake news from Wingnutville?
https://www.thesun.co.uk/news/11690895/mass-grave-brazil-coronavirus-diggers/
Brazil might be the one country with less competent leadership than the USA.
Trump’s likely response: The study is a fake. It was designed by my political enemies to bring me down. I’m the final authority on everything, since I know everything. I’m going to get the authors of the study fired. I’m a stable genius.
Obamagate!
“Well they didn’t test bleach did they, so they obviously hate Trump to begin with.”
No, he’ll say that the zinc supplement is missing in that study.
One thing I would like news outlets to address which I haven’t seen them address is why this drug is prescribed at all (ie, for malaria) if it is so dangerous. Does having malaria somehow make the drug less dangerous? Or is having malaria simply a bigger health risk than those posed by the drug? This is an important part of the rebuttal to the “what have you got to lose” crowd.
All drugs are dangerous to some extent. And they are all helpful to some extent. They get prescribed where the chance of helping is greater than the chance of hurting. If you have malaria, the risks are outweighed by the benefits. If you’ve got COVID-19, the risks far outweigh the non-existent benefits. Even more so if you have neither disease.
Yes, that’s one of the scenarios I posed as a question. But I’d like to hear a medical authority say it rather than assume it, and I’d like the media to get that fact (if that really is the fact of the matter) out there. I’ve seen many Trumpers challenge the riskiness of hydroxychloroquine on just these grounds.
Trumpsters are challenging basic logic. You don’t need medical professionals to counter the illogic.
“Or is having malaria simply a bigger health risk than those posed by the drug? ”
Yes. That’s why this drug was approved for this use.
” Or is having malaria simply a bigger health risk than those posed by the drug? This is an important part of the rebuttal to the “what have you got to lose” crowd.”
Yes — malaria is one of the most widespread diseases in the world and has a significant death rate. At least one million people die every year from malaria (even with many drugs available to combat it). On any given day on Earth, millions of people have an active case of malaria, that is, they are ill.
This is something that quacks & spiritual alt med promoters have never understood — that medicine is largely about weighing up risks vs benefits, and not about finding the perfect treatment miraculously provided by god or nature to fix up the problem in a body that was designed by god/nature to function perfectly.
CQ and HCQ are also used for conditions such as lupus and rheumatoid arthritis. I guess in those cases the outcome would actually be worse than the treatment.
No, it is not. In otherwise healthy (apart from the debilitating RA or Lupus) patients Chloroquine has few dangerous side effects. There are longterm ones, such as bull’s eye maculopathy, but that is only after years of use, which is not really in play here.
Covid 19 patients requiring hospitalisation are not ‘otherwise healthy’, they are cardio-pulmonarily compromised. Not a good idea to give them a drug that has several cardiac side effects in susceptible patients, as this study confirms.
As a prophylactic there are not many side effects to be feared, since not frequent. However, since it has not shown to have any prophylactic properties I’d advise against.
So you are on the right track. Not only is it used for malaria, but it is actually on the WHOs Model List of Essential Medicines and advertised by the CDC as a very safe anti-malarial.
If it is sooooo dangerous, how is it on those lists?
You haven’t read much on this page, have you.
Please. I’ve been following this blog for years…
And yet you missed clear explanations of why comments like “Is the claim that in a malaria infected body, hydroxychloroquine is fine, but in a COVID infected body, the COVID molecule and the hydroxchlorquine molecule combine to form cyanide?” are so ignorant.
And if you have been following WEIT for years, as you claim, you would know not to call it a blog.
In the WHO Model List of Essential Medicine hydroxychloroquine is listed as an “essential” medicine for use in specialized care facilities for the treatment of rheumatoid disorders and it is among a class of drugs specifically restricted to “medicine(s) require(s) specialist diagnostic or monitoring facilities, and/or specialist medical care, and/or specialist training for their use in children“.
It is not on the essential medicines list for use in adults or for the treatment of anything other than specialized care of children with rheumatoid disorders.
https://www.who.int/medicines/publications/essentialmedicines/en/
Given tRump’s maturity level, does he count as a child or as an infant?
No, I am hoping someone with medical knowledge (lots of very educated people in many fields read this site) can answer my question. And someone did. Read Nicolas Stempels reply.
Malaria (particularly falciparum malaria – think Central Africa) is a nasty-ass little parasite to host. Decades ago, going to Thailand my doc made me consider taking it and I decided against it b/c of the nasty side effects. Apparently the dreams are bonkers. D.A., J.D., NYC
ps I think T. is lying about taking it – again.
pps An osteopath is not a doctor, just called that b/c of some political shenenegans ages ago in the US.
Good grief, those are very damning results from a large study. As PCC(E) notes, the study doesn’t deal with whether the drugs have a preventative effect, but only a fool (“Hi, Donald!”) would choose to take them in the absence of any evidence of their safety and efficacy when used for that purpose.
The politicization of this drug is really unfortunate and we shouldn’t allow it to continue. Trump is an idiot, but the media and general population have now effectively hampered research into this drug because Trump is a jackass.
https://www.npr.org/2020/05/20/859261838/hydroxychloroquine-debate-interferes-with-recruiting-research-volunteers
How is this the fault of “the media”? (Unless by “the media” you mean Fox News and other right wing propaganda operations.)
I mean, as the interviewee mentioned in the very beginning of the link I included, the media blowing the dangers of the drug way out of proportion and thus making studying it more difficult (and, if it turns out it is effective at protecting from the virus, very likely making a lot of people afraid of taking it).
While it is useful to know the uselessness of hydroxychloroquine in this case, I hope that people with autoimmune disorders who are not experiencing side effects don’t get frightened into abandoning it or allow relatives and friends to harangue them into abandoning it. It is a useful drug.
That’s why it is better to listen to medical professionals and not compulsively lying presidents when it comes to health matters.
There are side effects that people aren’t even discussing. For example, increased sensitivity of the skin to UV radiation. While not a concern for Trump (under that heavy spray tan), people taking hydroxycholoroquine will often sunburn much easier and faster than usual.
This is a harsh drug that people should not take unless necessary – for conditions like malaria or lupus.
In case you missed it, Trump has finally worn a mask: https://www.nbcnews.com/politics/donald-trump/trump-refuses-wear-mask-front-cameras-during-ford-tour-n1212466cid=sm_npd_nn_tw_ma
I’m pretty confident Trump has not taken the drug. Here’s my theory on this debacle:
when Trump first discovered that hydroxycholoroquine might be a cure for COVID, he had Jared buy up as much of it as possible to corner the market. Much like they have done with the PPE and other fleecing of the government. So, Fauci comes out and says it is NOT a solution and that sends Trump into a panic. So he has to keep hawking it ad nauseum to the public and when that isn’t successful he finally comes out and states that he is taking it. The only reason he won’t let this go is because he needs to make money from it. He’s deplorable.
Possible treatment:
https://nypost.com/2020/05/21/scientists-believe-cannabis-could-help-prevent-treat-coronavirus/
If this works it, it puts the Evangelicals in a bit of a bind.
Cannabis cures all ailments. Also the best source for building materials, clothing, and manufacturing auto bodies. Doncha know?
Pass me that spliff.
Which drug makes you more obnoxious? That’s the one Trump is taking with both hands.
The office of the US presidency takes a physical toll on its occupants. If you look at the photo array of recent presidents below, they seem to have aged two years for every year in office. Barack, for example, entered office looking as sleek and young as an NBA point guard, left looking like he stepped of a converted rice box. 🙂
With Trump, his three-and-a-half years in the presidency appear to have resulted in his packing on about 40 pounds of fast-food and cortisol bloat.
FLOTUSes, OTOH, seem to thrive in the East Wing. Michelle didn’t age a day. And appearances suggest Melania adheres to a rigorous diet-and-exercise health-and-beauty regimen.
https://i.dailymail.co.uk/i/pix/2011/08/05/article-2022761-0D4FE42600000578-43_308x185.jpg
I suspect Melania’s “diet and exercise” regime involves packing in the carbs so she can run as far as possible …
I’ve got good green money to lay that the two of them will be wed no longer 12 months from the date Trump leaves office.
I’d also bet she’s already been shopping in strict confidentiality for a divorce lawyer who can break the pre-nup.
I think this may seem to be the case but there is no way that you can know how they would have aged if they had NOT been presidents! We cannot re-run the experiment. What the US needs is an identical twin as president! Know any one twin who’d be willing to run?! 😀
Mark Kelly, currently running for the Senate in Arizona has an identical twin brother. Both were astronauts. I could see him as Prez in 4 or more likely 8 years.
Come November, Mark Kelly is gonna kick the crap outta that halfwit desert rattlesnake Martha McSally. You mark my words.
BTW, can you even do such an experiment on twin astronauts?
Sounds like an Einstein gedankenexperiment.
NASA was quite excited to have twins–Scott spent a year on the Space Station, while Mark stayed on the ground. Ten teams worked on NASA’s Twins Study
— encompassing 12 universities and 84 researchers — following the duo before, during and after the flight, tracking the twins’ biology to see how the brothers changed over the course of the study.
Not sure how new or likely this possible cure is: https://www.bbc.co.uk/news/health-52754280
Dear Leader just came on the tube to announces he is overriding all contrary restrictions imposed by state governors to declare that “Houses of Worship” are “essential services” that must be permitted to open wide this weekend. (He did not pause to specify which provision of the United States constitution empowers him to wield such authority.)
Every time this dude endeavors to read from a prepared statement, he demonstrates his lack of mastery of basic phonics.
It’s hard to take your seriously any more professor due to your ideological takes. Hate Trump? Cool… But to make the case that Hydroxychlorquine is some radically dangerous drug simply discounts the fact that is one of the WHOs recommended items to have on hand per the WHO Model List of Essential Medicines. Further the CDC clearly advocates for its safety and effectiveness as a treatment for malaria.
You can argue that it is ineffective against COVID, but I think it is a stretch to think it is somehow a scourge of a tincture.
Is the claim that in a malaria infected body, hydroxychloroquine is fine, but in a COVID infected body, the COVID molecule and the hydroxchlorquine molecule combine to form cyanide? I mean surely you know better…
https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf?sequence=1&isAllowed=y
https://www.cdc.gov/malaria/resources/pdf/fsp/drugs/hydroxychloroquine.pdf
This post is purely about a large medical trial that found that the use of these drugs is ineffective – in fact, dangerous – for treating patients who have Covid-19. Nothing political about that!
Oops! Meant to mention that the medical study under discussion in no way relates to the effectiveness of the same drugs in cases of malaria.
I’m not talking about effectiveness. I can certainly believe that hydroxychloroquine is not an effective COVID treatment, but as the paper itself even mentions, the jury is still out on that.
What i find very difficult to believe is that somehow, a drug that has been in use for approaching 100 years for malaria and arthritis, is on the WHOs list of safe and required medicines and advocated for as safe by the CDC is now all of a sudden a death drug when used in a COVID infected person…
Does that make any sense to anyone?
It is evident from your comments here that you really don’t understand what you’re talking about. Just because a medicine can be safely used for some patients with certain diseases does NOT mean it is either safe or efficacious for different patients with different illnesses. This is a concept that is very simple to grasp.
Yes, it does make sense to me that a drug that is safe in one context might not be safe in another. There are many examples of drugs that are safe for relatively healthy people, but can cause a lot of issues when given to a sick person or a person with specific risk factors. For example the diabetic drug Metformin is extremely safe and effective for most people, but it can cause lactic acidosis and other issues in ill patients, and is usually held while people are sick in the hospital. Ibuprofen is relatively safe for most people, but very rarely is given to very sick patients in the hospital due to risk for heart failure, kidney failure, and other problems. I can think of many other examples.
Cardiac arrhythmia are relatively common in hospitalized COVID-19 patients, and we know that hydroxychloroquine, especially when given with certain antibiotics, can prolong the QT interval, which further increases the risk of cardiac arrhythmias.
Yes nothing political about the phrase, “a faux President being treated by a quack physician with a useless drug,”…
Again, I’m not trying to defend him, but I did always think this blog took a measure of rationality, vice emotive reaction, to issues…
Nothing political about the trial. The scientific evidence suggests that Trump’s claims that the drugs are effective in treating Covid-19 makes his pre-emptive promotion of them foolish and dangerous. The fact that the Commander in Chief is idiotic enough to take one of them himself,under the circumstances in which he claims to be, is beside the point.
So are you agreeing with me that the drug is not dangerous? But that you simply question the effectiveness?
The use of these drugs is fine in treating malaria and other conditions that they have been medically proven to be effective for, and where there is clinical evidence that the risk of side-effects are outweighed by the efficacy of the drugs. Their use to treat Covid-19 patients appears to be dangerous according to the article in The Lancet discussed in this post. Their use outside of conditions for which they have been clinically proven to be safe and effective is reckless, with the sole exception of further carefully monitored clinical trials.
RRR wrote:
“I’m not trying to defend him”
Now, that’s pretty funny.
+1
“..but in a COVID infected body, the COVID molecule and the hydroxchlorquine molecule combine to form cyanide? ”
This is gibberish.
Your first sentence here means that this will be the last day you post. You are not only rude, but insulting. And you clearly didn’t read what I wrote.
I guess you just have to insult the right people – “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!”
I read every word….like these – “Clearly, refraining from using these drugs is the wisest course of action.”
Maybe you can answer my question on the way out?
“Refraining from using these drugs is the wisest course of action” – absolutely, if you have Covid-19! Did you actually read this post or the journal article it linked to? Our host has no problem with you using these drugs if you have malaria or lupus or other conditions that these drugs have been clinically proven to be safe and effective to treat.
One more if I still have your attention. I’d be fascinated to hear your response to Eric Weinstein’s The Portal podcast, episode 19, where you are are called out by Brett Weinstein in his coverage of the suppression of his findings on telomere’s in mice.
I’ve enjoyed your blog over the years… Be well …
Jerry has never pretended to be anything other than Democrat. Accept that. And he has been very fair even saying he wishes Trump no I’ll – I cannot say that I do!
And this is NOT A BLOG!!!
My turn for an oops – bloody iPhone – I typed ill & it changed it!!! How does one turn off autocorrect on this device?! 😩
Say, there, Johnny Olson, do we have a parting gift for our contestant? How about the home version of the WEIT game?
All medicines have effects. Medical science selects for the beneficial effects (“treatment”), whilst attempting to minimise any harmful effects (“side effects”).
This paper shows us that the harms caused by potential side effects of CQ and HCQ, when they are used in active Covid-19, vastly outweigh any potential beneficial effects when they are used in the same disease.
It says absolutely nothing about the risk to benefit ratio in any other disease. Each disease/illness needs to be considered separately; in malaria the beneficial effects, “treatment”, far outweigh the potential of harm from unwanted “side effects”.
“Is the claim that in a malaria infected body…” etc? No. It’s your own misunderstanding of the use of evidence in medicine that leads you to that misinterpretation.
This is an observational study with low absolute risk. I’d warn against reading too much into this. And the many many people who take this drug for autoimmune diseases and other problems should continue to take it with little concern.
They note that placebo-controlled studies are urgently needed. Their final words;
“These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed.”
That’s right, the latest results do discount (or question) WHO’s current published stance on hydroxychloroquine. This drug has never received the scrutiny it now has, and we will be finding out more about it.
Do you trust the CDC and WHO?
No, but that’s irrelevant.
To quote Les McCann, compared to what?
Compared to Donald Trump? Absolutely.
Do I trust them absolutely? Absolutely not.
Mike, you’re wrong about this -it a well studied drug- and RRR is completely wrong about the Essential Medicines list. The drug has been through several trials, some decades old, for treating a variety of diseases. It has some therapeutic value in rheumtological disease (including lupus) and it is related to the quinolines, known anti-malarial drugs. It is not unusual – not at all- for drugs that showed value treating one disease (or condition) but which show effectiveness against another. A famous case in point is thalidomide – an effective anti nausea medicine with horrific birth defects if given to pregnant women but it is also an effective therapy against Hansen’s disease (leprosy).
People need to take a step back and look at this drug objectively. But I guess it can’t happen because the moron cheeto is involved and, like religion, he poisons everything.
To be clear, I am not arguing this is an effective treatment. Studies have not necessarily borne that out. But I do find it extremely odd that this drug is now all of a sudden dangerous when it has been used safely for decades.
Erroneously placed response – the above was intended to be a response to comment 19.
I would bet that while he might think he is taking it, he is given a placebo.
I heard on the radio that a trial of the drug is taking place in the UK with medical people as test subjects, as a preventative not treatment – https://www.bbc.co.uk/news/health-52737169
The fact that this study did not randomly assign patients does mean the results should be interpreted cautiously. It is entirely possible that the more seriously ill patients were more likely to be given hydroxychloroquine and therefore more likely to die.
If you read the study carefully, you’ll note a critical point: non-survivors were, not surprisingly, far more likely to have co-morbid conditions that increased their likelihood of not surviving (e.g., obesity, hypertension, cardiovascular disease), but ALSO of being given the study drugs in question (in fact, about twice as likely). In other words, the sicker patients who were already more likely to die from COVID-19 were twice as likely to get the drugs. 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. That question will require a randomized, placebo controlled trial where sicker patients aren’t preferentially given the intervention. Disappointing that in the paragraph describing the paper’s limitations they don’t call attention to this obvious weakness. And even more disappointing that the media haven’t pointed that out as well.
I agree.
I appreciate Alex pointing out the flaws in this study and saying what it really shows. I’ve added an update to the top of this post giving the caveats that he provides in the comment above and the one below.
Can you point to exactly where in the journal you’re seeing that? (My apologies for my failure to spot it myself.)
Doh! Ignore my last comment – I should have refreshed the page before posting!
Medicus ex machina.
Come to set the record straight. Thanks, Doc.
Then what does the bolded part in the following quote from the Lancet mean:
“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%),
– hydroxychloroquine with a macrolide (23·8%)
– chloroquine (16·4%)
– chloroquine with a macrolide (22·2%)
were each independently associated with an increased risk of in-hospital mortality”.
Doesn’t that mean they adjusted for these factors which included “baseline disease severity”.
Also this:
“Patients who received treatment with these regimens starting more than 48 h after COVID-19 diagnosis were excluded. We also excluded data from patients for whom treatment was initiated while they were on mechanical ventilation…
These specific exclusion criteria were established to avoid enrolment of patients in whom the treatment might have started at non-uniform times during the course of their COVID-19 illness and to exclude individuals for whom the drug regimen might have been used during a critical phase of illness, which could skew the interpretation of the results”
And this:
“For each treatment group, a separate matched control was identified using exact and propensity-score matched criteria with a calliper of 0·001. This method was used to provide a close approximation of demographics, comorbidities, disease severity, and baseline medications between patients. The propensity score was based on the following variables: age, BMI, gender, race or ethnicity, comorbidities, use of ACE inhibitors, use of statins, use of angiotensin receptor blockers, treatment with other antivirals, qSOFA score of less than 1, and SPO2 of less than 94% on room air. The patients were well matched, with standardised mean difference estimates of less than 10% for all matched parameters”
And check out the “Baseline Disease Severity” comparisons in this table. I think you’ll agree they are pretty similar:
https://www.thelancet.com/action/showFullTableHTML?isHtml=true&tableId=tbl2&pii=S0140-6736%2820%2931180-6
If I have misinterpreted the above, my apologies.
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.
Dr. Lickerman. Although it seems that Mehra et al did due diligence in trying to account for confounding factors in patients, I wonder about possible bias introduced by the characteristics of providers-hospitals, clinics and doctors. Given that hydroxychloroquine is now heavily politicized, I wonder whether in the sample of patients the drug was more likely to be administered by less competent or less well equipped providers, perhaps dominant in “Trump country”, thus accounting for the correlated higher mortality. I don’t know, of course, but I will remain skeptical about the mortality result until confirmed by a properly structured trial study with random assignment and placebos for the control group.
darwinwins,
One could certainly argue that any doctor who thinks it’s okay to give an unproven drug to a patient not in extremis (meaning under the rubric of “compassionate use”) outside of a randomized, controlled trial is less competent. I have no idea, however, if the widespread use of hydroxychloroquine splits itself along partisan lines. I do think mortality rates are likely to vary from locale to locale by quality of ICU care in general. I, too, remain skeptical about hydroxychloroquine–slightly more so about the increased risk than about the lack of benefit–and await the results of randomized trials.
One more comment: there aren’t any published trials yet that suggest taking hydroxychloroquine will reduce the risk of infection if you’re exposed. I wouldn’t take it for that either, given the known side effects. First do no harm. Especially because the risk of contracting the disease from an asymptomatic person–the kind you’re most likely to encounter–is so low.
Do no harm – ha!
There are lots of iatrogenic conditions. ☹️
It seems a lot of the time doctors have no clue why they do some things or how they work. I trust surgeons – body mechanics- but very often GP generalists do not manage to diagnose things.
🤭 no, they are alright really – as long as they warm the stethoscope first!
“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.”
What is the problem here? Trump and his supporters will die at a higher rate and suffer higher comorbidities than people who consider Trump a demon from hell, even if they don’t believe in hell. Again, what is the problem?
The study was designed to fail.
All of the anecdotal evidence involves a combination of HCQ and zinc. Because HCQ is a zinc ionophore, the hypothesis is that the HCQ serves to deliver zinc to the interior of cells, and that zinc is what actually busts the WuFlu in the snoot.
Testing HCQ without zinc is like testing a typewriter without putting paper in it. “Hey, it’s a dud, I don;t see any words! Do you?”
So, question to those of you who like to sneer at President Trump: Why shouldn’t I see this study design as politically motivated and in bad faith? ‘Cause I can’t explain it any other way.
I just listened to an interview of Biden by Steven Colbert. Biden was very sharp and rational. How refreshing.
I think the authors do a good job explaining the limitations of the study, they do say “Due to the observational study design, we cannot exclude the possibility of unmeasured confounding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred.”
Using statistics they did correct for “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” in the analysis. Sure there may be other confounders not corrected for, but that is a very reasonable list of things to correct for. Since they did correct for the major risk factors and baseline severity that is stronger evidence (but not proof) that the findings aren’t simply due to sicker people being more likely to get these medications.
Overall I think it is a nice observational study, better done than many I commonly read, but does suffer from the limitations that all well-done observational studies do.
On the subject of the Prezident and medical matters, apparently there’s a customary series of questions given to patients to assess their state of awareness which has resulted in an interesting Tw*tter thread –
Me: sir do you know where we are?
Patient: hospital
Me: ok, great. who’s the president of the United States?
Patient: fuck off
Me: *whispers to nurse* does that count?
https://twitter.com/jtrebach/status/1262699579490873344
cr
Oops, didn’t expect that to imbed.
cr