Widely disseminated hydroxychlroquine study retracted by authors | Hacker News Reader

Widely disseminated hydroxychlroquine study retracted by authors

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51 pointsed25519FUUU54 comments

So if I’m reading this right, the authors retracted the study because they weren’t able to get more details about the anonymous data they used, as the org who provided the anonymous data refuses to share more details about it on account of patient confidentiality agreements

Edit: I think I found the statement from the org who has the sensitive data ... https://surgisphere.com/2020/05/29/response-to-widespread-re...

It includes:

> We also take data privacy very seriously. Our registry is an aggregation of customers who use our QuartzClinical data platform. Our strong privacy standards are a major reason that hospitals trust Surgisphere and we have been able to collect data from over 1,200 institutions across 46 countries. While our data use agreements with these institutions prevents us from sharing patient level data or customer names, we are able to complete appropriate analyses and share aggregate findings to the wider scientific community.

And...

> We believe that an independent academic audit that validates those three functions as it relates to our papers in the New England Journal of Medicine and The Lancet will bring further transparency to our work, further highlight the quality of our work, and also continue to deserve the confidence of our work by our colleagues.

> This process will follow strict boundaries as it relates to our data use agreements, among other considerations. We are pursuing such an independent audit with all due haste while ensuring compliance with various legal and regulatory concerns. [my emphasis]

Science!

> these institutions prevents us from sharing patient level data ...

They are prevented from sharing the data, not just with the public, but with three of the authors of the paper! That's pretty tight security. I wonder if any of the other authors have seen it.

One of the authors of the paper is the founder/CEO of Surgisphere so presumably he has permission to see the "data" (assuming it exists) and has convinced his co-authors to take his word for it.

> The Surgisphere registry is an aggregation of the deidentified electronic health records of customers of QuartzClinical, Surgisphere’s machine learning program and data analytics platform. Surgisphere directly integrates with the EHRs of our hospital customers to provide them actionable data insights to improve efficiency and effectiveness.

I would be concerned if I was a patient whose doctor used Surgisphere. It sounds like Surgisphere has full access to electronic health data, and it's not clear if patients clearly consented to this...otherwise they'd be able to release more detailed information.

They say it's "deidentified", but if you have a list of age, gender, medical conditions, location, and medications taken (etc) how hard would it be to "reidentify" someone?

The Guardian published an article yesterday with their initial investigative findings about Surgisphere:

https://www.theguardian.com/world/2020/jun/03/covid-19-surgi...

There were also glaring issues with the statistics, as outlined in Andrew Gelman's blog[1].

[1] https://statmodeling.stat.columbia.edu/2020/05/25/this-contr... (one of the many posts there)

What troubles me is that people politicized a potentially life-saving treatment. That's how dangerous our political climate has gotten. Orange man says HCQ good, but orange man bad therefore HCQ bad.

Calling the President orange man makes you part of the problem, no?

Not OP but I don’t think so. He’s remarking on the phenomenon on how there’s a few people who have a strong bias against Trump and anything he touches

Sure, but he's doing it in a very inflammatory way. There are many alternative phrases which would have expressed the same idea without making it look like he's picking a fight.

"Orange man bad" is a meme or just shorthand to refer to anti-Trump bias. It's meant to be dismissive of it and is rather widely circulated.

The issue was also that “orange man” was not basing his statements on any convincing evidence.

However people across the world associate the prestige and respects of the POTUS office as conferring authority on his statements. They think he has access to sources of info they may not (His HCQ boosterism seems to have been based on tweets and watching Fox News cable hosts though, no inside info).

this is a stawman completely unrelated to the topic being posted

I have always found it strange that some people think Trump just says these things of his own volition. As if the President of the United States wouldn't be advised by some very, if not the most intelligent people our country has to offer. I guess some would say the blind faith is dangerous but at the same time I look at it as being common sense that our President would not advise something that could potentially kill people.

The POTUS is certainly advised by some very smart people but he has a mind of his own.

Analysis of his tweets have shown they often match the programming of his favorite Fox News TV shows exactly. (A time stamped remark based on something he sees on fox, then an equal delay and a new Tweet based on programming a similar amount later in the show).

This dynamic tension between the advice of experts and Fox News that Trump receives played out very visible in the HCQ saga where Dr. Fauci in the live press conferences kept trying to walk back Trump’s remarks in the same conferences. https://www.statnews.com/2020/03/20/trump-coronavirus-drug-j...

> WASHINGTON — President Trump on Friday admitted that his enthusiasm for an antimalarial drug unproven as a coronavirus treatment was based largely on gut instinct, after an open disagreement with the nation’s top infectious disease expert at a White House press briefing.

> When reporters asked Tony Fauci, the director of the National Institute of Allergy and Infectious Diseases, whether the drug hydroxychloroquine was effective at preventing coronavirus, he said simply: “The answer is no.”

> But when Trump came back to the microphone, he told reporters that “we ought to give it a try.”

> “I think we disagree a little bit,” Trump added. “I feel good about it. That’s all it is, just a feeling, you know, smart guy. I feel good about it.”

No, the French doctor, Raoult, who recommended the treatment did the research in the field. https://pubmed.ncbi.nlm.nih.gov/32205204/

Published a peer reviewed study, in March. But political opponents and people in favor of chaos, chose to bankroll a fake study and publish it in the so-called prestigious Lancet journal to make Trump look bad. Democrat governors like Michigan's threatened doctors for daring to prescribe the drug: https://news.yahoo.com/michigan-governor-threatens-doctors-p...

This is a drug that's been around for 60+ years. And the propaganda machine somehow turned it into a bad thing. I don't know who's behind the propaganda, maybe it's other pharm companies that want to profit, maybe it's political enemies...but I don't care, this is unacceptable and immoral.

The Raoult paper wasn't that great, to be honest. But it did ask some questions in the discussion section which are still (partly) unanswered today.

Yes, Raoult published a study. And previously to his study Chinese and South Korean doctors experimented with HCQ as a treatment as well as trying many other drugs.

Raoult’s study is problematic as you can see by reading it. He explicitly removed the person who was taking HCQ and got worse and died from the study. It also was not a RCT and generally speaking is basically not a very strong piece of data in favor of HCQ’s effectiveness.

Then Fox News hosts and other right wing people, who were opposed to non-pharmaceutical interventions to slow the spread of the coronavirus, began to tout HCQ as a “100%” cure for the virus which would mean that life could continue as normal.

The regulations in places like Michigan were because unqualified doctors were abusing their prescribing authority after they heard about the drug in the POTUS’ press conference. The spike in prescriptions correlates exactly to when POTUS made his statements , see https://www.nytimes.com/2020/04/25/us/coronavirus-trump-chlo... “ By that evening, first-time prescriptions of the drugs — chloroquine and hydroxychloroquine — poured into retail pharmacies at more than 46 times the rate of the average weekday, according to an analysis of prescription data by The New York Times. And the nearly 32,000 prescriptions came from across the spectrum — rheumatologists, cardiologists, dermatologists, psychiatrists and even podiatrists, the data shows.”

The regulations allowed the supply of the drug to continue for the people who have been taking it for ailments such as arthritis, where it’s been known to be effective for a long time and many patients depended on it only to have their drug supply locked up by abusive prescriptions.

I think even in the hyper politicized climate were in most people will trust their elected officials. People have been listening to the governor's for the most part. There have just been too many lies and doubling down on the lies from the president. Everything needs to be independently verified and all the verification of HCQ outside of this retracted study showed that it either didn't help or actively harmed.

all the verification of HCQ outside of this retracted study showed that it either didn't help or actively harmed

False. Not all. There's a reason why people were hopeful.

https://youtu.be/5i4BpTcBdrc?t=415

There are many more like this.

On one side we have peer reviewed, published, studies showing it doesn't work and causes harm when used to treat Covid-19, and on the other side we have youtube videos talking about tweets from some bloke calling himself MD but who isn't working as a doctor, talking about a "study" performed in India that wasn't actually a study -- they were not monitoring the impact on the people taking it; they didn't attempt a control group; we have no idea if the people who declined it were high risk or not; etc etc.

> On one side we have peer reviewed, published, studies

I don't think you fully caught the irony of what you just wrote.

> On one side we have peer reviewed, published, studies showing it doesn't work and causes harm

I understand the "doesn't work" at least when given late during the course of the disease (no idea when early, that's why we have RCTs to find out, otherwise it would be already done and deal), but causes harm? Aside the retracted study, even the deaths in the high dosage arm in the Brazil study, which prompted unmasking and lowered dosage, were defined "a statistically insignificant trend" (death is always serious, of course, but those words need to be taken into account).

Unless by "causes harm" you mean for availability for treatment of other diseases, of course.

> talking about tweets from some bloke calling himself MD but who isn't working as a doctor, talking about a "study" performed in India that wasn't actually a study

A bit unrelated, but during the peak, my parents shared a video kn Facebook that I found quite surprising.

A doctor, with a legitimate medical degree and patients, made a meme level conspiracy video about how since a patent existed on a vaccine for a previous coronavirus, it would also treat COVID-19, but somehow tied the patent owner to Bill Gated and into a conspiracy by Gates to depopulate the world.

I nornally consider doctors pretty intelligent people, but jesus christ.

"potentially" is the key word here

I could argue it was politicized the moment that politician claimed it was the be-all and end-all and his frenzied supporters declared it to work. All lack of success in science by the drug has already been dismissed as a political attack. Heck, the pandemic itself has been dismissed as a political attack too. The bodies are dismissed as a political attack.

And yet we still can't show the drug works.

I worry excess attention on this drug due to politic pressure is distracting from exploring life-saving treatments that aren't this drug.

There's an enormous pressure on science to deliver, and it has to actually prove it unlike the politicians.

> And yet we still can't show the drug works.

There has been just one trial done properly to my knowledge, and that was published yesterday. And even that is just applied in a narrow case (post-exposure prophylaxis, modulo some important study limitations).

That one's being attacked as we speak for certain poor controls on testing. This could lead to a compromised dataset and invalidating the whole thing.

Yes, I've read the limitations of the paper (after the Lancet debacle, I too learned my lesson and read a little more thoroughly).

I believe it was done the best they could, given that UMN had to use very little money for it (~100K USD, as far as I understand). That's why IMO the limitations need to be fully read and understood.

But I think it was done in good faith (unlike the Lancet study): the PI tried to his best to avoid spilling the beans until it was published to avoid sensationalism, and at the same time, he signed the open letter against the Lancet paper (after he sent the paper for review, so he knew the results already).

Larger studies will likely be needed. It's clear that the effect size (if any exists) is quite small, like with remedisivir.

Five studies. Key difference: Used with zinc and used with outpatients.

https://academic.oup.com/aje/advance-article/doi/10.1093/aje...

Since this is being repeated multiple times, quoting benmaraschino:

One of these "studies" is a 2-page Google Doc with no real data. Another is the discredited Raoult study, which is under investigation by the journal [1]. Another study cited is also by Raoult's team. The Brazil study (ref. 29) doesn't seem to have passed peer review (yet?) and has severe methodological flaws. Like the Raoult studies, the Brazil study was not randomized, but makes no attempt to control for confounding by indication or self-selection, such as with propensity score matching or similar methods commonly used in observational studies. The last study cited isn't a study, but an article from a local news station.

Actually we can, but timing and combination matters.

It should be taken early (either as preventative or early onset of symptoms) and with zinc. If so, then there is proof of success, see these five studies confirming its effectiveness in outpatients.

https://academic.oup.com/aje/advance-article/doi/10.1093/aje...

Since this is being repeated multiple times, quoting benmaraschino:

I don't know that it's political, per se, to observe that some people say stuff that most of the time seems unrelated to facts and thus acquire a behavior of discounting said people. Distrust can be earned regardless of politics.

This is a gross misrepresentation of what actually happened. A flawed study was published claiming HCQ was extremely effective. The right was clamoring to re-open the economy and started promoting HCQ as a miracle cure. Rational people pushed back, said the evidence was thin and more research was needed. The right accused those people of trying to sabotage the economy for political reasons.

I don't think that's a gross misrepresentation from the point of view of the average person at all. The average consumer of news that has already staked a political position will ignore the nuance you pointed out in your comment. So yes, for liberals, a class of drugs that have been used for decades to safely and effectively treat a number of conditions is all of a sudden deadly.

Which liberals? All of them? I highly doubt that. The vast majority of political leaders on the left have been highly deferential to health experts. I am sure you can find a stray tweet or two to support your narrative, but show me concrete examples of policy decisions by liberal leaders that were made regarding HCQ due to misinformation about its deadliness. Meanwhile, the Trump administration stockpiled HCQ and caused a run on supplies of the drug based on a flawed study. This put lupus patients at risk of not being able to access necessary medicine.

A better summary would "orange man not a medical researcher therefore HCQ needs evaluation."

Your version of this summary is disingenuous and not in the spirit of Hacker News conversation, where we try to take the best possible interpretation of the conversation as it happens. There is no way to take the text "orange man bad" as anything but a petty dismissal of anyone who is not entirely supportive of a particular politician.

People have interpreted a broad array of responses to Trump's advocacy to mean "orange man bad," from actual blind hatred to observations that full trials need to be put on to confirm effectiveness. I have no problem dismissing the former, but when calls for scientific rigor are met with "oh, you're just a Trump hater" we have a real problem -- in that the act of discovering a fact is now politically risky for anyone who suggests it.

Fortunately in this case the publication process is working; the paper came out, was questioned, those questions were investigated, and it was determined the data was insufficiently open to defend the study, so it was retracted.

Ask yourself what would have happened if a paper agreed with the president's assertions, but was based on faulty/unavailable data? Would anyone questioning the paper be met with "orange man bad" dismissals? What effect might that have on NIH/NSF-funded research, do you think?

A more accurate description is: politician with financial stake in HCQ and no medical background cherry picks the one study claiming HCQ can be used to treat COVID-19, but the study is a third-party review of unverifiable and highly questionable reports.

There is no conspiracy here. The extraordinary claims regarding HCQ need extraordinary evidence, and that evidence is not available.

Haven't there been several other studies showing it has largely been ineffective? There was a completely unrelated one yesterday about how it didn't seem to help prevent catching the virus.

https://www.nejm.org/doi/full/10.1056/NEJMe2020388

Indeed, it doesn't help post exposure. UMN is doing two other trials, one for pre exposure and one for treatment. IIRC, all of them do not use zinc or macrolides. (Some patients of the post exposure prophylaxis trial used zinc, but there's no statistical difference without, although the authors warn about confounding factors).

Some important limitations of the study, results notwithstanding:

- There were basically no PCR-confirmed tests, due to lack of testing materials, and patients reported symptoms themselves

- The whole thing (reporting) was done via email or telephone, no in person checks (even HCQ or placebo was shipped to the participants)

David Boulware (the study's PI) on Twitter, a couple of weeks ago, complained that he sought funding from the NIH for this trial, but he got none.

I thought it was all said and done for post exposure prophylaxis, but at least NEJM's editor is not of the same opinion, and mentions that even in this field of application there are still unknowns[1].

There are larger trials going on, like UK's RECOVERY, which will likely give firmer answers.

[1] https://www.nejm.org/doi/full/10.1056/NEJMe2020388

Thankfully, this was discovered by some tenacious independent researchers. Does anyone have the scoop on who sounded the alarm how they were able to bring the issue to light?

Edit: So apparently this study was just a preprint and not even peer reviewed yet. I don't see why it carried so much weight in the media and WHO decision if that's the case. I think it's probably a good thing that it was scrutinized before it even hit peer review. Found a pretty good writeup here:

https://statmodeling.stat.columbia.edu/2020/05/25/this-contr...

The media does not usually know how to report on scientific research. Unfortunately, the increase of pre-prints seems to have magnified this problem.

Taking a step back, scientific progress is poorly understood in general, even by many smart and inquisitive folks. In fact, I think no one really has a good concise, thorough description for how science unfolds. The reality of it is incredibly complex and messy (but nonetheless unbelievably effective).

Even something as seemingly basic as the “scientific method” as it is taught in schools and seen in popular discussion is pretty misleading. It is not a great model of how science is done.

Another concrete example of the confusion is the debates commonly seen about the definition of supposedly official scientific terms such as “law”, “theory” and “hypothesis ”.

Sean Carroll has a great episode on his Mindscape podcast that touches on this a bit and provides a decent if not fully satisfactory answer to the question of how science actually works. As a heads up, they spend a good chunk of time talking about the concept of truth and some related philosophy :) I found it interesting and useful, but I can guess not everyone will appreciate it.

https://www.preposterousuniverse.com/podcast/2020/05/04/95-l...

I wonder if the news that talked about the study so much when it was first published will spend as much time talking about the retraction.

FWIW, that never occurs.

EDIT: Although it is currently being mentioned on the front pages of NYT, WaPo, and WSJ.

Aw hell, for the past several years, they're just fine with editing their posts and hoping their error falls down the digital "memory hole."

https://en.wikipedia.org/wiki/Memory_hole

Retractions are troublesome even if published prominently.

https://en.wikipedia.org/wiki/Confirmation_bias#backfire_eff...

Oh, it happened in Germany in 1983 when the media realized that Hitler's diaries were fake. But that was one media outlet, who had purchased all the rights of the fake diaries, against all others.

https://en.wikipedia.org/wiki/Hitler_Diaries

It's front page on the Washington Post right now.

I haven't been on HN regularly in years; is promotion by the HN and silicon valley dabblers-and-blowhards crowd the reason the drug (one of dozens being tried) become so talked about? Did Elon Musk spend an hour browsing the preprints and tweet it to the world or something? I'm confused

Trump promoted it in a press conference, which prompted world-wide interest. Elon Musk also promoted it https://twitter.com/elonmusk/status/1239650597906898947?s=20

Background:

* https://www.nytimes.com/2020/04/17/health/trump-hydroxychlor... “ Trump Calls This Drug a ‘Game Changer.’ Doctors Aren’t So Sure: The malaria drug hydroxychloroquine has become a political litmus test. But doctors on the front lines of coronavirus say it’s just another tool in desperate times.”

* https://www.nytimes.com/2020/04/25/us/coronavirus-trump-chlo... “ Prescriptions Surged as Trump Praised Drugs in Coronavirus Fight: Prescriptions for two antimalarial drugs jumped by 46 times the average when the president promoted them on TV. There’s no proof they work against Covid-19.”

Submitting this as a tweet in isolation is teeing up for a flamey exchange in the comments here.

There's even more going on here. Take a look at the studies and note 1) the timing and 2) the lack of zinc. We've already had statistically significant results, where zinc is a significant factor with HCQ. Also the timing doesn't make sense. Wait 4 days after they show up so the virus can replicate, then give them a viral replication inhibitor? Huh?

Check out Dr. Martensen's videos. He's called this stuff earlier than anyone I'm aware of:

https://www.youtube.com/watch?v=IUD_wvkNhnk

Also, compare and contrast what the news media was saying at the time. Then, compare and contrast with this: (WHO report which also shows how safe HCQ is)

https://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxi...

I’ve never seen a published report on zinc and chloroquine, and this combination seems to only appear in YouTube videos. Do you have any links to clinical studies?

There's a study referenced here. The p-value for Zinc vs. No Zinc is 0.003.

https://youtu.be/IH2UoBUcW2I?t=1289

The study title, and authors are here: https://youtu.be/IH2UoBUcW2I?t=1008

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