Hydroxychloroquine Update For April 6

By Derek Lowe 6 April, 2020

There’s a lot of news to catch up on, and to keep things straight I’ll divide the hydroxychloroquine part out
into this post, and cover others in the next one. My previous reviews of the clinical data in this area are
here.

First up is this study from France. It’s another very small one, and all the usual warnings apply because of
that. It’s from a team at the University of Paris and Saint-Louis Hospital there, and they evaluated 11
consecutive patients admitted there with the same course of treatment as the Marseilles group first
reported (hydroxychloroquine 600mg/day and azithromycin, 500mg the first day and 250 mg/day
thereafter). The mean age of their patients was 58.7 years, and (notably) 8 of the 11 had significant
comorbidities (two obese, 5 with various forms of cancer, one with HIV). That’s a tough population, and
unfortunately, the HCQ/AZ combination did nothing. One patient died (and two others went on to the ICU)
and of the ten remaining, 8 were still positive for the virus by nasal swab on days 5/6 after treatment. One
patient had to discontinue therapy on day 4 because of QT prolongation, a known side effect of
hydroxychloroquine that can lead to fatal heart arrhythmia.

So while this is a small study and not a perfect match, it provides no evidence to show that the HCQ/AZ
combination had any benefit at all. While we’re on the subject of QT prolongation, there’s this
preprint from a medical team at NYU that was also treating patients with the same combination of drugs.
In 84 patients, they found notable QT prolongation in about 30% of them, and another 11% were to a level
(>500 milliseconds) that put them at a high risk for arrhythmia. This group’s mean age was 63, 74% male.
No cancer patients in this group, but 65% did have hypertension and 20% were diabetic (which from many
reports is actually a reasonable look at the patients most likely to progress to severe disease). The
strongest predictor of dangerous QT numbers was the development of renal trouble while on the drug
combination.

There are a couple of other things that need to be noted. One is that hydroxychloroquine itself
actually lowers the activity of the innate immune system; that’s why people take it for lupus and for
rheumatoid arthritis. Many people are saying that perhaps it will work best if taken early in the course of
infection, but this effect (which is mediated through TLR receptors) should be kept in mind. Another
potentially important point is raised in this preprint – which, it has to be said, is not human data but
mouse toxicology. But with that in mind, the authors report what looks like a bad interaction in that species
between HCQ and metformin. And by “bad”, I mean about 30% mortality. If this translates at all to humans,
it could be bad news, because (as mentioned above) diabetics look like a high-risk group and many
patients may well have been taking metformin when they present at the hospital. We need more
information on this. An investigational drug combination that showed this effect in mice would not move
forward in the normal course of things.

Finally, I would like to point out this preprint from a multi-country team (Denmark, Netherlands, and UK)
which goes back over the original Marseilles report and reanalyzes its statistics. The problems that many
noted with that paper show up in detail here, and the lessons that you take from it can vary a great deal
depending on the details that were not well reported or characterized:
Performing a Bayesian A/B test, we found that for the original data, there was strong statistical evidence
for the positive effect of HCQ mono improving the chances of viral reduction when compared to the
comparison group. However, we found that the level of evidence drops down to moderate evidence when
including the deteriorated patients, and it drops further to anecdotal evidence when excluding the patients
that were not tested on the day of the primary outcome (day 6). For context, anecdotal evidence is
generally considered ‘barely worth mentioning’ (Jeffreys, 1961) We were able to qualitatively reproduce
the finding of an improvement of HCQ +AZ over HCQ mono. However, although this finding was
statistically significant in the original finding, our reanalysis revealed only anecdotal evidence for the
positive effect of HCQ +AZ over HCQ mono. However, when we included the deteriorated patients into the
analysis, this evidence increased to moderate.

It’s no wonder that this work has set off so many arguments: statistically, it’s like a funhouse mirror. Here,
though, is where some of the folks pinging me on Twitter and sending me emails tend to get more worked
up, especially to that point about anecdotal data. I can see where they’re coming from: if you haven’t done
this stuff, you can look at a report of people responding to such a treatment and figure that the answer is
here – right here, and anyone who doesn’t see it must have some ulterior motives in ignoring what’s in
front of their face. But that’s not how it works.

It’s weird and startling, though, if you haven’t had the opportunity to go back through clinical research (and
even patient treatment) and seen how many things looked like they worked and really didn’t. It happens
again and again. Alzheimer’s drugs, obesity drugs, cardiovascular drugs, osteoporosis drugs: over and
over there have been what looked like positive results that evaporated on closer inspection. After you’ve
experienced this a few times, you take the lesson to heart that the only way to be sure about these things
is to run sufficiently powered controlled trials. No short cuts, no gut feelings – just data.

What do I mean by “sufficiently powered”? That gets to the concept of “effect size”, which is something that
most people outside of medical research probably don’t spend much time thinking about. One of the
favorite arguing points that I get sent my way is “You don’t have to run a controlled trial to see that
parachutes work! What are you going to do, take up a planeload of people and toss half of them
out without a chute to prove your point?” Ah, but the effect size of having a parachute at 10,000 feet is
very, very large. And the larger the effect size, the smaller a trial can be and still have meaning. In drug
research, though, we do not approach parachute levels of difference very often. Drugs help some parts of
the patient population, to varying degrees, whereas a parachute helps every single person who’s tossed
out of a plane (and the result shows up in a very hard, dramatic, and easily measurable endpoint!)

It may seem like the Covid-19 epidemic is more like the parachute situation, but consider that many people
get infected with the virus without ever really knowing that they’re sick – which is not the case with being
heaved out of an airplane, for the most part. Most of the people who get the coronavirus survive – the
fatality rate is of course being argued about, but is probably in the 1% range, give or take. Now, from a
public health standpoint, that’s an awful figure, ten times as bad as the seasonal flu and with a more
infectious virus as well. But for figuring out therapeutic options, it’s tricky: if most everyone will eventually
recover with the current standard of care, how do you test your new idea?

Well, you have to look at disease progression, for example: how many go on to the ICU, how long they’re
in the hospital total, and so on. These are very important things to improve, and you’ll notice that these are
patient-centered endpoints as well. Ideally, that’s what you want, as opposed to surrogate endpoints – in
this case, viral load would be an example of one of those. You would think that viral load would correlate
with the patient-centered ones, but that has to be proven and it might not be as tight a connection as you
would like, either. As more studies collect such data you can start to use surrogate endpoints once you
feel that they’re useful, but you should never just assume their utility up front. What counts in this epidemic
is how many people get sick, how sick they get, and how quickly they recover. There are a lot of variables
involved in all of those, and we need a lot of quality data to see what’s really going on.

One more point: someone last night was trying to tell me that my job was to “bring people hope” and that
my attitude wasn’t helping with that task. Let me clear that up. I am not a physician, and I am not a
clinician. I have spent my career in very early stage drug discovery, not at the bedside. Unfortunately, my
lab skills are not well matched to the current epidemic – my own research has been more oncology-
focused, and it’s way back in the pipeline. None of the last three companies I’ve worked for currently have
any antiviral research. So as for my contribution to fighting the coronavirus, well, you’re looking a
significant part of it right now. I can curate and annotate the news, add my own opinions after thirty years
of drug discovery work and (I hope) make people smarter about what’s going on.

But keep in mind, most of what I’ve done, the great vast majority of what I’ve done over that thirty years
has not worked in the clinic. Most things don’t. My job as a researcher has not to been to raise people’s
hopes without data in hand, my job has been to try to produce such data so as to raise hopes with some
reason to do so. When I see something to be hopeful about, I’ll say so, and when I think people are getting
ahead of what we know, I’ll say that, too. Go back to the first things I wrote about the
hydroxychloroquine/azithromycin work: I called it “potentially very interesting” and called for more data to
see if it was real. That’s where I still am. Raising hopes just for the sake of raising hopes is not where I am,
though, and in fact I find that whole idea to be cruel. We’re going to defeat this virus, this epidemic, by
being as hard-nosed as we can be about collecting real data on real-world outcomes as quickly as
efficiently as we can, not by talking vaguely about miracle cures and isn’t it something and wouldn’t it be
great. You’ll need to go somewhere else for that. Try Dr. Oz, he’s good at that crap. I’ll stick to what I’m
good at here.

Update: the society that publishes the journal where the initial Raoult report appeared has stated that the
paper does not meet the standards that they expect.

Update 2: some Swedish hospitals are reporting that they have stopped administering

hydroxychloroquine and the HCQ/AZ combination due to lack of evidence and worries about adverse
reactions.

Comparing HydroxyChloroquine Trials

By Derek Lowe 31 March, 2020

One minor side effect of the pandemic is that perhaps more people will learn about what drug research
and clinical trials can really be like. Today’s example: we have a clinical trial of hydroxychloroquine from
Wuhan that has just published on a preprint server. What’s good is that this one is blinded, randomized,
and controlled (like the earlier hydroxychloroquine which one I blogged about here from Zhejiang
University, so we can actually talk about it rather than just spend all our time wondering what the heck is
going on.
This time there were 31 patients in the treatment group and 31 in the control group. Median age was 44.7
years, male-female ratio almost even. Both groups got standard-of-care (oxygen therapy, antiviral drugs,
antibiotics – presumably against suspected bacterial pneumonia – and immunoglobulin, with or without
corticosteroids). In addition, the treatment group got 5 days of hydroxychloroquine, 200 mg b.i.d. All were
diagnosed with (relatively) mild illness, but all had pneumonia by CT scan. More patients in the treatment
group presented with fever and cough as compared to the control group.

After five days of treatment, the treatment group showed significant improvements in comparison to the
controls in fever, in cough, and in pneumonia (by CT scan). This is actually the first controlled study to
show any benefit for chloroquine or hydroxychloroquine therapy against the coronavirus – it may sound
odd to say that, but all the positive reports we have had up to now are anecdotal reports and open-label
studies without control groups. The one controlled study we have seen, as mentioned, showed no effect.
Here’s a comparison between the two:

So you can see that these two came out rather differently, with the Zhejiang study showing no detectable
difference on treatment and the Wuhan one showing what looks like a real effect, especially on radiological
progression of pneumonia (which I have to say is a very strong endpoint to measure). Here, then, is a
good exercise in interpreting clinical trial statistics: we are now one-and-one after two small
hydroxychloroquine trials: which one (if either) reflects the real-world situation?

Update, for medicinal chemists et al.: people have asked about the once-a-day dosing in the Zhejiang
study versus splitting to twice-a-day in the Wuhan one. The human pharmacokinetics of
hydroxychloroquine are well worked out (as they should be for a drug of that vintage). A 200mg oral dose
hits its Cmax in the 3-hour range, but boy, does it tail off slowly after that: plasma half-life is 123 days (!)
with a large volume of distribution (extensive uptake in tissue). About 10% of the dose is excreted as
parent, with metabolites still showing up in urine after three months. The metabolites peak in the blood
about the same time as the parent compound after a dose, so it’s not that the compound doesn’t get
metabolized – that long half-life is due to distribution. Kinetics were linear after 155mg and 310mg i.v.
doses, so you’d figure 200 and 400 oral would likely compare in the same way. I believe that toxicity and
QT prolongation are CMax driven, and that’s the likely reason for dosing b.i.d. Since we don’t have a good
idea of the mechanism for any antiviral effects, it’s hard to say if those are more CMax or more AUC
driven, though.

You could argue that overall we’re seeing either no benefit or some benefit here, which is good. As for
adverse events, neither trial reported anything serious, But both of them excluded patients with any sort of
cardiac arrhythmias, a wise precaution since one of the most acute worries with high doses of
hydroxychloroquine is QT-interval prolongation, and you don’t want to do that to anyone with any
underlying problems. So as long as such patients are excluded, for now hydroxychloroquine is in the
“might do nothing, might do some good” category, which under the current conditions seems sufficient for
treating patients, pending further data. You will notice that we are not exactly in the “total cure” category
that the Marseilles group has been putting itself in, but frankly, these results from China are more like what
I expect from the clinic (at best!) when using a repurposed drug against such a pathogen.

One thing to note about the clinical data in this situation: fatality rates are notoriously hard to estimate in an
epidemic, and often only become clear after things have completely settled down. But you would probably
not go far wrong estimating this one for the total infected population as around 1% – maybe a bit better,
maybe a bit worse. It’s higher when you look at the patients who are admitted into hospitals, naturally, and
it most certainly gets higher as you stratify by age groups. So if you want to see how many people you’re
keeping from dying with any given therapy, you need a larger sample than anything we’ve seen so far.
Getting people out of the hospital more quickly, or keeping them out of the ICU or off ventilators, though,
are very worthy goals in themselves, and if HCQ treatment can help with those it’ll be most welcome. We
have little or no data on these yet.

There are some things that need to be noted about this latest work, though. As Leonid Schneider has
commented on PubPeer, the original trial as registered in China looks quite different from what we see
here. Update: see this comment as well. The design was for 100 control patients, another 100 patients to
receive one dose of hydroxychloroquine, and 100 more to receive a higher dose. What we have, though,
are only two groups of 31 patients each, which suggests that there were problems with the inclusion
criteria for the trial and/or with patient recruitment. The trial design also called for endpoints of negative
results for viral RNA, and for “T cell recovery time”, to be collected by sputum and throat swabs and by
blood samples, respectively, and none of this shows up in the preprint at all.

Now, it may be that the 100-patient size numbers were in there as a placeholder and meant “Up to this
many depending on how many people we can enroll”. But the endpoints and sample collections seem to
have changed pretty thoroughly, and it would be good to know more about that, why these decisions were
made, whether any of these data were collected and what they were like. So my opinion of this latest study
is “cautious approval”, and that probably sums up my feelings about hydroxychloroquine as a therapy in
the Covid-19 epidemic in general. It’s a long way from “This is the cure and it’s unethical to disagree”,
that’s for sure. More data will be coming, and we’ll revisit the topic then.

Didier Raoult And The Hydroxychloroquine Controversy

( Part 1 )
Published Tuesday 28 April 2020

These are exceptional times and they need exceptional measures. Therefore, I am yet again deviating from
my policy of focussing exclusively on SCAM and welcome my French colleague Dr Lehmann posting a
series of articles on the hydroxychloroquine story.
Guest post by Christian Lehmann
 
The Elephant In The Room
This pandemic diary was begun just before lock down, already four weeks ago, and yet I have scarcely
touched on the elephant in the room. Our personal elephant is called Didier Raoult. White-haired with age,
venerable in appearance, he has been number one in the press, constantly in capitals in online news
headlines, waking hopes, feeding passions. And arousing the interest of a plethora of epidemiologists of
renown, from Valerie Boyer to Donald Trump, by way of Alain Soral and Alexandre Benalla.
Everything begins on 25 February 2020, when the microbiology professor from Marseille posts his famous
video “Coronavirus, game over”, since more modestly re-baptised “Coronavirus, towards a way out of the
crisis?”
Standing in front of a student audience out of camera, Didier Raoult reveals “a last-minute scoop, a very
important piece of news”: the Chinese, whom he regularly advises, rather than seeking a vaccine or new
products have been “repositioning”, trying old molecules, “known, old, without toxicity,” among them
chloroquine, which has shown itself to be effective in a daily dose of 500 mg per day “with a spectacular
improvement and it is recommended for all clinically positive cases of coronavirus. This is excellent news,
it is probably the easiest respiratory infection of all to treat” Here, the whole roomful laughs, with pleasure,
with relief, and I remember sharing these sentiments, briefly, but completely. Because this was 26th of
February, because like others I felt confusedly that the reassurances with which Agnes Buzyn ( then the
French Health Minister) was inundating us were built on sand, and that the virus would only laugh at little
notices in airports.
I knew Didier Raoult only by name, as a columnist in Point, I had read some of his articles and I had felt
simultaneously soothed by his smooth eloquence, attracted by some of his iconoclastic stances, but also
sometimes rather irritated by his Mandarin-style fake cool posturing. At the end of February, I immediately
reposted the video in the medical forums, on the walls of worried friends, explaining that, if the suggestions
of Didier Raoult were confirmed, we would have escaped with a scare which would soon be dispelled by
this “magic bullet”, this “game changer”.
Then between two consultations in my GP’s office, later that afternoon, I watched that video “Game Over”
again. How could such an important piece of news have reached me by means of a Youtube video?
Where were the overseas publications, the much vaunted Chinese study, the releases from
AgenceFrancePresse, Reuters, the first articles from the New York Times and the Guardian, proclaiming
from the rooftops that the pandemic we had so much feared was in fact only a technical hitch, easily
controllable by a widely available drug. It was at that second viewing that I balked. As a GP who had
worked in cardiac resuscitation some years ago, I was brought up short by hearing Didier Raoult talking up
a medicine “well known, and devoid of any toxicity”. If chloroquine or Nivaquine, to give it its commercial
name, is celebrated for the prevention of malaria, it is also a medicine known for its frightening toxicity as
soon as the dose is exceeded, with the risk of irreversible visual damage and extremely serious problems
with cardiac rhythm which can prove fatal. To say that chloroquine is without toxicity problems is in fact an
error, all the more so because the dose suggested by “the Chinese”, without an iota of proof at this stage,
is five times larger than the customary dose, 500 mg instead of 100 mg.
Deeply uneasy, I’m in discussion with doctor friends on Twitter when the video makes its appearance
there. We know nothing at this point about Didier Raoult’s past, or about his Marseille Institute. Neither the
enmity felt towards him by the Parisian intelligentsia represented by Agnes Buzyn and her husband, nor
the fact that his institute has just lost its INSERM and CNRS accreditations, nor the stance adopted by him
a month earlier explaining that coronavirus would never escape from China and that it was ridiculous to get
worked up about it because “the world has gone mad, something or other happens and three Chinese die
and that brings about a world-scale alert”.
Some of us, practitioners and first responders, knew well the toxicity of chloroquine, that it was to be
handled with care, and that was about all we said on Twitter. It was already too much. The next day in a 20
minute interview Didier Raoult brushed away his detractors. “Malicious gossip, I don’t give a damn about it.
When a medication has been shown to work on 100 people while all the world is busy having a nervous
breakdown, and there’s some idiots who say there’s no certainty that it works, I’m not interested! It would
honestly be medical misconduct not to use chloroquine to treat Chinese coronavirus”. And he drives the
point home. “People who have lived in Africa like me took chloroquine every day. Everybody who went to
hot countries took it throughout their time there, and for two months after they came home. Billions of
people have taken this medication. And it costs nothing: ten centimes per pill. It is a medication which is
extremely reliable and it’s the cheapest imaginable. So this is super amazing news. Everybody who learns
about these benefits should fall upon it.” This is no longer a mistake, this is grave medical misconduct.
Nobody who knows about therapeutics would use such words so lightly.
Cardiologists, resuscitation specialists, emergency doctors, GPs, public-health specialists, we are all
alarmed. Our first warnings are vehement and rational, reaffirming the toxicity of chloroquine in cardiology,
and the majority of us insisting on the senseless and significant risk which Didier Raoult is running.
Because it is familiar, prescribed for long stays in Africa in packages of 100 tablets, chloroquine is lying
around in many medicine cabinets. To declare as a fact that we should “fall upon it” in this agonising
pandemic context is to encourage unrestrained self-medication, and to endanger life. Incoherent,
dangerous, this announcement disturbs us deeply. Incredulous, not for a moment do we imagine just what
Didier Raoult will unleash, nor that the nightmare had already begun.

I’ve Lost All Trust In Medical Research – The Financial

Muscle Of Big Pharma Has Been Busy Distorting Science
During The Pandemic
4 Jul, 2020

By Malcolm Kendrick, doctor and author who works as a GP in the National Health Service in England.
His blog can be read here and his book, 'Doctoring Data – How to Sort Out Medical Advice from
Medical Nonsense,' is available here.

Evidence that a cheap, over-the-counter anti-malarial drug costing £7 combats Covid-19 gets
trashed. Why? Because the pharmaceutical giants want to sell you a treatment costing nearly
£2,000. It’s criminal.

A few years ago, I wrote a book called ‘Doctoring Data’. This was an attempt to help people understand
the background to the tidal wave of medical information that crashes over us each and every day.
Information that is often completely contradictory, viz ‘Coffee is good for you... no, wait it's bad for you...
no, wait, it’s good for you again,’ repeated ad nauseam.

I also pointed out some of the tricks, games and manipulations that are used to make medications seem
far more effective than they truly are, or vice versa. This, I have to say, can be a very dispiriting world to
enter. When I give talks on this subject, I often start with a few quotes.
For example, here is Dr Marcia Angell, who edited the New England Journal of Medicine for over 20
years, writing in 2009:

“It is simply no longer possible to believe much of the clinical research that is published, or to rely
on the judgments of trusted physicians or authoritative medical guidelines. I take no pleasure in
this conclusion, which I reached slowly and reluctantly over my two decades as editor.”

Have things got better? No, I believe they’ve got worse – if that were, indeed, possible. I was recently sent
the following email about a closed-door, no-recording-allowed discussion, held in May of this year under
no-disclosure Chatham House rules:

“A secretly recorded meeting between the editors-in-chief of The Lancet and the New England Journal of
Medicine reveal both men bemoaning the ‘criminal’ influence big pharma has on scientific research.
According to Philippe Douste-Blazy, France’s former health minister and 2017 candidate for WHO director,
the leaked 2020 Chatham House closed-door discussion was between the [editor-in-chiefs], whose
publications both retracted papers favorable to big pharma over fraudulent data.

The email continued with a quote from that recording: ‘Now we are not going to be able to … publish any
more clinical research data because the pharmaceutical companies are so financially powerful today, and
are able to use such methodologies, as to have us accept papers which are apparently methodologically
perfect, but which, in reality, manage to conclude what they want them to conclude,’ said The Lancet’s
editor-in-chief, Richard Horton.”

A YouTube video where this issue is discussed can be found here. It’s in French, but there are English
subtitles.

The New England Journal of Medicine and The Lancet are the two most influential, most highly resourced
medical journals in the world. If they no longer have the ability to detect what is essentially fraudulent
research, then… Then what? Then what, indeed?

In fact, things have generally taken a sharp turn for the worse since the Covid-19 pandemic struck. New
studies, new data, new information is arriving at breakneck speed, often with little or no effective review.
What can you believe? Who can you believe? Almost nothing would be the safest course of action.

One issue has played out over the past few months, stripping away any remaining vestiges of my trust in
medical research. It concerns the anti-malarial drug hydroxychloroquine. You may well be aware that
Donald Trump endorsed it – which presents a whole series of problems for many people.

However, before the pandemic hit, I was recommending to my local NHS trust that we should look to stock
up on hydroxychloroquine. There had been a great deal of research over the years strongly suggesting it
could inhibit the entry of viruses into cells, and that it also interfered with viral replication once inside the
cell.

This mechanism of action explains why it can help stop the malaria parasite from gaining entry into red
blood cells. The science is complex, but many researchers felt there was good reason for thinking
hydroxychloroquine may have some real, if not earth-shattering, benefits in Covid-19.
This idea was further reinforced by the knowledge that it has some effects on reducing the so-called
‘cytokine storm’ that is considered deadly with Covid-19. It’s prescribed in rheumatoid arthritis to reduce
the immune attack on joints.

The other reason for recommending hydroxychloroquine is that it’s extremely safe. It is, for example, the
most widely prescribed drug in India. Billions upon billions of doses have been prescribed. It is available
over the counter in most countries. So, I felt pretty comfortable in recommending that it could be tried. At
worst, no harm would be done.

Then hydroxychloroquine became the center of a worldwide storm. On one side, wearing the white hats,
were the researchers who’d used it early on, where it seemed to show some significant benefits. For
example, Professor Didier Raoult, of the Institut Hospitalo-universitaire Méditerranée Infection, in France:

“A renowned research professor in France has reported successful results from a new treatment for Covid-
19, with early tests suggesting it can stop the virus from being contagious in just six days.”

Then came this research from a Moroccan scientist at the University of Lille:

“Jaouad Zemmouri … believes that 78 percent of Europe’s Covid-19 deaths could have been
prevented if Europe had used hydroxychloroquine... Morocco, with a population of 36 million
[roughly one tenth that of the US], has only 10,079 confirmed cases of Covid-19 and only 214
deaths.

“Professor Zemmouri believes that Morocco’s use of hydroxychloroquine has resulted in an 82.5
percent recovery rate from Covid-19 and only a 2.1 percent fatality rate, in those admitted to
hospital.”

Just prior to this, on May 22, a study was published in The Lancet, stating that hydroxychloroquine actually
increased deaths. It then turned out that the data used could not be verified and was most likely made up.
The authors had major conflicts of interest with pharmaceutical companies making anti-viral drugs. In early
June, the entire article was retracted by Horton.

Then a UK study came out suggesting that hydroxychloroquine did not work at all. Discussing the results,
Professor Martin Landray, an Oxford University professor who is co-leading the Randomised Evaluation of
Covid-19 Therapy (RECOVERY) trial, stated:

“This is not a treatment for Covid-19. It doesn’t work. This result should change medical practice
worldwide. We can now stop using a drug that is useless.”

The study has since been heavily criticized by other researchers, who state that the dose of
hydroxychloroquine used was potentially toxic. It was also given far too late to have any positive effect.
Many of the patients were already on ventilators.

This week, I was sent a pre-proof copy of an article about a study that will be published in the International
Journal of Infectious Diseases. Its author has found that hydroxychloroquine “significantly” decreased the
death rate of patients involved in the analysis. The study analyzed 2,541 patients hospitalized in six
hospitals between March 10 and May 2 2020, and found 13 percent of those treated with
hydroxychloroquine died and 26 percent of those who did not receive the drug died.

When things get this messed up, I tend to look for the potential conflicts of interest. By which I mean, who
stands to make money from slamming the use of hydroxychloroquine, which is a generic drug that’s been
around since 1934 and costs about £7 for a bottle of 60 tablets?

In this case, first, it’s those companies who make the hugely expensive antiviral drugs such as Gilead
Sciences’ remdesivir, which, in the US, costs $2,340 for a typical five-day course. Second, it’s the
companies that are striving to get a vaccine to market. There are billions and billions of dollars at stake
here.

In this world, cheap drugs such as hydroxychloroquine don’t stand much chance. Neither do cheap
vitamins, such as vitamin C and vitamin D. Do they have benefits for Covid-19 sufferers? I’m sure they do.
Will such benefits be dismissed in studies that have been carefully manipulated to ensure they don’t work?
Of course. Remember these words: "Pharmaceutical companies are so financially powerful today,
and are able to use such methodologies, as to have us accept papers which are apparently
methodologically perfect, but which, in reality, manage to conclude what they want them to
conclude.” 

Unless and until governments and medical bodies act decisively to permanently sever the financial ties
between researchers and Big Pharma, these distortions and manipulations in the pursuit of Big Profit will
continue. Just please  don’t hold your breath in anticipation.

Moroccan Scientist: Morocco’s Hydroxychloroquine 82.5%

Success Reveals European Failures
Zemmouri believes 78% of Europe’s coronavirus-related deaths could have been avoided if European
states had mirrored Morocco’s hydroxychloroquine strategy.

Rabat – Jaouad Zemmouri, a Moroccan scientist and president of the Starklab industrial innovation
company in France, believes Morocco’s use of chloroquine and its derivatives proved life-saving for the
country’s COVID-19 patients.

The World Health Organization (WHO) announced on June 17 that the hydroxychloroquine (HCQ) “arm of
the Solidarity Trial to find an effective COVID-19 treatment was being stopped” because the medication
does not “result in the reduction of mortality of hospitalized COVID-19 patients when compared with
standard of care.” 

The decision, however, does not “apply to the use or evaluation of hydroxychloroquine in pre or post-
exposure prophylaxis in patients exposed to COVID-19.” In other words, HCQ may be appropriate as a
preventive treatment or in the first stage of infection. 
The move aligns with the position of French scientist Didier Raoult, who Zemmouri believes made it
abundantly clear that the anti-malarial medication is most effective in treating COVID-19 when used
immediately after contamination. 

Zemmouri, who is also a professor at the University of Lille in France, emphasized that Western clinical
studies targeted the effectiveness of HCQ in the hospitalization phase. 

“Professor Raoult has been repeating that hydroxychloroquine is useless for hospitalized patients, but
[efficient] in the first days of [infection],” Zemmouri said.

While WHO only recently came to this conclusion, countries like Morocco have been heeding the
instructions of Raoult since introducing hydroxychloroquine into their COVID-19 treatment options. 

The drug is a driving force behind Morocco’s 82.5% recovery rate and a “low fatality rate” of 2.1%, and
highlighted that Europe’s failure to properly administer the treatment cost thousands of lives. 

Jaouad Zemmouri

The hydroxychloroquine controversy

In March, Raoult announced results from clinical trials showing a 100% COVID-19 cure rate thanks to

HCQ, a chloroquine derivative: “Despite its small sample size our survey shows that hydroxychloroquine
treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its
effect is reinforced by azithromycin.” 

Raoult also challenged the study published on May 22 in the scientific journal “The Lancet.” The study
linked the use of chloroquine to a greater risk of death in COVID-19 patients, a conclusion the French
expert called “delusional fantasy.”

Raoult’s findings generated debate and controversy around the world, but he doubled down on the study,
saying, “I’m not going to change my mind because there is a messy study done with Big data that tells
something else, regardless of the newspaper in which it goes.”

While countries like the UK describe HCQ as “useless” against COVID-19, world leaders such as US
President Donald Trump — who called the drug a “game-changer” and began taking it daily as a
preventive treatment — are some of the drug’s biggest advocates.

Morocco’s ‘life-saving’ relationship with hydroxychloroquine 

As the world was embroiled in a debate about the side effects of using hydroxychloroquine as a treatment
for COVID-19 patients, Morocco asserted itself as in favor of the drug, a position Zemmouri believes saved
thousands of lives in the North African country.

Morocco uses HCQ in accordance with the recommendations of the French expert, but the country has
stressed its use of the drug and its derivatives is a “sovereign decision” based on consultations with the
Technical and Scientific Commission of the National Program for the Prevention and Control of Influenza
and Severe Acute Respiratory Infections.

Minister of Health Khalid Ait Taleb declared on May 27 that the drug helped prevent mass deaths in
Morocco. He said that while opinions on the matter may differ, “chloroquine is involved in viral inactivation
[of the virus],” and announced Morocco will continue to administer it to COVID-19 patients regardless of
the global controversy.

Now that WHO has affirmed hydroxychloroquine could be effective soon after contamination or as a
preventive treatment, Moroccan experts believe chloroquine and its derivatives will continue to be used in
COVID-19 treatment around the world. The director of University Hospital Center Ibn Rochd, Moulay
Hicham Afif, said the use of the anti-malarial drug will expand in several countries such as China, the US,
Tunisia, and France.

Zemmouri believes approximately 78% of Europe’s coronavirus-related deaths “could have been avoided”
if European countries had applied the “same hydroxychloroquine strategy as Morocco.” 

Comparing Morocco’s clinical COVID-19 response to that of Europe, the Moroccan scientist said Morocco
has 10,079 confirmed cases and 214 deaths against more than 2.5 million infections and 174,438 deaths
in Europe.

Zemmouri said the difference in numbers left him “perplexed.”

“It would not be incomprehensible that European officials would not consult their Moroccan counterparts to
learn. If Europe repeats the same mistake, we can no longer say that it is [a surprise] … it would become
criminal.”

Jaouad Zemmouri

Zemmouri acknowledged that the epidemiological situation in Morocco is improving, but the country is “far
from being clear of the pandemic.” However, he is hopeful Morocco will be able to effectively manage
“possible new waves of the virus.”

Related: Hydroxychloroquine and chloroquine: Morocco maintains its treatment, deplores Lancet’s data
review

Morocco’s Ministry of Health has adopted chloroquine and hydroxychloroquine to treat COVID-19 patients

Health Impact News: Dr. Meryl Nass Discovers Hydroxychloroquine Experiments Were Designed to Kill
COVID Patients – How Many Were Murdered?

Study|China- Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a

prospective open-label randomized controlled study

Preliminary Injunction Sought to Release Hydroxychloroquine to the US Public – Studies Show Benefits
Denmark: Chloroquine, but not hydroxychloroquine, prolongs the QT interval in a primary care population

Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients

hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France

A Mysterious Company’s Coronavirus Papers In Top

Medical Journals May Be Unraveling
By Kelly Servick, Martin EnserinkJun. 2, 2020 , 7:55 PM

Science’s COVID-19 reporting is supported by the Pulitzer Center.

On its face, it was a major finding: Antimalarial drugs touted by the White House as possible COVID-19
treatments looked to be not just ineffective, but downright deadly. A study published on 22 May in The
Lancet used hospital records procured by a little-known data analytics company called Surgisphere to
conclude that coronavirus patients taking chloroquine or hydroxychloroquine were more likely to show an
irregular heart rhythm—a known side effect thought to be rare—and were more likely to die in the
hospital.

Within days, some large randomized trials of the drugs—the type that might prove or disprove the
retrospective study’s analysis—screeched to a halt. Solidarity, the World Health Organization’s
(WHO’s) megatrial of potential COVID-19 treatments, paused recruitment into its hydroxychloroquine
arm, for example. (Update: At a briefing on 3 June WHO announced it would resume that arm of the
study.)

But just as quickly, the Lancet results have begun to unravel—and Surgisphere, which provided patient
data for two other high-profile COVID-19 papers, has come under withering online scrutiny from
researchers and amateur sleuths. They have pointed out many red flags in the Lancet paper, including the
astonishing number of patients involved and details about their demographics and prescribed dosing that
seem implausible. “It began to stretch and stretch and stretch credulity,” says Nicholas White, a malaria
researcher at Mahidol University in Bangkok.

Today, The Lancet issued an Expression of Concern (EOC) saying “important scientific questions have

been raised about data” in the paper and noting that “an independent audit of the provenance and validity
of the data has been commissioned by the authors not affiliated with Surgisphere and is ongoing, with
results expected very shortly.”

Hours earlier, The New England Journal of Medicine (NEJM) issued its own EOC about a second study
using Surgisphere data, published on 1 May. The paper reported that taking certain blood pressure
drugs including angiotensin-converting enzyme (ACE) inhibitors didn’t appear to increase the risk of death
among COVID-19 patients, as some researchers had suggested. (Several studies analyzing other groups
of COVID-19 patients support the NEJM results.) “Recently, substantive concerns have been raised about
the quality of the information in that database,” an NEJM statement noted. “We have asked the authors to
provide evidence that the data are reliable.”
A third COVID-19 study using Surgisphere data has also drawn fire. In a preprint first posted in early April,
Surgisphere founder and CEO Sapan Desai and co-authors conclude that Ivermectin, an Antiparasitic
drug, dramatically reduced mortality in COVID-19 patients. In Latin America, where ivermectin is widely
available, that study has led government officials to authorize the drug—although with precautions—
creating a surge in demand in several countries.

Chicago-based Surgisphere has not publicly released the data underlying the studies, but today Desai
told Science through a spokesperson that he was “arranging a nondisclosure agreement that will provide
the authors of the NEJM paper with the data access requested by NEJM.”

Meanwhile, the questions swirling around the Lancet paper have left leaders of the halted chloroquine
trials weighing whether to restart. “The problem is, we are left with all the damage that has been done,”
says White, a co-investigator on a trial of hydroxychloroquine for COVID-19 prevention that was halted at
the request of U.K. regulators last week. Headlines proclaiming deadly effects will make it hard to recruit
patients to key studies, he says. “The whole world thinks now that these drugs are poisonous.”

A striking observation
Desai’s co-authors on the Lancet paper were cardiologist Mandeep Mehra of Harvard University’s Brigham
and Women’s Hospital (BWH), cardiologist Frank Ruschitzka of the University Hospital Zürich, and cardiac
surgeon Amit Patel, who listed affiliations with the University of Utah and HCA Research Institute in
Nashville, Tennessee. Their study described an analysis of Surgisphere-provided electronic health record
data from patients already treated for COVID-19 at 671 hospitals on six continents.

According to the paper, the analysis included nearly 15,000 patients prescribed chloroquine or
hydroxychloroquine, alone or in combination with a class of antibiotics that has been suggested to boost its
effects. A control group consisted of more than 81,000 patients who hadn’t gotten the experimental drugs.
After controlling for potentially confounding factors such as age, race, pre-existing disease, and COVID-19
severity, the researchers found that the risk of dying in the hospital was 9.3% for the control group versus
23.8% for those getting hydroxychloroquine alongside an antibiotic—apparently the riskiest of the
treatment combinations. The results echoed a preprint published last month, based on a much smaller
group of patients in U.S. Veterans Health Administration medical centers, which suggested an increased
risk of death for patients who were prescribed hydroxychloroquine alone (though not in combination with
an antibiotic).

In 25 May media briefing, WHO Director-General Tedros Adhanom Ghebreyesus cited the Lancet results
in announcing a “temporary pause” in Solidarity’s hydroxychloroquine arm. Regulators in France and
the United Kingdom also instructed investigators, including White’s team, to halt enrollment in trials of the
malaria drug. And Sanofi, which manufactures the branded hydroxychloroquine drug Plaquenil, said it
would temporarily stop recruiting patients to its two clinical trials of the drug.

The Lancet authors acknowledged their results needed confirmation from more rigorous randomized trials,
but in an interview with TRT World, a Turkish channel for international news, Desai expressed
confidence. “The real question is: With data like this, do we even need a randomized controlled trial?” he
said.
Other researchers immediately took issue with the analysis. The study doesn’t properly control for the
likelihood that patients getting the experimental drugs were sicker than the controls, says Matthew Semler,
a critical care physician at Vanderbilt University. “If you have a physician sitting with two patients who have
coronavirus, and the physician chooses to give one of them hydroxychloroquine, they’re doing it for a
reason,” he says. The patient may be relying on high levels of supplemental oxygen, for example, or
getting worse over time. But those kinds of details aren’t available about the patients in the Lancet study,
he notes.

Other researchers were befuddled by the data themselves. Though 66% of the patients were reportedly
treated in North America, the reported doses tended to be higher than the guidelines set by the U.S. Food
and Drug Administration, White notes. The authors claim to have included 4402 patients in Africa, 561 of
whom died, but it seems unlikely that African hospitals would have detailed electronic health records for so
many patients, White says.

The study also reported more deaths in Australian hospitals than the country’s official COVID-19 death
statistics, The Guardian reported. On 29 May, The Lancet issued a correction updating a supplemental
table and saying that a hospital assigned to the study’s “Australasia” group should have been assigned to
Asia. “There have been no changes to the findings of the paper,” the correction notice said.

Deepening skepticism
The brief response left some researchers frustrated. “This was very, very annoying, that The Lancet were
just going to let them write this absurd reply … without addressing any of the other concerns,” says James
Watson, a statistician at Mahidol who on 28 May published an open letter to the journal and the study’s
co-authors, signed by more than 200 clinicians and researchers, that calls for the release of Surgisphere’s
hospital-level data, an independent validation of the results, and publication of the peer review comments
that led to the Lancet publication.

Today, many of the same researchers published an open letter to NEJM and the authors of the ACE
inhibitor study, citing similar problems in that journal’s paper. The letter notes a discrepancy between the
small number of hospitals in each country that are reported to have shared patient data with Surgisphere
and the high proportion of those countries’ confirmed COVID-19 cases reported in the study. It also notes
inconsistencies in the reported increases in the risk of COVID-19 death with increasing age of participants.

Mehra and Patel declined to speak to reporters about the various papers, referring inquiries to BWH, which
released a statement on Mehra’s behalf this evening saying “independent of Surgisphere, the remaining
co-authors of the recent studies published in The Lancet and The New England Journal of Medicine have
initiated independent reviews of the data used in both papers after learning of the concerns that have been
raised about the reliability of the database.” (Ruschitzka, who is on the Lancet paper, has not yet
responded to Science’s requests for comment.)

Oddities also appear in the ivermectin study, says Carlos Chaccour of the Institute for Global Health in
Barcelona, who knows the drug well because he’s studying its potential role in mosquito control. There’s
evidence that ivermectin has antiviral properties, and a study from an Australian team published
in Antiviral Research on 3 April showed that it inhibits SARS-CoV-2 in a test tube. A 6 April preprint co-
authored by Patel, Desai, and Mehra, along with David Grainger of the University of Utah, used
Surgisphere data reportedly collected at 169 hospitals around the world between 1 January and 1 March.
It included three patients in Africa who received ivermectin—despite the fact that only two COVID-19 cases
had been reported in all of Africa by 1 March, Chaccour and two colleagues note in a recent blog post.

Chaccour says after he inquired about the discrepancy, the authors posted a second, longer version of
the manuscript on 19 April, containing data collected between 1 January and 31 March. (The first version
was removed but Chaccour has archived it on his institute’s website.) The new manuscript contained
data on 704 COVID-19 patients treated with ivermectin and 704 controls in 169 hospitals on three
continents. It reported that ivermectin reduced the need for mechanical ventilation by 65% and slashed the
death rate by 83%.

But the revision had other problems, Chaccour and his colleagues wrote in their blog post. For example,
the data shown in a figure were wildly different from those reported in the text. (Science also attempted to
reach Grainger, but received no reply to an email and call.)

The ivermectin study has had a significant impact in Latin America, where the drug is well known and often
sold over the counter to treat scabies, Chaccour says. The Peruvian Health Ministry modified its COVID-19
treatment protocol to include ivermectin (as well as hydroxychloroquine) for mild and severe cases of
COVID-19. Demand for the drug in Peru has surged, and in the San Martín de Porres district, police
confiscated 20,000 bottles of veterinary ivermectin intended to be sold for human treatments. In Trinidad,
Bolivia, the city government aimed to hand out more than 350,000 free doses of ivermectin after the
country’s Ministry of Health authorized its use against COVID-19. Physicians in the Dominican Republic,
Peru, and Chile, citing the test tube study and the Surgisphere preprint, say they performed informal trials
of ivermectin with COVID-19 patients and saw good outcomes.

(In a guest editorial in The American Journal of Hygiene and Tropical Medicine, Chaccour and three
colleagues cautioned against the risks of using ivermectin without solid evidence and urged rigorous
clinical trials. Eighteen such studies are ongoing, according to the website ClinicalTrials.gov, including one
led by Chaccour in Pamplona, Spain.)

Surgisphere’s sparse online presence—the website doesn’t list any of its partner hospitals by name or
identify its scientific advisory board, for example—have prompted intense skepticism. Physician and
entrepreneur James Todaro of the investment fund Blocktown Capital wondered in a blog post why
Surgisphere’s enormous database doesn’t appear to have been used in peer-reviewed research studies
until May. Another post, from data scientist Peter Ellis of the management consulting firm Nous Group,
questioned how LinkedIn could list only five Surgisphere employees—all but Desai apparently lacking a
scientific or medical background—if the company really provides software to hundreds of hospitals to
coordinate the collection of sensitive data from electronic health records. (This morning, the number of
employees on LinkedIn had dropped to three.) And Chaccour wonders how such a tiny company was able
to reach data-sharing agreements with hundreds of hospitals around the world that use many different
languages and data recording systems, while adhering to the rules of 46 different countries on research
ethics and data protection.

Desai’s spokesperson responded to inquiries about the company by saying it has 11 employees and has
been developing its database since 2008. Desai, through the spokesperson, also said of the company’s
work with patient data: “We use a great deal of artificial intelligence and machine learning to automate this
process as much as possible, which is the only way a task like this is even possible.”
What next?
The potential of hydroxychloroquine for treating COVID-19 has become a political flashpoint, and the
questions around the Lancet paper have provided new fodder to the drug’s supporters. French
microbiologist Didier Raoult, whose own widely criticized studies suggested a benefit from the drug,
derided the new study in a video posted today, calling the authors “incompetent.” On social media, some
speculated that the paper was part of a conspiracy against hydroxychloroquine.

For scientists running randomized trials of hydroxychloroquine, an urgent question has been how to
respond to the paper and the many questions raised about it. Some studies were not halted at all. A
hydroxychloroquine trial known as ORCHID, funded by the U.S. National Heart, Lung, and Blood Institute,
opted to keep running after its data and safety monitoring board (DSMB) reviewed safety data from
already enrolled participants, says Semler, a co-investigator on the study.

WHO’s paused Solidarity trial is awaiting a similar review from its DSMB, says Soumya Swaminathan, the
organization’s chief scientist. The pause will allow time for a review of published studies and interim data
from Solidarity itself, she says. WHO paused the trial to show investigators and potential study participants
that the agency takes safety issues seriously, she says. “We want to reassure people that the WHO didn’t
make any kind of value judgment on the use of hydroxychloroquine.”

But some say WHO had a knee-jerk reaction to a questionable study. “This is a drug that has been used
for decades. It’s not like we know nothing about its safety,” says Miguel Hernán, a Harvard epidemiologist
and co-investigator on an ongoing trial of hydroxychloroquine in Spain and Latin America for COVID-19
prevention in health care workers.

The controversy has been an unfortunate distraction, Hernán adds. “If you do something as inflammatory
as this without a solid foundation, you are going to make a lot of people waste time trying to understand
what is going on.”

Chaccour says both NEJM and The Lancet should have scrutinized the provenance of Surgisphere’s data
more closely before publishing the studies. “Here we are in the middle of a pandemic with hundreds of
thousands of deaths, and the two most prestigious medical journals have failed us,” he says.

With reporting by Rodrigo Pérez Ortega, Charlie Piller, and John Travis.

*Correction, 4 June, 10:50 a.m.: An earlier version of this story said one problem with the ivermectin
study, according to Carlos Chaccour and his colleagues, was the strikingly low mortality rate, 21%, of
COVID-19 patients who needed mechanical ventilation. It stated that a case series in the New York City
area found that 88% of COVID-19 patients who needed ventilation died. However, that number was based
on a paper in JAMA that was later corrected because the actual mortality for this group was much
lower.  The sentence has been removed from the story.

Posted in: Health Coronavirus

doi:10.1126/science.abd1337
 A Study Out of Thin Air
by James M Todaro, MD (Columbia MD, @JamesTodaroMD)

May 29, 2020

Misinformation is bad. Misinformation in medicine is worse. Misinformation from a prestigious medical

journal is the worst.  Herein is a detailed look at the controversial Lancet study that resulted in the World
Health Organization ending worldwide clinical trials on hydroxychloroquine in order to focus on patented
therapeutics.

Study Overview

In brief, the Lancet studyis a multinational registry analysis assessing the effectiveness of
hydroxychloroquine or chloroquine with or without macrolide therapy (e.g. azithromycin) in treatment of
COVID-19 in hospitalized patients. The study was very large (perhaps impossibly so, but we will address
that later) and included 96,032 patients, of which 14,888 were in treatment groups. The study found that
hydroxychloroquine and chloroquine with or without macrolide therapy resulted in significantly increased
risk of both in-hospital mortality and de-novo ventricular arrhythmia during hospitalization. In summary, the
authors concluded that hydroxychloroquine and chloroquine are actually harmful and increase risk of death
when used for in-hospital treatment of COVID-19.

The Lancet study was released on Friday, May 22. After deliberating over a weekend, on Monday, May 25,
the World Health Organization hastily announced the cessation of all COVID-19 clinical trials on
hydroxychloroquine in 17 different countries. Instead of performing its own due diligence, the WHO
immediately relied on anobservational study cloaked in the reputation of the nearly 200-year old medical
journal The Lancet.

After its publication, a grass-roots investigation by hundreds of physicians and researchers worldwide
revealed irreconcilable inconsistencies in the data that The Lancet’s peer-review process overlooked. The
study is now found to have inconsistencies with data from national registries of hospitalized COVID-19
patients. The authors continue to hide data sources in a black box controlled by an unknown corporation
called Surgisphere.

Surgisphere

Only one peer-reviewed publication prior to the Lancet study.

Surgisphere appears to be the sole provider of the data for the Lancet study, and boasts itself to be a real-
time global research network that "performs cloud-based healthcare data analytics" using machine
learning and artificial intelligence.

Based on the Lancet study, it must be a very large, sophisticated network indeed to have partnered with
hundreds of hospitals worldwide with the capability of retrieving detailed patient data in real-time.

One would expect a multinational database such as this to be a treasure trove coveted by researchers.
Strangely, this is not so. Surgisphere has a razor thin folder of contributions to past publications. Besides
the Lancet publication, Surgisphere’s only other peer-reviewed publication is one entitled Cardiovascular,
Drug Therapy, and Mortality in Covid-19 that was published on May 1, 2020 in The New England Journal
of Medicine.

The Research section of Surgisphere's website features twenty-three “Case Studies from Around the
World” as evidence of their prior work and product features.  The vast majority of these “case studies” lack
scientific substance and actually consist of short letters, press releases or potential use-cases for its
database.

In place of actual research, the website appears primarily promotional and gives the impression of an
immature tech company with lofty goals as opposed to a global database with real-time data on millions of
patients.
A company with only five employees, most of which joined only two months ago.

According to LinkedIn, Surgisphere has five employees, only one of which has a medical degree—the
founder Dr. Sapan Desai. The remaining four employees appear to have little to no science or medical
background, but with a plethora of experience in business development and sales & marketing. The team's
personnel consist of a VP of Business Development and Strategy, VP of Sales and Marketing and two
freelance writers creating content for Surgisphere.

With the exception of the founder, the entire Surgisphere team joined the corporation only 2-3 months ago.
Actually, according to LinkedIn, the VP of Sales & Marketing is still employed by another tech company,
W.L. Gore & Associates. Prior to February 2020, Surgisphere appears to have had a single employee, the
founder.

A shrouded internet history.

The internet trail behind Surgisphere is peculiar to say the least. Mostly because it isn’t there. The Internet
Archive (Wayback Machine) has records on more than 439 billion web pages and has long served as a
tool to view webpages as they existed in the past. I’ve used the tool hundreds of times and am frequently
surprised by the breadth of its database. Even some of the most obscure webpages have historical
snapshots available. In the rare circumstances where a historical snapshot is not available, the Wayback
Machine’s response is “Wayback Machine doesn't have that page archived.” A far less common response
—one I’ve never seen before—is “Sorry. This URL has been excluded from the Wayback Machine.”
 It’s this last response that is delivered when
searching https://surgisphere.com/ in the
Wayback Machine.

There are primarily two ways for companies to

hide internet histories. First, they can insert

special codes into their websites to hide from
the Wayback Machine’s automated crawlers.
Secondly, companies can request the removal
of their historical snapshots, but there’s no
guarantee the Internet Archive will honor these
requests. Both of these practices are highly
unusual and almost exclusively used for obscuring nefarious activities.

A list of subsidiary companies without substance.

A deeper dive into Surgisphere reveals three subsidiary companies: Surgical Outcomes Collaborative,
Vascular Outcomes and Quartz Clinical. On each of the homepages of these three websites, the
Surgisphere copyright is publicly visible near the bottom of the page.

Surgical Outcomes Collaborative has almost no internet history and the page does not appear in the
Internet Archive until 2019, in which it just redirects to the webpage for Vascular Outcomes.

A search of https://vascularoutcomes.com in the Internet Archive returns one snapshot from December
2019. The snapshot shows a webpage that is largely similar to that of Surgical Outcomes Collaborative
and does not include any details about a team or published research.

Similarly, Quartz Clinical, another healthcare data analytics branch of Surgisphere, also appears to be
devoid of published research and without a publicly visible team.

Each of the company webpages above provide a LinkedIn link. Instead of showing company profiles with
track records, however, the links all direct to the profile of just one person, Dr. Sapan Desai.

Forming partnerships with hundreds of hospitals, formatting electronic medical records in dozens of
different languages and pushing the forefront of technology in machine learning and AI is an
insurmountable task for a large multi-talented team over many months, let alone one person in a few
weeks.

"Get in touch with us"

Just yesterday, the Get in touch with us link on Surgisphere’s homepage redirected to a strange
WordPress template for cryptocurrency. The Surgisphere website has since been changed and the link
deleted; however, this serves as just another example of incompleteness and unprofessionalism from a
company supposedly holding highly sensitive records on millions of patients.

Dr. Sapan Desai

Dr. Desai appears to be the founder of Surgisphere, which was formed in 2007. A PubMed search for
“Sapan Desai” shows 39 medical publications in the last five years. With the exception of the two very
recent COVID-19 papers, the Surgisphere database does not appear to have been used in any of the
other 37 publications. Why would the founder of Surgisphere have access to one of the largest
repositories of real-time patient data, but not use it until publishing on COVID-19?

If we ignore the image of multiple shell corporations enshrouding a hastily organized Surgisphere
Corporation and stick to analyzing the COVID-19 data from the Lancet study, the findings are even less
reassuring.

The Data

Surgisphere provides scant detail on their data sources. Not only does Surgisphere omit which hospitals
supposedly contributed, but they will not even specify the contributing countries. Instead, they categorize
hospitals and patient numbers by continent. Notably, the larger the pool of data, the easier it is to
obfuscate false data.

Data inconsistencies were found nonetheless.

Strike #1. Australia is unique because it is both a country and continent, which makes data obfuscation
more challenging. Thus, it is no surprise that false data was first discovered in Australia. The Guardian
reported yesterday that the number of COVID-19 deaths included in the Lancet study for Australia
exceeded the total nationally recorded number of COVID-19 deaths. The Lancet study reported 73 deaths
from the continent of Australia, but records show that Australia had only a total of 67 COVID-19 deaths by
April 21. When confronted with this inconsistency, the lead author of the study, Dr. MandeepMehra,
admitted the error but dismissed it as simply a single hospital that was accidentally designated to the
wrong continent.  

Strike #2. North American data from the study is highly suspicious. The study reports that 63,315
hospitalized patients with COVID-19 met inclusion criteria prior to April 14, 2020. A review of the well-
curated data from the COVID Tracking Project by The Atlantic shows that there were only 63,276 patients
hospitalized with COVID-19 by April 14. It is theoretically possible that Surgisphere also collected patient
data from Canada and Mexico. However, both of these countries had a tiny number of COVID-19
hospitalizations in comparison to the USA. On April 16, Canada reported 2,019 COVID-19 hospitalizations.
Although data is not readily available on COVID-19 hospitalizations in Mexico, the country had only 5,014
positive cases and 332 deaths by April 14. Based on common rates of case-to-hospitalization ratios, it is
likely that Mexico had fewer than 1,000 COVID-19 hospitalizations. Thus, the total number of COVID-19
hospitalizations in North America (USA, Canada and Mexico) by April 14 is about 66,000.

Are we to believe that Surgisphere truly had relationships and data exchange agreements with 559
hospitals in the USA, Canada and Mexico that captured detailed patient records for 63,315 COVID-19
patients out of a total of 66,000 patients? These figures do not even include the 2,230 patients with
COVID-19 who did not meet the inclusion criteria, meaning that Surgisphere is claiming they have patient
data on even a greater number than 63,315 patients.

Strike #3. The study reports patient data from Africa that requires sophisticated patient monitoring
technology and electronic medical record systems. An open letter to The Lancet signed by 146 physicians
and medical researchers believes this to be unlikely. For the data to be valid, nearly 25% of all COVID-19
cases and 40% of all deaths in the continent would have occurred in Surgisphere-affiliated hospitals with
sophisticated electronic patient data recording and monitoring capable of detecting and recording “non-
sustained [at least 6 sec] or sustained ventricular tachycardia or ventricular fibrillation.” In the setting of a
highly contagious virus, continuous cardiac monitoring is not always utilized as it increases high-risk
patient contact for healthcare workers. A combination of cardiac monitoring practices during COVID-19
and the sophisticated equipment necessary to do so make it highly unlikely that cardiac arrhythmia data is
available for such a large percentage of patients in Africa.

There are additional data oddities not mentioned above which include unusually small variances in patient
baseline characteristics, interventions and outcomes among continents.

Any one of the above findings warrants closer inspection of data for a study of this importance and with
such global implications on patient care.

Surgisphere Responds

Surgisphere responded to inquiries by refusing to provide any additional details on the data sources and
instead asking physicians and researchers to trust them.

Does a corporation that appeared out of thin air two months ago deserve this trust?

---

UPDATE May 30, 2020: The section "Dr. Sapan Desai" was added to reflect Dr. Desai's prior research
work.
Prominent Scientists Denounce End to
Coronavirus Grant
A group of 77 Nobel laureates wants the U.S. government to review a grant cancellation for research in
China directly related to preventing pandemics.

The funding provided by the National Institutes of Health supported researchers in China working with
bats, which can carry viruses like the one that causes Covid-19.Credit...EcoHealth Alliance

By James Gorman May 21, 2020

A group of 77 Nobel laureates has asked for an investigation into the cancellation of a federal grant to
EcoHealth Alliance, a group that researches bat coronaviruses in China.

The pre-eminent scientists characterized the explanation for the decision by the National Institutes of
Health as “preposterous.” The agency said the investigation into the sources of pandemics did not fit “with
program goals and agency priorities.”

The Nobel laureates’ letter followed by a day a letter of protest from the American Society for Biochemistry
and Molecular Biology to the National Institutes on behalf of 31 scientific societies. The societies include
tens of thousands of members, the letter stated. It said the grant cancelation politicized science and
concluded, “The action taken by the NIH must be immediately reconsidered.”
The Nobel recipients said the grant was canceled “just a few days after President Trump responded to a
question from a reporter who erroneously claimed that the grant awarded millions of dollars to
investigators in Wuhan.” President Trump said the grant would be ended immediately.

The grant had been given to EcoHealth Alliance, an organization with headquarters in New York that
studies the potential for spillover of animal viruses to humans around the globe. The group collaborated
with the Wuhan Institute of Virology, which has been at the center of conspiracy theories about how the
novel coronavirus originated. Virologists and intelligence agencies agree that the virus evolved in nature
and spread from animals to humans.

Days after the news conference in April, the National Institutes of Health emailed Peter Daszak, the head
of EcoHealth Alliance. They questioned his work with the Wuhan Institute, and after an exchange of
emails, he was informed that the renewal of his grant for more than $3 million was canceled.

Protest Letter From Prominent Scientists

77 Nobel laureates are asking the Trump administration for an investigation of the cancellation of an NIH
grant for virus research in China (PDF, 3 pages, 0.04 MB)
 3 pages, 0.04 MB
Harold E. Varmus, a former director of the N.I.H., said that the government always sets broad priorities for
research that some scientists may disagree with, including restrictions on use of embryonic stem cells, but
that this research was squarely in line with federal priorities. He called the cancellation “an outrageous
abuse of political power to control the way science works.”

Dr. Daszak said that the grant-making agencies score applications for grants. His application for renewal
went through the National Institutes of Allergy and Infectious Diseases, led by Dr. Anthony Fauci, which is
part of the National Institutes of Health. “We were in the top three percent of grants submitted. I’ve never
got a score that good. It clearly was a central, high-impact priority for N.I.H. to fund. And that was 10
months before, before it was terminated.”

Richard J. Roberts, of New England Biolabs, who organized the letter from the laureates, said that when
he emailed other Nobel recipients, “the response was overwhelmingly positive and everybody replied very
quickly.”

He pointed out the importance of researching the presence of coronaviruses in bats at a time when the
world is suffering a pandemic from a coronavirus that overwhelming evidence suggests originated in bats:
“If we’re going to cut off funds to someone who is so important in our fight against the coronavirus, where’s
it going to stop?”

The laureates sent their letter to Alex M. Azar II, secretary of the Department of Health and Human
Services, and Francis Collins, director of the National Institutes of Health. They asked the director and
secretary to “conduct a thorough review of the actions that led to the decision to terminate the grant, and
that, following this review, you take appropriate steps to rectify the injustices that may have been
committed in revoking it.”

The letter from the group of scientific societies said, “the decision sets a dangerous precedent” because it
offered no “justifiable rationale” for “revoking a grant that was awarded based upon scientific merit.”

At the moment, EcoHealth Alliance is still working in other parts of the world, but it has no ongoing
research in China.

Neither the N.I.H. nor the Health and Human Services Department responded to requests for comment in
time for publication.

WHO Halts Hydroxychloroquine Covid-19 Trials For Second

Time, Citing Its Ineffectiveness
4 Jul, 2020

The World Health Organization (WHO) has stopped the clinical trials of the anti-malarial drug
hydroxychloroquine as well as the anti-HIV medication lopinavir/ritonavir in coronavirus patients, following
preliminary results.
The United Nations health agency has said that the use of hydroxychloroquine – a drug once actively
endorsed by the US President Donald Trump as a treatment against Covid-19 – should be discontinued,
because it has little to no effect on halting the disease’s progression.

Also on rt.com ‘No evidence of benefit’: FDA says hydroxychloroquine no longer approved for Covid-19
emergency use

The decision was taken after the preliminary results of clinical trials conducted as part of the Solidarity
Initiative – a WHO-backed international program aimed at tackling the Covid-19 pandemic – were
received. The same study also showed that lopinavir/ritonavir – the two drugs normally used in anti-HIV
therapy, and also touted as a potential cure against Covid-19 – are similarly ineffective.

“Interim trial results show that hydroxychloroquine and lopinavir/ritonavir produce little or no reduction in
the mortality of hospitalized COVID-19 patients when compared to standard of care. Solidarity trial
investigators will interrupt the trials with immediate effect,” the organization said in a statement.

WHO accepted the recommendation from the Solidarity Trial’s International Steering Committee to
discontinue the trial’s hydroxychloroquine and the lopinavir/ritonavir arms. More
https://t.co/dCxHqBIwtr#COVID19#coronavirus

— World Health Organization (WHO) (@WHO) July 4, 2020

It noted, however, that the aforementioned results have not yet been peer-reviewed, and its
recommendations do not affect any potential use of the drugs in non-hospitalized patients or as a
prophylaxis – Trump’s own use of hydroxychloroquine.

The WHO had already halted its trials of hydroxychloroquine, citing “safety concerns,” after a prestigious
British medical journal, The Lancet, published a study on the side-effects of the drug, which included a
higher mortality rate among Covid-19 patients.

The move prompted many nations – among them, France, Italy, and Belgium – to ban the use of the drug
in the treatment of coronavirus. Others, such as Spain or Russia, declined to do so.

Eventually, the WHO resumed the trials, this time citing doubts over the side-effects research itself. Its
current position is that “the interim results do not provide solid evidence of increased mortality.”

Rush To Trash Hydroxychloroquine Based On Faulty

Surgisphere Data Exposes Fundamental Flaws In Profit-
Based Medical ‘Science’
4 Jun, 2020

Helen Buyniski is an American journalist and political commentator at RT. Follow her on
Twitter @velocirapture23
As the WHO and prestigious medical journal the Lancet back away from questionable data provided by
healthcare analytics firm Surgisphere, ulterior motives for the rush to demonize hydroxychloroquine
become clear.

The World Health Organization (WHO) sheepishly resumed testing the off-patent malaria drug
hydroxychloroquine on coronavirus patients on Wednesday after pausing that arm of its ‘Solidarity’ clinical
trial based on data that appeared to show the drug contributed to higher death rates among test subjects.
That data, it turned out, came from a tiny US healthcare analytics firm called Surgisphere, and calling it
faulty would be excessively charitable.

Not only is Surgisphere a company lacking in medical expertise – its employees included an “adult”
entertainer and a science-fiction writer – but its CEO Sapan Desai co-authored two of the damning studies
that used the firm’s data to smear hydroxychloroquine, already thoroughly demonized in the media thanks
to its promotion by US President Donald Trump, as a killer. All data is sourcedto a proprietary database
supposedly containing a veritable ocean of real-time, detailed patient information yet curiously absent from
existing medical literature. 

The Surgisphere-tainted study appeared to show increased risk of in-hospital deaths and heart problems
with no disease-fighting benefits, confirming the suspicions of medical-industry naysayers already inclined
to hate the off-patent drug due to the lack of profit potential and Trump’s incessant boosterism. Italy,
France, and Germany rushed to ban hydroxychloroquine, citing “an increased risk for adverse reactions
with little or no benefit.”

But such a shameless character assassination performed against a potentially-lifesaving drug – especially
one with a decades-long track record of safety in malaria, lupus, and arthritis patients that came highly
recommended by some of the world’s most eminent disease experts, including France’s Didier Raoult–
could only be accomplished with help from industry prejudice. It required ignoring numerous existing
studies showing hydroxychloroquine was beneficial in treating early-stage Covid-19 patients, as well as
anecdotal reports from thousands of doctors who’d successfully used it.

It also required trusting a fly-by-night company with next to no internet or media presence to make
decisions that could affect the lives of millions of people. It’s not like there weren’t warning signs
Surgisphere was something other than the top-notch medical analytics firm it presented itself as. The
company began life as a textbook publisher in 2008 and hired most of its 11 employees two month ago,
according to an investigationby the Guardian, yet it claimed ownership of a massive international database
of 96,000 patients in 1,200 hospitals worldwide. One expert interviewed by the outlet said it would be
difficult for even a national statistics agency to do in years what Surgisphere had supposedly done in
weeks, calling the database “almost certainly a scam.” Yet no one at the Lancet or WHO thought to look a
gift horse in the mouth – not when that gift drove a stake through the heart of hydroxychloroquine as
Covid-19 treatment.

And while Australian researchers found flaws in the Surgisphere data just days after the May 22
publication of the Lancet study, noting that the number of Covid-19 deaths cited by the study as coming
from five hospitals exceeded the entirety of Covid-19 deaths recorded in Australia at that time, the Lancet
– instead of investigating just who this Surgisphere company really was, and why it had made such a
glaring mistake – merely published a minor retraction related to the Australian data and put the
controversy to bed.

The full-frontal assault on hydroxychloroquine was instead allowed to continue unchecked in the
media, as mainstream outlets focused their energies on fluffing up Remdesivir – a costly, untested
drug manufactured by drug maker Gilead that has so far produced lackluster results in clinical
trials – and stumping for an eventual vaccine. Hydroxychloroquine’s off-patent status meant it was
a dead end as far as profits were concerned, while Remdesivir and whatever vaccine is ultimately
green-lighted will make a lot of people very rich. Perhaps hoping to throw their audiences off the
real reason for their hydroxychloroquine hatred, several outlets hinted that Trump stood to make
money off the drug (which costs about 60 cents per pill) – but even Snopes, no fan of the ‘Bad
Orange Man’, had topourcold water on that speculation.

The Lancet and New England Journal of Medicine have – belatedly – published “expressions of concern”
about the Surgisphere hydroxychloroquine study, and an independent audit is being conducted. But the
problem of biased health authorities selectively embracing some trial results while rejecting others is
unlikely to stop there.

The Lancet study is hardly the only one to show hydroxychloroquine lacks efficacy in treating Covid-19.
Multiple studies conducted by the US National Institutes of Health on hospitalized (i.e. severely-ill)
coronavirus patients have yielded poor results, but even the drug’s most ardent evangelists acknowledge it
doesn’t help end-stage or very sick patients. Raoult has even claimed France banned the drug’s use in all
but the most severely ill patients in order to discredit it as a treatment. The US National Institutes of Health
was publishing studies in its journal Virology touting chloroquine as “a potent inhibitor of SARS coronavirus
infection” as far back as 2005, yet ‘coronavirus czar’ Anthony Fauci throws shade at the drug whenever he
gets a chance.

As long as deadly diseases like Covid-19 are seen as profit sources first and human rights issues second
(or third, or tenth…), treatments that aren’t profitable will always be marginalized in favor of costly and
frequently less-effective pharmaceuticals. Drug industry profiteering has already killed hundreds of
thousands – if not millions – of people in the US alone. Taking the profit motive out of healthcare can help
ensure its body count stays as low as possible.

Top Medical Journal Retracts Covid-19 Study Criticizing

Hydroxychloroquine After Validity Of Research Data
Questioned
4 Jun, 2020 21:26

The Lancet, one of the top medical journals in the world, has retracted a study questioning the safety of
treating Covid-19 with anti-malaria drug hydroxychloroquine, following controversy surrounding the
research firm behind it.
The retraction officially came at the request of the study’s authors, who admitted on Thursday they could
“no longer vouch for the veracity of the primary data sources.”

"We deeply apologize to you, the editors and the journal readership for any embarrassment or
inconvenience that this may have caused,” the authors added. 

The data used in the study appeared to show that chloroquine and hydroxychloroquine caused higher
death rates in test subjects. It was cited far and wide as grounds to halt testing of both drugs in Covid-19
patients, including by the World Health Organization. 

Healthcare analytics firm Surgisphere, which provided the data, has come under serious scrutiny in recent
days as details about the company have come to light.

Though the firm claimed to have gathered their data from thousands of patients at hundreds of hospitals
worldwide, an independent investigation has questioned the accuracy of their research. The firm was also
found to have almost no online presence and only a handful of employees, one of whom is a science
fiction writer and another who is an “adult” entertainer. 

Lancet previously admitted “concern” over the study, after troubling facts about Surgisphere came to light,
but did not officially retract it until now.

The Surgisphere-based study went further than others that questioned the benefits provided by the anti-
malaria drugs, by actually suggesting those taking it had a higher mortality rate. This conclusion created
concerns in the medical community and halted global trials.

Hydroxychloroquine first got attention from many medical experts and the mainstream media after US
President Donald Trump promoted it as a possible treatment for patients suffering from Covid-19.

Surgisphere has responded to criticism of their research in a statement on their website where they defend
the validity of their data registry, and claim they "clearly outlined the limitations of an observational study
that cannot fully control for unobservable confounding measures."

WHO Says Hydroxychloroquine Trials For Covid-19 Will

Resume As Doubts Emerge Over Side-Effects Research
3 Jun, 2020 17:57

The World Health Organization has said that clinical trials involving the controversial drug
hydroxychloroquine will resume, following doubts about US research which had led to their suspension.

WHO chief TedrosAdhanom Ghebreyesus said Wednesday that the trials of the anti-malarial drug for
possible use against the novel coronavirus would be resumed, after they’d been paused over fears of
increased death rates.
The world health body said there was no reason to modify its clinical trial of the drug, adding that experts
had advised the continuation of “all arms” of the so-called Solidarity trial, including that concerning
hydroxychloroquine.

Last week, Italy, France and Germany banned the use of the drug to treat Covid-19 patients, citing new
clinical evidence indicating that there was “an increased risk for adverse reactions with little or no benefit.” 

The much-publicized study in medical journal The Lancet could not confirm any benefit from the drug
against Covid-19, and also reported that taking it was associated with increased risks of in-hospital deaths.
However, serious questions have been raised about the data used in that study.

The research, by US-based companySurgisphere, began to unravel in recent weeks as experts noticed
red flags and questioned the credulity of its data-gathering and reporting. The Lancet journal issued an
“expression of concern” over the study on Wednesday. 

We have published an Expression of Concern on the paper by Mehra et al on hydroxychloroquine

and chloroquine published on May 22, 2020 https://t.co/yQ9irhRHxxpic.twitter.com/5I1NXTKTjo

— The Lancet (@TheLancet) June 2, 2020

A Guardian investigation found that Surgisphere’s employees “have little or no data or scientific
background,” with one appearing to be a sci-fi author and fantasy artist. The firm’s chief executive
Sapan Desai has been named in three medical malpractice suits, the outlet said.

One WHO expert said hopefully trials of the drug will continue until there is a “definitive” answer on
whether or not it works, Reuters reported.

WHO Suspends Trials Of Trump-Chosen

Hydroxychloroquine Drug Over Safety Risks For Covid-19
Patients
25 May, 2020 17:31

The World Health Organization has paused the clinical trials of anti-malarial drug hydroxychloroquine in
coronavirus patients. It says the drug, notably taken and endorsed by US President Donald Trump, has
raised safety concerns.

The drug’s safety data is being reviewed by a monitoring board, and the trials have been put on hold, the
WHO chief TedrosAdhanom Ghebreyesus told reporters. It was being tested as part of the Solidarity
international program aimed at tackling the Covid-19 pandemic.

The UN health body took the step out of an “abundance of caution,” said Mike Ryan, the head of the
organization’s emergencies program.
The WHO move comes after a prestigious British medical journal, The Lancet, published a study on the
side effects of the drug. The article found a higher mortality rate among the Covid-19 patients that had
received it. This is in contrast with the earlier positive reviews of the drug, said to have observed just the
opposite.

Ghebreyesus said a monitor will now “review a comprehensive analysis and critical appraisal of all
evidence available globally” regarding the effects of hydroxychloroquine. The “likely side effects” of the
drug seen in patients suffering from “severe” Covid-19 cases involved “cardiac complications, including
development of cardiac arrhythmias,” Ryan said.

The WHO has previously advised against the widespread use of the drug in the treatment of Covid-19,
arguing that it should be reserved solely for clinical trials. However, it has been actively promoted by
Trump, who even took a two-week course of hydroxychloroquine as a preventive measure against the
coronavirus. In his latest interview, published Sunday, Trump said he'd finished the course and “is still
here.”

The US president’s statements – which rammed home the message that the cheap and decades-old drug
“saves lives” – have sparked a flurry of warnings and skeptical media commentary. Some channels rushed
to caution the drug might literally “kill” people, while others doubted Trump took it at all. The developments
prompted the White House physician, Sean Conley, to say that the benefits of such treatment
“outweighed” the risks – but he stopped short of directly confirming if the president took the course.

Major pharmaceutical companies have been engaged in a race to develop a vaccine against the dreaded
disease, although scientists warn it is unlikely to arrive any sooner than in 12-18 months.

In mid-May, Trump announced what he called “Operation Warp Speed” – a major effort to develop a
vaccine that would see the government investing in “all top vaccine candidates.” The number of those has
so far been narrowed down to 14 and will be cut down further. Trump said he “would love” to see a vaccine
not just developed but also manufactured and distributed by the end of the year.

In absence of vaccine, several companies have pushed their drugs as possible remedies against Covid-
19. One of them is remdesivir developed by Gilead Sciences, which has been touted as a “miracle” drug
against the disease, even though the results of its use against the coronavirus have been mixed at
best. Remdesivir is also estimated to cost between $390 and $4,500 per dose – hundreds of times more
than drugs like hydroxychloroquine, which costs less than one dollar.

Italy And Belgium Join France In Rejecting

Hydroxychloroquine For Covid-19 Treatment
27 May, 2020 14:26

Italy and Belgium have joined France in moving to ban the use of the controversial hydroxychloroquine to
treat Covid-19 patients as questions continue to mount over its safety.
On Wednesday, France revoked its decree authorizing the prescription of the anti-malarial drug for the
novel coronavirus following a decision from the government’s health advisory agency.

Now Belgium’s health body has warned against using the drug outside of ongoing registered clinical trials.

Italy’s health authorities also concluded that there is too little evidence to support the use of
hydroxychloroquine for Covid-19 and that the lack of proof means it should be banned outside of clinical
trials.

The Italian Medicines Agency (AIFA) also cited new clinical evidence on the use of the drug which
“indicates an increased risk for adverse reactions with little or no benefit.”

“Pending obtaining more solid evidence from the clinical trials that are underway both in Italy and in other
countries of the world,” the decision was made to suspend the authorization of its use in hospitals and at
home, AIFA said.

A new study published in the Lancet medical journal could not confirm a benefit of taking the drug as a
treatment against the virus. It found that taking the drug was actually associated with increased risks of in-
hospital death for Covid-19 patients.

Britain's pharmaceutical regulator also said Wednesday that a hydroxychloroquine trial by the University of
Oxford has been "paused" less than a week after it began due to safety concerns. It said other trials of the
anti-malaria drug for the treatment of Covid-19 remain "under close review."

The drug became a massively controversial treatment for the virus after it was touted by US President
Donald Trump as a potential miracle cure. Trump even said this month that he was taking a course of the
drug as a “preventive measure” against the infection.

Spain Will Not Ban Hydroxychloroquine, Unlike Other

European Nations Spooked By Reported Side Effects
28 May, 2020 09:18

The Spanish health watchdog has said it sees no reason to stop the use of hydroxychloroquine (HCQ), the
potentially dangerous medicine touted as a Covid-19 treatment by the US president.

Several European nations, including France, Italy and Belgium, have decided to suspend prescription of
the anti-malaria drug, which came to international prominence after US President Donald Trump said the
medicine could be used to tackle Covid-19 and that he himself was taking it.

The Spanish health watchdog, AEMPS, said the paper published by the magazine Lancet, which warned
about health risks associated with HCQ, was not conclusive enough to stop testing it at Spanish hospitals.
“It is an observational study, not a clinical trial,” a spokesman for AEMPS explained.
HCQ, which is also used to treat autoimmune diseases like lupus, has been widely prescribed in Spain to
Covid-19 patients, with the country enduring one of the worst outbreaks of the disease in Europe.
According to El Pais, 85 percent of patients taken to hospital with the coronavirus received the medicine.

The Lancet study found a higher mortality rate among Covid-19 patients who had received HCQ. The
World Health Organization (WHO) decided to pause clinical trials of the medicine for coronavirus treatment
following the report’s publication.

Russia Will Not Ban Hydroxychloroquine, Drug Taken By

US President Trump, For Use In Treating Covid-19
28 May, 2020 14:33

By Jonny Tickle

Russia’s Health Ministry announced it will not ban hydroxychloroquine, seen by some as potentially
dangerous. The drug, touted by US President Trump, has been suspended for use in treating Covid-19 in
France, Italy, and Belgium.

On Thursday, the Russian Health Ministry stated on its website that hydroxychloroquine’s effectiveness
and safety in the treatment of coronavirus is continually being monitored, but the ministry is not taking any
steps towards outlawing it. This decision is in sharp contrast to moves made by some European countries
which, due to safety concerns, have completely stopped the prescription of the drug to fight the
coronavirus.

“Several drugs are used to treat patients with Covid-19,” a ministry statement said. “Among these
drugs is hydroxychloroquine, which, due to its anti-inflammatory effect and effect on the immune
system, has been used for decades to treat malaria, rheumatoid arthritis, and systemic lupus
erythematosus.”

According to the Health Ministry, recommendations to use HCQ have come from various foreign studies
confirming its effectiveness, and it has been included in several national and international clinical
guidelines, including in Russia. As it stands, Russian doctors are able to give the drug to patients who
provide informed consent, taking into account potential side effects and risk factors.

“According to the results of monitoring the safety of hydroxychloroquine drugs during the Covid-19
pandemic in the Russian Federation, there were no fatal outcomes associated with rhythm disturbance in
patients with HCQ,” the ministry said.

The drug, most often used to treat malaria, rose to prominence on March 19 when US President Donald
Trump promoted the medication as a potential treatment for Covid-19. On May 25, the World Health
Organization (WHO) announced it would be suspending its hydroxychloroquine testing out of what it called
an “abundance of caution.” HCQ was just one part of a more extensive study of experimental coronavirus
treatments.
The WHO’s decision to stop the testing came after a study published in the prestigious British medical
journal the Lancet, which found an increased mortality rate in patients taking the drug.

Following the halting of the WHO’s trials, several nations, including France, Italy, and Belgium, opted to
suspend the prescription of the drug for Covid-19. Other countries, such as Spain, have decided to
continue giving HCQ to coronavirus patients.