clinical trials

Pfizer Applies For FDA Approval

Pfizer announced that today it will seek approval for its anti-CoV-2 vaccine. If approved, the vaccine can be distributed as early as December. Given the urgency, the FDA is expected to move quickly.

The final numbers, released last Wednesday, showed that of the 170 subjects in the trial who caught COVID-19, 162 had received the placebo, meaning that the vaccine was 95% effective. It also was 94% effective in people 65 and older. Nine of the 10 subjects who came down with severe COVID-19 had received the placebo, meaning that the vaccine protects against severe disease.

This is a momentous vaccine. It will be the first RNA vaccine and, by far, the fastest to be developed and distributed, which will revolutionize vaccinology. This moved rapidly for several reasons. 1) The RNA vaccine platform had already been developed and it was just a matter of inserting the genome sequence for the viral spike protein into it. 2) RNA vaccine technology greatly speeds vax development since it completely avoids the need to grow massive amounts of virus iteslf. 3) Genome sequencing is now done very rapidly. The Chinese published the CoV-2 genome sequence in just a few weeks after the new virus was identified. 4) Pfizer began mass production of the vaccine while it was still in the experimental stage and not yet approved, thereby eliminating the typical delay required to ramp up production capability. 5) Trump’s Operation Warp Speed pre-planned for the massive storage and distribution effort that will be needed so that as soon as approval is granted, the already manufactured vaccine can immediately be distributed.

After approval, vaccine for about 25 million people will be immediately available for distribution and the US is scheduled to receive half of that. 1.3 billion doses are expected to be produced next year, which will enough to vaccinate 650 million people. In the US, it is likely that the first doses will go to health-care workers, followed by those at high risk, people in nursing homes, and prisoners. The general public probably will not get access until the spring or summer. The US has agreed to pay Pfizer and BioNTech nearly $2 billion for 100 million doses, enough to vaccinate 50 million people at no charge to them.

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Great News On The CoV-2 Vaccine Front

The news: Pharma giant, Pfizer, and its German biotech partner, BioNTech, just announced that preliminary indications show that its two-shot anti-CoV-2 vaccine is 90% effective in preventing infection. The study is not yet complete, meaning that this is based on what is called interim data analysis. All large scale clinical trials schedule such interim analysis in order to detect potential problems with the study such as potential side effects, enrollment problems, and to make a preliminary assessment on the trial's outcomes. The review is done by a Data and Safety Monitoring Board (DSMB), an independent panel of scientists and statisticians who are not part of the study. Using an independent DSMB allows study personnel to remain blinded as the trial proceeds.

In this case, the interim review of data by the DSMB compared the number of subjects in the placebo control group who became infected to the number of infected subjects who received both vaccine doses. This showed that vaccinated subjects were 90% less likely to be infected. The interim analysis also showed negligible adverse effects in the group who received the vaccine. While still preliminary, these results are encouraging. The study will continue over the next couple of months and even beyond in order to learn how long the immunity lasts and how effective it is in different populations including the elderly and other high risk groups. There seems to be a good chance that final approval will come around the end of year and vaccinations begin shortly after that.

Pfizer began manufacturing the vaccine a few months ago so that they would have a stockpile ready to distribute as soon as FDA approval comes. While this eliminates the usual post-approval delay to ramp up production capability, this strategy is a major gamble for the company since it is not guaranteed that the vaccine would be approved. If the vaccine does not pan out, the company will have to eat the cost for manufacturing a useless vaccine. On the other hand, if the vax is approved, Pfizer is poised to immediately deliver hundreds of millions of doses while their production efforts continue.

This is the first RNA vaccine tested in humans. The potential advantage of this approach is that it completely avoids using the virus itself. “Old fashioned,” vaccines required growing the virus in mass quantities and then crippling or killing it for injection, which is labor intensive, entails certain risks, and is expensive. Instead, the Pfizer vaccine involves cloning part of the genome that is thought to be a target for the immune system, packaging it in an inert lipid nanoparticle, and injecting it in order to aggravate the immune system. The idea is that this fragment of the viral genome will be taken up by human cells and the cellular machinery will use it to produce the viral protein that can stimulate an immune response in the absence of the virus itself. The cells will soon degrade the cloned RNA fragment leaving only immunological memory with which to fight reinfection.

What is next? While this is encouraging news, this brings us to perhaps a larger problem to solve, which is how the early vaccine will be most effectively and fairly distributed. By the end of the year, Pfizer will have a few hundred million doses and predicts it can produce 1.3 billion doses in 2021. Since this is a two-dose vaccine, that means that that will be enough to vaccinate about 650 million people, or less than 10% of the 7.8 billion who live in the world. Who will have priority for the first doses of the vaccine? Will front line health care workers and high risk people be given the first doses? What about world-wide distribution? Since the vaccine is being tested and made by an American company (Pfizer) using technology developed by a German biotech (BioNTech), should those two countries reap the immediate benefit of the early limited doses of vaccine, while the rest of the world waits months for sufficient doses of the vax to meet their needs?

The WHO recommends that the vax be distributed to each country based on its population. Another recommendation from the National Academies of Sciences, Engineering, and Medicine is to distribute it based on each country's number of health care workers and high risk populations. Others argue that the US should base distribution on racial and socioeconomic disparities. U Penn doctor and medical ethicist, Ezekiel Emanuel (a primary author of Obamacare), proposed a Fair Priority Model that would favor countries with younger populations, weaker economies, and with poor health access--in other words, third world countries.

These suggestions seem moot since advanced purchase agreements already give 80% of that early vax supply to the US, UK, Canada, and Japan.

Another issue regarding distribution is that the vaccine needs to be stored and transported in ultra-cold conditions (-80 degree C. or -112 degrees F.). Such ultra-cold storage facilities are in short supply around the world, meaning that countries with poor health infrastructure will be at a significant disadvantage because they cannot store the vaccine. This ultra-cold storage requirement will also make it challenging for the vax to be administered in a normal doctor’s office or pharmacy, which typically do not have ultra-cold freezers. 

Logistics: Once the vaccine is approved, the enormous task of getting billions of doses distributed across the US and around the world begins. This is where Trump’s Operation Warp Speed comes into to play. Even though the Pfizer vaccine was not developed under that program, the logistics of its distribution will be part of Warp Speed, which also includes massive pre-planning for storing, distributing, and delivering two doses of the vaccine ultimately to 300 million Americans. The US Army Materiel Command, headed by four star general Gus Perna, has been tapped for this undertaking. He is the one who sees that American military forces around the globe have sufficient housing, clothing, food, and beer. So, he seems like a good choice to oversee the distribution of billions of doses of a vaccine. You can see more about this on the Nov 8 episode of 60 Minutes. The logistics and planning for this almost makes the development of the new vaccine a trivial issue.

There is joke that goes something like this: Hell is where the English are the cooks, Italians the managers, and Americans the soccer lovers. Heaven is where the English are the soccer lovers, Italians the cooks and Americans the managers. This is a good example of American large-scale management, so we must be in heaven.


Trump’s Treatment

Being, male, elderly (74 years old), and borderline clinically obese, Mr. Trump meets three high-risk criteria for severe COVID-19 disease. Despite reporting negligible symptoms at this point, his doctors at Walter Reed have him on aggressive precautionary therapeutic measures.

He has been given the anti-viral drug, Remdesivir that shows moderate effects against the CoV-2 virus and has become a standard-of-care treatment for hospitalized COVID-19 patients. He also has received an intravenous dose of Regeneron Pharmaceutical’s cocktail of two experimental anti-CoV-2 monoclonal antibodies. These are antibodies produced in the lab that are designed to mimic the naturally occurring antibodies the immune system produces in response to CoV-2 infection. They provide a boost to the natural immune system, especially during the early stages of infection when one’s natural immunity is still ramping up. While the monoclonal antibody therapy is experimental, early evidence suggests that it provides a significant protective effect. It was approved for Mr. Trump under a “compassionate use” clause for experimental therapies.

He reportedly also has been taking daily aspirin, which has anti-coagulant properties, as well as over-the-counter vitamin D and minerals needed for a healthy immune response. A paper published last month in the journal PLOS ONE found a higher rate of coronavirus cases in people who were deficient in vitamin D than in people who had normal levels of vitamin D. But this is just a correlation and more research is needed to confirm that there is a biological cause-and-effect relationship between vitamin D levels and COVID-19.

It is interesting that it appears Mr. Trump has not been taking hydroxychloroquine, which he earlier pushed, and which more recently has been pushed by some physicians and touted by many lay people to be a COVIID-19 cure despite growing scientific evidence showing that it is not effective, even when given to early stage COVID-19 patients.

Update (Sunday 10/4): It was reported today that Trump has displayed transient low oxygen levels that seemed to be taken care with supplemental oxygen. He also has been given dexamethasone, a steroid, in order to prevent inflammation of his lungs. His doctor expects him to be released from Walter Reed tomorrow (Monday).

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Science vs Nonscience In Understanding Hydroxychloroquine

A recently much shared video of America’s Frontline Doctors Summit shows several clinicians claiming that hydroxychloroquine (HCQ) is a "cure" for COVID-19. Their evidence for this claim is their personal experiences treating these patients with HCQ along with a cocktail of other drugs. The video was shared 14 million times before Facebook and other hosting services took it down, ostensibly for spreading inaccurate information. While the debate whether such censorship is reasonable, it is also reasonable to point out that the doctors were, in fact, sharing information that is not known to be accurate and that has a high chance to be inaccurate; in other words, scientifically unproven. They grossly overstated their conclusions from their non-scientific observations. It is irresponsible for a doctor to claim that her anecdotal experience “proves” the efficacy of any unproven therapy. If the docs had been honest, they should have said that their observations warranted further controlled clinical trials in order to prove or disprove their claims. 

One of these doctors said that she had treated 350 patients with the drug cocktail and that none died; therefore, she irresponsibly declared that she had a “cure” for the disease. While that sounds impressive, she did not do a controlled clinical trial, which means that we have no way of knowing whether the 350 also would have survived without the drug. She also claimed that her success was because the patients she treated with the cocktail were at the early stage of disease. Unfortunately, we don’t know what that means since she didn't report their clinical details as she would have been required to do in a gold standard clinical trial. This doctor also had a web page where she talked about how gynecological problems are caused by engaging in sex with demons, and that alien DNA was being used in modern medicines; all the more reason to suspect her credibility.

In other venues, I have pointed out these problems with the America’s Frontline Doctors Summit and received a lot of push-back from non-scientists. For some reason, some people bring a strong need to believe in HCQ without considering the science. So, they readily jump on ANY report that confirms their bias as proving that the drug is a cure. Several of these “experts” quickly pointed me to a recent report from the Henry Ford Health System that claimed that hydroxychloroquine saved lives. It was published earlier this month in the International Journal of Infectious Diseases. 

However, the Henry Ford report was not a clinical trial, but a much weaker retrospective chart review of more than a thousand COVID-19 patients seen in the system’s nine hospitals. In other words, the patients were not randomized, the “study” was not blinded, and patients were not treated according to a controlled, standardized study protocol. Hence, it was only marginally better than the undocumented anecdotes of America’s Frontline Doctors. At least, because the Henry Ford docs published a report on their personal observations, interested clinicians and researchers could look at the aggregate patient data. That was not the case regarding the claims by the America’s Frontline Doctors.

On Wednesday, in response to the Henry Ford report, the same journal published several scathing critiques claiming the report had serious errors. The major problem was that the patients given the HCQ cocktail regimen were healthier than the patients that were not given it. The patients not given the cocktail had more advanced disease and more frequent comorbidities that put them in a higher risk group compared to those who received the treatment. Furthermore, the HCQ treatment group was more aggressively treated and more than twice as likely to receive steroid therapy, which has been shown to help certain COVID-19 patients.

In other words, in this chart review of patient experiences, the two groups that were compared were very different and it is highly possible that the death rate difference between them would have been the same even if the HCQ protocol was not used. An important goal of randomized, blinded, controlled clinical trials is to make sure that the treatment and non-treatment comparison groups are as similar as possible in order to eliminate such bias that can skew the study’s results. This is why scientific clinical trials and not chart review reports are the gold standard for determining the best health care.

Unfortunately, people who take these anecdotal testimonies, and poorly controlled chart review reports as proof that HCQ is the panacea for COVID-19, also selectively ignore other recently reported gold standard clinical trials that show that HCQ is ineffective. This week, a randomized clinical trial in Brazil showed that hydroxychloroquine doesn't work to treat patients with Covid-19. Another randomized trial last month at the University of Minnesota showed it also doesn't help prevent infection. Other clinical trials -- one in the US, and one in the UK were halted early because interim data analysis showed the drug wasn’t working.

Like America’s Frontline Doctors emphasized, the authors of the Henry Ford report pointed out that HCQ worked for their patients because it was prescribed very early in their hospitalization. But, University of Albany researchers earlier reported that the HCQ cocktail approach was ineffective in a randomized, blinded trial employing subjects at the same point of disease as the patients in the Henry Ford report.

As reported earlier in these pages, because of similar negative clinical trials, the FDA recently pulled its approval for HCQ to treat COVID-19.

There is a very good reason why we rely on carefully designed and controlled clinical trials rather than anecdotal information or retrospective chart reviews in determining the best way to treat disease. The best the latter should contribute is to generate interest in testing the observations in controlled clinical trials to see if they are accurate.

While your humble blogger initially was enthused about the potential of HCQ to treat COVID-19, I increasingly sour on it as science continues to show it doesn’t work. So far, the reports claiming that HCQ is effective against COVID-19 are mostly based on unsubstantiated doctor’s anecdotes, or on uncontrolled retrospective chart reviews. In contrast, the reports that indicate that HCQ is ineffective are based on stronger randomized and controlled clinical trials.

Who are you going to believe?


Even More Good News On The Vaccine Front

The NIH just announced that a Phase 3 clinical trial of a CoV-2 RNA vaccine was launched today. The highly novel vaccine, developed by the National Institute of Allergy and Infectious Diseases and the biotech company, Moderna, uses no virus vehicle, just a segment of the CoV-2 RNA genome. This is a highly novel approach since no RNA vaccine has been developed to any pathogen. If successful, it will revolutionize vaccinology by eliminating any infectious vehicle that could cause side effects. It also will dramatically speed novel vaccine development since all you need is a genetic sequence of the pathogen, after which it is simple to produce in any lab. It is the second RNA vaccine under development that will soon enter phase 3 testing. The other vaccine is being developed by the pharma giant Pfizer and the German biotech company, BioNTech, and is expected to also enter phase 3 trials in a few days.

Since about 30,000 volunteers are needed for this trial, it is being conducted at 89 partner sites around the US, under the oversight of the The NIH Coronavirus Prevention Network (CoVPN). Adults who are interested in joining this study can visit www.coronaviruspreventionnetwork.org(link is external) or visit ClinicalTrials.gov and search identifier NCT04470427 to find a study center to volunteer.

Seeing how the virus continues to spread in most states, even accelerating its spread in many states, makes it increasingly possible that an effective vaccine will be available by the end of the year. Even if that happens, we will still need more time to understand other variables, such as how long the immunity lasts, and how well people over 60 are protected.


Good Progress On The Vaccine Front

At last tally 197 vaccine candidates against the CoV-2 virus are being developed around the world. On May 12, that number was 125. It seems that vaccine candidates are spreading as fast as the virus. According to the World Health Organization, 23 of these experimental vaccines already are in human trials. As reported two months ago in these pages, the vaccine that seems to have the early lead is being developed at England’s Oxford University in partnership with the pharma company AstraZeneca. On Monday, they reported encouraging results from their combination phase 1/2 study in the journal The Lancet.

Jenner instThe Jenner Institute, Oxford University

It also seems that two other vax candidates have caught up to the Oxford efforts and also have reported encouraging results in early combination phase 1/2 or phase 2 studies. One of the vaccines is being developed by the Chinese company CanSino Biologics, which also published its results from early phase 2 trials on 500 subjects in the same issue of The Lancet. Both the Oxford and Chinese labs are developing a recombinant vaccine in which the genetic sequence for the CoV-2 spike protein is engineered to be expressed as part of a crippled adenovirus genome. The adenovirus will infect human cells, but not replicate or cause disease. 

The third vaccine is being developed by the pharma giant Pfizer and the German biotech company, BioNTech. This is a highly novel RNA vaccine where just a simple genetic sequence from the CoV-2 virus is used to immunize patients. No virus is used at all, just some of the virus genetic material. They recently reported in a pre-print paper that has not yet been peer-reviewed, similarly encouraging results from a combination phase 1/2 trial on 60 subjects.

The results of the three studies were very similar. The vaccines were all safe and there were no serious side effects. The only problems were an occasional temporary fatigue, sore arm or headache, which were treated with Tylenol. These effects are much more pleasant than coming down with COVID-19.

Importantly, all three vaccines were shown to stimulate both arms of the adaptive immune response, which is a crucial factor for a successful vaccine. The first arm is the B cell, or bone marrow-derived lymphocyte response. B cells produce antibodies that neutralize the virus, but they fade away after the infection is cleared, not providing long term immunity. The second arm is the thymus-derived lymphocyte, or T cell, response. Activating a T cell response is particularly important for a successful vaccine because it is what oversees the whole immune response to a pathogen and, more importantly, produces long lived memory T cells that impart a long term sentry function to the pathogen, which is what “immunity” is. Memory cells are the basis for long-lived vaccine protection. A successful vaccination will produce memory cells that will sound an alarm if you are later exposed to the pathogen. This alarm rapidly mobilizes your immune system to make a very robust defense that prevents the infection from developing. Therefore, it is very encouraging that the experimental vaccines activated T cell responses.

The Oxford vaccine stimulated T cell immune responses within 14 days and antibody responses in 28 days. Both responses were also stimulated within 28 days in the Chinese study. The Oxford and Chinese studies showed that 85-90% of vaccinated subjects developed antibodies that neutralized the virus and that response was sustained up to 56 days, which is how long the longest study followed the recipients. T cell responses were also seen in 90-100% of the vaccine recipients. The Chinese study further reported that people over 55 developed weaker responses than younger subjects, which was expected. The Oxford study only enrolled volunteers under 55 years. While employing a much smaller sample size, the German study had results similar to the Oxford and Chinese studies.

It must be cautioned that these very encouraging phase 1 and 2 studies did not test whether the immune response could actually protect people from the virus. In other words, they did not test whether the vaccines produced memory cells that could confer long-term immunity. This will be tested in the large phase 3 trials that will begin as early as the end of July. These will be massive studies involving tens-of-thousands volunteers. Phase 3 studies also will take longer since they require the subjects to be naturally exposed to the virus and develop COVID-19. After a period of time, the number of unvaccinated control subjects who develop the disease will be compared to the COVID-19 incidence in vaccinated subjects in order to learn if, and to what extent, the vaccine can protect against the virus. These results should be forthcoming in a few months. Phase 3 trials also will pay attention to vaccine safety in a much larger cohort of subjects than tested in the earlier trials.

If the phase 3 studies show that the vaccines can protect people against future infection with the virus and are safe, then they will be approved. In anticipation of this, some large pharma companies, such as AstraZeneca and Pfizer are already producing the, still experimental, vaccines. This means that if they prove effective, there will be a stockpile of vaccine that can be immediately dispensed around the world. The companies also have pledged to provide the vaccines at cost.

Just a few weeks ago, worry was that the virus seemed to be petering out and that it would be hard to find sufficient numbers of volunteers to undertake large phase 3 studies. However, as the virus is rebounding in most US States and is gathering steam elsewhere in the world, that does not seem to be a problem anymore. Just one week after the National Institutes of Health launched a clinical trial network for vaccines and other prevention tools to fight the pandemic, they announced that 107,000 Americans have already volunteered for vax studies. It is estimated that 120,000 volunteers are needed to adequately test the four lead vaccine candidates under development in the US (assuming 30,000 subjects are needed to test each vaccine). So the high enrollment is a good sign that the vax studies will not be hampered by low enrollment.

Stay tuned. We will see.


More Confusion About Hydroxychloroquine

After negative reports about the ability of hydroxychloroquine to help COVID-19 patients, and the FDA’s withdrawal of its emergency approval of the drug to treat the disease, we now get a report by the Henry Ford Health System that it was effective.

I am not sure what to believe about hydroxychloroquine at this point. I have seen and reported on convincing reports that it has a good effect in COVID patients and I have seen and reported on convincing reports that it does not.

Someone needs to sit down and look at all the raw data of all these reports to see if there is some trend that can explain it all. For example, what were the doses given in the different studies, what was the timing of the doses, how long was it given, what were the statuses of the patients it was given to, etc? If we weren't in such an understandable rush to find a treatment for the disease, all these things would be hashed out in a couple of large clinical trials over a couple of years. But we have been very rushed. For a drug that had clearly obvious effects, such confusion probably would not be a problem. But hydroxychloroquine does not seem to be all that obvious.

All of this tells me that if the drug is beneficial, it is for a select range of patients, or at a narrow therapeutic window, or both.

We will see.


FDA Revokes Emergency Use Approval Of Hydroxychloroquine

The Food and Drug Administration has revoked its emergency use authorization for the drugs hydroxychloroquine and chloroquine for treatment of Covid-19.

“FDA has concluded that...it is no longer reasonable to believe that oral formulations of HCQ and CQ may be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks," FDA chief scientist Denise Hinton wrote in a letter to Gary Disbrow of the Biomedical Advanced Research and Development Authority (BARDA) on Monday.

Doctors can continue to legally prescribe the drugs off-label, as they can with any drug that's approved for other conditions. The FDA's emergency use authorization for hydroxychloroquine and chloroquine was narrow in scope, applying only to hospitalized Covid-19 patients and only to drugs donated to the Strategic National Stockpile.

The World Health Organization and other laboratories around the world are still testing hydroxychloroquine for Covid-19 treatment. The WHO had temporarily paused the trial in May due to concerns surrounding the drug's safety and in order to review its own data, but resumed the program earlier this month after an interim data analysis determined that they had not seen significant safety concerns.

We will see.

 


Mixed News About Hydroxychloroquine And The Coronavirus

A couple of weeks ago, headlines screamed that the WHO was stopping a large clinical trial testing the efficacy and safety of treating hospitalized COVID-19 patients with the anti-malaria drug, hydroxychloroquine (HCL). The WHO did this in response to a study published in the May 22 edition of the journal, Lancet, that reported that the drug provided no therapeutic benefit while increasing the risk of heart problems and death in treated patients. The flurry of headlines that resulted was misleading as reported in these pages on May 25. The WHO did not cancel its study; rather they made a mid-study pause so that a team of independent scientists could review the interim data that had been collected to see if it also showed increased risk to study patients as reported in the Lancet study. That interim data analysis is complete and the WHO just announced that the study was re-started. That means that the partial data they have collected did not reveal concerns about study subject safety.

The Lancet study was not a “gold-standard” blinded and controlled clinical trial, but a prospective “chart review” of medical records of 96,000 COVID-19 patients hospitalized in 671 hospitals across six continents. The study claimed to find a 30% increase in mortality in patients treated with the drug and based on this, the World Health Organization paused its global clinical trial of HCL, and many countries banned the drug as a COVID-19 treatment.

Since the Lancet study was published, more than 100 scientists around the world raised serious questions about the reported data and about Surgisphere, the organization that provided the data. They spotted glaring data errors. For example: Obesity and smoking rates in the study patients surprisingly were the same across the six continents. Well established population health data indicates that this is not true. Also, in a letter to Lancet’s editors last week, 120 scientists criticized the study’s sloppiness and aggregation of data from patients who were different in many respects including in the dose of hydroxychloroquine they received, and in the severity of their illness. The complaining scientists also pointed out that in the study Lancet failed to share all patient data. Surgisphere’s CEO, Sapan Desai, one of the study’s authors, claimed his hospital contracts did not allow these data to be shared. This raised more red flags since the reliability and accuracy of the chart data could not be independently confirmed, which is a serious breach of scientific standards.

It now looks like the study may have been based on questionable data from a dubious source. In vitro studies have indicated that hydroxychloroquine can block the virus’s replication, and the drug has been safely used to prevent and treat malaria in millions of people worldwide for 60 years. It is also used to safely treat rheumatoid arthritis and lupus. The Food and Drug Administration has approved it for emergency use for COVID-19 patients. Therefore, the study’s conclusions run counter to decades of experience with the drug.

Wednesday, June 3, Lancet published an “Expression of Concern” about the study and said it would undergo “an independent data audit.” That’s good, but the study's publication may have already done public-health harm. Study doctors are complaining that the negative press has made it difficult to recruit patients in the U.S. for ongoing clinical trials to study the drug’s effectiveness as a prophylactic or for early-stage treatment against Covid-19.

As a result of this brouhaha, the authors of the study recently retracted it. They decided to issue the retraction after Surgisphere Corp. refused to share the full, detailed data set as part of a review after outside researchers raised concerns.  “Based on this development, we can no longer vouch for the veracity of the primary data sources,” said the authors, Mandeep Mehra, Frank Ruschitzka and Amit Patel.

So, the WHO and other studies, including several in the US, such as at New York University, the University of Washington, and elsewhere, continue to study whether hydroxychloroquine can treat people exposed to the virus.

Can HCL treat people with COVID-19? The jury remains out despite this interruption. We will see.

Meanwhile, a different gold-standard, double-blind randomized clinical trial involving 821 subjects was also published last Wednesday in the New England Journal of Medicine and it concluded that the drug is ineffective at preventing infection. Study subjects took the drug or a placebo for 5 days and were followed for 2 more weeks. About 12% of those taking hydroxychloroquine came down with COVID-19 compared to 14% of the placebo group. The difference was not significant. Also, 40% of the subjects taking hydroxychloroquine reported mild side effects while only 17% of the placebo controls did. Nausea, upset stomach and diarrhea were the most common side effects, but none were considered serious.

The bottom line is that the news on HCL and COVID-19 is mixed and confusing. The research continues.

We will see.