Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Why 90% vs. 62% for the Efficacy of the AstraZeneca Vaccine Candidate?

 

There was a press release from AstraZeneca at 7 AM today. It includes two different dosing methods with two dramatically different rates of efficacy. One group received half a dose, followed by a month later by a full dose. The other group received a full dose, followed by a month later by another full dose.

 

One dosing regimen (n=2,741) showed vaccine efficacy of 90% when AZD1222 was given as a half dose, followed by a full dose at least one month apart, and another dosing regimen (n=8,895) showed 62% efficacy when given as two full doses at least one month apart. The combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70%. All results were statistically significant (p<=0.0001). More data will continue to accumulate and additional analysis will be conducted, refining the efficacy reading and establishing the duration of protection.

 

Usually, the result of the differences in dosing is to use the lowest effective dose, in order to minimize any side effects, which are usually dose related. A higher dose is expected to be more effective, but also to have more side effects.

 

The part people are having a hard time explaining is that the 90% efficacy is in the smaller dose group. This does not seem to make medical sense, but this is what people who understand statistics expect.

 

Why?

 

Daniel Kahneman explains this in his excellent book, Thinking, Fast and Slow. He uses the following example as an introduction:

 

A study of the incidence of kidney cancer in the 3,141 counties of the United States reveals a remarkable pattern. The counties in which the incidence of kidney cancer is lowest are mostly rural, sparsely populated, and located in traditionally Republican states in the Midwest, the South, and the West. What do you make of this?

 

This is known informally as the Law of Small Numbers. Intuitively, we can come up with many different explanations about a healthy rural lifestyle, or something else. Kahneman follows that with the statistics on counties with the highest incidence of kidney cancer, which are also mostly rural, sparsely populated, and located in traditionally Republican states in the Midwest, the South, and the West.

 

The important factor is not lifestyle, not politics, and not geography. The important factor is that these are all sparsely populated counties, which means that the number of cases of kidney cancer will be disproportionately affected by the addition/subtraction of a tiny number of cases.

 

The small sample size is the most likely explanation for the 90% efficacy in the half dose, then full dose group. When more cases of COVID-19 are diagnosed among those who have received the half dose, then the full dose, expect the estimate of benefit to drop closer to 70%. The 70% efficacy is also based on small numbers, but those numbers (including the 90% sample) are more than four times the size of the 90% sample. This is not certain. This is statistical probability. A reasonable person should feel comfortable in placing a wager on the results dropping to near 70%.

 

In other words, the news is worse than expected, although still good news. There is another vaccine candidate that, based on the preliminary numbers, meets the approval criteria of better than 50% efficacy.

 

.

 

What Do the Moderna Vaccine Candidate Press Releases Tell Us?


 

I had thought that the vaccine studies would only be recruiting people up to 55 years old, which was the age limit on the phase 1 studies, but there is significant representation of people over 65 and people with serious comorbidities. This is excellent news.

 

According to one press release from Moderna:

The COVE study includes more than 7,000 Americans over the age of 65. It also includes more than 5,000 Americans who are under the age of 65 but have high-risk chronic diseases that put them at increased risk of severe COVID-19, such as diabetes, severe obesity and cardiac disease.

 

The other important concern I had was the need to store the vaccine at around -80 degrees C, which would limit access for a lot of people, even in America. From another press release, dated 4 minutes earlier, Moderna:

today announced new data showing that mRNA-1273, its COVID-19 vaccine candidate, remains stable at 2° to 8°C (36° to 46°F), the temperature of a standard home or medical refrigerator, for 30 days. Stability testing supports this extension from an earlier estimate of 7 days. mRNA-1273 remains stable at -20° C (-4°F) for up to six months, at refrigerated conditions for up to 30 days and at room temperature for up to 12 hours.

 

There is an excellent analysis of the press release on preliminary efficacy results at STAT News, which has been ahead of the rest of the media in recognizing the serious nature of this pandemic.

 

It is important to remember that a press release, even about something this serious, is a commercial, intended to promote the company’s product. The information provided by Moderna in the press releases has not been peer reviewed. The numbers may change as mistakes are caught and conclusions are examined. That is OK, because there will be thorough analysis of the results before any vaccine candidate is approved for use outside of these experiments.

 

How will we know when a vaccine is safe and effective? I provided my criteria in August, when I wrote about a vaccine approved by President Putin, based on inadequate research:

I want to see recommendation of a vaccine by the people who know the most about vaccines – Paul Offit, Michael Osterholm, Peter Hotez, and Anthony Fauci. They need to be able to see all of the evidence. The only reasonable conclusion about a refusal to share the evidence with any of them is that there is something bad being hidden. These are not politicians. None of these medical experts have shown signs of being influenced by political pressure.

 

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2020 ACLS Repeats the Mistakes of 2015 ACLS

 

 

The International Liaison Committee on Resuscitation (ILCOR) has updated the ACLS (Advanced Cardiac Life Support) recommendations by making excuses for the evidence.

 

We have been using epinephrine for 50 years without evidence of improved outcomes that matter to patients.

 

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest (Paramedic2) shows that epinephrine does not improve outcomes for prehospital patients.

 

In conclusion, in this randomized trial involving patients with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of survival at 30 days than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.

 

Rather than limit treatments to those with high quality evidence that they improve outcomes that matter to patients, the recommendation is to keep giving epinephrine, because eventually someone might provide something – anything – to support epinephrine.

 

What about amiodarone?

 

Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest (ALPS) showed that amiodarone also does not improve outcomes.

 

Conclusions Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

 

If amiodarone was mentioned, I missed it. Both epinephrine and amiodarone had large placebo-controlled research results released showing that the outcomes are worse with epinephrine and worse with amiodarone.

 

There is still no evidence that any ventilation produces better outcomes than compression-only resuscitation, but it looks like the intervention will continue to be recommended.

 

In the absence of evidence of benefit, inadequately tested interventions should be avoided.

 

The goal is to protect the patients, not to protect the interventions.

 

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What Treatments Will the Anti-Science President Use?

Now that President Trump’s attempts to prevent himself from developing COVID-19 have failed, for the president and for many of those around him, will the president continue to reject science, when it comes to treatment?

President Trump promoted hydroxychloroquine[1], [2], [3], which is a useful treatment for several medical conditions, but not effective against COVID-19. Should President Trump expose himself to the side effects, when there is no expectation of any benefit?

A reasonable person would not take hydroxychloroquine. A superstitious person might. This is a version of Pascal’s wager.[4] You have everything to gain, but nothing to lose. Except that Pascal’s wager ignores the more probable harms that comes from the preferred choice and assumes that all harm comes from not making the preferred choice. Therefore, Pascal’s wager is actually, You have everything to lose, but only a ridiculously long shot at any gain. Being unreasonable, Pascal’s is a losing wager.

President Trump promoted oleandrin[5], which is not a useful treatment for anything, unless you are trying for suicide or murder. Should President Trump take poison, when there is no expectation of any benefit? I suspect that many of the people who have been harmed by President Trump would say, Yes, but that is not the way medicine works.

The role of medicine is to provide the most effective treatment, taking into consideration the potential harm, in order to improve the outcome for the patient. Killing people, other than as part of medically assisted suicide (where the goal is to end the suffering of the patient at the request of the patient), is for other professions.

President Trump promoted convalescent plasma[6], which is only supported by low quality evidence and no completed high quality research. Maybe convalescent plasma works, but we may not know for a long time, because the high quality research will have trouble continuing. The EUA (Emergency Use Authorization) makes convalescent plasma available to patients outside of controlled research.

Since doctors have trouble understanding science, how do we expect patients to understand?

I was involved in a discussion with one experienced emergency physician who claimed that he should be able to give hydroxychloroquine to patients outside of controlled trials, because he would be giving hope. I asked how this is any different from what alternative medicine does? He responded just as an alternative medicine promoter would – with logical fallacies about What if . . . ? We should actually hope for better from doctors, who are supposed to understand medicine. This willful ignorance is probably the most deadly medicine doctors prescribe.

Will President Trump be as smart as British Prime Minister Boris Johnson and leave the science to the scientists? President Trump has not provided any evidence to expect reasonable decisions, yet.

What does work? If given early, remdesivir might be effective.[7] On the other hand, remdesivir might not be that effective.[8] If oxygen is used to treat low oxygen saturation, dexamethasone[9], [10] is the most effective treatment.

If you want to minimize your chances of having to make these choices, wear a mask and eye protection, stay physically away from other people, and wash your hands.

Footnotes:

Some of the footnotes are to what I have previously written about these treatments. They contain links to the research on the proposed treatments, rather than add footnotes for all of links to research and other evidence.

[1] Hydroxychloroquine – The More You Know, The Worse It Looks

Rogue Medic

May 22, 2020

Article

[2] What’s the Good News on Hydroxychloroquine?

Rogue Medic

June 6, 2020

Article

[3] Is Hydroxychloroquine Effective Against COVID-19?

Rogue Medic

July 31, 2020

Article

[4] Pascal’s wager

Wikipedia

Article

Criticism of Pascal’s Wager began in his own day, and came from both atheists, who questioned the “benefits” of a deity whose “realm” is beyond reason, and the religiously orthodox, who primarily took issue with the wager’s deistic and agnostic language. It is criticized for not proving God’s existence, the encouragement of false belief, and the problem of which religion and which God should be worshipped.[4][15]

[5] The Oleandrin Scam Exposes Incompetent Doctors

Rogue Medic

August 23, 2020

Article

[6] Is convalescent plasma safe and effective? We answer the major questions about the Covid-19 treatment

STAT

Lev Facher

August 23, 2020

Article

[7] Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial

Christoph D Spinner 1, Robert L Gottlieb 2, Gerard J Criner 3, José Ramón Arribas López 4, Anna Maria Cattelan 5, Alex Soriano Viladomiu 6, Onyema Ogbuagu 7, Prashant Malhotra 8, Kathleen M Mullane 9, Antonella Castagna 10, Louis Yi Ann Chai 11, Meta Roestenberg 12, Owen Tak Yin Tsang 13, Enos Bernasconi 14, Paul Le Turnier 15, Shan-Chwen Chang 16, Devi SenGupta 17, Robert H Hyland 17, Anu O Osinusi 17, Huyen Cao 17, Christiana Blair 17, Hongyuan Wang 17, Anuj Gaggar 17, Diana M Brainard 17, Mark J McPhail 18, Sanjay Bhagani 19, Mi Young Ahn 20, Arun J Sanyal 21, Gregory Huhn 22, Francisco M Marty 23, GS-US-540-5774 Investigators

JAMA. 2020 Sep 15;324(11):1048-1057. doi: 10.1001/jama.2020.16349.

PMID: 32821939 PMCID: PMC7442954 DOI: 10.1001/jama.2020.16349

Free Full Text from JAMA

[8] Remdesivir and COVID-19

The Lancet

October 3, 2020 (Yes, that is tomorrow’s date.)

DOI: https://doi.org/10.1016/S0140-6736(20)32021-3

Article

[9] Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report

RECOVERY Collaborative Group; Peter Horby 1, Wei Shen Lim 1, Jonathan R Emberson 1, Marion Mafham 1, Jennifer L Bell 1, Louise Linsell 1, Natalie Staplin 1, Christopher Brightling 1, Andrew Ustianowski 1, Einas Elmahi 1, Benjamin Prudon 1, Christopher Green 1, Timothy Felton 1, David Chadwick 1, Kanchan Rege 1, Christopher Fegan 1, Lucy C Chappell 1, Saul N Faust 1, Thomas Jaki 1, Katie Jeffery 1, Alan Montgomery 1, Kathryn Rowan 1, Edmund Juszczak 1, J Kenneth Baillie 1, Richard Haynes 1, Martin J Landray 1

July 17, 2020

N Engl J Med. 2020 Jul 17; NEJMoa2021436. doi: 10.1056/NEJMoa2021436. Online ahead of print.

PMID: 32678530 PMCID: PMC7383595 DOI: 10.1056/NEJMoa2021436

Free Full Text from NEJM

[10] The RECOVERY Trial: Dexamethasone for COVID-19?

REBEL EM

June 23, 2020

Article

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Mask vs. Vaccine – Which is More Effective?

Currently, mask vs. vaccine is an easy answer. Masks are 100% more effective than something that is not available. Eventually, mask plus vaccine may be the best answer.

According to the evidence, the the masks decrease the amount of virus that is able to be detected on the other side of the mask, regardless of whether the mask is being worn by an infectious person trying to avoid infecting others or the mask is being worn by a healthy person trying to avoid becoming infected.

The dose of virus does seem to matter in transmission of disease.

This does not mean that vaccines will not help, assuming that a safe and effective vaccine is eventually available. The stated cut off level to be applied for approval of a vaccine is currently at least 50% effective. Masks are already more than 50% effective.

“I might even go so far as to say that this face mask is more guaranteed to protect me against COVID than when I take a COVID vaccine, because the immunogenicity may be 70%,” Redfield said in testimony before a Senate appropriations committee. “And if I don’t get an immune response, the vaccine is not going to protect me. This face mask will.”[1]

That statement was later contradicted by President Trump, but that statement was not contradicted by any credible scientist and was not contradicted by any credible physician. Oddly, the article title suggests that Dr. Redfield walked back his statement, although the article never states that. This may be because the headline is often not written by the person writing the article, but by an editor, looking to get more clicks.

Masks work.

Vaccines are not available and probably will not be available until sometime next year.

If we want the economy to recover, we need to be aggressive about wearing masks to protect others and to protect ourselves.

This is from a paper written in 2009 about influenza, which is transmitted the same way SARS-CoV 2 is transmitted. These were people with influenza, wearing masks, and coughing. The results with an N95 mask and a surgical mask show that both decreased the amount of virus, that would be spread by a cough, to the undetectable level.[2]

Masks do not protect your eyes, so you should consider wearing eye protection. Masks also do not protect your hands, so wash your hands. Typhoid Mary might not have killed anyone if she had washed her hands.

**********************

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Footnotes:

.

[1] CDC Chief Walks Back Masks v. Vaccine Comments
By Ralph Ellis
WebMD
Article

.

[2] A Quantitative Assessment of the Efficacy of Surgical and N95 Masks to Filter Influenza Virus in Patients with Acute Influenza Infection
D. F. Johnson, J. D. Druce, C. Birch, M. L. Grayson
Clinical Infectious Diseases, Volume 49, Issue 2, 15 July 2009, Pages 275–277, 
https://doi.org/10.1086/600041 Published: 15 July 2009

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The Oleandrin Scam Exposes Incompetent Doctors

President Trump has made another medical recommendation. This one is more dangerous than the last. As long as a lot of physicians are willing to harm patients in order to promote their political agenda, President Trump is willing to keep playing doctor and providing them with ways to harm patients. We can hope that the FDA (Food and Drug Administration) takes action to protect patients from such doctors.

Hydroxychloroquine was supported by low-quality research, but some physicians couldn’t wait to promoted it. That is alternative medicine – the opposite of competent medicine.

When high-quality evidence on the use of hydroxychloroquine in humans with COVID-19 was published, these physicians insisted that the research was politically motivated, each time a new high-quality study was published. That is the argument used by alternative medicine, not real medicine. Every high-quality study shows that there is no benefit from hydroxychloroquine for COVID-19 patients. The risks are greater than the potential benefits. Competent and ethical physicians should limit the use of hydroxychloroquine to well-controlled research.

Now we have a more extreme danger to patients from alternative medicine and promoted by President Trump. Oleandrin is an extract of the oleander plant and is not supported by any research in humans. The only research supporting oleandrin as a COVID-19 treatment is in test tubes, which means that this is not even as well tested as the vaccine approved by President Putin earlier this month. If there is any use in humans, it would be in a Phase 1 trial. Not even that level of research has been done, yet.

The obvious image to use to explain this is from xkcd.

The mouse over text states: Now, if it selectively kills cancer cells in a petri dish, you can be sure it’s at least a great breakthrough for everyone suffering from petri dish cancer.

Oleandrin, and thousands millions of other chemicals, kill coronaviruses in petri dishes. Killing cells in petri dishes does nothing to help patients.

For more detailed information read this article or this article or listen to this podcast.

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What Does the Approval of a Russian Vaccine Mean?



Today, after testing on a grand total of 76 people, President Putin announced the approval of a vaccine in Russia, Sputnik-V, to prevent COVID-19.

We knew another pandemic was coming, because we understand evolution. We should have been prepared. We were prepared under the Bush administration. We were prepared under the Obama administration. The current administration chose to stop wasting money on being prepared.

There are three human phases of testing generally required before the approval of a vaccine or drug, after testing in other animals. Phase I is testing in humans for common adverse effects, dosing ranges, and to generally learn how the body reacts. For the most discussed vaccine trial, Moderna had 45 people (three groups of 15 people each receiving different doses of vaccine) in their Phase I trial.

Phase II expands the use to people who are not as healthy as the people in Phase I and to a more people. Phase III is refining this, based on the results of the earlier trials. Phase I and II are being combined in some vaccine trials. Phase II and II are being combined in others.

The Moderna Phase III trial of mRNA-1273 (mRNA is messenger RiboNucleic Acid – the stock ticker for Moderna, Inc. is also MRNA) is expected to enroll 30,000 people who have no evidence of previous COVID-19 infection.[1] Half will get mRNA-1273 and half will get a meningitis vaccine as a placeboish control. While a placebo often means inert, a saline solution injection would not produce the temporary fever, soreness, and/or redness to the site at the same rate as an actual vaccine. This is expected to keep the volunteers from being able to tell which they have received and it provides a benefit to those in the placebo group.

Russia has enrolled 76 people in Phase I and President Putin has announced that Phase III will happen at the same time as the mass vaccination of the people most likely to be exposed to infection. This is Phase IV – post approval study.

Russia has not announced any challenge testing, which might have been a more ethical approach than skipping Phase III. Challenge testing has not being announced anywhere for COVID-19 vaccine testing, because of the ethical concerns. With an expected 1/2% to 1% fatality rate, a much higher rate of serious complications, and an unknown rate of long term complications that appear to be related to COVID-19, it is difficult to justify intentionally exposing people to infection with a vaccine of unknown ability to protect the people being exposed. Thousands of people dying each day, thousands more developing serious complications each day, and thousands more developing long term complications each day. Where is the line drawn between approving challenge testing and not approving it? Where is the line drawn between challenge testing and skipping Phase III trials?

When will the Russian vaccine be given to people? Some time in October.

What could go wrong?

Meanwhile the Moscow-based Association of Clinical Trials Organizations (Acto), which represents the world’s top drug companies in Russia, urged the health ministry to postpone approval until after phase-three trials.

Acto executive director Svetlana Zavidova told the Russian MedPortal site that a decision on mass vaccination had been carried out after a combined first- and second-phase tests on 76 people, and that it was impossible to confirm the efficacy of a drug on this basis.[2]

Will this be just another political intervention, like hydroxychloroquine? Only time will tell.

What would indicate that the United States has a safe and effective vaccine?

I want to see recommendation of a vaccine by the people who know the most about vaccines – Paul Offit, Michael Osterholm, Peter Hotez, and Anthony Fauci. They need to be able to see all of the evidence. The only reasonable conclusion about a refusal to share the evidence with any of them is that there is something bad being hidden. These are not politicians. None of these medical experts have shown signs of being influenced by political pressure.

The pandemic was not at all a surprise. The conspiracy theorists will misrepresent this video, because of their lack of understanding of what they are hearing. If it doesn’t support their prejudices, they don’t seem to hear anything at all, as if they have been programmed to ignore valid evidence and logic.

Pandemic Preparedness in the Next Administration: Keynote Address by Anthony S. Fauci – Feb. 14, 2017 – Almost 3 years before COVID-19, but the medically competent audience understood that this was a reasonable prediction to make in 2017. If you don’t understand that, watch the whole video.



Every reasonable person should have known there would be another pandemic, but we have media that discourage understanding, especially about science.


Late addition – 10:55 – 8/12/2020 – For further information, Carl Zimmer has an article in The New York Times going into more detail. A couple of important quotes from the article are below.

‘This Is All Beyond Stupid.’ Experts Worry About Russia’s Rushed Vaccine
August 11, 2020
by Carl Zimmer. Andrew Kramer and Katherine J. Wu contributed reporting.
The New York Times
Article

“This is all beyond stupid,” said John Moore, a virologist at Weill Cornell Medical College in New York City. “Putin doesn’t have a vaccine, he’s just making a political statement.”

Dr. Nicole Lurie, a former assistant secretary for preparedness and response at the U.S. Department of Health and Human Services and currently an adviser at the Coalition for Epidemic Preparedness Innovations, said the lesson that the U.S. government should draw from Mr. Putin’s announcement is clear.

“This is exactly the situation that Americans expect our government to avoid,” she said.

Footnotes:

[1] Phase 3 clinical trial of investigational vaccine for COVID-19 begins – Multi-site trial to test candidate developed by Moderna and NIH.
Monday, July 27, 2020
NIH (National Institutes of Health)
News Release

[2] Coronavirus: Putin says vaccine has been approved for use
Analysis by Fergus Walsh, Medical correspondent
BBC
Article

.

Is Hydroxychloroquine Effective Against COVID-19?

     
As with any popular treatment, there are plenty of people who want us to ignore the research, or to focus on giving people hope. That is not a reasonable, or ethical, approach to medicine. That is not even a medical approach to medicine. If we lower our standards enough, we can claim that everything works, but that would kill a lot more people than only using treatments based on EBM (Evidence Based Medicine). Should we make excuses for lowering our standards, and killing people, or should we insist on raising our standards?

There is currently a pandemic, so there is a bit of a rush to find something that works, which some people mistake for a need to provide hope. If you want hope, you can pray and there should not be any harmful effects of praying. However knowing that you were being prayed for by others has been associated with a significantly higher incidence of complications. In other words, praying for yourself or others is fine, but telling others that you are going to pray for them is probably harmful, even though your intent is to help.[1]

The reasonable way to look at taking medicine is take only those treatments that have been demonstrated to improve outcomes for people with the studied diagnosis, when you have that diagnosis. Everything else is a crap shoot, where you don’t even know the risks – and there probably is no benefit.

Why do I state that the risks to the person taking the treatment are unlimited, but the benefits probably do not exist?

That is the history of the study of treatments. Almost everything proposed as a treatment has been more harmful than beneficial. It would be nice if this were not true, but reality doesn’t care about being nice. All of alternative medicine falls into the category of probably more harmful than safe and unlikely to be of any benefit, other than a benefit to the finances of the person selling the alt med.

Is hydroxychloroquine alternative medicine? Hydroxychloroquine is approved as real medicine for malaria, lupus erythematosus, and rheumatoid arthritis.[2] For these diagnoses, hydroxychloroquine is not alternative medicine. For everything else, the use is off-label, which is a legal way of saying alternative medicine, as far as the FDA (Food and Drug Administration) is concerned. Sometimes off-label use can be supported by good evidence, but the treatment has not been submitted to the FDA for approval for that diagnosis, but that is not the case with hydroxychloroquine. The FDA issued an EUA (Emergency Use Authorization) for hydroxychloroquine limited to adults and adolescents who weigh 50 kg (approximately 110 pounds) or more, who were hospitalized with COVID-19, and for whom participation in a clinical trial was not available, or participation was not feasible.[3]

Why are those limitations important?

1. If a treatment is effective, diverting patients from clinical trials will delay learning that the treatment is effective, which will significantly decrease the number of lives saved.

2. If a treatment is not effective, diverting patients from clinical trials will delay learning that the treatment is not effective, which will significantly decrease the number of lives saved, because patients are receiving a useless distraction from effective treatment.

3. If a treatment is harmful, which is much worse than just being not effective, diverting patients from clinical trials will delay learning that the treatment is harmful, which will significantly increase the number of patients killed.

All of those results – and those are the possibilities – are ignored by those who reject research. No treatment, however good, will be purely beneficial. All treatments have adverse effects. however, the reverse of that is not true. A treatment that is harmful often does not provide any benefit.

The odds are always against the patient. Any doctor trying to just do something is endangering patients. Kitchen sink medicine (throwing everything at the patient, just in case) has always been bad medicine.

There is a good discussion of the evidence in two podcasts:

15. Covid-19: Is There a Case for Hydroxychloroquine?
Stimulus with Rob Orman, MD (who also hosts the ERCast)
July 30, 2020
Podcast page

Dr. Orman does not specifically mention the Arshad study, which claims to show a benefit in patients treated with HCQ (HydroxyChloroQuine), AZM (AZithroMycin), and HCQ+AZM (HydroxyChloroQuine + AZithroMycin), but that does not change the conclusion of an examination of the evidence.[4]


COVID-19 Treatment Update: Can We Just Stop Wasting Time on Hydroxychloroquine
Written by Salim Rezaie
July 6, 2020
Podcast page

Here is the most important point from Salim Rezaie about the outcomes from the Arshad study:

As most patients in this trial receiving HCQ or HCQ + AZM received steroids and the patients receiving AZM alone or neither therapy had far fewer patients receiving steroids, the likely mortality benefit of this trial is due to the steroids and not the HCQ or HCQ + AZM


Dr. Rezaie concludes: This study should not change clinical practice of not prescribing these medications.

The Arshad study is being used by proponents of hydroxychloroquine alternative medicine to try to contradicting higher quality research, which is the reason it is not real medicine. When there is only low quality evidence, we should be cautious in recommending any treatment. When the high quality evidence shows that the low quality evidence is misleading, we should ignore the low quality evidence until there is high quality evidence to support the findings of the low quality evidence. Don’t expect that to happen.

The reason most medical research is overturned is the reliance on low quality evidence.[5], [6], [7], [8]


Footnotes:

[1] Study of the Therapeutic Effects of Intercessory Prayer (STEP) in cardiac bypass patients: a multicenter randomized trial of uncertainty and certainty of receiving intercessory prayer
Herbert Benson 1, Jeffery A Dusek, Jane B Sherwood, Peter Lam, Charles F Bethea, William Carpenter, Sidney Levitsky, Peter C Hill, Donald W Clem Jr, Manoj K Jain, David Drumel, Stephen L Kopecky, Paul S Mueller, Dean Marek, Sue Rollins, Patricia L Hibberd
Am Heart J. 2006 Apr;151(4):934-42. doi: 10.1016/j.ahj.2005.05.028.
PMID: 16569567

Our study had 2 main findings. First, intercessory prayer itself had no effect on whether complications occurred after CABG. Second, patients who were certain that intercessors would pray for them had a higher rate of complications than patients who were uncertain but did receive intercessory prayer.



[2] Hydroxychloroquine Sulfate tablet
INDICATIONS AND USAGE
Daily Med
FDA Label


[3] Frequently Asked Questions on the Revocation of the Emergency Use Authorization for Hydroxychloroquine Sulfate and Chloroquine Phosphate
FDA
Page as PDF download

Q. Why did FDA grant the EUA for hydroxychloroquine sulfate (HCQ) and chloroquine phosphate (CQ) for the treatment of COVID-19 initially?
A. On March 28, 2020, BARDA requested and FDA issued an Emergency Use Authorization (EUA) for emergency use of oral formulations of chloroquine phosphate (CQ) and hydroxychloroquine sulfate (HCQ) for the treatment of COVID-19. Based on the scientific information available to FDA as of that date, the Agency determined that CQ and HCQ may be effective in treating COVID-19 and that the known and potential benefits of CQ and HCQ outweighed the known and potential risks for this use. The agency limited the use of authorized products to adults and adolescents who weigh 50 kg (approximately 110 pounds) or more, who were hospitalized with COVID-19, and for whom participation in a clinical trial was not available, or participation was not feasible.



[4] Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19
Samia Arshad,a Paul Kilgore,b,c Zohra S. Chaudhry,a Gordon Jacobsen,e Dee Dee Wang,d Kylie Huitsing,a Indira Brar,a George J. Alangaden,a,c Mayur S. Ramesh,a John E. McKinnon,a William O’Neill,d Marcus Zervos,a,c,⁎ and Henry Ford COVID-19 Task Force1
Int J Infect Dis. 2020 Aug; 97: 396–403.
Published online 2020 Jul 2. doi: 10.1016/j.ijid.2020.06.099
PMID: 32623082

PMCID: PMC7330574 (Free Full Text from PubMed Central)


[5] Why Most Published Research Findings Are False
John P. A. Ioannidis
PLoS Med. 2005 Aug; 2(8): e124.
Published online 2005 Aug 30. doi: 10.1371/journal.pmed.0020124
PMID: 16060722

PMCID: PMC1182327 (Free Full Text from PubMed Central)

The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance.



[6] Evidence-based de-implementation for contradicted, unproven, and aspiring healthcare practices
Vinay Prasad and John PA Ioannidis
Implement Sci. 2014; 9: 1.
Published online 2014 Jan 8. doi: 10.1186/1748-5908-9-1
PMID: 24398253

PMCID: PMC3892018 (Free Full Text from PubMed Central)

Abandoning ineffective medical practices and mitigating the risks of untested practices are important for improving patient health and containing healthcare costs. Historically, this process has relied on the evidence base, societal values, cultural tensions, and political sway, but not necessarily in that order. We propose a conceptual framework to guide and prioritize this process, shifting emphasis toward the principles of evidence-based medicine, acknowledging that evidence may still be misinterpreted or distorted by recalcitrant proponents of entrenched practices and other biases.


[7] Observational studies often make clinical practice recommendations: an empirical evaluation of authors’ attitudes
Vinay Prasad 1, Joel Jorgenson, John P A Ioannidis, Adam Cifu
J Clin Epidemiol.
2013 Apr;66(4):361-366.e4.
PMID: 23384591   DOI: 10.1016/j.jclinepi.2012.11.005

It is common to see new studies contradict previous adopted standards of care [25,26]. Even the results of highly cited studies can be refuted [7], and the replication rate tends to be low for claims made from observational designs [7]. We have previously noted that the most common correlate for reversal of standards of care was the original adoption of a practice based on nonrandomized evidence alone [27]. The studies examined here offer many recommendations that may be precarious or erroneous. If adopted, such practices may need to be reversed in the future after having been detrimental to health, health finances, and the reputation of medical science.



[8] Contradicted and initially stronger effects in highly cited clinical research
John P A Ioannidis
JAMA. 2005 Jul 13;294(2):218-28. doi: 10.1001/jama.294.2.218.
PMID: 16014596   DOI: 10.1001/jama.294.2.218

Free Full Text from JAMA

Of the 45 eligible highly cited studies with efficacy claims (Table 2), 7 (16%) were contradicted by subsequent research, and another 7 (16%) were found to have initially stronger effects. In all these 14 cases (BOX 1), subsequent studies were either larger or better controlled (randomized vs a nonrandomized original study). The findings of 20 highly cited articles (44%) were replicated (also with a larger sample size in subsequent research compared with the original highly cited study) and 11 (24%) had remained largely unchallenged.58-78



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