Using Hydroxychloroquine (HCQ) for
Early Treatment
of Outpatients
Editing Notes:
1. Date of original blogpost: Aug. 18, 2020
2. Aug. 20, 2020: added Endnotes section in blue font. Any other edits (minor) within the original blogpostalso appear in blue font.
a. The point about "high risk" patients is critical. (See Endnote #1.)
b. I added links to two interviews which may be a quicker way to convey the message. (See Endnote #3, Dr. Risch's follow-on interview to his CNN interview).
3. Aug. 29, 2020: added Endnote #6.
Blogpost:
On July 28, 2020, a Tweet and blogpost by Martin Armstong caught my attention. The blogpost contained a controversial video on the so-called America's Frontline Doctors. The doctors in the video claimed that a combination of HCQ taken in low doses and Zinc could help (a) in preventing coronavirus infection and (b) more importantly, in treating the disease in its early stages.
This video was subsequently banned by mainstream media with the reason, according to Fox News, being that it would "hurt the Biden presidential campaign" (i.e. help Trump's presidential campaign had it not been banned). An ER physician who had appeared in the video, Dr. Simone Gold, was fired from her job shortly thereafter. Source. (The implication is that "forces" behind Biden are more powerful than those behind Trump. Time will tell.)
To be clear, their message was that there is a simple and cheap way of treating Covid-19 patients at the early outset of symptoms. This was the message that has been suppressed by mainstream media.
Meanwhile, Dr. Anthony Fauci, the FDA and NIH have taken a hard stance against the use of HCQ for treatment of Covid-19. The say that not until RCTs (randomized controlled trials) are carried out should HCQ be prescribed. The benefit of an RCT is that it would establish without reasonable doubt whether or not HCQ was an effective treatment for the disease. The problem is that an RCT takes time, months or years. Meanwhile, more and more people are getting infected, many have died or continue to die, the health care system has been overloaded, and the global economy has taken an unprecedented hit. A Yale epidemiologist named Dr. Harvey Risch advocates the combined use of HCQ with AZ (azythromycin, an antibiotic) for treatment of early stages of infection in outpatients who are at high risk. I emphasize the words "early stages" and "outpatients". (More on "high risk" in the Endnotes.) His prescription does not apply to inpatients (those hospitalized) nor to those with advanced stages of the disease (i.e with severe respiratory issues).
(See Endnotes re Dr. Risch's rebuttal of Dr. Fauci's stance on RCTs.)
I asked a few physician friends for their opinion. (I am not a physician.) I thought that their response would settle the matter. However, I received mixed responses. So I decided to investigate for myself by going to the source, which meant reading Dr. Risch's academic paper.
Side note: An article from MedPage Today dated July 31, 2020 is excellent in that covers the issue thoroughly and references many relevant sources including Dr. Risch's paper. If you'd like to get an overview and find links to major articles, this would be the go-to article. However here in this blogpost, my focus is something different. It is to look at Dr. Harvey's analysis directly instead of listening to other people's opinion or interpretation of it.
As a historical note, I started my investigation via this Google search: "dr harvey risch hydroxychloroquine". (If you click on the previous link, you'd be able to see the search results for yourself. The aforementioned article from MedPage Today was the second search result.)
So, let's look at Dr. Risch's academic paper, the one which leads him to recommend HCQ+AZ for early treatment of outpatients with Covid-19. But before we do that, let's check his credentials. They may be found on Yale's website.
My opinion after checking him out is that he has not only credible but outstanding credentials as an epidemiologist, which is what counts. He is the author of 325 original research publications and has an h-index of 88. But what does an h-index of 88 mean? According to this source, "after 20 years of research, an h-index of 20 is good, 40 is outstanding, and 60 is truly exceptional." Risch obtained his PhD in 1980, so he has had more than 40 years of research under his belt. Second, according this Wikipedia article on the h-index, "among 36 new inductees in the National Academy of Sciences in biological and biomedical sciences in 2005, the median h-index was 57." Dr. Risch's index is higher than this median, and we are talking about the median among a select group of scientists. So far so good.
Dr. Risch's paper may be accessed here. It was published on May 27. (Note that at the top of the PDF file containing this paper, not to be overlooked are 3 critiques of Dr. Risch's paper and 2 rebuttals by him. I don't treat these other works here, but simply mention that Dr. Risch's 2nd response -- file "kwaa152" -- is worth checking out: See Table 1 on p.8 which summarizes 12 studies all with the same conclusion: "reduced risk". )
Excerpts from Dr. Risch's paper, with titles by me.
Is outpatient infection different from inpatient distress?
"Symptomatic outpatient infection is a pathologically and clinically different disease than the life-threatening inpatient acute respiratory distress syndrome caused by SARS-CoV-2, thus there is little reason to think that the same treatment would be useful for both."
What is the purpose of this paper?
What is the purpose of this paper?
"In reviewing all available evidence, I will show that HCQ+AZ and HCQ+doxycycline are generally safe for short-term use in the early treatment of most symptomatic high-risk outpatients, where not contraindicated, and that they are effective in preventing hospitalization for the overwhelming majority of such patients."
(HCQ = hydroxychloroquine. AZ = azithromycin)
What is the available evidence on the efficacy of HCQ+AZ?
"Available evidence of efficacy of HCQ+AZ has been repeatedly described in the media as “anecdotal,” but most certainly is not. The evidence is not perfect either."
Can lack of randomization be a weakness of the First Study (Marseille group, P. Gautret, D. Raoult)?
"If [this] study had shown a 2-fold or perhaps 3-fold benefit, that magnitude of result could be postulated to have occurred because of subject-group differences from lack of randomization. However, the 25-fold or 50-fold benefit found in this study is not amenable to lack of randomization as the sole reason for such a huge magnitude of benefit."
Side note: Both the first and second studies may be accessed via the above MedPage Today article.
Why is smallness not an issue with the First Study?
"The study has also been described as “small,” but that criticism only applies to studies not finding statistical significance."
What were the results of the Second Study (also Marseille Group)?
"A second study of the Marseilles group involved 1061 patients tested positive for SARS-CoV-2 and treated with HCQ+AZ for at least 3 days and followed for at least 9 days. The authors state “No cardiac toxicity was observed.” Good clinical outcome and virological cure were seen in 973 patients (92%). Five patients died, and the remainder were in various stages of recovery."
What were the results of the Third Study (Dr. Vladimir Zelenko, New York)?
"Of the 1450 patients, 1045 were classified as low-risk and sent home to recuperate without active medications. No deaths or hospitalizations occurred among them. Of the remaining 405 treated with the combined regimen, 6 were ultimately hospitalized and 2 died."
"Of the 1450 patients, 1045 were classified as low-risk and sent home to recuperate without active medications. No deaths or hospitalizations occurred among them. Of the remaining 405 treated with the combined regimen, 6 were ultimately hospitalized and 2 died."
Are FDA, NIH and cardiology society warnings borne out in real-world usage of this treatment?
"This discussion thus shows that the FDA, NIH and cardiology society warnings about cardiac arrhythmia adverse events, while appropriate for theoretical and physiological considerations about use of these medications, are not borne out in mortality in real-world usage of them. Treatment-failure mortality will be much higher, but even that pales in comparison to the lives saved. It would therefore be incumbent upon all three organizations to reevaluate their positions as soon as possible."
Preamble to why differing scientific worldviews might be involved.
"Given that a detailed and dispassionate review of all of the available relevant evidence leads to conclusions about outpatient HCQ+AZ use different than those of the FDA and NIH panels (which comprise wider expertise than the cardiology societies), I address how different underlying scientific worldviews might be involved."
Are we talking about the same disease?
"For Covid-19, inpatient acute respiratory distress syndrome is typically a florid immune-system overreaction, whereas initial outpatient illness is a viral multiplication problem involving the beginnings of immune response. These are different diseases."
What are the facts?
"The fact that epidemiologic data to-date show strong evidence for efficacy of combined HCQ+AZ in early outpatient treatment, even if not “proof” yet at the level of several successful RCTs, is evidence that this medication regimen works in that context."
(RCT = randomized controlled trial)
(RCT = randomized controlled trial)
What is Risch's point?
"It is my point to say ...that HCQ+AZ has been directly studied in actual early high-risk outpatient use with all of its temporal considerations and found empirically to have sufficient epidemiologic evidence for its effective and safe employment that way, and that requiring delay of such general use until availability of additional RCT evidence is untenable because of the ongoing and projected continuing mortality. No studies of Covid-19 outpatient HCQ+AZ use have shown higher mortality with such use than without, cardiac arrhythmias included, thus there is no empirical downside to this combined medication use."
How prevalent is the use of HCQ+AZ in the world for treating Covid-19?
"I strongly urge these panels [(e.g. FDA, NIH)] to reconsider the data and arguments discussed above. Substantial fractions of physicians treating Covid-19 patients in Europe and elsewhere report use of HCQ+AZ: 72% in Spain, 49% in Italy, 41% in Brazil, 39% in Mexico, 28% in France, 23% in the US, 17% in Germany, 16% in Canada, 13% in the UK."
What are Risch's concluding remarks?
"We have a solution, imperfect, to attempt to deal with the disease. We have to let physicians employing good clinical judgement use it and informed patients choose it. There is a small chance that it may not work. But the urgency demands that we at least start to take that risk and evaluate what happens, and if our situation does not improve we can stop it, but we will know that we did everything that we could instead of sitting by and letting hundreds of thousands die because we did not have the courage to act according to our rational calculations." [emphasis mine]
What is the main takeaway from this paper?
"Five studies including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy of treatment with Hydroxychloroquine + Azithromycin."
This concludes my excerpts from Dr. Risch's paper. You may want to read his paper firsthand or perhaps read the article that he wrote in Newsweek on July 23.
Housekeeping
Dr. Risch's 2nd rebuttal (file "kwaa152") contained an interesting reference ("5") whose headline said, "Media and Big Pharma are in lockstep to suppress a cheap, life-saving Covid-19 therapy in order to reap pandemic-sized profits." Time will tell.
Practical question for the reader
Would you take HCQ+AZ (+ also Zinc) if you were to develop Covid-19 symptoms?
I know I would given that I don't have any existing heart conditions. (Crossed out and modified below during Aug. 20's edits.)
but without any existing heart conditions. (Crossed out during Aug. 29's edits. The risk to people with heart conditions was quoted as either 9-in-10,000 or 9-in-100,000 by Dr. Risch. Citation needed.)
Would you take HCQ+AZ (+ also Zinc) if you were to develop Covid-19 symptoms?
1. "High risk". In my original blogpost, I hadn't picked up Dr. Risch's point that his proposed treatment is suitable only for high risk patients. I picked this up from his interview (item #3 below). High risk means high probability of mortality (e.g. 10-15%). People older than 60 who have coexisting conditions are considered high risk.
2. Dr. Risch's interview on Fox News. Published Aug. 3, 2020
3. Dr. Risch's follow-on interview to his CNN interview. Published Aug. 3, 2020. Dr. Risch makes his case starting at minute 4:25.
4. Dr. Risch mentions that historically many drugs that have been admitted for patient treatment haven't been subjected to RCT (randomized controlled trial). So it is rather strange that Dr. Fauci is now bringing up RCT as the requirement for allowing treatment with HCQ, in my opinion.
5. Disclosure: I am not a die-hard Trump fan by any means!
6. Dr. Risch answers questions on Fox News: part 1, part 2. Published Aug. 23, 2020.
2. Dr. Risch's interview on Fox News. Published Aug. 3, 2020
3. Dr. Risch's follow-on interview to his CNN interview. Published Aug. 3, 2020. Dr. Risch makes his case starting at minute 4:25.
4. Dr. Risch mentions that historically many drugs that have been admitted for patient treatment haven't been subjected to RCT (randomized controlled trial). So it is rather strange that Dr. Fauci is now bringing up RCT as the requirement for allowing treatment with HCQ, in my opinion.
5. Disclosure: I am not a die-hard Trump fan by any means!
6. Dr. Risch answers questions on Fox News: part 1, part 2. Published Aug. 23, 2020.
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