The Non-Verdict on HCQ

OK, so let’s analyze the latest hydroxychloroquine (HCQ) study.

This study comes out of Brazil.  It was published in the New England Journal of Medince on 7/23/2020.  It is entitled:  Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.  It’s authors are:  Alexandre B. Cavalcanti, M.D., Ph.D., Fernando G. Zampieri, M.D., Ph.D., Regis G. Rosa, M.D., Ph.D., Luciano C.P. Azevedo, M.D., Ph.D., Viviane C. Veiga, M.D., Ph.D., Alvaro Avezum, M.D., Ph.D., Lucas P. Damiani, M.Sc., Aline Marcadenti, Ph.D., Letícia Kawano-Dourado, M.D., Ph.D., Thiago Lisboa, M.D., Ph.D., Debora L. M. Junqueira, M.D., Pedro G.M. de Barros e Silva, M.D., Ph.D., Lucas Tramujas, M.D., Erlon O. Abreu-Silva, M.D., Ligia N. Laranjeira, Ph.D., Aline T. Soares, M.D., Ph.D., Leandro S. Echenique, M.D., Adriano J. Pereira, M.D., Ph.D., Flávio G.R. Freitas, M.D., Ph.D., Otávio C.E. Gebara, M.D., Ph.D., Vicente C.S. Dantas, M.D., Ph.D., Remo H.M. Furtado, M.D., Ph.D., Eveline P. Milan, M.D., Ph.D., Nicole A. Golin, M.D., Fábio F. Cardoso, M.D., Israel S. Maia, M.D., Conrado R. Hoffmann Filho, M.D., Adrian P.M. Kormann, M.D., Roberto B. Amazonas, M.D., Ph.D., Monalisa F. Bocchi de Oliveira, M.D., Ary Serpa-Neto, M.D., Ph.D., Maicon Falavigna, M.D., Ph.D., Renato D. Lopes, M.D., Ph.D., Flávia R. Machado, M.D., Ph.D., and Otavio Berwanger, M.D., Ph.D.et al., for the Coalition Covid-19 Brazil I Investigators.

Analyzing  this study is treacherous because COVID-19 is as much a political disease as it is a real disease.  Doctors and patients have chosen sides, and we hate each other’s guts.  We stand champing at the bit to take each other down.

My bias:  I despise Dr. Fauci and Coach K.  I believe Dr. Fauci to be a war criminal, and I can back up my beliefs.

Financial interests:  None from Corporate America or anywhere else.  I just want my life back.

With that stated, let’s get to the study.

I will preface my remarks by stating that too many authors might spoil the broth.

First let’s note that the study was limited to 667 total patients. 438 of those patients received hydroxychloroquine, 229 patients did not. Of the 438 patients who received hydroxychloroquine, 217 of them also received azithromycin.

I would hardly call this a huge study.  For me for 400 patients is the lower limit of what I would accept for a study to be meaningful.  

On a slightly humorous note, this study took place over 55 hospitals. I find this humorous because for the last four months we have been regaled with hysterical accounts of “the medical war zone.”  So, you’re telling me that you had to do this study over 55 hospitals?  If we truly had medical war zones, one or two hospitals should’ve been enough.  

That this study took place over 55 hospitals is worrisome to me because it indicates that one is less likely to maintain consistency in how the patients are cared for, how they are monitored or ultimately graded.  

That’s a big flaw for me.

Another red flag for me is that the study appears in the New England Journal of Medicine. The New England Journal of Medicine to me is Corporate America’s journal.  I don’t trust the objectivity of the New England Journal of Medicine. They’ve already had to retract at least one article regarding the coronavirus.  The NEJM is now to medicine what The Economist is to world affairs – a mouthpiece for globalism.

Now, let’s get to the authors’ stated limitations of the study.  These are their own words.

Our trial has several limitations. First, although the point estimate of effect suggests no major difference between the groups with respect to the primary outcome, the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm. For the comparison between hydroxychloroquine and control, for example, our data are compatible with odds ratios as low as 0.69 and as high as 2.11. Second, the trial was not blinded. Third, despite intense efforts to maintain adherence to the assigned treatments, a lack of medications that were perceived as beneficial by clinicians and patients led to some protocol deviations. Fourth, the use of hydroxychloroquine plus azithromycin was widespread among patients hospitalized with Covid-19 in participating hospitals. The enrollment of patients with no previous use of these medications was challenging, so we decided to enroll patients provided that their previous use since the onset of symptoms was limited to 24 hours. Finally, although the median time from symptom onset to randomization was 7 days, we included patients up to 14 days after the beginning of symptoms; it is conceivable that interventions that may limit viral replication (e.g., hydroxychloroquine) may be more effective earlier in the course of the disease.

1  the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm.

Okay, then why are Dr. Fauci and his cheerleaders claiming that this study vindicates them?  I don’t see the study vindicating them at all.  I think this study is a point in their favor, but I also think that a more controlled study is in order.

2  the trial was not blinded.  

This is huge.  Suppose a doctor with a bias against HCQ decided to not be aggressive with other treatment modalities.   Suppose the patients assigned to the HCQ “team” were the most sick and least likely to have a good outcome.

3  despite intense efforts to maintain adherence to the assigned treatments, a lack of medications that were perceived as beneficial by clinicians and patients led to some protocol deviations.

Again, this is huge.  What are these deviations? Were these deviations skewed against the patients receiving hydroxychloroquine?

4  the use of hydroxychloroquine plus azithromycin was widespread among patients hospitalized with Covid-19 in participating hospitals. The enrollment of patients with no previous use of these medications was challenging, so we decided to enroll patients provided that their previous use since the onset of symptoms was limited to 24 hours.

So are they saying that people who were assigned to the control group, those not receiving HCQ, actually did receive HCQ for a day?  This probably is not that big a deal.  

5  We recruited 667 patients, including 504 patients with confirmed Covid-19.

Only 504 of the 667 patients had confirmed COVID-19?  I am trying to be as fair as I can, but shouldn’t all the patients have been confirmed as COVID-19?  Is there something I’m missing here?  Is it standard research procedure to incorporate blanks into your study?  How can you possibly call your study valid if not all your people are confirmed to have the disease you are intending to study?  Is a clinical diagnosis alone valid?  If these patients were as bad off as we believe them to be in order to warrant being included in the study, shouldn’t they have been positive for COVID-19? Are we saying that the virus couldn’t be found in their body?

Finally, a metaphysical  comment.  If it were so tough to find patients who had not been treated with HCQ over 55 hospitals, what does that say about what doctors think about HCQ?  Evidently, they must like the drug or have a gut feel that it works.

Of course, we must be fair.  I am always fair.  Whether I am reviewing a lousy restaurant or a study, I am always fair.

This study indicates that we should be cautious about viewing HCQ as a cure-all for a miracle drug for COVID-19.  But in no way, does this study rule out HCQ as a partner in the armamentarium against the coronavirus.

As for the side effects, I find the elevation of liver enzymes minimal. The QTc prolongation evidently has not prevented doctors at 55 hospitals from prescribing the drug.  As any doctor knows, there are many drugs that prolong the QTc interval. That we would deny someone a potentially life saving drug based upon QTc prolongation seems extreme.

Ruling:  Doctors in the United States should be allowed to prescribe HCQ for COVID-19.

 Thank you.

 

Sincerely,

Archer Crosley, MD

McAllen, TX 

Thursday, July 30, 2020

Copyright 2020   Archer Crosley   All Rights Reserved