#hydrochloroquine

What does the research really say about  Hydroxychloroquine?

Dr. Harvey A. Risch of Yale has publicly stated that Hydroxychloroquine does work on Covid-19. He believes politicization is keeping the drug from being used. He says,  "I am fighting for a treatment that the data fully support but which, for reasons having nothing to do with a correct understanding of the science, has been pushed to the sidelines." So, what are to make of Dr. Risch, a well educated, widely published, respected doctor’s opinion on this matter?

Given Dr. Risch’s status, I didn’t just dismiss his claim. Although, his claim is in conflict with all of our major health institutions and wide population of health experts around the world. I decided to do some serious research and get to the bottom of this question. In order to do this, I began by reading Dr. Risch’s published article that this article refers to. I also read two published criticisms of Dr. Risch’s article by doctors  Nathan Peiffer-Smadja1 , Dominique Costagliola, and Dr. Vincent Fleury. I also spent time searching for studies on the efficacy of  Hydroxychloroquine.

My First Impressions of Dr. Risch’s Paper

Dr. Risch did not perform research himself. Instead, his paper reviews five studies and discusses observations in a couple countries. I was uneasy early in his article due to an impatience when he said, “In this context, we cannot afford the luxury of perfect knowledge and must evaluate, now and on an ongoing basis, the evidence for benefit and risk of these medications.” 

I recognized his the first study, and that was a small study coming out of  Marseilles, France. I recognized this, because it’s been highly criticized and the publisher later admitted that they should not have allowed the study because it did not meet their publishing standards. Besides, the study only had 42 participants. 

I was surprised that he had found five studies that came to the opposite conclusion as many others. However, I found out that only two of the five studies have actually been published. This is significant, because if these other researchers are unable to publish their work, then there must be flaws in their study. It stands to reason that anyone who felt they discovered something significant on Covid-19 would be trying to publish for both the public good and their careers. These were things I knew right off the bat that took away from Dr. Risch’s claim. 

The Criticism

Let’s get straight to the issues. 

Dr. Fleury focuses his criticism on the other published paper included in Dr. Risch’s review written by Million et al. This study focused on the mortality rate, but Fleury found significant miscalculations in the study that misrepresented the perceived benefit in mortality rates. In actuality, the rates were not different than those of the general population. He goes on to explain that within the Million et al study, the sample population did not have consistent at-risk ratings. It came to light that out of 1,466 test subjects only 405 of them were at high risk for death. The remaining 1,061 were of varying levels of risk, and at times had no risk factors. Because a majority of the people in the study had varying risk factors, it’s impossible to accurately gauge effectiveness of the drug vs natural immune protection. Not only were the subjects risk factors not consistent, but the cohort of subjects was unusually young. The average of patients in this study was 44 years old, with the youngest being 14. Mathematically, we can see that a large number of the people in the study must have been on the younger side. Again, because everyone in the study has vastly different levels of health, this seriously skews the study. Naturally, with more young people in the study who are healthy, the rate of mortality will be low. These are just the biggest criticisms. Given the lack of control over factors in the study, I don’t see how anyone could take this study seriously. 

Doctors Peiffer and Costagliola pointed their criticism at the paper written by Guatret et al. They pointed out that Dr. Risch defends the small study size by claiming that size matters only when no evidence is found. However, anyone who has ever done research before knows that is not true. Size is critical to the validity of a study no matter what your findings. They claim that this paper is fraught with missing data and unacceptable methodology. For example, the researchers did correctly design the study to know the effectiveness of HYDR + AZI together. Additionally, the study lacked randomization or double blind conditions, which Dr. Risch acknowledged. The doctors go into detail about issues with the methodology of other studies mentioned by Dr. Risch in his article. 

The Evidence

Dr. Risch refers to, what he calls, “natural experiments” in his article. These are discussed in the Newsweek article. What he is really talking about are observing correlations. Anyone familiar with research knows that these general observations cannot stand as real evidence against controlled studies. So, Dr. Risch has only presented 5 studies with some serious flaws that he says support the use of Hydroxychloroquine. What do other studies say? After surveying what information is available through Google, I found that study after study clearly shows that HYDR shows no effectiveness in either prevention or treatment. I’ll leave a short list of studies that show ineffectiveness at the bottom. The wonderful part about science is that consensus is easy to find, because properly done experiments will always yield the same results. What we see here, with a few contrary studies and a majority in agreement, is typical of early research on any issue. We are human and people make mistakes, but it is statistically very unlikely that the majority of scientists around the world will all make the same mistake. It’s much more realistic that the small handful of contradictory studies have mistakes within them. 

Even if these five studies had been solid evidence that the drug worked, all other, much larger, studies have shown it not to work. Given this situation, no one could logically justify coming to the firm conclusion that the drug works. At best, we must conclude that reexamination of studies are needed and further research is needed. Dr. Risch is clearly wrong when he says the issue is politicization, because the breath of research defies his claim.

Conclusion

Given the number and size of studies that all show the drug to be ineffective in comparison to a handful with serious flaws that disagree, I can only conclude that the evidence firmly points against Hydroxychloroquine. 

Here is the list of major studies that show HYDR to be ineffective. 

New England Journal of Medicine

Journal of The American Medical Association

RECOVERY trial

Nation Institute of Health

Science Daily

Annals of Internal Medicine

Screening guidelines for HCQ monitoring and testing strategies have changed over the past 20 years, helping us to better detect early retina changes before they are visible in the fundus.

Visual field testing and spectral-domain optical coherence tomography (SD-OCT) are now the primary screening tests.

Widefield testing is indicated for patients of Asian descent to detect the changes that develop more commonly beyond the central retina.

New objective tests include multifocal electroretinogram (mfERG) to confirm visual field findings and fundus autofluorescence (FAF) to show fundus damage.

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