Thread by @Tsarorius

Hi American Journal of Epidemiology @AmJEpi.

I just read thit article published on your website.

I suppose you have been hacked.

Oh, you haven't ?

ARE YOU SERIOUS ?! 🔽
academic.oup.com/aje/advance-ar…

Let me read with you the "review of evidence" by the author of this article (Harvey Risch) on the efficacy of HCQ +/- AZ.

In advance : sorry for my bad english.

Harvey Risch criticizes the NIH and the FDA because "[they] have omitted the two critical aspects of reasoning about these drugs : use of HCQ combined with AZ or with doxycycline, and use in the outpatient setting"

Let me remind some facts to Harvey Risch :

1) The hype for HCQ is due to a video posted on february 25th by Pr Didier Raoult on Youtube in which he says that HCQ is effective on Covid-19. HCQ alone. Not HCQ+AZ.

How can one be seriously criticizing the fact that researchers further tested the efficacy of HCQ and not HCQ+AZ?

2) The claim that HCQ was effective relied on no proof at all. Pr Didier Raoult said that "chinese researches have proven the efficacy of HCQ".

It was a false statement. No study was published before 25th of february 2020 on the efficacy of HCQ.

3) Pr Didier Raoult led a clinical trial to prove the efficacy of HCQ. His trial was a trial of HCQ vs. no-HCQ. HCQ alone. Not HCQ+AZ.

In this trial, he enrolled patients who developped Covid-19 pneumonia. The authors of this study claim for efficacy of HCQ and even more efficacy of HCQ+AZ... based on a subgroup analysis of 6 patients treated by HCQ !

Harvey Risch claims that "For example, the Veterans' Administration Medical Centersstudy (ref 18) examined treated hospitalizedpatients and was fatally flawed (ref 19)."

Ref 19 is a letter from Pr Didier Raoult to Magagnoli et al.

Harvey Risch agrees with Pr Didier Raoult that Magagnoli et al. study is "flawed". Let us see how Didier Raoult criticizes Magagnoli et al. study :

1) Didier Raoult claims that Magagnoli et al. conclude their article sayying that HCQ treated patients die twice as much as no-HCQ patients. This is a false statement : the authors do not say that, they discuss the bias of their own study, and conclude that RCTs are needed.

2) Didier Raoult focus on lymphopenia. This is knocking an open door since Magagnoli et al. discuss this issue and this issue was taken into account by the fact that the authors computed a propensity score.

3) The other criticism by Pr Didier Raoult show that he didn't understand Magagnoli et al. study at all. It appears that Didier Raoult did not understand that there were 3 groups of patients (HCQ, HCQ+AZ, no-HCQ) made by two different methods, such as in a sensitivity analysis.

First method : treatment exposure on all the study period. Second method : treatment exposure only before mechanical ventilation. The first method is the normal method to study drug exposure.

The second method is obviously performed to favor the HCQ groups if HCQ is effective on early stages (before mechanical ventilation, as was claimed by Pr Didier Raoult) ! Criticizing this sensitivity analysis and concluding to fraud is nothing but completely stupid.

How can Harvey Risch endorse this criticism?

Harvey Risch claims that "The same point about outpatient use of the combined medications has been raised by a panel of distinguished French physicians (ref 20)". "distinguished"? Is that a joke?

The authors of the study in ref 20 are totally unknown. They have never published anything. The study in ref 20 is a total mess. How can Harvey Risch not see that ?!

Harvey Risch writes that "In reviewing all available evidence, I will show that HCQ+AZ and HCQ+doxycycline are are effective in preventing hospitalization for the overwhelming majority of such patients."

What a joke. Harvey Risch did not review all available evidence. He only picked up five studies. We will take a look at them and how Harvey Risch comments on them.

I.) - 1st study picked by Harvey Risch : Gautret et al. 2020, clinical trial.

The authors of this study claim that HCQ and HCQ+AZ are effective against Covid-19. Harvey Risch claims that this study shows efficacy of HCQ+AZ. He claims to have "reanalysed the raw study data" and found the same conclusion.

Harvey Risch adds that the only valid criticism against Gautret et al. is the lack of randomization. He rejects the criticism about the "small study size", saying that criticism on size matters only when no evidence is found.

How can a Journal of Epidemiology accept that?

a) "lack of randomization" and "small study size" were not the only valid criticism against Gautret et al.
Other criticisms were :

- Open label
- All the patients of HCQ group were treated at IHU of Marseille, all the patients of control group are from other cities.
- Follow up was not the same for all patients

- Study was planned for 2 weeks, authors ended the study after 6 days and never provided follow up data
- A patient died at D3 with a negative viral load at D2 (Pr Raoult claimed in a video that "if you get rid of the virus, you are saved")

- The method used to deal with missing data was highly in favor of HCQ group, resulting in "PCR not performed" considered postive in control group and negative in HCQ group !

- Authors compared 3 groups with only one global Chi² test. They didn't perform post-hoc analysis. For a simple reason : post-hoc analysis shows that HCQ more effective than control but HCQ+AZ not more effective than HCQ alone !

All these criticism are swept away by Harvey Risch who only focuses on the 6 patients (1 died, 3 transfered to ICU) who were excluded from analysis (which is what can be called a true scientific misconduct !).

b) Harvey Risch seems to not understand the importance of a large sample size. A large sample size is important to detect a difference, but it is way more important to have a robust estimator with tight confidence interval !

c) Harvey Risch claims that this study shows that HCQ+AZ must be given very early. But that's not even what Pr Didier Raoult said on March 25th. He said that patients must be treated when they have moderate Covid-19 or starting aggravation Covid-19 !

II.) - 2nd study highlighted by Harvey Risch is Million et al. from IHU of Marseille.
This study has no control group ! The authors conclude to efficacy. A study with no control group can't conclude to efficacy. How can Harvey Risch not know that?

III.) - 3rd study is Zelenko study, which data are not even published ! How can Harvey Risch comment on a study which is not even published? That's incredible. timesofisrael.com/jewish-md-who-…

IV.) - 4th study is a "controlled non-randomized trial of HCQ+AZ in 636 symptomatic high-risk outpatients in São Paulo,Brazil" published on... Wordpress !? Please...

V.) - The 5th study highlighted by Harvey Risch is "a small study isongoing in a long-term care facility in Long Island, NY". And that's all. No data. No article. No preprint. Nothing.

This review by Harvey Risch is a joke, @AmJEpi. Retract now. Quicker.

⏹️

Oh, @AmJEpi, in the second study cited by Harvey Risch, Harvey Risch says that "Five patients died,and the remainder were in various stages of recovery". However, the article published in Travel Medicine and Infectious Disease states that there are 10 deaths among the patients

of this study. And follow up was not over for all patients at the time the authors published their article.