Critical analysis of Professor Raoult's therapeutic protocol

Tribune of Pr Dominique Baudon, general medical inspector of the Armed Forces Health Service, Commander of the National Order of Merit, Officer of the Order of the Legion of Honor and Knight of Academic Palms. He is also a specialist in medical biology and a former professor in epidemiology and tropical public health.

The objective that I have in this forum is to analyze the criticisms made to Professor Raoult and his team on the therapeutic protocol used in the management of Covid 19. Too often the media, but also certain “scientists" criticize without really knowing. (Ultracrepidarian). I also think that the results have not always been well defended, even by those who favored it.

This forum is primarily intended for citizens and not specifically for "scientists"

In order to perform a critical analysis of the Therapeutic Protocol, it is necessary to know precisely this protocol, the target population who benefit from the Treatment, the side effects of the drugs used. It is also necessary to understand a minimum of scientific term, in particular what are mortality and lethality. At the end of this column I gave a list of indicators referenced in the text with their calculation method, with the sources for obtaining these data; I also gave some definitions for the understanding of this text.

The target population for treatment.

These are patients with clinical signs suggestive of Covid 19, without serious complications, and therefore do not require immediate hospitalization. These are not people screened without symptoms called "asymptomatic carriers".

They were suspected of the disease by a general practitioner who referred them to the IHU Marseille (Institute Hospitalo Universities Marseille Mediterranean Infection) for a biological diagnosis and possible treatment. Sometimes, patients went to the IHU on their own for biological screening.

I call this population

"The patients of general medicine"; It is also this population for which the health authorities have asked to stay at home after medical consultation (physical or by tele-consultation), and to call "15" in case of complications (respiratory failure in particular).

The therapeutic protocol

It is well known: it is the association "Hydroxychloroquine with azithromycin"

The dosage in Professor Raoult's protocol was a maximum of 6 g of hydroxychloroquine in 10 days associated with 1.25 g of azithromycin in 6 days (minimum 3 days of treatment); the treatment was in fact adapted to each patient according to his clinical situation.

The pre-treatment assessments and the treatment itself were carried out in outpatient hospitalization at the IHU.

Taking into account the side effects of Hydroxychloroquine.

They are well known and have been controlled at the doses used in the protocol. Arrhythmias have been particularly sought after (initial and control electrocardiogram) and search for serum potassium. I worked as a doctor and researcher in intertropical Africa for 20 years; I have conducted many studies on Malaria and I have treated many African and expatriate patients.

Until the 1990s, the effective treatment was chloroquine (Nivaquine) for the simple forms, and for the more serious forms quinine.

The dosage used to treat malaria was chloroquine at a total dose of 2.4 g in three days. (Chloroquine has not been used in the treatment of malaria in intertropical Africa for more than 30 years because the parasite responsible for malaria is resistant to chloroquine)

What the studies have shown

With this protocol, viral carriage, once the diagnosis of Covid 19 was made (PCR +), varied from 5 to 10 days. Chinese and other studies have shown that this carriage is usually 15 to 20 days, sometimes even longer in the pauci symptomatic subjects; this is now accepted and should be considered as the benchmark. There are two positive consequences for the use of this protocol: one for the patient who heals faster, the other for the population since the subject is contagious for less time. There was no heart trouble.  

Nothing else has been shown. Professor Raoult never spoke of a "miracle drug";

He never even recommended this treatment; he said what he had done, with the results obtained.

On June 30, in Marseille, Pr Raoult's team diagnosed and treated 3,342 patients at the IHU; there have been 18 deaths. The percentage of deaths among the treated cases was 0.5% (apparent lethality).

(Ref .: www.mediterranee-infection.com/covid-19)

As of June 30 in France, the number of PCR + cases declared by the health authorities was 197,885 with 29,734 deaths (ref. www.santepubliquefrance), an apparent lethality of 15%. Of course we cannot compare these two different populations.

The top three critics

On the Efficacy of the treatment: What has been said and written by the media and scientists: "In any case, 98% of patients recover spontaneously, and the mortality rate of Covid 19 is 0.5%, rate which would have been obtained in the studies of Pr Raoult ”.  Both of these claims are false.

What is probably true is that 98% of infected subjects recover spontaneously: but this includes not only PCR + confirmed patients, but also suspect cases that have not been screened, and especially asymptomatic carriers. I estimated more precisely that approximately 95% of the infected subjects did not develop the disease (* 4).

The following statement is also false: "The mortality rate for Covid 19 is 0.5%, a rate obtained in the studies of Professor Raoult". I quote from the open letter from a University professor, Hospital Practitioner, signed "Sigaps", member of the Think Tank Lisa, published on 02-06-2020: "The problem here is that natural mortality of Covid-19 was estimated according to a mathematical modelling which is difficult to discuss at 0.53% [0.3; 0.9] in France, during confinement. In other words, you get a death rate equivalent (and not lower) than expected. No difference. What do you think ? "

There is a confusion here the mortality rate in the sick, (apparent lethality * 1), and the natural mortality rate in the infected subjects (real lethality * 2)

I have estimated the actual lethality to date at 0.77% (number of deaths among infected subjects) (* 4); it is probably to this lethality that "Sigaps" refers.

The 0.5% obtained in Pr Raoult's studies relates to apparent lethality (mortality of the patient population) and not that among infected subjects.

On toxicity: Yes, this toxicity exists depending on the dosages given. At the recommended doses and by taking the conventional precautions in the prescription of drugs, the risk of side effects is almost zero.

I still do not understand the virulence of the critics on this subject.

On the methodology: "There was no control group" however I will however validate the protocol. Here are the reasons:

This is an « observational » study (* 5), on patients (early stage) presenting to the IHU for a possible diagnosis of Covid 19. All previous studies had shown that viral carriage was in the order of 15 to 20 days. For me, it is the results of these studies that represent the "control group", the benchmark for comparison. By demonstrating that with the treatment the portage was only 5 to 10 days, why make a control group in this emergency circumstance. The control group would have been necessary if at the outset we did not know the duration of the viral port.

Why did the scientists who criticized the protocol from the first publication, with the considerable number of patients existing at the time, not carry out the survey with a control group to verify the effectiveness of the protocol? This question has often been asked to me and I am amazed at the lack of answer.

And yet it’s obvious and that ties in with what I said at the start. Hospital workers see patients at the stage of complications, general practitioners at the beginning stage. Everyone has their role. Prof. Raoult, a man of the field, understood that it was necessary to "recruit" the patients at the first symptoms, and for this he worked in liaison with the general practitioners.

My main criticism of the media and some scientists.

Professor Raoult’s protocol was completely ignored and everyone focused only on hydroxychloroquine.

Thus, in all the research work published on the efficacy of hydroxychloroquine, whatever the  conditions of use of this product, (associations or not with other products - variable doses - studies conducted only in hospitals) , if the study did not show efficacy, the conclusion was drawn that Pr Raoult's protocol was ineffective !!

To my knowledge, no other study on the Hydroxychloroquine + Azithromycin protocol given to patients at the start of infection, without serious pathology requiring immediate hospitalization, according to the indicated dosages.

To show sometimes the bad faith of rare journalists, I would like to inform you of the remarks made last June 6 by a journalist of a news channel (I will not quote either) trying to demonstrate, I quote «  that on the toxicity of hydroxychloroquine, Professor Raoult says everything and its opposite ” » . 

His demonstration was based on two interviews, one in French explaining that hydroxychloroquine at the doses given in his protocol was not toxic, and another in English saying that hydroxychloroquine at very high doses could be toxic; there is of course no contradiction there, but the viewer not necessarily warned on the subject, can believe this journalist.

I wanted to give my opinion, only on this protocol. Pr Raoult's behaviour, his statements should not interfere with the results obtained. I employed the term Ultracrepidarian, behaviour which consists in giving one's opinion on subjects on which one has no knowledge. This is sometimes the case among the media. In conclusion, I find the criticisms of Professor Raoult's Protocol unjustified and unfounded.  

Translated by @Smackenziekerr & @PaulGreeff

Sources, calculation and definitions Sources : Santé Publique France- South China Morning Post   (https://www.scmp.com)-www.mediterranee-infection-www.covidminute.com (G. Zagury and C. Gabay) - (Ref. Johns Hopkins —https://coronavirus.jhu.edu/map.html)

Some figures and definitions

Situation of Covid 19, as of June 25, 2020 in France • Number of confirmed Covid 19 cases (PCR + patients) = 19,885 (Incidence since the start of the epidemic), • Number of cases per million inhabitants = 29,536 cases / 1M (197,885 / 67M) • Number of deaths from Covid 19 = 29,734 (specific mortality from Covid 19)

• Number of deaths per million inhabitants = 443.8 / 1M

Text references *

Lethality: it is a percentage of deaths among cases

(* 1) Apparent lethality (or case fatality rate (CFR) in English = Number of deaths among PCR patients + = 15% (29734/197,885) Apparent lethality Protocol Pr Raoult = Number of deaths among patients PCR + = 0.54% (18/3342) (Note that we do not have precise figures on the number of subjects not sick but systematically screened PCR +; we cannot calculate the lethality on this population) (* 2) Actual lethality (fatality rate infection) = Number of deaths among infected subjects = 0.77% (0.0077) (* 3) Estimated number of subjects infected with the virus. According to the Institute Pasteur Paris, 5.7% of the French population has been infected, for a total of 3,819,000 infected subjects (Infected subjects represents the sum of asymptomatic carrier subjects not detected, non-sick PCR + subjects during systematic screening, and confirmed PCR + sick subjects) (* 4) Estimate of the percentage of infected subjects who have not developed the disease (natural healing): number of subjects with spontaneous healing = 3,621,115 (3,819,000 infected subjects -197,885 PCR + patients), i.e. almost 95% of infected subjects . (29,734 / 3.8 million) (* 5) Observational studies In epidemiology and statistics, an observational study draws conclusions on the possible effect of a treatment on the participants, when the allocation of the participants to a treatment group compared to a control group is not within the competence of the investigator. In some cases, observational studies constitute the most appropriate methodology (the pathological condition studied is rare, emergency.) ...