Chloroquine: the biggest (French) health scandal of the century?
posted the October 25, 2020by Gérard Maudrux
The verdict of the National Medicines Safety Agency has just fallen: no ATU (Temporary Authorization for Use) for hydroxychloroquine, in response to Professor Raoult who had requested it. End of debate? Not sure, on the contrary. Will it lead to the biggest health scandal that France has known?
" To date, the available data, which are very heterogeneous and uneven, do not allow us to predict a benefit from hydroxychloroquine, alone or in combination, for the treatment or prevention of Covid-19 disease", argues the ANSM. What data does it have? I have the impression that they are not the same as everyone (except those broadcast by the French press which will not have been neutral in this affair).
It's been a while since I wanted to make a summary of all the contradictory publications on HCQ for 8 months, in order to see what trend we could draw from them by adding them together, doubt being sown on all sides. As I tackle it, I see that others have done it, so I will be inspired by it.
EARLY PHASE: ZERO STUDY SHOWING INEFFICIENCY
First of all, a little reminder: There are 2 phases in the disease: the phase of development of the virus, before the constitution of natural defenses, on which the virucides can act, by killing or slowing down the virus, then the phase of the effects secondary, inflammatory, respiratory and vascular, which make the severity of the disease, and on which virucides have no effect.
First observation, and not the least: how many studies demonstrate the ineffectiveness of HCQ in the early phase and only early? In France ? Zero. Elsewhere, ditto to my knowledge. Who can give me? However, it is in this indication that the ATU was requested, on what basis was the ANSM able to pronounce itself in the absence of these publications?
In France, 3 studies were carried out in the early phase, and all three are opposed to the statements of the ANSM: that of the IHU of Marseille, soon 9,000 cases, that prohibited of 800 cases of liberal doctors (" let them prescribe ”), and Hycovid d'Angers. The first two are criticized by purists where the method takes precedence over the result, ignoring the observation of caregivers in the field for the benefit of statisticians. And yet 9,000 cases, mortality of 0.5%, compared to the placebo group of 1 million infected with a mortality of 3.4% (much lowered thanks to large tests, from 20% to 3.4%, then that it has always been stable in Marseille over the same period). Considering the number in each cohort, the quality of the groups must be statistically homogeneous according to the law of large numbers, more reliable than the drawing of lots.
Regarding Hycovid, it was to be a study of 1,300 cases, randomized double-blind, conducted by the University Hospital of Angers with 36 other establishments. Criteria: effectiveness judged on the number of times in intensive care, in subjects at risk, presenting at least one comorbidity (obesity, hypertension, diabetes, need for oxygen). The stated aim of the study: to put an end to the controversy. Failed for this first objective, given the sequence of events: only 250 cases included, due to the premature termination of the study, the reasons for which are not clear: neither accident nor ineffectiveness. Some mention the Lancetgate affair and the WHO attitude, but the Lancet dates from May 22, (retracted June 5), the last patient included on May 21, and the WHO resumed on June 3 and continued until July 4. False explanations. the attitude of the ANSM which had a great influence to close the study on June 9.
That being said, the results , promised for the end of June, the beginning of July, were put online under pressure on October 19: a 50% reduction in mortality at 28 days. Conclusion: "statistically insignificant linked to the small size of the patient cohort "! I leave you to judge this conclusion made to remain in the political correctness. Furthermore, 0 deaths or intubation in the HCQ + AZI group, this group of 10 patients is admittedly too small, but when there are 3 deaths out of 11 patients in the corresponding placebo group, this still raises questions for the doctors, not for the statisticians. !
Thus on our territory, 3 studies and only 3 studies in the early phase, which all three go in the same direction of a certain effectiveness, and no study proving the contrary, whereas the detractors are numerous, but powerless to prove what 'they advance with something other than words. We can add a fourth, with leaks , (not verifiable for the moment, but not contradicted), concerning Discovery which also show the same results, all also truncated by an unexplained premature shutdown.
What about other world publications? I found two meta-analyzes, one on 147 studies, the other on 118, which I retained because it was clearer. The conclusions for the early part, with 19 publications, are clear: “Early treatment is the most effective, with 100% of studies reporting a positive effect and an estimated reduction of 63% of the effect measured (death, hospitalization, etc.) using a random effects meta-analysis, RR 0.37 [0.30-0.47] ” . Average of studies: 63% positive effects and zero studies with negative effects.
And a little graphic from Yale Medical School to finish:
Now the other studies, more or less early:
CHARGED STUDIES
Already in April I was surprised to a certain bias of the authorities and the press : "We procrastinating on quality e of public ations instead of knowing s' it must be treated or not. It is has been a first publication in favor in February on 100 cases, in 10 centers (Wuhan, Jingzhou, Guangzhou, Beijing, Shanghai, Chongqing, Ningbo). Response from our experts : no randomized. Then they nou s released a study ineffective, randomized beginning in March of the ' University of Zhejiang, 15 treaties, 15 placebo, excuse the little number not significant. Rebelote in China at the end of March, 62 patients, this time randomized (2 x 31, but they n ' have more a lot of patients with stroke st). Apr degree in 5 days 80% improvement in the treated, 55% among the non treated. Response to Critics : this n ' is not an issue, but a preprint, which in addition will match not to the statement prior mandatory ! "
Then, it's the big nonsense: this study , praised by our minister to parliamentarians, where HCQ was administered to the most serious cases in bedridden people, such an extreme anointing, to demonstrate ineffectiveness. And then Mehra and The Lancet, vast intellectual swindle, just as much touted by the Minister, the ANSM, the WHO, leading to the termination of many studies. There was, however, a sentence in this study that should have appealed to them, regardless of the rest: "Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred." These data do not apply to the use of any treatment regimen used in the ambulatory, out-of-hospital setting. " In short: these findings do not apply to patients treated on an outpatient basis, outside the hospital. The Lancet recanted, with apologies, not our officials.
The French press and our leaders, ministers and ANSM in the lead paid attention only to these studies, taking care not to inform us about the hundred other more serious studies.
FAVORABLE STUDIES
What about the Brazilian study in April, 636 patients, 412 treated, 224 no, 3 times more hospitalized in the second group. What about this Italian multicenter study , 3451 patients in 33 centers, 76.3% received HCQ, halving the mortality. In June it is the Henri Ford Foundation which has many hospitals, and which treated 2541 patients in 6 hospitals in Detroit with HCQ + AZI, the death rate was reduced by 71%, no side effects. Also in June, it is another study, in 8 hospitals in New York , 6,493 patients including 3,708 hospitalized, with a further division by 2 of the number of deaths, still without side effects. There it is in Saudi Arabia, 7,892 positive patients confirmed by PCR in 238 outpatient establishments: 1 criterion: hospitalization within 28 days. Result: half as much in the HCQ group. Again in the Netherlands , 1064 patients in 14 hospitals, with a 53% reduction in intensive care admissions. In Italy , another multicenter study, 3451 patients in 33 centers, 76% with HCQ, the rest without, mortality rate divided by 2. Belgium , 8075 hospitalized patients, 4542 with HCQ, 3533 without, first group mortality 17.7%, in the second 27.1%, ie 70% more. All these multicenter studies (there are others), are a guarantee against manipulation by a single team.
One of the last Chinese study in August , 2882 hospitalized and severe patients, 278 on HCQ, including 48 critical condition. Mortality 3 times higher in the group without. And in Spain, first study on 1645 hospitalized: "we find that the risk of death was significantly lower for patients treated with azithromycin, prednisone and, in particular hydroxychloroquine." , and second study on 502 patients (including 85% with pneumonia) concludes with "a reduction in the burden of the hospital pressure with less serious patients". 0 deaths. And finally, icing on the cake, a publication of August 20 from the only hospital on Reunion Island (France) out of 164 hospitalized for Covid: "Despite the risk profile of patients with severe hypoxemic pneumonia, the mortality rate was 0%. This may be due to the treatment pack used in our hospital (early hospitalization, treatment with HCQ / AZT and / or corticosteroids, non-invasive respiratory assistance, etc.). "
SYNTHESIS
What about the summary of meta analyzes, on more than 100 publications and which exclude questionable publications? They all confirm significant efficacy at all stages, less than in the early phase. The authors find that the results for all studies are mixed, but they still report that 68% show positive effects. They also find that: “Negative studies mainly fall into the following categories: they show evidence of significant unadjusted confusion, including confusion by indication; the use is extremely late; or they use too high a dose. " We have seen it for months in the only studies published in France, with the most serious cases voluntarily placed in the HCQ group, average younger ages, overdoses, “in extremis” prescriptions, etc.
RANDOMIZED STUDIES
With regard to the only randomized studies, the results are superimposable to the non-randomized ones, with an amusing finding of the authors, whose human logic will not please the defenders of the randomization: 87.5% of the prospective studies report positive effects, against 69.8% of retrospective studies. Would the authors be influenced by their convictions in their retrospective studies ? “Even with the small number of RCTs to date, there is a strong indication of efficacy. Excluding late treatment, 100% of RCTs to date report positive results ”. The authors conclude that while these randomized studies are very valuable and minimize potential bias, they are neither necessary nor sufficient, and find that well-designed observational studies do not systematically overestimate the magnitude of treatment effects compared to randomized studies. . In short: all doctors who do not randomize are not liars.
PROPHYLACTIC STUDIES
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They also analyzed studies on prophylaxis, with 74% positive. Logic would have it that the results are the same as in the early phase, but the authors report that the negative series is found in carriers of autoimmune diseases (long-term treated with HCQ), pathologies which do not necessarily mix well. with the Covid.
All the details, the methodology and the sources on https://hcqmeta.com For the details see especially in appendices 1) Methods and results, and 2) Analyzes with exclusions. See also other meta analyzes: https://c19study.com (149 studies), https://hcqtrial.com (80 studies), Without forgetting the meta analyzes of the IHU of Marseille . When one eliminates the questionable, doctored studies, not reread by others, all agree to demonstrate the effectiveness of HCQ in the early phase, but also later, and have the same figures. There are others, but the smaller they are, the more tendentious they can be. In France, our elites retain only a few manipulated studies.
Moreover, I did not dig into a point well indicated by the IHU of Marseille: the decrease in the viral load, also studied in a few foreign articles. Who says less virus says less contaminating and for a shorter period of time, therefore less extension of the epidemic.
Another point, France is an extraordinary country, it seems to be one of the few where, according to the authorities, the HCQ molecule has mutated. This is a classic thing with viruses, which can become more or less virulent, but a first concerning a drug molecule. Harmless for 70 years, it has become dangerous, disrupting the benefit / risk factor at the origin of the ANSM's decision.
CONCLUSION
In view of French and global studies, it is undeniable that Hydroxychloroquine has an effect on COVID-19. The earlier the prescription, the more effective it is, going from 100% to 60-70% positive effects. Surprisingly, it would only be in France that this does not work.
Regarding these positive effects, the most measurable and indisputable are hospitalization and death, reduced by 50% in all meta-analyzes. The problem in France is access to hospitalization, here is an easy and inexpensive solution, which the authorities, behaving like the monkeys of Buddhist mythology, do not want to see, nor to hear, nor to discuss, an attitude which goes costing dearly in lives and GDP.
In this context, the latest decision of the ANSM is not medical, we must look elsewhere for the reasons. It also seems like many, she only reads the mainstream press which rushes over the dependent articles and ignores the others. The authors of the analysis, which I used extensively, noted that it was not only in France that this problem existed. So they point out that the New York Times has only ever published articles showing ineffectiveness, none showing the contrary. The explanation should probably be sought from the newspaper's sponsors. Everywhere there is more article showing the (discussed) effectiveness of Remdesivir, than of HCQ, while there is only one study that says so for the first, and more than 100 for the second ...
HCQ may not be the panacea, it does not have 100% positive effects like some indisputable treatments, and even if it only relieves 30% of patients instead of 60% as studies show, in the absence of other treatments always wins, and at least 10,000 lives. Not to mention the placebo effect, as in any drug, which can calm the mind and relieve, reassure many fellow citizens ( see my article ), because in this case, let's not forget that it is not only the Covid, there are also patients, and fellow citizens worried about an absence or refusal of treatment.
Almost all the countries in the world, either advise HCQ (compare their mortality per capita with ours, it is 10 times less), or are neutral, but in all cases let the doctors do their job. The unfortunate thing is that with us, it is politicians and senior officials who treat, not doctors. The title of the article by an American doctor published in Covexit calls out to me: “Thing truth and chose life”. Why ? Because we are the opposite: “choose lie and choose death. "
