RE:The article itself acknowledges (in the Discussion) that most random control trials (RCTs) of hydroxychloroquine show no benefit.
I direct you to the REASONS for the RCTs and their limitations. It says
[QUOTE]
Both trials should be considered as late treatment trials as the randomization occurred upon hospital admission, including as an ICU patient. Both suffer from significant methodological problems, as the HCQ doses during the first 24 h (2400 mg) were four times higher than the highest recommended dose of 600 mg. Mortality was no different between the treatment and control groups, but a careful review of the causes of mortality in the two groups would be worth investigating.
[END QUOTE]
Other RCTs they investigated suffer from small sample size, were underpowered and reach inaccurate conclusions, but as a whole serve as a reference for policy makers.
However, in the large sample sizes. Here is what the study observes:
[QUOTE]
several large observational retrospective studies published in the literature, including a total of 47,516 patients report a benefit of using HCQ on the mortality of COVID-19 patients.
The number of patients involved in these studies largely overweighs the number of patients included in RCTs.
Interestingly, these observational studies report that HCQ is associated with survival and the effect is greater in early treatment.
[END QUOTE]
I also direct you to the CONCLUSION of the article.
It says:
“Overall, this study represents the largest single-center study evaluating HCQ-AZ in the treatment of COVID-19. Similarly, to other large observational studies, it concludes that HCQ would have saved lives.”
You may disagree with its conclusions, but this article makes this conclusion even as it acknowledges the limitations of this study ( many such medical articles do that as well. )
My wife has taken hydroxychloroquine for decades for an autoimmune disease. It is a critical drug for her.
She was hospitalized in 2020 for COVID. They refused to allow her to take her HCQ. They were apparently afraid it would cure the COVID.
There us NO reasoning, with a bot.
Seriously.
The posting style/frequency is just too obvious.
So?
What is going on here is an attempt by McCullough and (perhaps) coauthors to make the case that a retrospective observational study is more robust than a randomized control trial.
It is not.
The "methodological problem" in which 4x the FDA recommended dose of hydroxychloroquine (HCQ) was administered to the patients and no effect was seen does NOT imply that the FDA recommended dose would have had an antiviral effect. With 4x the dose, any antiviral effect of HCQ would have been augmented. (Like if you have a headache, taking two NSAID pills is more effective than taking one.) All that this study showed was that increasing the dose of HCQ by four-fold was not harmful to the patients.
Enrolling a patient "late" into a treatment trial is not a methodological flaw. It's hard to enroll patients ahead of time in a trial of treatment for an acute condition. How can anyone possibly know ahead of time that they are going to catch a severe enough case of Covid to require an ICU stay?
RCTs are, in fact, quite robust. Ideally, no one knows whether the enrolled patients are in the treatment arm(s) or the control arm of the study. Ideally, the randomization occurs in a way as to "match" the patients in control and treatment group in terms of age, gender, obesity, heart conditions, etc. Ideally, the randomizer's only contribution to the trial is to randomize study participants and keep records so that after the trial, the patient data can be sorted and analyzed appropriately.
Other RCTs they investigated suffer from small sample size, were underpowered and reach inaccurate conclusions, but as a whole serve as a reference for policy makers.
Again, these are not significant methodological limitations. The trial only has to be large enough to ensure that it contains enough patients for the deaths in the participant population statistically match deaths expected in the entire population. Patients in the ICU for severe Covid have a fairly high death rate* as compared to patients who only have to quarantine at home. Since the death rate is high and the purpose of the study is to show whether HCQ decreases deaths, the study can be small and still show acceptable statistical significance. In addition, since the purpose of the RCT is to compare efficacy of a specific treatment, all other factors in the trial are kept as consistent as possible. All patients in the trial receive standard-of-care.
On the other hand, retrospective observational studies can have significant drawbacks. For one thing, depending on the variable being observed, there is considerable bias in sample selection, especially if the study author has a preconceived notion of what the study is supposed to prove. For example, a study that purports to show that HCQ improves survival might separate the patient population in such a way that the controls who did not receive HCQ are older than the recipients of HCQ. In this example, there would be a higher survival rate of patients receiving HCQ, simply because they are younger and the mortality of Covid increases with age. There can be bias involved in formulating the underlying assumptions about the study. There is also variability of treatment modality, making it difficult to separate the effects of HCQ specifically from the effects of the other treatments given to the patient. Etc.
I did use an observational study for one of the references below of how deadly Covid is in patients with severe enough disease to warrant ICU care. This study is a little better than an observational study which depends on combing through medical records to try to discern efficacy of treatment. The only criteria for study inclusion was that patients with lab-confirmed Covid were admitted into the ICU. The only outcome measure was whether they survived. There was no attempt to determine efficacy of treatment protocols.
*Mortality in patients admitted to intensive care with COVID‐19: an updated systematic review and meta‐analysis of observational studies. --41.6% mortality of Covid ICU patients.
ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019. --28.6% mortality in Covid ICU patients.
Overall, this study represents the largest single-center study evaluating HCQ-AZ in the treatment of COVID-19. Similarly, to other large observational studies, it concludes that HCQ would have saved lives.
So, this is a retrospective observational study of patients who received two drugs, not just one. I think that I already pointed out that the antibiotic can improve the chance of survival by suppressing bacterial infections that often occur as a result of viral infection. In order to say that HCQ conferred a survival benefit, they would have had to compare mortality of patients who received HCQ-AZ with mortality of patients who received neither drug or who received only one of the drugs.
Etc. Do you really think I did not read the McCullough et al. discussion of RCTs and why (they say) I shouldn't place much weight on RCT outcomes? Of course I read it.