What should have been done in the Marseille study?
The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?
The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.
In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.
It would take 1,000 patients, and then, even without a control arm, we would have an answer.
On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.
We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
What are the other studies on hydroxychloroquine that could give us answers?
There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.
It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs … perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.
I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.
That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!
If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?
Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.
