Why were the Marseille IHU (IHUm) and its ex-director Didier Raoult not sanctioned when they broke many rules during the Covid-19 crisis? This is the question posed by 16 learned societies – which represent thousands of doctors – in a column published on Sunday May 28 in The world. The signatories point in particular to the systematic prescriptions of hydroxychloroquine, zinc, ivermectin or azithromycin for patients with Covid-19 until at least 2022, more than a year after the demonstration of their ineffectiveness.
Worse still, they denounce a scientific study by the IHUm describing the impact of these prescriptions on 30,000 patients, proof according to them that the Marseilles institute has probably conducted “the largest wild therapeutic trial known to date”. And this without the slightest reaction from the administrative, ordinal or judicial authorities, while the Jardé law strictly frames research on the human person (RIPH). The two coordinators of the forum, Professor Mathieu Molimard, signatory for the French Society of Pharmacology and Therapeutics, and Doctor Amélie Boissier Descombes, President of the association of victims of these potential illegal clinical trials, still do not understand how this situation could have occurred.
Mathieu Molimard and Amélie Boissier Descombes are the two coordinators of the forum denouncing “the largest wild clinical trial” conducted by the IHUm.
© / Molimard/Boissier Descombes for L’Express
L’Express: A search took place on Wednesday May 31 at the IHUm, officially as part of the investigation opened last September following up on reports of the General Inspectorate of Social Affairs (IGAS) and of the National Medicines Safety Agency (ANSM). Originally, this investigation did not relate to the potential uncontrolled clinical trial that you denounce, but justice could still be interested in it. Does this mark a victory for you?
Mathieu Molimard: Either this search has been planned for a long time and it is a happy coincidence, or the tribune has accelerated the legal agenda. But that would be unfortunate, because it would mean that you have to go through texts signed by learned societies for the authority to get going.
Amelie Boissier Descombes: It’s a good thing there’s a search. We wrote this column so that the anomalies that we have been denouncing for so long finally find an answer, but also to put the safety and well-being of patients back at the forefront.
Why do you think the IHUm conducted the largest wild clinical trial ever?
MM: The IHUm had launched, in 2020, a first trial including 10,000 patients. It should be remembered that at the start of the epidemic, there was an authorization to prescribe hydroxychloroquine for city medicine. At the time, pharmacovigilance data showed 100 desirable effects, including eight cardiac arrests and four deaths. The authorization was therefore canceled in March 2020. The decree which granted temporary authorization to the hospital was also canceled on May 16, 2020. After that, we returned to the classic framework of a drug which did not have no marketing authorization (MA) and which can be prescribed either in clinical trials or “off-label” on three conditions: that it be exceptional and on a case-by-case basis, in the interest of the patient and based on scientific data.
One would have thought that the IHUm would therefore stop its prescriptions. Yet they continued. The preprint [une étude publiée sur Internet, non relue ni vérifiée par des pairs, NDLR] of the IHUm published this year shows that they even included 20,000 more patients in their initial study. However, their prescriptions absolutely did not meet the three conditions of “off-label”. They were neither exceptional, nor in the interest of patients, nor based on science, since the protocol of the IHUm indicated that they were systematic “for all patients, whatever their symptoms” and that the studies already clearly showed, from 2020, that hydroxychloroquine, whether or not combined with other drugs, was not effective in treating Covid-19 and was even at risk.
Moreover, the IHUm had requested a temporary authorization for use from the National Agency for the Safety of Medicines and Health Products (ANSM) in 2020, which had answered in the negative on October 23 of the same year specifying that the scientific data did not justify this authorization. Thousands of people who were systematically administered hydroxychloroquine and told that it was an effective treatment were therefore abused.
So if this could not be qualified as off-label prescriptions, it was necessarily a therapeutic trial conducted without authorization, in your opinion. Are there other wild clinical trials of a similar magnitude?
MM The one that comes closest is Jean-Bernard Fourtillan’s essay. He believed that valentonine, a derivative of melatonin, was effective in treating Parkinson’s and Alzheimer’s disease. He had organized a test, without authorization, on 350 people in an abbey of Poitiers. His experiment, which concerned 100 times fewer people, was stopped and Jean-Bernard Fourtillan went to prison.
How do you explain that the IHUm was not worried?
MM Because the safeguards have failed. 30,000 patients were exposed to a risk without benefit without anyone noticing and putting an end to it. This is the real scandal.
Where does the failure in the control and warning system come from?
MM The people who should have reacted are those who deal with the operation of the IHUm, the control of its activity and the control of clinical research. There are therefore responsibilities of the IHUm and its management, but also of its supervision, the University Hospitals of Marseille (AP-HM), even if the relationship between the two was very complicated. The Regional Health Agency, which is responsible for hospitalizations, did nothing either. No more than the Council of the Order of Physicians and the National Council of the Order.
As for the ANSM, it sent an inspection because L’Express had published two investigations on the IHUm (the inspection was also motivated after an investigation by Médiapart, editor’s note). And she just announced that it plans to look into this clinical trial which “could be qualified as a category 1 RIPH […] which should have received a favorable opinion from a committee for the protection of persons and authorization to be implemented”.
Didier Raoult benefit from any protection?
MM I don’t know, but during his second visit to the IHUm, Emmanuel Macron declared: “Didier Raoult is a great scientist”. This may have been perceived as a message to let things go and perhaps explains the inertia of the authorities.
ADB Didier Raoult has an important aura. He has won Inserm prizes and was at the head of the IHUm, which has an international reputation and has formidable teams, such as that of Xavier de Lamballerie. From this aura stems a certain impunity.
What would be the appropriate sanction in your opinion?
MM It is not my role or my subject to talk about sanctions. Our forum aims to point out the dysfunctions of the authorities so that this never happens again and that patients are safe, that they have confidence in French clinical research and its supervision by law.
ADB If the guarantors of research allow potentially wild clinical trials to take place, that’s the end of patient safety as we know it and that’s the end of clinical research. The results of clinical trials must be secure, because without reliable data, they will be useless and it will be the patients who will be the victims.
You were supposed to debate with Didier Raoult on BFMTV, but he refused. Does this surprise you?
MM When you are a scientist, you accept scientific debate. He has always refused, whether on a television set or elsewhere. His approach has long since ceased to be scientific. Such an approach would have involved asking oneself: “is hydroxychloroquine beneficial for my patients?”, then torturing this hypothesis by subjecting it to batteries of tests. Didier Raoult, he started from an affirmation and twisted the data so that they correspond to his initial certainty. He tortured the data instead of torturing the hypothesis.
In addition to the publication of the forum, you also created an association of victims, for what purpose?
ADB Our association offers to support people who are victims of illegal clinical trials, if these clinical trials are recognized as such. Before that, the ANSM must conclude that the clinical trial of the IHUm is a category 1 RIPH carried out without authorization and file a complaint. The association will then be founded to assist the victims.
How many people showed up?
ADB The association was launched only a few days ago, but we have already been contacted by several people. We do not want to communicate on this subject for the moment, because the interest of patients and medical secrecy take precedence. But there are potentially 30,000 legitimate complaints, since all the people included in the trial, whether they experienced adverse effects or not, are concerned. We will be there to support them medically and legally in order to protect their interests.