The French version of this article is available here: Didier Raoult: 30 years of wild experimentation on humans
It lasted one year, from October 1993 to October 1994. The homeless people who showed at the emergency rooms of “Hôpitaux de Marseille” were treated by local medical teams. Of these, 43 were admitted to the hospital and underwent a whole series of exams and blood tests. During the same period, blood was also taken from 57 hospital patients who were not homeless. Finally, one of the team’s doctors also went out to meet the homeless people in the city’s shelters, again to collect blood. 211 people had their blood drawn. The goal of this huge operation ? To detect traces of infection in homeless people witha bacterium – Bartonella quintana – transmitted by lice and responsible for trench fever. This research was led by a promising doctor, Didier Raoult, who was unknown to the general public at the time.
He and his team published their findings of this work in the scientific journal Clinical Infectious Disease in 1996. The problem was that the article made no mention of any authorization to conduct experiments on human beings. When asked about this, Professor Raoult did not respond to our requests. As for his colleague, Professor Philippe Brouqui, the first author of the article, he did not wish to reply.
It was apparently at this time that a kind of “Marseille Doctrine” on human experimentation was established. It could be summed up in a few words: this is not a research project, but rather standard care. The main advantage of this vision is that, unlike human research, care does not require any control, authorization or agreement from a personal protection committee or an ethics committee. This same argument was used by Didier Raoult and his team to justify the unprecedented clinical trial conducted with HCQ at the University Hospital Institute of Marseille (IHU) on more than 30,000 patients during the Covid pandemic. The trial was described as a retrospective observational study – i.e. one that would have been carried out a posteriori on patients treated at the IHU as part of routine care – and criticised by many doctors. However, the study is now considered illegal by the French Medicines Agency (ANSM), which has taken the matter to court.
But let’s go back to the study launched in 1993. Several criteria suggest that this was not standard care, but research: the blood tests of the homeless hospitalized patients were compared with those of 57 non-homeless patients. What was the goal, if not to compare the results of the homeless with those of a so-called control, non-homeless population ? Research, then. Then there’s the doctor who took blood samples from 211 homeless people in shelters – healthy volunteers, in other words, who weren’t sick. Research again.
“We keep coming back to the same argument, which dependson the interpretation of what has been done. Is it research or care ? As long as there are healthy volunteers, it can’t be health care. So it is research”, explains Thibaud Haaser, coordinator of the Ethics and Health Research Center at the University Hospital of Bordeaux and chairman of the South-West Overseas III Committee for the Protection of Individuals (CPP).
In 1993, such research was governed by the 1988 Huriet Law. As stated in the legislation, it should have been subject to the prior opinion of an Advisory Committee for the Protection of Human Subjects in Biomedical Research (CCPPRB). This may sound like administrative quibble, but the role of the CCPPRB is crucial. It ensures that scientists do not conduct unnecessary and unauthorized experiments. It checks that the research project is relevant, that the people carrying it out are properly qualified, that the participants receive the protection they are entitled to, and that they are informed of their rights, in particular their right not to take part in a trial or to be compensated for their participation. There is nothing in the publication to indicate that all of these measures were taken. The lead authors declined to answer our questions. If the absence of CCPPRB opinion is confirmed this study would, to our knowledge, be the first illegal experiment carried out by Didier Raoult and his colleagues. Thirty years ago already !
This work on trench fever among the homeless preceded a new study, the results of which were published in 1999. The procedure is the same. No ethical approval is given in the text of the article. However, the Marseille team once again took additional blood samples from homeless people, including healthy volunteers. An act that further demonstrates that this is still illegal research and not routine care.
“What’s disturbing about these studies with the homeless is that they are a particularly vulnerable population in socially speaking. One might question the abilityof these people to genuinely volunteer to take part in a study. This does not mean that such research should not be carried out, but it is not possible to consider a homeless population as a traditional population. In addition, there are other complex associated conditions: people who cannot read well, who have addiction problems or psychiatric pathologies, for example. Under these conditions, considerable precautions are needed to obtain informed, voluntary and free consent, etc.” adds Thibaud Haaser.
This article on the homeless was flagged on Pubpeer in July 2022 for ethical problems. This website, well known to scientists, aims to improve the quality of research by warning of possible fraud and ethical breaches in publications. Stung by the remarks made about the paper of which he is the first author, Professor Philippe Brouqui has left a highly instructive comment on Pubpeer. In particular, he considers that this is not research but routine care. This would mean that it would not require the prior approval of a CCPPRB.
We therefore asked the head of research at Assistance Publique – Hôpitaux de Marseille (AP-HM) to shed some light on the matter. Their analysis concurred with ours: ” some points are unclear. First, there is no clearly identified instigator for this study. Secondly, at that time – patients included in 1997 – the research was established under the Huriet Sérusclat law: the article refers to 250 serum samples taken from healthy donors. According to the publication, these samples would have required the opinion of a Consultative Committee for the Protection of Individuals in Biomedical Research (CCPPRB). The positioning of this procedure as standard care is not supported”.
This last sentence definitively invalidates the argument put forward by Prof Philippe Brouqui on Pubpeer. Even more worrying, the doctor states, again on the Pubpeer website, that this study had no protocol, no inclusion criteria and no initial research question. An embarrassing admission, because it ticks all the boxes of an unauthorized study.
This desire to conduct research on humans without any controls can lead to serious abuses. A perfect illustration of this can be found in recent studies conducted at the IHU on the homeless, which have been criticized by the health authorities. In August 2022, following an investigation, the General Inspection of Social Affairs (IGAS) revealed that the Marseille facility had conducted unauthorized clinical trials on the diagnosis of tuberculosis (Mycobac trial). Some of the patients enrolled in this trial received in-house treatment, a protocol that did not comply with international recommendations for the treatment of this disease. This protocol included molecules such as sulfadiazine, which, according to the National Reference Center for Mycobacteria and Mycobacterial Resistance to Antituberculosis Drugs, have no place in the treatment of tuberculosis. The IGAS concludes: “The mission considers that patients have not received treatment that complies with current standards and that they may have suffered a loss of chance”. This treatment will also be the cause of serious adverse events.
Among the patients who took part in this unauthorized trial, the mission found a minor, non-French speakers, as well as homeless people. There is nothing in the medical records to indicate that the patients were informed that they were taking part in an experimental protocol. On the contrary, one patient’s medical record states that she didn’t even speak French. In addition to the fact that these prescriptions are unjustified, some drugs are prescribed “off-label”, i.e. outside the indications for which they have been authorized. This practice will become systematic with hydroxychloroquine in the treatment of Covid. In addition, the IGAS report states that drugs with proven efficacy in the treatment of tuberculosis have not been administered. The mission considers that risks were taken in establishing this IHU protocol: “These facts are likely to be classified as criminal offenses”.
Our investigation led us down another path, that of studies carried out on another infectious disease well known to IHU physicians: AIDS. An initial suspicious article was published in the scientific journal Journal of Medical Microbiology in June 2017. The protocol involves rectal self-collection. This protocol is similar to that used, without authorisation, in another study carried out on medical students and published in 2020. It was this unauthorised experimentation in 2020 that led the ANSM to take health-policy measures against the IHU in June 2022, prohibiting any new human research at the Institute.
Let’s go back to 2017. IHU researchers claim to have all the necessary authorisations, in particular a favorable recommendation from the IHU’s internal ethics committee dating from 2016. Except that the study began in January 2014 and ended in December 2015. The favorable opinion was therefore issued after the fact, two years later ! Just like the 2020 experiment on medical students. In any case, this recommendation is of little value, since this research once again required the approval of a Committee for the Protection of Individuals (CPP) and the ANSM.
When alerted to these practices, the journal’s editor placed this blunt note at the top of the publication: “This article is currently being examined as part of an ‘investigation into scientific misconduct’ by the University of Aix-Marseille and the French authorities”. To the best of our knowledge, the ANSM has not reacted to this information, depriving patients of their rights of appeal and information regarding their participation in an unauthorized trial. Didier Raoult, the lead author of this study, did not respond to our questions. Nor did he answer any questions about the study we are about to discuss.
It was published a year earlier in the journal BMJ Open Gastroenterology and focused, once again, on AIDS. It involved patients who were carriers of the virus and healthy volunteers. Stool and blood samples were taken. The article again claims to have all the necessary authorizations to conduct this research on humans. In particular, it cites an approval from a local ethics committee. The notice bears the number 09-022. This number is well known to those who have been interested in the IHU’s activities for some time. It has been used nearly 250 times over a dozen years on a wide variety of topics.
However, authorization from an ethics committee is only granted for research with a precisely defined protocol and objectives. The same authorization cannot therefore be reused for other research. As we were unable to obtain any information from the IHU, we asked Professor Yves Lévy, co-author of the publication and former President of Inserm from 2014 to 2018: “Nobody, and probably not the ANRS, was aware of the ‘local’ ethics committee at the time. In this respect, there is an ambiguity that certainly misled all of us, especially the supervisory authorities and the ANSM: the “local” was interpreted as the Marseille CPP (personal protection committee) and no one imagined that it was an “internal” CPP at the IHU, whose operating methods we do not know. This information – local CPP and number of studies – has only recently come to light since the investigations conducted into the IHU.
Even more confusing is the fact that the publication also mentions authorizations obtained as part of the “ANRS EP55 Microgut” project supervised by Inserm. This becomes rather comical when we learn from the Clinical Trials Registry that this project was authorized by a CPP in 2014 and enrolled its first participant in December of the same year.. However, in the study led by Didier Raoult, the first participants were included… two years earlier, in 2012, without permission. Once again, this temporal anomaly shows that the study was an unapproved trial chase that escaped the scrutiny of the regulatory authorities.
Inserm, which we contacted, has acknowledged that the dates given in the publication do not correspond to those of the Microgut project. As for the number 09-022 mentioned in the article, Inserm confirms that it does not correspond to the official CPP number obtained for the ANRS EP55 MICROGUT trial. The person we contacted concluded: “Inserm was not aware of this anomaly. If it were to highlight any ethical breaches, Inserm and ANRS, as sponsors of the ANRS EP55 MICROGUT study, would have to assume their responsibilities in conjunction with the competent authorities.”
Will the ANSM again have to refer the case of these unauthorized trials conducted at the IHU to the judicial authorities ? In a tweet on June 13, Didier Raoult quoted Churchill as proof of his determination: “This is not the end, nor even the beginning of the end, but perhaps the end of the beginning (of war)”. Does he still believe that ?
