Governance veering off course :
The Méditerranée Infection (MI) University Hospital Institute (IHU) was created in 2011 as a scientific cooperation foundation (FCS) by the Fondation Méditerranée infection (FMI) following the call for IHU projects in 2010 as part of the first investments for the future program (PIA).
The foundation, chaired by Dr. Obadia, initially had seven founding members : the Assistance publique des hôpitaux de Marseille (AP-HM), the French National Centre for Scientific Research (CNRS), the French Blood Institution (EFS), the French National Institute of Health and Medical Research (Inserm), the Institut MÉRIEUX, the French National Research Institute for Development (IRD), and Aix-Marseille University (AMU). The CNRS and Inserm withdrew in 2016 and 2019 respectively, while the French Armed Forces Health Service (SSA) became a founding member in 2017.
Inaugurated in 2018, the MI IHU specializes in infectious and tropical diseases and pools diagnosis, care, research, monitoring and information on infectious diseases under one roof. The IHU is home to the entire “infectious and tropical diseases” (MIT) department of the AP-HM, including three 25-bed care units, including a biosafety level 3 (NSB3) unit, day admissions, consultations and the microbiology laboratory, four mixed research units (microbes, evolution, phylogeny and infection [MEPHI], emerging virus unit [UVE], Vectors – Tropical and Mediterranean Infections [VITROME], health economic & social sciences & medical information processing [SESSTIM]), two SSA research units as well as three national reference centers (CNR). It is also a global training center, in particular for countries in the south, in the field of infectious and tropical disease research in collaboration with the IRD and the SSA. The IHU is also a start-up incubator by offering a space dedicated to technology transfer. There are currently five start-ups working there.
The IHU’s 2021 annual report indicates that there are 864 staff in total, with the AP-HM being the main employer with 463 staff. Rather than IHU staff, it would be more accurate to say “people working or studying in the IHU building”, because this figure of 864 includes joint research unit staff who do not consider themselves or are not considered to be part of the IHU entity, and also students and doctoral candidates.
If we look at the foundation’s staff in the strict sense of the term, the staff register for 2021 lists 43 staff members, including 33 employees with permanent and works contracts, and 10 with fixed-term contracts. The foundation previously decided to have a basic administration and to rely on external expertise : accounting expertise, legal advice, etc.
In application of the provisions of law n°87-571 of July 23, 1987 on sponsorship and of articles L344-11 to L344-16 of the French Research Code, the foundation of scientific cooperation is governed by its original unamended statutes of 2011, approved by decree on November 30, 2011. The FCS bodies are : the board of directors currently comprising six founding members (whereas the statutes provide for seven initial founding members), ten advisory board members, two representatives of research professors, professors and researchers as well as five permanent observers (non-voting members) who provide consultancy, including the chief education officer of the Aix-Marseille education district, government commissioner, and a scientific council consisting of twelve further members. Since it was founded, the director of the IHU has been Professor Didier Raoult, whose term of office is due to end in the fall of 2022, and a process for appointing a new director has been initiated under the direction of Louis Schweitzer, chairman of the selection committee.
While they are supplemented by the foundation’s internal regulations, the statutes lack clarity on certain substantial elements, in particular the procedures for appointing its director. The statutes should be revised to conform to the standard statutes for foundations of public interest (FRUP), the latest changes to which were made in 2020.
The founding members should take advantage of the fact that all agreements governing relations between the foundation and its founding members will expire in 2022 to negotiate a new foundation agreement that will ensure they are more involved in the activity of the IHU and the sharing of its breakthroughs.
Different bodies look at IHUs from different perspectives (scientific strategy, evaluation of research units, overall monitoring, legal control), to a certain extent over extended periods, and it is up to the founding members to make use of this, provided that they have the means to do so.
As in all FCSs with IHUs, the decision-making capacity of the founding members on the board of directors is disproportionate to their contribution to the operation of the IHU. While the founding members of the MI IHU are no exception to this, it seems that it is only recently that they have sought to take more of an active role in the foundation’s fate, in particular by taking on the responsibility that the statutes conferred on them for the appointment of advisory board members to the board of directors.
Beyond their role in the institutional governance of the foundation, the founding members have generally been passive and have not developed the means to influence the running of the IHU. Despite Inserm deciding in 2019 to leave its role as a founder, the other founding members did not take advantage of this departure to lay the foundations for a new framework for their involvement in the IHU. For those who are experiencing poor working conditions at the IHU, this passiveness feels like a form of complicity, if not of acceptance by their employers, particularly the AP-HM and AMU, of the omnipotence of the IHU management team. This feeling has been somewhat dispelled recently since the arrival of new managers at the head of the AMU and AP-HM. In fact, as soon as the new Director General of the AP-HM started in the summer of 2021, relations with the IHU management became strained and occasionally led to disputes.
The strong personality of the director influences the content of the board meetings, while the president of the foundation does not exercise any opposing authority ; the governance of the foundation is thus unbalanced to the benefit of its executive members, all the more so since the director has been able to vote at the board as an advisory member in violation of the rules governing foundations and without any reaction from the Ministry of Higher Education, Research and Innovation (MESRI), and has had a great deal of influence on the choice of advisory board members, who are in the majority on the board of directors. In the end, governance is almost totally based on affinity with the director, which totally contravenes the spirit and the letter of the law and in fact allows the concentration of most of the power to be held by a single person. This is all the more damaging given that the scientific approach and medical practice, which constitute the core mission of the IHU, are essentially fueled by debate, contradiction and respect for the practitioner’s decision-making autonomy. The mission urges that the rules on the governance of scientific cooperation foundations are strictly adhered to.
The scientific council has been unable to influence the scientific directions of the IHU sufficiently, even if some of its recommendations have been taken into account by the IHU management. It is particularly unfortunate that the scientific council’s findings were not used by the foundation’s board of directors to propose changes in the IHU’s action plan.
A management system and practices that prevent debate and inhibit individual initiative :
The management of the IHU is largely structured around its director, setting up various management bodies for care, research and training activities, whose meetings are scheduled every week or month. These bodies include the management committee, the “COVID” meeting, an “engineering”, “emerging” or “valuation” meeting, an “epidemiology” staff meeting, a “microbiology” staff meeting, a weekly “work in progress” meeting, the “kits and ethics” staff meeting, etc. The day-to-day organization is therefore extensive, scheduled and monitored, thus demonstrating a very domineering way of doing things that, given the people involved, is very restricted and controlled.
The general organization chart of the IHU includes a limited list of people in charge, who each have a great deal of responsibility, and makes it possible to have a decision-making team of university professor–hospital practitioners built around its director for a large number of aspects of the life of the IHU, and for those who work and train there. All the testimonies gathered indicate the same thing : Professor Raoult is omnipresent and is the final decision-maker for a whole series of subjects in all fields. If Professor Raoult is the initial influencer in many cases, his decisions have been followed and applied by the other managers who express the same views concerning the place and the role of the IHU, and this occurs in total conformity with the director’s opinions collected by the mission or expressed in the media. As a result, the omnipresence of the director in the running of the IHU, including all the ins and outs, combined with the very little room left for contradiction and debate highlighted by various stakeholders at all levels, has resulted in a strong censorship of the IHU, which is hugely detrimental to the quality of the research and medical activities that occur there.
This concentration of power has been made worse and magnified by the construction of the building that hosts and brings together all the activities of the IHU, which were previously spread across several AP-HM institutions. In the opinion of several of the people we spoke to, having everything on site has finished off a model in which commitment, subjection, sometimes the fear of immediately being asked to the site, and the almost systematic tendency to check what is being done, by whom and when, have created a submissive culture that some have just gone along with and others have resisted.
A gradually deteriorating financial situation :
The foundation’s financial situation is still healthy, but it is deteriorating, which calls for the development of a new economic model. Excluding 2020, operating revenues have decreased slightly since 2017 from €7.9M to €7.3M (mainly due to the decrease in the payment from the French National Research Agency (ANR) as part of the review of the allocations paid to the IHUs in 2019). However, total operating expenses have increased from €7.2 million in 2017 to €8.8 million in the 2022 forecast, which represents an increase of approximately 22%. Even if the foundation’s governance believes that the situation is under control in view of the strong position in terms of its equity capital (€12M in 2021), and also of its capacity to manage variable costs, one of the priorities of the new director will be to work on a new realistic business model.
At the outset, one of the main financial challenges was to find ways to cover the costs of the 27,000 m² building, which was commissioned in 2017. This floor space is divided between different entities under contractual agreements – memoranda of understanding, leases, and occupancy agreements – which were signed in 2016 and have been amended several times. In 2021, the various occupants paid €2.7 million in exchange for occupying the premises, which balances the expenses related to running the building.
Management methods and management team behaviors creating malaise at work or even harassment impacting the medical and scientific process :
Various conflicts and disputes regularly occur in the course of running the IHU. This contentious and sometimes vindictive atmosphere severely affects the relations of the IHU management with the representatives of most of the founding members. Evidently, this concerns certain partners who do not wish to be associated with a tarnished image, but also wastes energy and resources, which is hardly conducive to the smooth running of a leading scientific institute in the field of infectious diseases.
Following the recommendations of the scientific council, the IHU director has implemented a very powerful communication policy, particularly supported by the YouTube channel created for this purpose and through social networks. But this very ambitious communication policy has generated an equally intense media response.
The legal framework applicable to labor relations and industrial relations dialogue at the IHU is based on several legal sources of different types and levels, given the diversity of the institutions that employ servants and contract staff from the State civil service or the public hospital system, staff from public scientific and technological research establishments (EPST), or private law employees covered by the French Labor Code. Thus, there is a well established legal framework for labor relations within the IHU, but without a broader vision or a shared approach among the various stakeholders, since it has gradually become fragmented due to a lack of coordination. However, the complexity of this framework makes it difficult to understand and therefore difficult to resort to for the agents and employees working in the building.
Some of the rules are applicable to only some of the staff (internal regulations of the FMI, internal regulations of the joint research units, single occupational risk assessment documents (DUERP), while others concern all of them (rules for working within the IHU Méditerranée infection, IHU memos, ethics charter). The diversity, the lack of updates to and the lack of links within this legal framework that structures the relations and the working conditions common to all the occupants require work to clarify the respective application scopes and the responsibilities of all involved, by conducting a robust consultation during their drafting and to update the delegations of authority and signatures on the part of the “supervisory” institutions. Taking into account the experience gained since 2017, it would be appropriate to clarify and remind all occupants of the respective responsibilities of the representatives of the stakeholder employers and the IHU management in terms of health and safety and compliance with common rules on the site and to arrange consultation of the staff representative bodies on the subject.
Furthermore, even though a health and safety unit for the foundation and two UMRs was set up in 2017, which is supposed to consist of prevention assistants from each unit or department, its actual functioning, which in fact only involves half of the services present at the IHU, does not allow the stakeholder employers to get a full picture of the problems common to all the occupants of the building. As a result, we recommend formalizing a framework agreement concerning the management of working conditions and relations formalized with all employers and creating a representative body specifically for the common issues of staff working in the IHU.
In general, there is an occupational risk assessment process in practice, but there is insufficient coordination between the various units that work together in the building despite the common risks. We therefore consider it necessary to update the DUERPs in a coordinated manner, to take into account the lessons learned from the pandemic and to summarize the preventive measures to be implemented by closely involving all the stakeholders in order to make shared observations and by completing them on the prevention of psychosocial risks.
Medical check-ups for staff working at the IHU is split between several departments and does not facilitate a comprehensive view of the working conditions of the people employed on the site and particularly of a shared vision of issues related to psychosocial risks. There is a need to improve the coordination between the various occupational healthcare and prevention services that monitor the public servants and employees working on the IHU site and also appoint a lead physician.
Even if it is presented as inclusive by the IHU director, the decision-making process is very centralized and is magnified by a very authoritarian and pyramidal management style with no real internal balance. This may have, if it did not directly create it, at least paved the way for a sense of malaise in the workplace, which is demonstrated by the “abnormal” events in terms of work relations, events corroborated by the interviews conducted by various stakeholders and the Inspectorate mission. Around fifty interviews conducted by the mission clearly highlight a situation with staff experiencing malaise to severe suffering linked to their professional activity, whether the people interviewed are still working at the IHU or have already left. In particular, many testimonies repeatedly describe an often brutal, sometimes humiliating management style, either in public or within individual relations. These interviews describe situations ranging from clearly expressed discomfort to descriptions of offensive or harassing behaviors. The interviews conducted by the Director General (DG) of the AP-HM between September and October also describe certain very difficult situations experienced by hospital practitioners or AP-HM staff. Overall, the body of evidence and testimonies gathered by the mission from those that the mission spoke with highlights a management style that results in psychosocial risks for certain staff categories and situations that can border on sexist and sexual violence. In addition, this management style has negatively affected the functioning of the scientific approach, which is based on critical thinking and medical reasoning.
The mission recommends replacing the medical management team of the IHU and overhauling the managerial practices.
The slow reaction of the supervisory authorities between 2018 and 2021 has contributed to a strong feeling of skepticism among the staff working at the IHU. Firstly, it is therefore necessary to immediately mobilize the supervisory authorities in conjunction with the new management of the IHU and the staff representative bodies around a common charter for the prevention of harassment in all its forms and for the improvement of the quality of life at work, and secondly, to rapidly organize training for all IHU managers in the prevention of psychosocial risks and sexual and psychological harassment, and to focus on protecting mental health within the single occupational risk assessment documents submitted to the various representative bodies.
A strategy to be reviewed and formalized :
The IHU’s high-level technical capacities are made available to clinicians and researchers in the following fields whose discoveries have been the subject of scientific publications for many years : giant viruses, microbiota, fungi, antibiotics, beta-lactamases, Archaea, small microbes or candidate phyla radiation, and electron microscopy. The COVID field has of course become particularly important since March 2020.
The MI IHU’s capacity to respond and take action in the areas of care and research was demonstrated during the COVID-19 pandemic. Nearly one million PCR tests were carried out, enabling the diagnosis of 75,270 infected patients. The mission stresses the significant contribution made by the MIT department and the MI IHU during a pandemic linked to an infectious disease.
The strategy developed at the MI IHU involves applying a method of scientific discovery that combines clinical observation and high-level technology to the wider field of infectious and tropical diseases. The overall architecture of the scientific strategy is mainly based on 2 pillars : samples taken in the course of care, which are used to build sample bases and databases for research and publication purposes, and the analysis of samples resulting in the creation of cohorts and collections, which is presented as largely retrospective.
Publication is a key objective for the IHU. Between 2012 and 2021 inclusive, the number of publications in which at least one of the professionals listed in the MI IHU directory has participated is 6,790, giving an average of 679 per year. This figure makes the MI IHU the top IHU in this regard, even if it has now been matched or even surpassed by other IHUs. A precise ranking based on the content of the publications shows that, cumulatively, between 2011 and 2021, the MI IHU’s articles account for 30.5% of the articles published in France on zoonotic diseases, 17.5% of the articles on virology/infectious diseases and 7.5% of the articles dedicated to antibiotics and antimicrobials. These figures confirm the MI IHU’s specialization and its standing at national and international level. However, the mission also notes the limitations of a strategy that aims for speed of publication. The share of publications in E-rated or unrated journals is higher than that of other IHUs : 19.5% on average compared to 13.5% for the other IHUs. Correspondingly, the share published in A-rated or B-rated journals is lower than that of other IHUs : 46.3% compared to an average of 57.4% for all IHUs.
The MI IHU’s positioning has resulted in it becoming distanced from basic research institutes ; two key founders in the area of basic research, CNRS and Inserm, therefore withdrew at a very early stage. Internally, at the MI IHU itself, the scientific work is carried out with the full involvement of the MEPHI and VITROME joint research units as well as that of the SESSTIM and UVE joint reserach units, albeit in a less direct way.
As the IHU’s policy aims to avoid dependency on external research funding, this subsequently results in the institution’s isolation and may well undermine the quality of its work. The mission was aware that the number of responses to national calls for proposals has been very limited : just 7 since 2016. The COVID-19 crisis has further isolated the MI IHU. The discussions held by the MI IHU’s scientific council make this clear, implicitly pointing to its isolation and explicitly stating the need to reduce it. In particular, the MI IHU does not participate in major national calls for proposals, nor is its involvement sought at national level despite its technological and scientific capabilities. The mission stresses how important it is for the IHU to develop a strategy that incorporates the revival of partnerships and takes the recommendations of the international jury into account, so that a roadmap can be developed and subsequently approved by the FMI’s Board of Directors.
Under the terms of the initial call for proposals, all IHUs must ensure the training of top-level professionals in the area of care and research, and enable better coordination between research, teaching and care in connection with major health challenges. More than 3,000 students have been trained since the IHU was first established, with just over half of these students being involved in health-related studies, a further 500 undertaking a master’s degree and just over 400 completing their PhD. Of the one thousand students who have completed a master’s degree, PhD or postdoctoral degree since 2011, only about a quarter are French, confirming the IHU’s appeal to foreign students (32 different countries of origin), a third of whom come from Africa. However, generally speaking, the IHU has little information on what ultimately becomes of these foreign PhD students, most of whom return to their countries of origin. A system needs to be put in place to monitor outcomes for these students, as one of the defining features of the IHU is its desire to focus on the countries of the Global South.
In particular, the IHU welcomes interns preparing to specialize in “infectious and tropical diseases”, a clinical medical discipline that focuses on the management of infectious and tropical diseases at both an individual and collective level. The mission revealed certain shortcomings or situations that it considered to be abnormal, although the testimonies gathered painted a mixed picture, with some embracing the system that is in place and others rejecting it. These testimonies reveal that there is an unusual amount of pressure felt to obtain results for the research undertaken ; this situation, which can be explained by the “speed of publication” strategy mentioned earlier, is also accompanied by a very specific context in which sometimes “you need to prove the initial hypothesis”, with young researchers stating that they intentionally water down results and data, or exclude things that do not work, in order to avoid feeling pressured. This pressure to obtain research results is accompanied by the expectation placed on doctors in training, both external and internal, to obtain consent from individuals so that they can be included in clinical research cohorts. According to several former interns, patients who would be incapable of giving their consent are simply informed of their inclusion, which presents a legal and ethical issue. Furthermore, care is characterized by a lack of general reflection, which is linked to its strict protocolization, with doctors reporting a dogma and a willingness to act contrary to national and international recommendations. According to other interns, although they are not obliged to follow these internal protocols, in practice they are under a great deal of pressure to do so ; in order to change how the patient is treated, they have to find one or more contraindications which can be backed up by robust arguments.
There is no summary paper setting out or outlining the IHU’s general commercial development policy, which seems to primarily concern medical diagnostic devices. In addition, despite discussions regarding a draft agreement on the commercial exploitation of intellectual property between the AP-HM and the FMI as part of their scientific collaboration, no such agreement has been entered into with the various founders. Despite this lack of a formalized framework, since the IHU’s creation, 39 patents have been filed by the foundation itself and 9 start-ups have been created, 5 of which still existed at the reporting date. In 2022, commercial development activities within the IHU came close to breaking even, with €2.6 million in accrued expenses compared to €2.5 million in generated revenue.
Non-compliant medical and scientific practices widespread within the IHU :
The infectious and tropical diseases (MIT) department has set out a large number of formalized protocols in various documents entitled Assessment, Kit and Point of Care (POC), thus standardizing diagnostic and therapeutic management.
Emergency microbiological diagnoses are carried out at “POC” facilities 24 hours a day, 7 days a week based on a panel of biological tests that allow for the rapid syndromic diagnosis of infectious diseases using microscopic, immunological or molecular biological techniques. Clinicians are therefore provided with ready-to-use syndromic diagnostic kits containing all the tubes required to diagnose the pathology for which they are screening and the corresponding syndromic test form in a single pack, even though the use of such syndromic kits has not been validated, the Infectious Diseases Society of America (IDSA) opposes their use, and the international jury has asked for their value to be demonstrated through clinical trials. All these systematically prescribed tests go beyond the scope of proper care. This raises the question of how relevant these procedures are as well as what happens to the various frozen fluids of human origin and how these are subsequently used. Furthermore, the conditions for diagnosing malaria are not in line with current national recommendations, which may mean a loss of opportunity for the patient.
Formalized protocols regulate therapeutic treatment : antibiotic treatment, tuberculosis, osteitis, Whipple’s disease, Q fever, etc. The “guide to prescribing anti-infectives” adopted by the IHU does not reflect current standards in a number of instances and the references cited at the end of the guide are mostly old or even obsolete. These points have been confirmed by the société de pathologie infectieuse de langue française (French Society of Infectious Disease). This guide formalizes prescription practices that do not comply with the French Public Health Code, which could result in a criminal offence being committed.
The IHU clearly pursues a more diagnosis-based than treatment-based strategy in order to avoid ties with pharmaceutical laboratories. This institution’s therapeutic innovations are generally based around the use of old molecules in the treatment of diseases for which they were not developed. All infectious disease diagnosis and treatment protocols need to be updated within the MIT department and standardized at AP-HM level to ensure that they meet current standards. In particular, the mission recommends retaining Nice as the only regional center for antibiotic treatment/antibiotic stewardship in Provence-Alpes-Côte d’Azur.
In particular, the IHU has a protocol for the biological treatment of patients suspected of having tuberculosis, which involves a “tuberculosis” diagnostic kit. Unlike at other hospitals, strains of resistant mycobacteria are sent to the National Reference Centre for Mycobacteria and Mycobacterial Resistance to Antituberculosis Drugs (CNR-MyRMA). The protocols used are not in line with widely established recommendations and two of the molecules, sulfadiazine and minocycline, are not even referenced. It is the view of the CNR-MyRMA team and the French Society of Infectious Disease that there is, to date, “no rationale for the clinical prescription of sulfadiazine/cotrimoxazole or minocycline to treat MDR TB. The use of cotrimoxazole may be considered if all recognized treatment resources listed by the WHO have been exhausted”, yet the review of 35 medical records confirms the use of non-recommended molecules. There were six cases in which these treatments were used to treat drug-susceptible tuberculosis and resulted in serious adverse events (SAE) as described by the French National Agency for the Safety of Medicines and Health Products (ANSM). The treatments used by the IHU are not in line with international recommendations, and some are also prescribed “off-label”. Molecules that have been shown to be effective are not prescribed for MDR or XDR tuberculosis. It is the mission’s opinion that health risks have been taken by establishing these IHU protocols. It could be asked whether this results in a loss of opportunity for certain patients. These practices are likely to be deemed a criminal offence.
The “Mycobac” protocol contains several serious violations of clinical research regulations : incomplete signed consent forms ; minors being included in the study contrary to protocol ; consent forms being signed by persons included in the study who do not speak French ; the use of consent forms relating to other research ; continuing to collect consent beyond the end of the study under the same EudraCT number despite a substantial modification having been made, without knowing what these consents were for and yet again with the inclusion of minors who do not speak French. These practices are likely to be deemed a criminal offence.
The MIT department has established its own diagnostic and treatment protocols for the management of COVID-19. Despite the ban on prescribing hydroxychloroquine (HCQ) in community healthcare facilities or hospitals for patients with COVID-19, as set out in the decree of May 26, 2020, the latest IHU protocol, dated May 2022, still indicates off-label treatment using HCQ, azithromycin and zinc ; where there is a contraindication to the use of HCQ, ivermectin is prescribed, which differs from the protocol issued by the AP-HM. A number of doctors working at the IHU have stated that they try to find as many contraindications as possible to avoid prescribing HCQ, despite frequent “reminders”. These practices are likely to be deemed a criminal offence.
It is the view of the MIT department that when treating COVID, classifying patients as outpatients is justified by their prophylactic isolation and the specific measures put in place to implement this. In addition, outpatient appointments are arranged directly for the patient through Doctolib. It is the responsibility of the regional health agency (ARS), as part of its annual inspection program, and of the regional management of health insurance systems’s medical service to verify the compliance of these day admissions. The use of these treatments, some of which are iterative, in outpatient care, has resulted in a great deal of human and material resources being used, to the detriment of other diseases.
The methods used to validate biological test results still do not comply with regulations. Automatic validation of positive and negative results was put in place from October 12, 2020 to take the pressure off biologists. However, regulations specify that the results must undergo biological validation before being transmitted. Although the automatic validation of positive results was in fact discontinued on September 8, 2021, almost a year after it was first implemented, negative results are still subject to automatic validation.
The MIT department uses molecules for purposes not covered by the relevant market approval (MA), particularly to treat tuberculosis (sulfadiazine, minocycline, disulone) or COVID-19 (HCQ, AZM, ivermectin), even though these protocols that are not covered by the MA do not fall within the scope of the allowances made for early access and compassionate use and do not form part of authorized clinical trials. Additionally, the doctor has an even greater obligation to inform the patient of the following : that the treatment is being prescribed off-label, that there is no alternative treatment offering equivalent benefit, the risks involved and the potential benefits, and that the health product prescribed is not covered by health insurance. They must ensure that the words “off-label” are written on the prescription and that the reasons why the patient has agreed to an off-label prescription are noted in the patient’s record. However, patient information, informed consent and the reasons for their decision are very rarely included in records. Failure to comply with these conditions may result in the doctor who prescribed the treatment off-label being held liable on ethical, civil, or administrative and criminal grounds.
Although prescribing is an individual responsibility, there is a great deal of pressure placed on practitioners and interns by university professor–hospital practitioners to ensure that the IHU’s protocols are followed. The mission intentionally refers to the “IHU”, as the MIT department is exempt from AP-HM protocols. These protocols are approved and decisions concerning care are made within the IHU’s own bodies. Overall, such practices are likely to be deemed a criminal offence.
The thing that sets the MI IHU apart is the intrinsic links between care and research, which have resulted in the MIT department’s and AP-HM microbiology laboratory’s clinical activities relocating to the IHU’s premises. The clinical research activities carried out within the MI IHU are becoming increasingly autonomous, while the links between the FMI and AP-HM are permanent and an intrinsic part of the system as a whole. Within this context, the FMI and the MIT department have been trying to ensure the autonomy of the clinical research activities conducted on the MI IHU’s premises since 2016, on the regularly cited grounds of delays and failures on the part of the management in charge of the AP-HM’s clinical research. The arrangements for the promotion of clinical research by the FMI do not guarantee compliance with regulations. The FMI promoted research without the AP-HM being kept informed of the studies being conducted, in contravention of the French Public Health Code, and without an agreement in place between the investigators and the sponsor. There are also flaws in how the data concentrator is implemented. The mission therefore recommends that a clinical research management agreement defining project management arrangements, the resources required, ownership of samples and data, and the economic model be entered into between the AP-HM and FMI.
The procedures for carrying out clinical research do not ensure compliance with regulations and guarantee patients’ protection. The mission notes serious shortcomings, many of which are based on a lack of compliance with rules that are considered restrictive, which could be observed up until very recently (end of 2021/beginning of 2022), but also on a frequently encountered lack of knowledge regarding the regulations. The latter are often presented as an impediment to the agility of research, despite their primary aim being to ensure the health and freedom of choice of those involved in clinical trials.
The IHU has its own ethics committee, but the composition of this committee does not sufficiently guarantee its independence and its working methods do not allow for informed decisions to be made.
The creation of a large database, including samples, is an integral part of the IHU’s strategy. The foundations on which the biobank and data concentrator are based are inadequate and must be rectified by a general ownership agreement between the AP-HM and FMI.
The mission identified two main categories of deviations from regulations : deviations in the protection of personal data and consent and deviations in the conducting of research involving human beings.
The identified deviations in how personal data and patient consent are managed concern the implementation of the law governing non-opposition, instances of non-compliance regarding how opposition is organized, non-compliance of the procedure used to report opposition to the French data protection authority (CNIL) with the General Data Protection Regulation (GDPR), and the consent of individuals who do not speak French.
The mission found that several studies had been conducted in violation of the provisions of the French Public Health Code concerning research involving human beings. The mission points out that these rules are set out in law in order to protect patients. Violations of these provisions are covered by the French Criminal Code.
ABBREVIATIONS & ACRONYMS
|MA :||Mmarket approval|
|AMU :||Aix-Marseille University|
|AP-HM :||Assistance publique des hôpitaux de Marseille|
|AP-HP :||Assistance publique des hôpitaux de Paris|
|CNR-MyRMA :||Centre national de référence des mycobactéries et de la résistance des mycobactéries aux antituberculeux (National Reference Centre for Mycobacteria and Mycobacterial Resistance to Antituberculosis Drugs)|
|CNRS :||Centre national de la recherche scientifique (National Centre for Scientific Research)|
|EFS :||Établissement français du sang (French Blood Institution)|
|FCS :||Fondation de coopération scientifique (Scientific Cooperation Foundation)|
|FMI :||Fondation Méditerranée infection|
|IHU :||Institut hospitalo-universitaire (university hospital institute)|
|INSERM :||Institut national de la santé et de la recherche médicale (French National Institute of Health and Medical Research)|
|IRD :||Institut de recherche pour le développement (Research Institute for Development)|
|MDR :||Multi-drug resistant|
|MEPHI :||Microbes, Evolution, Phylogeny and Infection|
|MESRI :||Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation (Ministry of Higher Education, Research and Innovation)|
|MI :||Méditerranée infection|
|MIT :||Maladies infectieuses et tropicales (infectious and tropical diseases)|
|NSB3 :||Niveau Sécurité Biologique 3 (biosafety level 3)|
|SESSTIM :||Sciences Économiques & Sociales de la Santé & Traitement de l’Information Médicale (health economic & social sciences & medical information processing)|
|UVE :||Unité des virus émergents (emerging virus unit)|
|VITROME :||Vecteurs – Infections Tropicales et Méditerranéennes (Vectors – Tropical and Mediterranean Infections)|