PRESS RELEASE - May 22nd, 2016
Investigation into the accident during the clinical trial in Rennes: The three major shortcomings of the IGAS
Rennes, May 22nd, 2016
The medical research center in Rennes, Biotrial, was shocked to discover this evening (Sunday, May 22nd), that the General Inspectorate of Social Affairs’ (IGAS) final report, which has still not been shared with the center, was sent to the press through a series of carefully orchestrated leaks, the evening before the press conference held by the Health Minister, Marisol Touraine.
Biotrial deplores the methods used by the IGAS during their investigation and contests the conclusions in their report.
The mission entrusted to the IGAS by the Health Minister following the accident during the BIA 10-2474 clinical trial was to establish the responsibility of the different parties in regards to the requirements and proper organizational and professional practices.
However, it would seem that the IGAS committed three major shortcomings during its investigation and in drawing up its report, which removes all credibility of its conclusions.
1. The IGAS committee did not respect the adversarial principle
A first status report was made public at the beginning of February 2016, even though the investigations were still ongoing and despite the fact that there were no exchanges with the Biotrial research center in regards to the alleged shortcomings.
The first conclusions published in this status report were therefore put together hastily, solely relying on the inspectors’ opinions, on the basis of fragmented information and without the knowledge of certain regulations, and above all without applying the adversarial principle.
In its final report, the committeedeemed necessary, in order not to go back on its statements, to maintain its initial observations without taking into consideration clarifications provided by Biotrial.
In order to respect the adversarial principle, prior to publishing the status report, it would have been essential to question Biotrial as well as the other parties involved in regards to the alleged shortcomings – in order to create a constructive exchange on the subject of certain regulations and good practices which are subject to interpretation.
2. The IGAS committee did not respect the rights of the people interviewed
Biotrial discovered with amazement that during the interviews of members of its personnel performed by the IGAS inspectors, that no minutes were taken, and that the inspectors sometimes, but not always, took brief notes.
The absence of minutes, which is contrary to the most fundamental principle of certifying that both parties have understood and agreed to what was said, discredits the investigation as well as the report that was drawn up.
In addition, Biotrial deeply deplores certain interview methods used by the inspectors, who took the liberty of, outside of any procedural structure, contacting multiple employees directly on their personal cell phones, on the weekend, in order to make them come in and/or add to their statements.
Biotrial also deplores that the IGAS committee did not meet with any of the Rennes University Hospital emergency room personnel, but yet makes reference to a timeline of events established one month after the fact by the CHU directors and therefore after the publication of the status report.
In order to guarantee the quality and impartiality of their investigation, it would have been necessary that the IGAS inspectors:
- keep minutes of the interviews conducted
- not allow themselves to make direct contact with Biotrial personnel on their cell phones and attempt to put pressure on them
- question all parties involved, and not only members of the Biotrial personnel as if they were the only ones involved – thus resulting in a biased report.
3. The IGAS committee omitted to mention any possible conflicts of interest, taking away from any objectivity in its report
In order to safeguard the objectivity of the investigation and the report, it would have been appropriate that the existence of any prior professional collaboration between the IGAS inspectors and the general directors of the two public entities directly linked to the accident, in this case the Rennes University Hospital and the National Agency for the Safety of Medicines (ANSM), be made public.
These circumstances, which greatly affect the impartiality of the report, were surprisingly never brought to light – neither in the status report, nor in the draft of the final report by the IGAS.
In the interest of transparency, it would have been essential that these professional relationships be clearly indicated in order to allow all parties to request, if deemed appropriate, the nomination of another inspector in order to avoid the risk that the impartiality of the conclusions reported by the committee be challenged.
With the weight of these three major shortcomings, Biotrial reserves the right to petition the court for a nullification of the report. Biotrial calls upon the IGAS to commit to reforming its procedures, similarly to other administrative bodies, in order to align with European Standards. It is particularly unfortunate that, despite the seriousness and absolutely exceptional nature of this event, there was such a lack of professionalism – which prevents the report from being a constructive tool, used by all parties for improvement.
CONCLUSION: Biotrial contests all of the reproaches made by the IGAS in their report
First of all, the report specifies that the timeline of events, as it was to have happened in the hospital wards, on January 10th and 11th, 2016, was only provided by the University Hospital’s General Direction on February 29th, 2016, which was one month and a half after the hospitalization of the first volunteer, but especially more than three weeks after the publication of the status report made by the IGAS committee.
Therefore, at the time that the committee affirmed publicly, and by a presumptive manner and not using the adversarial principle, that the Biotrial research center had committed three major errors, it did not have any specific information regarding the timelines.
This simple fact undermines the quality of the investigation performed.
a) Regarding the first alleged shortcoming, the committee criticizes Biotrial for not having tried to get news as to the health of the hospitalized volunteer, and thus for not guaranteeing the safety of the other volunteers.
However, seeking out this information would not have had, under any circumstance, any impact on the other volunteers. In fact, the health of the volunteer hospitalized was only revealed to have worsened at the same time, or after, the administration of the study medication on Monday morning, as was outlined in the protocol (that was validated by the ANSM) and to which Biotrial strictly adhered to.
Furthermore, one can only be surprised that the IGAS report disregards the French medical confidentiality regulations (doctor/patient privilege) that would have prevented the University Hospital personnel from responding to any request of information from Biotrial.
It is important, as well, to reiterate the obligation of assistance to a person in danger that is required of hospital personnel, as they were duly informed of the study protocol. As a result, if the emergency department was aware, early in the morning, of the worsening of the health of the hospitalized volunteer, it was their responsibility to immediately inform Biotrial so that any appropriate measures could immediately be taken to suspend the administration to the other volunteers on the Monday morning, as was scheduled in the protocol.
b) Regarding the second alleged shortcoming, the committee criticizes Biotrial that no new informed consent forms were collected from the other volunteers on the Monday morning.
First of all, Biotrial points out that this second alleged shortcoming is directly related to the first one. In addition, as previously stated, the health of the volunteer hospitalized was only revealed to have worsened at the same time, or after, the next tests. As a result, Biotrial could not have requested a new informed consent regarding an event that had not already happened or that was happening at the same time.
More generally speaking, the IGAS committee’s analysis reveals an overall lack of knowledge of the law and the conditions of the exercise of informed consent by the volunteers. In fact, informed consent is ascertained under strict conditions, defined by international regulations and that Biotrial rigorously followed.
c) Regarding the third alleged shortcoming, the committee criticizes Biotrial for having delayed in informing the authorities.
This shortcoming is also based on an erroneous interpretation of the regulatory text, even though the IGAS committee points out the fact that the regulation is unclear.
Even more serious, one notes that the IGAS committee does not have extensive knowledge of the applicable texts, especially when it refers to repealed texts!
Finally, it is an error to write, as the committee did, that Biotrial did not reinforce the monitoring of the other volunteers.
Biotrial strictly respected the ANSM and the ARS (Regional Health Agency) emergency recommendations in allowing neurological monitoring by the University Hospital, as requested by the authorities, as well as putting into place its own monitoring plan.
It is clear from these elements, that the IGAS’ final report did not take into consideration the input provided by Biotrial in order to avoid any contradiction that this might bring with the first status report, which was hastily published in February 2016 and that did not follow the adversarial principle that was expected.
Biotrial deplores this situation as it has been perfectly established that it is the Portuguese laboratory Bial’s compound that, by its unexpected and unforeseen toxicity, would be the origin of the accident.
Guillaume Didier +33 6 74 08 27 17
BIOTRIAL is a private center for medical research licensed by the Ministry of Health (based in Rennes and present internationally). It conducts Phase I clinical trials, i.e. for a first administration to humans, on behalf of laboratories and biotechnology companies.