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the facts: Drama rare after a clinical trial
the mission considers that the responsibility for Biotrial center which was conducted experiment, like that Bial, laboratory trial sponsor, are incurred. It accuses Biotrial “three major shortcomings” in the conduct of the trial and Bial a “delay information of the health authority” and a choice “insufficiently cautious” to move to the 50 mg dose in multiple ascending doses.
A lack of information voluntary
First question analyzed by the two inspectors, Christine Autume and Gilles Duhamel, one of authorization, granted June 26, 2015 by ANSM, testing BIA 10-2474 molecule. The mission notes that “preclinical data authorization dossier completed with applications ANSM, were relevant and sufficient and allowed the administration to humans. “
The prospective risk level with the BIA 10-2474 would it be justified to refuse permission from Rennes clinical trial? The committee on protection of persons participating in biomedical research (CPP, whose prior opinion is essential for a trial) West VI Brest ANSM have both said no. However, according to testimony and documents cited by Le Figaro and Mediapart , the volunteers in the trial were not informed of the side effects – neurological or pulmonary – recognized when tested in animals
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They would thus not received Biotrial “objective, fair and understandable to the subject ‘, as provided by law, with the ” Newsletter and consent form healthy volunteers “. These documents Biotrial previously covered by Bial, were communicated to the CPP and to ANSM before the start of the test. ANSM side, it indicates that it is common that these forms do not refer in detail to the side effects seen in animals.
The protocol itself was not free reproaches, according IGAS. Analyzing the phase preceding the first serious adverse event that resulted in the deaths of 17 January Guillaume Molinet, 49, the two rapporteurs point out that it was not “a sufficient framework for optimal protection of the participants. “ Similarly, they evoke ” The unclear division of roles between Bial and Biotrial in reporting of serious adverse events and developments [which] were not conducive to rapid information to authorities . “
Another major point, that of escalating doses during the trial. The report recalls that “are admitted and the conditions of progression doses did not violate the rules. “ However, the inspectors were surprised to lack of caution: ” Bial was not deemed necessary, given the level of risk it anticipated to provide for special precautions to limit simultaneous exposure of several volunteers product. Its assessment can elicit discussion. “ This especially that during the passage of a dose of 20 mg to 50 mg, investigators had to data than the 10 mg dose and therefore no indication on the product behavior in volunteers receiving the 20 mg dose.
the mission IGAS “regrets the lack of observations of it on the dose escalation conditions. “ It is the same for the MPC West VI Brest. However, to decide on the authorization granted by the ANSM, “given the remaining issues, the mission recommends that this be the subject of further consideration as part of an independent committee international experts. “
The report arrive to ask a basic question deserving a ” public debate at an international level “ that ” well even -based test. “ They question ” the decision to expose volunteers to risk by definition not completely predictable an experimental drug “ from the time where “the potential added value of the product in the therapeutic arsenal could be in doubt in the eyes of some experts. “ The BIA 10-2474 protocol was referring to ” a wide range of future potential therapeutic benefits without arguing the expected specific contribution of the product compared to other molecules “ inspectors emphasize
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If the conduct of the test was “per protocol” , the inspectors come “three major shortcomings” in the management of first serious adverse events that engage the responsibility of Bial and Biotrial on several points. The first “is the lack of research information in a timely manner on developments in the health status of the first volunteer and the corresponding non-suspension of the administration of the product to other volunteers” the group to which he belonged.
Indeed after hospitalization Mr. Molinet, Biotrial “proceeded the next morning at the usual time, administration product (6th dose) other voluntary cohort, without being informed in advance of changes in the health status of this voluntary, hospitalized for more than 10 hours. “ Both Inspectors believe that the experimenter center” has not given the resources that would allow it to decide, knowingly, for the prosecution “ of this administration and thus “Biotrial breached its volunteers to protect” . They dismiss the responsibility of Rennes University Hospital.
The second major failure on the part of Biotrial, “the absence of confirmation of their consent to the other volunteers Monday, January 11, prior to administration product “, unlike that provided for the information letter and consent form distributed to volunteers in case of ” significant new information that could affect their willingness to continue the study “. An obligation under the Public Health Code
Third major breach common to Bial and Biotrial. Non-compliance with the duty to inform without delay the competent health authority. “The regulation provides that in the event again because of security, the proponent must immediately notify the health authority and the measures taken to ensure volunteer safety” , said the mission that “finds that this information was performed Thursday, January 14″ , while Mr. Molinet had been hospitalized in the evening of 10 January, after neurological symptoms appeared in the post noon.
the test was suspended in Biotrial the day of January 11, after the morning administration to volunteers BIA 10-2474. After this stop, “Biotrial has not otherwise implemented enhanced monitoring of other volunteers including neurologically” , the report said.
Establish new repositories
in its final section, the IGAS report stresses that “is important to understand the causes of serious events occurred and to reconsider the framework to protect volunteers in the first administration of tests to man “, as was the case after serious accidents in a clinical trial in London in March 2006. following these events, new benchmarks were established in 2007 by the European Medicines Agency.
Along with the investigation of IGAS, the judicial investigation ongoing task will be to establish the responsibilities of actors and possible faults committed.
Biotrial disputes the findings of the IGAS
the center Biotrial search has “refuted all accusations” addressed to it in the report of the General Inspectorate of social Affairs (IGAS) concerning the fatal clinical trial in Rennes.
in a statement, the Rennes facility estimated IGAS has not respected the principle of contradiction, tried to exert pressure on staff and did not record the hearings in minutes and has no mention of “conflicts of interest” between IGAS, the Rennes University Hospital and the drug agency (ANSM).
Biotrial, which criminalizes the molecule Portuguese Bial laboratory, “reserves the right to seek the French courts to quash the report” .