CRO Biotrial and its Portuguese pharma partner Bial have been told by the French health minister that they must accept some responsibility for a trial that left 5 seriously injured and one dead in January.
French health minister Marisol Touraine said today (Monday, 23 May) that both companies are “partly liable” for the serious failings and issues that arose for the trial, according to news wire Reuters. "A final investigation report confirms that the conditions under which the test was approved did not breach existing legislation," Touraine told journalists. "Inspectors consider, however, that Bial and Biotrial are responsible on several counts; regarding the dosage prescribed [...] and the time taken to alert authorities," she said.
In a government report, released Monday, the authors said that Biotrial did not properly inform volunteers and implemented a “flawed protocol.”
This is according to France's social affairs inspectorate (IGAS), which also pointed to Portuguese company Bial, the maker of the experimental drug, for delays in informing health authorities--but cleared the National Agency of Drug Safety that it said gave relevant and sufficient information.
The French CRO was running a Phase I trial in its home base of Rennes, France, on behalf of Portuguese drugmaker Bial, administering a medicine that blocks the enzyme FAAH to treat anxiety.
The drug's mechanism is well-known to the industry but had not shown safety concerns in previous testing, although French news reports surfaced in March that there had been some unusual deaths and issues in preclinical trials of the drug, which had seemingly not been acted upon.
In all, around 100 patients had taken the drug, but in January, 6 trial participants took a higher dose form of the treatment, with one becoming brain dead and later dying. Five others were seriously ill but have been said to be improving.
An initial report found that the first accident with the drug was on a Sunday evening--yet authorities were not alerted until the following Thursday.
Touraine, talking to journalists about the report on Monday, added that Biotrial must also provide an “action plan” within a month to guarantee that “major breaches” cannot happen again.
She has for the last 5 months been critical of both companies, saying back in February Biotrial "should have halted the tests" after the first person was hospitalized. This didn't happen, however, and 5 more people were given the medicine the next day. She has not however until today placed any blame on the partners.
Touraine stressed however that the investigation by the health administration showed that the conditions under which the trial by the Rennes-based firm were authorized were “compliant with the current legislation.”
Touraine has also presented a plan to tighten up the rules regarding human drug trials, according to the Associated Press.
In late April a report ordered from the French National Agency for Medicines and Health Products Safety (ANSM) said common sense “was lacking” from the two companies, but ultimately blamed the toxicity of the compound, and its unprecedented effects, as being the primary culprit for the death and the injuries.
It too said that a major overhaul of safety standards should be made to stop this from happening again.
In order to achieve this, the minister said France will work with the European Commission and the European Medicines Agency to improve trial practices at an international level. In addition to the IGAS investigation, the affair is the subject of a separate judicial inquiry. The EMA told FierceCRO that it was now in fact already reviewing preclinical and Phase I trial protocols across Europe as a result of these reports, and would seek to make changes to tighten up study rules later this year.
Biotrial has however reacted angrily to the report, saying it was not privy to its details until today, even though several French newspapers printed excerpts from the reports yesterday.
In a statement, the CRO said: “Biotrial, once again, contests the conclusions from the IGAS final report which, in order to stay consistent with the report that was hastily published in February, would not allow itself to include the input provided by Biotrial. The center deplores the methods, contrary to legal procedures, that were used to put together the report and that therefore remove all of its credibility.”
It added that it “deplores this situation, especially since it has always strictly respected the test protocol validated by the ANSM.”
It also appeared to shift the blame toward its pharma partner, saying: “It has been shown that it is the Portuguese Laboratory Bial’s compound, by it unexpected and unpredictable toxicity, which is at fault for the accident.”
- check out Reuters' take
- go over to FierceBiotech and see its take on the EMA trial review plans
- see the AP story
- read Le Monde’s take (in French)
- see the IGAS report here (In French)
- have a look at Biotrial's statement