An inquiry has found fault with both companies involved in a clinical trial in France that left one patient dead and five others hospitalised.
Health Minister Marisol Touraine said yesterday that Portuguese pharma company Bial and French contract research organisation (CRO) Biotrial were found to be at fault – in several respects – in an investigation conducted by France’s Inspectorate General for Social Affairs (IGAS).
Touraine also unveiled a plan to tighten up regulations governing the conduct of clinical trials, while Biotrial has been ordered to come up with an action plan to make sure the tragedy can never happen again. Failure to do so will result in Biotrial having its license to operate suspended, said the Minister.
The IGAS launched the probe in January in the wake of the death of Guillaume Molinet, which occurred in a first-in-man trial at Biotrial’s phase I trial facility in Rennes.
The trial involved 90 healthy volunteers who were given Bial’s BIA 10-2474 – a candidate drug for mood and motor disorders associated with neurodegenerative disorders and anxiety.
The agency had no issues with the protocol used in the trial as approved by France’s medicines regulator the ANSM, but said the implementation of the trial had a number of shortcomings.
In particular, the IGAS found that Biotrial continued to administer the drug to patients even after the first patient was taken to hospital, while the CRO – and Bial – also delayed reporting the adverse reactions to the ANSM.
The first hospitalisation took place on January 10 but dosing was not halted until the following day and the adverse events were not reported until January 14.
Questions have also been raised about the dosage of BIA 10-2474 used in the trial, and a failure to follow informed consent procedures.
Anonymised records on the 90 patients enrolled in the trial will now be sent for analysis by independent experts and a review by the European Commission, said Touraine.
Touraine said the government plans to tighten up the conditions for securing approval for first-in-man studies, as well as reporting requirements, and will ask the ANSM to inspect all clinical trial facilities in France and remind them of their compliance obligations. She would also like to see a dedicated unit set up within the ANSM to oversee first-in-man studies.
Meanwhile, the matter has also been elevated to the EU level, with two working groups set up at the Commission to see how guidelines on the protection of healthy volunteers in clinical trials can be strengthened.
Biotrial “strongly contests” findings
Biotrial said in a statement that it was “astonished at the behaviour of the IGAS”, claiming it had only received a copy of the report as a press conference – to which it was not invited – was ending. Journalists were given access to the report the previous evening.
The CRO said it had already implemented an action plan following discussions with the ANSM and said it would submit this to the Minister, saying it is “surprising that she did not seek it out, nor even ask if it existed”.
It also vehemently contests the findings of the IGAS report, saying it failed to take into account Biotrial’s input and position and was “hastily published”.
“Biotrial deplores this situation, especially since it has always strictly respected the test protocol validated by the ANSM,” said the CRO.
“It has been shown that it is … Bial’s compound, by its unexpected and unpredictable toxicity, which is at fault for the accident.”