It is a year since the clinical trial of a promising experimental painkiller ended in a volunteer鈥檚 death. Incredibly, it is still not possible to fully learn the lessons that could make drug research safer. That must change.
BIA 10-2474 was being tested in a first-in-human trial in Rennes, France, to see if it was safe for people and at what dose. Things began to go wrong on 10 January when one participant, a 49-year-old man, complained of blurred vision, swallowing difficulties and speech problems.
He was the first of six volunteers to receive a fifth dose of 50 milligrams 鈥� a cumulative 250 milligram dose that had never been administered to a person before. That evening he was sent to hospital but deteriorated overnight and was in a coma the day after. He died a week later.
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The Portuguese drug company Bial, which developed BIA 10-2474, and its French contractor Biotrial, which carried out the test, were criticised for not stopping the trial immediately after the man fell ill. Instead, the day after he was hospitalised, the drug was given to five more volunteers.
Four of these suffered neurological symptoms including memory loss, headaches, motor disorders and tremors. Scans revealed brain lesions. Two have still not fully recovered.
Bial and Biotrial point out that they followed a protocol approved by France鈥檚 medical regulator, the (ANSM). They say that nothing seen at lower doses of the drug in people or from research in rats, mice, dogs and monkeys could have allowed them to predict what would happen, and that the man who died had a pre-existing condition that might explain why he reacted so badly to the drug.
Data release
Last month, I was the only journalist in the room when Bial for the first time publicly released some human data from the trial at the in London. The firm revealed that 10 other volunteers who received lower doses of the drug experienced neurological side effects including dizziness and blurred vision, although it stressed these were 鈥渕ild and transient鈥�.
Under questioning from scientists at the meeting, Bial also said it that would prove fatal. Both revelations raise important questions about how the trial was conducted and how similar tests are authorised in future.
At the moment, we have to take Bial鈥檚 assertion that the severe reactions were unpredictable largely on trust. Despite repeated , the company has neither released the full trial data nor a detailed dossier of pre-clinical research. It seems that the authors of an had access to this information, but it was not made public when they published their assessment of what happened.
That matters because it means other experts can only second guess how the authors reached their view and must rely on their interpretation of the data. Only by studying all details will the wider scientific community be able to judge whether anything could have helped predict the outcome.
To try to prevent such a tragedy from happening again, scientists need the full data, not just some of it.
The French and European authorities must go beyond the actions they have taken so far 鈥� investigations and new guidance for drug trials 鈥� and ensure transparency. A year after this tragedy, the safety of participants in similar clinical trials in Europe remains at stake.
