Clinical research trials have been the gold standard to study the safety and effectiveness of new drugs in the human beings for several decades. Even though the “Good Clinical Practice” protocols (GCP) have been refined by expert professionals with the supervision of competent, national authorities, there is still much to be done for the safety of the participants.
A November editorial in the prestigious New England Journal of Medicine discusses the tragic consequences of a phase 1 clinical trial in France that left one patient dead and three others with severe neurological damage after they were given doses of an experimental drug dubbed as BIA 10-2474. It is a fatty acid hydrolase inhibitor that targets the endo-cannabinoid system.
The question of potential risks compared to benefits of any drug must be carefully evaluated, even in Phase I where the emphasis is on its safety as it involves healthy volunteers that do not have anything to gain from its use. Other drug companies had tested that drug before and determined that there was insufficient evidence of its efficacy to warrant a costly clinical trial.
Its “first-in-human” phase I clinical trial started in January 2016 in France with eight volunteers, six of whom received 50 mg daily of BIA 10-2474 and two were given a placebo as control. Four of these volunteers were admitted to Rennes University Hospital for an acute neurological syndrome with headaches, cerebellar signs, memory loss and altered consciousness. One became brain dead, two others improved but one has residual deficits.
The clinical and radiological data suggested direct toxicity of the drug in an “off-target” location as increasing daily doses were used. On day five the volunteer that eventually died presented with blurred vision and gait problems; by day seven he was hypotensive and his heart rate dropped to 40/ minute. In spite of this development, the trial was not stopped immediately.
Even if they follow the protocol, investigators must have clinically-guided common sense to know when to stop a trial in spite of the potential financial losses. If this grave incident happened in a country like France, with its long civic tradition of protection of individual citizens’ rights, what can we expect in other countries with less patients’ safeguards?
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