CLINICAL TRIALS – A CAUTIONARY TALE
This was big news several months ago. A phase I drug Clinical Trials in France resulted in a death in 1 healthy volunteer and neurological deficits in 3 others. The details were published in the New England Journal of Medicine, November 3, 2016. The drug was considered to be an analgesic, anti-inflammatory, and possibly effective for neuropathic pain. It targeted the endocannabinoid system. The manufacturer was Bial, a pharmaceutical company based in Portugal.
The medication seemed safe in animal testing, and this led to a phase I trial, which is designed to test safety and not efficacy in humans. Bial went ahead with the study even though other drug companies had tested molecules that were similar and seemed ineffective.
This trial started in January 2016, with 8 volunteers. Two received placebo and six a 50 mg dose of the medication. All 6 of the treated patients were hospitalized with adverse effects, starting on the fifth day of drug administration. Nevertheless, the researchers continued to treat the other patients.
The toxicity was neurological. MRI showed hyperintense lesions, mainly in the brainstem and hippocampal areas.
Lessons are obvious. Researchers should know when to stop. The dosing should have been staggered rather than all patients being treated at the same time.
Volunteers in phase I trials have no possibility of benefit from the trial, unlike patients in phase II and phase III trials. They do so largely because they are being compensated. Several years ago The New Yorker published an article explaining that there is a group of young men for whom clinical trials are their livelihood. Phase I trials are essential in development of medications. They are ethical as long as there is true informed consent and appropriate safeguards are in place.
See Neurology Today, December 8, 2016.
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