One person is in a coma and five others are in critical condition after a drug trial in France went terribly wrong, the country’s health ministry announced Friday.
In a statement, French Health Minister Marisol Touraine reported that a “serious accident” occurred during a Phase 1 clinical trial of an oral drug meant to treat certain mood disorders and neurodgenerative conditions. The testing, which was being conducted by Biotrial, a laboratory based in Rennes, has been suspended, and all volunteers recalled.
The ministry did not name the drug involved in the trials, saying only that it was “a drug taken orally being developed by a European laboratory.” Correcting initial media reports, Touraine said that the drug did not contain any cannabis or cannabis derivatives, but rather that it acts upon cannabinoid receptors in the brain.
A total of 90 people were involved in the trial, according to Reuters. Those sickened by the drug are being treated in the University Hospital of Rennes.
Of the six people injured, one was fully brain dead and at least four others were in critical neurological condition. According to Dr. Gilles Edan, a neurologist at the University of Rennes Hospital Center who has evaluated the patients, “three already have a severe enough clinical picture to fear that even in the best situation there will be an irreversible handicap.”
All six volunteers were men between the ages of 28 and 49, and were in good health prior to taking the oral medication at their homes. They all received multiple doses of the medication, the first of which was given on January 7th. The first symptoms appeared three days later, on January 10th, and the trial was stopped the next day.
Since doctor’s don’t know how the drug affects humans, all participants–even those without symptoms–will need to be monitored very closely, and even then, “[w]e cannot make a definitive prognosis,” said Dr. Edan.
Clinical trials are necessary in order to bring new drugs and treatments to the market. Before any new drug can be given to patients, it must first undergo extensive testing for both safety and effectiveness. (And before even being considered for use in human trials, all drugs must go through extensive preclinical testing, followed by animal testing.) Human clinical trials often last years and involve hundreds, if not thousands, of volunteers, during the various stages of testing.
In the initial Phase I testing, the new drug is given to a small group of healthy volunteers to ensure basic safety and tolerance at different doses before exposing more vulnerable patients to the drug. “Such trials start with a small dose which is then steadily increased over a few days. Also, the doses are most often given to the patients in a staggered fashion in order to minimize the risk of all volunteers experiencing a serious adverse effect,” Dr. Ben Whalley, Professor of Neuropharmacology at the University of Reading, and member of the British Pharmacological Society, explained in a statement.
“It is therefore unusual for reports to mention that up to 6 people have been affected unless the adverse event has taken several days to appear,” he said.
Europe has very strict regulatory standards governing the conduct of clinical trials, and Phase I trials are subject to particular scrutiny to minimize any risk to human health, said Prof. Jayne Lawrence, Chief Scientist at the Royal Pharmaceutical Society. “Those in charge of the trial would have had to have shown they had done everything they could to protect patient safety before the trial was allowed to go ahead,” she said.
The French Health Authorities and Ministry has begun a full investigation in order to understand what went wrong.
The main question this case is whether there were any failures of the study protocol that led to more harm than necessary. As Dr. Whalley alluded to, it is possible that they administered the drug to all volunteers at once, instead of staggering it to make sure the first doses were tolerated before exposing more participants.
That’s what happened ten years ago, when six participants suffered severe organ damage during a U.K.-based clinical trial for an experimental immune stimulant. Had they staggered the administration of the medication, the damage may have been limited to fewer people.
Thankfully, tragedies like this are rare. Millions of people participate in clinical trials each year, and serious adverse effects are uncommon, experienced by fewer than 0.31 percent of all participants. Fatal events are even rarer occurrences.