In an unprecedented clinical trial disaster, six men participating in the drug trial of a painkiller were hospitalized, with one brain dead and three others with possible permanent brain damage. While investigations are under way to determine what went wrong, the botched trial in western France raises a question of safety procedures in other clinical drug trials that put perfectly healthy individuals at great risk.
The six*, who were reportedly between the ages of 28 and 49, were part of a group of approximately 90 people in the Brittany region who volunteered for the trial of a drug for reducing pain and anxiety for those suffering from a variety of medical conditions. According to the French government, all of the participants were given varying oral doses of the medication at the offices of Biotrial, a drug evaluation firm in Rennes with offices in London and America. Biotrial was conducting the tests for Bial, a Portuguese pharmaceutical company founded in 1924.
Biotrial applied to conduct the trial on April 30, 2015. The French Agency for the Safety of Health Products, the nation’s drug regulatory body, authorized the trial on June 26, and it began on July 9.
Bial claimed that the drug was given to 108 patients “without any moderate or serious adverse reaction.” However, the six were reportedly given doses at higher levels than others on Jan. 7. The first was hospitalized three days later. Three of the five others were hospitalized midweek. Only one has not shown adverse effects, but he is being closely watched.
Biotrial issued a statement that the clinical trial was being conducted in full compliance with international regulations and that appropriate procedures were followed at every stage, including the emergency transfer of subjects to the hospital. “The authorization (for clinical trials) provides for a maximum dose. We were far from reaching that” when the accident occurred, according to François Peaucelle, general director of Biotrial. He added, “Our thoughts remain fundamentally with the victims and their families but our energy this morning is entirely dedicated to helping the investigators and collaborating fully with the probes that are under way.”
Investigators are now trying to determine whether the botched drug trial in France was caused by an error in the testing procedure or by the drug molecule itself. Peucelle told reporters that his firm has not found any evidence of a procedural or safety error on their part.
According to the Pharmaceutical Research and Manufacturers of America (PhRMA), which represents leading biopharmaceutical research and biotechnology companies in the U.S., researchers conduct exhaustive studies in cells, tissues and animal models to determine whether the target can be influenced by a possible compound that could become a medicine. Drugs are then typically tested on animals. Less than 12 percent of those efforts even make it into Phase 1 clinical trials, like the one that was being conducted in France. Fairly similar processes are used in other Western countries.
Experts indicated that serious injuries during early-stage clinical trials are rare but are investigated thoroughly since they made otherwise healthy subjects fall ill. The British Medical Journal reported in a meta-analysis of noncancer Phase 1 drug trials that serious adverse events occurred in only 0.31 percent of participants, and no deaths. However, this botched drug trial in France, which has been suspended, will undoubtedly raise safety questions for other trials and will clearly make healthy people more hesitant to participate in drug studies.
* Note: Bial claims that five were hospitalized and the French government reports that it was six.
Written and edited by Dyanne Weiss
New York Times: 6 Hospitalized, One of Them Brain-Dead, After Drug Trial in France
PhRMA.org: Clinical Trials
CNN: Drug trial participant brain dead, 5 others hospitalized in France
The Telegraph: Multiple investigations launched into France drug trial that left man brain dead
Washington Post: Botched drug trial leaves one person brain dead, five others hospitalized in France
Photo courtesy of Justin Ling’s Flickr Page – Creative Commons license