Last week, a disastrous clinical trial held at a clinical trial unit in Rennes left one man dead, three others suffering from "irreversible" mental handicaps and another with neurological problems. ?
It comes less than 10 years after the last clinical disaster, the so-called Elephant Man Trial of the TGN1412 compound at the Northwick Park Hospital in May 2006. Regulators need to find out what went wrong. But it is easier to overlook whether that which went wrong has happened before and has now happened again. We need to know whether these human disasters in France and London have common features that should have been avoided, but were not.
Read more: Overhaul of regulation may not prevent another Northwick Park incident
The disaster in Rennes is reported to be a Phase I clinical trial. “Phase I” usually means that the drug has never been tested on humans before and is being tested to see if the dose can be tolerated safely. Was it right to allow 128 volunteers to participate in this study, of whom 90 received the drug?
Only the minimum number of volunteers should be used that is necessary to give an accurate result. These numbers are more suggestive of a Phase II study designed to test the efficacy of the drug as well as its toxicity. The “Northwick Park Disaster” was a Phase I study, involving 32 subjects divided into groups of eight. Of this first group, six were critically injured. These six became casualties in part because they had been dosed with the drug at short intervals.
As a result of an inquiry into the result of the TGN1412 trial, short interval dosing was discouraged in first-in-human trials of novel agents and replaced by the use of a “sentinel” subject who could be observed in good time before the others. So what sort of dosing regimen had been applied at Rennes? It is reported that there is no known antidote to this experimental drug. Was there a sentinel, and if not why not?
The injured volunteers were reported to be in the research unit when they fell ill. So if it took a week for this catastrophe to unfold, then what rescue strategy had been put in place to deal with this sort of emergency and why was it seemingly ineffective in the case of these six? And what about the state of the previous research that underpinned this study? Was the risk of adverse reaction shown in the scientific literature? Had it been read by the researchers and the risk communicated to the subjects? ?
The final question is whether the regulatory system is at fault. There are two approval bodies involved in every drug trial taking place in every European Union country: the competent authority for drugs licensing and the ethics committee. After the Northwick Park Disaster, there never was an independent public inquiry into the role of the ethics committee that approved the TGN1412 study. So the public have no real assurance that these approval bodies are collaborating in a safe and effective way in the United Kingdom.
I do not think that they are. That is why I am a former member of an ethics committee. The disaster at Rennes is a signal to re-examine the safety of this entire system.?
Christopher Roy-Toole was a member of the Newcastle and North Tyneside Number 1 ethics committee, which oversees NHS clinical trials, from 2006 to 2015.
