John Meredith, Head of Education and Outreach, asks whether the recent death in a clinical trial in France should make us reconsider the value of animal research for safety testing.
The hospital in Rennes where the man who had been left brain dead in a French drug trial has died. Picture: AFP/Damien MeyerSource:AFP
Last week, a young man in France died after taking part in a phase 1 clinical trial run by Biotrial on behalf of the Portuguese pharmaceutical company Bial. Phase 1 trials are where new medicines are given to humans – usually healthy young men - for the first time. Five other volunteers were hospitalised although in stable condition, though a further eighty-four people who took the drug at previous stages during the trial do not appear to be suffering serious side effects.
This tragedy comes ten years after a similar disaster struck in London, when a group of six young men narrowly survived adverse reactions to a new monoclonal antibody called TGN1412 being trialled at Northwick Park Hospital in London. The Northwick Park disaster led to a protracted period of soul searching within the biosciences. An in-depth investigation was launched, with the pre-clinical testing of new medicines on animals being of particular concern: wasn’t animal testing supposed to predict just this sort of adverse reaction and to protect the safety of human volunteers? Didn’t its failure prove the point that had repeatedly been made by animal rights groups, that animals were not useful models for human disease or medicine?
Although the full details of the Biotrial case are not clear, we can expect similar concerns to be raised in its wake, some genuine and some opportunistic. A decade ago abolitionist organisations in the UK were quick to represent Northwick Park as a perfect illustration of the inadequacy of animal models for predicting human responses to new medicines. Organisations like the BUAV, Animal Aid, the Dr Hadwen Trust and the Safer Medicines Trust repeatedly pointed to the disaster in making their arguments for the abolition of animal research. Those of us working to improve understanding of the humane use of animals in science constantly ran up against the name Northwick Park, often presented as the killer argument, the final refutation of the claim that animals made adequate models for human disease or drug response.
But the Duff Report, which followed the investigation into the Northwick Park trial, told a different story. The report found that significant improvements could be made to how Phase 1 trials were run that would improve their safety, requiring much better communication between regulatory bodies and the teams designing trial before permission to proceed is granted.
One of the requirements is that a trial should incorporate a suitable delay between volunteers as they started the regime. This does not seem to be the case in the French trial.
The Northwick Park trial was specifically criticised for poor design, dosing all participants at once instead of starting with a single volunteer and then slightly increasing the dose for the next volunteer after a suitable period of time and so on, while keeping them all under close observation. However, although problems were identified in the specific animal models used for TGN1412, the report emphatically rejected the view that animals had no predictive value or that animal tests could not improve safety for human volunteers.
The 22 recommendations made by the Duff report were designed to significantly improve safety in Phase 1 trials and to make events such as Northwick Park much less likely in future. But the report did not claim that perfect safety could ever be guaranteed before clinical trials. If it could, why would we need Phase 1 trials at all? Speaking at the time Prof David Webb, professor of therapeutics and clinical pharmacology at the University of Edinburgh and vice president of the British Pharmacological Society, said to the BBC: “You can mitigate against the risks, but nothing is 100% certain. We can never be sure."
The terrible events in France demonstrate the truth of Prof Webb’s remarks: no pre-clinical testing can guarantee safety. But a look at the clinical trial safety record in recent years shows how close to the ideal we can get. In the UK alone, more than 200 Phase 1 clinical trials are authorized by the regulatory body MHRA each year. The fact that the Biotrial disaster stands out as such a shocking event illustrates just how rare it has become for there to be life-threatening adverse effects among clinical volunteers. In the UK, there have been no deaths in clinical trials in modern times, and no serious adverse effects since Northwick Park ten years ago. What lies behind that excellent safety record is, to a substantial degree, excellent pharmacology and safety testing involving animals.
As the investigation into Biotrial continues, there will be many people and organisations trying to use the tragedy as a rhetorical weapon to attack all animal research. But they will be wrong . Animal models continue to provide the research basis for countless medical breakthroughs and to be an essential part of maximising safety before giving medicines to human volunteers. It is up to the bioscience sector to make sure that the world knows that the abolitionists are wrong and to keep on making sure that all the arguments for the humane, well-regulated use of animals in the development of new medicines continue to be heard.
http://www.nature.com/news/researchers-question-design-of-fatal-french-clinical-trial-1.19221
Last edited: 4 April 2022 17:15
