Pharmaceutical producers performing clinical trials with new drugs should be much more careful in the design of studies, an academic panel reviewing a recent deadly incident in France, has concluded.

Reviewers of the recent phase I trial by the Portuguese company Bial in Rennes, France, which left one volunteer dead and five others seriously impacted, has also proposed that tighter restrictions should be placed on such studies.

In an editorial published in the British Journal of Clinical Pharmacology, experts from the UK and the Netherlands provided a detailed account of what went wrong in the trial and concluded that a stricter process of “systematic risk assessment” is needed for all trials involving new compounds.

The panel’s review said 90 trial participants were initially given single doses of the drug, a fatty acid amide hydrolase (FAAH) inhibitor codenamed BIA 10-2474. The dosage was then gradually increased from 0.25 mg to 100 mg and was planned to finally progress to daily doses of up to 50 mg.

No serious side-effects were reported, they said, until near the end of the trial, when a group of six volunteers was due to receive the maximum 50 mg dose for 10 consecutive days. The Bial drug was considered low-risk as it had been tested in non-human primates with no ill effects at higher doses than those given in the first-in-man trial.

In the British editorial, Michael Eddleston, professor of clinical toxicology at the University of Edinburgh, is quoted as recommending greater use of “sequential dosing,” in which only one person receives each new dose, with a delay to monitor side-effects before it is given to others.

David Webb, professor of clinical pharmacology, also at the University of Edinburgh, is quoted as saying the Rennes incident has exposed flaws in the system. “A pharmacological approach to dosing and a comprehensive assessment of risk for each drug,” he concluded, “not just those thought to be high risk.

The review panel has called for the release of all trial data involving the drug tested by Bial and has advised that regulators be given more information from pre-clinical studies before allowing first-in-human trials to proceed.

According to documents obtained by the French press, volunteers who took BIA 10-2474 were each paid €1,900 for taking part.