Leading article: A safety-first approach

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The Independent Online

New drugs have brought huge benefits to millions of patients - and substantial profits to pharmaceutical companies. Before reaching the market, every one will have undergone extensive testing - including, at some point, its first trial in humans.

Professor Gordon Duff's report into the implications for human drug trials of the disaster at Northwick Park Hospital last March, in which six young men nearly lost their lives, is right to stress that the potential rewards of drug development must never be allowed to override the protection of the guinea-pigs.

The men were testing the new monoclonal antibody TGN1412, a potential treatment for leukaemia and rheumatoid arthritis. The severity of the reaction they suffered, within minutes of the drug being administered, was both unprecedented and unanticipated. Monkeys tested with a dose 500 times greater had shown no ill effects.

To make future trials safer, the Duff report makes 22 recommendations ranging from better measures for sharing information and obtaining expert advice to refinements in laboratory testing. Where there is reason to believe that humans may react differently to a drug from animals, as in this case, testing in the laboratory will be crucial.

Some of the shortcomings in drug trial regulation revealed by the report are shocking. This was a novel biological agent, the first immune system agonist (stimulant) to be tested against a new receptor. It sent the immune systems of the volunteers into overdrive, causing a "cytokine storm" which led to widespread inflammation and organ failure.

Yet the first doses of the drug were given in a single bolus infused over a few minutes, to all six patients almost simultaneously without waiting to see how they reacted. As Raste Khan, one of the trial volunteers who was fortunate to receive the placebo, said yesterday, it is only common sense that a new drug should be given over hours, not minutes, and to each patient in turn, so that a halt can be called if anything untoward occurs. Only now is the Duff report recommending such an approach.

Professor Duff stressed yesterday that while the risks inherent in testing new drugs can be reduced, they cannot be eliminated. Yet testing must continue - the future of medicine depends on it. One challenge for companies involved in this work will be how to ensure volunteers are properly informed about the risks, and how to reward those first in line for testing a new agent. Another will be to ensure that the high level of vigilance engendered by this tragedy is not allowed to slip. Every future "first-in-man" drug trial application will require the minutest scrutiny.

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