Northwick Park drug trial disaster - could it happen again?


Before any new medicine can be given to patients, detailed information about how it works and how safe it is must be collected.

Clinical trials are the key to getting that data - and without volunteers to take part in the trials, there would be no new treatments for serious diseases such as cancer, multiple sclerosis and arthritis.

But one disastrous drug trial at a London hospital in 2006 threatened to derail that system.

In what became known as the Elephant Man trial, six healthy young men were treated for organ failure after experiencing a serious reaction within hours of taking the drug TGN1412 in a clinical trial.

After they were all admitted to intensive care, two became critically ill, the worst affected lost his fingers and toes, and all the men were subsequently told they would be likely to develop cancers or auto-immune diseases as a result of their exposure to the drug.

In follow-up interviews, the men described feeling like their brains were "on fire" and their "eyeballs were going to pop out".

Experts queued up to say the outcome of the trial had been unprecedented and exceptional, but could it happen again?

Prof David Webb, professor of therapeutics and clinical pharmacology at the University of Edinburgh and vice president of the British Pharmacological Society, says it is "much less likely to happen again".

He says things have changed for the better since 2006, following a number of recommendations made in the Duff Report, written in response to the trial.

"The MHRA [Medicines and Health products Regulatory Agency] now ensures committees look at pre-clinical data, to decide whether the first dose given to humans is the right dose and has rules for stopping if things don't go as expected."

This is particularly important when trials involve drugs that affect the immune system, he says.

But is it possible to eliminate the risks entirely?

"You can mitigate against the risks, but nothing is 100% certain. We can never be sure," Prof Webb says.

The trial, which was privately run at a research facility at Northwick Park Hospital in north London, involved the first testing of a new drug on humans. This is the initial phase in assessing the safety of a drug before moving onto larger-scales studies in patients themselves.

The report said Parexel, the company managing the trial, had been unclear about a safe dose to start testing on humans and it should have tested the drug on one person at a time.

The MHRA, which regulates clinical trials and medicines in the UK, and which was criticised at the time for giving the green light to the TGN1412 trial, says the conduct on these phase-one trials "has moved on significantly".

"Additional provisions and guidance has been put in place for certain novel products to provide as much assurance on safety as possible," the agency says.

It adds that it has simplified and streamlined the regulation of clinical trials and collaborated with other bodies and experts to collect as much information as possible on risk factors before a trial is authorised.

Phase-one trials, when drugs are tested on humans for the first time, only happen after extensive testing on tissue samples and animals in the lab.

Getting this stage right before moving onto research in humans is crucial.

Dr Catherine Elliott, director of clinical research interests at the Medical Research Council, which funds clinical trials in the UK and globally, says there is a move to refine the models used at the pre-clinical stage.