'We need to know about the failures'

By Helen Sharp
Producer, The Future of Drug Trials

Successful trials tend to get more attention

In 1993, Professor Terry Hamblin, of the University of Southampton, was investigating the effects of a new cancer drug.

At the time, a wonder drug was being used to treat people with serious cancer diagnoses, called Interleukin 2.

It was incredibly effective but had very toxic side-effects: drops in blood pressure, fevers and back pain.

Professor Hamblin's new drug was being tested to see if it was any more effective but without the side-effects.

"The idea was to stimulate the lymphocytes, the defence cells in the body, to attack the cancer," he said.

Slow infusion

As the drug had never been tested on humans, he tried it on one patient first.

He gave the man the drug through an infusion into his vein over a number of hours, so if anything went wrong he would be able to stop the test before the patient's body was overwhelmed with the drug.

Soon it was clear the drug was having a therapeutic effect on the cancer - but it was also causing side-effects that were the same as those of Interleukin 2 and the trial was halted.

Professor Hamblin said: "It stimulated many cells in the body so patients regularly got high fevers, shivering attacks, their blood pressures fell, they had headaches, they vomited, they had diarrhoea, they had a rash where their skin began to peel off, very similar symptoms in fact to what the patients at Northwick Park developed."

The scientific community should take responsibility for letting us know what's important in a particular area Professor Deborah Saltman

Professor Hamblin's drug and TGN1412, the drug given during the drug trial, work in similar ways.

They both want to stimulate part of the immune system to produce an immune response in the body.

During the trial at Northwick Park Hospital, six men were given the drug intravenously, over a period of minutes.

But within an hour, side-effects much like those in Professor Hamblin's trial were being seen.

Not published

However, TeGenero, the makers of TGN1412, did not know about Professor Hamblin's work because, at the time, a failed trial with a drug that was less effective than one already on the market would not have been published.

But his observations would have been helpful to TeGenero and possibly to other drug companies working on similar treatments.

Since the TeGenero trial, the government has set up an Expert Scientific Committee to look into how early-stage drug trials should be carried out.

They recommend that work such as Professor Hamblin's should be published on a database, which those doing the trial and those regulating the trial have access to.

This way, those involved can see if work has been done previously that could give some indication of the outcome of the trial.

In fact scientists have been working, together with drug companies, to produce something like this for the last 20 years.

There are various places on the internet where people can publish their results - including negative and null results.

Professor Deborah Saltman, editorial director of medicine for Bio Med Central, one of the largest open-access publishers on the web, says that choosing the important results to publish is key.

"We have what's called peer review: if your colleagues, scientists working in the area consider it's important, it should be published.

"The scientific community should take responsibility for letting us know what's important in a particular area."

Rethink needed

The Expert Scientific Committee has reached various conclusions, and one is that the dose given to the men was wrong.

Professor Gordon Duff, who chaired the committee highlights that the way in which drugs trials are organised needs to be looked at.

"The dose was undoubtedly too high which is why we saw all six recipients get ill and so severely ill.

"What that tells us is the methods used to calculate the dose failed to predict a safe dose.

"Those methods were largely based on the current norms, the regulatory guidelines that were operating at the time."

The TGN1412 trial took place at a laboratory on the Northwick Park Hospital site, but was nothing to do with the hospital.

The Future Of Drug Trials will be broadcast on Tuesday 26 September on BBC Radio 4 at 2000 BST. You can also listen online for 7 days after that at Radio 4's Listen again page.