Drug trial ignored guideline on safety

DRUG trials that left six healthy volunteers fighting for their lives did not conform to best medical practice, The Times has been told.

Senior doctors expressed concern that all six were given the same dose of the experimental drug TGN1412 at the same time. According to the standard medical text, trials of this sort should avoid giving all the doses simultaneously. The Textbook of Pharmaceutical Medicine specifically gives warning that such practices can be �very difficult to manage� and �put subjects at unnecessary risk�.

Last night the Medical and Healthcare Products Regulatory Agency was urgently investigating what went wrong in the the trials, as families kept up a vigil at the patients bedsides. It is trying to determine whether it was a fault in production, contamination or more likely an intrinsic problem with the drug itself.

�They haven�t got a cure,� said Myfanwy Marshall, whose boyfriend fell ill 90 minutes after taking the drug. �This is a drug they have never tested on humans before so they don�t know what they are dealing with. It�s completely messed up their vital organs.�

There was confusion last night about whether the drug had been tested successfully on animals before the tests on human volunteers.

�They [the drugs company] said there was an oversensitivity in monkeys,� Ms Marshall said. She went on to say that in the tests a �dog and some animals had died . . . so they reduced the amount to humans�.

Thomas Hanke, chief scientific officer of TeGenero, last night refused at a press conference to say whether animals had died during earlier tests. �There has been no issue on the safety of the drug on animals. This is not relevant,� he said. He said the drug had been tested on mammals but not dogs or rats.

He said that the company had apologised to relatives of the six ill volunteers. �We are devastated at these shocking developments which we were not anticipating. The investigation must proceed as quickly as possible (into) the testing of a new medicine which showed no signs of any safety problems in previous testing.�

Lawyers have been instructed on behalf of at least one of the victims. All six remained in care at Northwick Park Hospital, northwest London. Two were said to be in critical condition and the other four were serious, but showing signs of improvement. Relatives met doctors and staff from the two companies involved � the German biotech company, TeGenero, and Parexel, the contract company that was conducting the trial.

The trial protocol had been agreed with the MHPRA and was carried out �according to strict ethical and regulatory requirements�, according to Parexel.

The MHPRA yesterday refused to give precise details, citing commercial confidentiality, and questions to Parexel went unanswered. But TeGenero confirmed that all six volunteers had been given scaled doses of the drug according to their body weight. The tragedy, experts said, should result in a review into the way future trial are carried out.

Professor Sheila Bird, from the Medical Research Council�s Biostatistics Unit at Cambridge, said: �It is very unusual to have a tragedy in one volunteer in a trial like this, far less to have all six involved. �

That could have been avoided, she said, if at the start only one of the volunteers had been given the drug.

All were healthy young men who had volunteered for the first human trials of a new arthritus drug, developed in Germany.

Professor Bird, citing the recommendations made in The Textbook of Pharmaceutical Medicine, a standard work on the subject. suggested that the trial would have been better to test two or three volunteers on day one, before other volunteers were given their dose.

However, Chris Springall of Covance Clinical Research, a company based in Yorkshire that carries out drug trials, said that the practice by which the whole group was given a dose at the same time was normal in the industry. But it was not considered risky because side-effects were so extremely rare.

�I've been in this business 20 years and I've never known anything of this nature before,� he said.

Source