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Last Updated: Thursday, 7 December 2006, 12:01 GMT
Q&A: Drug trials
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Six men were treated in intensive care after experiencing a serious reaction to a drug taken during a clinical drugs trial in north-west London.

What happened to make the men ill, and how is such research governed?

What happened?

The six healthy men, all under 40, had volunteered to take part in a trial of an anti-inflammatory drug, called TGN1412, to treat conditions such as rheumatoid arthritis and leukaemia being tested at an independent research unit based at Northwick Park Hospital.

The six suffered multiple organ failure, and two were said to be critically ill.

Another two men, who had been given a dummy version of the drug in the trial, did not fall ill.

The trial was stopped as soon as the men fell ill.

What is the drug?

TGN1412 is a class of drug known as a monoclonal antibody.

Antibodies are produced in the body in response to infection. Monoclonal antibodies are made in the lab - and some are already on the market being used safely and effectively.

The drug in this trial had been thought to be particularly effective form of this kind of drug, because it is capable of boosting the action of killer immune cells to help them fight cancer cells, which they usually cannot normally do.

What went wrong?

Parexel say it followed all the rules set in place for drug research.

A spokesman for the German company TeGenero, whose drug was being tested, said the results were "completely unexpected" and "did not reflect the results we obtained from initial laboratory studies".

Dr Benedikte Hatz, chief executive officer for the company, said the drug had been developed in line with all regulatory and clinical guidelines, and had been shown to be safe in earlier non-human studies.

The MHRA's preliminary findings appear to back up what TeGenero have said.

It said the drug being tested was given in correct doses and there was no sign of contamination or manufacturing errors, but added its findings were not conclusive and more tests were planned.

It added: "It would indicate that this product showed a pharmacological effect in man which was not seen in pre-clinical tests in animals at much higher doses."

What are drugs trials and how are they organised?

Drug trials refer to the process by which medicines are developed.

Before a drug is tested in humans, it would have been through laboratory and animal testing.

Medicines are also tested for toxicity before being given to people.

There are then three stages of drug testing in humans - and any such trials have to be approved by ethics committee.

  • Phase one - this stage tests for safety. A small number of people, sometimes healthy, and sometimes with a medical condition, are given a tiny dose of the drug under careful supervision, not to test if the drug works, but in order to check for any side effects

    This is the stage which the Parexel research was at.

  • Phase two - the drug is given to people who have the condition to see if it does indeed help them

  • Phase three - large scale studies usually involving tens or thousands of people

    Participants are often randomly allocated to either get the drug or a dummy version

    In most cases neither the scientists nor the patients know who has got the real drug so that the results cannot be skewed by expectations.

Once a drug has been through all these stages of testing - which can take up to 10 years - it will be considered for licensing.

But even then, pharmaceutical companies must keep carrying out research to ensure a drug is still safe and effective.

Who gives permission for them to go ahead?

All trials which take place in the UK have to be authorised by the MHRA, which decides if they are scientifically valid and properly designed.

Local ethical committees also have to decide if the research is in the best interests of patients.

Trials are run by charitable and academic institutions, as well specialist companies, such as Parexel, whose units are usually based at NHS hospitals so they are close to scientific and medical expertise.

These companies carry out research on behalf of clients from the pharmaceutical industry, like the TeGenero, who are developing this drug.

The MHRA has announced that following events at Northwick Park first-in-man trials of drugs like TGN1412 will not be authorised without additional expert advice.

Who takes part in such trials?

Researchers recruit volunteers to take part in studies. Phase one trials, because they often need healthy people, may advertise in magazines, on the internet or in the local area.

Such research can require people to spend two or three weeks in the research unit, so many of those taking part are students.

However, women of reproductive age would not be involved if there was any chance they were pregnant, in case there were effects on a foetus.

The ABPI, which has set down guidelines on how trials should be carried out, says people should not be given financial incentives to take part in research.

However, they should be recompensed for the time they are giving up. The standard rate is between 150 and 200 a day.

For phase two and three trials, where patients with a certain condition are needed, adverts may also be placed in patient newsletters or in particular clinics.

It is estimated that just a few hundred healthy people take part in phase one trials in the UK each year.

Altogether, over 100,000 will be taking part in some kind of trial.

Do people know things could go wrong?

Anybody who takes part has to be told what risks are involved and what known side effects might be.

They would also be told what compensation would be in place if something unexpected went wrong.

Legal experts said it was important any financial payouts were approved quickly and without dispute between the companies involved so that people were not deterred from taking part in drug trials.

Ben Hayes of the ABPI said people should not take part in trials if they feel they have not been given sufficient information.

But he said trials were taking place for the good of the wider population: "At some point, scientists have to translate the theory into humans."

How common are problems such as those seen in this trial?

Drug trials are sometimes stopped early. An HRT trial in the US was stopped when researchers linked the drug to an increased risk of stroke.

However, this study was a phase three trial, so was at a much later stage than the London research.

The MHRA said it had never seen a situation such as that seen at Northwick Park before.

And Richard Ley, of the Association of the British Pharmaceutical Industry (ABPI), added: "This is an absolutely exceptional occurrence.

"I cannot remember anything comparable."

What have experts recommended future trials?

Scientists are looking for ways of ensuring that no future trial has the same result.

An expert working group issued a report to government with 22 recommendations, including the advice that it may be best to test some drugs, such as TGN 1412, on people who are already ill rather than on healthy volunteers.

The Duff report also emphasises the need to collect safety information from unpublished clinical studies.

And an expert group should be set up to advise the government's drug regulatory body, it says.

The drug industry has backed the report.

An earlier report from the Medicines and Healthcare Products Regulatory Agency found that Parexel had not adhered to rules about the administration of drug trials.

Six taken ill after drug trials
15 Mar 06 |  London


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