Licensed to kill - facts the drug firms conceal

The industry has sponsored trials of new drugs which have held out great promise for patients with cancer, heart disease, mental health problems and other illnesses.

But tests on the same drugs in independent trials paid for by non-profit organizations - Governments, medical institutions or charities - have yielded very different results.

Drugs for abnormal heart rhythm introduced in the late 1970s were killing more Americans every year by 1990 than the Vietnam War.

Yet early evidence suggesting the drugs were lethal, which might have saved thousands of lives, went unpublished.

Expensive cancer drugs introduced in the past 10 years and claiming to offer major benefits have increasingly been questioned.

Evidence published in the Journal of the American Medical Association showed that 38 per cent of independent studies of the drugs reached unfavourable conclusions about them, compared with 5 per cent of the studies paid for by the pharmaceutical industry.

In the latest case, researchers commissioned by the National Institute for Clinical Excellence to develop guidelines for the prescribing of anti-depressant drugs to children say they were refused access to unpublished trials of the drugs held by the pharmaceutical companies.

Published evidence suggested that the anti-depressant drugs were safe and effective for children.

But when they obtained the unpublished evidence by contacting individual researchers who had worked on the trials and other sources, a different picture emerged - one of an increase in suicidal thoughts and attempted suicide. Only one of the drugs, Prozac, emerged as safe.

Anti-depressant drugs, though not recommended for children, were widely prescribed in Britain until last year, when the Medicines and Healthcare Products Regulatory Agency issued a warning to doctors, prohibiting their use.

This followed safety concerns raised by campaigners and taken up in two BBC TV Panorama broadcasts which brought the biggest response in the programme's history.

Writing in the Lancet medical magazine, the researchers say: "On the basis of published evidence alone, we could have considered at least tentatively recommending use of these drugs for children and young people with depression."

"However, our review of combined published and unpublished data ... suggest that they are not efficacious."

One of the researchers, Tim Kendall from the Royal College of Psychiatrists, said he and his colleagues had been "unnerved" by the possibility that the National Institute for Clinical Excellence could have given wrong or even harmful advice because it did not have access to the full data.

"That is the over-riding issue. How can we trust the published data?" he said.

The same concerns would apply to advice issued about other drugs in other specialist areas, Dr Kendall said.

Guidelines were being drawn up for the use of anti-depressants in adults based on 1000 published trials but it was possible tens or hundreds of other trials had been conducted without the results being published.

He said senior people at the National Institute for Clinical Excellence were taken aback by the researchers' findings, but were pleased the study had been done.

"They said it was a significant and important advance in knowledge."

In an editorial, the Lancet says the possibility that the suicide of a child could be provoked by a supposedly beneficial drug would be a catastrophe, and the idea of the drug's use being based on "selective reporting of favourable research" should be "unimaginable."

It says the story of research into anti-depressants for children "is one of confusion, manipulation and institutional failure."

It cites an internal GlaxoSmithKline memo, published in the Canadian Medical Association Journal last month, referring to a study of the antidepressant Seroxat (chemical name, paroxetine) in children.

The memo said: "It would be unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine."

Billions of pounds in health care resources are spent on the basis of published evidence, the Lancet says.

"This process is made redundant if its results are so easily manipulated by those with potentially massive financial gains."

GlaxoSmithKline sold nearly $5 billion worth of Seroxat.

Andrew Dillon, chief executive of the National Institute for Clinical Excellence, said: "The institute's ultimate objective is to be given and to be able to use freely all data relevant to the guidance which it is asked to develop. We continue to work towards that objective."

- INDEPENDENT