Owen Dyer from bmj.com {British Medical Journal, a premiere peer review publication}, London.
The British pharmaceutical giant
GlaxoSmithKline (GSK) is facing a major lawsuit in the United States over alleged concealment of negative
trial results involving its antidepressant paroxetine (marketed there as Paxil and in Britain as Seroxat).
The civil suit, filed by New York state's attorney general, Eliot
Spitzer, charges the drug company with "repeated and persistent fraud" in concealing the results of studies that
suggested that paroxetine was ineffective in treating depression in adolescents. It is the first time
a US public authority has pursued a drug company for misreporting trial data.
Five studies have attracted
particular attention. Two of these showed no benefit from paroxetine compared with placebo in depressed adolescents.
Three showed evidence of an increase in suicidal thoughts and behaviour, though there were no actual suicides.
Mr. Spitzer has an internal SmithKline Beecham
memo from 1998 which stated that it would be "commercially unacceptable" to admit that paroxetine did
not work in children. It went on to say that the company would have to "effectively manage the dissemination
of these data in order to minimise any potential negative impact." The
document was published by the journal of the Canadian Medical Association, CMAJ, in February and reported
in the BMJ that month (21 February, p 422). The
negative trial data came out when one of the participating researchers, Dr Robert Milin, presented results at the
1999 meeting of the American Academy of Child and Adolescent Psychiatry. He said the company did not
try to stop him.
In a statement, GSK said: "GlaxoSmithKline
has acted responsibly in conducting clinical studies in paediatric patients and disseminating data from
those studies. All paediatric studies have been made available to the FDA [US Food and Drug Administration] and
regulatory agencies worldwide. We have publicly communicated data from all paediatric studies. As for
the 1998 memo, it is inconsistent with the facts and does not reflect the company position."
The company's share price fell
sharply last Wednesday when the suit was announced, but recovered somewhat as analysts predicted that
potential damages would be unlikely to surpass $250m (£136m; 203m). Mr. Spitzer said off-label
prescribing of paroxetine to under 18s had accounted for about $55m in sales in the United States in
2002.
The case has reignited debate
in the United States about a national trials registry that would record all clinical trials from the outset.
GlaxoWellcome was considering setting up a company trials registry when it merged with SmithKline Beecham in 1998,
but it never implemented the plan.
David Fassler, a Vermont psychiatrist
who is on the council of the American Academy of Child and Adolescent Psychiatry, said he believed that
a national registry would probably be set up in the next few years. "This case is a healthy development."
GSK's treatment of paroxetine
data has also come under scrutiny in Britain, where the Medicines and Healthcare products Regulatory
Agency has been investigating the case for nine months. The MHRA has not yet decided whether to take action against
GSK, but expects the investigation to conclude in the next few weeks.
There is a fundamental conflict
between fair reporting of results and funding the research which yields hundreds of millions of dollars in profits.
There is a fundamental conflict between having those who run the FDA coming from the pharmaceutical industry and public safety.
And there is a fundamental conflict between acting in the public interest and receiving every year 10s of millions of dollars
in campaign contributions.--jk
