October 5, 2012
I’m back after a (very) long summer break.
There were two significant events in July. One was a US fine of $3 billion for Glaxo Smith Kline for mis-selling various medicines and other bad practices. The other was the publication by the European Commission of a proposal to revise the directive governing clinical trials.
The GSK fine included a number of criminal and civil penalties; details are on the website of the US Department of Justice. For those without the time, here is a summary of one of the criminal charges – involving the use or abuse of science. The full charge sheet is here
GSK pleaded guilty to the criminal charge of promoting an anti-depressant, Paxil, to children and adolescents from 1999 to 2003 when it was not approved for such use. According to the charge sheet, they did this in the following ways:
1 GSK carried out three studies on Paxil in children and adolescents, none of which showed any efficacy for the medicine for such patients.
2 For one of the studies (Study 329) GSK helped write and approved a “false and misleading” article in a medical journal that claimed that Paxil was effective in treating depression in adolescents. An early draft of the article described the serious adverse effects from Paxil as follows:
“worsening depression, emotional lability, headache and hostility were considered related or possibly related to treatment.” GSK asked for this to be changed and the final version read “Of the 11 patients (who had serious adverse effects when taking Paxil), only headache (1 patient) was considered by the treating investigator to be related to (Paxil) treatment.”
2 The results for the other two studies were never published, but were submitted to the FDA after some time.
3 GSK used the journal article to promote Paxil for use in children and adolescents. The marketing department sent the article to some 1900 medical reps, with a memo saying “Paxil demonstrates REMARKABLE Efficacy and Safety in the treatment of adolescent depression“.
4 GSK paid a child psychiatrist to speak at a launch meeting and reported him as saying that as a result of the study “we can say that paroxetine has both efficacy and safety data in the treatment of adolescents.”
5 At four “Paxil Forum” events for invited doctors (at expensive resorts) a paid speaker, a child psychiatrist, claimed that Study 329 showed “significantly greater improvement” in patients taking Paxil compared to placebos. Later, GSK reps gave some doctors copies of the speaker’s slides – slides that were “false and misleading”, according to the charge sheet.
6 GSK sponsored dinner programs, lunch programs, spa programs and other similar activities to promote the use for Paxil for children and adolescents.
7 GSK used samples to promote the use of Paxil for children and adolescents.
In 2003, after GSK had submitted the results of its three Paxil studies, the FDA recommended that Paxil not be used to treat children and adolescents.
No doubt the company would argue that these unfortunate events were a long time ago and would not happen nowadays – but how can we be sure? There have been some changes since, in relation to entertainment of doctors; there is slightly more transparency in terms of registration and reporting of clinical trials but not nearly enough and not in a properly systematic way. A system to promote transparency and access to information on clinical trials is no good unless it gets to the information, data and results that the companies would prefer not to release. This and similar cases may have a deterrent effect for some time but surely regulation has an important role here. More later on this point.ENDAuthor : Jim Murray