Unethical Conduct Paxil 2010-01-27 Global ++Manufacturer of Paxil Is Unethical During Clinical Trials for Paxil in Regard to Placebo Washout
Summary:

Paragraphs 5 & 7 and part of 8 read:  "They offered an example from GlaxoSmithKline's ghostwriting program for its anti-depressant Paxil, dubbed CASPPER, for "Case Study Publications for Peer Review." In it, data from a "wash-out" period before the formal trial -- during which past medications use is washed from the participants' bodies to ensure a clean trial -- is included, which alters the study's conclusions."

"Instead of showing a higher chance of suicide, the eventual study showed the opposite."
"Placebo-controlled trials often include a placebo wash-out phase, in which all participants initially receive placebo prior to some participants then switching to the drug under investigation. For example, a study may use a 3-week period of placebo washout, followed by 8 weeks of patients receiving either drug or placebo. It should be obvious that the comparison of efficacy and safety between drug and placebo should begin during the fourth week, when half of the participants have started receiving active medication. Yet some manufacturers of antidepressants counted suicidal behaviour in the placebo wash-out phase against placebo in their comparisons of drug to placebo. Comparing suicidal acts on 11 weeks on placebo to 8 weeks on a drug helped to drive up apparent rates of suicidal behaviour on placebo, which made the drugs appear safe in comparison."


http://thestar.blogs.com/ethics/2010/01/science-as-marketing.html




January 27, 2010




Science as marketing

A new peer-reviewed study paints a disturbing picture of the use and abuse of science by pharmaceutical companies to help them sell drugs.

Published in the latest edition of the Journal of Bioethical Inquiry, the study goes through several case studies of big drug companies using questionable science to boost the apparent effectiveness and/or safety of their products. Authors Glen Spielmans and Peter Parry sifted through internal court documents released to the public through lawsuits against the drug companies in one of the first peer-reviewed studies to rely on such documents.

They outline several ways they say that companies used science improperly to market their drugs, including selective use of trial results (or "data fishing") to suppress or spin negative results, and ghostwriting -- in which a report written by or for a drug company to give a psitive review to one of its products is then published under the name of a respected academic or research who had little (if anything) to do with its preparation.

In most cases, the study says, the "authors" are not even allowed to see the raw data -- a fatal flaw, the authors say, because the raw data can sometimes point to a different conclusion that the data the company has selected to share with the outside world, or its "authors" of ghostwritten articles.

By participating in such schemes, Spielmans and Parry say, "honorary academic authors are not just padding their vitae, they are also potentially harming public health when they fail to carefully review data presented in studies on which their names appear as authors."

They offered an example from GlaxoSmithKline's ghostwriting program for its anti-depressant Paxil, dubbed CASPPER, for "Case Study Publications for Peer Review." In it, data from a "wash-out" period before the formal trial -- during which past medications use is washed from the participants' bodies to ensure a clean trial -- is included, which alters the study's conclusions.

Instead of showing a higher chance of suicide, the eventual study showed the opposite.

Placebo-controlled trials often include a placebo wash-out phase, in which all participants initially receive placebo prior to some participants then switching to the drug under investigation. For example, a study may use a 3-week period of placebo washout, followed by 8 weeks of patients receiving either drug or placebo. It should be obvious that the comparison of efficacy and safety between drug and placebo should begin during the fourth week, when half of the participants have started receiving active medication. Yet some manufacturers of antidepressants counted suicidal behaviour in the placebo wash-out phase against placebo in their comparisons of drug to placebo. Comparing suicidal acts on 11 weeks on placebo to 8 weeks on a drug helped to drive up apparent rates of suicidal behaviour on placebo, which made the drugs appear safe in comparison. Indeed, an article was published in 1995 allegedly showing that paroxetine reduces suicidality. The academic author admitted that he had not seen the actual raw data; rather, he had been provided data tables by the manufacturer, which he then helped to convert into an article (Glenmullen 2007). However, the data in the article included suicide attempts which occurred during the placebo washout phase, though this was not stated in the manuscript. GSK has since posted its own analysis online, in which it notes an increased risk of suicidal behaviour among patients taking paroxetine relative to placebo (GlaxoSmithKline undated). Nearly anyone reading a journal article will assume that the named authors had access to raw data rather than misleading data tables provided by a drug firm. While not technically ghost authorship, the manner in which the data were translated into final form is clearly outside of the norms of science.

The authors call for more access to raw data, and recommend that perhaps journal articles should be read with a grain of salt.

The article also provides links to several web site containing internal drug company files made public due to lawsuits: furiousseasons.com/ zyprexadocs.html, furiousseasons.com/ zip/seroqueldocs.zip and healthyskepticism.org/ documents/Antipsychotics.php. There is also the Drug Industry Document Archive at the University of California, San Francisco, which has a searchable database of company files from several court cases.