It's the morning of the trial. The jury will shortly be sworn in.
The crux of the matter in Dolin Vs GSK is whether or not Paxil caused Stewart Dolin to kill himself whilst under Paxil's influence.
Dolin's widow, Wendy, intends to show the jury details of GSK's prior knowledge of the Paxil suicide link. Furthermore, how GSK hid this link with skullduggery; ie; they carried out underhanded and unscrupulous behavior to keep the truth from healthcare professionals, regulators and, more importantly, patients.
In 1989, GSK submitted its “Integrated Summary of Safety Information” to obtain approval of Paxil to treat adult depression. Amongst other adverse event statistics, the Safety Summary reported the number of suicides and suicide attempts experienced by patients who took Paxil, a placebo or a comparator drug during GSK’s initial clinical trials.
In GSK's presentation they compared the suicide attempts with patients in the Paxil group and those patients in the placebo group; and here's how they hid the fact that more patients in the Paxil group had a far higher (significant number) of suicides and suicide attempts.
During the run-in period (which is also called wash-out), patients taking part in a clinical trial are taken off of any medications they may be taking and given a placebo (commonly known as a dummy or sugar pill) instead. In this way, a person’s system is “washed out” of other drugs and all patients start the trial on a drug-free basis at “baseline,” i.e. at the actual beginning of the clinical trial.
Because people who are stopping medications during this wash-out period may experience adverse events associated with withdrawing from the medication they were on, adverse events experienced during this period are not properly counted as occurring during the clinical trial. Adverse events that occur during run-in periods cannot be included when calculating adverse event ratios for clinical trials. This is standard practise for clinical trials.
The FDA's Dr. Martin Brecher had mentioned in testimony that it is “scientifically illegitimate” to count placebo run-in/washout events. Furthermore, Michael Seika, another FDA medical reviewer, explained why run-in adverse events should not be counted. According to a December 8, 1999 GSK memo of a conversation with the FDA:
Specifically, I [Thomas Kline, Assistant Director of Regulatory Affairs at GSK] asked [Michael Seika] if a patient were to die during placebo run-in, i.e. prior to randomization, should that patient be included in the calculation for placebo deaths. He clearly stated that such a patient should not be counted in our analyses, since such a patient would not comprise the “controlled” portion of a trial.Despite GSK knowing that counting adverse events during placebo run-in was improper they included them in their 1989 “Integrated Summary of Safety Information”
When the 1989 “Integrated Summary of Safety Information” is properly dissected we see that patients taking Paxil were at an 8.9 times greater risk of experiencing a suicide event than those on placebo.
GSK knew this but, by including the count for the placebo run-in/washout events, they were able to hide the risk of suicide from the FDA and, subsequently, prescribing doctors and patients.
By increasing the number of suicide attempts of patients taking placebo and reducing the number of Paxil patients attempting suicide, the percentages between Paxil and placebo became approximately the same - ergo Paxil patients had an equal chance of feeling suicidal if they had taken placebo. Because of this, the percentage of Paxil patients attempting suicide went down from the original submission because GSK reduced the number of Paxil suicide attempts from 42 to 40.
So, by removing the run-in suicide attempt events, Glaxo hid the fact that the correct number was 40 suicide attempts while on Paxil versus 1 attempt on placebo, an approximately 7.5 fold increase of suicide attempt risk for Paxil patients.
Paxil was approved by the FDA in 1992. The approval was based on GSK's false placebo numbers and the incorrect conclusions based on them.
Additionally, once Paxil was approved by the FDA, GSK then went out en masse via a massive promotional campaign touting Paxil as safe and effective, they did this by using the false placebo numbers.
A year prior to Paxil's official launch GSK's (then SmithKline Beecham) Dr. Geoffrey Dunbar and Sarah Mewett presented a paper entitled 'Evaluation of Suicidal Thoughts and Acts with Paroxetine' at a medical conference, in order to address the then-recent concerns linking suicidality to SSRI antidepressants. In their presentations they claimed that “Suicides and suicide attempts occurred less frequently with Paxil than with either placebo or active controls - they made this claim using the false placebo numbers.
Furthermore, in 1995 GSK's Dunbar, along with two psychiatrists, submitted an article in the Medical Journal of European Neuropsychopharmacology. The article was published and claimed that Paxil actually reduced suicides and suicides attempts.
With this peer reviewed article in place GSK then instructed its saleforce team (reps) to play down the suicide risk associated with Paxil - (at the time reports via the media were suggesting there was a connection between Paxil and suicide)
GSK made billions of dollars from Paxil knowing that the data they submitted was false, meantime, patients on Paxil were feeling suicidal, many were completing suicide.
However, this wasn't enough for GSK.
On April 11, 2002, GSK submitted a Supplemental New Drug Application (“sNDA”) to FDA proposing the use of Paxil to treat children and adolescents with major depressive disorder and obsessive compulsive disorder. During its review of GSK's application the FDA's Dr. Andrew Mosholder noted that the most prominent adverse reactions in the Paxil clinical trials were “behavioral effects,” but he stated “these events were coded with terms such as hostility and emotional lability.
In other words, GSK, once again, strove to hide the suicide link in Paxil - remember, this application was for children! The actual figures showed that Paxil demonstrated a relative risk 3.0 times greater than placebo.
If you don't know the answer to why they hid the suicide information in both adult and children's Paxil clinical trials, then you probably don't know how business works. GSK hid the risks in both; they made lots of money from Paxil by getting it prescribed to adults, they wanted to do the same in the children's market - but the FDA and British drug regulatory agency never granted it a license for use in children. It was, however, still prescribed to children - once again on the back of GSK's salesforce team convincing doctors that it was safe and effective - they did this by showing prescribing doctors articles by prominent pediatric psychiatrists. What they didn't show the prescribing doctors was that the published material they were showing them was ghost-written by a PR company hired by GSK - prominent child psychiatrists merely put their names to the published material.
This, ladies and gentlemen, is how GSK operate. This is how they were able to hide the suicide link. This is how they have made billions of dollars off the back of Paxil. This is why Stewart Dolin killed himself.
I'm off to the courthouse. Will blog about days events later.
Dolin Back Stories.