Seroxat Link 3 : The Yugoslavia Trials : GSK & Paroxetine


Ok, so we know that Seroxat (chemical : paroxetine ) first emerged from the labs at Ferossan , and we know that B.I. (boehringer-ingelheim) originally filed paroxetine in the class of “hypnotics”..

So how did GSK get it passed by the drug Regulators as an anti-depressant?…

This is how…. (for the full transcript of Breggins Article , click on the text )

From 1980-1991, approximately 5000 patients were tested on Paxil during SKB’s clinical trials.Eighty-three (83) different Paxil trials were conducted.Various time periods were involved in the individual trials.Many patients were tested for only a month or 6 weeks.Some were tested longer, including approximately 400 who were in trials longer than a year.SKB pulled out all the stops to ensure the trials were successful.Only two (2) positive trials are required for FDA market approval.By any reasonable person’s perspective, Paxil’s track record in the clinical trials was poor.After a decade of juggling data in the 83 different trials, SKB was finally able to cite four (4) “positive” trials and three (3) “supportive” trials to justify Paxil’s approval.Dropouts in most trials were rampant.Most of the dropouts occurred because Paxil caused adverse experiences, and the victims wanted nothing more to do with the drug.

Paxil’s clinical trials were a statistical sham.Rather than deal with real numbers, SKB created a fraudulent measuring standard called “patient years” (or “patient exposure years”).The need for “patient years” became obvious in the 1980’s.It was obvious in the late 1980’s and into the 1990’s that Paxil clinical patients were attempting suicide and suffering “adverse experiences” at an alarmingly high rate.Moreover, as indicated above, hundreds of Paxil volunteers dropped out because they could not tolerate the drug.The dropout rate was 20%.Fifty-eight (58) patients alone attempted suicide after they were given Paxil.Hundreds of additional Paxil patients suffered adverse experiences caused by the drug.In 1991, SKB “ran the numbers” and discovered the absolutely horrible Paxil record.The 58 attempted suicides out of the patient base constituted a suicide rate of 0.77% in real numbers.Under clinical standards, a rate of 1% is considered a “frequent” occurrence.On those numbers, Paxil patients approached a “frequent” suicide rate.This was a far greater suicide rate than “placebo” or the other active drug being tested on the patient population.To avoid a company disaster on the Paxil project, SKB had to change the rules, and shift to the “patient years” sham.

22.The “patient years” standard is a sham by anyone’s common sense.It works like this.Assume 366 patients are selected at random to test Paxil.Three hundred and sixty five (365) patients take Paxil and suffer horribly the first day–immediately quitting the test.These patients are called, not surprisingly, “losers.”The 366th patient, however, tolerates Paxil quite well, and even improves on the drug, staying in one or more trials for a full year.This patient is a “winner” by SKB standards.Like a champion race horse, this “winner” is entered in all the sweepstake trials for Paxil–and these trials are intentionally programmed to be long.Knowing they have a champion race horse, SKB racks up “points.”By anyone’s common sense standards, 365 failures out of 366 attempts would render the drug a dismal failure.But not so under “patient years.”Under patient years, the one Paxil patient who tolerated the drug for one year counts the same as the 365 patients who couldn’t tolerate the drug and dropped out the first day.The “score” in this example is “one patient year” for each side.Not surprisingly, the mathematicians who go along with this voodoo math are subordinate to the physicians and clinicians in the corporate chain of command, and the physicians at the top of the FDA chain of command.

In Paxil’s clinical trials, SKB ultimately achieved positive results–as it were–because of emphasis on “subjective” testing data.Objective data is very scientific.Subjective data is less scientific.The latter requires more stringent controls to be applied scientifically.Subjective data is subject to the biases, opinions, and prejudices of the person(s) collecting the data.SKB’s subjective data to justify Paxil’s approval was obtained both from physicians, principal investigators (“PI”) (most of whom were physicians) and from patients.The physicians and PI’s were compensated handsomely by SKB for their participation in the trials.On information and belief, plaintiffs allege these individuals were hired only after appropriate screening to ensure they were friendly to the drug industry and SKB.

.It was in mid 1992 that Dr. Laughren was directed by the FDA to be the staff point person for the October 5, 1992 Paxil committee hearing.Dr. Laughren had earlier concluded he would recommend Paxil’s approval.Dr. Laughren was also getting promoted and had only recently assumed the higher position.He was being assigned to take over the position occupied by the FDA official who had telephoned SKB on the PR nature of the Prozac problem.Dr. Laughren was taking over the higher position very late in the game insofar as Paxil’s application was concerned.The earlier incumbent–as described–had already taken a position favoring Paxil’s approval, and was not modest in voicing full support for SSRI’s.It would have been highly unusual for the FDA to place in that position an individual who would upset the apple cart and refute what his/her predecessor had committed to on the Paxil decision–and of course that didn’t happen.Dr. Laughren fell in line with his predecessor and validated all of his predecessor’s findings.In preparation for the upcoming October 5, 1992 committee proceedings, Dr. Laughren wished to be “hands on” before committee members.His wished to make it appear that the FDA staff was totally in command of their domain.Here, however, is where the FDA regulatory system breaks down–and was broken in this instance.It is where, essentially, the government bureaucrat depended on the “regulated” in order to look good in the job and get through a particular project–and that’s what happened here.Both players–FDA staff and SKB–recognized they were dependent on each other to look good before the committee.Like the telephone tipoff on the suicide issue, this was a poor environment for checks and balances, or fostering effective FDA regulation on behalf of public safety.For several weeks leading up to October 5, 1992, Dr. Laughren depended on SKB to get up to speed for his expected presentation before the committee.This was notwithstanding that FDA had been provided all of Paxil’s trial documentation as the clinical trials had progressed throughout the previous decade.As Dr. Laughren was preparing for the committee hearing, he made several urgent fax appeals to SKB headquarters to help him prepare his presentation.He was not modest.He asked numerous questions.He asked for numerous, individualized research scenarios.Some were provided immediately from SKB’s computer.Others had to be specially gathered by SKB and forwarded later.To facilitate Dr. Laughren’s support for their product, SKB promptly and fully complied with all of his requests.These SKB and FDA principals operated on a “first name” basis in their fax exchanges.SKB officials were so friendly with Dr. Laughren, they addressed him as “Tom” in front of the committee podium.

When the FDA committee convened in Rockville, Maryland, on October 5, 1992, the FDA staff made their presentation first.SKB’s presentation followed.Dr. Laughren’s presentation was lengthy, and essentially constituted the FDA staff’s position on Paxil.In his overview to the committee, Dr. Laughren addressed many Paxil issues.Knowing the six (6) voting members would be interested in the “withdrawal” issue, Dr. Laughren felt obligated to explain to the committee FDA’s understanding on the Yugoslavia trial.That was that the Paxil withdrawal issue was not formally studied during the tests.Laughren told the committee in regard to the Yugoslavia trial:”There was no systematic effort really to look at the withdrawal syndrome, but in looking at the patients coming off of…(Paxil)…in the clinical trials, there was no strong suggestion of a withdrawal syndrome.”That was strange language coming from a top FDA official commenting on clinical trials.Proper science and clinical analysis do not permit a “strong suggestion” of anything without scientifically imposed controls to justify such a conclusion.

.At that juncture, SKB’s plan for the committee was proceeding smoothly.The FDA was in their corner, and the FDA staff had told the committee exactly what SKB had hoped they would.Then in the afternoon it was SKB’s turn to address the committee.SKB was not content to rest on Dr. Laughren’s commentary regarding the Yugoslavia study.SKB boldly went to the next level.SKB asserted to the committee that SKB had studied “whether or not there is a discontinuation syndrome in patients who are abruptly discontinued from Paxil.”The SKB representative continued:”To end with a brief discussion of whether or not there is a clear withdrawal syndrome, we have pulled upon the …(Yugoslavia trial)…”Then, SKB made an outrageous and categorical falsehood.The SKB representative told the committee SKB in the Yugoslavia trial attempted to “systematically assess a discontinuation syndrome.”This statement was in direct contradiction of Dr. Laughren’s earlier statement in the day that “There was no systematic effort really to look at the withdrawal syndrome.”Having refuted the FDA representation that there were no “systematic” tests on Paxil withdrawal, SKB then further claimed the tests were successful in that regard.The SKB representative told the committee they examined the data on the Phase II placebo group and that “few numbers of patients experienced any adverse event after being randomized off…(Paxil)…into the placebo group and the percentages are certainly very small.”What SKB failed to add was that no “adverse events” were reported on the placebo group because the eighteen (18) placebo victims’ symptoms were reported by SKB to have been “relapse” symptoms.Given the high bar established by SKB for relapse, the 18 placebo victims constituted a staggeringly high 45% of the placebo group.Had a reasonable clinical standard for “relapse” been set, it is quite possible 75% or 90% an or even higher casualty rate would have been recorded.

.Then a most startling and telling exchange occurred before the committee.The SKB proclamation that “systematic” withdrawal testing had been accomplished in the Yugoslavia trial caught the FDA staff representative, Dr. Laughren, completely off guard.Hearing the SKB representative directly contradict him on “systematic” withdrawal testing, and further hearing that placebo patients suffered no adverse effects after being taken off Paxil, Dr. Laughren interrupted the SKB speaker.From his perspective sitting in the audience, Dr. Laughren understood there were “crossed signals” before the committee between the FDA staff and SKB, and that the discrepancy required immediate correction.Dr. Laughren additionally understood there was now a gap in the testimony.Dr. Laughren understood the placebo group’s statistics meant nothing without comparison to the Paxil group.He then yelled up to the podium to the SKB representative, and the following exchange occurred:
Laughren:”Unfortunately you did not contrast…(the placebo group)…with the rates…(of adverse experiences)…in the patients who continued on…(Paxil)…”
SKB:”Right.I know the point you are going to raise, that it really does not look that different…”
Laughren:”That was my impression.”
SKB:”…from what you saw in the…(Paxil)…group, and that is a well founded point.So we very much agree with your earlier conclusion that there is no clear withdrawal syndrome but this was our attempt to try and investigate it in somewhat of a controlled fashion.”
In effect, SKB had just pulled off a coup.SKB had successfully and deceitfully maneuvered Dr. Laughren into making the case before the committee that withdrawal tests were conducted, and they proved Paxil “clean” on the withdrawal issue.SKB got Dr. Laughren to do their heavy lifting before the committee on a subject the FDA official had no personal knowledge of.SKB simply stepped aside and put icing on the cake with a polite “we very much agree with…(Dr. Laughren’s)…earlier conclusion that there is no clear…(Paxil)…withdrawal syndrome.”

.SKB’s tactic to skirt the withdrawal issue at the committee hearing was thus successful.After representation to them that Paxil had been systematically tested for withdrawal and that the tests were successful, the committee voted to approve Paxil.

seroxat withdrawal