ASTON VILLA V MANCHESTER UNITED

League Cup Final today at Wembley Stadium.

Just like to wish Aston Villa all the best.



Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

Glaxo and the Secret Avandia Tapes

Image: nestaquin.files.wordpress.com

Jim Edwards of BNET has wrote an excellent article regarding GlaxoSmithKline's diabetes drug, Avandia. As some of you know Avandia has hit the headlines with regard to its link to heart attacks. Glaxo, of course, deny this.

Edwards points out that Steve Nissen, the Cleveland Clinic researcher who first went public with a study showing that Avandia increases heart-attack risk, secretly taped a meeting he had with GSK officials and caught them dissembling.

A couple of names spring up in Jim Edward's article, notably Tachi Yamada and Chris Viehbacher

I urge you to read Edward's article over at BNET.

Secret Tapes Lay Bare Glaxo's Scorched-Earth Corporate Culture

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

Charlie 'Bling Bling' Nemeroff - Dined & Dashed by GSK

Image: asneurochem.org


I'm reminded of a famous quote by Mary Anne Rhyne, spokesperson for GlaxoSmithKline:

"Obviously doctors are very busy people, and their day is packed with patients. The question is how do doctors get information about medicines and new research into treatments and disease, and one of the easiest ways is this kind of presentation [”dine and dash”]. We think this is a benefit to both physicians and patients.” - Mary Ann Rhyne, GlaxoSmithKline spokesperson 11/11/2002

With that quote in mind, it should come as no surprise that Glaxo would 'dine and dash' prominent psychiatrists - in particular to promote the use of their medicines.

One such person was Dr. Charles B. Nemeroff. M.D., Ph.D. Nemeroff was the psychiatry chair at Emory University who failed to report hundreds of thousands of dollars in payments from GlaxoSmithKline.

Those payments [expenses] are now available for the world to see.

Page after page of meetings, dinner's, flights, top class hotels and 'miscellaneous' expense claims that makes the UK MP expense scandal seem trivial by comparison.

The GSK confidential papers were provided to the committee on finance pursuant to senate rule XXIX and can be downloaded HERE

Special thanks to Stephany who writes the Soulful Sepulcher blog for passing me the link

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

Louise Slaughter: Quote of the Day

Image: media.washingtonpost.com


And us Brits thought the NHS was bad!

"I even had one constituent—you will not believe this, and I know you won't, but it's true—her sister died. This poor woman had no dentures—she wore her dead sister's teeth, which of course were uncomfortable, did not fit. Did you ever believe that in America that that's where we would be? This is the last chance as far as I'm concerned, particularly on the export business. We have fallen behind, we're no longer the biggest manufacturer in the world, we've lost our technological edge. We have an opportunity to do that, but a major part of the success of that is getting this health care passed."

Rep. Louise Slaughter of New York, speaking at the health-care summit.



Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

GlaxoSmithKline Loses Bid for Immunity From Suicidal Behavior Lawsuits

Image: bahairants.com


Reproduced with kind permission.

Paxil’s manufacturer, GlaxoSmithKline [Glaxo] has lost its bid for immunity from suicidal behavior lawsuits. A Federal Court of Appeals in Chicago rejected Glaxo’s attempt to throw out a case arising from the suicide of a 23-year-old university student who was taking Paxil at the time she died. Her parents claim that Glaxo failed to warn that Paxil causes suicidal behavior.


Glaxo argued that FDA approval of a drug should shield its manufacturer from fault even when the company learns of harmful negative reactions after FDA approval. This theory, known as “preemption,” asserts that FDA approval “preempts” or nullifies any lawsuits against a drug. If Glaxo had succeeded, it would have made it extremely difficult for other injured consumers to seek compensation in Court.


In a unanimous opinion, the Court of Appeals rejected Glaxo’s arguments and refused to give immunity to drug manufacturers. The Court confirmed that injured consumers should be allowed to have their claims tried in a court of law and manufacturers must be held accountable for failing to disclose harmful negative reactions to their drugs—the manufacturers retain their obligation to warn of risks even after the FDA approves the drug for marketing.


Background to the case HERE

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

GSK - PAXIL TACTICAL PLAN - ISAAC Vs CASPPER

I understand that this particular document has been online since Nov 2009, however, I have just learned of its existence.

We have heard of Caspper before, I wrote about it here. Basically, the objectives of Caspper were to 'strengthen the product positioning and overcome competitive issues.'

Some of the target areas for topic were:

**Anxiety disorders [eg; panic disorder, social anxiety disorder, and Obsessive Compulsive Disorder [OCD]

**Long term use of Paxil

**Use in the elderly

**SSRi use in women

** Successful management of sexual dysfunction

Quite ironic that they should target these particular topics. Long term use of Paxil has always been a grey area, in fact I don't even think GlaxoSmithKline have any answers to what damage prolonged use of Paxil can cause those taking it... if they do, then they are hiding it well.

So with Caspper all alone in the world of GSK, he needed a little friend. Step forward Isaac... or 'Initiative for Social Anxiety Assessment and Care.'



ISAAC had pretty much the same intentions of it's ghostly friend, Caspper. It's target audience was psychiatrists.

ISAAC is designed to promote physician awareness about social anxiety and its occurrence within the population. An expert advisory panel of practitioners and academicians sponsored by Duke University Medical center in conjunction with SB have created the ISAAC program.

ISAAC provides real-time, patient-specific reporting to physicians. The 4-page color report enables physicians to see assessment data on the patients emotional disability, quality of life, comorbid conditions and severity of social anxiety disorder. These data give the physician a starting point from which to initiate a discussion with the patient. Physicians receive an administrative fee payment of $100 per patient for each patient who enrolls in the program for up to 10 patients ($1000 maximum).

Saeening with ISAAC has shown to increase new prescriptions of social anxiety disorder medications, including Paxil, by u p to 20%. In addition, it enables you to build value-added relationships with your key physicians and secure future detailing visits.

To enroll your physician into ISAAC:

1. Call the ISAAC sales consultant support line at 1-800-492-0312 to obtain program materials. Enter your 5-digit employee number, followed by your 5-digit pin number, which is "PAXIL" (72945).
2. Read the color overview brochure and become familiar with the ISAAC kit components.
3. Identify and orient physicians in your territory to ISAAC using the color brochure.
4. Enroll a physician into ISAAC by faxing the completed ISAAC Physician Participation/Consent form and W-9 form to InfoMedics at 1-800-934-6760, while still in the physicians office. Remember to include your name on the form.
5. An ISAAC Program Kit will be mailed directly to the physician. InfoMedics will call you when the kit is mailed, so you can set up an ISAAC kit orientation meeting with your newly enrolled physician.
6. You can check the enrollment status of your invited physicians, or secure more ISAAC supplies by calling the ISAAC sales consultant support line at 1-800-492-0312.
7. Follow up with your physicians regularly to ensure that they are screening and enrolling patients.
Target Audience: psychiatrists

The 1999 Tactical Plan for Paxil [Seroxat] can be downloaded via the Drug Industry Document Archive (DIDA) - HERE

You will note from this screen capture of the document that the makers of Paxil had some great ideas for a big promotion push. The page, entitled, 'YOU ASKED FOR IT!', seemed to be on a mission to PROMOTE, PROMOTE, PROMOTE...Even at the movies! All this, despite what we know about Paxil now... and what its makers knew about it back then, although they keep on denying this.



Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

RIP MICHAEL CORRY

Image: Wellbeingfoundation.com


Sad news. A great campaigner.

This from the Wellbeing Foundation:

We are extremely sad to announce that Dr Michael Corry has died after a short illness.

Dr Corry has been a fearless campaigner for the rights of mental health service users and all those suffering psychological distress; an opponent of bio-psychiatry and its exclusive reliance on psycho-pharmacology; an implacable campaigner for the abolition of ECT as a so-called 'therapy"; and a compassionate healer appreciated by thousands of patients.

His career spanned work as a hospital doctor in Uganda in the Amin era before he qualified as a psychiatrist and psychotherapist, work as a public service consultant psychiatrist in St Brendan's Hospital, Dublin, and private practice. His imagination and desire to get things done powered both his work as director of the EU-sponsored Resocialisation Project at St Brendan's in the early 1980s, and being a founder of the privately-funded Clane Hospital in Kildare, where he served as consultant psychiatrist from the early days.

He was one of the founders of the Institute of Psychosocial Medicine in Dun Laoghaire in 1987, which developed from a four-partner practice into an organisation with over 20 practitioners and nationwide renown as a healing centre, and which also provides training courses and encourages research and advocacy.

In 2004, Michael began a series of articles on depression in the Irish Times which led to the establishment of the monthly Depression Dialogues seminars which he moderated with his partner, Dr Aine Tubridy, and to the launch of the depressiondialogues website on Valentine's Day 2005.

In 2006 he, together with a number of mental health campaigners who supported his humanist, existential approach to the treatment of psychological distress, set up The Wellbeing Foundation to pursue the aim of substituting a rounded, holistic and compassionate approach to mental health for the exclusively pharmaceutical, and often dangerous and ineffective, approach of conventional psychiatry.

Most recently, his work in campaigning for an end to electro-shock 'therapy' led to a private members Bill being introduced into the Senate which would bar the forced use of ECT — use without the informed consent of any patient. While the Government did not accept the Bill as proposed, the Minister in charge, John Moloney, has initiated a comprehensive consultation process which we hope will lead to the first steps being taken towards ending this barbaric practice.

That would be a fitting memorial to Michael's memory.

Funeral arrangements:
Dr Corry's funeral will be a humanist ceremony. It will take place at Mount Jerome Crematorium, Harolds Cross, Dublin 6 on Thursday 25 February at 2.30 pm. No flowers, please — instead, donations if desired to the Blackrock Hospice.

Michael will be deeply missed by his beloved partner Áine; his dearly-loved children Louise, Amelia and Julian; their mother Anne, his brothers Martin and John, sisters Ann and Sr. Premula, and his extended family, many friends, colleagues and patients.

Condolences:

The Irish Times allows users to sign a Book of Condolences online:
http://notices.irishtimes.com/3607459

Fid

Read the new book, The Evidence, However, Is Clear...The Seroxat Scandal

By Bob Fiddaman

ISBN: 978-1-84991-120-7
CHIPMUNKA PUBLISHING

AVAILABLE FOR DOWNLOAD HERE


PAPERBACK COMING SOON

Glaxo Birth Defect Litigation Reveals Paxil Promoters on Speed Dial

Part III of Evie Pringle's investigation into GlaxoSmithKline, Paxil, [Seroxat] children born with defects and payments made to key opinion leaders [KOLs]



Evie has given me permission to publish this, her third article on this matter, in its entirety.

Part I can be read HERE
Part II HERE



Glaxo Birth Defect Litigation Reveals Paxil Promoters on Speed Dial

In the first Paxil birth defect trial against GlaxoSmithKline, much of evidence focused on the doctors on Glaxo's payroll involved in the corruption of the medical literature and seminars given to promote the off label use of Paxil with pregnant and nursing mothers.

On October 13, 2009, the trial of Kilker v Glaxo ended with a Philadelphia jury awarding $2.5 million in compensatory damages to the family of Lyam Kilker, after finding that Glaxo “negligently failed to warn” the doctor treating Lyam's mother about the risks of Paxil and the drug was a “factual cause” of the child's heart defects.

Glaxo's lead attorney at trial was King & Spalding partner Chilton Varner, and the family's lead attorney was Sean Tracey from Houston.

During his opening statement on September 15, 2009, Tracey told the jury that Doctor David Healy is “one of the most, if not the (most) world-recognized expert on pharmaceutical industry influence and the medicine, he is up there in the top five.”

Healy “is going to explain to you how GSK corrupted the medical literature,” he said, “how they used their money and influence to have doctors that they paid put out literature into the world so doctors ... could read literature that looked like literature, looked like science, smelled like science, appeared to be science, from very important people, people that were on boards, people that were professors, people that published hundreds of articles.”

Healy is going to explain to you that what they didn't tell people ... “is, we are paying these doctors to do all these things,” Tracey told the jury.

“There is a book, it looks like a telephone book,” he said, “of names of doctors, influential doctors, on their payroll, the names of these doctors you will see on this literature that looks and smells like science.”

“And just coincidentally, this science that they are going to parade before you, all seemed to help them,” he told the jury. “Some of this happened in the last couple weeks before this trial started.”

Advisory Panels and KOLs
While testifying, Tracey had Healy explain the concept of key opinion leaders (KOLs) and drug company advisory boards.

“When a pharmaceutical company is bringing a drug to market,” Healy said, “a few years before they bring the drug to the market they look at the academic physicians in the field and work out who will be the key people who will be the advocates for the drug.”

“They recruit advisory panels for the drug, which will be senior figures within the field who they believe they will be able to depend on to persuade the rest of their colleagues to think seriously about using this drug,” he noted.

In explaining a “national” advisory board, Healy said, when “a drug comes to market, they will have a range of senior people in the field, it could be 10 or 12 different people from different parts of the country whom they think are going to be the most influential in helping to get their drug moving within the market here in the U.S. or the U.K.”

“Then there is a further group of people down below,” Healy said, “who are called the key opinion leaders or KOL for short.”

“These, again, are fairly senior doctors,” he told the jury. “These are the people whom it is thought will go out and give lectures on the drug to the doctors who are actually doing most of the prescribing of the drug.”

In the early 1990s, Healy was on a Paxil advisory board around the time the drug was launched in the UK. People who did not think Paxil was a great product would usually be dropped from the advisory panel, he told the jury.

In fact, Tracey produced a Glaxo memo that stated: “if after this meeting anyone on the advisory board who doesn't passionately believe Paxil's uniqueness for anxiety should quietly be replaced.”

Naming Names
During the trial, Tracey wanted Healy to specifically testify about Doctors, Charles Nemeroff and Zachery Stowe, and apparently Glaxo did not want the jury to hear the sordid tale because their attorneys strongly objected.

On September 16, Tracy argued his case to the judge in chambers outside the hearing of the jury. “Doctor Nemeroff is generally considered, or was before his fall from grace, the most powerful man in psychiatry in the United States,” Tracey told the judge.

“Doctor Healy is uniquely qualified to talk about Doctor Nemeroff's role in the corruption of medical literature related specifically to Paxil as orchestrated by GSK and Doctor Nemeroff,” he argued.

“Same with Doctor Stowe,” Tracey said. “Doctor Stowe specifically carried out a campaign to market through GSK or GSK through Doctor Stowe to pregnant women and women of childbearing age.”

“I need to show the jury that an enormous amount of money changed hands between Stowe and Nemeroff and others,” he said, “and that all of these doctors were on GSK's Paxil advisory board.”

“It goes to the credibility of these doctors,” Tracey pointed out.

“These are the doctors that are writing the literature that is out there in the peer reviewed literature that doctors are relying on,” he told the judge.

These doctors were required ethically “by their universities to disclose to the Federal Government how much money GSK was paying them,” Tracey said. “They did not do that.”

He also wanted the jury to know that “Emory University has actually stripped Doctor Nemeroff of his chair over this very issue of failing to disclose payments from GSK,” he told the judge.

Tracey wanted to prove these allegations with testimony from Healy about Senator Charles Grassley's investigation of Nemeroff and Stowe and the results that were made public. In the end, the judge refused to allow Healy to testify about the amounts Nemeroff and Stowe were paid by Glaxo, why Nemeroff lost the chairmanship, or the disciplining of Stowe.

“Whether or not Emory had a battle with them about disclosure is not relevant in my mind,”the judge told Tracey. “What is relevant is that they were prominent individuals who wrote in favor of this drug, that they were on the advisory board, that they received honorariums of money, and that he believes in his opinion that these articles are wrong that they wrote.”

“He can offer his opinion that they were wrong and why they were wrong,” he said. “I am going to keep out the argument about the doctors being sanctioned for failing to disclose.”

Nemeroff's “credibility from Emory would involve a mini trial of the issue with Emory and him,” the judge said.

The Emory investigation, in fact, found Nemeroff was paid more than $960,000 by Glaxo, from 2000 through 2006, but listed less than $35,000 on his disclosure forms. All totaled, he had earnings of $2.8 million from speaking and consulting arrangements with drug companies between 2000 and 2007, but failed to disclose at least $1.2 million, according to Senate Finance Committee reports.

In 2008, Stowe was the primary investigator for a National Institutes of Health grant where the stated purpose was “to stimulate vigorous debate with the emphasis on the reproductive safety of antidepressant medications,” according to a June 2, 2009 letter to the president of Emory from Grassley.

Glaxo paid Stowe $154,400 for fifty-seven promotional talks in 2007. He also received $99,300 from Glaxo in the first ten months of 2008 for thirty-eight talks for antidepressants, according to Grassley.

During a deposition, Stowe testified that around “80% of his Emory salary ($187,000) comes from his NIH grants,” the letter notes. His total Emory salary was $232,000.

In a June 11, 2008 statement on the Senate Floor, in describing his investigation, Grassley said, “I have been looking at how drug companies try and influence medical care in America. Companies can do this by, for example, creating studies favorable to their drugs, by hiring doctors to promote their products, and in some cases even intimidating critics of their drugs.”

On this date, Grassley was announcing his investigation of Glaxo regarding revelations in reports filed in Paxil suicide litigation by Dr Joseph Glenmullen, showing the company had manipulated the numbers on adverse events related to suicidality in clinical trials all the way back in 1989, before the drug was FDA approved, to make it appear that Paxil did not increase the risk of suicidal behavior when, in fact, trial subjects on Paxil were eight times more likely to attempt or commit suicide than patients taking a placebo.

“So what did GlaxoSmithKline do with these reports?” Grassley said. “Well, the company tried to hide them.”

“They went to the judge and asked to have Dr. Glenmullen's report and all the confirming documents placed under seal-that means that no member of the public could see them,” he said. “In fact, Glaxo has been doing everything possible to ensure that this information remains under court seal.”

“It seems to me that GlaxoSmithKline tried to hide these reports because they seem to demonstrate what the company knew-that Paxil was associated with an increased risk of suicide based on the company's own studies,” Grassley noted.

“Essentially, it looks like GlaxoSmithKline bamboozled the FDA,” he pointed out.

For easy reference, psychiatric academics identified by Grassley's investigation to date, as not fully disclosing money from drug companies, include Joseph Biederman, Thomas Spencer and Timothy Wilens at Harvard, Charles Nemeroff and Zackery Stowe from Emory; Melissa DelBello at the University of Cincinnati; Alan Schatzberg, president of the American Psychiatric Association, from Stanford; Martin Keller at Brown University; Karen Wagner and A John Rush from the University of Texas; and Fred Goodwin, the former host of the radio show, “Infinite Minds,” broadcast for years by National Pubic Radio, before it was thrown off the air.

Paxil All-Star Team
During direct examination of Healy, Tracey introduced an exhibit on a 2002 forum called, “Perspectives on Psychiatry for the Future, Summary of Program Evaluations,” along with a list of doctors who gave presentations.

“What I would like to do is use this document to prove that these are a list of doctors that are out promoting Paxil for the defendant, and to have Dr. Healy explain, as he has published, how GSK sought to change the culture of how doctors view Paroxetine and pregnancy,” he told the judge.

Tracey went through several of the presentations and named off doctors that included Daniel Christensen, Zachary Stowe, Philip Perera, Dean Hamer, Dwight Evans, Karen Wagner, Katherine Beebe, and Prakash Masand.

Healy said he believed that most of the doctors mentioned were on the Paxil speaking team.

Zachary Stowe was listed for a presentation on the topic of, “Use of Antidepressants in Pregnant and Breastfeeding Women.”

Page 10 of the document asked: “As a result of the program, what changes, if any, will you make in your practice?”

Healy testified that after talks at this type of program, the audience will be asked to rate the points that are made. Tracey read some of the comments made by doctors attending the seminar, which included: “Possibly less fearful of treating pregnant women,” “Increased comfort in treating pregnant women,” “Increase use of Paxil - Will reassess the use or nonuse of SSRIs in pregnant/lactating clients,” and “More aggressive in treatment of special population, children and pregnant women.”

Healy testified that this document supported his opinion that Glaxo did influence doctors' prescribing practices with respect to Paxil and pregnancy and “they were quite successful at this.”

“I don't think you can find a single comment which says, I will be more cautious about treating pregnant women with Paxil,” he pointed out.

The jury was also shown a “Protocol” where Stowe had applied to Glaxo for funds to do research on the issue of Paxil in breast milk. Under the objectives for performing the study, there were five possible boxes to check, and Glaxo checked the box for “image enhancement.”

Healy knew of no article that ever appeared in peer-reviewed literature or was published in a reputable journal where the author said the purpose of the study was image enhancement. The odds of getting a paper published in a leading journal “would be remote to nonexistent,” if you told the journal that the reason for the study was to enhance the image of the drug, he said.

Tracey then introduced a January 10, 2000 email from Jillian, at the Cohn and Wolfe PR firm, to Scott Sproull and others at Glaxo, that showed Stowe was going on a publicity tour and would issue a press release for the Paxil breast milk study on Emory letterhead to lend credibility to the study in the media.

The email stated: “Scott, please review the attached press release and forward me any comments or edits.”

“As you may know,” Jillian said, “Dr. Stowe is on board for publicity efforts and Sherrie and I are coordinating time to meet with him next week to arm him with key messages for this announcement, which is slated for February.”

“We are sending the release for his review at the same time in efforts to secure distribution on Emory letterhead,” the email said, “as you know would provide further credibility to data for media.”

Healy had never hired PR firms to disseminate his published literature or lent his name to go on publicity tours for drug companies, he told the jury.

Tracy presented another protocol for a Paxil study, with Stowe as the investigator, where the objective checked was again “image enhancement.” As a scientist looking at the design of this protocol, Healy said, “this appears to be part of the positioning of Paxil as a drug that will be favorable to women of childbearing years.”

The budget for the study showed that Glaxo would pay $600 for each patient enrolled and the cost would be about $9,000.

Prior to 2005, Healy testified, he was not aware that Glaxo “spent any money to actually determine if the drug could be causing birth defects in human children.”

Tracey produced another document from a September seminar held in Philadelphia, at which Kimberly Yonkers was speaking to a Women's Health Advisory Board. Healy said Yonkers was a professor of psychiatry from Yale University and she was on Glaxo's Women's Health Advisory Board.

He told the jury that Yonkers was particularly influential “from the point of view of issues to do with women's mental health.”

Glaxo's Speed Dial
During the trial, Tracey wanted to use an exhibit that he referred to as a “telephone book,” full of influential doctors on Glaxo’s speakers' bureau for Paxil and have Healy go through some of the names.

“What I would like to do is put it into the record and have him identify who these people are,” Tracey explained to the judge in chambers, outside the hearing of the jury.

“Many of them are influential psychiatrists who have published on Paxil,” he said. “I want him to go through seven or eight names so later when the jury hears literature by these authors they will be able to put it into context.”

What I am going to do “is show the jury how all-encompassing their strategy for identifying and cultivating psychiatrists were in the country,” Tracey said.

“That's part of Doctor Healy's opinion,” he said, “how they identified these hundreds of doctors across the country to change the culture that existed.”

While Healy was testifying, Tracey introduced the 171 page list and had Healy identify some of the doctors.

Healy testified that Lori Altshuler is “a figure who is very well known in the field of women's mental health and would have written some key articles on the idea that it may be appropriate to use antidepressant drugs for women who are pregnant.”

He identified Vivian Burt as “a person who is a fairly big name in the women's mental health field and, again, a person who is an advocate for using antidepressants in women of childbearing years, and in particular, has talked regularly about the use of Paxil for women of childbearing years.”

He said Lee Cohen had been on the Paxil advisory board. “Dr. Cohen wrote an article that has since become quite famous,” he told the jury. “It became famous not because of the contents of the article, but because Dr. Cohen and co-authors, most of whom are on this list, failed to disclose the links to GSK or the other companies in the field that they had.”

Some of Cohen's co-authors on this study titled, “Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment,” included Lori Atshuler, Vivian Burt, Jeffrey Newport, Zachary Stowe, and Aadele Viguera.

On July 11, 2006, with the headline, “Financial Ties to Industry Cloud Major Depression Study,” the Wall Street Journal reported that, “the study and resulting television and newspaper reports of the research failed to note that most of the 13 authors are paid as consultants or lecturers by the makers of antidepressants,” and “the authors failed to disclose more than 60 different financial relationships with drug companies.”

Most of the authors, the Journal said, were psychiatrists at Harvard’s Massachusetts General Hospital, Emory University, and the University of California Los Angeles.

The Journal noted that Cohen was a longtime consultant to three antidepressant makers, a paid speaker for seven, and had research funded by four drug companies. Adele Viguera, associate director of the Mass General perinatal psychiatry program and professor at Harvard, failed to disclose a paid speaking relationship with Glaxo.

Lori Altshuler, director of the Mood Disorders Research Program at University of California Los Angeles, failed to disclose that she was a speaker or consultant for at least five antidepressant makers. "Two of her colleagues -- Vivien Burt and Victoria Hendrick -- were also authors who didn't report financial relationships they have with antidepressant makers," the Journal reported.

In an expert witness report for the Novak Paxil birth defect case, Dr Dee Mangin points out that: “The Cohen study was not a controlled study, used a highly selected population likely to have a high relapse rate and not representative of a primary care patient population.”

“In addition,” she said, “it is not clear that subjects had a tapered withdrawal, which would increase the likelihood of misclassification of withdrawal symptoms as relapse.”

Mangin reports that in the year the study was published, one KOL (with the name redacted), received $72,000 from Glaxo in the first 6 months of 2006 alone, for giving 28 talks, which works out to $2,880 per talk.

The next name on the list read to the jury was Katherine Wisner, “a figure who has published quite extensively on the issue of it being often quite good to treat women of childbearing years and even women who are actually pregnant with antidepressants,” Healy said.

“She puts forward the point of view that it may be more harmful to leave the condition untreated,” he told the jury.

Charles Nemeroff's name was on page 110. “He was probably the leading figure in the field or the leading person on this list,” Healy said.

Zachary Stowe was on page 151, and last name read was Kimberly Yonkers. Healy called her “extremely influential.”

Convenient Report Appears
During cross-examination, Varner asked Healy about a report that was co-published in the journals, Obstetrics and Gynecology and General Hospital Psychiatry, in September 2009, the very month that the first Paxil birth defect trial was scheduled to start, which she claimed was a joint statement from the American Psychiatric Association and the American College of Obstetrics and Gynecology.

The report was titled, “The Management of Depression During Pregnancy.” “The purpose of this deliberation,” Varner said to Healy, “was to come up with a statement from those two organizations that would assist prescribers in making their decisions about how to treat depression min pregnant women, correct?”

“We do not know that this was endorsed by APA,” Healy said. “We don't know if it was endorsed by ACOG.”

“We don't know whether it was a collection of individuals who just got together and because they belonged to both APA and ACOG, thought that they could put this kind of title on the piece,” he told the jury.

“It's correct, is it not,” Varner asked Healy, “that ACOG and APA describe some of the risks that were found (with SSRIs) that were, quote, extremely small and not replicated by other studies?”

“It's not correct to say that at all,” Healy said. “APA and ACOG have not said this.”

“What you got is a number of authors here who are linked to either APA or ACOG who have said this,” he told Varner. “The reason that I make this point is I have been party to processes like this on behalf of the British Association for Psychopharmacology and I can tell you exactly, if you want, how statements like this arise.”

“I'm not asking that,” Varner stated, cutting Healy off.

In fact, during the trial, the jury saw a January 2009 paper published in the ACOG Journal, by authors from Yale, in which Paxil was number two on a list of commonly prescribed “teratogenic” drugs.

It should also be noted that in 2006, about 30% of the American Psychiatric Association’s $62.5 million in financing, came from the pharmaceutical industry, which means the group received close to $19 million from drug companies in 2006 alone.

During Healy's testimony, Varner read a portion of the study that stated: “While some linked database reports find that compared to unexposed offspring, those exposed to Paroxetine during the first trimester are at higher risk. These results are disputed by other reports including several large case cohort studies.”

The actual study lists citations to papers that supposedly support this statement, which included papers by Louik and Alwan. On redirect, Tracey asked Healy: “Do those two papers stand for that proposition?”

“No, they don't,” Healy said. “They both show an increase in risk with Paxil.”

Tracey pointed out that this study “curiously enough came out this month.”

“It did,” Healy said. “This was quite curious in its own right.”

They then went over the names of some of the authors that were not read during Varner's questioning. Authors one and two were Kimberly Yonkers and Katherine Wisner. Healy testified that Yonkers and Wisner are affiliated with Glaxo and Yonkers was part of the women's health advisory board for Paxil. “They have been strongly associated with efforts to change the cultures,” he told the jury.

The disclosures for the study showed Wisner was on the speaker's board of Glaxo and Yonkers had received a research grant from Eli Lilly in the past year and had received a study drug from Pfizer for a National Institute of Mental Health trial.

Tracey noted that Glaxo was not mentioned in Yonkers' disclosures. “It's curiously not,” Healy said.

A likely explanation for Yonkers' non-disclosure is that she is a member of the DSM-V Task Force and according to the conflict of interest statement on the Task Force website, “Yonkers has agreed that, for the calendar year 2007 and continuing for the duration of her work on the DSM-V Task Force, her aggregate annual income derived from industry sources (excluding unrestricted research grants) will not exceed $10,000 during any calendar year.”

Diana Dell and Nada Stotland, the past president of the APA, were also co-authors and online disclosures show them listed as members of Glaxo speaker's bureau.

A website called “Bio-med Experts,” contains papers authored or co-authored by Yonkers. A “preview profile” lists Yonkers' co-publications with Katherine Wisner, Viguera Adele, Lori Altshuler, Diana Dell, Nata Stotland and a total of five with Lee Cohen.

She also co-authored 12 papers with Martin Keller, six with John Rush, and several with Allen Schatzberg and Zachary Stowe, all of whom were exposed by Grassley's investigation as not properly disclosing all of their financial benefits from drug companies.

Throughout the trial, Glaxo maintained that it did not market Paxil to women of childbearing years or pregnant women. In fact, in her opening statement, Varner told the jury: “You will hear from that chair the folks who made the marketing decisions at GSK.”

“They will tell you that GSK did not, repeat, did not target pregnant women, did not target women of childbearing age,” she said.

Yet, in a 2003 supplement titled, “Special Issues Related to the Treatment of Depression in Women,” for the Journal of Clinical Psychiatry, Yonkers published an article derived from the teleconference, “Treating Depression: New Choices for a Chronic Problem,” supported by an unrestricted educational grant from Glaxo, which promoted the use of SSRIs by women from youth to old age.

In the conclusion section, Yonkers wrote, “SRIs (SSRIs) appear to be an efficacious treatment for women suffering from various depressive disorders throughout the life cycle. These agents have expanded treatment options for many women, especially women who experience intermittent symptoms such as with PMDD, and side effects of SRIs are typically less severe than those of TCAs.”

“SSRIs appear to improve depressive symptoms in pregnant women and women suffering from postpartum depression, and they are a relatively safe option for breastfeeding mothers,” she said. “Additionally, their effectiveness appears to be enhanced by estrogen, making them a favorable treatment option for older women suffering from postmenopausal depression.”

In 2004, Yonkers, Cohen, and authors that included two Glaxo employees, published a paper in, “Psychosomatic Medicine,” on a study titled, “Paroxetine Controlled Release for Premenstrual MDysphoric Disorder: A Double-Blind, Placebo Controlled Trial.”

In the November 1, 2006 issue of “Journal of Women’s Health,” Yonkers, Cohen and others, published a paper titled, “Expert Guidelines for the Treatment of Severe PMS, PMDD, and Comorbidities: The Role of SSRIs.”

This work was supported by an educational grant-in-aid from Glaxo, the disclosure advised. “Several treatment modalities are beneficial in PMDD and severe PMS, but the selective serotonin reuptake inhibitors (SSRIs) have emerged as first-line therapy,” the abstract states.

“A burgeoning body of literature has emerged that supports the role of the SSRIs as first-line treatment of PMDD and severe PMS,” the authors wrote in the discussion section.

Back in December 2005, Yonkers was out doing damage control for Glaxo when the FDA changed the Paxil pregnancy category from C to D, and warned that, “studies in pregnant women (controlled or observational) have demonstrated a risk to the fetus,” and said the FDA “has determined that exposure to paroxetine in the first trimester of pregnancy may increase the risk for congenital malformations, particularly cardiac malformations.”

On December 14, 2005, the Washington Post wrote, Kim Yonkers “cautioned that the database studies that the FDA had used had limitations: Unlike controlled studies, Paxil may have been prescribed far more than other drugs, skewing the results.”

She also claimed the databases sometimes concealed unrelated medical problems that could alter outcomes, the Post reported.

“Depression is still undertreated,” Yonkers said. “Pregnant women in particular are immensely undertreated, and you worry about people being unduly frightened.”

Yonkers' September, 2009 report noted that in 2003, approximately 13% of pregnant women took an antidepressant sometime during their pregnancy. There are over 4 million babies born each year in the US, according to the CDC, which means about 520,000 pregnant women took antidepressants in 2003, and that would only cover live births. There is no telling how many infants may have died before birth, Mas a result of their mother's use of SSRIs.

In 2006, Yonkers became president of the North American Society for Psychosocial Obstetrics and Gynecology, after Diana Dell turned the job down. The April 2006 Spring Newsletter discussed this group's annual meeting, held in Hawaii no less. “The symposia at our 33rd Annual Meeting were fabulous, and we all appreciated the luxurious hotel and beautiful Big Island’s many charms,” the newsletter stated.

“Kim Yonkers’ unending drive, and with significant assistance from Meir Steiner and Claudio Soars culminated in our Sponsors contributing generously towards the symposia,” it said. The sponsors listed Mincluded the drug companies Berlex, Sepracor, and Wyeth.

Although the judge ruled that Healy could not elaborate on the Nemeroff and Stowe saga, during cross examination, Varner opened the door a crack by directly asking Healy about the reputations of the various doctors shown to be on Glaxo's payroll.

“The last question I have about the documents that you reviewed with Mr. Tracey yesterday goes to the portion of your testimony when you and Mr. Tracey talked about various doctors who had received honoraria from GSK for various speaking engagements,” she said.

“And you listed Doctor Altshuler, Doctor Wisner, Doctor Burt, Doctor Yonkers, Doctor Cohen, Doctor Nemeroff, Doctor Stowe, and Doctor Szuba,” she pointed out.

“They are generally respected in the medical community?,” she asked Healy.

“The issue of the degree of respect within the medical community is one that's open to question at the moment,” Healy said.

“It would be interesting to know what the degree of respect for Doctor Nemeroff or Doctor Stowe in the medical community is at the moment,” he added.

The latest news on Nemeroff came on January 4, 2010, when Pharmalot carried the headline: “Charles Nemeroff and the House That Glaxo Built?”, and Ed Silverman wrote, “the controversial psychiatry professor who became a subject of a US Senate Finance Committee inquiry into academic research and pharma industry influence, is joining the University of Miami’s Miller School of Medicine.”

“Of course, this means leaving his previous job at Emory University in Atlanta and so he’s just purchased a $1.9 million house in the Coconut Grove section of Miami,” Silverman said. “The 5,204- square-foot home has six bedrooms and seven bathrooms,” according BlockShopper.

Nemeroff “came to the Senate committee’s attention because he was accepting sizeable consulting fees from Glaxo at the same that he was the primary investigator on an NIH-funded grant for research into a Glaxo drug,” he pointed out.

“In any event,” Silverman wrote, “the new home appears big enough to house plenty of consulting materials.”

Amazingly, none of the KOLs or advisory panel members on Glaxo's payroll discussed above, who are so “generally respected in the medical community,” according to Varner, were recruited to testify for Glaxo in the first birth defect trial.

Ghostbusting

Yonkers now works at Yale, but she received her medical training at the Columbia College of Physicians and Surgeons, and completed a residency and fellowship at McLean Hospital, Harvard Medical School. Lee Cohen and Adele Viguera are still at Harvard.

The month after the trial ended, in November 2009, Grassley sent letters to ten medical schools asking them to describe their policies on plagiarism and ghostwriting and to identify any complaints or investigations of faculty members dating back to 2004. The Universities included Columbia, Yale, Harvard, Duke, Stanford, Johns Hopkins, University of Pennsylvania, Washington University, University of California at San Francisco, and University of Washington.

“Essentially, the companies are using the reputation of prestigious academic researchers and their institutions to promote the sale of drugs and devices,” Grassley said in the letters.

“Articles published in medical journals are widely read by practitioners and are relied upon as being objective and scientific in nature,” he wrote. “The information in these articles can have a significant impact on doctors’ prescribing behavior and, in turn, on the American taxpayer, as the Medicare and Medicaid programs pay billions of dollars for prescription drugs and medical devices. "

“Any attempt to manipulate the scientific literature, which can in turn mislead doctors to prescribe treatments that may be ineffective and/or cause harm to their patients, is very troubling,” Grassley said.

“Students are disciplined for not acknowledging that a paper they turned in was written by somebody else,” Grassley said. “But what happens when researchers at the same university publish medical studies without acknowledging that they were written by somebody else?”

Back July 2009, Grassley asked eight medical journals to describe their policies and practices regarding ghostwriting. “Articles published in medical journals are widely read by practitioners and are relied upon as being objective and scientific in nature,” he said in letters to the journals. “Concerns have been raised, however, that some medical literature may be little more than subtle advertisements rather than independent research.”

On January 3, 2010, the New York Times ran the headline: “Harvard Teaching Hospitals Cap Outside Pay”. “Senior officials at the two hospitals, Massachusetts General and Brigham and Women’s Hospitals in Boston, must limit their pay for serving as outside directors to what the policy calls “a level befitting an academic role” — no more than $5,000 a day for actual work for the board,” reporter Duff Wilson wrote.

“Some had been receiving more than $200,000 a year,” he said. “Also, they may no longer accept stock. “

As an example, the Times noted that Dr Daniel Podolsky was the original chairman of the Partners policy commission in 2007, when “he was the chief academic officer at Partners and a $191,000-a-year board member at GlaxoSmithKline.”

Partners HealthCare is also forbidding speaker’s fees from drug companies for any employee, “including nearly 8,000 with Harvard faculty appointments,” the Times reported.

Evelyn Pringle
(The Paxil Birth Defect Litigation Update Series is sponsored by the Houston law firm of Vickery, Waldner and Mallia at www.justiceseekers.com)

(Evelyn Pringle is an investigative Journalist and Researcher focused on exposing corruption in government and corporate America)



ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

PROMOTIONAL VIDEO - THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

Glaxo Drug Faces More Scrutiny

Image: malariaconsortium.org

By ALICIA MUNDY - Wall Street Journal

A Senate report that revives concerns about a GlaxoSmithKline PLC diabetes drug's link to heart attacks is putting pressure on the Food and Drug Administration to make changes to its drug-safety program.

People familiar with the situation say agency leaders held calls over the weekend to discuss how to address complaints from Sens. Max Baucus (D., Mont.) and Chuck Grassley (R., Iowa), who released a new report Saturday on the Glaxo drug, called Avandia.

The FDA is trying to assemble a timeline of what the FDA knew of risks associated with Avandia, these people say, and plans to call a meeting of an outside advisory committee in the next few months to look at recent information on the drug, which Glaxo reported as having global sales of £771 million ($1.2 billion) in 2009.

According to a two-year investigation by the Senate Finance Committee, Glaxo knew about data linking Avandia to elevated risk of cardiovascular events for several years, but played down the information and tried to suppress doctors who raised concerns. Starting in 1999, Glaxo executives complained to superiors about researchers who questioned Avandia's safety, the report says.

FULL STORY

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

IF YOU TOLERATE THIS THEN YOUR CHILDREN WILL BE NEXT

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

Musical Interlude - Jimmy Barnes

My favourite song of all time. This version was recorded live at the Sydney Opera House. 'Barnsie', best damn vocalist in the world.

FLAME TREES by Jimmy Barnes



Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

The Truthman is back - GSK Licence To Kill

Image: truthman30.wordpress.com


The Truthman has updated his excellent blog, GSK Licence To Kill with a summation of recent news regarding Glaxo's antidepressant, Seroxat.

He writes:

There has been a flurry of news in relation to Seroxat’s effects on pregnant mothers and a string of successful lawsuits in America has resulted in litigation for GSK ...

Indeed there has. Truthman had previously wrote about malformations in babies taking Seroxat - his article, Paroxetine Womb : Foetus Poisoning was written in 2007.

I hope The Truthman continues to post on a more regular basis. His hard hitting research is missed.

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

Confidential Government Report Recommends GSK's Avandia Be Pulled From The Market.

Image: media.cnbc.com


Hundreds of people taking Avandia, a controversial diabetes medicine, needlessly suffer heart attacks and heart failure each month, according to confidential government reports that recommend the drug be removed from the market, writes Gardiner Harris of the New York Times.

The article continues:

The reports, obtained by The New York Times, say that if every diabetic now taking Avandia were instead given a similar pill named Actos, about 500 heart attacks and 300 cases of heart failure would be averted every month because Avandia can hurt the heart. Avandia, intended to treat Type 2 diabetes, is known as rosiglitazone and was linked to 304 deaths during the third quarter of 2009.

“Rosiglitazone should be removed from the market,” one report, by Dr. David Graham and Dr. Kate Gelperin of the Food and Drug Administration, concludes. Both authors recommended that Avandia be withdrawn.

The internal F.D.A. reports are part of a fierce debate within the agency over what to do about Avandia, manufactured by GlaxoSmithKline. Some agency officials want the drug withdrawn because they believe there is a safer alternative; others insist that studies of the drug provide contradictory information and that Avandia should continue to be an option for doctors and patients. GlaxoSmithKline said that it had studied Avandia extensively and that “scientific evidence simply does not establish that Avandia increases” the risk of heart attacks.

The battle has been brewing for years but has been brought to a head by disagreement over a new clinical trial and a Senate investigation that concluded that GlaxoSmithKline should have warned patients earlier of the drug’s potential risks.

FULL STORY HERE

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

GNASH GNASH GNASH - Another GSK product pulled!

GlaxoSmithKline Consumer Healthcare Inc. announced yesterday it will stop selling denture creams containing zinc, after facing a number of lawsuits and questions about product safety.

GlaxoSmithKline said it’s a precautionary measure to prevent any potential long-term health problems in people who use zinc-containing Poli-Grip in excess of the amount indicated on the label.

FULL STORY

I previously wrote about Poli-Grip back in 2009





Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

Paxil Birth Defect Trial - Battle of the Experts

Image: waytoohip.com


Part II of Evie Pringle's investigation into GlaxoSmithKline, Paxil [Seroxat] and children born with defects.

Part I can be read HERE

Evie has given me permission to publish her article in its entirety on my blog.

Paxil Birth Defect Trial - Battle of the Experts
By Evelyn Pringle

In the first Paxil birth defect trial that resulted in a $2.5 million verdict against GlaxoSmithKline in October 2009, the infant, Lyam Kilker, was born with three heart defects; an atrial septal defect, a ventricular septal defect, and an interrupted aortic arch, after his mother took Paxil while pregnant.

Pregnant women cannot participate in clinical trials on drugs due to the risk of harm to the fetus. But after a drug has been on the market for a while, epidemiology studies can review the medical records of women who have taken a new drug while pregnant and the records of women who were not exposed to the drug while pregnant and compare the outcomes of the infants.

The plaintiff's experts, Doctors Ra-id Abdulla, David Healy, Shira Kramer and Suzanne Parisian, all testified that they believed Paxil (paroxetine) caused Lyam's defects, based in part, on the scientific literature on studies available on Paxil to date.

Battle of the Experts
During her September 15, 2009 opening statement, Glaxo's lead attorney, Chilton Varner, told the jury, the “experts in the case diverge sharply on how they interpret that body of scientific literature.”

The “plaintiffs' experts say that these scientific studies prove causation, they prove that Paxil causes cardiac defects and IAA,” she noted.

“They get there by ... lumping all cardiac defects together and looking at the numbers for cardiac defects as a group,” she said, “They also get there by rejecting any application of the tool of statistical significance.”

“The plaintiffs' experts will tell you they believe that as long as there is a difference between the two groups, and the Paxil group is higher than the control group, that's enough,” Varner told the jury.

“GSK's experts, on the other hand, are anti-lumping,” she said. “They say that you can't lump all heart defects together because they form for different reasons at different times by different processes and that you can't use evidence as to one kind of defect to imply that it also applies to another kind of cardiac defect.”

“And GSK's experts will tell you that statistical significance matters,” she stated, “that without applying the tool of statistical significance, you have no idea whether the difference between the two groups is real and meaningful or whether it is simply the operation of chance or coincidence.”

Studies Designed to Fail
During his September 15, 2009 opening statement, the family's lead attorney, Sean Tracey, told the jury: “You are going to hear from experts in this case that there are ways to design studies to fail.”

“If you truly don't want to know the truth,” he said, “very smart people can design studies that won't show you the truth.”

Dr Shira Kramer, an epidemiologist, testified as an expert for the plaintiffs. Kramer was asked to explain what is meant by “inclusive by design.” It's “a very, very serious problem that has been written about quite a bit,” she told the jury.

The reason for “the tremendous amount of concern and literature on this topic,” she said, “is many of these studies look like they have been designed to fail.”

It's the “deliberate design of epidemiological studies in such a way as to make it, if not impossible, extraordinarily difficult to detect relationship between an exposure and an outcome or a disease,” Kramer explained.

In the Paxil studies, many of the “designed characteristics have been such that they would minimize or make it more difficult to detect an increased risk,” she said. “And despite that, these studies have shown consistency in showing an increased risk of cardiac malformations associated with first trimester Paroxetine exposure.”

“The pressure is always against the ability to detect increased risk in the way these studies are designed,” Kramer said. “And, yet, despite that, we are seeing consistently elevated risks associated with Paxil, which is very, very important, very compelling, and very alarming actually.”

Kramer described the difference between association and causation as meaning that a single study with a finding of an elevated risk of birth defects would only show an association. “When you have a body of literature which shows through multiple studies consistently elevated findings, then you move from association in one study to causation, that this factor causes the disease,” she told the jury.

During closing arguments on October 8, 2009, Tracey told the jury that, “Defense lawyers can't stand the word 'causal.'”

“Causal” is the “kiss of death” for a defense lawyer, he said, because they know that is one of the questions the jury will be asked.

“The second question you are going to be asked,” he told the jury, is “Do you find that Michelle David's ingestion of defendant's drug Paxil was a factual cause in bringing about the heart defects?”

Epidemiology 101
While testifying, Kramer explained what is meant by relative risks and confidence intervals. “Our real interest in epidemiology is to measure rates of disease and excess risk,” she said. “But we also want to know really how precise is this measure.”

“And the precision of this measure is very much tied to the size of the population that you are studying and the number of exposed people,” she explained.

“In other words,” she said, “if we were to go into a large population and do the same study a hundred times, how many times out of a hundred would we find the same exact answer?”

“It is similar to tossing a coin,” she noted. ”If you are looking at the proportion of heads and tails in a coin toss, and you toss that coin a thousand times ... you are going to come up with that 50/50 proportion pretty much all the time.”

“That's a very precise answer,” she pointed out.

“So if you think about it that way,” Kramer said, “the larger the sample size, the larger the number of people that you study, the more precise your study estimate of that relative risk is.”

“And we estimate the precision of this relative risk by calculating something called confidence interval,” she told the jury. “If you were to repeat this study, let's say 95 times out of a hundred, what would that range be?”

For instance, where the relative risk in a study is 2, and they calculate statistically a 95 percent confidence interval with a range of between 1.5 and 2.5, the actual relative risk would fall somewhere in this range. That “means 95 trials out of a hundred would generate results in this range,” Kramer stated.

A test that is not statistically significant should not be discarded, she said. The “practice of statistical significance testing has been very much rejected in epidemiology because it was never developed really to study health or biomedical or human health problems.”

“This whole issue of rejection of a hypothesis, yes-no answers,” she explained, “was created for agricultural and industrial studies, whether or not a certain widget would be produced more efficiently in one production method than another or whether one field is more productive than another in an agricultural setting, these are easy yes-no answers and don't impact human health.”

A single-minded focus on significance testing is dangerous from a public health perspective, she said, because “it leads to discarding very important and relevant data and studies.”

Glaxo's Own Meta-Analysis
While testifying, Kramer explained that a “meta-analysis is an analysis of all the data that have been generated on a subject, so it's an agglomeration, a statistical analysis of all the data to come up with a summary risk for all of the studies together.”

“It's an attempt to overcome the issue of small sample sizes,” she said, “so the individual doing the meta-analysis will take all of the studies and will actually combine all of the results into summary statistics so that there is more power and there is some attempt to come up with a summary of all of the data that have been generated to date.”

The famous neuropsychopharmacology expert from Wales, Dr David Healy, also testified for the plaintiffs. During his testimony, the jury was presented with two charts from Glaxo's own website, showing the results of its own internal meta-analysis of the existing epidemiological studies.

The analysis had only been put on the website recently, he noted, maybe last year. One chart showed all birth defects lumped together, or combined, and the other showed cardiac birth defects.

In discussing the chart on combined birth defects, Healy said, “what everybody here needs to see is ... the little dots in the middle of the lines.”

If you “look at the pattern of dots there, you will see that of all the studies that have now been done, most of the dots fall on the right-hand side,” he noted. “This means that there is an increased risk that Paxil causes birth defects.”

“What I want you to look at here ... is the consistency,” he told the jury. “The dots are all falling on the right-hand side of the line, which shows an increased risk.”

“When GlaxoSmithKline added all this up,” Healy said, “you see the dot at the bottom, that is statistically significant.”

“They say there is no chance that Paxil is not causing these birth defects. Chance is gone. It is causing the birth defects,” he told the jury.

With the chart on cardiac birth defects, “again, you see the patterns of dots are mostly on the right,” Healy pointed out.

“What you see here at the end,” he said, “shows you a 1.5-fold increase in risk.”

This “comes from their Web site,” he stated, “I have had no part in trying to generate these data at all.”

While testifying, Healy discussed several of the studies in Glaxo's analysis, including the abstract for a presentation given at a conference in 2001, referred to as Unfred, which also had an author named Chambers. The full paper on the study, with Chambers as the author, had never been published but the data was in Glaxo's database.

“These data almost 10 years later,” Healy said, “showing a fivefold increased risk in heart defects and a tenfold increased risk in birth defects in general has not been published.”

Second Expert Opinion
During her testimony, Kramer also went over Glaxo's meta-analysis and explained what it showed. “GSK determined that the odds ratio for cardiac malformation as a broad class was 1.48,” she told the jury. “That is a 48-percent increased risk where they have combined data from all of the studies that they could find to date.”

“They also found an odds ratio of 1.67 for septal defects,” she said. “That is a 67 percent increased risk of septal defects associated with first trimester Paroxetine exposure for all the studies, for the three studies where there was actually data on septal defects.”

“And then for their summary odds ratio for right ventricular outflow tract obstruction defects,” she added, “the two case control studies which actually looked at those types of defects they found a summary odds ratio of 2.85.”

Most of the studies in the meta-analysis did not break down the cardiac defects into subcategories, Kramer said. “Either because they simply didn't have enough individuals in their studies or they set up their study rules which preclude them from doing so.”

It would be inappropriate to conclude that if a specific cardiac defect was not found in these studies that Paxil did not cause it, she said. “It would be very much inappropriate and erroneous to assume that because that subcategory is not mentioned ... that there is no increased risk associated with it.”

Kramer also testified about the Wurst study, published only 12 or 13 days before she
testified. The “GlaxoSmithKline meta-analysis that we just discussed was not
published,” she told the jury. The “Wurst study is the published version ... but
updated with one additional study.”

She was asked whether there was anything new or different in the Wurst study. “Well, the only thing that is different in ... the published version versus unpublished version,” she said, “is that they did not publish any subgroupings of cardiac abnormalities, birth defects in the published version.”

They only “analyzed and published the summary odds ratio for all cardiac birth defects combined,” she noted.

“And that summary odds ratio was very similar to the first one,” she said. “It's 1.46. That is a 46-percent increased risk for all cardiac defects combined.”

During cross-examination, Glaxo attorney, Todd Davis, told Kramer, “despite every single one of those studies looking at that those different patient populations over different time periods, there is not a single case in any of the studies that you talked about ... that identifies a patient who was exposed to Paroxetine or Paxil who had an IAA ...”

He noted that Lyam “was diagnosed with an interrupted aortic arch Type A,” and asked Kramer: “Can you -- can you point to the jury in your report where you mention anything about interrupted aortic arch of any kind?”

“I probably didn't because there is no specific study that analyzed that specific defect as a stand alone category,” she replied.

Kramer pointed out that “the epidemiological studies that have been conducted never individually analyzed the rates of the risk of interrupted aortic arch Type A associated with first trimester Paxil exposure.”

Because it is so very rare, she said, it would be impossible to do given the required sample size of “something over a million” subjects in order to conduct such a study.

“And since no such study was ever done,” she told the jury, “you would not expect to find any specific study that would have been able to analyze interrupted aortic arch Type A as a specific subgroup.”

Most of the studies, she said, “just reported on all cardiac malformations as a group and even those that ... did any kind of subgroup analysis restricted them to the most common subgroups.”

There were several studies where they restricted any analysis to subgroups where they had at least 200 women whose child suffered a specific birth defect, “which would automatically exclude IAA Type A,” she explained.

The Louik paper restricted the analysis to subgroups of 100, she said. But the “Louik study itself very clearly lists IAA as a specific cardiac malformation under conotruncal defects in their appendix where they list specific subgroups that they looked at and considered,” Kramer told the jury.

Louik Study
The Louik study was funded by Glaxo and conducted out of the Slone Epidemiology Center For Birth Defects. While Kramer was testifying earlier, Tracey put up a slide entitled, “Louik, et al - GSK involvement,” and told her to tell “the jury what GSK's involvement in this study was both publicly and then privately.”

Davis objected to this testimony. “There is nothing in Doctor Kramer's expert report that discusses anything about communications with GSK that somehow impacted the Louik study, so there has been no notice to GSK that she would be offering those opinions today,” he argued to the judge, while the jury was out of the courtroom.

“Your Honor,” Tracey told the judge, “this issue is something that has been percolating for a number of years.”

“This information about GSK's involvement and manipulation of the Louik study is something that has recently come to light,” Tracey said. “In fact, the deposition of their epidemiologist, Sara Ephross, was taken after ... the deadline for Doctor Kramer's report.”

“And, in fact, last week, while we were in trial,” he told the judge, “a Federal Court in Boston has ordered the Slone Epidemiology Center and GSK to turn over documents related to their involvement in this study.”

“Quite frankly,” he said, “the only people prejudiced by this are the plaintiffs, because GSK knows exactly what they did and when they did it, and we have been trying to get this information for some time.”

The judge excluded testimony about an email exchange between Dr Loiuk and Ephross.

But the comments by Louik, not seen by the jury, that appeared in court filings, stated in part: “we did not accept your changes. We are trying to avoid reinforcing the widely held perception that ‘statistical significance’ is a standard by which to judge the validity of a study finding. Significance is a function of study size, and while a single non-significant result might not be credible, in this case it supports findings from other studies and should not be dismissed for reasons of significance alone.”

In the affidavit filed in the Federal Court that ordered the release of the communications between Glaxo and the Slone Center, Louik wrote: “We rejected all of GSK’s suggestions that might have served to weaken our findings and conclusions.”

“GSK suggested that our ‘overall’ findings did not support the hypothesis that Paxil increases the risk of cardiac defects,” she stated. “We rejected that suggestion as well.”

Birth Defect Numbers Halt
When Paxil was first approved in the US, although Glaxo did not list the number of birth defect cases reported on the label, if a doctor contacted the firm wanting information, Glaxo sent out medical information letters with the number of birth defects reported.

Tracey entered three such letters into evidence. The first letter listed 36, the second 42, and the third 64. Then in the late 1990s, instead of including the number of birth defects reported, the letters started only listing the percentages, and after that they went to listing nothing, Tracey told the jury in closing arguments. “It goes from numbers to percentages to nothing.”

During the trial, a Doctor Hobbiger testified that Glaxo enacted a policy not to give doctors the numbers because doctors were incapable of putting them into context. “The funny thing about that to me,” Tracey told the jury, “is why were the doctors capable of putting the numbers in context when the numbers were low?”

“How did they magically become incapable of rational thought once the numbers became high?,” he pointed out.

He noted that a big thing happened in1998. Glaxo analyzed all the data they had been receiving on Paxil, and the person writing the report made the following finding: “The number of reports we have of women with birth defects is an alarmingly high number. We should not see this number of birth defects. It's four to five times what we would expect to see.”

“This is an internal document that nobody has ever seen before, not the FDA, not anyone,” Tracey said.

Earlier in the trial, he had showed the jury a letter from 1984, in which the FDA specifically told Glaxo they needed to tell the FDA “whether or not you receive any alarming information either in animal studies or in the human population.”

“And in1998 this is their language, not mine,” Tracy told the jury. “The incidence rate of congenital abnormalities as observed in data reported in this document is 13.3 percent.”

This is a problem, he said, because the background rate “is 2-1/2 to 4 percent, depending on who you believe.”

Birth Defect Info Request Refused
During the trial, the jury learned that in 2001, Glaxo received two emails from a woman specifically asking for any information Glaxo might have on birth outcomes of babies born to mothers who took Paxil.

The woman reported that she had recently gotten married and immediately became pregnant because they wanted lots of children. But when she was six months along, the pregnancy had to be terminated after tests showed the baby had a rare heart defect and would likely not survive to term or survive the necessary open heart surgery to save his life if born alive.

“To say the least, I was absolutely distraught with this news,” the woman said. “I thought this was something that I did ... because I stayed on the Paxil for selfish reasons.”

“I wanted to know if you could direct me to any information you might have of any woman that has taken Paxil and still had healthy babies,” the woman wrote in late May 2001.

“My husband and I are ready to try again to get pregnant in the next month or two,” she said. “I am so nervous.”

The woman had been on Paxil for over four years and loved how the drug worked for panic attacks. “I don't want to stop taking my miracle pill,” she wrote. “But, then again, if there is a chance that this might hurt or affect the baby, I want to know upfront.”

“And I will somehow stop taking it for the time being,” she added. “Please contact me as soon as possible. Please don't forget about me.”

The woman sent a second email on June 1, 2001, and stated: “This response is in regards to an e-mail that I had sent you previously.”

“I was asking to see if you have any or are in the process of any clinical trials for women who are currently on Paxil and pregnant,” she said. “I wanted to find out information to see how many women were on Paxil during pregnancy and if they were able to successfully have healthy babies.”

“I love the product, and I don't think I could have gotten through my panic attacks without the wonderful help of this miracle drug,” she told Glaxo.

“I just want to start to try and get pregnant again soon,” she wrote. “I do not want to put my unborn child through anything that would hurt him/her.”

“Please, if you do not have this information, where is this information held?” she wrote. “Does anyone do studies like this? Please, any information you may give me would be great.”

Glaxo wrote back on June 6, 2001. “We are attaching a copy of our current product information for Paxil. Please review the section on use during pregnancy,” the letter read.

“Further questions about your treatment should be directed to the physician, pharmacist or healthcare provider who has the most complete information about your medical condition,” they said. “Because patient care is individualised, we encourage patients to direct questions about their medical condition and treatment to their physician.”

“We believe that because your physician knows your medical history, he or she is best suited to answer your questions,” Glaxo wrote. “Our drug information department is available to answer any questions your physician or pharmacist may have about our products.”

Glaxo sent the woman basically a form letter on June 13, 2001, asking for a signature on an authorization to get her medical records, but provided no answers to the woman's questions.

On a Glaxo internal document with the same date, the box “almost certain” was checked for “Relatedness assessment to medication.” There is no higher category of certainty that Paxil caused the birth defect than the box checked.

Jane Nieman, a Glaxo employee at the time, was listed as the contact person on a report sent to the FDA. Before trial, Tracey took Neiman's deposition and questioned her about Glaxo's policy for reviewing adverse event reports prior to showing her the documents about the mother who aborted her baby that said it was “almost certain” that Paxil caused the defect.

Portions of the deposition were played for the jury. Before Nieman knew about the “almost certain” document, she testified that when a causality assessment was made a physician was involved and it was a team effort. “I think it is very much a team,” she said. “I think that's really how they worked.“

“They would look at the case and they would form a medical opinion as to whether there was a possible, probable or no causality,” she stated.

Tracey told the jury that Nieman was “stunned” when she saw the document with “almost certain,” checked so he asked her whether she was uncomfortable with the fact that the assessment was made. “It was made. It's a fact,” she said in the deposition. “I don't feel uncomfortable with it.”

Later in the deposition, Nieman claimed she did not know who checked that box. “Somebody from GSK filled that in,” she said. “There’s a possibility someone made a mistake and checked the box wrong.”

During the trial, Glaxo had Doctors, Stephen Hobbiger and Judith Jones, testify that the checked box was definitely a mistake because they don't do causality assessments in the US citing “almost certain,” that they only do it that way in France.

During cross-examination, Tracey showed Jones a causality assessment from Canada that had “almost certain,” and she said well, maybe they do it that way in Canada. He then showed her one from the US that also had “almost certain.”

In the documents sent to the FDA, Glaxo did not include the words “almost certain,” according to testimony by Dr Suzanne Parisian, a former FDA official.

Glaxo also never changed the Paxil label after receiving the report and the rules are that a drug company has to change or strengthen the warning on the label, if “they have reasonable evidence of an association with the report for their product and an adverse experience,” Parisian explained.

Smoke and Mirrors
Throughout the trial, Glaxo attorneys focused on Lyam's IAA defect and harped on about “statistical significance,” when as described above, the studies were designed to ensure that a “statistically significant” increased risk in rare defects would not be detected.

During closing arguments on October 8, 2009, Tracey told the jury he wanted to talk about Glaxo's “obsession” with ignoring the fact that Lyam had three cardiac defects. “All they want to talk about is this interrupted aortic arch,” he pointed out.

The “reason that they want to talk about it so much is because they know this, they're never going to look for this,” he told the jury.

“The only ones that would have the money, time and effort to undertake a study of 1.5 million women would be them,” Tracey said. “And they know it's never going to get done.”

“So they're in a can't lose position if you buy their argument,” he told the jury.

“They admit, though,” he pointed out, “that they have two cases now in their own database of interrupted aortic arch.”

During closing arguments, Tracey recounted how he had put up Glaxo's own meta- analysis from the company's website, with 9 different studies, and “each and every one of them says Paxil increases the risk of heart defects,” he pointed out.

“And this is a document that I know pains them,” Tracey said. “Because ... the author of their own meta-analysis, Charlie Poole, the author that they hired ..., when he looked at the data privately, privately, outside of courtrooms, he said: This begs the key question. Do we think the best explanation at present is that first trimester paroxetine use increases the birth prevalence of cardiac malformations? I do.”

“I do,” Poole said. “Outside the courtroom,” Tracey told the jury.

“But when this document got published, by the time it went through everybody's hands, by the time the editing was over, that statement disappears,” he said. “It is not in the npeer-reviewed literature.”

In her closing, Varner told the jury, “the final fact that matters is that no regulatory agency or medical organization has ever concluded or said that Paxil causes birth defects. Only plaintiffs' experts have said so and in this courtroom,” she said.

In his final summation, Tracy said, “I want to put something to bed that Ms. Varner said immediately, and that's this: Ms. Varner said that no regulatory agency in the world has ever said Paxil is a teratogen.”

“That is simply untrue,” he told the jury. “This is what the FDA says right here, There is positive evidence of human fetal risk,” reading from a letter from the FDA.

He also noted that Paxil's label, under “Teratogenic Effects” states: ”Epidemiological studies have shown that infants exposed to first trimester exposure to paroxetine have an increased risk of congenital malformations, particularly heart defects.”

Evelyn Pringle
epringle05@yahoo.com
(The Paxil Birth Defect Litigation Update Series is sponsored by the Houston law firm of Vickery, Waldner and Mallia at www.justiceseekers.com )



ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING

GlaxoSmithKline/XenoPort get negative response from FDA

Image: i.dailymail.co.uk


UK drugs giant GlaxoSmithKline and partner XenoPort have received a negative response from the US Food and Drug Administration regarding their marketing application for their restless legs syndrome (RLS) drug.

FULL STORY

Fid

ORDER THE PAPERBACK
'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman
SIGNED COPIES HERE OR UNSIGNED FROM CHIPMUNKA PUBLISHING