Jim Thomson and the EAASM – what’s really going on then?

I notice a bit of news recently from the European Alliance for Access to Safe Medicines (EAASM).

It seems that the EAASM reckons the parallel trade in drugs in the EU puts patients at risk… but there is world of difference between the legal parallel trade and drug counterfeiting. But not as far as my old mate Jim Thomson is concerned and the EAASM is Jim’s latest drug company funded venture.

The cynical amongst you might think that Jim and the EAASM only link the parallel trade with counterfeit drugs because the EAASM has actually been set up with pharmaceutical money in order to play its part to tarnish a legitimate practice (parallel trading) that poses competition to the major pharmaceutical industries.

The cynical amongst you might think that – I couldn’t possibly comment…

Parallel trading works like this: prices for patent medicines are generally set lower in, for example, Greece, Spain and France than in the UK, Germany and Holland. Drug companies negotiate the highest price they can with each separate government. Traders buy ‘low’ in the ‘cheap’ countries, transport the products to the ‘expensive’, repackage them in the language of the importing state, and sell them there at a higher price.

Just a thought, but if drug companies were always fair in the price they charged for their patent medicines and they had a fixed price for each medicine, then there would be no parallel trade…

Anyway for more about Jim and his previous good works please read on:

What a tangled web we weave…

National Depression week 2005…

Depression Alliance…

Yet more on Cymbalta marketing…

Jim used to be Sales and Marketing Director for Innervate. Read more on the links below about this:

Innervate Ltd, Jim Thomson and the Centre for Mental Health

The good works of the Diabetes Monitoring Forum

More Astroturfing?

Advertisement

Marty Keller – Key Opinion Leader – do the FBI want to talk to him about Study 329?

It seems the FBI might want to know more about Study 329 and it’s ‘author’ ‘Marty’ Keller… “The prosecutor and FBI “were quite interested in how Study 329 was used to promote Paxil for teenagers and kids by clinical researchers Glaxo had underwritten”.

If the FBI are looking in and want more information, can I suggest typing “Study 329” or “Keller” into the search box on the left. Happy reading!

GlaxoSmithKline’s Study 329 of medication for adolescent depression failed to demonstrate any benefit for paroxetine over placebo in adolescents and demonstrated a worrying profile of adverse events for paroxetine.

The study was ultimately published in 2001 by the Journal of the American Academy of Child and Adolescent Psychiatry with Keller as the primary author. This misleading paper has been a focus of interest for Healthy Skepticism since 2002. In 2003 they wrote to the Editor of JAACAP raising concerns about the misleading reporting by the authors that exaggerated benefit and downplayed adverse effects. (They also questioned editorial functioning, which drew an angry response from the Editor).

In 2004 CMAJ published an Editorial which showed that in 1998 an internal GSK document clearly acknowledged that GSK were aware that 329 was negative. A subsequent law suit by New York Attorney General, Eliot Spitzer, was settled out of court.

In 2006, HS wrote to the Lancet to point out that internal documents from another United States law suit (Smith versus GSK) revealed further concerns about study 329:

The study was ghostwritten – see here.

Misleadingly positive interpretations of the study were promoted to drug reps and other GSK staff – see here.

An illusion of efficacy was achieved by re-inventing primary and secondary end points – see here.

Eventually GSK had to acknowledge the failure of all three of their child and adolescent paroxetine depression studies – see here.

Click here for Peter Mansfield’s summary of all trials of newer antidepressants in children and adolescents.

Click here for J & E Jureidini’s summary of citations of the Keller paper.

FDA Didn’t Get Paxil/Seroxat Risk Documents

From Furious Seasons:

This is just up on the excellent WSJ Health Blog. The news is that the FDA got left out of some of the documents around suicidality data on Paxil. From the paper’s Alicia Mundy:

“Here’s how things went down. Plaintiffs attorneys in Los Angeles got permission last year from Glaxo’s defense team to give the Justice Department (at DOJ’s request) access to a ton of confidential material, including the right to discuss details about it all with the plaintiffs lawyers. Glaxo had insisted previously on having them sealed in Federal Court. “Several months later, when the plaintiffs lawyers at Baum Hedlund asked for permission to give the same stuff to the FDA, Glaxo’s defense team balked.

“On Oct. 15, 2007, Glaxo’s outside lawyers at King and Spalding in Atlanta said that the FDA had already looked at Paxil and suicide, and therefore, they wrote, ‘If the FDA wanted additional information, such as the internal documents you propose providing it, they could have requested them from GSK.’

“That prompted Baum Hedlund’s Skip Murgatroyd to tell the Health Blog, ‘How the heck can the FDA ask for information they don’t have, when they don’t know about it?’ Fair point. An FDA official, who asked for anonymity, said the same thing to the Health Blog when we read the letter to him.”

There’s more to this, so go read it. As a journalist, it’s interesting to me that the Journal is all over this story while the New York Times is virtually silent.

I think Phil is right to make this last point – where’s the mainstream media reporting of all of this?

US Investigation Into Glaxo And Paxil/Seroxat Widens

This just in from Pharmalot:

A Justice Department investigation of Glaxo’s handling of the marketing and safety research of its antidepressant, appears to be widening, The Wall Street Journal reports. The drugmaker confirmed that a previously disclosed Colorado-based Justice Department investigation of marketing practices also includes the US Attorney’s office in Boston and is being coordinated by the agency in Washington.

At a meeting convened in Boston by an agency prosecutor last year, plaintiffs’ lawyers representing families suing Glaxo say they were asked about info, documents and depositions concerning Paxil’s potential link to suicidal behavior in adolescents and adults, and how the company portrayed that risk to doctors and the FDA, the Journal writes.

This follows a recent demand by Chuck Grassley, the ranking Republican on the Senate Finance Committee, for an FDA investigation. Glaxo issued a statement to the paper saying it has responded to questions from the government and cooperated fully with the department, but couldn’t comment further, but has requested a meeting with Grassley’s staff to clarify “misunderstandings.”

According to the Journal, on June 14, 2007, two lawyers from the Los Angeles law firm of Baum Hedlund met in Boston with Assistant US Attorney Patrick Jasperse, a lawyer in the Office of Consumer Litigation, FBI agents and representatives from the Health and Human Services Department, at the Justice Department’s request.

The lawyers, George “Skip” Murgatroyd and Karen Barth Menzies, said in interviews that they were asked in detail about info they had collected for lawsuits about what Glaxo told the FDA about Paxil’s potential risk of suicidal behavior, between 1989 and 1992, while the drug’s approval was pending, the Journal writes.

They were also asked if they had info about any activities by company reps involving the promotion of Paxil’s safety and efficacy for teens and children, they told the paper. “They (government officials) wanted to know about the research Glaxo did that said there were no suicidality problems, and what the data really showed,” Murgatroyd tells the Journal.

Glaxo says it didn’t promote Paxil off-label to adolescents. However, the paper writes that, in 1998, the FDA sent a warning letter to SmithKline Beecham, which merged with Glaxo Wellcome in 2000, about a T-shirt distributed “by or on behalf of SKB” at a children’s health affair in Florida, saying the T-shirt “is promoting an unapproved use of Paxil.”

In setting up the conference, Menzies tells the paper, Jasperse told her his efforts “could take a while.” The Justice Department said it doesn’t comment about ongoing cases. A different witness who testified later in Boston confirmed to the Journal that he was asked about Paxil’s safety data, but he declined to give the date of his appearance.

The Justice Department was particularly interested in controversial documents disputing research conclusions that Glaxo submitted to the FDA on suicidality. Those documents had been sealed at Glaxo’s request, but the Journal reports the Justice Department asked Glaxo to release confidential material to them prior to their meeting.

In the meeting, Justice officials asked detailed questions related to a controversial medical analysis paid for by Glaxo that has become known as the infamous Study 329, which indicated Paxil was safe and efficacious for teens and children. You can read about 329 here.

The 2001 study has come under fire from several independent medical researchers. The prosecutor and FBI “were quite interested in how Study 329 was used to promote Paxil for teenagers and kids by clinical researchers Glaxo had underwritten,” Murgatroyd tells the paper.

The company defended its safety research in a statement given the Journal: “We acted properly and responsibly in the conduct of our clinical trials program for Paxil, documentation and submission of results from studies to regulators, and communication of important safety information to regulatory agencies, the scientific community, and the public.”

And this is interesting: Glaxo hasn’t allowed Baum Hedlund’s lawyers to share with the FDA the same sealed info the company gave the Justice Department. Glaxo’s outside counsel wrote, “If the FDA wanted additional information, such as the internal documents you propose providing it, they could have requested them from GSK,” in an October 15, 2007, letter. This is the letter.

This past March, UK authorities concluded a four-year investigation on whether Glaxo failed to inform regulators in a timely manner about a link between Paxil and suicidality in children and teens. But the government didn’t pursue a criminal prosecution of Glaxo because UK laws were unclear on whether companies were obligated to report certain drug data.

But the regulator said it was “concerned that GSK could and should have reported this information earlier than they did.” Glaxo at the time said: “We firmly believe we acted properly and responsibly.”

Glaxo marketing strategy under threat from the FDA

What I find most amazing about this story is this quote from Christopher Viehbacher, president of North American pharmaceuticals for Glaxo. Says Viehbacher “…it is harder to get approval for variations of drugs because the FDA now demands to know why they are better than the original.”

Well excuse me, Chris – what do think the FDA should do?

A well known tactic that companies like Glaxo undertake in order to maximise revenue from best selling drugs about to go out of patent is this: they simply create a slightly different version of the drug and start to market the ‘new, improved’ version. Maybe it’s simply a slow release version, or maybe it has a few different molecules. Whatever, the important thing is that it must be able to be patented once again.

And now the FDA is spoiling the party by having the cheek to ask Glaxo to prove the new versions of drugs are better than the old versions… the truth is they’re better for the drug companies because they make yet more money for them.

Here’s the story from This is Money:

The strategy of GlaxoSmithKline to extend sales of its biggest-selling drugs is under threat from the US Food and Drug Administration, critics of the agency say.

The FDA is accused of posing new questions to Glaxo as it re-submits previously approved drugs.

Nomura analyst Mike Ward, said: ‘The whole industry is finding it difficult because the FDA is understaffed, and focusing on things they think are more innovative and important.’

The agency approved Glaxo’s Parkinson’s disease treatment Requip XL, a modified version of the older drug Requip, at the weekend. But delays mean a generic version is already on the market.

Christopher Viehbacher, president of North American pharmaceuticals for Glaxo, said it is harder to get approval for variations of drugs because the FDA now demands to know why they are better than the original.

More on Paxil and suicide – “Glaxo was aware of this risk, and hid it”

This from the Wall Street Journal By ALICIA MUNDY and JEANNE WHALEN (with thanks to Truthman30):

Unsealed Report Claims Suicide Risk Was Miscalculated

WASHINGTON — GlaxoSmithKline PLC faces new questions about whether it deliberately misrepresented data on suicide risk for its antidepressant Paxil when it applied for the drug’s approval to the U.S. Food and Drug Administration at an advisory committee meeting in 1991, a charge the company has denied.
A study by a Harvard psychiatry instructor, underwritten by plaintiffs’ lawyers and previously kept under seal by a court order, says that Glaxo “improperly” counted patients taking placebos during clinical studies. From 1989 through 1991, Glaxo then submitted information to the FDA that indicated no major difference in risk of suicidal behavior, or suicidality, as doctors call it, between patients who took Paxil and those who took a placebo.

However, Glaxo’s counting minimized the differences between suicidality rates in the Paxil and placebo groups, according to the report. For instance, the company counted placebo patients who had attempted or committed suicide before the study formally started, which enhanced the results for Paxil.

The real risk for suicidality from Paxil, says the report’s author, Joseph Glenmullen, was eight times its risk for patients on placebo. “Glaxo was aware of this risk, and hid it,” Dr. Glenmullen’s report states. The drug was approved for sale in the U.S. in 1992. Dr. Glenmullen said, in an interview Thursday, that if Glaxo had given the agency the “correct” data in 1991, the FDA would likely have added warnings about the risk for suicidality when it approved Paxil

In 2004, the FDA called for added warnings on popular antidepressants known as selective serotonin-reuptake inhibitors, or SSRIs, about potential links to suicidal behavior. In 2006, Glaxo sent a letter to doctors stating that its studies showed that the risk of suicidality in depressed adults was 6.7 times as high in patients taking Paxil as in those taking a placebo.

Thursday, Sen. Chuck Grassley, an Iowa Republican, released Dr. Glenmullen’s study and a letter to the FDA, asking it to investigate the original approval process for Paxil and Glaxo’s application in light of Dr. Glenmullen’s report.

A Glaxo spokeswoman emailed a company statement that was originally issued Feb. 6, when an earlier version of Dr. Glenmullen’s report was first unsealed by a court. That version was missing nine pages that included information on Glaxo’s counting methods.

“GlaxoSmithKline has provided the U.S. Food and Drug Administration over the years with numerous reports from its clinical studies,” the statement says. “As soon as GlaxoSmithKline became aware of a potential increased risk in certain populations, it proactively brought it to the attention of FDA and other regulatory bodies.”

The statement notes that Dr. Glenmullen was hired by plaintiffs’ lawyers, and calls his report “unscientific and misleading.”

Sen. Grassley also raised concerns about a British investigation that concluded this year that Glaxo should have alerted British regulators earlier than it did about a link between Paxil and suicidal behavior. He said evidence in the two reports raises questions about whether the company kept U.S., as well as British health officials, in the dark.

In March, British authorities concluded a four-year investigation on whether Glaxo failed to inform the U.K. drug regulator in a timely manner about a link between Paxil and suicidality in children and teens. They said they saw no basis for criminal prosecution of Glaxo because U.K. laws were unclear about whether companies were obligated to report certain drug data. But the regulator said it remained “concerned that GSK could and should have reported this information earlier than they did.”

Glaxo at the time said: “We firmly believe we acted properly and responsibly.”

Paxil was made by SmithKline Beecham, which merged with Glaxo Wellcome in 2000. SmithKline’s former top executive, Jean-Pierre Garnier, who was Glaxo’s CEO until last month, said in a 2006 deposition in a lawsuit that the original data given to the FDA shouldn’t have included some of the placebo patients. In another 2006 court document, Glaxo “admits that five of six ‘attempted suicide’ events” in the placebo group took place before the studies began.

During the 1991 meeting, members of the FDA’s advisory committee repeatedly said they wished there were more data to review on suicidality, but, the report said, “unbeknownst to the committee, the data already existed.”

Write to Alicia Mundy at alicia.mundy@wsj.com and Jeanne Whalen at jeanne.whalen@wsj.com

Missing report pages seen for the first time – proof that Glaxo hid paxil risk?

This from Pharmalot:

Last week, US Senator Chuck Grassley called for a probe into Glaxo and the FDA over their handling of the Paxil antidepressant. At issue are the long-standing allegations that the drugmaker knew about suicide risks in children for nearly 15 years but obscured evidence.

In demanding the probe, Grassley cited a report prepared by Joseph Glenmullen, a Harvard psychiatry professor, for litigation in federal court in California over Paxil side effects. The report was unsealed earlier this year, but was missing some pages. Last week, those pages became available and include a section that describes in some detail how Glaxo allegedly manipulated so-called placebo suicides.

These are deaths that occur among patients who are taken off other meds so they can participate in a trial. “The rationale from washing out all drugs is to prevent them from confounding the results of the study, so that all patients start out the study in similar conditions,” according to the Glenmullen report, which goes on to maintain Glaxo “improperly” minimized the differences between Paxil and placebo suicide data in order to obtain favorable results.

As a result, the actual suicide risk was eight times its risk for patients on placebo. “Glaxo was aware of this risk, and hid it,” the report states, as The Wall Street Journal noted over the weekend in a story that refers to the previously missing pages. Here is the full report and page 47 offers a summary of Glaxo’s efforts.

US senator seeks FDA probe of Glaxo’s Paxil data – was safety information withheld in the USA?

U.S. Sen. Charles Grassley asked U.S. regulators on Thursday to investigate whether drugmaker GlaxoSmithKline Plc withheld data about a risk of suicide linked to its anxiety disorder drug Paxil.

Grassley, a Republican from Iowa, said in a letter that a British regulatory agency had found Glaxo knew Paxil was associated with a higher risk of suicidal behavior in adolescents as far back as 1998.

“I would like you to take a look at the information that agency gathered and determine if the company has withheld safety information here as well,” Grassley wrote in the letter to the heads of the U.S. Department of Health and Human Services and the Food and Drug Administration.

Grassley also asked the FDA to review a report by a Harvard psychiatrist who has submitted information as part of several lawsuits. The report found Glaxo “had to know of Paxil’s suicide risk when it sought FDA approval for the drug,” a statement from the senator said.

The senator has long been critical of both the FDA’s and the pharmaceutical industry’s handling of drug safety information, digging into various cases since Merck and Co Inc’s withdrawal of its pain drug Vioxx in 2004.
Antidepressants, including Paxil, have stirred particular concern after studies showed an increased risk of suicidal thoughts and actions in children and young adults taking the drugs. The FDA called for new warnings in 2004.

Paxil, known generically as paroxetine hydrochloride, is a type of antidepressant known as a selective serotonin reuptake inhibitor and is sold in Britain as Seroxat.

FDA spokeswoman Sandy Walsh said the agency would review Grassley’s request and respond to him.
Grassley asked Glaxo in February when it knew of Paxil’s risks. Glaxo has said it provided the FDA a variety of information on suicidal risk in Paxil patients.

“We do feel like we gave Senator Grassley a full and fair response,” company spokeswoman Mary Anne Rhyne told Reuters on Thursday.

Paxil Study 329 – lest we forget

Thanks to Healthy Skepticism and Pharmagossip for this:

GlaxoSmithKline’s Study 329 of medication for adolescent depression failed to demonstrate any benefit for paroxetine over placebo in adolescents and demonstrated a worrying profile of adverse events for paroxetine.

The study was ultimately published in 2001 by the Journal of the American Academy of Child and Adolescent Psychiatry with Keller as the primary author. This misleading paper has been a focus of interest for Healthy Skepticism since 2002. In 2003 they wrote to the Editor of JAACAP raising concerns about the misleading reporting by the authors that exaggerated benefit and downplayed adverse effects. (They also questioned editorial functioning, which drew an angry response from the Editor).

In 2004 CMAJ published an Editorial which showed that in 1998 an internal GSK document clearly acknowledged that GSK were aware that 329 was negative. A subsequent law suit by New York Attorney General, Eliot Spitzer, was settled out of court.

In 2006, HS wrote to the Lancet to point out that internal documents from another United States law suit (Smith versus GSK) revealed further concerns about study 329:

The study was ghostwritten – see here.

Misleadingly positive interpretations of the study were promoted to drug reps and other GSK staff – see here.

An illusion of efficacy was achieved by re-inventing primary and secondary end points – see here.

Eventually GSK had to acknowledge the failure of all three of their child and adolescent paroxetine depression studies – see here.

Click here for Peter Mansfield’s summary of all trials of newer antidepressants in children and adolescents.

Click here for J & E Jureidini’s summary of citations of the Keller paper.