Dr Peter Breggin: $11.9 Million Paxil Suicide Verdict: The Inside Story


https://www.madinamerica.com/2016/10/11-9-million-paxil-suicide-verdict-inside-story/

$11.9 Million Paxil Suicide Verdict: The Inside Story

No one expected a very large award, let alone $11.9 million, in this suicide malpractice case involving the antidepressant Paxil (paroxetine). The jury verdict on September 15, 2016 was gratifying and encouraging (Family of Pennsylvania jail suicide victim awarded $11.9M$11.8M Federal Medical Malpractice Verdict For Prison Inmate’s Suicide). It demonstrates that the judicial system and the public are becoming increasingly aware of the hazards of psychiatric drugs, including their capacity to make people behave in ways that are harmful to themselves and others, and contrary to their past behavior and character.

Great success seemed unlikely in this case. To begin with, suicide malpractice suits are very difficult to win. Juries understandably want to hold people responsible for their behavior when they kill themselves. I was going to testify that a single dose of Prozac 30 mg was the main cause of his suicide, a conclusion that other experts would vigorously challenge.

In addition, the case was in an area of the country where juries are conservative about giving monetary awards to plaintiffs. It was in the U.S. District Court for middle Pennsylvania in the city of Scranton.

Juries also tend to look askance at claims made on behalf of people in jail.  Mr. Mumun  Barbaros, the deceased victim, was in his fourth day of incarceration, awaiting release on bail. The judge did not allow the jury to know the nature of his alleged crime or the charges against him, and I was not permitted to comment on them. If allowed, I would have testified that Paxil-induced disinhibition drove him to vandalize the property of a man in a competing business.

Some people are also less sympathetic to naturalized citizens with strong ties to their countries of origin. Mr. Barbaros was a Bulgarian who became a citizen, but his wife and children spent only part of the year with him and he sent back large amounts of his earnings from his tavern to his extended family back home.

Finally, the case had scientific complexities that the jury had to understand.

The defendants were the independent healthcare provider to the jail, PrimeCare, and several of its personnel or contractors assigned to the jail. Mr. Barbaros had been taking Paxil for anxiety for many years, along with the sedating antidepressant trazodone to help him sleep.

At the time of his arrest, Mr. Barbaros reported that he needed his medication.  Due to a series of errors upon the part of the healthcare personnel, his request for medication went unfilled for four days.  By the second and third day, Mr. Barbaros develop headaches and hypertension, and his chronic stomach problem worsened, but no one attributed these symptoms to withdrawal. However, his intake evaluation and contacts with healthcare providers documented an absence of suicidal thoughts and revealed no great distress.

When the staff finally confirmed Mr. Barbaros’ medications, a licensed practical nurse (LPN) from the jail phoned the psychiatrist on call and asked him to prescribe the Paxil 30 mg and trazodone 100 mg. The LPN did not offer the doctor any information about Mr. Barbaros, such as his age, the reason he was taking the medications, how long he had been taking them, and how long he had been without them in jail. The psychiatrist, in turn, did not ask the nurse any questions, but simply authorized the drugs.

I testified that the psychiatrist’s actions were worse than practicing medicine negligently—he was not practicing medicine at all. He was more like a vending machine. I further testified that this was callous disregard, especially since he admitted to knowing that the drug had dangers associated with it, including suicide, and yet asked no information about the patient, did not come in to see him, and ordered no special supervision.

Following his first morning dose of the Paxil, Mr. Barbaros was seen for a routine evaluation by a staff psychologist in the mid-afternoon. At this point, Mr. Barbaros was drastically changed. He was no longer a man who conversed easily and showed no signs of significant stress, anxiety or depression. According to the psychologist’s deposition, Mr. Barbaros now looked extremely anxious and like a “cornered rat,” spoke very little, made poor eye contact, and looked hunched over and withdrawn. In the psychologist’s scantily written report, his only diagnosis was “rule out depression,” an entirely new diagnosis for Mr. Barbaros.

I attributed these drastic changes in Mr. Barbaros’ condition to the impact of the large dose of Paxil. The psychologist had not checked to see what medications Mr. Barbaros was taking. He did not check the medical record and therefore did not know that his current severely anxious and withdrawn state was entirely new for him during his incarceration.  He did not ask his patient if he was suicidal.

In my direct examination, I testified that restarting the patient on his regular dose of Paxil 30 mg, despite a hiatus of at least four days without the medication, was a direct cause of the suicide later on the same day. Restarting him on Paxil 30 mg, when most of the drug was out of his system, caused akathisia (agitation with hyperactivity) and suicide. I also found that the doctor and the psychologist were negligent in several other ways, including their failure to evaluate the patient and to order careful monitoring.

I further explained that Paxil (paroxetine) is a selective serotonin reuptake inhibitor (SSRI) antidepressant. All antidepressants can cause suicidal and homicidal behavior, especially those like the SSRIs that routinely cause stimulation or activation, including akathisia, agitation, insomnia, disinhibition, emotional lability, hypomania and mania, and a general worsening of the patient’s condition. Of all the antidepressants, Paxil was the only one to show a statistically significant association with suicide in depressed adults in the short and deeply flawed clinical trials used for FDA approval of the drug.

To back me up, I brought a number of documents, including a 2006 letter from the manufacturer to all healthcare providers admitting to the association between Paxil and suicide in depressed adult patients, and further warning that this risk might apply to patients with other diagnoses. I also brought a copy of the 2006 Full Prescribing Information for Paxil that carried the same warning about suicide in adults, before the drug company got the FDA to delete it in later editions. I had written about the subject of medication-induced suicide in my book, Medication Madness: The Role of Psychiatric Drugs in Cases of Violence, Suicide and Crime.

One of the more dramatic moments in my testimony came on the first series of questions during cross-examination. When I began reviewing the case, I was asked to focus on Mr. Barbaros’ medical record going back approximately six years to the time when his primary care doctor had started him on Paxil 10 mg, apparently without difficulty, and then raised it gradually to 20 mg and then 30 mg. To be thorough, I examined all the remaining extensive medical records and came upon something remarkable buried within them that had previously escaped attention.

The day after his first dose of Paxil 10 mg, Mr. Barbaros became so anxious that he thought he was having a heart attack and sought immediate help at a local medical clinic separate from his primary care physician who prescribed the Paxil. That clinic referred him to a cardiologist on an emergency basis who evaluated him and found no physical disorder. These doctors treated Mr. Barbaros’ anxiety with prescriptions for a benzodiazepine tranquilizer.

Mr. Barbaros had experienced a very severe anxiety reaction to his first dose of Paxil, but it apparently never entered his mind that Paxil was causing it. From the medical record, it looks like he never told the emergency clinic or the cardiologist he had recently started taking Paxil and he never told his primary care doctor, when he returned for follow up later on, that he had been so anxious that he went to a cardiologist and received sedative tranquilizers. It is very common for individuals to fail to realize that their acute psychiatric emergencies are being caused by their psychiatric medication.  I call this phenomenon “medication spellbinding” or intoxication anosognosia.

As a medical expert in a product liability case against GlaxoSmithKline, the manufacturer of Paxil, I had discovered from the company’s secret files that Paxil frequently caused severe psychiatric adverse reactions during the first few doses. I had published an article about this in the hope of alerting people to the risk. This earlier work of mine enhanced the credibility of my discussion.

So… when I was asked at the beginning of cross-examination to explain why Mr. Barbaros would have such a bad reaction to being restarted on Paxil since he never had a bad reaction to being started many years earlier, I had an unexpected answer. I could reply and document from the medical records that, in fact, he had a drastic psychiatric reaction to the original 10 mg dose but no one recognized that it was related to the Paxil. The defense attorney was so flummoxed by my revelation that he never even asked to see the relevant medical records. The cross-examination then went on for an unexpectedly long time, requiring me to come back a second day. The defense probably was hoping that the jury would forget the revelation I had disclosed in the first few minutes.

The jury not only found that PrimeCare and several of its practitioners and staff had been negligent, they further concluded that the company and most of the individual defendants acted with deliberate indifference to Mr. Barbaros’ medical needs.

Despite a vigorous challenge by the defendants’ attorneys, the judge qualified me as an expert in psychiatry, psychopharmacology and the specific drug Paxil. In the trial, other experts testified for the plaintiffs concerning the nursing care and administrative policies of the healthcare provider, as well as the violent method of Mr. Barbaros’ death by gagging himself.

The jury award included $2.8 million for negligence, $1.06 million for federal deliberate indifference and $8 million for punitive damages. The case is Ponzini et al. v. Monroe County et al., case number 3:11-cv-00413, in the U.S. District Court for the Middle District of Pennsylvania. The attorney for the plaintiff was Brian Chacker of Philadelphia. He worked extraordinarily hard and with great diligence on the case.

I do believe that the success of this case reflects greater awareness within the public and the judicial system concerning the dangers of psychiatric drugs.

Seroxat/Paxil Study 329: Response to Keller & Colleagues


http://davidhealy.org/study-329-response-to-keller-colleagues/#comments

Study 329: Response to Keller & Colleagues

April, 6, 2016 | 5 Comments

Original Seroxat (Paxil) Study 329 Authors’ Belligerent And Glib Response To Damning Seroxat Child Suicide Study In The BMJ


http://www.bmj.com/content/351/bmj.h4320/rr-27

Paroxetine treatment in youth does not appear to significantly differ from other SSRIs in the risk of suicidal ideation or attempts and whether SSRIs increase or decrease completed suicide remains an open question

In the abstract we stated “Conclusions: Paroxetine is generally well tolerated and effective for major depression in adolescents.” In this sample and with the state of knowledge at the time, it was justified and appropriate.

Sincerely,

Martin B. Keller, M.D.
Boris Birmaher, M.D.
Gabrielle A. Carlson, MD
Gregory N. Clarke, Ph.D.
Graham J. Emslie, M.D.
Harold Koplewicz, M.D.
Stan Kutcher, M.D.
Neal Ryan, M.D.
William H. Sack, M.D.
Michael Strober, Ph.D.

Regular readers of this blog would be very much aware of the recent RIAT re-analysis of GSK’s Seroxat (Paxil) study 329 published in the BMJ last year. This study was damning not just for GSK and for Seroxat, but it was also damning because it showed up the original authors as little more than charlatans. The original ‘authors’ were not so much ‘authors’ in the traditional sense of the word, because they basically just sold their names to the study- most of it was written by a PR pharma ghost writer  (Sally Laden)- hired by GSK.

However, because the ‘authors’ were big names in medicine and psychiatry at the time, GSK’s marketing department used them so that they could push Seroxat (Paxil) to under 18’s. Seroxat should never ever have been prescribed to kids (and in my opinion Seroxat is just as dangerous in the adult population). Many kids died from Seroxat induced suicide, some self harmed from it, some committed acts of violence against themselves and others,  and many were severely damaged (and this happened to adults too).

So you would think, considering the immense harm that this study has done, and considering the agony that Seroxat has caused many tens of thousands of people globally (adults and children)- that the original authors would be ashamed that their names were used in this manner wouldn’t you?  You’d think that they would be utterly appalled to learn that kids died from Seroxat, and you’d think that they would attempt to retract this study from the academic record, and you’d think that- they would be deeply sorry that they were so easily led by a greedy, sociopathic drug company, wouldn’t you? You’d think they’d care..

But, no..

The authors aren’t really concerned about any of this at all…

It seems, judging by their glib, belligerent and arrogant response- in the BMJ- that the study authors really couldn’t give a damn at all..

Why are we surprised?

They did, after all, lend their names to the original fraudulent study.. so why wouldn’t they lend their names to a rebuttal?

But now, in defending the indefensible it seems the only traits I can see remaining in the ‘characters’ of these ‘key opinion leaders’, are ones that resemble stone cold sociopaths.

I find it extremely disturbing how these academics seem to be more concerned with smearing the RIAT authors reputations, playing word games, and muddying the waters with other nonsense, than the stark fact that- a corrupted study they lent their names to- ended up being used to drug kids (literally) to death…

We’re talking about a drug which makes kids kill themselves…isn’t that f*cked up?

I was 21 when I was prescribed Seroxat, and it was a horrible experience..

It was horrendous…  I can’t imagine what it would be like for a child..

You can’t defend the indefensible…

Only psychopaths, serial killers and sociopaths would attempt to do that…Study 329 was a disgusting example of ‘doctors’ and psychiatrists selling their reputations to amoral drug companies, there is no defending it..

It was abhorrent..


Seroxat Study 329: How open data can improve medicine


How open data can improve medicine

A study arguing an antidepressant isn’t safe for teens has researchers calling for open data

Christopher Labos

  0

Depression. (Sandy Honig/Getty Images)

Jon Jureidini, a research leader of the University of Adelaide’s critical and ethical mental health research group, remembers when he first read Study 329. The paper, published 14 years ago in the Journal of the American Academy of Child and Adolescent Psychiatry, found that antidepressants, in particular paroxetine (brand name Paxil), were safe and effective. Its results would be used as proof that such drugs could and should be used by adolescents. A staunch opponent of prescribing antidepressants to teens, Jureidini assumed that he had it all wrong. But the more he read, the more he started to see problems with the paper. “It was seemingly deliberately misleading. And I got more and more worried about it,” he says.

But now, Jureidini and an international group of researchers have reassessed the original findings after a long and protracted fight with the drug’s manufacturer to gain access to the original raw data. In a study published in the British Medical Journal, they argue that scientific data published all of those years ago, claiming the antidepressant was safe and effective, were manipulated to cast the drugs in a more favourable light. They found that the drug was not only ineffective in teens, it also increased the risk of suicidal thoughts and behaviour. The maker of Paxil, Glaxo­SmithKline (GSK), disagrees with the BMJ findings and stands behind Study 329, saying “it accurately reflects the honestly held views of the clinical investigator authors.”

The saga of Study 329 has had many twists and turns. Its publication led to soaring numbers of off-label prescriptions for Paxil to adolescents and children. But almost immediately, the criticism from scientists started. Many questioned the statistical analysis. In 2003, reports linking Paxil to increased risk of suicidal thinking, suicide attempts or self-harm led GSK, following discussions with Health Canada, to issue a warning that Paxil should not be used in anyone under 18 until further information was available.

In 2004, GSK reached a US$2.5-million settlement with the New York attorney general over misrepresenting data on prescribing Paxil to juveniles. In 2012, it paid US$3 billion to the U.S. Department of Justice, to, in part, resolve liability over how it “unlawfully promoted Paxil for treating depression in patients under age 18.”

Related: Inside your teen’s scary brain

As part of the New York settlement, GSK was required to post clinical study reports from the trials on its website. Scientists should have been able to evaluate the Study 329 data. But they couldn’t. Peter Doshi of the University of Maryland’s school of pharmacy noticed that some of the appendices were missing. After prodding from the attorney general, GSK uploaded more pages, but one appendix was still missing. After lengthy negotiations, Jureidini and his collaborators got to see the missing data, but only under restrictive conditions. They had to view the 77,000 pages via a website that only allowed one person to view the data at a time and didn’t allow them to print, annotate, or sort. It took 1,000 hours of work to review just one-third of the documents. “It needn’t have been that hard,” says Doshi. “The amount of effort, the amount of letters, the amount of lobbying, the difficulty of using the data sources once they’re provided. You see many obstacles to making this go smoothly.”

Doshi explains that, historically, scientists haven’t had access to raw data because it is considered “confidential business information.” The issue here, scientists argue, is that without independent confirmation, it becomes too easy to manipulate data. In 2013, Doshi and a group of other researchers founded the restoring invisible and abandoned trials (RIAT) initiative. RIAT is trying to make study data openly available to researchers.

Jureidini and his team’s reanalysis of Study 329 found that the discrepancy between the findings of the original study and the current one lay in how adverse effects were recorded. In the original, serious events were grouped with more benign symptoms. Episodes of headaches were lumped together with psychiatric events under the category of “nervous system.” After examining the raw data of 93 participants, Jureidini and his colleagues found 11 suicide or self-harm attempts in patients taking Paxil compared to one definite case in those taking a placebo. The original paper referred to “suicidal ideation/gestures” as “emotional lability.”

Erick Turner, a psychiatrist at Oregon Health and Science University, has conducted research that made him worry about how data from studies is handled. In 2008, Turner was lead author in an article in the New England Journal of Medicine. He found that nearly a third of the trials on antidepressants submitted to the Food and Drug Administration had never been published publicly. But more worrisome was that the unpublished studies largely showed no benefit to these medications. When you consider all the data, both published and unpublished, half the studies suggest that they’re not effective. “Clearly these drugs are not as effective as we would like them to be,” says Turner.

But Turner warns that this is not an issue of just antidepressants. At its core, the issue is how science handles its data. He, like many physicians, used to believe that the published literature was the authoritative source. He no longer believes that. Jureidini says that the message of his paper is about trust in the scientific process and access to study data. “Without that access,” he warns, “you can’t be sure of the integrity of any journal article.” Doshi says it is no longer acceptable to keep data secret because “those who possess the data control the story.” After 14 years of scientific and legal battles, the complete story of Study 329 is finally public.

Remembering Seroxat Causing Self-harm (2004)


http://www.network54.com/Forum/281849/thread/1097319908/1097337553/%26quot%3Bless+than+a+small+class+size+would+have+these+suicidal+thoughts+or+attempts%26quot%3B

just 16 but within a week of starting seroxat had began self harming.

October 9 2004, 4:59 PM 

Sarah Thompson says she
self harmed on Seroxat

Sarah Thompson was prescribed Seroxat for depression three years ago. She was just 16 at the time.

She had never had suicidal thoughts before taking the drug, but within a week had began self harming.

She told the programme: “I’d never thought about suicide before I took Seroxat and when I was taking it. I was obsessed about death it was part of my every day life.

“I would cut myself mainly and then I started to burn myself and found other methods, but it was mainly cutting myself to start with.

Three years on, she has strong views about the regulation of the drug: “Looking back at what happened to me because of Seroxat, and the great affect it has had on my life and to my relationships with my family and my future.

“I don’t think that the regulators are doing their job properly, because they allowed me to take a drug that has in effect taken away part of my childhood.”

The Real-Life Human Damage, Death And Destruction Behind GSK’s Crimes And Fines


http://www.forbes.com/sites/robwaters/2012/07/12/glaxosmithklines-3-billion-hit-deterrent-or-business-expense/2/

Eight years ago, I wrote a cover story for the Sunday magazine of the San Francisco Chronicle. It began with the story of a teenage girl I called Angela Reich who became depressed after enduring months of grueling chemotherapy for leukemia. She resisted suggestions that she try antidepressants and saw a therapist for a while but her sadness and despair didn’t lift. So she relented and saw a psychiatrist, who started her on Paxil, an antidepressant made by the British pharmaceutical company GlaxoSmithKline.

The doctor increased the dose a little at a time, even after Reich told him she was feeling strange in her body and worse than she had before. She became increasingly anxious and jittery, with a relentless discomfort inside her body that caused her to constantly shake her leg. Finally, one morning, she attempted suicide by trying to swallow multiple doses of Ativan, Paxil and other medications she found around her house. Her father broke down the door of the bathroom, interrupting her pill-binge and rushed her to the hospital. His action may have saved her life.

English: Paxil 10mg 日本語: パキシル10mg錠剤English: Paxil 10mg 日本語: パキシル10mg錠剤 (Photo credit: Wikipedia)

Other teenage Paxil users were not so lucky. Jake Garrison, a 15-year-old who suffered from acne, was prescribed Paxil by his dermatologist for “body dysmorphic disorder,” a condition that leaves people feeling preoccupied with their own perceived physical defects. He took the medicine for a while, then stopped, and then, in September 2002, began taking it again. Three days later, he shot himself to death.

As I looked into the story at the time, several things became clear: GlaxoSmithKline was promoting the drug for use by teenagers even though it had never been cleared by the FDA for anyone under 18. The company also knew—but hadn’t revealed to doctors and patients—that, in some children, Paxil seemed to magnify their distress and increase their risk of thinking about or attempting suicide. GSK also seemed to be manipulating data from its clinical trials to minimize the number of suicides or attempts that might be blamed on its pills—“cooking the books,” in the words of a former Navy lawyer who took on the British pharma giant.

Last week, the U.S. Department of Justice announced that GlaxoSmithKline had agreed to pay $3 billion in criminal and civil fines for its misdeeds in inappropriately marketing Paxil and another antidepressant, Wellbutrin; for withholding information on the cardiovascular risks of Avandia, a diabetes drug that has been shown to cause heart attacks; and for promoting Advair, an inhaled lung drug, to patients with mild asthma even though it wasn’t approved or appropriate for them. The fine was the largest ever imposed by the U.S. on a pharmaceutical company and settled both civil and criminal charges.

The settlement agreement and the attached documents were full of juicy details that have now been widely reported: How GSK orchestrated the publication of a “misleading,” ghost-written study purporting to show that Paxil helped children when evidence suggested the opposite. How the company paid doctors, including “Dr. Drew” Pinsky, to promote Wellbutrin and how sales reps pitched Wellbutrin to doctors as the “happy, horny, skinny drug,” claiming it was also good for obesity and sexual dysfunction although it was approved only for depression.

As I read through company documents released by government lawyers, I began thinking about some of the victims I’ve interviewed during two decades of reporting on the pharmaceutical industry and its marketing of flawed, sometimes dangerous drugs—people like Angela Reich and the anguished parents of other children who died. I also thought about the statements made by Sir Andrew Witty, Glaxo’s chief executive officer, who expressed “regret,” said the company had learned from “the mistakes that were made” and asserted that under his leadership the company was now “putting patients first, acting transparently…and displaying integrity in everything we do.”

I wanted to talk to some of the people who had been harmed by taking GlaxoSmithKline’s drugs and the lawyers who represented them to see how they felt about the company’s admission of guilt and its $3 billion fine. First, I connected with Angela Reich, who was back in the Bay Area from an eastern school where she is now pursuing a PhD in literature. (She again asked that her name be changed, as it was when I first wrote about her in 2004.)

She recalled her Paxil experience and her subsequent effort to wean herself from the drug as a nightmare, and was outraged that the company failed to warn patients about the dangers.

“I think it’s despicable what they did and I think a $3 billion fine is pathetic,” when the company’s earnings are considered, she told me. “No specific individual executive has been prosecuted or punished or fined; there’s nothing to take away the incentives for huge drug companies to commit fraud. I’m infuriated.”

In fact, Glaxo’s legal and financial liability goes beyond the DOJ settlement. The company has been hit with jury verdicts and settled thousands of cases alleging that Paxil caused suicides, addiction and birth defects in babies whose mothers using the drug during pregnancy. A couple of years ago, my former colleagues at Bloomberg News estimated that Glaxo had paid out about $1 billion to settle Paxil-related cases. That was before a raft of birth-defect cases had been settled or tried.

Michael Baum, a partner at Baum-Hedlund, a Los Angeles firm that handled some of those cases, told me about 1500 had settled and a few remained. Both he and Sean Tracey, the Houston attorney whose firm handled most of the birth-defect cases, declined to estimate the value of the settled cases because they were made secret under the terms of the settlements.

Then there’s Avandia. Baum thinks that GSK’s apology and partial admission of guilt may make it harder and more expensive for the company to settle a number of still-unsettled Avandia cases. He estimated the number at about 1800 and says his office is involved in 180 of them. About 50,000 Avandia cases have been settled.

“Their admissions in the plea agreement and the information (the criminal complaint) puts GSK’s experts and corporate representatives in a corner,” Baum said. “It makes it difficult for them to say they did not hide information from physicians.”

As part of the plea agreement, the company made a commitment: it had to pledge that its executives won’t lie in the future. That requirement, Baum said, “is going to make it difficult for them.”

So will the penalties imposed on GSK really deter nefarious behavior in the future? Baum agreed with his former client, Angela Reich, that while the fine itself is serious money, it doesn’t compare to the revenue the company made from fraudulent marketing. “The public exposure of the conduct may be more of a deterrent than the fines,” Baum said.

Last year, GSK had a net profit of 5.3 billion pounds ($8.2 billion) on revenue of 27.4 billion pounds ($42.6 billion). Paxil, which entered the U.S. market in 1993, had sales of $11.7 billion in the nine years starting in 1997. Avandia came on the market in 1999, reached peak annual sales of $3 billion in 2006, then fell to $1.2 billion in 2009, two years after a study in the New England Journal of Medicine linked Avandia to a 43 percent increased risk of heart attack.

“If pharma companies can flout the law and then simply write a check when they get caught, they’re never going to stop,” said Sean Tracey. “The money is too large. Until and unless someone’s liberty comes to jeopardy, they simply consider this the cost of doing business.”

The full set of documents relating to GSK’s suppression of information on the cardiovascular risks of Avandia has still not come to light and GSK is still working to keep those documents under wraps, Baum said.  “They’re fighting us on releasing these documents that show what really happened,” he said. “They should allow the press and the public to see them.”

Tracey, meanwhile, is gearing up for another battle. Two years ago, he won a $2.5 million judgment against GSK for the family of a three-year-old boy, Lyam Kilker, whose mother took Paxil while she was pregnant. He subsequently settled 35 other cases. Now, on behalf of 150 clients, he is preparing to take on Pfizer, the maker of Zoloft, an antidepressant that came on the market around the same time as Paxil, and has also been alleged to cause birth defects. Stay tuned.

The Great Glaxo Transparency Swindle


For those who believe in the fairy-tale that Glaxo will ever manifest any real sense of transparency -or  give uncensored/uncontrolled access to their private trove of clinical trial data..    

..get real.

329 2

GSK 329

 

http://www.pharmalive.com/glaxo-falls-short-of-open-data-disclosure-jureidini-explains

Glaxo ‘Falls Short Of Open Data Disclosure:’ Jureidini Explains

Over the past few months, a group of researchers has been haggling with GlaxoSmithKline over access to detailed data for an infamous 2001 study of its Paxil antidepressant called 329 that tested the pill for treating depression in adolescents. The researchers, who are led by Jon Jureidini, a clinical professor of psychiatry at the University of Adelaide in Australia, want a 1998 clinical study report that they hope to reanalyze and republish. The original results reported that Paxil was effective, but the trial actually missed its endpoints and figured in a ghostwriting controversy (here is the study). As a result, Glaxo signed a consent order with the New York State Attorney General to publicly disclose trial data and has since vowed to do so. But the drugmaker says that Jureidini, who also led an unsuccessful quest to have the study retracted (see this), must follow its new system for submitting proposals (back story and more here). We spoke with Jureidini about his efforts. This is an excerpt of our conversation…

Pharmalot: Why did you make this request?

Jureidni: I’ve been occupied with trying to get some truth about that study for a long time. And just because it had such an impact in child psychiatry in Australia at the time it came out. It was used to try to shift the approach to (treating) childhood depression and (Paxil) became first line (therapy). I looked at it the first time I read it and thought perhaps medication is the answer. But then, I reread it and spotted some problems. I then had others look at it, and it seemed flaw and then deliberately so. This was in 2002 and 2003.

Pharmalot: Why does this matter now, though?

Jureidini: We have an editorial failure by a major medical journal. We have a failure of the peer review process. We have misconduct by a major pharmaceutical company. Most worrying for me is that we have a careless, at least, and probably more than careless, work by senior academics. And we have the whole issue of ghostwriting. Most of all, we have harm potentially done to children. Those sound like pretty significant issues to me.

Pharmalot: So what exactly are you seeking?

Jureidini: The primary goal is to get the data… We want to use the data to check what they published… Our guess is that the representation of the efficacy data in the clinical study report is accurate, but we have real concerns about the accuracy with which the adverse event data that has been transferred from individual patient records to the clinical study report, which is why we wanted individual patient records. The fact that it serves as a test of GSK resolve (to disclose trial data) is welcome to us, but not our primary interest.

Pharmalot: Glaxo has said publicly, though, that it has procedures for releasing data now and will review researcher requests.

Jureidini: The procedure doesn’t meet our requirements. That’s the problem. One of the positive things about us testing their process is that we’ve already illustrated we’re carrying out a project with GSK data, but the system doesn’t meet the needs of the research group.

Pharmalot: Which is….?

Jureidini: They won’t provide individual patient records. They’ve defined what they will make available and make it sound that’s all anybody what would want in order to behave ethically. We’re concerned that this (approach) gives them a level of control over the data, which might facilitate them withholding inconvenient truths. We haven’t been given any data yet, but you’ll see from the letters from Shannon (James Shannon, Glaxo’s chief medical officer) that the process doesn’t allow them to provide the kind of data we’re requesting.

Pharmalot: And what does he say?

Juredini: In the last letter, he says he’d like to have a phone call about that process and how it might change. I said I‘d like to do this by email, but haven’t heard back. But they have made clear it’s not the kind of information they’ll make available, even though they’re advertising it as open disclosure. It falls short of that.

I’ve done what they’ve requested, which is to put the application on the (new) web site (for data disclosure)…  And we’ll do what they request, which is to apply their analytical plan to the data, but we want to go a step further and ensure what’s in the data taggles collected by GSK reflects what was reported by patients to the (Paxil) researchers.

Pharmalot: When did this last exchange occur?

Jureidini: On November 5, he suggested a phone call. On November 8, I wrote back saying thanking him and didn’t think a phone conversation was best way to proceed.

Pharmalot: Why insist on e-mail and not a phone call?

Jureidini: Well, for one thing, I’m representing a team.  I’m not an individual functioning alone here. And it’s also partly because part of this process is to document interaction with GSK. Another reason is that I expect that it’s likely Shannon is a more skilled communicator than I am, so it’s more neutral, I think, to communicate in writing.

Unless they can come up with some plausible reason why there are genuine ethical concerns about providing the data, which may satisfy an independent appraisal, then you’d have to suggest there are other reasons why they don’t want us to see it. But we should be clear that GSK hasn’t said no to this request and I don’t want them backed into a corner of being acused of not providing information. I‘m not accusing them of that at all.

But the ability is there. It’s really easy. It’s a small expense to render documents confidential. It’s a question of whether there are more bad things happening that needn’t be hidden. It would be they had something to hide.

Pharmalot: Beyond this one study, what do you expect to accomplish?

Jureidini: There’s some good that can be done here. We can bring to account different parties that failed the community in the process of the publication of the (original) article – the company, the key opinion leaders… And we’re hoping that other people will be interested to make (the same sort of request). It’s an onerous task, but if you form a group, it can be done in the margins of your ordinary working life.

STORY ENDS HERE

Would The Real Ben Goldacre Please Stand Up?


Ben Goldacre is a doctor, journalist, blogger and writer whose media profile has risen exponentially over the past few years, particularly with the release of his last book on the pharmaceutical industry, Bad Pharma.  But who is the real Ben Goldacre- and what does he really stand for?

   Whilst Bad Pharma catapulted Ben Goldacre’s career firmly into the mainstream (and his trendy hip-doctor/guardian-journo persona seemed to capture the interest of the public imagination)- the content of Bad Pharma had more or less been covered already by other writers such as David Healy , Marcia Angell and others- over the years.

   Actually, most of the topics and issues in Goldacre’s book had also already been covered on this blog alone – predating the content of his book by five years ( I set up this blog in 2007- Bad Pharma was published in 2012).

   In other words- for a seasoned pharmaceutical industry critic, patient advocate, ex-Seroxat addict and blogger like me – what he had to ‘reveal’ about the badness and misdeeds of pharmaceutical companies was hardly revelatory at all. I could  have written it myself as I was certainly familiar with most of the information.

All that aside- what interests me most about Goldacre is his association with GlaxoSmithKline.

   Back in 2003- Goldacre received the GSK/ABSW award for his Guardian article ‘never mind the facts’. The article itself was basically a rebuttal piece in defense of MMR Vaccines and thus in turn- a defense of the pharmaceutical companies who make them and somewhat of an attack on those who claim that they can cause harm.

   I am no expert on vaccines or their link to Autism, nor would I ever claim to be- but I am well versed in pharmaceutical misdeeds- in particular those of GSK (I have been researching and blogging about GSK related issues for over 7 years now). I am aware that one of GSK’s vaccines, Pluserix was banned in 1992 and like other GSK medicines-  such as Seroxat and Avandia- not only was it causing immense harm- but GSK were allegedly aware of it.

  From my own experience of Seroxat- I would like to categorically state that I believe GSK were aware that Seroxat might harm me but like many instances with many other GSK products, they failed to warn- because all that matters to GSK is the health of GSK. Profit is the bottom line. Patients- like me- are merely collateral damage. However, considering that Goldacre is a psychiatrist (a fact he seems resistant to overtly publicize) maybe he just doesn’t care much for those who claim to be harmed by psychiatric drugs like Seroxat? Nonetheless- there is surely enough quackery and pseudo-science in Seroxat marketing which could keep a self-proclaimed quack-buster like Goldacre steeped in column inches for months.

   GSK have a murky history of malpractice and deception- their corporate history is littered with headline after headline of disturbing unscrupulous behavior. They are quite simply- pathologically sociopathic when it comes to harming the public. As a physician- I am surprised that Ben Goldacre would be so quick to jump to their defense- surely fraudulent clinical trials, intimidation of critics and widespread corruption resulting in damage to patients- would go entirely against the physician’s hippocratic oath?

Not so- it seems… in Ben Goldacre’s world.

Below is a picture of Goldacre receiving his BSW/GSK ‘science writers’ award from (none other than) GSK’s infamous Seroxat apologist Alastair Benbow (pictured right) in 2003. Apparently the award includes a 2000 pound bursary. (see link) http://www.badscience.net/2006/07/test-2/

6a00d8357f3f2969e2013485f7e002970c

Benbow was interviewed by BBC Panorama for their Seroxat documentaries and in (a diabolically delivered) defense of Seroxat he basically eventually admitted that Seroxat caused some children to commit suicide (after previously denying this in the Panorama documentary before it). Chillingly, Benbow seemed to think that this fatal side effect was almost inconsequential in the grand scheme of pharmaceutical depression treatment.

   The year Mr Goldacre was receiving awards from GSK for writing articles in favor of the pharmaceutical industry, was also the year that coroners in the UK were calling for a withdrawal of GSK’s Seroxat from the market (see here).

   2003 was also the year that (due to overwhelming evidence from the public) GSK were forced to abandon their no addiction claim about Seroxat. (see here)

   The year that Ben was posing with an award from a GSK funded initiative is also the year that the UK regulator banned Seroxat for under-18’s due to it’s propensity to make them suicidal- a sinister fact that GSK failed to inform the public of- for years. (see here)

 (Thankfully, for users of Seroxat, it was Ben Goldacre’s colleague- Sarah Boseley of the Guardian -who covered most of these stories)

   According to a tweet (screen-grab below) sent in 2010 in response to Seroxat Secrets, Goldacre, knows the’ Seroxat story well‘ and apparently he thinks it’s ‘vile‘. If this is the case then perhaps he would relay his opinion on Seroxat to his chum Andrew Witty because Mr Witty doesn’t seem to give a damn about Seroxat at all. If Goldacre really thinks that the Seroxat story is so vile- then why be so chummy with GSK?

gold

   Goldacre’s stance on pharmaceutical companies seemed to take a sharp turn with the release of Bad Pharma, which on the surface paints them in a very negative light. However, since most of the content of Bad Pharma had already been covered either online,  by blogs, in news-articles or in print form already- one would have to question whether it really had any negative impact at all on the reputation of the industry? Did it enlighten us to anything we did not know already?

   An insightful (albeit also complex) review of Bad Pharma from David Healy (not so bad pharma) seems to conclude that the problem with Bad Pharma rests not upon the repetition of content already covered, or the many flawed arguments raised which seem to rally against the pharmaceutical  industry but actually often work in their favor, “but on the premium Ben puts on controlled trials not found in other books”.

  You would have to read Healy’s review a few times to understand just how flawed and  -dare I say it- impotent –Bad Pharma is- particularly from a patient’s (or patient advocate’s) perspective. Perhaps it’s justified to ask- if a book highlighting the badness of Pharma actually serves to work in their favor in the long term- what use is it for the benefit of the public? Are we any safer? Possibly not.

   In a video of a parliamentary discussion of clinical trial transparency in the UK parliament from April 2013- Goldacre sits alongside GSK exec- James Shannon, and William Burns from Roche (19:06:00). In this inquiry, Goldacre refers to GSK as being ‘rather badly behaved‘ in the past- he then goes on to congratulate them on their current progress towards atonement (a fairy-tale like ‘atonement agenda’ which Goldacre seems to be swallowing hook-line-and sinker). The irony of this is- GSK have no intention of giving any access to clinical trials which predate 2000- therefore trials on drugs like Seroxat will not be released for inspection (Seroxat Trials pre-date the 90’s).

   I find Goldacre’s choice of words also quite astounding- ‘rather badly behaved‘ really doesn’t describe the destruction of life from a defective drug like Avandia or Seroxat.  “Rather badly behaved‘ doesn’t illustrate the magnitude of a 3 Billion dollar fine for fraud and corruption does it? “Rather badly behaved‘ is the kind of phrase we might use in regards to naughty children who won’t do their homework- not the UK’s biggest drug company (with the responsibility and power to enhance or extinguish human life on any given day depending on which way their ethical compass intends to sway). Goldacre then proceeds to  heavily criticize Roche and their Tamiflu debacle -conveniently leaving GSK looking much more ethical by comparison.

In an interview from March 2013– Goldacre says that he met Andrew Witty, CEO of GSK, before the announcement that GSK will release all trial data relating to its current products, with older data being released over several years. “He’d obviously thought very carefully about the practicalities of it, and that reassures me – he’d thought about how to do it, what the costs would be, and I think it’s to his enormous credit.”  Following the announcement Among one of many celebratory tweets, Goldacre said the news was: “Amazing. Fantastic. Historic.

   Thanking GSK for its decision, he added: “This is the beginning of the end for a dark era in medical history.” This ‘end of an era‘- and ‘the beginning of a new ethical GSK’ concept– has long been the mantra of Andrew Witty and GSK- particularly in regards to crimes that were committed prior to Andrew Witty’s tenture as CEO. I’m sure that GSK is delighted to have people like Goldacre championing (and echoing) its PR agenda- tweets from Ben Goldacre (with 250,000 followers) go far and wide.   Furthermore, these are just the perfect type of glowing PR sound-bytes that- pharmaceutical reputation management consultants- can’t even buy for GSK. Goldacre’s support must therefore be -utterly invaluable to them…

   And here we come back  again to Ben Goldacre and his association with GSK. At every given opening in the clinical trial transparency debate- it seems Ben Goldacre  just can’t resist an opportunity to lavish praise upon GSK CEO Andrew Witty. In an article from October last year (2012) he says:

“I think Andrew Witty, the current head of GSK, is a good guy, and I discuss this at length in the afterword of Bad Pharma: because I don’t realistically think that we can rely on one person in one company being nice, as a strategy to address ongoing regulatory failure in a global $600bn industry where lives are at stake.” (see here

   Perhaps Goldacre is incredibly naive, easily manipulated, under a spell, or utterly gullible? or maybe he genuinely does believe that GSK have changed their spots? I really have no idea

  However, considering that Andrew Witty has worked for GSK in various high level positions for most of his adult life I think it would be safe to assume that as CEO now he would have knowledge of most things that have – and do occur -within the company- including those things which would often undoubtedly come under the banner of big bad pharma

   And Ben… “good guys don’t become CEO’s of Billion-dollar Global Pharmaceutical companies”…

“You cannot hope to bribe or twist,
Thank God, the British Journalist,
For seeing what the man will do
Unbribed, there’s no occasion to.1

What is true cannot be minted

into a falsehood, even by

the most distinguished professor. 4

1 Anon.
4 Samuel Hahnemann.”

(Quotes Kindly Taken From http://www.whale.to/b/dwarfs01.pdf)

Hey Hey GSK: The Seroxat Hidden Data Debate Won’t Go Away


http://pharmagossip.blogspot.ie/2013/11/bmj-hidden-data-putting-glaxosmithkline.html

FRIDAY, NOVEMBER 15, 2013

BMJ – Hidden Data Putting GlaxoSmithKline to the test over paroxetine

Cite this as: BMJ 2013;347:f6754
  1. Peter Doshi, associate editor

Author Affiliations

  1. pdoshi@bmj.com

Blockbuster antidepressant paroxetine is no stranger to headlines. The drug is now back centre stage as requests for clinical data from one of its trials are testing manufacturer GlaxoSmithKline’s commitment to full transparency, Peter Doshi reports

When the Journal of the American Academy of Child and Adolescent Psychiatry(JAACAP) published study 329 in 2001,1 its editors could have had no idea that the paper would spark a controversy, not only about the use of the antidepressant paroxetine in children but also about secrecy in clinical trials. It is a controversy that rages to this day and that goes to the heart of recent campaigns to gain access to drug companies’ trial data.

By most accounts, GlaxoSmithKline is leading the pack in its efforts to liberate access to its clinical trial data. It was the first major pharmaceutical company to sign up to the international AllTrials petition calling for all trials to be registered with the full methods and the results reported.2 Whereas companies like AbbVie and InterMune have lodged lawsuits aiming to block access to clinical trial data,3 GSK has forged ahead with a new website enabling third party access to deidentified participant level data “because it is the right thing to do, both scientifically and for society.”4 GSK’s website states that five requests have been approved up to 20 September. None have been rejected. One is under review.

But one group’s request for data is testing the limits of GSK’s commitment to full transparency. Jon Jureidini, clinical professor of psychiatry at the University of Adelaide, is leading a team to reanalyse and republish the results of GSK’s study 329—a randomised, double blind, placebo controlled trial of paroxetine for the treatment of depression in adolescents. For over a decade, Jureidini has been critical of how the study was reported in JAACAP in 2001. In 2003, Jureidini and Tonkin wrote toJAACAP: “We believe that the Keller et al study shows evidence of distorted and unbalanced reporting that seems to have evaded the scrutiny of your editorial process.”5 They noted that “on neither of [the study’s two primary outcome] measures did paroxetine differ significantly from placebo”—yet the Keller et al paper concluded that “paroxetine is generally well tolerated and effective for major depression in adolescents.”1

Jureidini was subsequently contracted to provide expert advice as part of a class action lawsuit against GSK in 2004. Through this legal action, some internal company documents were released into the public domain, and Jureidini and colleagues reported that study 329 had an additional six secondary outcomes specified in the protocol.6 Paroxetine was not more effective than placebo on any of these outcomes either.

TROUBLED HISTORY

Paroxetine was a blockbuster antidepressant, known by its trade names Paxil in the United States and Seroxat in the United Kingdom, and was widely prescribed “off label” for use in children and adolescents. The drug came under heightened attention in the early 2000s, after a decade of rising antidepressant use among youths,7 over concerns about a link between paroxetine and suicidality in children.

In 2003, the UK Committee on Safety of Medicines recommended that paroxetine not be used in children and adolescents for the treatment of depressive illness because of concerns about an increased risk of self harm and potentially suicidal behaviour.  And in 2004, the US Food and Drug placed a boxed warning, its most serious type of warning, on all antidepressants, stating that they increase the risk of suicidal thinking and suicidal behaviour in these age groups.8

In 2012, GSK agreed to pay $3bn (£2bn; €2.4bn) in a fraud settlement with the United States government. In a statement connected with the lawsuit, the Department of Justice declared that “the centerpiece of GSK’s efforts to market Paxil for childhood depression was the GSK funded Study 329,” about which the published JAACAP“article distorted the study results and gave the false impression that the study’s findings were primarily positive, when they were, in fact, primarily negative.”9

Jureidini and colleagues have led a long campaign to compel the journal to correct or retract the article, which was authored by both academics and GSK employees.10Earlier this year, Jureidini presented GSK’s chief executive, Andrew Witty, with a final plea to help correct the scientific record. “Your corporation has so far failed to take responsibility for a published report that has harmed young patients who were prescribed paroxetine on the basis of this misleading article. As the CEO of GSK, you have the opportunity to correct the scientific record. I respectfully urge you to do so,” Jureidini wrote (see data supplement on bmj.com ).

But GSK defended the integrity of the 2001 publication. “GSK does not agree that the article is false, fraudulent or misleading,” John E Kraus, head of medical governance, wrote to Jureidini.

Jureidini has responded by assembling a team to reanalyse and republish study 329. In July they publicly declared their intention to produce a new journal report of study 329, written in accordance with the BMJ endorsed restoring invisible and abandoned trials (RIAT) initiative, which calls for third party authors to publish or republish unpublished and misreported clinical trials.11 The team’s starting place is a trove of over 6000 pages from a previously internal clinical study report written by SmithKline Beecham in 1998 that was forced into the public domain as a condition of a consent order GlaxoSmithKline agreed to in the settlement of a 2004 lawsuit with the New York State Attorney General.12 (SmithKline Beecham and Glaxo Wellcome merged in 2000 forming GSK.) The pages include a report of the trial, the study protocol, statistical analysis plan, blank case report forms, and numerous data tables, which Jureidini’s team will use for its analysis.

But GSK’s public posting of its internal report on study 329 is incomplete, lacking an unknown number of pages containing original case report forms from Appendix H. Jureidini and colleagues have therefore asked GSK for access to the deidentified case report forms and the corresponding deidentified electronic participant level data, “so that we can restore the publication of trial 329 in a fair, complete and publicly transparent way.”

“With regard to the electronic database,” James Shannon, GSK’s chief medical officer, wrote to Jureidini on 11 October, “I would ask that you do indeed submit an analysis plan via the website and sign a data sharing agreement.” Jureidini had initially rejected submitting an analysis plan arguing that “such a plan is irrelevant when restoring a publication where our primary focus is the original analysis plan drawn up and implemented by your own statisticians.” Nonetheless, Jureidini complied, and submitted an analysis plan—mostly a direct copy and paste from the protocol contained in the company’s 1998 clinical study report—placing GSK’s independent review panel in the unusual position of refereeing the appropriateness of the manufacturer’s own analysis plan.

As for the case report forms, GSK initially rejected Jureidini’s request, explaining, “We do not publicly disclose Case Report Forms (CRFs) and we do not provide them to other researchers. Complete CRFs are available to regulatory authorities for audit and for them to assure the integrity of the data sets and CSRs.” However, last week the company suggested a phone call with Jureidini, “to explore with you how we can help with this.”

COMMITMENT TO TRANSPARENCY

GSK’s wavering responses contrast with the many upbeat public proclamations by its executives about the company’s commitment to transparency. “Increasing transparency about our research is a critical area we’ve been pursuing at GlaxoSmithKline for almost a decade,” Shannon wrote in a September editorial in theHuffington Post.13 “We’ve also launched a new website allowing scientists to request access to the very detailed, anonymised patient-level data sitting behind the results of our clinical trials. This will mean independent researchers, with a fresh perspective, can conduct further research which could advance medical science and improve patient care.”

Transparency is “at the core of how we work,” Shannon explains. “People have asked me, ‘what if a new side effect comes to light for one of your medicines? Or what if a scientist discovers that you made a mistake in your research?’ My answer back is ‘why wouldn’t we want that to happen? Isn’t it better that we know? There is always the potential for us to find a better way to do things.’”13

Last month, Witty took it one step further in a television interview with the US Fox News. “We’re not simply going to publish data on trials still to come, but we’re going to go back, and we’re going to publish all the data for all the trials that have been done since the company was formed.”14

Witty’s phrase “all the data” sounds straightforward, but the company’s 11 October response to Jureidini implied that “all the data” would not include case report forms from study 329—or, it would seem, any other study. Nor, it seems, is GSK going to “publish” any of the deidentified patient level data on its new website, if “publish” means to make something public and freely accessible.

CAVEATS

A more careful reading of GSK’s stance is that it believes in what it calls a “closed-access system,”4 in which only approved researchers are permitted to query (but not download) data in preapproved ways. To gain access to GSK’s participant level data, requestors must first submit and have their analysis plan approved by an “independent review panel” and sign a data sharing agreement. A sample agreement posted on GSK’s website indicates that researchers are expected to run only preapproved analyses: “GSK and Researcher agree that GSK will provide the Researcher with access to patient level data from the GSK-sponsored clinical studies listed in Exhibit A for the sole purpose of analysis according to Researcher’s approved research plan (the “Analysis”) attached as Exhibit B and for no other purpose.”15

GSK suggests that such a system is necessary to protect the privacy of research participants. It is not enough to simply remove personally identifiable information from the participant level dataset. “It may be possible to combine deidentified data with other information to identify individuals. To minimize any such risk, our approach will be to provide access to anonymous patient-level data on a password-protected website that has controls in place to prevent data from being downloaded or transferred.”4

This concern is underscored in an editorial, published in the Lancet, coauthored by Patrick Vallance, GSK president of pharmaceuticals research and development, and Iain Chalmers, one of the founders of the Cochrane Collaboration and now coordinator of the James Lind Initiative.16 They write that “the protection of privacy is vital in IPD [individual participant data] analyses,” but point out that the process of deidentification can be carried out so thoroughly as to render the scientific value of the data useless. Deidentify the data insufficiently, and trial participants may be re-identified, violating their privacy. Vallance and Chalmers posit that a “controlled system” of restricted access offers a possible solution to the reidentification problem.16

It is therefore unsurprising that GSK initially refused Jureidini and colleagues access to the case report forms on grounds of protecting the privacy of trial participants. “The content of Appendix H is not posted on our website because it contains information (such as names) that can be used to readily identify the patients concerned.”

But Jureidini and company are challenging GSK. “As a group we do not accept your argument about patient confidentiality . . . The blank case report forms (CRFs) in the Clinical Study Reports (CSRs) make it clear that the only patient identifiers in any CRF not contained in the CSRs were initials. Redacting initials is the work of minutes.” Jureidini adds that reidentification of patients “is not our intention. We think anyone in our group attempting to do this would do significant damage to the data access cause. We are happy to sign agreements that there will be no effort to identify anyone and that the de-identified CRFs will not be shared with anyone outside the 329 group, with access limited to two to three designated individuals within our group.”

Jureidini also questioned GSK’s commitment to its patients: “noting the concern you expressed in your letter for the wellbeing of patients who participate in clinical trials, can we enquire as to GSK’s follow-up of patients who were in Study 329? For instance, were those who became suicidal or violent on Paxil subsequently advised of the possible role of the drug in their dangerous and distressing feelings/actions and counselled that it may be better for them to avoid SSRIs [selective serotonin reuptake inhibitors] in future?”

Perhaps most concerning, Jureidini explained to GSK that his team has concerns about how some of the adverse event data were reported in the 1998 clinical study report and therefore needs the additional requested data.

Recently, GSK has softened its position and seems willing to discuss the possibility of rethinking its previous position. “I recognize, however, that you believe you need to see the CRFs and I would like to explore with you how we can help with this,” Shannon wrote. “Please could we arrange a telephone call to discuss this more fully and agree a way forward?”

Jureidini has declined the telephone call, and requested keeping the interactions by email. “I would be grateful if you could indicate what in your opinion is the safest way of getting all CRFs from study to me, suitably de-identified, but otherwise complete with narrative elements intact.”

“RESPONSIBLE” DATA SHARING

Jureidini’s quest to access the complete participant level data for study 329 highlights some of the anxieties surrounding disclosure of clinical trial data.

Looming large are concerns about misuse of data. “We believe that there are public health risks if the proposed analyses are not scientifically robust and give rise to erroneous concerns about safety or false hopes of a potential benefit for patients,” GSK has declared.4 This fear of misleading analyses is embodied in an adjective gaining popularity among discussions over data sharing: “responsible.” The Institute of Medicine has named its ongoing consensus study on the topic “Strategies for Responsible Sharing of Clinical Trial Data” and a recent essay in the New England Journal of Medicine entitled Preparing for Responsible Sharing of Clinical Trial Data, warns that “poor-quality analyses can harm rather than advance public health, it must ensure responsible use of data.”17

IRONY OF STUDY 329

There is a certain irony in the story of study 329 and its 2001 publication in JAACAP. In a letter to Jureidini, GSK explained that the JAACAP publication “was subjected to peer review on three occasions” and “accurately reflects the honestly-held views of the clinical investigator authors.” But a more pertinent question is whether the published article accurately reflects the trial.

In their most recent letter to GSK, Jureidini and his colleagues reiterate their need for the study 329 case report forms and their intention to analyse study 329 “following the original analytic plan.” As such, Jureidini’s team’s efforts to independently analyse and publish the results of study 329 can be viewed as perhaps the most “responsible” of all analyses—and one that it seems may yet overturn the JAACAP publication that GSK continues to defend.

Story of study 329

  • 1994-98: SmithKline Beecham conducts study 329, a study of 275 adolescents with depression

  • 24 November 1998: Date of SmithKline Beecham’s internal clinical study report for study 329, which was made public by the 2004 consent order

  • July 2001: Keller et al publish study 329 in the Journal of the American Academy of Child and Adolescent Psychiatry1

  • 26 August 2004: GSK signs consent order with the New York State Attorney General, agreeing to pay $2.5m and publicly post clinical study reports for GSK sponsored trials of paroxetine in children and adolescents

  • 2 July 2012: US Department of Justice announced that GSK “agreed to plead guilty and to pay $3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs, its failure to report certain safety data, and its civil liability for alleged false price reporting practices”18

  • 26 April 2013: Jureidini writes to GSK chief executive requesting his help in retracting the Keller et al JAACAP article

  • 3 May 2013: GSK responds that “GSK does not agree that the article is false, fraudulent or misleading”

  • 13 June 2013: BMJ publishes the restoring abandoned and invisible trials (RIAT) declaration11

  • 25 June 2013: GSK expresses support for RIAT, stating that “by making the Clinical Study Reports available we are very happy for others to publish on the records if they wish to and if journals consider the work to be of scientific merit”

  • 15 July 2013: Jureidini publicly announces his team’s intent to republish study 329 in accordance with the RIAT initiative

  • 28 October 2013: Jureidini and colleagues formally submit a request for deidentified electronic participant level data through GSK’s website. The result of their request is pending review by GSK’s independent review panel

NOTES

Cite this as: BMJ 2013;347:f6754

FOOTNOTES

  • Competing interests: I have read and understood the BMJ policy on declaration of interests and declare the following interests: I am the first author of the RIAT declaration, which was co-authored by David Healy, who is part of Jureidini’s team. I am providing the Jureidini team with unpaid advice on the RIAT process. I am also a member of a Cochrane review of neuraminidase inhibitors that is based in part on clinical study reports provided by GSK for zanamivir. I initiated an inquiry in 2012 that resulted in an additional 38 781 pages from the clinical study reports of study 329 and eight other studies to be publicly posted on GSK’s website.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

REFERENCES

  1. Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, et al. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry2001;40:762-72.
  2. Kmietowicz Z. GSK backs campaign for disclosure of trial data. BMJ2013;346:f819.
  3. Hawkes N. Industry and drug regulators disagree on which data should remain confidential. BMJ2013;347f5390.
  4. Nisen P, Rockhold F. Access to patient-level data from GlaxoSmithKline clinical trials. N Engl J Med2013;369:475-8.
  5. Jureidini J, Tonkin A. Paroxetine in major depression. J Am Acad Child Adolesc Psychiatry2003;42:514, author reply 514-5.
  6. Jureidini JN, McHenry LB, Mansfield PR. Clinical trials and drug promotion: selective reporting of study 329. Int J Risk Saf Med2008;20:73-81.
  7. Zito JM, Safer DJ, dosReis S, Gardner JF, Soeken K, Boles M, et al. Rising prevalence of antidepressants among US youths. Pediatrics2002;109:721-7.
  8. Olfson M, Marcus SC, Druss BG. Effects of food and drug administration warnings on antidepressant use in a national sample. Arch Gen Psychiatry2008;65:94–101.
  9. United States ex rel. Greg Thorpe, et al v. GlaxoSmithKline plc, and GlaxoSmithKline llc. United States’ complaint. C.A. No. 11-10398-RWZ. 2011 www.justice.gov/opa/documents/gsk/us-complaint.pdf.
  10. Newman M. The rules of retraction. BMJ2010;341:c6985.
  11. Doshi P, Dickersin K, Healy D, Vedula SS, Jefferson T. Restoring invisible and abandoned trials: a call for people to publish the findings. BMJ2013;346:f2865.
  12. Civil Action No 04-V-5304 MGC. People of the State of New York against GlaxoSmithKline, plc and SmithKline Beecham Corporation. Consent order & judgment. 2004. www.ag.ny.gov/sites/default/files/press-releases/archived/aug26a_04_attach1.pdf.
  13. Shannon J. Unlocking access to clinical trial data— what are we afraid of? Huffington Post2013 Sep 9. www.huffingtonpost.co.uk/james-shannon/clinical-trial-data_b_3859734.html.
  14. GlaxoSmithKline CEO on increasing transparency of clinical trials. Fox Business2013 Oct 10, http://video.foxbusiness.com/v/2735629915001/glaxosmithkline-ceo-on-increasing-transparency-of-clinical-trials/.
  15. Vallance P, Chalmers I. Secure use of individual patient data from clinical trials. Lancet2013;382:1073-4.
  16. Mello MM, Francer JK, Wilenzick M, Teden P, Bierer BE, Barnes M. Preparing for responsible sharing of clinical trial data. N Engl J Med 2013;369:1651-8.
  17. US Department of Justice. GlaxoSmithKline to plead guilty and pay $3 billion to resolve fraud allegations and failure to report safety data. 2012. www.justice.gov/opa/pr/2012/July/12-civ-842.html.

Dr David Healy: The Church of GSKology


David Healy continues his brilliant blog posts on GSK…

http://davidhealy.org/the-church-of-gskology/

Editorial Note: This post is about midway through a series of posts that are broadly part of the AbbVie series. The series began with GSK’s Ttransparency and Access Journey, moved on to The House of GSK and will have at least two more posts after this. 

Reading the Minneapolis StarTribune, it was the reference to privacy that clinched it.

Facing a sexual abuse lawsuit, the archdiocese of St Paul and Minneapolis made a big deal of putting an independent panel in place to investigate.  They put the Reverend Reginald Whitt in charge of appointing the panel and receiving its reports on behalf of the archdiocese.

An Independent Panel that Sticks to the Rules

Rev. Whitt told priests and deacons that the task force may review specific files to determine whether the policies of the archdiocese concerning clergy sexual misconduct were properly followed. But, he wrote, “Access to these files will be within my control, and limited only to what is necessary for the task force.”

He also wrote that he recognized that many priests and deacons “may be anxious about your right to privacy and a good reputation.” He assured them that the archdiocese will proceed according to the principles of due process and uniform application of canon policy.

This sounds terribly like the approach Sir Andrew Witty is attempting to put in place for GSK, AbbVie and the rest of the branded pharmaceutical industry vis-a-vis abuses, including child abuse committed in their name.

Investigating Abuse

Is Abuse too strong a word? In Study 329, a controlled trial of Paxil given to children, there was a statistically significant increase in suicidality on Paxil compared to placebo. These children were unquestionably injured but it seems about as likely that GSK have contacted the children involved to tell them what happened as the Catholic Church have voluntarily got in touch with anyone who has been affected by their priests or nuns to inquire about their wellbeing.

In Study 329, the consent form tells parents and children that the child will not be exposed to any danger or risks beyond what would be found in normal clinical practice – but the protocol for the study involved an attempt to force titrate children up to a dose of 300 mg of imipramine. This is double the standard dose used for adults – at least in Europe. One reasonable hypothesis as to why this might have been done was that it was an effort to make Paxil look good. Pretty grim if it was.

Privacy Rights 

Just as the Church is insisting on the Privacy Rights of its priests, GSK, AbbVie and others have taken a legal action against the European Medicines Agency in an effort to claim Corporate Privacy Rights (See Let’s Do the AbbVie Again,  Avoiding Adverse Events).

Just as we respect an individual’s right to believe what they want – to be a Muslim, Hindu, Christian or Jew – and defend a pregnant woman’s right to control what happens to her body, GSK and AbbVie are claiming a comparable right to decide what the clinical trial data they hold means.

They are asserting their right to spin their version of what it is you put in your body even though this clashes fundamentally with your right to know what you are putting in your body.

Canon Law

Companies operate their own version of Canon Law. Canon law is the Church’s own internal legal system that the Church insists has primacy over national judicial systems. The Bishops and Cardinals adhere to this rather than the laws of the US or other countries. Whether intended or not, this is a system that favors the clerical abusers over abused children. It is this that has fueled the anger of those who have been abused. There would be little problem if the Church’s legal system were harder on the Clerics than on Children. But using a system that defies natural justice to safeguard Clerics not unsurprisingly causes anger.

GSK and other companies run something similar. They actively attempt to over-ride the legal systems of the United States and other countries with claims that unless findings are demonstrated in controlled trials to a statistically significant extent that they simply aren’t happening.

The US Federal Judicial Manual states that convincing evidence of challenge, dechallenge and rechallenge is the way to demonstrate that a drug has caused an adverse event. No place here for statistical significance.

With a flourish worthy of the best Jesuits, internally GSK and other companies apply exactly the approach advocated by the Federal Judicial Manual when assessing whether Paxil has caused a birth defect or suicide, but even after deciding in private their drug is guilty, in public they insist there is no absolutely no evidence that their drug has caused a problem.

This can even leave GSK personnel stating in public that they are not aware of a single side effect that is caused by Paxil or likely any of their drugs. See Burn in Hell.

The US Supreme Court has weighed in on this question and decided that GSK’s model is wrong. People have a right to make up their own minds as to what an adverse event profile means. The only people who have this right at the moment though are investors. Patients and doctors have no rights – at least not established.

Church of GSKology

GSK have applied to be treated as engaged in Science. They say that what they do has all the features of Science – clinical trials, peer reviewed publications.

Ideally the Courts would decide that rather than being a Science they are a Church – they operate a system that requires belief without evidence. There is less doubt that their publications are ghost-written than the Bible is.

While they have people with great public relations skills like James Shannon who say all the right things in public, like the Catholic Church GSK appear to operate an Opus Dei like arm which enables them to place their people close to heart of Britain’s regulator the MHRA and other bodies. They are close to being the Established Church in England.

In the face of abuse, GSK make a big deal about apparent reform but the Rev Whitt described the mechanism GSK have put in place perfectly: “Access to these files will be within my control, and limited only to what is necessary for a Responsible research proposal.”

Waiting for a Frances?

When it comes to reform it seems Andrew is a Ben not a Frankie.

We need some Martin Sixsmith or Dan Brown to write a book and make a movie on the lines of The Lost Child of Philomena Lee.

Don’t hold your breath. GSK are a lot scarier than the Catholic Church.

– See more at: http://davidhealy.org/the-church-of-gskology/#sthash.d1qIlFwJ.dpuf