Patrick Vallance: “Alltrials is not pushing for that level of data availability and neither are we”
“If I’m a shareholder, which I am, I don’t want a company to be hiding something that might come to light”…
Yesterday I posted an interview with GSK’s CEO Andrew Witty. In that interview Witty was very clearly (and visibly) uncomfortable when questioned by BBC’s Newsnight’s Evan Davis about GSK’s bribery scandal in China and their corruption of doctors.
In an interview (see Audio above) with BBC 4’s ‘Life Scientific‘ radio series today with Jim Al-Khalili, GSK’s (head of R and D and admitted GSK share-holder) Patrick Vallance, is asked about Seroxat harming kids, and his response is really very unsettling. He casually glosses over the harm to (potentially) millions of kids from GSK’s dangerous Paroxetine (Paxil/Seroxat/Aropax) over the past 15 years in a very matter of fact way, as if he was discussing a certain flavor of tooth-paste or the symptoms of a very mild head ache.
Vallance says (when asked about Seroxat killing kids) that:
“It’s inevitable that side effects things will occur from time to time”
“I’d rather know them than not know them”
(but isn’t this the whole point Pat- we weren’t warned of the side effects such as suicide, withdrawal and self harm so many millions of people didn’t know the side effects and were harmed by Seroxat- me included- purely on the basis that we didn’t know and were not told about them).
Wow, is that really your answer to the Seroxat scandal Pat? It’s inevitable that people get killed and maimed is it? It’s inevitable that GSK push drugs like Seroxat on under 18’s (when GSK knew from its own studies that Seroxat could harm them). That’s inevitable, all above board and expected is it? Is it all just inevitable really because that’s the nature of the drugs business? Or do scandals like Seroxat happen because of human greed, profit and sociopathic corporate behavior? I’d go with the latter…
It’s inevitable that it might rain tomorrow, it is not inevitable for a drug company to push its dangerous anti-depressant on young people when it knew it might make them kill themselves… How about making sure that your drugs are safe? Now there’s a novel idea Pat…
When asked about GSK’s endorsement of Alltrials GSK’s Pat Vallance admits that the Alltrials agenda is not about access to data at all ( data is the meat of the drugs industry, without access to it we just don’t know the dangers or efficacy of the drugs we take- see study329.org for more). Vallance also spins the well worn GSK yarn that they have been always publishing their trials on the clinical trials register but the truth (and what the GSK spin machine always omits) is that GSK were forced by two separate department of justice investigations into the company which have compelled them to publish trials- they did not do this willingly).
When asked by the interviewer, Jim Al-Khalili : “Is this about making clinical trial data available to all people”?
Pat Vallance responds that: “Alltrials is not pushing for that level of availability and neither are we”
Vallance’s answer is really very telling, and it reveals why GSK were so eager to jump on board the Alltrials/Ben Goldacre bandwagon. Access to data is what is needed here, not access to drug company’s published trials. Alltrials is a red herring, it gives GSK more control, and Ben Goldacre really has a lot to answer for in this regard. However since he seems to be enamored with Witty and Vallance, I won’t hold my breath for him to challenge them anytime soon. (I’ve written about these issues here, and Dr David Healy’s been banging the drum about Alltrials on his blog too- see here).
Furthermore, one of the only ways to get access to the data, is often only through litigation or department of justice investigations etc. People shouldn’t have to wait decades before they know the harms of a drug Mr Vallance. This is not acceptable nor inevitable. Seroxat has harmed immeasurably. The long term damage hasn’t even begun to be assessed.
Just like Andrew Witty, your attitude towards those damaged by your drugs like seroxat seems to be… “well that’s just tough”..
And your company still makes a profit on Seroxat, it’s still being sold, which means that you and Witty are still profiting directly (and knowingly) from death, human damage, addiction and child suicide…
Advair is one of the biggest blockbusters in pharmaceutical history.
The asthma drug has generated more than $80 billion in global revenues for its maker, GlaxoSmithKline, since its U.S. approval in 2000. With its distinctive purple inhaler, Advair has helped legions of asthma sufferers achieve control of their symptoms.
But recent federal research suggests that a significant percentage of asthma patients begin using Advair inappropriately, taking on what the drug’s label describes as an increased “risk of asthma-related death” from one of its two ingredients.
Concerns about that ingredient — salmeterol — emerged in a 1993 study, and more troubling results became known in early 2003. But it took the Food and Drug Administration seven more years to require Glaxo and makers of drugs similar to Advair to launch studies big enough to assess the risks.
Results aren’t due until 2017. Meantime, millions of patients on the drugs — a class long dominated by Advair — remain exposed.
Portions of Advair’s story have been told before, but a ProPublica examination, based on previously undisclosed or overlooked documents, shows that the traditional guardians of U.S. drug safety — manufacturers, regulators, doctors and the courts — have repeatedly failed to stop misuse of Advair or unlock its secrets.
Before Advair’s approval, a Glaxo scientist told the FDA that it wasn’t appropriate for patients with mild asthma. The agency agreed, a Glaxo document states, but it took five years to make that clear on the drug’s label.
When a handful of state Medicaid agencies moved to limit access to Advair, based on concerns about misuse, Glaxo lobbied aggressively to stop what was viewed internally as an “infestation” of such policies.
GlaxoSmithKline headquarters in London. (Matthew Lloyd/Bloomberg via Getty Images)
And Glaxo has faced scores of lawsuits and claims brought by people whose relatives have died while taking Advair, quietly settling some when pushed to the brink of disclosing sensitive documents.
Through it all, Glaxo’s muscular Advair marketing machine, abetted by broad doctor and patient support, has continued to chalk up huge sales.
Glaxo paid $700 million in 2012 to settle federal civil allegations that unlawful promotion of Advair contributed to extensive misuse, but regulators reported last year that overutilization remained a problem even after more urgent warnings to doctors and patients in 2010.
Glaxo vigorously denied the false-marketing claims brought by the Justice Department. The British-based company said it has changed its practices by ending certain financial payments to doctors and eliminating targets for sales reps. Its marketing policies, for Advair and other drugs, have always required that the company follow FDA rules, Glaxo said in a statement.
The company said Advair is safe when used properly and that dozens of studies have shown its “positive safety profile” and superiority to other asthma treatments. There have been no asthma-related deaths in more than 15 years of Advair trials involving 30,000 patients, Glaxo said.
“We are proud to be in the forefront of research and development in the respiratory field and to have helped millions of patients with asthma,” the company said, adding that patients could suffer if they stopped taking Advair because of too much emphasis on risk.
The FDA said in a statement that Advair “was approved more than a decade ago based on evidence that supported its safety and efficacy.” Although it later required warnings and new trials, the agency said it still believes the benefits of Advair and similar drugs are substantial.
Some 3,500 people die from asthma every year in the United States. Although no deaths have been definitively linked to Advair, in 2003 Glaxo shut down a study of salmeterol earlier than originally intended after 13 patients died.
An FDA scientist later summarized the results: one excess asthma death for every 1,300 users of salmeterol. A prominent FDA epidemiologist, Dr. David Graham, even called for Advair and similar drugs to be banned for treating asthma, calling their ongoing use a “natural experiment.”
But Graham was in a distinct minority; others in the agency said that Advair’s benefits outweighed any risks, which could be managed.
That was also the predominant view among asthma specialists and researchers — although a few broke from the pack. Within the latter group was Dr. Fernando Martinez, a prolific asthma researcher who runs a top respiratory center at the University of Arizona.
Fernando Martinez, shown in his lab at the University of Arizona, championed Advair but became concerned about risks posed by one of its ingredients, salmeterol. (Chris Hinkle for ProPublica)
Martinez helped lead calls for the large-scale trials the FDA eventually required for Advair and similar drugs. His center treats thousands of patients, and as a youth he watched his mother suffer with the disease.
Martinez felt that Advair was appropriate for many patients. But he was also concerned about the consequences of over-medicating and felt the need to speak out.
Without answers from the ongoing safety trials, he said in an interview, “You are putting at risk people who do not even need the medicine.”
A ‘Very Successful’ Label
Asthma is among the most common chronic diseases in the world, affecting roughly 25 million Americans, including 7 million children.
It causes sufferers’ airways to narrow and become inflamed, impairing breathing and causing bouts of wheezing, gasping and sleepless nights.
Some patients, about 35 percent, have only intermittent symptoms, according to the Centers for Disease Control and Prevention. Those with persistent asthma can be diagnosed as mild, moderate or severe.
There is no cure. Overall, asthma deaths are relatively rare. They declined from 2001 through 2009, according to the CDC, but have subsequently nudged upward. More than 400,000 people are hospitalized in the United States each year for acute attacks.
Asthma and Advair
Asthma is a chronic disease in which the airways become inflamed and narrow, causing shortness of breath, coughing and wheezing. Acute asthma attacks can require hospitalization. The cause is unknown, but allergies, childhood lung infections and genetics may contribute.
Source: National Institutes of Health, GlaxoSmithKline. Graphic by Al Granberg for ProPublica.
Salmeterol is in a class of drugs called long-acting beta-agonists, or LABAs, that have been shown to increase the risk of asthma-related death. Studies are under way to better determine who is most affected and if combination drugs like Advair have the same risk.
Misuse: Studies have shown that many patients taking Advair and other LABAs start them inappropriately, meaning when symptoms are mild and intermittent or when a corticosteroid alone will control their disease.
Before Advair, patients often had to juggle more than one medication to keep their symptoms in check. Studies show that many asthma sufferers didn’t follow their doctors’ orders and ended up undertreated.
Advair was designed to address those problems. It combined two established ingredients — a corticosteroid to reduce inflammation and salmeterol to open airways — in one simple inhaler.
Advair’s two main components had each previously undergone clinical trials to prove their safety and efficacy before winning regulatory approval. Still, questions arose about the safety of salmeterol, one in a class of asthma medications called long-acting beta-agonists, or LABAs.
A 1993 study found that patients in the United Kingdom taking Glaxo’s salmeterol-only drug, Serevent, had a higher rate of asthma mortality, although the finding wasn’t statistically significant. The FDA approved Serevent, but when reports of asthma deaths came in soon after, Glaxo began a large-scale safety study.
That research was still in progress in 1999, when Advair came up for approval. Glaxo submitted results from small trials that showed its combination drug was effective and had no serious adverse effects.
The FDA also had to consider which patients should get the drug and how to describe the appropriate population under the “usage” section of Advair’s label.
The issue arose at a 1999 meeting of experts the FDA had convened to seek advice about the label and other matters. For those with only “mild asthma” controlled by a single medication, the “combination therapy would be inappropriate,” Dr. Tushar Shah, then Glaxo’s director of respiratory clinical research, stated at the session.
Yet the language Glaxo proposed for Advair’s label wasn’t nearly as direct — it did not specifically rule out mild asthma. Particularly for family physicians and other non-specialists, it offered “a fairly vague statement,” observed Dr. Michael Niederman, chief of pulmonology at Winthrop-University Hospital in Mineola, New York.
Dr. Robert Meyer, then director of the FDA’s pulmonary division, agreed with Niederman, but others argued that physicians needed flexibility. Meyer cautioned that it wasn’t the FDA’s role “to be either tacitly endorsing or restricting the practice of medicine.”
He said the FDA hoped to work with Glaxo “to perhaps better define the population” of patients for Advair. When the agency’s medical review was completed in January 2000, the author wrote that the FDA would revise Advair’s package insert to “clarify” the matter.
That August, the FDA approved Advair as generally safe and effective. But the label’s “usage” section simply said Advair was for “maintenance treatment of asthma in patients 12 years of age and older.”
Inside Glaxo, officials were aware that the “FDA is not comfortable that Advair be used or promoted for mild disease,” according to a company memo written on the eve of the FDA’s decision.
On an April day in 2001, more than 2,000 Glaxo salespeople flocked to the Paris Las Vegas hotel for events to launch Advair. Spotlights swirled and the room glowed purple, matching a giant replica of the drug’s inhaler.
Jim Daly, the Glaxo manager nicknamed “Mr. Advair,” took the stage sporting a purple tie. “There are people in this room who are going to make an ungodly sum of money selling Advair,” he told the cheering throng.
The 50 salespeople who persuaded physicians to prescribe the most Advair would get $10,000 bonuses on top of healthy commissions.
Glaxo executives, sales reps launch Advair in 2001.
“I think we can make some millionaires out there,” declared Glaxo’s then-president of pharmaceutical operations, David Stout.
Stan Hull, the company’s senior vice president at the time, rhetorically asked the crowd, “What patient is not appropriate for Advair?”
According to the label’s “usage” language, virtually all asthmatics over 12 were potential Advair customers. Yet treatment guidelines generally called for starting patients with mild or intermittent asthma on other drugs, such as Glaxo’s Flovent, the steroid component of Advair.
Glaxo had strong incentive to prefer patients get its new drug — Advair sold for much more. (Currently, it can cost more than $300 a month, about 50 percent more than Flovent.)
Despite its higher price, Advair won over doctors and patients almost immediately, surpassing even the ambitious sales goals set in Las Vegas. Some 10 million prescriptions were dispensed in the drug’s introductory year. In 2002, Advair amassed $1.4 billion in sales.
One of those early prescriptions went to Lisa Wade, an athletic high schooler who lived in the rural town of Leesport, Pennsylvania.
Lisa’s symptoms had included a few serious asthma attacks a year — “not that bad,” according to her father, Jeff, who managed computers at a bank.
“The selling point was convenience,” said her mother, Mary Kay, an emergency room nurse.
For several months after Lisa started Advair, her symptoms stayed about the same. But beginning in the spring of 2002, her flare-ups increased in severity and frequency, scaring her family.
On the night of Sept. 17, Lisa was home alone, filling out a college application on her computer, when a serious attack struck. She managed to call 911 before collapsing. It took the ambulance just four minutes to arrive, but Lisa couldn’t be revived.
Mary Kay was on duty at the ER when they brought in her daughter. Just past midnight, doctors pronounced Lisa dead. It was three weeks after her 17th birthday.
Jeff and Mary Kay Wade keep a memorial case dedicated to their daughter, Lisa. (Mark Makela for ProPublica)
In their grief, the Wades set about researching Advair. Spurred by a news article, Mary Kay learned about studies linking salmeterol with an increased risk of death. She called the FDA, which collects reports on bad drug reactions, to explain what happened to Lisa, saying she’d heard about 12 similar deaths.
“The guy said to me, ‘I guess your daughter just made it 13,’ ” Mary Kay recalled.
The Wades sued Glaxo for wrongful death in Philadelphia’s common pleas court. The company denied liability.
As part of the litigation, Lisa’s body was exhumed and autopsied, but even that didn’t bring certainty about the cause of death. The report, by a forensic pathologist, concluded Lisa died of “acute cardiac arrhythmia and heart failure due to complications of bronchial asthma or its therapy.”
In a statement to ProPublica, Glaxo said, “We are prohibited from discussing any specific patient, his or her asthma condition, prescription drug use and a host of other critical factors that may be useful in evaluating medical causation and alternative medical causation.”
The Wades’ case was settled confidentially.
A Call To ‘Clear the Air’ About Excess Deaths
As the Wades sought answers about their daughter, the asthma community got a jolt. Glaxo halted its salmeterol safety trial earlier than expected.
Begun in 1996, the study was known by the acronym SMART and had become the biggest asthma drug trial ever conducted, involving 26,000 patients. But after 13 patients on salmeterol died and participation flagged, the study’s safety board recommended either enrolling more patients or closing it down.
In January 2003, Glaxo ended the trial and notified the public and health-care providers of the results: The rate of asthma-related death for patients on salmeterol was four times higher than for patients on a placebo.
To Arizona researcher Martinez, the demise of SMART struck like a “lightning bolt.” He had started out as an Advair fan, “happy with the medicine,” as he put it. Although Martinez still believed Advair was the best choice for some patients, the salmeterol risk was troubling.
Compounding the issue, Glaxo’s initial analysis of the SMART results made the numbers look better than they were.
Without telling the FDA, the company included patient outcomes that occurred up to six months after the study period ended. The effect was to boost the number of asthma deaths for patients on placebos, shrinking the gap with salmeterol.
The FDA noticed, and Glaxo had to resubmit its results. The agency later called the initial analysis “artificial.”
In a statement about the matter, the company said it “actively communicated the outcomes to regulatory bodies and other stakeholders, and the information was promptly made public.”
Within months, the FDA approved new warnings for packaging on all LABA drugs, including Advair.
By early 2005, the SMART study was still being widely debated in the asthma community. The FDA invited Martinez and other experts to help decide what to do next.
In private discussions with the FDA, Glaxo had argued that the steroid ingredient in Advair ameliorated the risk of the salmeterol compound. The agency had rejected that contention as unproved.
That July, the agency convened its Pulmonary-Allergy Drugs Advisory Committee to consider whether additional warnings were needed.
As the discussion unfolded, one panelist — David A. Schoenfeld,a Harvard professor of medicine and statistics — calculated the risk of death for salmeterol users, based on SMART. He put it at one excess death for every 700 patients with a year of exposure.
The figure alarmed members of Glaxo’s team, who worried that the estimate “might appear in the public domain without appropriate caveats” and be a “disservice to patients.” Instead, the company cited studies where it didn’t “see an attributable risk of that sort.”
A company presenter, Dr. Katherine Knobil, said there were too few deaths during SMART to provide “any clear explanation of the results.”
Martinez acknowledged Glaxo’s theory that Advair’s steroid ingredient might offset the risk of salmeterol. But he said SMART wasn’t designed to answer that question. “I do not think that the data, as I see it today, justifies saying that this risk is decreased by steroids,” he told the group.
Instead, Martinez suspected drugs like salmeterol might be backfiring in a small population of patients, including those with rare genetic variations. For that population, “the main expression of the disease is severe attacks that are not only not controlled by these medications,” he said, “but may be rendered worse” by them.
Martinez came away convinced that the answer was more research — and that the drug makers should be digging deeper.
That December, he took the unusual step of publishing an essay in the New England Journal of Medicine. “Until the manufacturers of these drugs undertake the appropriate studies needed to clear the air,” Martinez wrote, the safety of drugs like Advair “will remain uncertain.”
Doctors ‘Aren’t Going to Listen’ to the FDA
The FDA did not order studies. But the month before Martinez’s article appeared, the agency did revisit Advair’s broadly worded label.
In late 2005, the drug regulator required new “usage” language saying “physicians should only prescribe” the drug to patients whose asthma wasn’t already controlled by inhalers like Flovent, or whose asthma “clearly warrants” more than one medication.
Publicly, Glaxo executives shrugged. Although manufacturers can’t promote drugs for off-label use, doctors are free to prescribe them as they see fit.
The revised label “is not going to have a big effect” on Glaxo’s blockbuster drug, CEO Jean-Pierre Garnier told Wall Street analysts in January 2006. Doctors, he said, “are not going to listen to the FDA.”
Inside Glaxo, executives weren’t as sanguine.
The company’s marketers had been targeting “high volume Medicaid” doctors to boost Advair sales, according to documents in the Justice Department case that were unsealed at ProPublica’s request.
A top company executive had even boasted about the results in a briefing for investors, the documents show.
Jeff and Mary Kay Wade filed a wrongful death lawsuit faulting Advair after their daughter, Lisa, had an asthma attack an died. Glaxo denied liability in that case and other lawsuits over the drug. (Mark Makela for ProPublica)
After the FDA’s label changes, though, Medicaid officials in Arkansas moved to limit access to the drug. A state analysis confirmed that most Medicaid patients with mild cases of asthma were getting Advair despite treatment guidelines saying they shouldn’t.
“People were being treated with the most expensive, the most risky combination, jumping right to the top of the mountain with no evidence they needed it,” said Dr. Mark Helm, who headed the Arkansas study.
Arkansas’ Medicaid program started requiring doctors to get prior approval before prescribing Advair. The change dramatically cut prescriptions without adverse health consequences to patients, Helm said.
But when Helm and his colleagues began sharing their approach with Medicaid officials in other states, Glaxo launched a counteroffensive to make sure that what happened in Arkansas stayed in Arkansas.
After Ohio proposed restrictions, a company lobbyist reported testimony from a doctor who called them an “unnecessary burden” that would be “dangerous for patients,” an April 2007 email chain shows.
Ohio ultimately adopted limits, but the company’s opposition strung out the debate for an additional three months. The delay was valuable enough to Glaxo that executives nominated those involved for “Spirit Awards,” according to one of the company emails.
After a few years, only eight states restricted Advair in Medicaid.
Responding to questions about lobbying, Glaxo said in a statement that it has worked with many states to “assure the availability” of drugs, including Advair, and that it disagrees with efforts that “deny treatment to appropriate patients as recommended in national guidelines.”
In the Courts, A Fight Over Disclosure
Glaxo fended off one threat. Now its lawyers grappled with another: A growing stack of lawsuits had been filed against the company blaming Advair for deaths or harm from severe asthma attacks.
In the summer of 2006, a case in rural Alabama took on added importance as plaintiffs’ attorneys pushed for the disclosure of a cache of internal Glaxo documents about Advair.
The plaintiff was an Alabama truck driver named Earl Faulk, who contended that the death of his 20-year-old son, Marcus, was linked to use of Advair and Serevent.
The company’s attorneys resisted Faulk’s demand for documents, saying Glaxo had already released more than 1 million pages. The additional documents included private communications between the company and its attorneys and should not have to be turned over, they argued.
The decision fell to Christina Crow, a lawyer engaged as a special master by the judge presiding over the case.
Crow questioned Glaxo’s claim of attorney-client privilege. The documents “weren’t seeking advice,” she said in an interview. “They seemed to be copying an attorney just so privilege could be invoked.”
Crow ordered the company to hand over more than 100 documents. Before the records could change hands, however, Glaxo and the Faulks resolved the case confidentially.
Other cases also ended abruptly after lawyers sought the same cache of documents, according to one plaintiff’s lawyer, Lynn Seithel. A former Republican legislator in South Carolina, Seithel estimates she “worked on about 250 cases” involving Advair. None went to trial, records show.
As in the Wades’ lawsuit, Glaxo denied liability and said it could not comment about the cases or their resolution.
Crow may be the only person outside Glaxo or its attorneys to have seen the documents Faulk sought.
“I learned a lot about asthma and Advair,” Crow said. While she is prohibited from disclosing what they say, Crow said it was a relief that members of her family “don’t have the disease or take the medicine.”
‘How Can We Justify Exposing Millions?’
The legal settlements kept some of Advair’s secrets out of view, but they didn’t diminish the debate over its safety.
In December 2008, the dispute spilled out into full view when FDA scientists split over whether Advair should still be approved to treat asthma. The agency declined to make officials available for interviews.
1993: A study in Britain of GlaxoSmithKline’s inhaler Serevent, finds a small number of excess asthma-related deaths.
2012: Justice Department and Glaxo announce settlement of whistleblower case; company denies wrongdoing regarding Advair but agrees to change marketing practices and pay $700 million.
2013: Advair’s U.S. sales reach $4.6 billion.
2014: FDA study says 2010 actions had little impact on reducing overuse of Advair and similar drugs.
Sources: FDA and Justice Department documents, ProPublica research.
Martinez was in attendance as the FDA convened three different advisory groups to discuss what to do about long-acting beta-agonists like salmeterol, the Advair ingredient linked to asthma deaths.
With more than 3 million asthma users, Advair dominated all combination LABA drugs. The medications are also used to treat chronic obstructive pulmonary disease (COPD), but an increased mortality risk hasn’t been demonstrated for COPD.
The FDA’s Dr. Andrew Mosholder recounted the findings from SMART, the study Glaxo had shut down five years earlier: Salmeterol was linked to one excess asthma death for every 1,300 patients in the 28-week trial. Expressed in terms of a full year, that is the equivalent of the one-in-700 estimate that Harvard’s Schoenfeld cited in 2005.
Graham, part of a surveillance and epidemiological team with Mosholder and others, said there was no evidence the risks for Advair weren’t as high or worse. Taking on his agency, he said the FDA should have ordered Glaxo to do a large safety trial “many, many years ago.” The company “apparently didn’t volunteer” to do one either, he noted.
“How can we justify exposing millions to what we must conclude is an extremely high risk of death?” Graham said, referring to Advair and other combination LABA products.
He and Mosholder couldn’t, Graham said. The two recommended that the FDA no longer endorse the drugs for asthma care.
The stance put them at odds with the FDA’s pulmonary experts. Dr. Badrul Chowdhury, head of the agency’s pulmonary division, countered that taking Advair away could make things worse.
Chowdhury said asthma deaths had trended down since Advair hit the market. Patients might turn to less-effective drugs or make more frequent use of rescue inhalers, which also carry a mortality risk, he said.
“This shift will not reduce mortality, but may increase it,” Chowdhury said. He also cited an FDA meta-analysis of multiple studies that collectively suggested Advair was safer than other LABA drugs. Any risks can be managed with appropriate labeling, he said.
In a statement to ProPublica, Glaxo said excess asthma deaths like those seen in the SMART study “would have suggested a significant increase in asthma fatalities rather than the observed decline” in recent years.
Advair supporters — from families with asthma-stricken kids to physicians — also defended the drug at the FDA meeting.
Ultimately, the advisers went with Chowdury. Martinez joined a unanimous vote affirming that Advair’s benefits outweighed any risks in adults. By a narrow margin, the group also backed continued use by children.
Four months later, another influential voice entered the debate.
Dr. Jeffrey Drazen was both editor-in-chief of the New England Journal of Medicine and a veteran asthma researcher at Harvard Medical School. Years of inaction on the issue of LABA safety studies disappointed him.
In an editorial, Drazen and a co-author from Canada wrote that if drug makers didn’t launch new trials to address the matter, the FDA should force them to do so. “As members of a community of physicians, we must demand that such studies be done, be done soon, and be done correctly,” the two wrote.
With sales of Advair and similar drugs topping $6 billion a year, even a big trial would cost the equivalent of only a couple of weeks of profits, they said.
It took nearly a year for the FDA to move.
In February of 2010, the agency required Glaxo and three other manufacturers to conduct studies large enough to measure the risk of asthma death and life-threatening hospitalizations for their drugs.
Advair had been on the market for almost a decade. Utilization studies confirmed what Helm found in Arkansas — that Advair was being prescribed inappropriately to most of the patients who got it.
The FDA initiative included stronger language on the drugs’ labels, emphasizing that they should only be prescribed if other therapies were inadequate and that they should be discontinued as soon as possible.
Marketing and ‘Massive Overutilization’
While the FDA’s regulators moved forward, its investigators began working with federal prosecutors on a probe that had Glaxo and Advair quietly in its crosshairs.
Years earlier, current and former Glaxo sales reps had filed lawsuits under the U.S. False Claims Act, alleging the company had unlawfully marketed several of its drugs and defrauded federal health programs.
The Justice Department eventually joined the cases, providing the plaintiffs access to millions of records subpoenaed from Glaxo.
Initially, the case had focused on other Glaxo products. But in 2009, at a meeting with government prosecutors in Boston, the whistleblowers’ lawyers laid out evidence that Glaxo marketed Advair to mild asthmatics, despite knowing it might not be appropriate, court documents show.
In 2011, the Justice Department filed — still under seal — a civil fraud complaint alleging, among other things, that Glaxo had unlawfully promoted Advair, exposing patients to “significant safety risks without demonstrated treatment benefits.”
The result was ” massive overutilization of Advair” by people who, according to federal treatment guidelines, shouldn’t have been taking it, the government’s case alleged.
Relying in part on the subpoenaed Glaxo documents, the complaint estimated the misuse at between 50 percent and 90 percent. Moreover, Glaxo had promoted Advair over its less-expensive Flovent, even when Flovent was medically appropriate, the government said.
The allegations didn’t become public until the summer of 2012, when the government and Glaxo settled. Although Glaxo denied wrongdoing with regard to Advair, the company agreed to pay more than $700 million related to the drug, part of a $3 billion deal involving eight medications.
“The settlement was a way to resolve the government’s allegations and move forward,” the company told ProPublica.
Glaxo also agreed to reform its marketing practices. It changed bonus arrangements for its sales force in 2011 and last year committed to end the practice of paying doctors to speak on behalf of its drugs. “We’ve taken responsibility for past conduct, learned from our mistakes and have changed as a company,” Glaxo said in a statement.
News accounts of the July 2012 settlement focused mostly on Glaxo’s other drugs, rather than Advair, which largely retained its halo among doctors and patients. Sales exceeded $4 billion in the United States that year, more than five times what Glaxo paid to resolve the government claims.
A Genetic Clue, Years After A Pitch
The FDA-ordered safety trials began in 2011, and Glaxo said it is “working diligently” to meet the agency’s mandate.
In response to critics like Drazen, Martinez and Graham, who say the company should have initiated a trial, Glaxo said in a statement that none of the drug makers doing studies had done so as they “awaited the direction” of the FDA.
Glaxo said there have been no asthma deaths in the trial. The company also said results for adult and adolescent subgroups should be ready this fall, which would make Glaxo the first to report its findings. A separate pediatric study is expected to be completed ahead of the FDA deadline, the company said.
As part of the trial, Glaxo said it collected genetic data for further research, even though the FDA did not require it.
Eight years ago, however, the company passed up a chance to pursue a line of genetic research that has since proved fruitful.
In 2007, Glaxo sent Martinez an email inquiring about his interest in investigating whether genetics might explain severe asthma attacks in patients taking LABA drugs. Martinez wrote back, asking “how seriously GSK [Glaxo] would want to pursue these issues.”
He proposed a study of rare gene variants, saying it could put Glaxo “at the forefront of severe asthma genetics,” according to emails obtained under Arizona public records law. Glaxo scientist Steve Yancey later visited Tucson to meet Martinez, who was paid a small consulting fee.
Glaxo and Martinez never teamed up. But last year, Lancet Respiratory Medicine, an arm of the prestigious British medical journal, published a study that was essentially the same as the one Martinez had proposed.
The authors found that patients with rare genetic variations who took a LABA drug had twice the rate of asthma-related hospitalizations and a higher incidence of asthma attacks.
Asked why Glaxo didn’t follow up with Martinez, the company said it lacked a sufficient genetic database at the time. Glaxo said it now has enough data for its own study and expects results this fall.
Misuse of Advair and other drugs with long-acting beta-agonists persists, according to a team of FDA and independent researchers.
Their lengthy, little-noticed study, released in January 2014, examined the effect of the label changes and patient guides the FDA mandated in 2010. It found little or no impact: The portion of patients who inappropriately started taking LABAs held at about 27 percent. The length of time patients used the drugs didn’t budge, either.
The findings came two years after Glaxo sent the FDA its own utilization study, contending that a decline in Advair prescriptions between 2005 and 2011 demonstrated that its safety communications were working.
Martinez noted that the biggest declines were in pediatric dispensing, while adults accounted for more than 80 percent of Advair users in Glaxo’s study.
In an email, Glaxo criticized the FDA’s study because it relied on insurance claims data, which don’t reflect asthma severity or other factors a doctor might consider when prescribing Advair. “It is the physician who is best suited for making the correct decision about which therapy to initiate for a patient,” the company said.
Brennan Passons (Courtesy of Passons family)
About one out of every six Americans with asthma takes Advair or a similar drug, according to the FDA study. Although competitors have taken some of Advair’s market share, with sales dipping to $3 billion last year, it remains the top-selling combination asthma medicine.
Drazen, the Harvard asthma expert, said doctors remain loyal to Advair because they see patients get better. “One of the reasons it’s hard to convince lung doctors of the risk is that the drug is so effective,” he said.
A few who’ve been affected by Advair need no convincing about risks.
Tim and Sarah Passons’ daughter, Brennan, was a straight-A student at Queen of Angels Catholic School north of Atlanta. She had taken Advair continuously for four years when, on an October night in 2011, she couldn’t breathe and was rushed to the hospital.
Brennan died in less than an hour, her parents said. An autopsy showed that her airways were filled with mucus. She was 11 years old.
Like the Wades a decade earlier, the Passonses scoured FDA material and talked to health-care professionals to find an explanation. They also looked at the Justice Department case.
Sarah Passons came to believe that Advair contributed to Brennan’s death — and that the FDA, Glaxo and the medical community had failed to adequately communicate the drug’s true risks.
Now, the family is encouraging pharmacies to do more to alert patients about the medication risks listed in drug package inserts. Advair’s insert, including a medication guide for patients, is more than 60 pages long.
Inserts can go unread, as the patient representative at the FDA’s 2008 advisory meeting acknowledged.
“I have to tell you,” said Andrea Holka, a Nebraskan with two asthmatic sons, “we’ve been taking different medications for the last 10 years for asthma, and I have yet to actually, embarrassedly, sit down and read an entire patient insert.”
Said Sarah: “I don’t want to see another child die.”
Editor’s note: The Sandler Foundation, the largest donor to ProPublica, also contributes to research into asthma, primarily through the American Asthma Foundation and the Sandler Asthma Basic Research Center at the University of California, San Francisco.
(NaturalNews) While the debate rages on about whether or not vaccines cause autism, a confidential document has surfaced that makes clear what science has led Natural News readers to believe: Yes, vaccines are linked to autism.
The document,[PDF] which runs over 1,000 pages, is from the fraudulent and corrupt GlaxoSmithKline. Several hundred pages in, it’s revealed that vaccines are tied to autism. It’s blatantly outlined in a chart, along with a long list of other conditions caused by vaccines, including “motor development delay,” “tremor” and “altered state of consciousness.” Autism is listed in this chart as a nervous system and mental impairment disorder associated with receiving GSK’s Infanrix hexa vaccine.(1)
Signed by Dr. Felix Arellano, the Vice President and Head of Biological Safety and Pharmacovigilance of GlaxoSmithKline Biologicals, the document’s introduction states:
This summary bridging report integrates the information presented in the two Combined Diphtheria, Tetanus and Acellular Pertussis, Hepatitis B enhanced Inactivated Poliomyelitis and Haemophilus influenzae type B vaccine (Infanrix™ hexa) periodic safety update reports (PSURs) covering the two year period from 23 October 2009 to 22 October 2011.(1)
Vaccine is “favourable,” despite long list of health conditions
The document suggests that, although there are several adverse health effects associated with vaccine, the risk is not deemed to be problematic:
The Company will continue to monitor cases of anaemia haemolytic autoimmune, thrombocytopenia, thrombocytopenic purpura, autoimmune thrombocytopenia, idiopathic thrombocytopenic purpura, haemolytic anemia, cyanosis, injection site nodule, abcess and injection site abscess, Kawasaki’s disease, important neurological events (including encephalitis and encephalopathy), Henoch-Schonlein purpura, petechiae, purpura, haematochezia, allergic reactions (including anaphylactic and anaphylactoid reactions) cases of lack of effectiveness as well as fatal cases.(1)
Yet, despite the long list of health problems mentioned, the document maintains, “The benefit/risk profile of Infanrix hexa continues to be favourable.”(1)
In 2014, Infanrix was ruled by an Italian court to be responsible for a young Milan boy developing autism shortly after receiving the GlaxoSmithKline vaccine. As such, the decision was to award the boy for his vaccine-induced autism.(2)
The child received a series of Infanrix hexa injections in 2006, a vaccine designed to protect children from polio, tetanus, hepatitis B, diphtheria, pertussis and Haemophilus influenzae type B. Instead of being protected, his health declined: He developed autism. Medical experts in the Italian Court pointed to the confidential document, suggesting that the boy likely developed the condition due to the variety of antigens and thimerosal (a mercury-containing preservative now banned in Italy due to its neurotoxicity) and a host of other toxic ingredients that were in the vaccine at the time.(2)
Of Infanrix hexa’s thimerosal, the Court noted that it was “in concentrations greatly exceeding the maximum recommended levels for infants weighing only a few kilograms.”(2)
Despite irrefutable proof that vaccines cause autism, court appeals are in the works
Interestingly, in 2012, the Italian courts made a judgement in a similar situation in which they ruled that the MMR (measles, mumps and rubella) vaccine caused a child’s autism. Just like the Infanrix hexa ruling, however, this finding has not set well with the Ministry of Health; they initially denied compensation to the family. Ultimately, the court granted compensation. Still, in the case of the young boy who was given the Infanrix hexa vaccine, the Ministry of Health has appealed, a process that’s expected to take several years to sort out.(2)
Such rulings should be applauded, although it’s disturbing 1) that appeals have ensued, and 2) that the United States has yet to come close to such court decisions.
This document — straight from the horse’s mouth, GlaxoSmithKline themselves — blatantly shows that vaccines are linked to autism and other conditions. What more is there to question, when the proof exists before our very eyes?
Former University Professor Martin Keller published a 2001 paper on the drug Paxil that has allegedly been ghostwritten by GlaxoSmithKline.
Two weeks ago, Edmund Levin and George Stewart, members of the American Academy of Child and Adolescent Psychiatry, sent a letter to the editor of the Academy’s journal, requesting an explanation as to why a controversial study led by former Brown Professor Emeritus of Psychiatry and Human Behavior Martin Keller has not been retracted.
The paper — which details the findings of Study 329 and focuses on the effects of the drug Paxil on adolescent depression — has been continually criticized since its publication in 2001.
While Levin and Stewart have worked to get the paper retracted, Jon Jureidini, a professor at the University of Adelaide in Australia and a member of the nonprofit Healthy Skepticism, has been working with his team to reanalyze the original data and republish the results.
A controversial history
Since its publication, Keller’s paper, which suggests that Paxil is an effective treatment for adolescent depression, has been criticized for being ghostwritten by associates of GlaxoSmithKline — the drug company that makes Paxil.
In 2006, Keller publicly acknowledged that GSK had given him tens of thousands of dollars during and after the time the study was conducted. Keller did not respond to multiple requests for comment for this article.
A Senate investigation in response to a U.S. Department of Justice lawsuit confirmed the presence of ghostwriting in the paper, said Paul Thacker, a fellow at the Edmond J. Safra Center for Ethics at Harvard who participated in the Senate inquiry.
But Rachel Klein, one of the 22 cited authors on the Keller paper and a professor at New York University, said while she thinks GSK played a role in writing the paper, it was not ghostwritten.
Continued research in the years after the article’s publication has suggested Paxil is linked with an increase in suicidal ideation in adolescents, The Herald previously reported.
The study is continually cited in other papers as evidence of Paxil’s effectiveness, Jureidini said. That a fraudulent paper is still cited “really has to be addressed,” he added.
“I think the concern is legitimate,” Klein said. “But I think it is too bad because the paper presents everything. As long as you give the information, you’re not misleading.”
The University has declined to support any efforts to have the paper retracted, The Herald previously reported.
Leemon McHenry, a member of Healthy Skepticism, and Jureidini have written to the University administration to ask for support in having the article retracted, but administrators have refused, McHenry said.
“The University takes seriously any questions about the soundness of faculty-conducted research,” said Marisa Quinn, vice president for public affairs and University relations. “While the University cannot comment on individual personnel cases, it does take appropriate actions whenever such questions are raised… We have effective policies in place, and those policies are consistently applied, although they are confidential.”
Clinical Professor of Family Medicine David Egilman ’74 MD ’78 said though no institution has ever punished a faculty member due to ghostwriting, “It’s a social responsibility to make sure that fraudulent information is not published by faculty.”
Retracting the paper
Levin said he first became interested in Study 329 due to his association with AACAP.
Though 13 years have passed since the publication — and despite the Senate investigation finding the Keller article to be fraudulent — there “still has been no effective action in getting it retracted,” Levin said.
Levin and Stewart’s regional division of AACAP has sent two different letters to Andres Martin, the editor of the journal. In addition to the one sent two weeks ago, the group sent a first letter requesting the study’s retraction.
In response to the first letter, Martin wrote that the paper did not meet the criteria for retraction, Stewart wrote in an email to The Herald.
The group was also informed that AACAP leadership had instructed the ethics committee not to investigate the article, Stewart said, adding that he was not sure why the committee had been “muzzled.”
Martin has not yet responded to the group’s second letter, asking for an explanation, Stewart wrote.
Martin did not return The Herald’s requests for comment.
Reanalyzing the data
Jureidini, along with four team members, is currently reanalyzing the data from Study 329 to “write the paper as it should have been written,” he said.
The decision to do so came in the wake of the British Medical Journal’s Restoring Invisible and Abandoned Trials initiative, announced June 2013. The initiative “calls for third party authors to publish or republish unpublished and misreported clinical trials,” according to a document released by the BMJ.
In the document, the BMJ named Study 329 an “abandoned study” — a study no one is working on but which is “misreported” and has not been corrected or retracted.
Jureidini said he and his team have been reanalyzing the data since late last summer and hope to have a draft completed in the next month.
“What they have found is that the fraud and corruption in the Keller article is far worse than anyone ever expected,” McHenry, who has worked closely with Jureidini, said. Specifically, the paper is far worse in terms of safety and efficacy, he added.
Very few people, including Keller, ever looked at all the raw data, McHenry said, adding that most of this was done by statisticians associated with GSK.
It is “ironic” that his team has looked at the data more than any of the authors of the Keller article, Jureidini said.
Levin and Stewart both said they support the study’s reanalysis. It may “be unrecognizable when Jureidini publishes it,” Levin said.
Jureidini said he hopes the original Keller article will be retracted in the wake of the republished one.
But Klein said she does not think the new results will show the Keller article to be fraudulent.
“I’m all for the data being examined,” she said. “If it is true that the results are very different, that would be a very different situation, but I can’t imagine that that would be the case,” she said.
A clinical perspective
Despite the Keller paper’s suggestion of the efficacy of Paxil, many psychiatrists said they do not prescribe the drug to patients.
Multiple psychiatrists interviewed said Paxil has worse side effects and withdrawal symptoms than other antidepressants and should not be prescribed as a first-line drug.
Allegations of ghostwriting and the role GSK played in Study 329 raise issues related to the relationship between psychiatrists and drug companies.
Study 329 and the Keller article are “a very good soap box from which to talk about the atrociously dishonest and morally unethical things the pharmaceutical industry has done,” Levin said.
Thacker said studies like Study 329 show that psychiatry is not independent from drug companies, and pharmaceuticals have “captured and owned the field of psychiatry.”
“You can’t live with them and you can’t live without them,” said Louis Velazquez, a practicing child and adolescent psychiatrist, referencing drug companies.
Research psychiatrists also rely on pharmaceutical companies to fund their research, said John Fanton, a child and adolescent psychiatrist at Baystate Medical Center and an assistant professor of psychiatry at Tufts University School of Medicine, who was completing his residency at Brown when the allegations about Study 329 arose.
When there is an economic downturn, there is “a legitimate need to identify and access other finding streams,” he said, adding that pharmaceuticals often will provide the most money for research.
But there is an “inherent conflict” between researchers and pharmaceutical companies, because researchers are required to share both good and bad knowledge, and pharmaceutical companies may have different goals, Fanton said.
If the paper is retracted, it will create “ongoing problems” for GSK, Thacker said. “There’s a lot of egos and a lot of money at stake.”
Active pharmaceutical ingredients manufactured by GlaxoSmithKline in Cork have been found to be contaminated from its pharmaceutical waste tank.
The US Food and Drug Administration said the company became aware of the contamination of the ingredient, which is in anti-depressant drugs that go by brand names Paxil and Seroxat, at its plant in Currabinny, Carrigaline, as far back as January 2012.
It said GSK completed risk assessments to determine the impact on its products, but said potentially contaminated batches were distributed after it became aware of the “significant deviation”.
The FDA told GSK: “Until all corrections have been completed and FDA has confirmed corrections of the deviations and your firm’s compliance with current good manufacturing practice, FDA may withhold approval of any new applications or supplements listing your firm as an [active pharmaceutical ingredients] manufacturer.”
The FDA said failure to correct the deviations could result in the FDA refusing admission of “articles” manufactured at the company.
GSK has issued a recall for 47 batches affected, dating from March 2011 to February 2012. It said regulatory bodies in countries where the batches ended up will issue the recalls. A company spokeswoman in Ireland was unable to confirm whether any of the batches went into circulation here.
GSK last night said it had carried out a full assessment and determined there was no risk to human health.
I think that some of the comments on this articulate my opinion better than I can myself today…
I’ll blog more on this later…
“Maybe I’m misreading this, but wasn’t this spurred by the fact that they got caught committing a crime in China?”
“Evidently we are supposed to applaud this news: one of the largest drug making companies, repeatedly caught in unethical and manipulative behavior designed to increase its already enormous market share, is now going to behave slightly better, without admitting in any way that it’s done anything wrong”
“As a former pharmaceutical sales representative, sales manager, marketing director and regional president of a pharmaceutical company I have observed the declining ethics in the industry in the last fifty years.
There were many companies,generally headed by a physician, offering a very wide range of products, both over the counter and prescription.
In my company, sales representatives were either pharmacists or had pre-med college backgrounds.
Marketing was educationally oriented. Before each two month sales program a meeting to update all research and published information was held.
Marketing information was given only to pharmacists and physicians.
As the companies were generally headed by a physician, they were very patient and service oriented.
Now there are a few, monopolistic companies. The range of products is limited by their potential sales volume.
Sales representatives preferred are “pom pom” girls because they have better “personalities” to react with the physicians. Especially when promoting erectile dysfunction products.
Marketing is to the consumer in TV, magazines, etc. emphasizing possible benefits in photos and large print and limiting possible dangerous side effect in microscopic volumes.
The advertising directly to the public is the most unethical of all. Instilling doubt, suggesting benefits and obscuring risks to a public which is not educated to evaluate is gross.”
Glaxo Says It Will Stop Paying Doctors to Promote Drugs
Glaxo is first among its peers to announce a plan to end paid-speaker programs, but it is not the only one considering such a move, said Pratap Khedkar, who oversees the pharmaceutical practice at ZS Associates, a global sales and marketing firm.
He said a handful of drug makers were weighing similar actions for several reasons, including concerns about the reaction to the required disclosure of such payments that will begin next fall under a provision of the health care law. Glaxo and several other major companies already report many such payments, but Mr. Khedkar said the new requirements may go farther than what some companies are reporting, and will be accessible on a searchable government website.
Previously, “It wasn’t really made public in some big, splashy way,” he said.
Jeff Francer, vice president and senior counsel at the Pharmaceutical Research and Manufacturers of America, the industry trade group, said many other companies were looking for ways to better reach increasingly busy doctors — who may not have time to travel to a conference in the first place — and Glaxo’s actions represent just one example.
“Of course all of our companies are looking for ways in which they can refine their relationship with physicians to make sure they’re making the best use of physicians’ time,” he said.
Beginning in 2015, Glaxo will also no longer compensate sales representatives based on the number of prescriptions doctors write, a standard practice that some have said pushed pharmaceutical sales officials to inappropriately promote drugs to doctors. In 2012, Glaxo paid a record $3 billion in fines to resolve charges that it had marketed drugs for unapproved uses. It is one of several major companies to have settled such cases in recent years.
Glaxo said its sales representatives worldwide would instead be paid based on their technical knowledge, the quality of service they provided to clients to improve patient care, and the company’s business performance. The company made such changes in the United States in 2011 — and is required to continue the new program under a corporate integrity agreement with the Justice Department — but will now extend the practices to its global business.
Mr. Khedkar said some other companies were also experimenting with ways to compensate sales representatives, but they must tread carefully.
“You remove the incentive to do anything inappropriate, but you also remove the incentive to do what is appropriate, which is to promote the on-label use of your product,” he said.
Mr. Witty said the experience in the United States had been positive and had improved relationships with doctors and medical institutions.
Dr. Raed Dweik, the new chairman of the innovation management and conflict of interest committee at the Cleveland Clinic, said he hoped other companies would follow suit.
“As a physician, I periodically meet with these sales reps and they usually come in armed with information about me that I don’t even know,” he said, like the number of prescriptions he writes for the drug company’s product. “I feel that’s not really a comfortable interaction to have.”
A group of 38 British people who developed narcolepsy after receiving the “Pandemrix” swine flu vaccine have launched a legal claim against its manufacturer.
The Government admitted in September that evidence suggests the jab can cause the neurological disorder, which results in excessive drowsiness and severely disrupted sleeping patterns.
Lawyers representing the group, most of whom are children, claim each could be due to £1 million in compensation after launching a class action against its manufacturer, GlaxoSmithKline (GSK).
But any award is likely to be paid for by the taxpayer because an indemnity agreed between GSK and the Department of Health states that any compensation claims and costs must be paid by the government.
The vaccine was administered to high-risk groups including children and adults with asthma, diabetes and heart disease at the height of the swine flu pandemic in 2009-10.
Evidence compiled by the Health Protection Agency earlier this year suggests that about one in 55,000 vaccinated children – or about 20 in total in the UK – may have gone on to develop narcolepsy.
The condition causes serious disruption to patients’ sleep and everyday life, and in some cases sufferers develop a related condition called cataplexy which results in total loss of muscle control.
Peter Todd, a solicitor at Hodge Jones & Allen, who is representing the 38 families, described the indemnity agreed between GSK and the government as “almost unprecedented”.
He added: “I did not expect GSK to invoke their entitlement to be indemnified by the UK Government – however they have done so immediately after the UK Government itself admitted a link between the vaccine and narcolepsy.
“Narcolepsy is a serious, incurable condition requiring a lifetime of medication and management. Many of the activities that most people take for granted can be totally compromised, such as study, work and the ability to have sole care of young children. The innocent victims of this deserve support and provision for their futures.”
A GSK spokesman said the government had agreed to “manage and share the responsibility of any legal claims” because of the “unprecedented” scale and speed of vaccination programmes against H1N1 pandemic flu.
“Patient safety is our number one priority and we are actively researching how narcolepsy is triggered and how this vaccine might have interacted with other risk factors in affected individuals,” they added.
A Department of Health spokesperson said: “We are aware of this claim and are working with GlaxoSmithKline to consider it as quickly as practicable.”
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.
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.
“All I’ll say is that from all my dealings with GSK I know that they are a very important, very decent and strong British business that is a long-term investor in China and it’s a business that very much does think about the long-term development of its products and its businesses,” he said.”
Simply astounding comments by David Cameron in his defense of GSK in China. It seems a bit pathetic in my opinion- that GSK need to get the UK prime minister to give them a character reference.
He’s only short of breaking into morris dancing, leaping into a silly-walk or blurting out three hail mary’s and a bloody novena.
You couldn’t make this shit up…
It’s all very python-esque methinks..
(Apparently the bribing of Chinese doctors by GSK has been going on since 2007)
British Prime Minister David Cameron gestures as he delivers a speech to students during his trip in China at Shanghai Jiao Tong University in Shanghai, December 3, 2013.
CREDIT: REUTERS/CHINA DAILY
(Reuters) – British Prime Minister David Cameron on Tuesday mounted a robust defence of GlaxoSmithKline’s business practices in China – where it is being investigated for alleged bribery – calling the firm “very decent”.
Cameron’s intervention came a day after he raised GSK’s situation with China’s top leadership in a move one person familiar with the conversation said was designed to draw a line under the company’s woes and ensure it was treated fairly.
Cameron is on a trade promotion trip to China with around 100 executives, including GSK Chief Executive Andrew Witty, and is trying to help the firm grapple with the aftermath of accusations it funnelled up to 3 billion yuan ($492 million) to travel agencies to facilitate bribes to boost its drug sales.
The claims are the most serious against a multinational in China in years. Police detained four Chinese GSK executives as well as Peter Humphrey, a British man running a risk advisory group. He is still being held.
Cameron on Tuesday gave reporters what amounted to a strong character reference for GSK, making it clear he was happy to fight its corner.
“All I’ll say is that from all my dealings with GSK I know that they are a very important, very decent and strong British business that is a long-term investor in China and it’s a business that very much does think about the long-term development of its products and its businesses,” he said.
“I think it is right to raise a case like that. Britain has a record of properly standing up for British businesses and British individuals, raising individual cases in the right way and about having a proper dialogue with the Chinese authorities about the issues.”
The person familiar with the matter said Britain had detected a softening in China’s position, saying it had encouraged GSK’s Witty to join Cameron in China.
Witty himself has declined to comment on the investigation into alleged illegal payments by GSK to doctors and officials, but told Reuters in Beijing on Monday that the British drugmaker would have something to say “quite soon”.
GSK is Britain’s largest pharmaceuticals business and a major employer of skilled workers, including many scientists. Witty has advised Cameron on business matters in the past and recently wrote a report on universities for the government.
The scandal has tarnished the image of both GSK and its CEO, who has sworn to get to the bottom of any wrongdoing.
GSK’s sales in China dived 61 percent in the third quarter after hospital staff shunned visits by its sales teams in the wake of the investigation.
Legal and industry sources told Reuters last month that police were likely to charge some of GSK’s Chinese executives but not the company itself. One person with direct knowledge of the situation said the police investigation was likely to be concluded by around early December.
GSK has said some of its senior Chinese executives appear to have broken the law. It has also said it has zero tolerance for bribery, calling the allegations in China “shameful”.
GSK sold 759 million pounds ($1.2 billion) of pharmaceuticals and vaccines in China in 2012, up 17 percent on 2011, representing about 3.5 percent of its worldwide total.
Whilst researching Hudson’s GSK career on the web I came across these two very interesting articles. Since this blog was set up 6 years ago in order to document the Seroxat Scandal- and all that it entails -it seems Ian Hudson might be a major player in unravelling the truth about Seroxat- therefore some coverage of him is entirely warranted.
I would realy like to know what he knows about Seroxat… What was his role at GSK? Did it involve Seroxat? Does he know what GSK have hidden in their Seroxat files? As the previous head of “Global Safety” at GSK and now the guy responsible for safe-guarding the UK public from potentially harmful drugs such as Seroxat and Avandia how does Ian Hudson reconcile his conscience when a drug he once defended has been proven to kill?
Does Ian Hudson still take the stance of his previous employers (GSK) in regards to Seroxat efficacy and safety? It was- after all- way back in 2001 when Ian Hudson defended Seroxat (Paxil) in a case where GSK were found guilty. Since that time- there have been numerous settlements involving Paxil withdrawal cases, suicides and birth defect class actions in the US. There have been petitions, documentaries, web-sites, patient groups and media coverage on the dangers of Seroxat/Paxil and much public outcry about the behavior of GSK (Ian Hudsons previous paymasters). Since 2001, GSK have paid Billions in fines, and been found guilty of numerous crimes of fraud and corruption – crimes and lies which have cost patients their lives. I wonder does Ian Hudson still stand by the credibility of GSK now- in light of their current reputation? Does he still believe their word is trustworthy?…
What was his role in all of this way back when he was working for GSK defending Seroxat in court cases in the US? As CEO of the medicines regulator, is he on the side of patients or the pharmaceutical industry?
A City MP is demanding to know why the UK is being represented in a European review of the antidepressant drug Seroxat by a man who used to work for GlaxoSmithKline (GSK).
Parmjit Dhanda, MP for Gloucester, is asking the Government why they allowed Dr Ian Hudson to take part in the European Medicines Evaluation Agency (EMEA)’s review of Seroxat. As well as working as worldwide safety director for GSK – the manufacturers of Seroxat – from 1999 until 2001, Dr Hudson acted as witness for the defence in a trial in which Seroxat was accused of triggering a man’s violent and suicidal behaviour.
But the Government’s Medicines and Healthcare Products Regulatory Agency (MHRA) says it is satisfied Dr Hudson’s previous links with GSK will not compromise the review.
They say he will not be allowed to participate in Seroxat discussions during the review.
Mr Dhanda said: “I am really determined to get to the bottom of this.
“We need to make people aware that there are representatives involved in this inquiry into the drug who have worked with GSK in the past.
“Secondly, we have got to change this completely and we need to get some fully independent people involved.”
Mr Dhanda yesterday tabled four questions in the House of Commons demanding answers from the Secretary of State for Health, John Reid.
Earlier this year, a UK review into Seroxat was disbanded after it emerged many of the members held interests in GSK.
Alongside another representative from the MHRA, Dr Peter Arlett, Dr Hudson is part of a team of 30 experts from across Europe who are evaluating the safety of Seroxat following concerns raised in the UK and in the United States.
Noel Wadhion, head of the post-licensing of human medicines at the EMEA, told The Citizen: “We are looking at safety concerns relating to a potential risk of emotional changes and withdrawal reactions in the use of Paroxetine – the medical name for Seroxat.”
The experts, who began their review in June, hope to announce their results by the end of this year.
According to the EMEA, there are four possible recommendations to come as a result of their review – no action, change advice about the drug given to doctors, suspend the drug or withdraw it altogether.
Their recommendation will then be passed to the European Commission who will then make a final decision to be implemented throughout Europe.
GSK maintains that Seroxat – now the company’s best selling drug – is an effective treatment that has helped tens of millions of patients worldwide to lead fuller and more productive lives.
The appointment of Dr Hudson has angered Seroxat users in Gloucestershire who still hope for a full independent inquiry into the drug they claim has destroyed their lives.
Faye Elliott, spokeswoman for the Gloucestershire Seroxat Support Group, said: “Knowing that the European decision will be final, it is very worrying for the thousands of us who are still suffering with either side-effects or withdrawal symptoms from this drug.
“We would like to see this drug banned, as we believe there is enough evidence to suggest that this drug can cause suicidal ideation and self-harming.”
But the EMEA remain confident of its ability to reach a fair conclusion.
Mr Wadhion said: “We ask all members of our committee if there is any potential conflict of interest that we should be aware of.
“They must declare their interests before a debate can take place and must leave the room if a conflict arises.”
A spokesman for the MHRA said: “The Government actively encourages interchange between the Civil Service and industry, but takes care to ensure that there are no conflicts of interests.
“In line with this principle, Dr Hudson has had no involvement in matters relating to Seroxat since joining the agency and will have no involvement in the referral.”
In my last post, Psychotic doubt, we saw the most successful maneuver that has ever been devised for hiding dead bodies and silencing us when we are injured. We saw a mechanism that acts like the authority of a psychoanalyst (when Freud was still in vogue), or an ecclesiastical authority (until recently), to silence dissent and cause someone who has been abused to doubt their sanity and blame themselves for something done to them. This mechanism that allows companies, regulators, and academics to hide dead bodies by an appeal to evidence that in actual fact shows an increased risk of death on treatment is not just psychosis-inducing; it also has a Burn in Hell component to it. This is how it happens. Here is Ronald Krall being deposed in 2007. He is the head of Global Safety at GlaxoSmithkline. Q: Are you willing to tell the jury under oath that you are not aware of a single side effect that is caused by Paxil? A: I am prepared to say to the jury that I am not sufficiently familiar with all of the data for all of the adverse events to tell you that there is an adverse event that is caused by Paxil. Here is Ian Hudson being deposed in 2001, then head of Global Safety at GSK, later a member of the British regulatory apparatus, the MHRA:Q. Okay. So, your view is: It’s simply impossible for SmithKline Beecham to decide whether Paxil did or did not contribute to the homicidal or suicidal behavior of any one given individual; is that your testimony?A. We would certainly gather all the information, but on an individual case basis it would be impossible to decide whether paroxetine caused an event or not… It is impossible, on an individual case basis, from individual reports, to assign causality especially in a very complicated area such as this. That’s why, when we have issues, we review all the available data and make a determination, on the basis of all the available data, whether there is an issue or not.Q. Okay. Do you believe that it is possible that Paxil has caused any person, worldwide, to commit an act of homicide or suicide?A: I have seen no evidence to suggest that at all.If there is even a small possibility the problem could have been caused by chance, then it has been caused by chance.Hudson and Krall are demonstrating the standard company approach to determining causality. In this case GSK had lots of reports of suicide, aggression, birth defects, or dependence. In many cases the doctor, or patient, or a company employee notes that the problem happened soon after the drug was started, cleared up when the drug was stopped, and reappeared when the drug was restarted. As a result in many cases a GSK employee has said the drug has caused the problem. Both men know this, but for Hudson and Krall there is still no evidence that their drug causes a problem — even when the dependence on Paxil (Seroxat) is universally recognized. Why not? For Hudson and Krall and regulators like Bob Temple or Ian Hudson (who is now a member of the British regulatory apparatus), if a clinical trial hasn’t confirmed a statistically significant link between treatment and an adverse event, then the adverse event hasn’t been shown to be caused by the treatment. If there is even a small possibility the problem could have been caused by chance, then it has been caused by chance. The refusal to do a study while events pour in that meet all the standard criteria for causality is the real Burn in Hell moment. While the company avoids doing a sufficiently large clinical trial to test out the link, there will never be any evidence that the drug causes a problem. The refusal to do a study while events pour into the company that meet all the standard criteria for causality is the real Burn in Hell moment. Thousands of reports can pour in, each making a compelling case that the drug has caused the problem, but a Hudson or Krall or Temple will feel comfortable saying under oath they have seen no scientific evidence that the drug causes a problem.
Unbelievable though it will seem, lawyers for pharmaceutical companies have recently advised that company coding staff, when faced with convincing evidence a drug has caused a problem (that is, when a problem appears after the drug is started and clears when it is stopped and reappears when it is restarted), should not code this as caused by the drug as they have been doing.
When patients report problems to the company and ask if there is any evidence the drug might be contributing, they are commonly referred back to the doctor who has prescribed the drug — who will be faced with the scientific literature, which will say there is no evidence that the drug has caused the problem. When patients ask for evidence on a drug, they are referred back to their doctor — who will be faced with the literature, which will say there is no evidence that the drug has caused the problem. Here is an unknown woman in 2001 contacting GSK. She terminated her first pregnancy, after radiology showed the baby had a serious heart defect (truncus arteriosus) and would likely not survive. The response from GSK is as follows:
‘We are attaching a copy of our current product information for Paxil… Please review the section on USE DURING PREGNANCY.Further questions about your treatment should be directed to the physician, pharmacist or healthcare provider who has the most complete information about your medical condition. Because patient care is individualized, we encourage patients to direct questions about their medical condition and treatment to their physician. We believe because you physician knows your medical history, he or she is best suited to answer your questions. Our Drug Information department is available to answer any questions your physician or pharmacist may have about our products.
‘This response is in regards to an email I sent you preciously [sic]. I was asking to see if you have any, or were in the process of any clinical trials for women who are currently on Paxil and pregnant. I wanted to find out any information on women who were on Paxil during pregnancy and if they were able to have healthy babies. I am in no way insinuating your product did this to my child. I love the product and don’t think that I could have gotten through my panic attacks without the wonderful help of this miracle drug. I just want to get pregnant again soon. I do not want to put my unborn child through anything that would hurt him/her. Please, if you do not have information, where is this information held? Does anyone do studies like this? Please any information that you may give me would be great’.
The birth defects this woman’s child had suffered were coded as almost certainly linked to Paxil but neither she nor her doctor were told this. In internal company documents, the birth defects this woman’s child had suffered were coded as almost certainly linked to Paxil but neither she nor her doctor were told this.
This seems eerily reminiscent of appeals by Catholic cardinals to Canon Law (an idiosyncratic take on legal significance) when asked to account for their handling of abuse cases in the Church.
 Deposition of R Krall, Head of Global Safety GlaxoSmithKline, 2007.
 Deposition of Ian Hudson in Tobin vs SmithKline Beecham, December 15th 2000, 30–33.
THE Medicines and Healthcare products Regulatory Agency (MHRA) is one of those super regulators of which Labour is so fond.
But while many superwatchdogs like Ofcom appear to be hyperactive, the MHRA is earning a reputation for sleepiness and lack of transparency.
Nowhere has this been more obvious than in its recent dealings with GlaxoSmithKline.
To its credit, the agency moved with some speed a year ago to clamp down on the use of antidepressant Paxil/Seroxat by young people after it discovered potential suicide risks.
It also launched an investigation into why it had taken GSK so long to disclose a series of studies to regulators showing potential problems with Seroxat among young people.
One complication for the MHRA is that Dr Ian Hudson, currently director of licensing, was worldwide safety director for GSK until 2001. This potentially raised conflict of interest problems.
But until last week everything went quiet. That was when New York attorney general Eliot Spitzer launched his missile at GSK, accusing it of fraudulently suppressing research suggesting that the antidepressant was unsafe in treating young children.
The inquiries on both sides of the Atlantic are of a piece. Both focus on GSK’s methods and the way it presents data to the authorities, not on the substance of whether Paxil/Seroxat can be harmful in certain circumstances.
In fact, the problem is accepted by GSK which, in co- operation with the MHRA, sent out new instructions to medical practitioners last year.
A comparison could be made with Shell. The problem for the oil giant this year is not just that its reserves turned out to be less than it reported to the markets, but that bosses engaged in an elaborate cover-up to prevent this becoming public.
In the weekend press Jean-Pierre Garnier, GSK’s highly-paid, Philadelphia-based chief executive, fought back against Spitzer, accusing him of ‘bullying tactics’ and failing to alert GSK to what was coming.
It is interesting to note, however, that Garnier acknowledged that GSK’s research record has not been perfect.
Garnier and GSK cannot afford to ignore Spitzer. He is notably careful in preparing his cases and the Wall Street experience, where he brought to a head the market scandal, shows that he does not go on fishing expeditions. His cases are based mostly on hard evidence that walks through the door of his Manhattan office.
A settlement between Spitzer and GSK – if that is the route they take – could open the floodgates of compensation claims from the families of young Paxil/Seroxat users.
As important for the UK drugs industry is that the present cosy relationship between the MHRA and GSK – in which disputes rarely come into the open – is ended.
Moreover, the MHRA falls under the heavy hand of the Department of Health, which has little experience or apparent knowledge of cutting- edge commercial and pharmaceutical issues.
If it is to be an effective and trusted watchdog, the agency needs to be cut loose from government and the drugs industry. Nothing less will do to restore confidence in the approval process.
The resignation last night of Richard Brook, the chief executive of the mental health charity Mind, from an expert working group on antidepressants has prompted calls for a review of the system of regulating and licensing medical drugs.
Mr Brook was appointed as a lay member of the group, set up by the Committee on the Safety of Medicines last year for a thorough look at all the allegations against the antidepressant Seroxat, after years of patients’ and consumer groups’ concern about the side-effects of modern antidepressants. Some people say they cannot stop taking them, because withdrawal makes them feel so bad, others say the drugs have made them violent or suicidal.
On Thursday the CSM issued a warning to doctors about the appropriate dosage of Seroxat, a warning for which Mr Brook had been pressing in the light of trial data more than 14 years old which the CSM failed to consider in three successive reviews of the drug.
Mr Brook’s appointment was a departure from the CSM’s normal practices of drawing on a pool of scientists and drug experts who, with few exceptions, have or in the past had links with the drug companies, from shareholdings to research grants to their universities. All members have to declare their interests and either withdraw from the room or not vote when conflicts arise. Even so, there have been allegations of “institutional bias”.
The suggestion is that the regulating authorities and the drug companies are too closely interrelated. Key figures not only on the CSM but also in the Medicines and Healthcare Products Regulatory Agency – the drug licensing body which it advises – have a history of consultancy, research or even employment by pharmaceutical companies. Ian Hudson, for instance, the worldwide safety director of GlaxoSmithKline (GSK) until 2001, is now director of licensing at the MHRA.
The MHRA and CSM say that they have to draw on the expertise of a relatively small pool of highly qualified individuals who inevitably have gained their experience in the industry, but critics say it would be possible to find academics who are completely independent.
One of the fiercest critics, Charles Medawar of the consumer group Social Audit, will allege in a book to be published on Tuesday, Medicines Out of Control?, that the system is dangerously secretive, riddled with conflicts of interest, and indelibly flawed by chaotic and incompetent procedures for evaluating drug benefits and risks.
“These revelations [of the Seroxat trials] provide compelling evidence of the need for transparency in drug regulation. Had the evidence from these dose-ranging studies been made publicly available the regulators’ errors would have been apparent years ago,” he said.
Mr Medawar believes that there may be problems with the dosage of many other drugs, not only antidepressants. Eli Lilly, he points out, conducted a study of its own SSRI (selective serotonin reuptake inhibitor) drug Prozac in both 20mg and 5mg formulations. About 53% of patients responded satisfactorily to the low dose and 64% to the higher dose. Yet the 20mg tablet was licensed for everybody. “That means 50% of people are being exposed to four times the dose they need.”
Mr Medawar is one of those who are troubled by the revolving door between the drug regulators and the pharmaceutical industry. The MHRA chairman, Sir Alastair Breckenridge, resigned his position on Glaxo’s scientific advisory committee to take up his previous position as chairman of the CSM, although he has usually left the room when Seroxat has been discussed.
“For many years Breckenridge had close ties with the manufacturers of Seroxat, yet he played a key role in the regulation of that drug,” Mr Medawar said. While he was still on GSK’s advisory board Professor Breckenridge took part in the Seroxat licensing discussions, although he did not vote.
The data at the heart of the matter showed Seroxat to be ineffective and unsafe at high doses. An estimated 17,000 patients were put on doses higher than the recommended 20mg last year, according to the Department of Health. Seroxat is made by GSK in 20mg and 30mg tablets. But higher doses are no more effective than the 20mg pill, and carry the risk of increased side-effects.
The data on the drug comes from one of the original trials carried out to establish the effect and safety of different doses before GSK applied for a licence to sell it in 1990. Patients in the trial, which was conducted in 1985-86, were started on 10, 20, 30 or 40mg doses. Many of those on the higher doses dropped out because of the side-effects.
The MHRA and CSM were given this information by the company and they licensed it for depression, with 20mg as the recommended dose.
The MHRA, it is understood, did not employ statisticians at the time of the 1990 licence approval and must therefore have relied on GSK (then SmithKline Beecham) for an explanation of the data.
David Healy, director of the North Wales department of psychological medicine of the University of Wales, who claims that there is a suicide risk for a minority of patients on SSRIs, said: “This would look like a case of the MHRA taking what the company said. It’s only when they get pushed beyond a certain point that they begin to systematically check things out.”
Alastair Benbow, GSK’s head of European clinical psychiatry, said yesterday that GSK did not agree with the MHRA’s interpretation of the early study. He said the dosage study had been carried out in a way that would not be done today and that other studies, which had started patients on 20mg and then gradually increased the dose, should have been taken into account. Gradually increasing the dose was safe and some patients would benefit from taking doses of more than 20mg a day.
This is an industry that has succeeded in building a culture in which even good descriptions of the effects of drugs are dismissed as anecdotes – except of course for patients reporting stunning benefits on treatment.
An industry where Ian Hudson, then of GSK, now head of Britain’s FDA (MHRA), can get hundreds of reports of a problem like violence on Paxil-Seroxat and still say he has seen no evidence that Paxil-Seroxat causes any problems (See Burn in Hell).