Bad Pharma: How drug companies mislead doctors and harm patients

Here’s an unashamed plug for new book by Dr Ben Goldacre that’s out in a week or so.

‘Bad Science’ hilariously exposed the tricks that quacks and journalists use to distort science, becoming a 400,000 copy bestseller. Now Ben Goldacre puts the $600bn global pharmaceutical industry under the microscope. What he reveals is a fascinating, terrifying mess.

Doctors and patients need good scientific evidence to make informed decisions. But instead, companies run bad trials on their own drugs, which distort and exaggerate the benefits by design. When these trials produce unflattering results, the data is simply buried. All of this is perfectly legal. In fact, even government regulators withhold vitally important data from the people who need it most. Doctors and patient groups have stood by too, and failed to protect us. Instead, they take money and favours, in a world so fractured that medics and nurses are now educated by the drugs industry.

Patients are harmed in huge numbers.

‘Bad Pharma’ is a clear and witty attack, showing exactly how the science has been distorted, how our systems have been broken, and how easy it would be to fix them.

The Amazon link for pre order is here.

If you live in London and want to see Ben talk about this in person, then head to the Royal Institution on 2 October

The link for tickets is here.

Tony Scott and depression

From a quick look around the internet this morning, it appears that Tony Scott, who took his own life, may have been struggling to deal with depression.

It’s “speculative” and “unconfirmed”, but clearly jumping off a bridge is not what someone who is well would do.

When you’re in the throes of depression you don’t think about your family and friends; suicide looks to be a logical step – the only way to find peace – a way out.

But I think questions need to be asked – if, in fact, he was being treated for depression then I think we have to know if antidepressants were being prescribed and exactly what his prescription history was.

The link between antidepressants and suicide is not well understood, but in some cases there is a clear linkage – perhaps a change of medication was involved or even just a change in dosage.

Coroners and medical examiners should routinely be examining medical records and making details public so important information is not missed.

Because of Tony Scott’s fame we have the chance to talk about this now – and we should be doing all we can in order to understand why he took his own life.

My thoughts are with his family at this tragic time.

Inside Paxil Study 329, Courtesy the Justice Department

This is from Dr Howard Brody’s blog – Hooked: Ethics, Medicine, and Pharma

It sums up the story of Study 329 (with links to the original DoJ documents) and dovetails with the current scandal over Glaxo’s record $3 billion fine for witholding negative drug trial data for Avandia, the illegal marketing of drugs and bribing doctors to prescribe Glaxo products.

Remember, Study 329 was not covered by the latest $3 billion fine – Study 329 was yet another example of Glaxo’s lying and cheating to sell its drugs.

Now read on:

I’ve previously discussed the now-infamous Study 329, which took discouraging data on the efficacy and safety of paroxetine (Paxil) in kids and spun it into an article claiming excellent results:
http://brodyhooked.blogspot.com/2011/11/will-brown-university-investigate.html

Thanks to the U.S. Justice Dept. complaint in the suit recently settled by GlaxoSmithKline for a record $3B: http://www.justice.gov/opa/documents/gsk/us-complaint.pdf
–we can follow the history of this study in more detail, based on the internal GSK documents discovered during the proceedings, and see just how the data were manipulated for marketing purposes.

Study 329, directed by Dr. Martin Keller of Brown University, was one of 3 clinical studies in children and adolescents that were all interpreted by GSK scientists between August and October, 1998 to be discouraging. Study 329′s protocol specified two primary endpoints, and on neither measure did Paxil do better than placebo. The study also logged in 11 serious adverse reactions to Paxil, much more than in the placebo group, including 5 with agitated or suicidal behavior, the major risk for which eventually the FDA issued a black-box warning for the SSRI class of antidepressants.

Undaunted, GSK contracted in April 1998 with Scientific Therapeutics Information, Inc. to prepare an article for journal publication based on 329. As we know from other sources, STI writers basically wrote the paper and later did revisions, with minimal input from the supposed scientific authors, meaning that the paper was largely if not completely ghostwritten. As part of the laundering process, STI decided to downplay the primary endpoints and instead inserted 8 “efficacy measures,” none of which had been specified in the original study protocol. By what’s called data-dredging, STI was able to show that Paxil was statistically better than placebo on 4 of the 8 newly invented measures.

Initially the purported authors sent the paper to JAMA, claiming in the abstract that Paxil was “a safe and effective treatment for major depression in adolescents.” In December, 1999 JAMA rejected the paper, and reviewers’ comments indicated that the scientific reviewers had seen through the fog and realized that there were no solid data to show the superiority of Paxil. One internal memo then indicated that GSK and Dr. Keller agreed to send the manuscript to “a less demanding journal.”

Even the less-demanding Journal of the American Academy of Child and Adolescent Psychiatry originally couldn’t swallow the revised manuscript that Keller and company sent them in June 2000. Their reviewers detected some of the same problems as the earlier JAMA review.  GSK had STI go back to work responding to the reviewers’ comments and eventually JAACAP accepted the manuscript in February 2001.

According again to the Federal complaint, even with the recommended changes, GSK and STI (with the willing acquiescence of Dr. Keller and his co-authors, we presume) managed to slip in a number of incorrect and misleading statements. The abstract stated that the drug “is generally well tolerated and effective for major depression in adolescents.” The article mentioned the primary endpoints but failed to make clear that by neither was Paxil statistically superior to placebo. The article falsely implied that Paxil was superior on one of the primary endpoints by deliberately conflating one of the later “efficacy measures” with that endpoint. The article consistently downplayed all the measures where Paxil failed to show superiority to placebo and focused on the few, invented-later measures where a statistically significant result had been found.

More important, the 11 patients with serious adverse reactions due to Paxil, and the 5 of them with specifically suicidal or agitated symptoms, magically disappeared. In the revised manuscript the investigators suddenly decided that only one of the reactions (headache) was actually caused by Paxil, and the other bad outcomes were unrelated to the drug. When the FDA got its hands on the raw data from 329, it eventually determined that 10 of 93 patients taking Paxil had experienced a potentially suicidal reaction–a far different and scarier picture than that portrayed in any of the drafts or in the final manuscript.

To be sure that child psychiatrists heard the correct marketing message, GSK sponsored 8 “Forum” meetings at lavish resorts such as Rio Mar Beach Resort in Hawaii and Renaissance Esmerelda Resort in Palm Springs, CA. The psychiatrists who attended had their airfare and hotel paid plus a $750 honorarium, and in many cases their spouses were also paid for (a practice supposedly prohibited in the 2002 PhRMA code of conduct). The hired speakers who told them how wonderful Paxil was for treating kids received $2500 honoraria in addition.

Talking of speakers’ bureaus, another media summary of the complaint:
http://finance.yahoo.com/news/glaxosmithklines-gsk-3-billion-whistleblower-154800879.html
–reported that GSK had enrolled 49,000 health professionals to be on its speakers’ bureau for Paxil and other drugs. Two conclusions are possible: 1) there are 49,000 really excellent and scientifically informed speakers out there whose talents are needed to inform their fellow practitioners; or 2) a “speaker’s bureau” is really nothing but a disguised bribe to get all those docs to prescribe a lot of the drugs they are paid to speak about.

Hat tip to Dr. Roy Poses of Health Care Renewal blog for sending me the link to the full complaint (all 76 pages, for anyone who wants some fun reading).

14 documents from Glaxosmithkline’s $3 billion drug marketing scandal that will disgust you

Here’s a piece from Business Insider’s Jim Edwards.

The link contains copies of documents filed in Court by the Dept of Justice.

Go and have a look at Jim’s article and you’ll get a glimpse into the world of drug ‘marketing’ and what Glaxo thinks is an acceptable way of doing business.

Andrew Witty claims that none of this goes on any more – I don’t believe him for one second as I think that the illegal activities are simply too ingrained in the way Glaxo does business. What Witty said was “I want to express our regret and reiterate that we have learned from the mistakes we made.”

What have you learned then, Andrew?

How not to get caught?

Here’s that link again.

Britains biggest corporate crook? – GlaxoSmithKline a clear winner

Here’s a take on the Glaxo scandal from today’s Guardian by Terry Macalister.

GlaxoSmithKline, Britain’s biggest pharmaceutical group, has been selling anti-depressant drugs in the US for unapproved uses on children, concealing critical evidence from US regulator the Food and Drug Administration (FDA) relating to a diabetes product, and offering lavish entertainment to doctors willing to promote its medicines.

The problems came to light because of whistleblowers inside the company and adds to a string of other settlements with pharmaceutical firms that lead critics to claim problems are endemic in the sector.

Last month, Abbott Laboratories was forced to pay $1.6bn over its marketing of the antipsychotic treatment Depakote, while the total cost of industry fines is over $20bn covering the last two decades.

But the GSK case has shaken even the most hardened of industry observers, as prosecutors found the company had been allotting over half a million dollars a year to its district sales representatives to offer doctors regular golf lessons, fishing trips, and basketball tickets while promoting the use of antidepressant drug Paxil in children. The GSK sales campaign also involved helping to publish an article in a medical journal that misreported evidence from a clinical trial.

Meanwhile the company was also being accused of marketing the drug Wellbutrin for sexual dysfunction and weight loss, when it had only received official consent from the FDA to treat depression. Some of its drugs reps were reportedly describing Wellbutrin as “the happy, horny, skinny pill”.

In the case of a third treatment, Avandia, the company did not report to the FDA studies it had carried out that showed there were safety concerns about heart risks. Critics had been calling for the drug to be banned four years ago yet it was only in 2010 that restrictions were finally slapped on its use.

What’s happened to the perpetrators?

GSK has agreed to pay a $3bn fine to settle criminal and civil charges with federal and state governments stemming from illegal activity over 10 years. This is the biggest-ever fine of its kind but there seem no plans at this stage to pursue executives or other individuals in positions of power at the time. Through some of the period covered by the fine, the firm was run by the highly paid Frenchman Jean-Pierre Garnier, whose entitlement to a £22m “golden parachute” payoff if he left the company enraged shareholders and caused a historic investor revolt.

In response to last week’s announcement by regulators, the pharmaceuticals company said it had changed the way its sales staff are paid by eliminating individual sales targets.

Sir Andrew Witty, GSK’s chief executive, said the settlement brought a resolution to “difficult, long-standing matters for GSK” adding: “I want to express our regret and reiterate that we have learned from the mistakes we made.”

Critics point out that other executives directly named as having been told of concerns continue in top jobs, albeit in different companies.

Whistleblower Greg Thorpe first alerted the company to the entertainment offered to doctors and the culture that allegedly put profits above ethics in 2001. He raised his concerns with David Stout, who was then head of the US business, and Bob Ingram, GSK’s chief operating officer. When he was forced out of the company, he took his case to the regulators, which spent almost 10 years investigating the issues.

Stout became a non-executive director of another London-listed pharmaceutical company, Shire, and Ingram is chairman of the biotechnology firm Elan.

What’s the public image of the industry?

Rock bottom, despite drugs firms’ best efforts. GSK’s corporate responsibility report runs to more than 100 pages, and details its pledges to improve access to healthcare in the developing world, and cut its carbon footprint. Witty insists: “We firmly believe that operating in a responsible and ethical way is essential for the success of our business.”

But after last week’s case, there can be little doubt that Big Pharma is top of the table for misbehaviour ahead of the arms industry, which has hogged the limelight for the past 100 years.

Some point to a long-running pattern of behaviour reaching back much farther than the most recent revelations. Eliot Spitzer, who as New York’s attorney general sued GSK over similar allegations eight years ago, told the New York Times that companies like GSK seem incorrigible. “What we are learning is that money [ie fines] do not deter corporate malfeasance. The only thing that will work in my view is chief executive officers and officials being forced to resign and individual culpability being enforced.”

Sidney Wolfe, a doctor and director of consumer organisation Public Citizen’s health research group, goes further: “Until more meaningful penalties and the prospect of jail time for company heads who are responsible for such activity become commonplace, companies will continue defrauding the government and putting patients’ lives in danger.”

What’s the reality?

Despite the large fine, $3bn is far less than the profits made from the drugs. Avandia has made $10.4bn in sales, Paxil took $11.6bn, and Wellbutrin sales were $5.9bn during the years covered by the settlement, according to IMS Health, which provides information for the pharmaceutical sector.

The fact that the profits available from bestselling drugs dwarf the fines handed out if anything goes wrong means the kinds of misdemeanours picked up in the settlement are bound to happen, says Wolfe. His conclusion is that, for Big Pharma, “crime pays”.

What’s the UK doing about it?

All of GSK’s problems have come to light in the US, where corporate abuse is taken very seriously. Britain is different, and the FDA’s equivalent, the Medicines and Healthcare products Regulatory Agency (MHRA), appears to engage in lighter-touch regulation. The MHRA has never successfully prosecuted a company since it was established nearly 10 years ago. It did investigate GSK over alleged inappropriate use of a drug in 2008 but abandoned the case. Since then, the total amount of fines imposed on individuals engaged in counterfeiting is £73,300. Confiscation orders under proceeds of crime legislation have totalled £18.9m and the MHRA says it has issued 467 warnings and 151 cautions.

They sold us ‘happy pills’ – but all we got was suicide and misery

Slowly the mainstream media is catching up with the Seroxat scandal – but Peter Hitchins of the Daily Mail has been writing about Seroxat for a while now.

I’d guess that either he, or someone he’s close to, has been through the Seroxat experience

This is his latest commentary on GSK’s record $3 billion fine for mis-selling, bribery and hiding negative drug trial data.

I’d like to suggest that his paper starts a camapign for a judge-led investigation into GSK and the Seroxat scandal – what do you think Peter?

Here’s the article:

A scandal can exist for ages before anyone notices. Here is one such. Ten years from now we will look back in shame and regret at the  way the drug companies bamboozled us into swallowing  dangerous, useless ‘antidepressant’ pills.

You’d be far better off taking a brisk walk. The moment of truth must come soon, though most of Britain’s complacent, sheep-like media will be among the last to spot it.

I would have thought it was blaring, front-page, top-of- the-bulletin news that GlaxoSmithKline, one of our biggest companies, has just been fined £2 billion (yes, you heard that right, £2 billion) in the US for – among other things – bribing doctors, and encouraging the prescription of unsuitable drugs to children.

Its drug Paxil, sold here as Seroxat, was promoted as suitable for teenagers and children, even though trials had shown it was not.

Doctors were sent on free trips where they were treated to snorkelling, sailing, deep-sea fishing, balloon rides and spa treatments (and cash payments), to persuade them to prescribe these drugs, or to reward them for doing so.

A medically-qualified radio host was allegedly paid more than £150,000 to plug one GSK antidepressant for unapproved uses. GSK paid for articles approving its drugs to appear in reputable medical journals.

It is well known now among doctors that other drug companies have suppressed unwelcome test results on modern antidepressants. These results show they are largely useless for their stated purpose. In many cases they were not significantly more effective than dummy tablets in lifting the moods of patients. Thanks to Freedom of Information investigations, the truth is now out.

Even worse than this is the growing suggestion that, far from making their users happy, these pills can increase suicidal thoughts in their minds, perhaps with tragic results.

The Medicines and Healthcare Products Regulatory Agency undertook trials which showed that teenagers and children who took Seroxat were significantly more likely to experience such thoughts.

Sara Carlin, an 18-year-old Canadian student with everything to live for, hanged herself in 2007 despite official warnings (and warnings from her mother) that the drug could lead to self-harm.

Quite why it should magically be safe for adults, I am not sure. Nor was the coroner in the 2003 inquest on Colin Whitfield, a retired headmaster, aged 56, who slit his wrists in his garden shed two weeks after starting to take Seroxat. The coroner recorded an open verdict and said the drug should be withdrawn until detailed national studies were made.

Mr Whitfield’s widow Kathryn said: ‘We have no doubt that it was the drug that caused him to do it.’

I would also remind readers of the recent statement by Dr Declan Gilsenan, Ireland’s former Assistant State Pathologist, who says he has seen ‘too many suicides’ after people had started taking antidepressants and is sure the evidence is ‘more than anecdotal’.

The defenders of this nasty, profiteering enterprise – including doctors who ought to know better – will come up with the usual bleat of ‘correlation is not causation’.

Just remember that this was the same sly song that Big Tobacco sang, when it first became obvious that cigarettes caused cancer. It is time for a proper investigation, with evidence on oath and the power of subpoena.

GlaxoSmithKline (GSK) is to pay $3bn (£1.9bn) in the largest healthcare fraud settlement in US history

Don’t talk to me about ethics and trust. Don’t talk to me about company culture and values.

That’s one hell of a fine for Glaxo – the biggest healthcare fraud settlement in history… but in reality, it’s simply not enough – it goes nowhere near as far as it should.

There should be criminal prosecutions brought, because what we’re talking about here is not just illegal marketing of drugs – not just bribing doctors to prescribe GSK products – what we’re talking about here is dead people.

Patients have died because they were taking drugs that weren’t safe, drugs that weren’t even approved for their treatment.

In the case of Avandia, the drug is so dangerous that it can no longer be prescribed in Europe – it had to be withdrawn from the market because of high levels of heart attack, heart failure and stroke in patients.

It had to be withdrawn from the market because it killed too many people.

It makes you wonder how a drug like Avandia ever got a licence in the first place… how could the doctors running the drug trials have failed to see the dangers?

I think we should remember at this point it was GSK that paid for those very drug trials that painted Avandia in such a positive light. And Paxil. And Wellbutrin.

GSK has also admitted charges that it held back data and made unsupported safety claims over Avandia.

People have died. A fine is not enough.

Here’s the story from the BBC:

The drug giant is to plead guilty to promoting two drugs for unapproved uses and failing to report safety data about a diabetes drug to the Food and Drug Administration (FDA).

The settlement will cover criminal fines as well as civil settlements with the federal and state governments.
The case concerns the drugs Paxil, Wellbutrin and Avandia.

Deputy US Attorney General James Cole told a news conference in Washington DC that the settlement was “unprecedented in both size and scope”.

Doctors bribed
GSK, one of the world’s largest healthcare and pharmaceuticals companies, admitted to promoting antidepressants Paxil and Wellbutrin for unapproved uses, including treatment of children and adolescents.

The company also conceded charges that it held back data and made unsupported safety claims over its diabetes drug Avandia.

In addition, GSK has been found guilty of paying kickbacks to doctors.

“The sales force bribed physicians to prescribe GSK products using every imaginable form of high-priced entertainment, from Hawaiian vacations [and] paying doctors millions of dollars to go on speaking tours, to tickets to Madonna concerts,” said US attorney Carmin Ortiz.

As part of the settlement, GSK agreed to be monitored by government officials for five years.

GSK said in a statement it would pay the fines through existing cash resources.

Andrew Witty, the firm’s chief executive, said procedures for compliance, marketing and selling had been changed at GSK’s US unit.

“We have learnt from the mistakes that were made,” Mr Witty said. “When necessary, we have removed employees who have engaged in misconduct.”

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