Sunday, April 20, 2014

PhiztraZeneca

Pfizer mulls $100 bln bid for AstraZeneca - report

(Reuters) - U.S. pharmaceutical giant Pfizer has approached British rival AstraZeneca to propose a 60 billion pound ($101 billion) takeover, the Sunday Times reported on Sunday.

The paper said, citing senior investment bankers and industry sources, that informal conversations about a deal had taken place between the two firms but that no talks were currently under way after AstraZeneca resisted the approach.

AstraZeneca is Britain's second-biggest pharmaceuticals group with a current market valuation of around $80 billion, compared with Pfizer, which is valued at $193 billion, according to Thomson Reuters data.

Earnings at AstraZeneca fell 6 percent in the fourth quarter of 2013, and the drugmaker has said it expects them to keep falling in 2014 as generic competition to Nexium, its popular heartburn and ulcer drug, takes a big bite out of U.S. profits from late May.

AstraZeneca has suffered a dry period in drug discovery in recent years and badly needs to find new medicines to replace blockbusters such as Nexium and Crestor, a treatment for high cholesterol that will lose patent protection in a few years.

Pfizer is facing similar issues with patent expirations on top-selling drugs such as Viagra and anti-cholesterol treatment Lipitor.

Pfizer's last big acquisition was in 2009, when it bought U.S. rival Wyeth for $68 billion.

Officials at neither AstraZeneca nor Pfizer could immediately be reached for comment. ($1 = 0.5949 British Pounds) (Reporting by Stephen Eisenhammer; editing by Jane Baird)

http://uk.reuters.com/article/2014/04/20/pfizer-astrazeneca-bid-idUKL6N0NC0AV20140420?rpc=401&feedType=RSS&feedName=americasMergersNews&rpc=401

Free samples of prescription drugs are costly to patients, study says

By Karen Kaplan
April 16, 2014, 3:42 p.m.

Free samples of prescription drugs may seem like a great deal for patients. But even when doctors think they’re doing patients a favor by handing out the freebies, the real beneficiaries are the drug manufacturers, according to new research in the journal JAMA Dermatology.

Medical groups have grown increasingly wary about free drug samples, and they've already been banned by Kaiser Permanente, many academic medical centers, the Veterans Health Administration, the U.S. military and plenty of private medical clinics. Critics of the practice say it encourages doctors to prescribe drugs that are more expensive and potentially less safe  than the work-horse generics that are just as effective. If the goal is to make costly medications available to low-income and uninsured patients, there are better ways, they say.

Yet $6.3 billion worth of free samples were handed out to doctors in 2011, according to the market research firm Cegedim Strategic Data (as quoted by American Medical News). Among physicians, dermatologists are particularly likely to give free samples to their patients.

A group of researchers from Stanford University took a close look at how those free samples might be influencing the prescriptions written by dermatologists. They focused on prescriptions for patients with a new diagnosis of adult acne (either acne vulgaris or rosacea).

Based on survey data from the National Disease and Therapeutic Index, the researchers found that dermatologists were still enamored with free samples. In 2010, 18% of all prescriptions they wrote came with a free sample, up from 12% in 2001. That was in marked contrast to doctors from other specialties: Only 4% of their combined prescriptions were accompanied by a free sample in 2010, down from 7% in 2001.

Dermatologists were especially likely to give free samples to their adult acne patients – 25% of their prescriptions came with a free sample in 2010, up from 10% in 2001. Very often, the drugs that were most frequently prescribed with a free sample were also the most frequently prescribed overall. In 2005, for instance, the four acne medications most often prescribed with a free sample – Differin, Duac, Benzaclin and Retin-A Micro – were the four most-prescribed acne drugs as well, the researchers found.

It’s not just that these four drugs were perennial favorites. The list of top five acne drugs changed considerably between 2001 and 2010, according to the study. But the favorites were usually closely aligned with the drugs that doctors had available for free in their offices.

In 2010, nine of the 10 most popular acne drugs nationwide were either brand-name drugs or branded generics (which companies sell at a premium), and free samples for them are typically available. To get a sense of whether things would be different in the absence of free samples, the researchers examined the prescribing behavior of dermatologists at an academic medical center that had a policy against freebies. In this group, nine of the 10 most popular acne drugs were low-cost generics (which don’t come with free samples).

Similarly, in 2010, 79% of acne prescriptions in private practices were for name-brand or branded generic drugs, compared with 17% of prescriptions written by the academic dermatologists.

“Prescribing preferences are at least in part related to what is contemporaneously available as free samples,” the Stanford researchers wrote.

It doesn’t seem that the free samples wound up saving patients much money. Those who were seen in private practices walked away with prescriptions for $465 worth of medications, on average, while the patients treated at the academic medical center got prescriptions that cost about $200 to fill. “In other words, the national mean retail cost of the prescriptions received at an office visit for acne is conservatively two imes higher compared with the AMC (academic medical center), where samples were unavailable,” the researchers concluded.

In an editorial that accompanied the study, three dermatologists noted that this pattern had been documented before. A 2008 study in the journal Medical Care found that patients seeking treatment for a variety of ailments paid more out of their own pockets when they got free samples compared with patients who didn’t. But everyone pays, since “samples increase the cost of medicines for all patients by encouraging doctors to prescribe more expensive drugs,” they wrote.

The trio called on their fellow dermatologists and other physicians to steer clear of free samples: “Alongside those other inappropriate tools of drug marketing – sports tickets, Caribbean junkets, and free pens – samples belong not in dermatologists’ closets, but in our dustbins.”

http://www.latimes.com/science/sciencenow/la-sci-sn-free-drug-samples-generics-dermatology-20140416,0,1035454.story

Thursday, April 17, 2014

The List gets longer and longer

GSK adds Jordan and Lebanon to bribery investigations list

GlaxoSmithKline

GlaxoSmithKline has added Jordan and Lebanon to a growing list of countries where it is investigating allegations of bribery.

The British drug giant's latest admission marks the third and fourth bribery investigations it has disclosed in the last ten days.

It said it is investigating allegations "regarding the activity of a small number of individuals" in its operations in Jordan and Lebanon, where it employs a combined 140 staff.

"We started investigating using internal and external teams as soon as we became aware of the claims," said a company spokesman. “We have zero tolerance for unethical or illegal behaviour."

Around a week ago it emerged that GSK was investigating allegations of corruption against the company's Iraqi arm, where it employs around 60 people. The company was accused of hiring government-employed doctors and pharmacists as paid sales representatives to boost sales of its products.

The recent disclosures add to the pressures of a major bribery scandal in China, where in July authorities accused the company of paying as much as £320m in bribes to win market share.

The company has admitted that its own investigation into the allegations unearthed evidence of wrongdoing by a handful of sales staff, but maintains they worked outside GSK’s control systems. It has called the allegations “shameful” and said it is cooperating with the ongoing Chinese investigation. The scandal has hit sales of GSK products in China, where it makes around 3pc of global revenues.

Despite the numerous investigations, the company spokesman has maintained that GSK does not have a systemic issue with unethical behaviour.

He added that GSK last year received 161 complaints related to staff breaching its sales and marketing policies, and fired 48 of them. "These numbers are very similar to those reported by other companies in our sector," he said.

GSK last year became the first drug maker to end payments to doctors to promote its drugs and scrap individual sales targets for staff in an effort to tackle breaches of its code.

Despite GSK’s compliance problems in emerging economies, it continues to see these markets as crucial for the business. Last week it unveiled a $200m (£120m) investment in sub-Saharan Africa.

“We continue to believe that with robust compliance systems and, by working closely with local governments, our presence in these markets can help improve access to medicines and broader healthcare,” said the company spokesman.

http://www.telegraph.co.uk/finance/newsbysector/pharmaceuticalsandchemicals/10771122/GSK-adds-Jordan-and-Lebanon-to-bribery-investigations-list.html

Wednesday, April 16, 2014

And they try to tell you Big Pharma's Misdeeds Are All in the Past!

Whistleblower Lawsuits On The Rise

Whistleblower Lawsuit Trends

Posted on April 16, 2014 in Risperdal LawsuitsWhistleblower

Whistleblower claims, or “qui tam” lawsuits, brought under the federal False Claims Act, increased to 753 in 2013, an increase of almost 20% over the previous year.*  These claims resulted in aggregate net recoveries to the federal government of $3.8 billion last year.  For the past four years, whistleblower lawsuits have produced recoveries to the federal government exceeding an aggregate amount of $3 billion.

What is driving the rise in whistleblower lawsuits under the False Claims Act?  False claims involving healthcare and pharmaceuticals produced the largest share of recoveries in 2013, totaling $2.6 billion.  Procurement fraud, involving fraud in the bidding and award of government contracts, net recoveries to the federal government totaling almost $900 million.

Escalating whistleblower lawsuits involving the federal False Claims Act are prompting the federal government to devote increased resources towards the improvement of compliance with existing federal law.  The government has determined that reducing the number of False Claims Act lawsuits through improved compliance is a potentially more cost-effective approach than pursuing recoveries through protracted litigation.

Within the healthcare and pharmaceutical industries, drug “misbranding” cases are being most often pursued by the federal government.  These cases often involve “off-label” promotion of drugs by manufacturers and/or distributors who market the drug for uses other than those specifically approved by the FDA.

Specific whistleblower and qui tam lawsuits within the pharmaceutical and healthcare sectors in 2013 included Johnson & Johnson’s marketing of the antipsychotic drug Risperdal.  In November 2013, Johnson & Johnson paid $2.2 billion to resolve civil and criminal actions alleging kickbacks and off-label marketing of a litany of drugs including Risperdal, Invega, and Natrecor.

Audet & Partners, LLP is a leading plaintiff’s law firm in the pursuit of claims for dangerous pharmaceuticals, as well as whistleblower lawsuits and qui tam actions for violations based on the federal False Claims Act.  If you have information suggesting that a company has presented false claims that may have defrauded the federal government, you are urged to contact a whistleblower lawyer at Audet & Partners, LLP for a free, completely confidential consultation by calling (800) 965-1461, or by completing and submitting our inquiry form on the right side of this page.

* http://www.justice.gov/civil/docs_forms/C-FRAUDS_FCA_Statistics.pdf

Tuesday, April 15, 2014

Doctor Richard Saul: ADHD Does Not Exist


Adderall
Getty Images

Over the course of my career, I have found more than 20 conditions that can lead to symptoms of ADHD, each of which requires its own approach to treatment. Raising a generation of children — and now adults — who can't live without stimulants is no solution

This Wednesday, an article in the New York Times reported that from 2008 to 2012 the number of adults taking medications for ADHD increased by 53% and that among young American adults, it nearly doubled. While this is a staggering statistic and points to younger generations becoming frequently reliant on stimulants, frankly, I’m not too surprised. Over my 50-year career in behavioral neurology and treating patients with ADHD, it has been in the past decade that I have seen these diagnoses truly skyrocket. Every day my colleagues and I see more and more people coming in claiming they have trouble paying attention at school or work and diagnosing themselves with ADHD.

And why shouldn’t they?

If someone finds it difficult to pay attention or feels somewhat hyperactive, attention-deficit/hyperactivity disorder has those symptoms right there in its name. It’s an easy catchall phrase that saves time for doctors to boot. But can we really lump all these people together? What if there are other things causing people to feel distracted? I don’t deny that we, as a population, are more distracted today than we ever were before. And I don’t deny that some of these patients who are distracted and impulsive need help. What I do deny is the generally accepted definition of ADHD, which is long overdue for an update. In short, I’ve come to believe based on decades of treating patients that ADHD — as currently defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and as understood in the public imagination — does not exist.

Allow me to explain what I mean.

Ever since 1937, when Dr. Charles Bradley discovered that children who displayed symptoms of attention deficit and hyperactivity responded well to Benzedrine, a stimulant, we have been thinking about this “disorder” in almost the same way. Soon after Bradley’s discovery, the medical community began labeling children with these symptoms as having minimal brain dysfunction, or MBD, and treating them with the stimulants Ritalin and Cylert. In the intervening years, the DSM changed the label numerous times, from hyperkinetic reaction of childhood (it wasn’t until 1980 that the DSM-III introduced a classification for adults with the condition) to the current label, ADHD. But regardless of the label, we have been giving patients different variants of stimulant medication to cover up the symptoms. You’d think that after decades of advancements in neuroscience, we would shift our thinking.

Today, the fifth edition of the DSM only requires one to exhibit five of 18 possible symptoms to qualify for an ADHD diagnosis. If you haven’t seen the list, look it up. It will probably bother you. How many of us can claim that we have difficulty with organization or a tendency to lose things; that we are frequently forgetful or distracted or fail to pay close attention to details? Under these subjective criteria, the entire U.S. population could potentially qualify. We’ve all had these moments, and in moderate amounts they’re a normal part of the human condition.

However, there are some instances in which attention symptoms are severe enough that patients truly need help. Over the course of my career, I have found more than 20 conditions that can lead to symptoms of ADHD, each of which requires its own approach to treatment. Among these are sleep disorders, undiagnosed vision and hearing problems, substance abuse (marijuana and alcohol in particular), iron deficiency, allergies (especially airborne and gluten intolerance), bipolar and major depressive disorder, obsessive-compulsive disorder and even learning disabilities like dyslexia, to name a few. Anyone with these issues will fit the ADHD criteria outlined by the DSM, but stimulants are not the way to treat them.

What’s so bad about stimulants? you might wonder. They seem to help a lot of people, don’t they? The article in the Times mentions that the “drugs can temper hallmark symptoms like severe inattention and hyperactivity but also carry risks like sleep deprivation, appetite suppression and, more rarely, addiction and hallucinations.” But this is only part of the picture.

First, addiction to stimulant medication is not rare; it is common. The drugs’ addictive qualities are obvious. We only need to observe the many patients who are forced to periodically increase their dosage if they want to concentrate. This is because the body stops producing the appropriate levels of neurotransmitters that ADHD meds replace — a trademark of addictive substances. I worry that a generation of Americans won’t be able to concentrate without this medication; Big Pharma is understandably not as concerned.

Second, there are many side effects to ADHD medication that most people are not aware of: increased anxiety, irritable or depressed mood, severe weight loss due to appetite suppression, and even potential for suicide. But there are also consequences that are even less well known. For example, many patients on stimulants report having erectile dysfunction when they are on the medication.

Third, stimulants work for many people in the short term, but for those with an underlying condition causing them to feel distracted, the drugs serve as Band-Aids at best, masking and sometimes exacerbating the source of the problem.

In my view, there are two types of people who are diagnosed with ADHD: those who exhibit a normal level of distraction and impulsiveness, and those who have another condition or disorder that requires individual treatment.

For my patients who are in the first category, I recommend that they eat right, exercise more often, get eight hours of quality sleep a night, minimize caffeine intake in the afternoon, monitor their cell-phone use while they’re working and, most important, do something they’re passionate about. Like many children who act out because they are not challenged enough in the classroom, adults whose jobs or class work are not personally fulfilling or who don’t engage in a meaningful hobby will understandably become bored, depressed and distracted. In addition, today’s rising standards are pressuring children and adults to perform better and longer at school and at work. I too often see patients who hope to excel on four hours of sleep a night with help from stimulants, but this is a dangerous, unhealthy and unsustainable way of living over the long term.

For my second group of patients with severe attention issues, I require a full evaluation to find the source of the problem. Usually, once the original condition is found and treated, the ADHD symptoms go away.

It’s time to rethink our understanding of this condition, offer more thorough diagnostic work and help people get the right treatment for attention deficit and hyperactivity.

Dr. Richard Saul is a behavioral neurologist practicing in the Chicago area. His book,ADHD Does Not Exist, is published by HarperCollins.

http://time.com/25370/doctor-adhd-does-not-exist/

Monday, April 14, 2014

GSK Poland - Shelley Jofre writes in the BMJ

  1. Shelley Jofre, BBC Panorama correspondent
  1. shelley.jofre@bbc.co.uk
The company may have broken US and UK laws on bribery, says Shelley Jofre
GlaxoSmithKline (GSK) recently announced that by 2016 it will end direct payments to doctors for promotional talks and stop setting individual targets for its sales reps.1 The announcement by GSK, which last year made profits of £6.6bn (€7.9bn; $11.0bn), was broadly welcomed in an industry that has long been tarnished by accusations of corruption and aggressive marketing.
But just as Britain’s largest drug company attempts to rebuild its image, it has emerged that the company is now facing new allegations of bribery in Poland and Iraq.2 A BBC Panorama report, entitled “Who’s paying your doctor?,” has found that GSK is under investigation in Poland for allegedly bribing doctors there.
It’s alleged that GSK sales reps in the region of Lodz, Poland’s third largest city, paid doctors as recently as 2012 to boost prescriptions of some of the company’s best known drugs.
A spokesman for the Lodz public prosecutor’s office, Krzysztof Kopania, toldPanorama that one GSK regional manager and 11 doctors have been charged in connection with corruption allegations for offences committed in 2010-12.
One doctor has already admitted guilt, been fined, and given a suspended sentence. He told Panorama he took money but only under pressure from a GSK drug rep. The investigation is ongoing.
A former sales rep for GSK in Lodz, Jarek Wiśniewski, told Panorama that money from the company’s £1m annual marketing programme for GSK’s blockbuster asthma drug, fluticasone (which it markets as Seretide), was used to bribe doctors to boost sales of the drug.
“There is a simple equation,” Wiśniewski told Panorama. “We pay doctors, they give us prescriptions. We don’t pay doctors, we don’t see prescriptions for our drugs.”

Educational services

The whistleblower explained that the bribes were disguised as fees for “educational services.”
“We cannot go to doctors and say to them, ‘I need 20 more prescriptions’,” said Wiśniewski. “So we prepare an agreement for them to give a talk to patients—we pay one hundred pounds, but we expect more than a hundred prescriptions for this drug.”
Wiśniewski confirmed that the doctors understood clearly that they must produce a certain number of prescriptions in return for the money. It’s a bribe, he said.
The Polish investigation has established, independently of former employees, that contracts were signed and payments made to doctors in at least a dozen different health centres across the region of Lodz where there was no evidence that “patient education” had taken place.
The payments were often small by UK standards—according to the prosecutor most were for several hundred zloty, but some were for several thousands (100 zloty = £20 (€24; $33)). But for Polish doctors, who earn around £700 a month, the sums are considerable.
Another former GSK rep in Poland, who spoke to Panorama on condition of anonymity, confirmed the payments influenced doctors’ prescribing:
“This worked on the principle of a kind of obligation. The doctor feels obliged and he tries to a greater or lesser degree to fulfil that obligation. I think that—as with many colleagues—my feelings were very negative and unpleasant but such was the working culture. It is not easy to find a job.”
In response to Panorama’s questions about the case, GSK confirmed that it ran a programme in Poland in 2010-12 to help improve diagnostic standards and medical training for the benefit of patients with respiratory disease.
“[Some] sessions were delivered by specialist healthcare professionals who, based on contracts signed with GSK, received payments appropriate to the scope of work as well as their level of knowledge and experience. The provision of sessions under this programme was agreed with the Polish healthcare centres.
“Following receipt of allegations regarding the conduct of the programme in the Lodz region, GSK has investigated the matter, using resources from both inside and outside the company,” the company added. “The investigation found evidence of inappropriate communication in contravention of GSK policy by a single employee. The employee concerned was reprimanded and disciplined as a result. We continue to investigate these matters and are co-operating fully with the CBA [the anti-corruption bureau in Poland].”
GSK said it agreed that “there is a need to modernise interactions between the pharmaceutical industry and healthcare professionals to ensure patients’ interests are always put first and to eliminate even a perception of a conflict of interest. This is why we have made, and will continue to make, fundamental changes to our business such as opening up access to our clinical trial data, changing how we pay our sales representatives and stopping payments to healthcare professionals for speaking engagements and for attendance at medical conferences.”
Meanwhile, in Poland, doctors face jail sentences of six months to eight years if they are found guilty of giving or accepting bribes, and GKS’s Lodz manager faces one to 10 years if found guilty of bribery.
Wiśniewski first raised his concerns with his bosses at GSK in Poland in May 2011. He says they carried out an investigation, then he was moved to another department. In September 2012 he was eventually fired for “poor performance” even though he says he had been singled out as a high flier in previous years. He is now unemployed.
GSK did not respond to questions about how the Polish whistleblower was treated.

Cases in US and China

The details of the case emerge as GSK attempts to rebuild its image after pleading guilty in 2012 to criminal charges in the United States and paying $3bn (£1.8bn) in fines for promoting some of its best selling antidepressants for unapproved uses, bribing doctors, and failing to report safety data about its drug for the treatment of diabetes.3 The allegations dated to the mid-2000s, and Andrew Witty, who took over as chief executive in 2008, claimed the behaviour dated from a different era.
Similar allegations emerged last year in China, where authorities have accused GSK of funnelling substantial sums in expenses to doctors and officials in 2007-10 to encourage them to use its drugs. GSK’s funding for all advertising, promotional, and training activity in China during the relevant period was around ¥3bn (£288m; €350m; $483m). The extent to which this funding was used fraudulently remains under investigation. The company again said such behaviour was not sanctioned at a corporate level and that claimed senior executives of GSK China had “acted outside of our processes and controls.”4 GSK has said it is “cooperating fully with the investigation in China.”
The head of GSK China was replaced in 2013, and GSK has reportedly just sacked more of its Chinese staff.5
GSK confirmed recently that it is also investigating bribery accusations in Iraq.

Views from Public Citizen

But Sydney Wolfe, founder of US campaign group Public Citizen, is sceptical of GSK’s recent pledge to change its ways. He recently analysed all the fines paid out by the drug industry in the US over the past 21 years and says that GSK is a repeat offender that tops the list.6
“Glaxo was the number one with $7.6bn in these penalties and the number one company in the world in terms of total criminal and civil penalties. The penalties are not large enough to deter these illegal activities. They keep doing it over and over again, and in one year Glaxo makes more money in terms of profits than all the penalties they’ve paid over the 21 years.”
GSK challenged Public Citizen’s calculations, however, telling Panorama that they included $3.4bn, which was “not a penalty or a fine and did not relate to sales and marketing practises.” GSK said the sum was “from a resolution we reached in 2006 with the US Internal Revenue Service (IRS) to pay tax related to transfer pricing.”
If the new allegations are shown to be true, then GSK might have violated both the UK’s Bribery Act and the US’s Foreign Corrupt Practices Act (FCPA). In both countries it is illegal for companies based there to bribe government employees abroad. In the US, some drug companies have already paid out settlements after allegations they contravened the FCPA.
The Bribery Act came into force in the UK only in 2010, and there have not yet been any drug company prosecutions.
The US has taken a tough stance in recent years on drug industry corruption at home and abroad, making extensive use of whistleblowing legislation, which rewards employees who come forward with information about law breaking.
It was evidence from some of GSK’s former employees in the US that resulted in the $3bn payout in 2012. Blair Hamrick, a GSK sales rep in Colorado for seven years until 2002, told Panorama he often made large payments to doctors for “educational” talks that were, in reality, purely promotional:
“We would have these Continuing Medical Education programmes that would get CME credit for the doctors, and they were nothing but a commercial,” he said.
“There was what’s called an ROI analysis [return on investment] about six months after a specific speaker programme. So if we spent $5000 on a speaker and we spent $20 000 on tickets and food, that’s $25 000 invested. They would take all those physicians and they would track their prescription volume, and they would want to see an increase in prescriptions greater than $25 000 worth of business.”
Hamrick adds, “The abhorrent behaviour that was going on, it was not only condoned, but we were compensated heavily for doing it.”
GSK announced in December that it is going to scrap the link between its reps’ pay and drug sales targets globally by 2016.
A Washington lawyer who represented two other GSK whistleblowers, however, points out that this was something the company had already agreed to do in the US, as part of a Corporate Integrity Agreement drawn up during negotiations for the $3bn settlement.
Erika Kelton of law firm Philips and Cohen told Panorama: “There were prospective requirements for ongoing compliance that were imposed on Glaxo. In the past, GlaxoSmithKline had compensated sales representatives by paying them bonuses based on the amount of revenue that they generated. That kind of incentive compensation that’s geared to how much revenue you’re bringing in encourages off-label marketing, encourages borderline or over the line practices to get more sales.”
The latest allegations against GSK are likely to prompt further debate over how little is known about industry payments made to doctors in the UK, even if they are not breaking the law.
In the US, GSK was forced to detail exactly how much it pays individual named doctors, and the company’s payments to US physicians have since plummeted by 75%, from $56.7m in 2010 to $14.6m in 2013. A similar effect has been seen with many other drug companies that have been forced to publish such details in the US.
Since 1 April 2014, when the Sunshine Act came into effect, all pharmaceutical companies must now detail their payments to named physicians in the US. By contrast, drug companies in the UK have been obliged only since last year to supply an aggregate total. There is no way of finding out which individual doctors are being paid or how much.
The latest UK figures published by the ABPI (Association of the British Pharmaceutical Industry) on 3 April show that payments from the pharmaceutical industry to healthcare professionals last year totalled around £38.5m, roughly level with the previous year.
Stephen Whitehead, ABPI’s chief executive, told Panorama: “You need to work with healthcare professionals to get understanding of the new science coming through, and that is a legitimate relationship. What you need to have to maintain confidence in these relationships is absolute crystal clear transparency about the money that changes hands. Then let people make their own judgment as to whether they think that’s appropriate.”
Whitehead says the ABPI is committed to full disclosure of payments in the UK by 2016 and is currently developing a searchable, centrally hosted register for payments in collaboration with the medical community.

Timeline

  • July 2012—GSK pleads guilty to criminal charges over its business in the US in the early 2000s and pays $3bn (£1.8bn; €2.16) in fines, the largest settlement ever involving a pharmaceutical company
  • January 2013—First reports emerge that GSK faces allegations of widespread corruption in its Chinese workforce in 2007-10
  • December 2013—GSK becomes first major drug company to agree to full disclosure of all its trial data.
  • 2014—Allegations of bribery by GSK in Iraq (as recently as 2012) and Poland (in 2010-12) reported
  • 2016—GSK to end direct payments to doctors for promotional talks and attending conferences and stop setting individual targets for its sales reps

Notes

Cite this as: BMJ 2014;348:g2768

Footnotes

  • The Panorama programme “Who’s Paying Your Doctor?” it to be broadcast at 8.30 pm on Monday 14 April on BBC 1.

References

Panorama - Who's Paying Your Doctor?

UK drug company GSK 'paid bribes to Polish doctors'

14 April 2014 Last updated at 00:04
Glaxo logo

UK drug company GlaxoSmithKline is facing a criminal investigation in Poland for allegedly bribing doctors, BBC Panorama has discovered.

Eleven doctors and a GSK regional manager have been charged over alleged corruption between 2010 and 2012.

A former sales rep said doctors were paid to promote GSK's asthma drug Seretide.

The company said one employee had been disciplined and it was co-operating with investigations.

If the allegations are proved, GSK may have violated both the UK Bribery Act and the US Foreign Corrupt Practices Act. It is illegal for companies based in either country to bribe government employees abroad.

'Financial gains'

A former sales rep for GSK in the Polish region of Lodz, Jarek Wisniewski, said: "There is a simple equation," he said. "We pay doctors, they give us prescriptions. We don't pay doctors, we don't see prescriptions for our drugs.

"We cannot go to doctors and say to them, 'I need 20 more prescriptions'. So we prepare an agreement for them to give a talk to patients, we pay £100, but we expect more than 100 prescriptions for this drug.

"It's a bribe," Mr Wisniewski said, confirming that although on paper the payments were for educational services, the doctors understood very clearly that they must produce a certain number of prescriptions in return.

Panorama: Find out more

BBC Panorama logo
  • Panorama - Who's Paying Your Doctor?
  • BBC One, Monday, 14 April, at 20:30 BST

The Lodz public prosecutor found evidence in documents given to doctors by GSK to support claims of corrupt payments in more than a dozen different health centres where there was no evidence "patient education" had taken place.

Spokesman Krzysztof Kopania said: "We have evidence that in more than a dozen cases it was a camouflaged form of a bribe.

"In return for the financial gains the doctors would favour the product proposed by the pharmaceutical company and they prescribed that medicine."

One doctor has already admitted guilt, been fined and given a suspended sentence. He said he accepted £100 for a single lecture he never gave, but only under pressure from a GSK drugs rep.

He told Panorama: "They kept tempting, and I am just a man."

Reprimanded and disciplined

The company said a GSK training programme to help improve diagnostic standards and medical training in respiratory disease was run by doctors in Poland from 2010 to 2012.

A statement said: "These sessions were delivered by specialist healthcare professionals who, based on contracts signed with GSK, received payments appropriate to the scope of work as well as their level of knowledge and experience. The provision of sessions under this programme was agreed with the Polish healthcare centres.

"Following receipt of allegations regarding the conduct of the programme in the Lodz region, GSK has investigated the matter, using resources from both inside and outside the company. The investigation found evidence of inappropriate communication in contravention of GSK policy by a single employee. The employee concerned was reprimanded and disciplined as a result.

"We continue to investigate these matters and are co-operating fully with the CBA [Poland's Central Anticorruption Office]."

In 2012, GSK paid $3bn (£1.9bn) in the largest healthcare fraud settlement in US history after pleading guilty to promoting two drugs for unapproved uses and failing to report safety data about a diabetes drug to the Food and Drug Administration.

Last December, the company announced it was making major changes to its incentive schemes after a damaging corruption scandal in China.

The Chinese Ministry of Public Security has claimed that between 2007 and 2010 GSK funnelled three billion Chinese yuan (£300m) through travel agencies.

It said it would end direct payments to doctors for promotional talks and stop setting individual targets for its sales reps as part of a wider effort to improve transparency.

Panorama: Who's Paying Your Doctor?, BBC One, Monday, 14 April at 20:30 BST and then available in the UK on the BBC iPlayer.

http://www.bbc.co.uk/news/business-26970873?

GlaxoChinaGate contd. - next stop, Poland

Drugs giant GlaxoSmithKline bribed doctors to boost sales, says whistleblower

Britain’s biggest drug company, GlaxoSmithKline, allegedly bribed doctors in Poland using money that was meant to be spent on educating patients, according to new evidence revealed today by the BBC Panorama programme.

A GSK whistleblower claims that money put aside to teach patients in Poland about an asthma drug, Seretide, actually went towards paying doctors to prescribe more of the medicine.

Jarek Wisniewiski, who was with the company for eight years until 2012, worked on a marketing programme across the country in 2010 to push the asthma drug.

He told Panorama that although officially the money was to be spent on medical training, in reality it was used to bribe doctors to boost the company’s sales.

“I pay for education and in the same meeting I said that I need more prescriptions for Seretide. So… they knew exactly what I pay for,” he said. “We pay agreement for a speech; we pay £100 but we expect more than 100 prescriptions for this drug.”

Mr Wisniewiski says he told GSK that he was unhappy with the arrangement – an admission that he says resulted in him being sidelined at work and eventually sacked.

Another former employee, who did not want to be identified, confirmed that the company paid doctors for lectures that never happened but which would result in a greater number of prescriptions.

A criminal investigation has been launched, and 11 doctors and one GSK regional manager have been charged. The public prosecutor’s office in Lodz has examined the contracts that doctors were given by GSK, and says that it has found evidence to support claims of corrupt payments.

A spokesman said: “We have evidence to claim that in more than a dozen cases it was a camouflaged form of a bribe.In return for the financial gain, the doctors would favour the product proposed by the pharmaceutical company, and they prescribed that medicine.”

GSK sells some of the world’s best-known medicines and has an annual turnover of more than £26bn. However, allegations of bribery have hounded the company in recent months. The most recent claims come just a week after reports that GSK hired Iraqi government doctors and pharmacists to act as sales representatives for the Brentford-based company, to boost revenues for its medicines.

The company is also waiting to find out whether it will face prosecution in China following claims it paid £300m to doctors and government officials there.

The company’s Chinese sales plummeted by 61 per cent in the third quarter of last year, and 18 per cent in the final quarter, after its offices were raided by Chinese police and its staff arrested.

The allegations have not been established but if found to be true, GSK may have violated both the UK’s Bribery Act and the US Foreign Corrupt Practices Act. In both countries it is illegal for companies operating there to bribe government employees abroad.

In response to Panorama’s questions about the case, GSK confirmed that it had run a programme in Poland from 2010 to 2012 to help improve diagnostic standards and medical training for the benefit of patients with respiratory disease.

GSK says it is investigating the allegations. A chief executive has stated that the company has “zero tolerance” with respect to the issues raised in the allegations and is co-operating fully with investigators.

http://www.independent.co.uk/news/uk/crime/drugs-giant-glaxosmithkline-bribed-doctors-to-boost-sales-says-whistleblower-9257850.html

Friday, April 11, 2014

Ben Goldacre eviscerates Roche and Tamiflu

Today we found out that Tamiflu doesn't work so well after all. Roche, the drug company behind it, withheld vital information on its clinical trials for half a decade, but the Cochrane Collaboration, a global not-for-profit organisation of 14,000 academics, finally obtained all the information. Putting the evidence together, it has found that Tamiflu has little or no impact on complications of flu infection, such as pneumonia.

That is a scandal because the UK government spent £0.5bn stockpiling this drug in the hope that it would help prevent serious side-effects from flu infection. But the bigger scandal is that Roche broke no law by withholding vital information on how well its drug works. In fact, the methods and results of clinical trials on the drugs we use today are still routinely and legally being withheld from doctors, researchers and patients. It is simple bad luck for Roche that Tamiflu became, arbitrarily, the poster child for the missing-data story.

And it is a great poster child. The battle over Tamiflu perfectly illustrates the need for full transparency around clinical trials, the importance of access to obscure documentation, and the failure of the regulatory system. Crucially, it is also an illustration of how science, at its best, is built on transparency and openness to criticism, because the saga of the Cochrane Tamiflu review began with a simple online comment.

In 2009, there was widespread concern about a new flu pandemic, and billions were being spent stockpiling Tamiflu around the world. Because of this, the UK and Australian governments specifically asked the Cochrane Collaboration to update its earlier reviews on the drug. Cochrane reviews are the gold-standard in medicine: they summarise all the data on a given treatment, and they are in a constant review cycle, because evidence changes over time as new trials are published. This should have been a pretty everyday piece of work: the previous review, in 2008, had found some evidence that Tamiflu does, indeed, reduce the rate of complications such as pneumonia. But then a Japanese paediatrician called Keiji Hayashi left a comment that would trigger a revolution in our understanding of how evidence-based medicine should work. This wasn't in a publication, or even a letter: it was a simple online comment, posted informally underneath the Tamiflu review on the Cochrane website, almost like a blog comment.

Tamiflu being made by Roche
The UK government spent £0.5bn stockpiling Tamiflu. Photograph: Hanodut/EPA
Cochrane had summarised the data from all the trials, explained Hayashi, but its positive conclusion was driven by data from just one of the papers it cited: an industry-funded summary of 10 previous trials, led by an author called Kaiser. From these 10 trials, only two had ever been published in the scientific literature. For the remaining eight, the only available information on the methods used came from the brief summary in this secondary source, created by industry. That's not reliable enough.

This is science at its best. The Cochrane review is readily accessible online; it explains transparently the methods by which it looked for trials, and then analysed them, so any informed reader can pull the review apart, and understand where the conclusions came from. Cochrane provides an easy way for readers to raise criticisms. And, crucially, these criticisms did not fall on deaf ears. Dr Tom Jefferson is the head of the Cochrane respiratory group, and the lead author on the 2008 review. He realised immediately that he had made a mistake in blindly trusting the Kaiser data. He said so, without defensiveness, and then set about getting the information needed.

First, the Cochrane researchers wrote to the authors of the Kaiser paper. By reply, they were told that this team no longer had the files: they should contact Roche. Here the problems began. Roche said it would hand over some information, but the Cochrane reviewers would need to sign a confidentiality agreement. This was tricky: Cochrane reviews are built around showing their working, but Roche's proposed contract would require them to keep the information behind their reasoning secret from readers. More than this, the contract said they were not allowed to discuss the terms of their secrecy agreement, or publicly acknowledge that it even existed. Roche was demanding a secret contract, with secret terms, requiring secrecy about the methods and results of trials, in a discussion about the safety and efficacy of a drug that has been taken by hundreds of thousands of people around the world, and on which governments had spent billions. Roche's demand, worryingly, is not unusual. At this point, many in medicine would either acquiesce, or give up. Jefferson asked Roche for clarification about why the contract was necessary. He never received a reply.

Then, in October 2009, the company changed tack. It would like to hand over the data, it explained, but another academic review on Tamiflu was being conducted elsewhere. Roche had given this other group the study reports, so Cochrane couldn't have them. This was a non-sequitur: there is no reason why many groups should not all work on the same question. In fact, since replication is the cornerstone of good science, this would be actively desirable.

Then, one week later, unannounced, Roche sent seven documents, each around a dozen pages long. These contained excerpts of internal company documents on each of the clinical trials in the Kaiser meta-analysis. It was a start, but nothing like the information Cochrane needed to assess the benefits, or the rate of adverse events, or fully to understand the design of the trials.

Packets of Tamiflu
Packets of Tamiflu in a drawer at a German pharmacy. Photograph: Wolfgang Rattay/Reuters
At the same time, it was rapidly becoming clear that there were odd inconsistencies in the information on this drug. Crucially, different organisations around the world had drawn vastly different conclusions about its effectiveness. The US Food and Drug Administration (FDA) said it gave no benefits on complications such as pneumonia, while the US Centers for Disease Control and Prevention said it did. The Japanese regulator made no claim for complications, but the European Medicines Agency (EMA) said there was a benefit. There are only two explanations for this, and both can only be resolved by full transparency. Either these organisations saw different data, in which case we need to build a collective list, add up all the trials, and work out the effects of the drug overall. Or this is a close call, and there is reasonable disagreement on how to interpret the trials, in which case we need full access to their methods and results, for an informed public debate in the medical academic community.

This is particularly important, since there can often be shortcomings in the design of a clinical trial, which mean it is no longer a fair test of which treatment is best. We now know this was the case in many of the Tamiflu trials, where, for example, participants were sometimes very unrepresentative of real-world patients. Similarly, in trials described as "double blinded" – where neither doctor nor patient should be able to tell whether they're getting a placebo or the real drug – the active and placebo pills were different colours. Even more oddly, in almost all Tamiflu trials, it seems a diagnosis of pneumonia was measured by patients' self-reporting: many researchers would have expected a clear diagnostic algorithm, perhaps a chest x-ray, at least.

Since the Cochrane team were still being denied the information needed to spot these flaws, they decided to exclude all this data from their analysis, leaving the review in limbo. It was published in December 2009, with a note explaining their reasoning, and a small flurry of activity followed. Roche posted their brief excerpts online, and committed to make full study reports available. For four years, they then failed to do so.

During this period, the global medical academic community began to realise that the brief, published academic papers on trials – which we have relied on for many years – can be incomplete, and even misleading. Much more detail is available in a clinical study report (CSR), the intermediate document that stands between the raw data and a journal article: the precise plan for analysing the data statistically, detailed descriptions of adverse events, and so on.

By 2009, Roche had shared just small portions of the CSRs, but even this was enough to see there were problems. For example, looking at the two papers out of 10 in the Kaiser review that were published, one said: "There were no drug-related serious adverse events", and the other doesn't mention adverse events. But in the CSR documents shared on these same two studies, 10 serious adverse events were listed, of which three are classified as being possibly related to Tamiflu.

Roche HQ in Basel, Switzerland
Roche HQ in Basel, Switzerland. Photograph: Bloomberg/Bloomberg via Getty Images
By setting out all the known trials side by side, the researchers were able to identify peculiar discrepancies: for example, the largest "phase three" trial – one of the large trials that are done to get a drug on to the market – was never published, and is rarely mentioned in regulatory documents.

The chase continued, and it exemplifies the attitude of industry towards transparency. In June 2010, Roche told Cochrane it was sorry, but it had thought they already had what they wanted. In July, it announced that it was worried about patient confidentiality. By now, Roche had been refusing to publish the study reports for a year. Suddenly, it began to raise odd personal concerns. It claimed that some Cochrane researchers had made untrue statements about the drug, and about the company, but refused to say who, or what, or where. "Certain members of Cochrane Group," it said, "are unlikely to approach the review with the independence that is both necessary and justified." This is hard to credit, but even if true, it should be irrelevant: bad science is often published, and is shot down in public, in academic journals, by people with good arguments. This is how science works. No company or researcher should be allowed to choose who has access to trial data. Still Roche refused to hand over the study reports.

Then Roche complained that the Cochrane reviewers had begun to copy in journalists, including me, on their emails when responding to Roche staff. At the same time, the company was raising the broken arguments that are eerily familiar to anyone who has followed the campaign for greater trials transparency. Key among these was one that cuts to the core of the culture war between evidence-based medicine, and the older "eminence-based medicine" that we are supposed to have left behind. It is simply not the job of academics to make these decisions about benefit and risk, said Roche, it is the job of regulators.

This argument fails on two fronts. First, as with many other drugs, it now seems that not even the regulators had seen all the information on all the trials. But more than that, regulators miss things. Many of the most notable problems with medicines over the past few years – with the arthritis drug Vioxx; with the diabetes drug rosiglitazone, marketed as Avandia; and with the evidence base for Tamiflu – weren't spotted primarily by regulators, but rather by independent doctors and academics. Regulators don't miss things because they are corrupt, or incompetent. They miss things because detecting signals of risk and benefit in reviews of clinical trials is a difficult business and so, like all difficult questions in science, it benefits from having many eyes on the problem.

While the battle for access to Tamiflu trials has gone on, the world of medicine has begun to shift, albeit at a painful pace, with the European Ombudsman and several British select committees joining the push for transparency. The AllTrials campaign, which I co-founded last year, now has the support of almost all medical and academic professional bodies in the UK, and many more worldwide, as well as more than 100 patient groups, and the drug company GSK. We have seen new codes of conduct, and European legislation, proposing improvements in access: all riddled with loopholes, but improvements nonetheless. Crucially, withholding data has become a headline issue, and much less defensible.

Last year, in the context of this wider shift, under ceaseless questions from Cochrane and the British Medical Journal, after half a decade, Roche finally gave Cochrane the information it needed.

So does Tamiflu work? From the Cochrane analysis – fully public – Tamiflu does not reduce the number of hospitalisations. There wasn't enough data to see if it reduces the number of deaths. It does reduce the number of self-reported, unverified cases of pneumonia, but when you look at the five trials with a detailed diagnostic form for pneumonia, there is no significant benefit. It might help prevent flu symptoms, but not asymptomatic spread, and the evidence here is mixed. It will take a few hours off the duration of your flu symptoms. But all this comes at a significant cost of side-effects. Since percentages are hard to visualise, we can make those numbers more tangible by taking the figures from the Cochrane review, and applying them. For example, if a million people take Tamiflu in a pandemic, 45,000 will experience vomiting, 31,000 will experience headache and 11,000 will have psychiatric side-effects. Remember, though, that those figures all assume we are only giving Tamiflu to a million people: if things kick off, we have stockpiled enough for 80% of the population. That's quite a lot of vomit.

Roche has issued a press release saying it contests these conclusions, but giving no reasons: so now we can finally let science begin. It can shoot down the details of the Cochrane review – I hope it will – and we will edge towards the truth. This is what science looks like. Roche also denies being dragged to transparency, and says it simply didn't know how to respond to Cochrane. This, again, speaks to the pace of change. I have no idea why it was withholding information: but I rather suspect it was simply because that's what people have always done, and sharing it was a hassle, requiring new norms to be developed. That's reassuring and depressing at the same time.

Should we have spent half a billion on this drug? That's a tricky question. If you picture yourself in a bunker, watching a catastrophic pandemic unfold, confronting the end of human civilisation, you could probably persuade yourself that Tamiflu might be worth buying anyway, even knowing the risks and benefits. But that final clause is the key. We often choose to use treatments in medicine, knowing that they have limited benefit, and significant side-effects: but we make an informed decision, balancing the risks and benefits for ourselves.

And in any case, that £500m is the tip of the iceberg. Tamiflu is a side show, the one place where a single team of dogged academics said "enough" and the company caved in. But the results of clinical trials are still being routinely and legally withheld on the medicines we use today and nothing about a final answer on Tamiflu will help plug this gaping hole.

Star anise
Star anise provides the principal component of Tamiflu. Photograph: Adrian Bradshaw/EPA
More importantly, for all that there is progress, so far we have only sentiment, and half measures. None of the changes to European legislation or codes of conduct get us access to the information we need, because they all refer only to new trials, so they share a loophole that excludes – remarkably – all the trials on all the medicines we use today, and will continue to use for decades. To take one concrete and topical example: they wouldn't have made a blind bit of difference on Tamiflu. We have seen voluntary pledges for greater transparency from many individual companies – Johnson & Johnson, Roche, GSK, now Roche, and more – which are welcome, but similar promises have been given before, and then reversed a few years later.

This is a pivotal moment in the history of medicine. Trials transparency is finally on the agenda, and this may be our only opportunity to fix it in a decade. We cannot make informed decisions about which treatment is best while information about clinical trials is routinely and legally withheld from doctors, researchers, and patients. Anyone who stands in the way of transparency is exposing patients to avoidable harm. We need regulators, legislators, and professional bodies to demand full transparency. We need clear audit on what information is missing, and who is withholding it.

Finally, more than anything – because culture shift will be as powerful as legislation – we need to do something even more difficult. We need to praise, encourage, and support the companies and individuals who are beginning to do the right thing. This now includes Roche. And so, paradoxically, after everything you have read above, with the outrage fresh in your mind, on the day when it feels harder than any other, I hope you will join me in saying: Bravo, Roche. Now let's do better.

Ben Goldacre is a doctor and the author of Bad Pharma.

http://www.theguardian.com/business/2014/apr/10/tamiflu-saga-drug-trials-big-pharma