Saturday, July 26, 2014

Broken

Friday, July 25, 2014

Dr. Frances Oldham Kelsey is 100

Happy 100th birthday to Dr. Frances Oldham Kelsey, the pharmacologist whose bold stance against inadequate drug testing saved countless newborns from the perils of thalidomide, a drug which caused severe birth defects in over 10,000 infants. On her first month on the job at the U.S. Food and Drug Administration in 1960, the Canadian-born scientist resisted pressure from thalidomide's manufacturer to quickly approve the drug, which was already being widely prescribed in Europe as a painkiller for pregnant women. As a result of Dr. Kelsey's insistence on further safety testing, the drug was never approved in the US, saving an untold number of children from its devastating effects.
When Dr. Kelsey started working at the FDA, she was part of a new generation of scientists who wanted to ensure that drugs were proven safe and effective before being marketed to the public. At the time, the FDA did not have the authority to enforce these requirements and pharmaceutical companies often engaged in minimal safety testing. It was even a common practice for companies to send new or experimental drugs to doctors for them to try out on their patients.
When Dr. Kelsey received the application from the Richardson-Merrell Company for approval of thalidomide, the company expected a fast approval since the drug was already in use in numerous countries including Germany, the UK, and Australia. Distrustful of the information provided by the company and, as she later explained, feeling that its representatives were "at no time being wholly frank with me" about the drug's safety, Dr. Kelsey told the company further tests were needed. Over several months, the company continued to submit their application and Dr. Kelsey continued to reject it citing the need for additional tests.
Throughout this period, the company complained to her supervisors, contacted her repeatedly, and, as written in a 1962 Washington Post story, she "[lived] the while with insinuations that she was a bureaucratic nitpicker, unreasonable – even, she said, stupid." Dr. Kelsey's determined stance was vindicated eight months after the company's initial filing when evidence from Europe showed that thalidomide was the cause of severe birth defects. In Germany alone, between 5,000 and 7,000 children were born without limbs or with flipper-like limbs, of which only 40% survived, and numerous cases emerged in other countries.
After news of the thalidomide disaster broke, there was huge public outcry for better drug testing and the U.S. Congress unanimously passed the Kefauver Harris Amendment in 1962 to strengthen drug regulations and gave the FDA enforcement authority. Dr. Kelsey was selected to help write the rules governing clinical trials -- rules that have since been adopted throughout the industrialized world -- and then oversee their enforcement as the chief of the Division of New Drugs.
On August 7, 1962, Dr. Kelsey became the second woman ever to receive the country's highest civilian honor when President John F. Kennedy awarded her the President's Award for Distinguished Federal Civilian Service. Dr. Kelsey's far-reaching impact on science and drug testing was described by Harvard historian Daniel Carpenter as follows: "She had a huge effect on the science that we all take for granted today... She and the F.D.A. had a huge role in determining the terms and sequence of what is now modern clinical science."
Dr. Kelsey retired from the FDA in 2005, after 45 years of service, at the age of 90. The FDA has established the Dr. Frances O. Kelsey Award to "celebrate courage and scientific decision-making."
To read more about Dr. Kelsey, the NY Times wrote an excellent tribute for her 96th birthday at http://nyti.ms/1ukFtYA

Sunday, July 20, 2014

Poetry Corner - Cancer's a funny thing

J.B.S. Haldane retained his wit even while undergoing cancer treatments — he wrote this poem in a hospital in 1964:

I wish I had the voice of Homer
To sing of rectal carcinoma,
Which kills a lot more chaps, in fact,
Than were bumped off when Troy was sacked.

Yet, thanks to modern surgeon’s skills,
It can be killed before it kills
Upon a scientific basis
In nineteen out of twenty cases.

I noticed I was passing blood
(Only a few drops, not a flood).
So pausing on my homeward way
From Tallahassee to Bombay
I asked a doctor, now my friend,
To peer into my hinder end,
To prove or to disprove the rumour
That I had a malignant tumour.
They pumped in BaS04
Till I could really stand no more,
And, when sufficient had been pressed in,
They photographed my large intestine.
In order to decide the issue
They next scraped out some bits of tissue.
(Before they did so, some good pal
Had knocked me out with pentothal,
Whose action is extremely quick,
And does not leave me feeling sick.)
The microscope returned the answer
That I had certainly got cancer,
So I was wheeled into the theatre
Where holes were made to make me better.
One set is in my perineum
Where I can feel, but can’t yet see ‘em.
Another made me like a kipper
Or female prey of Jack the Ripper,
Through this incision, I don’t doubt,
The neoplasm was taken out,
Along with colon, and lymph nodes
Where cancer cells might find abodes.
A third much smaller hole is meant
To function as a ventral vent:
So now I am like two-faced Janus
The only* god who sees his anus.

*In India there are several more
With extra faces, up to four,
But both in Brahma and in Shiva
I own myself an unbeliever.

I’ll swear, without the risk of perjury,
It was a snappy bit of surgery.
My rectum is a serious loss to me,
But I’ve a very neat colostomy,
And hope, as soon as I am able,
To make it keep a fixed time-table.
So do not wait for aches and pains
To have a surgeon mend your drains;
If he says “cancer” you’re a dunce
Unless you have it out at once,
For if you wait it’s sure to swell,
And may have progeny as well.
My final word, before I’m done,
Is “Cancer can be rather fun.”
Thanks to the nurses and Nye Bevan
The NHS is quite like heaven
Provided one confronts the tumour
With a sufficient sense of humour.
I know that cancer often kills,
But so do cars and sleeping pills;
And it can hurt one till one sweats,
So can bad teeth and unpaid debts.
A spot of laughter, I am sure,
Often accelerates one’s cure;
So let us patients do our bit
To help the surgeons make us fit.

-

Haldane succumbed to his cancer in December 1964.

Hat tip: http://www.futilitycloset.com/2014/07/11/good-humor/

http://en.m.wikipedia.org/wiki/J._B._S._Haldane


Thursday, July 17, 2014

GlaxoChinaGate contd. - now GSK admit they had previous form

GlaxoSmithKline China: Company admits to bribery scandal in 2001

GlaxoSmithKline (GSK) has admitted that members of its staff were caught bribing Chinese officials back in 2001, according to the Financial Times.

The new information has emerged as the pharmaceutical giant faces intense scrutiny from authorities in the UK and US regarding the alleged bribing of doctors and officials to boost drug sales to China. Police in the country have accused GSK of "ordering" the bribes.

The FT report suggests that GSK was forced to fire 30 employees back in 2001 after it found staff were taking kickbacks and bribing Chinese officials.

The older allegations are relevant to the new case because if it were to emerge that there was a pattern of such behaviour from GSK, the US department of Justice (DoJ) would be likely to treat the current allegations more seriously and impose tougher sanctions. 

The current GSK chief executive, Sir Andrew Witty, was in charge of the company's operations in Asia Pacific in 2001, but China was not within his purview. GSK has said that Witty was neither involved in, nor aware of, the case. 

Chris Baron was head of the vaccination program in China at the time. Mr. Baron indicated that he was cleared of wrongdoing, but that it was suggested he should have exercised greater diligence.

http://www.cityam.com/1405576762/glaxosmithkline-china-scandal-company-admits-bribery-scandal-2001?

Wednesday, July 16, 2014

AllTrials News - Out of 400 trials on ClinicalTrials.gov, 30% haven’t reported results


A new study found that 118 of 400 clinical trials had not reported results four years later in either a journal or on ClinicalTrials.gov. The researchers randomly selected trials that were registered on ClinicalTrials.gov and listed as completed in 2008. They found that trials were equally likely to report results regardless of whether or not they were funded by industry.

This is yet one more study to look at the reporting of clinical trial results. The best available evidence is still that around half of all clinical trials have never been published or reported their results.

Dr Christopher Gill, the study’s lead author and director of Boston University School of Public Health’s Pharmaceuticals Program:

Promoting transparency in clinical trials is an intrinsic public health good.

Individuals who volunteer for clinical trials often do so out of a sense of altruism. I can imagine that many would be dismayed to learn that the results of a study that they participated in, that they took physical risks for, might never generate results known beyond the company that sponsored the trial.

Science learns from mistakes, as well as successes. If we only learn about the scientific success stories, we are really only seeing part of the picture.

Dr Ben Goldacre, co-founder of the AllTrials campaign:

We should never lose sight of how frightening these results are. Many in industry and academia have tried to brush this problem under the carpet: AllTrials is the beginning of that being impossible. Now that the mainstream narrative has shifted, we need concerted, concrete action from patient groups, professional bodies, regulators, policy makers, health services, and individual companies. The entire medical community needs to work together to ensure that the full methods and results of all trials, on all uses, of all currently prescribed treatments are made fully available. Without that, doctors and patients cannot make informed decisions about which treatment is best.



http://www.alltrials.net/news/out-of-400-trials-on-clinicaltrials-gov-30-havent-reported-results/

Thursday, July 10, 2014

Big Pharma pushes the Snake Oil approach

FDA has free-speech, safety issues to weigh in review of ‘off-label’ drug marketing rules

Should a pharmaceutical sales rep be allowed to tell a doctor that Topamax, a drug approved to treat seizures and prevent migraine headaches, might also help combat alcohol dependence? Or suggest the epilepsy drug Neurontin could also help treat bipolar disorders or insomnia? Or offer data showing that any number of other drugs could have uses beyond those listed on their labels?

For decades, the answer overwhelmingly has been no. The Justice Department has aggressively pursued companies that run afoul of rules against such “off-label” marketing — racking up billions of dollars in settlements. And the Food and Drug Administration has held firm to the idea that sales pitches generally should not include information on uses not approved by the agency.

But in the long-running conflict between federal regulators and drugmakers over how companies promote their drugs for unapproved uses, the landscape could be shifting, if only in subtle ways, and the outcome could affect doctors and patients alike.

Prompted in part by recent federal court decisions, the FDA is reviewing its rules on what kind of data drug companies should be allowed to distribute to doctors regarding off-label uses, as well as how they should respond to unsolicited questions from physicians about those uses. Its goal is to issue new guidelines by the end of the year.

Critics of the current rules say allowing pharmaceutical companies, which know the most about their drugs, to share more information about off-label uses would lead to better-informed physicians and ultimately benefit patients. Others are skeptical, saying the industry could exploit even a minor loosening of the restrictions to hype drugs for unapproved uses, exposing patients to ineffective and potentially harmful treatments.


Tablets of varying doses of Johnson & Johnson's Topamax migraine medicine. (JB Reed/Bloomberg News)

Traditionally, the FDA has approved drugs for specific conditions, and only after rigorous clinical trials for safety and effectiveness. It bars companies from promoting their products for off-label uses, a practice known as “misbranding.” Doctors are free to prescribe drugs for unapproved uses, and many do. The government, through Medicare, recognizes some off-label uses and covers their prescription.

In recent years, pharmaceutical companies have petitioned the FDA for clearer guidance, arguing that the rules are confusing and overly restrictive, especially in an age of social media and widespread access to reams of data beyond what is on any drug label. In addition, high-profile court decisions have bolstered drugmakers’ argument that the off-label rules violate their free-speech rights under the First Amendment, as long as the information being provided to doctors is truthful and not misleading.

In 2011, the Supreme Court struck down a Vermont law banning drugmakers and data-mining companies from accessing records about the prescribing habits of doctors as part of their marketing strategies. In late 2012, a federal appeals court reversed the conviction of a New York pharmaceutical representative, Alfred Caronia, who had been charged with promoting a litany of off-label uses of the narcolepsy drug Xyrem. Caronia, whose conversations with doctors had been recorded, argued that the government had violated his free-speech rights because it had not shown that his sales pitches were false or misleading. By a 2-to-1 vote, the federal appeals court agreed. The government chose not to appeal the case.

Some industry officials say the FDA has been slow to adjust to the reality of those court rulings.

“They were in denial,” said John Kamp, executive director of the Coalition for Healthcare Communication, which represents drug marketing agencies and medical publishers. “If doctors can talk to each other and major researchers can talk about off-label uses, the drug’s manufacturer should be able to talk about those uses, too.. . . If something is true and can be said by one party, it can be said by all other parties.”

That interpretation worries some regulators and public health officials who say relaxing the rules could undermine the FDA’s traditional gatekeeper role.

If First Amendment legal challenges prove successful, they “would turn back FDA’s proactive role in American medicine and jeopardize the safety of patients, as well as the future of innovation and medical progress,” FDA Commissioner Margaret A. Hamburg said in a 2010 speech.

She pointed to legislation, passed by Congress a half-century earlier, requiring drug manufacturers to provide robust evidence of a drug’s effectiveness before it begins promoting it. That meant “the best drugs, rather than the most aggressively marketed drugs, could rise to the top,” she said, adding, “Removing these protections would ignore the lessons of history.”

There are practical problems, too, said Aaron Kesselheim, a Harvard Medical School professor who has studied off-label promotion. Who gets to decide what qualifies as “truthful” information when it comes to sharing data about unapproved drug uses?

“Is it what the company with a financial conflict of interest says it is?” he said. “Or is it what a scientist at the FDA says it is? That’s the central tension here.”

So why don’t drugmakers more routinely seek FDA approval for new uses for existing drugs?

“In the ideal world, clinical trials would be quick, easy to conduct and free. Unfortunately, none of those conditions are true,” said Jeff Francer, vice president and senior counsel at the Pharmaceutical Research and Manufacturers of America. “Depending on where a drug is in its life cycle, it may not make economic sense for a company to pay for years of clinical study when the medicine is going to lose its patent in a short amount of time.”

That does not mean pharmaceutical companies should be barred from giving doctors legitimate information that comes to light after a drug’s initial FDA approval, Francer said. “Right now, the FDA essentially prohibits the communication of large swaths of information that is truthful and not misleading,” he said. “That information can be extremely beneficial.”

But doctors in hectic, real-life settings often do not have the time to sort through the literature or decipher which data is solid and which is suspect, said Michael Wilkes, a medical professor at the University of California at Davis who has written about drug promotion. “It’s hard to know what’s legitimate and what’s not,” he said. “I’d like to see [the FDA] err on the side of overregulation and making companies prove that these drugs work” for off-label uses.

For their part, FDA officials say they are trying to find a reasonable balance. In a statement, the agency said that given “the emerging case law,” it is working to “harmonize the fundamental public health interests underlying FDA’s mission and statutory framework with the interests in the dissemination of truthful and non-misleading information.”

The agency permits companies to share certain off-label information with doctors, though with plenty of strings attached. For instance, the FDA has said manufacturers can distribute certain peer-reviewed medical-journal articles, but the articles should be unabridged and handed out separately from drug promotional materials. Also, the FDA says, companies should disclose any funding of the research behind such articles.

Thus far, the wrangling over the rules appears to have had little effect on the Justice Department’s determination to take on misbranding cases.

Last fall, Johnson & Johnson agreed to pay $2.2 billion to resolve civil and criminal allegations involving the marketing of off-label, unapproved uses for the antipsychotic drug Risperdal to the elderly, children and mentally disabled people, among other accusations. The previous summer, British manufacturerGlaxoSmithKline agreed to plead guilty to criminal offenses and to pay $3 billion to settle charges that included promoting its best-selling antidepressants for off-label uses.

Kamp, of the Coalition for Healthcare Communication, said the FDA has an opportunity this year to provide clarity on what has long remained a murky and contentious issue. 

“As this plays out and the rules get more clear and more consistent with the First Amendment, the doctors who prescribe drugs and the patients who take them are going to know more about the safety and efficacy of those drugs than they would without these changes in the rules,” Kamp said. “It’s going to be a step forward.”

Wilkes, the medical professor, disagrees. Without maintaining stringent rules and harsh penalties for violating them, he says, companies could too easily push drugs for uses without the solid evidence to support them.

He pointed to the case of Vioxx, a once-popular painkiller that Merck, its manufacturer, illegally promoted for rheumatoid arthritis before the drug was discovered to actually increase risks for heart attacks.

“Our fiduciary responsibility is to our patients. This isn’t about profits. It’s really about patient safety,” Wilkes said. “As a rule, we ought to be offering our patients treatments and cures and interventions that have been proven to work.”

http://www.washingtonpost.com/national/health-science/fda-has-free-speech-safety-issues-to-weigh-in-review-of-off-label-drug-marketing-rules/2014/07/09/3708dd6a-fbc4-11e3-8176-f2c941cf35f1_story.html?

Wednesday, July 09, 2014

Servier distort competition

BRUSSELS — The European Union's antitrust body is imposing a fine of 428 million euros ($580 million) on France's pharmaceutical company Servier and five producers of generic medicines for distorting competition.

The 28-nation bloc's executive Commission on Wednesday said Servier struck a series of deals with the producers of generic medicines to protect its bestselling blood pressure medicine, Perindopril, from price competition.

EU competition chief Joaquin Almunia says Servier's practices of "systematically buying out any competitive threats" to protect its market was "clearly anti-competitive and abusive."

The Commission says Servier must pay a fine of 331 million euros ($450 million). The remaining fine of about 100 million euros is split between the five producers of generic medicines according to the extent of their involvement. They are Niche/Unichem, Matrix, Teva, Krka and Lupin.

http://www.startribune.com/lifestyle/health/266394181.html?

Tuesday, July 08, 2014

Advocate Groups Reach Out to President's Science Advisors Ahead of Antibiotics Meeting | Food Safety News


The President’s Council of Advisors on Science and Technology (PCAST) will meet Friday to discuss its work on antibiotic resistance and nanotechnology and to hear from speakers about oceans policy.

A group of public health, consumer, and environmental protection organizations have sent a letter to PCAST expressing concern that the U.S. Food and Drug Administration’s Guidance for Industry #213 and a proposed Veterinary Feed Directive (VFD) rule do not go far enough in addressing antibiotic overuse on farms.

By March, FDA had heard from 25 of the 26 drug manufacturers affected by Guidance #213 that they would comply. In a six-month progress report issued last week, the agency announced that the final sponsor has also confirmed its engagement.

The letter to PCAST reiterates the criticism that the focus on removing growth promotion from labels will still allow for overuse under the guise of “disease prevention.”

And a recent letter to FDA from Keep Antibiotics Working noted that companies might still continue extra-label marketing for growth promotion and other benefits.

“Another key policy flaw is the proposed removal from the existing VFD regulations of a federal valid veterinary-client-patient relationship (VCPR) standard,” reads the PCAST letter. “FDA has stated that one of the goals of the revision is to end over-the-counter use in feed, but there is no clear substitute in federal or state law that ensures on-farm veterinary engagement regarding antibiotic use in animal feed.”

The list of more than 20 signatories includes the American Academy of Pediatrics, the Center for Foodborne Illness Research and Prevention, the Center for Science in the Public Interest, the Consumers Union, the Environmental Working Group, Food and Water Watch, the Johns Hopkins Center for a Livable Future, Keep Antibiotics Working, the Natural Resources Defense Council and the Pew Charitable Trusts.

The groups are calling for PCAST to recommend restoring the CVPR standard and “additional policy measures that would rein in all indiscriminate, untargeted, and unnecessary antibiotic use in meat and poultry production.”

Laura Rogers, director of Pew’s campaign on human health and industrial farming, told Food Safety News that the groups were worried that PCAST seemed uncertain as to how to proceed after its initial meeting regarding antibiotics in April.

The committee was trying to ascertain just how much agriculture usage contributes to the antibiotic resistance problem in humans, but this is a very difficult question to answer because of lack of pertinent data.

Pew and many others await PCAST’s report on antimicrobial resistance. It won’t be issued before Friday, but it could come soon after.

“Our worry is that because it’s the animal side and they were asking questions like, ‘What’s the biggest contributor?,’ that they’re going to cordon off this issue and set it aside and just focus on human medicine and the need for spurring innovation of new drugs,” Rogers said.

She added that Salmonella antibiotic resistance data released by the National Antimicrobial Resistance Monitoring System (NARMS) last week illustrates the need for more granular-level data to figure out how to stop creating superbugs.

In early May, the World Health Organization (WHO) released a global report finding that surveillance of antibiotic resistance is generally “neither coordinated nor harmonized, compromising the ability to assess and monitor the situation.”

“I can’t imagine a [PCAST] report that would come out that wouldn’t address the need for better surveillance both in human medicine — how we’re using them and why — and on the animal side,” Rogers said. “We have enough data to act, but we need more information to know the strategic ways we can go in and cut out broad overuses of the drugs.”

The U.S. is “woefully behind much of the rest of the world,” especially Europe, in terms of confronting antibiotics overuse, Rogers added.

France recently published an assessment of the risks of emerging antimicrobial resistance related to patterns of antibiotic use in animal health, following the government’s decision to reduce the use of antibiotics in veterinary medicine over the 2012-2017 period (the Ecoantibio 2017 plan).

Sweden has challenged the European Union to match its own livestock welfare standards, which include medicating animals only when they are ill.

On June 25, the Netherlands hosted an international conference on antibiotic resistance as a follow-up to the WHO report. During her address, the Dutch Minister of Health, Welfare and Sport, Edith Schippers, said that, “When it comes to agriculture — it is my firm belief that we should ban the use of our last-resort antibiotics in animal husbandry all together.”

And, on July 1, U.K. Prime Minister David Cameron announced the creation of a new review panel that will investigate antibiotic overuse generally and why new drugs are not being developed.

“To my knowledge, no one with an equivalent position in the US government has ever spoken so directly or substantially about antibiotic resistance — and particularly not about the politically contentious (though scientifically settled) problem of drug use in agriculture,” wrote Maryn McKenna in her Wired blog post about Schippers and Cameron. “Imagine Obama speaking out about antibiotic resistance. What a powerful statement of priorities that would be.”

Although the PCAST report on its own will not be able to compel FDA action, Rogers said she hopes it will prompt the Obama administration to follow with an action plan on how to address the issue.

“FDA has taken this step [with Guidance #213], but the agency is just moving at a pace that is not equal to the public health crisis that we’re facing when it comes to antibiotic resistance,” she said. “Hopefully, the report will add some fire to getting the agency to move more quickly.”

http://www.foodsafetynews.com/2014/07/advocate-groups-reach-out-to-presidents-science-advisors-ahead-of-antibiotics-meeting/

What is called "guolaosi" in Chinese and "karoshi" in Japanese?

Answer: http://arbroath.blogspot.it/2014/07/chinese-man-praised-as-being-example-to.html

Monday, July 07, 2014

Larry Husten writes

Merck Uses Legal Threats To Stifle Negative Advice About Zetia And Vytorin In Italy

In response to repeated legal threats, a public health doctor in Italy has withdrawn advice to curtail use of a controversial drug. The drug, ezetimibe, is a key ingredient in Zetia and Vytorin, which is manufactured by Merck . The cholesterol-lowering drug has been the subject of fierce controversy because it has never been shown to improve clinical outcomes. Despite the controversy, in 2013 the drugs had combined sales of more than $2.6 billion.

MSD Italy, the Italian arm of the company, sent two “cease and desist” letters to Alberto Donzelli, who is “the head of education, appropriateness, and evidence based medicine at the public health authority of Milan (Milan Healthcare),” according to The  BMJwhich published a news report of the affair. The letter was also sent to Milan Healthcare’s director general and to Roberto Carlo Rossi, the president of the physicians’ regulatory organization in Milan.

As reported in The BMJ, after the first letter Rossi replied that the medical commission had concluded “that there was no reason to object on ethical grounds to Donzelli’s behaviour. Donzelli also replied to each point raised in the letter. ‘I exercised my right to tell the general practitioners what emerged from our in-depth analyses of the published literature, on a peer to peer basis.’”

In a second letter MSD Italy “reaffirmed its intention to go to court unless Donzelli stopped his ‘seriously damaging activity, [that was] tarnishing the company’s and the drug’s image and reputation.’” MSD’s medical director, Patrizia Nardini, told The BMJ: “We are in favour of balanced information, and we decided to write those letters because we didn’t see a willingness to evaluate all the information in a balanced way.”

Last month Donzelli capitulated and removed the contentious material from his website “until the issue is further clarified within the scientific community,” The BMJreports.

In a published statement, quoted by The BMJ, the editors of five Italian publications expressed support for Donzelli: “In the educational and informational process, the disagreement should be expressed on the pages of scientific journals as a debate among peers, including the readers who will be able to decide freely what is the most appropriate choice for patients.”

Donzelli is hardly alone in criticizing the continued use of ezetimibe despite the absence of evidence for clinical benefit. Just recently, ACP Internist, an internal medicine blog, raised the question: “Why are we still prescribing what appears to be a useless drug?” The continued use of ezetimibe in clinical practice was also the subject of a news feature in JAMA.

http://www.forbes.com/sites/larryhusten/2014/07/06/merck-uses-legal-threats-to-stifle-negative-advice-about-zetia-and-vytorin-in-italy/?

Tuesday, July 01, 2014

Tokyo prosecutor to charge Novartis Japan unit as well as ex-employee over manipulating data


(Reuters) - Tokyo prosecutors said on Tuesday they will charge the Japanese unit of Novartis AG and a former employee in connection with allegations of data manipulation in promoting its best-selling blood pressure drug Diovan.

The prosecutors office said in a statement that it had decided to arrest Nobuo Shiraishi on allegations he gave false data to researchers whose work was used for advertising. Shiraishi was initially detained in June.

The prosecutor also said that Novartis Pharma KK, the Swiss drugmaker's wholly owned local subsidiary, will be charged in connection with the case under a provision that alleges responsibility for failing to oversee an employee.

Novartis said it was cooperating with an ongoing investigation by the Japanese authorities and had taken corrective measures, including replacing senior management of its Japan subsidiary.

"Novartis and NPKK have already undertaken decisive action to address problems with the company's Investigator-Initiated Trial (IIT) research programmes in Japan," David Epstein, the company's global division head, said in a statement.

"We are committed to changing the culture at Novartis Pharma KK and demonstrating ethical leadership among pharmaceutical companies in Japan," he added.

Any individual found guilty of exaggerated advertising of drugs in Japan can be punished with up to two years in prison or a fine of as much as 2 million yen ($19,700) or both. ($1 = 101.4600 Japanese Yen) (Reporting by Tim Kelly; Editing by Edmund Klamann and Miral Fahmy)

http://www.reuters.com/article/2014/07/01/novartis-japan-idUSL4N0PC1X220140701?rpc=401&feedType=RSS&feedName=rbssAdvertisingMarketing&rpc=401

Investigators Face Trial Amid GSK Sex Tape Revelations


South China Morning Post’s Toh Han Shih reports that British/Chinese-American corporate investigator couple Peter Humphrey and Yu Yingzheng, who werearrested last summer during a bribery investigation into their clients GlaxoSmithKlinewill stand trial in Shanghai on July 29th.

Chinese prosecutors originally wanted to charge Humphrey and Yu with several offences, including some relating to illegal business operations.

But they decided to drop all of them except for one of illegally buying information, a source close to the family said.

Although each faced only one charge, they risked being jailed if found guilty, the source added.

Prosecutors had made Humphrey and Yu’s lawyers sign a non-disclosure agreement preventing them from revealing certain information to the couple, the source said. [Source]

News of the trial follows reports about a covert sex tape of GSK’s top China executive, which the pair had been hired to investigate. From Laurie Burkitt at The Wall Street Journal:

The British drug maker regarded the video—apparently shot without the executive’s knowledge—as a breach of security, the person said.

The executive in the video, Mark Reilly, directed the company to hire a Shanghai-based private investigation firm run by a British national and his Chinese-born wife to investigate the breach, the person said.

[…] Until this weekend’s disclosure about the video, it wasn’t clear whether ChinaWhys had been working for Glaxo when its owners were seized by authorities. The details of the video were reported by Britain’s Sunday Times newspaper.

[…] Chinese law enforcement in May accused Mr. Reilly of ordering subordinates to commit bribery that generated billions of yuan in revenue for Glaxo’s China operations. Authorities alleged that Mr. Reilly, a Briton, ordered his sales team and other employees to bribe hospital doctors, health-care organizations and other parties on “a large scale” to boost drug sales in China. [Source]

Hannah Beech at TIME discussed the constant threat of surveillance in China and her own suspected experience of it in light of the tape’s unknown origins.

 Surveillance — or the threat of surveillance — is a constant in China. As a journalist, I may be more interesting to the powers that be than some other foreigners here. But other expat friends who’ve been followed, hacked or otherwise tracked in China include diplomats, NGO staff and businesspeople. Also, artists and academics.

Sometimes, the scrutiny can yield helpful consequences. A diplomat in China remembers commenting to his wife in his then nearly empty apartment that they were out of toilet paper. A few minutes later, there was a knock on the door and a bearer of new rolls arrived.

In most instances, it is in no way reassuring to have your email auto-forwarding mysteriously activated or to be tailed by a black Audi while on assignment in the Chinese countryside. Nor are foreigners the only ones subject to such treatment. The days of communist neighborhood-committee grannies poking their noses into residents’ sex lives may be over, but it’s hard to feel completely private in China. Each Chinese citizen still has a dedicated personal file kept by local authorities. The contents are supposed to be secret but a friend who once gained accessed to hers found, among other things, an old high school paper and a copy of a letter from an ex-boyfriend. [Source]

http://chinadigitaltimes.net/2014/06/gsk-sex-tape-says-surveillance/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+chinadigitaltimes%2FbKzO+%28China+Digital+Times+%28CDT%29%29

Monday, June 30, 2014

GlaxoChinaGate contd. - sex, lies and video - Who made and who leaked the Mark Reilly Sex Tape?

A covert sex tape involving a senior executive and his Chinese lover was the trigger for a major investigation into corruption at British drugs giant GlaxoSmith-Kline, it was revealed yesterday. 


The video of married Mark Reilly and his girlfriend was filmed by secret camera and emailed anonymously to board members of the pharmaceutical firm. 


It led to an investigation that has rocked the £76billion company – which stands accused of bribing doctors and other health officials in China with £320million of gifts, including sexual favours from prostitutes, to persuade them to prescribe its drugs.


Mr Reilly, who ran the company’s Chinese business, was charged six weeks ago with running a ‘massive bribery network’ involving £90million of illegal sales and banned from leaving the country. 

It was the culmination of a year-long corruption investigation into the FTSE 100 firm. 


But yesterday, it was revealed the scandal first erupted after the sex tape was emailed by ‘GSK whistleblower’ to board members, including chief executive Andrew Witty, in March 2013, in what was believed to be a threat or blackmail attempt. 


The footage showed father-of-two Mr Reilly, who is separated from his wife, having sex with his Chinese girlfriend. 


He was given permission to hire investigator Peter Humphrey, 58, to find out who had hidden the camera in his Shanghai flat and who had sent two separate emails making serious fraud allegations.

The £20,000 probe, codenamed Project Scorpion, focused on disgruntled former employee Vivien Shi, 49, a prominent businesswoman whose family is part of Shanghai’s communist elite.


But a few months after starting to investigate Miss Shi, Mr Humphrey was arrested along with his wife Yu Yingzeng, a US citizen and daughter of one of China’s most eminent atomic weapons scientists.

According to the Sunday Times, Mr Humphrey’s arrest and detention in July was at around the same time that China began a police probe into GSK’s alleged bribery.


Mr Reilly, 52, of Sawbridgeworth, Hertfordshire, stepped down from his post as China manager soon after Mr Humphrey’s arrest but remains a GSK employee.


He returned to Britain around the same time but voluntarily went back to China within days to assist police with their inquiries. 


He was charged in May this year and accused by police of presiding over a web of corruption and pressing his sales teams to bribe health officials to meet targets.

If found guilty, Mr Reilly, who has a PhD in pharmacology and neurosciences from University College London, could face life in prison.

Mr Reilly joined GSK in 1989 and has worked in Singapore, Hong Kong and China. He is separated from Jill, 49, with whom he has two teenage daughters, and has moved out of their £1.2million home.


Email: The footage was apparently sent to executives including chief executive Andrew Witty

It is understood he met Mrs Reilly at university, where she was studying psychology. Like her husband, she took up a post at GSK, working as a director of capital planning.

Yesterday, a neighbour said he did not know Mr and Mrs Riley had split and said he had not seen either for months.

The first email from ‘GSK whistleblower’ was sent in January last year. In March, the sex tape was sent from the same account, followed by a third email in May. 

The emails laid out a series of sales and marketing practices described as ‘pervasive corruption’.
GSK launched an internal investigation but found ‘no specific evidence’ to substantiate the claims.

However, the accusations are  virtually identical to the charges laid by police against Mr Reilly and 45 other suspects.

Last month, Britain’s Serious Fraud Office announced it is to investigate the company’s ‘commercial practices’.

Yesterday, GSK confirmed the sex tape’s existence and added in a statement: ‘The issues relating to our China business are very difficult and complicated. 

The investigation by the Chinese authorities remains ongoing and we are co-operating fully with this investigation.’



Read more: http://www.dailymail.co.uk/news/article-2673963/How-secret-sex-tape-plunged-British-drugs-giant-Glaxo-90million-bribery-probe.html#ixzz3660VHnzZ 
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Sunday, June 29, 2014

Dutch farmers use less antibiotics


The use of antibiotics in livestock in the Netherlands was further reduced in 2013. This is according to figures from the Dutch Authority of Veterinary Medicines (SDa). At the same time, an international conference is being held to further reduce antibiotic resistance.

Dutch farmers use less antibiotics
Photo: Henk Riswick

Between 2012 and 2013, the use of antibiotics in the Dutch pig industry dropped the most, by 30%. Also in the poultry sector, less antibiotics were uses - 25% less compared to 2012. In the veal calf sector, antibiotic use decreased by 15%. In the cattle industry, the antibiotic use remained stable. The decrease in the use of antibiotics is also shown in the sales figures of antibiotics. In 2013, sales were 57.7% down from 2009. SDa is positive about the continued decrease of the antibiotics use but stresses that farmers and veterinarians need to continue to use even less in the near future. The SDa wants to use a more animal-specific approach for this, target values that take scientific knowledge about resistance formation are taken into account.

Netherlands is average user

According to a comparison by the European Medicines Agency (EMA), the Netherlands is an average user of antibiotics in livestock, compared to other European countries. The comparison was made of the 2011 figures and is the most recent comparison available. In 2007, the Netherlands was considered one of the top users in Europe. The highest users in 2011 were Cyprus, followed by Italy and Spain. Norway used the lowest volume of antibiotics.

Comparison is difficult

The differences between the EU members states are large, partly due to the large differences in the type of livestock in the countries. Some countries focus more on cattle and some more on pig and poultry production. A comparison between Europe and other continents is even more difficult as data collection of the use (and sales) of antibiotics is different (or lacking), depending on the country. In 2011, US livestock producers purchased 29.9 million pounds of antimicrobials, according to the FDA. It is unknown how much of this was used as preventive in-feed antibiotics, so therefore it is difficult to compare with the European situation.

International conference

Although antibiotic use in many countries is being reduced, antibiotic resistance remains an important topic. On June 25 (today) and 26, international political leaders, leaders of the WHO, FAO and OIE, physicians, veterinarians and other experts from 55 countries are gathered at the international conference on antibiotic resistance, held in The Hague, the Netherlands. The goal is to make an action plan to reduce the increasing antibiotic resistance, both from a human as livestock perspective. A statement, released by the World Alliance Against Antibiotic Resistance prior to the conference, includes ten priorities to fight resistance. One of the priorities is to increase knowledge about the topic among the public and healthcare professionals. There is also a proposal to include antibiotics in the UNESCO list of cultural heritage.

http://www.allaboutfeed.net/Nutrition/Feed-Additives/2014/6/Dutch-farmers-use-less-antibiotics-1548030W/

Friday, June 27, 2014

Tuesday, June 17, 2014

Cartoon - New Yorker


Christopher Snowbeck writes

Medtronic's Covidien deal spurs debate about corporate taxes

Is Medtronic's massive international corporate merger a billion-dollar tax dodge, an indictment of the U.S. tax code, or a business-savvy work-around that would spur investment and growth in the Twin Cities?

The answer depends on who you talk to.

The $42.9 billion cash-and-stock purchase of Covidien, announced Sunday, comes with plans for Medtronic to decamp its executive suite to Ireland, where Covidien is based.

It also will nearly double the size of the Fridley-based medical device maker, and likely result in no significant change in its 8,000-strong Twin Cities workforce. The company is talking about adding 1,000 workers locally.

The move is designed to allow Medtronic to avoid U.S. corporate tax rates in repatriating foreign earnings and cash held overseas, potentially letting the company invest billions in the United States.

But critics questioned whether Medtronic would unfairly shift its tax burden to others. Some questioned whether the move will diminish Medtronic's role in Minnesota, where it's been central to a 50-year local narrative of innovation and business development.

Minnesota politicians of both stripes were critical.

"This clearly highlights the need to fix our broken tax code so American companies can be more competitive," said Republican U.S. Rep. Erik Paulsen. A statement from the Minnesota GOP blamed a medical-device tax associated with Obamacare.

And U.S. Sen. Al Franken, a Democrat, said: "Deals that result in companies reincorporating abroad often mean that they can shelter profits overseas, costing taxpayers billions of dollars -- which I find troubling."

Under the merger agreement announced Sunday, Medtronic Chief Executive Officer Omar Ishrak would lead the merged company, with operational headquarters remaining in Fridley. Principal executive offices would move to Ireland, where Medtronic already has operations.

Different countries impose different tax rates on corporations, and the disparity has prompted firms in high-tax nations to consider these so-called "inversion" deals for many years.

The United States has one of the world's highest corporate tax rates at 35 percent, while Ireland's is relatively low at 12.5 percent, said Ken Levinson, a partner with Faegre Baker Daniels LLP in Minneapolis who leads the firm's international tax practice.

Pulling off an inversion isn't easy.

It Medtronic's shareholders, for example, wind up owning 80 percent or more of the new holding company, the U.S. government wouldn't recognize the new entity as a foreign company, Levinson said, no matter where its executives are based.

The government would decide Medtronic had simply "substituted a different mailbox," he said, and would subject the holding company to regulatory requirements and treatment as a U.S. corporation for tax purposes.

If Medtronic shareholders obtain at least 60 percent of the new holding company, it must pay tax on what's called an "inversion gain" to Internal Revenue Service, Levinson said, and will be subject to certainly regulatory compliance requirements for about 10 years. But up-front costs in that scenario could make sense for the company considering in long-run tax savings, he said.

"In the Covidien transaction, the prior Covidien shareholders would own 30 percent of the resulting equity," Levinson said. "(The companies) have taken pains to fall below the 80 percent threshold -- and they are apparently going to be above the 60 percent threshold."

If Medtronic avoids taxes through an inversion, is that unfair to other U.S. taxpayers?

"Fair or unfair is in the eyes of the policymakers, which changes from time to time," Levinson said. "There have been a number of these transactions over the years. You can see where this makes economic sense."

Last year, Medtronic had about $20.5 billion in undistributed earnings from non-U.S. subsidiaries. It's unclear whether U.S. taxes are owed on the sums, but if so, the merger might provide a chance to get out from under the burden, said Matt Gardner of the Institute on Taxation and Economic Policy, in Washington, D.C.

The Covidien deal could lighten the company's tax burden going forward, Gardner said, adding: "In the long run, we'll all have to pay higher taxes to pay for what Medtronic is doing."

But Medtronic spokesman Rob Clark said such comments mischaracterize the deal. There's no change to the U.S. taxes Medtronic is currently paying, he said, and much of the profit sitting overseas still will be subject to U.S. taxes.

During a conference call with stock analysts Monday, Chief Financial Officer Gary Ellis said the merger "provides us the opportunity to significantly increase our flexibility on the cash side, especially for what capital we can invest back in the United States."

Medtronic's proposal is not unlike the current structure for Covidien, said Brooks West, a stock analyst with Piper Jaffray in Minneapolis. Covidien is based in Ireland, but decision-makers work from a headquarters in Massachusetts.

Medtronic has made assurances that Minnesota will play a key role in the company's future operations, and could see 1,000 new jobs over the next five years.

"I really would be shocked to see much of an employment risk just from Medtronic being domiciled in Ireland," West said. "Minneapolis has got a great base of med-tech talent ... I would be really surprised to see a shift."

Christopher Snowbeck can be reached at 651-228-5479. Follow him atwww.twitter.com/chrissnowbeck.

http://www.twincities.com/business/ci_25975280/medtronics-covidien-deal-spurs-debate-about-corporate-taxes?

Friday, June 13, 2014

Baron and Budd Announces $177 Million Settlement for Seven States Against Avandia Manufacturer GlaxoSmithKline

DALLAS, Jun 13, 2014 (BUSINESS WIRE) -- The national law firm of Baron and Budd has reached a $177 million settlement with GlaxoSmithKline on behalf of the states of Kentucky, Maryland, Mississippi, New Mexico, South Carolina, Utah and West Virginia regarding the deceptive advertising of the diabetes drug Avandia. This result represents the largest settlement of a pharmaceutical case ever for several of the involved states, and a much higher settlement for each individual state than what they would otherwise have received in a multistate settlement reached in 2012. Baron and Budd attorneys Russell Budd, Burton LeBlanc, Laura Baughman and S. Ann Saucer served in the litigation alongside co-counsel and each state’s Office of the Attorney General.


In the lawsuit, GlaxoSmithKline, the manufacturer of Avandia, was accused of misrepresenting the safety and efficacy of the drug, specifically stating that Avandia reduced adverse cardiac events, when it actually increased them.

Baron and Budd worked with the office of each state’s Attorney General, including Jack Conway, the Attorney General of Kentucky; Doug Gansler, the Attorney General of Maryland; Jim Hood, the Attorney General of Mississippi; Gary King, the Attorney General of New Mexico; Alan Wilson, the Attorney General of South Carolina; Sean Reyes, the Attorney General of Utah; and Patrick Morrisey, the Attorney General of West Virginia.

“These states truly made a wise move to opt out of the nationwide Avandia settlement and, instead, pursue independent litigation,” said Russell Budd. "We are honored to have represented them."

With more than 35 years of experience, Baron and Budd has established itself as one of the nation’s leading plaintiffs’ law firms, spearheading meaningful litigation on behalf of consumers. Over the past year, the firm has taken a leadership role in negotiating settlements on behalf of the states of West Virginia, Mississippi and Hawaii regarding the deceptive marketing practices of credit card payment protection plans. To date, these settlements total more than $21 million. The firm has helped negotiate sweeping national settlements regarding excessive bank overdraft fees, including a $410 million settlement with Bank of America and a $110 million settlement with JPMorgan Chase. Baron and Budd shareholder Burton LeBlanc currently serves on the Plaintiff’s Steering Committee in litigation surrounding GranuFlo, a product used in dialysis and administered at Fresenius Medical Clinics across the country.

About Baron & Budd, P.C.

With a history of over 35 years “Protecting What’s Right” for individuals, communities, and governmental entities, Baron and Budd is a well-established law firm devoted to making a positive difference. With offices in Dallas, Austin, Los Angeles and Baton Rouge, Baron and Budd is able to take on complicated and expensive cases within the realms of dangerous drugs and medical devices, asbestos-related illnesses, consumer fraud, water contamination, the Gulf oil spill and fraudulent financial practices.

http://www.marketwatch.com/story/baron-and-budd-announces-177-million-settlement-for-seven-states-against-avandia-manufacturer-glaxosmithkline-2014-06-13?

Thursday, June 12, 2014

Things that make you go hmmm! EMA policy on transparency is “strikingly” similar to deal struck with drug company, say experts

  1. Peter Doshi
http://www.bmj.com/content/348/bmj.g3852?sso=
A US drug company seems to have influenced the European Medicines Agency’s (EMA) draft policy on access to clinical trial data, which academics have claimed keeps too much information hidden.
Documents obtained by The BMJ under a freedom of information request showed a significant overlap between what the US drug giant AbbVie had agreed with the EMA could be released about its drug adalimumab (marketed as Humira) and the agency’s draft policy on providing public access to drug company data.
In 2012 the EMA announced a new, “proactive” transparency policy that would give full public access to clinical trial data about drugs authorised for marketing in the European Union from January 2014.1 But draft policy documents on how the system will work have been criticised for being overly restrictive. For example, the “view on screen only” policy will prohibit saving, downloading, or transferring data, limiting how the data can be analysed.2
Beate Wieseler, head of drug assessment at the German Institute for Quality and Efficiency in Health Care (IQWiG) and a vocal proponent of transparency, noted a “striking” similarity between the EMA’s redaction principles and particular elements that AbbVie and the EMA had agreed to redact in the adalimumab clinical study reports (CSRs).
CSRs are detailed reports of drug trials that companies submit to regulators as part of a marketing application. Since November 2010 the EMA has been releasing these documents in response to requests. By late 2012 it had released nearly two million pages of documents, 29% of which were released fully unredacted.
But in 2013 AbbVie took out an injunction to prevent the EMA releasing documents on adalimumab to a competitor. After more than a year of legal wrangling the lawsuits were withdrawn3—which, The BMJ has learnt, came after a series of negotiations between the EMA and AbbVie. During these consultations the EMA agreed a set of redactions in the adalimumab CSRs proposed by AbbVie, which were more extensive than the agency was originally willing to accept.
In a press release in April 2014 the EMA said that the resulting clinical study reports contained “very limited redactions.” But documents obtained by The BMJ have shown the extent of the redactions, which included the determination of trial sample size, exploratory efficacy subgroup analysis, and exploratory secondary endpoint results.
Wieseler said that “redaction of exploratory endpoints and analyses is a problem because these study results are often important for decision making outside regulatory agencies.” As had occurred with the released adalimumab CSRs, the EMA’s draft “redaction principles” document stated that safety and efficacy variables from exploratory analyses “may have to be redacted.”
“The similarity is striking,” said Wieseler, who challenged the notion that the proposed redactions constituted commercially confidential information. The EMA’s redaction “approach contradicts EMA’s own policy in other areas,” she wrote in a letter to The BMJ.4
Noting the quality of life as a prime example, she said, “We found that health related quality of life is often investigated as an exploratory endpoint. These data are very relevant for our benefit assessment; therefore, presentation of these study results should not be at the discretion of the study sponsors.” Wieseler and her colleagues recently studied 101 trials with CSRs and found that outcomes such as quality of life were often reported only in CSRs, not in journal publications.5
When asked about the purported similarities between its policy document and what it had agreed with AbbVie, the EMA said that “any observations concerning similarity are a direct result of having a single standard for what is considered CCI [commercially confidential information] regardless of access route.” But Trudo Lemmens, a professor of law at the University of Toronto, said that the EMA “seems to have returned very much to the former approach of giving companies a lot of leeway in deciding what they consider to be confidential.”
In 2012 Guido Rasi, executive director of the EMA, had said, “We are not here to decide if we publish clinical trial data, but how.” However, in their letter to The BMJ Wieseler and her colleagues wrote, “One and a half years later, the ‘if’ is at stake.”
The EMA rejected this characterisation. “The agency maintains that the vast majority of data within the CSR is not CCI and will be accessible to the public upon decision. The small remainder which may be CCI is open to a justification and review process which the agency controls,” a spokesperson said.
The BMJ asked AbbVie why it considered the redactions to its documents on adalimumab necessary and whether they undermined researchers’ ability to analyse the data. Dirk van Eeden, senior director of public affairs at AbbVie, responded, “AbbVie and the EMA agreed that a significant portion of data would be disclosed while protecting the information that is commercially sensitive. This allowed the EMA to revise its decision regarding AbbVie’s study reports.”

Notes

Cite this as: BMJ 2014;348:g3852

Footnotes

  • Competing interests: The BMJ has campaigned for more transparency at EMA, notably for oseltamivir data, and I am a member of the Cochrane review group that analysed these data. I also personally know Beate Wieseler and Trudo Lemmens and recently coauthored a blog with Trudo Lemmens on this topic.

References