China detains GlaxoSmithKline staff for fraud: reports

Chinese police detained employees of GlaxoSmithKline Plc in the cities of Beijing, Shanghai and Changsha after allegations of data fraud and bribery, the South China Morning Post reported today, citing an unidentified person from Shanghai's pharmaceutical sector.

The official Xinhua News Agency reported yesterday that police in Changsha were investigating senior managers at the drugmaker's local unit for suspected involvement in "economic crimes." Xinhua didn't say how many people were involved.

GlaxoSmithKline will cooperate with the investigation, London-based spokesman Simon Steel said late yesterday in response to questions about the probe as reported by Xinhua. "At this stage, it is unclear what the precise nature or purpose of the investigation is," he said.

Steel didn't immediately respond to an email today seeking comment on the South China Morning Post report.

http://www.watoday.com.au/world/china-detains-glaxosmithkline-staff-for-fraud-reports-20130701-2p66z.html?

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Get in the sack

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Tamiflu saga continues - NYT. By Katie Thomas

Breaking the Seal on Drug Research

PETER DOSHI walked across the campus of Johns Hopkins University in a rumpled polo shirt and stonewashed jeans, a backpack slung over one shoulder. An unremarkable presence on a campus filled with backpack-toters, he is 32, and not sure where he’ll be working come August, when his postdoctoral fellowship ends. And yet, even without a medical degree, he is one of the most influential voices in medical research today.

Dr. Doshi’s renown comes not from solving the puzzles of cancer or discovering the next blockbuster drug, but from pushing the world’s biggest pharmaceutical companies to open their records to outsiders in an effort to better understand the benefits and potential harms of the drugs that billions of people take every day. Together with a band of far-flung researchers and activists, he is trying to unearth data from clinical trials — complex studies that last for years and often involve thousands of patients across many countries — and make it public.

The current system, the activists say, is one in which the meager details of clinical trials published in medical journals, often by authors with financial ties to the companies whose drugs they are writing about, is insufficient to the point of being misleading.

There is an underdog feel to this fight, with postdocs and academics flinging stones at well-fortified corporations. But they are making headway. Last fall, after prodding by Dr. Doshi and others, the drug giant GlaxoSmithKline announced that it would share detailed data from all global clinical trials conducted since 2007, a pledge it later expanded to all products dating to 2000. Though that data has not yet been produced, it would amount to more than 1,000 clinical trials involving more than 90 drugs, a remarkable first for a major drug maker.

The European Medicines Agency, which oversees drug approvals for the European Union, is considering a policy to make trial data public whenever a drug is approved. And on June 17, the medical world saw how valuable such transparency could be, as outside researchers published a review of a spinal treatment from the device maker Medtronic. The review, which concluded that the treatment was no better than an older one, relied on detailed data the company provided to the researchers.

For years, researchers have talked about the problem of publication bias, or selectively publishing results of trials. Concern about such bias gathered force in the 1990s and early 2000s, when researchers documented how, time and again, positive results were published while negative ones were not. Taken together, studies have shownthat results of only about half of clinical trials make their way into medical journals.

Problems with data about high-profile drugs have led to scandals over the past decade, like one involving contentions that the number of heart attacks was underreported in research about the painkiller Vioxx. Another involved accusations of misleading data about links between the antidepressant Paxil and the risk of suicide among teenagers.

To those who have followed this issue for years, the moves toward openness are unfolding with surprising speed.

“This problem has been very well documented for at least three decades now in medicine, with no substantive fix,” said Dr. Ben Goldacre, a British author and an ally of Dr. Doshi. “Things have changed almost unimaginably fast over the past six months.”

Much of that change is happening because of what Dr. Goldacre calls an “accident of history.” In 2009, Dr. Doshi and his colleagues set out to answer a simple question about the anti-flu drugTamiflu: Does it work? Resolving that question has been far harder than they ever envisioned, and, four years later, there is still no definitive answer. But the quest to determine Tamiflu’s efficacy transformed Dr. Doshi and others into activists for transparency — and turned the tables on drug makers. Until recently, the idea that companies should routinely hand over detailed data about their clinical trials might have sounded far-fetched. Now, the onus is on the industry to explain why it shouldn’t.

IN summer 2009, Dr. Doshi received a call from Dr. Tom Jefferson, a British epidemiologist based in Rome. That year, the swine flupandemic was spreading worldwide, and Dr. Jefferson had been hired by the British and Australian governments to update an earlier review of Tamiflu, a drug produced by the Swiss companyRoche, aimed at reducing the flu’s severity and preventing more serious complications. He asked if Dr. Doshi wanted to help.

Determining Tamiflu’s efficacy had significant economic as well as health consequences. Around the world, private companies and governments — including that of the United States — were stockpiling Tamiflu in case of influenza outbreaks, and their spending accounted for almost 60 percent of the drug’s $3 billion in sales in 2009.

The review of Tamiflu was being conducted under the auspices of the Cochrane Collaboration, a well-regarded network of independent researchers, including Dr. Jefferson, who evaluate medical treatments’ effectiveness by analyzing all available research.

At the time, Dr. Doshi knew little about clinical trials or even much about the drug industry. But he knew Dr. Jefferson. Dr. Doshi, after receiving undergraduate and master’s degrees in anthropology and East Asian studies from Brown and Harvard, had shifted focus and was pursuing a doctorate at M.I.T., studying the intersection of medicine and politics. He met Dr. Jefferson, a prominent skeptic of the flu vaccine, after researching whether the Centers for Disease Control was exaggerating the deadliness of the disease.

“We were both lone wolves in the field of influenza,” Dr. Doshi recalled.

Dr. Jefferson had conducted a Cochrane review of Tamiflu’s effectiveness a few years earlier, concluding that the drug reduced the risk of complications from the flu. He assured Dr. Doshi and other researchers on his team that the update would be fairly simple.

But just as their work was getting under way, a simple commentarrived on the Cochrane Web site that changed the course of the research and would ultimately fuel a worldwide effort to force drug companies to be more transparent.

The author of that comment, Dr. Keiji Hayashi, had no connection to the Cochrane group; he was a pediatrician in Japan who had prescribed Tamiflu to children in his practice, but had come to question its efficacy. He was curious about one of the main studies on which Dr. Jefferson had relied in his previous analysis. Called theKaiser study, it pooled the results of 10 clinical trials. But Dr. Hayashi noticed that the results of only two of those trials had been fully published in medical journals. Given that details of eight trials were unknown, how could the researchers be certain of their conclusion that Tamiflu reduced risk of complications from flu?

“We should appraise the eight trials rigidly,” Dr. Hayashi wrote.

Page 2 of 3

Reviews by the Cochrane group are known for being among the most thoroughly researched medical analyses available. But in trying to answer the pediatrician’s question, Dr. Jefferson realized that there was a flaw: they relied too heavily on the assumption that the articles published in journals accurately represented the results of all clinical trials that had been conducted.

As he tried to track down the authors of the Kaiser study and the two published trials, Dr. Jefferson said he hit dead ends: One author said he had moved offices and no longer had the files; another said he had never seen the primary trial data, instead relying on a summary analysis provided by Roche. All the authors suggested that he contact the company.

“We took it on faith — on trust,” Dr. Jefferson, 59, said recently in a phone interview. Dr. Hayashi’s question had tested that faith. Dr. Jefferson began typing each new discovery in a private journal he called Hayashi’s Problem, which, he said, “charted my transformation from Dr. Jekyll to Mr. Hyde.”

Dr. Doshi said that medicine “relies on hierarchies of trust.” He added: “A patient is not going to be in a position to review the entire evidence base themselves. But they trust that there is a watchdog out there.”

As they dug into the Tamiflu research, Dr. Doshi said, he realized that such a watchdog didn’t exist. Instead, he said, “we have partial watchdogs who see part of the full picture.” It became his mission to see the full picture.

Having struck out with the authors of the disputed Kaiser paper and the two other published trials, Dr. Jefferson approached Roche itself, asking for the underlying data from the missing trials. But when he declined to sign a confidentiality agreement, Roche decided not to cooperate with the researchers.

Without more complete data about the clinical trials, the Cochrane group decided that it could not include the disputed study that summarized those results. In December 2009, the team reportedthat Tamiflu could not be shown to reduce complications likepneumonia or hospitalizations.

The British Medical Journal, which printed the team’s conclusions, also published its own investigation, showing that Roche had hired ghost writers to author some of the articles involving Tamiflu, and that those writers had said they were under pressure to highlight positive messages about the drug. Roche responded that hiring such writers was common industry practice at the time of the articles, and it rejected the idea that they had been pressured to write positively about the drug.

The articles in the British journal created a sensation, and the Cochrane Collaboration’s efforts became a cause célèbre. “Everyone knows about publication bias,” said Dr. Steven Woloshin, a professor of medicine at the Dartmouth Institute for Health Policy and Clinical Practice and an advocate of more widespread sharing of clinical trial data. “But they just had so much energy and they brought so much attention to it.”

The group’s efforts seemed to make a difference: After the articles in the British journal, Roche turned over partial copies of study reports, amounting to a little more than 3,000 pages. Then, in 2011, the European Medicines Agency turned over more than 22,000 pages of documents for 19 trial reports to Dr. Jefferson and his team.

The door had been opened. As they read through the records, the researchers discovered the importance of documents called clinical study reports, which are thousands of pages long and contain details as varied as descriptions of trial protocol and design and the ingredients of the placebo pills.

“We used to know that there was a published paper and there were data behind it,” said Dr. Fiona Godlee, the editor of the British Medical Journal. “But people haven’t talked about these things, like clinical study reports, that are now being talked about a great deal.” Last fall, the journal said it would publish the results of clinical trials only if drug companies and researchers agreed to provide data upon request.

In April, Roche said it would make available to the Cochrane researchers clinical study reports for all Roche-sponsored trials of Tamiflu. Dr. Jefferson, Dr. Doshi and their colleagues hope to complete another update to their review of the drug by year-end.

Some said it was a shame that it took this long for the company to relent. “All these years later, and we still don’t know if Tamiflu is effective,” said Dr. Harlan Krumholz, the Yale cardiologist who oversaw the review of Medtronic’s bone treatment. “It’s perplexing to have a billion-dollar drug, and you’re still not willing to share everything you’ve got to know whether this thing is effective and safe.”

THOUGH the Tamiflu question is not yet resolved, the Cochrane researchers have succeeded in a bigger way: by helping to change the conversation around companies’ responsibility to reveal drug trial data.

Drug companies do not always credit the Cochrane Collaboration. In February, Roche followed Glaxo’s lead and announced that it, too, would release detailed clinical data to outside researchers, upon request. But Daniel O’Day, chief operating officer of pharmaceuticals at Roche, denied that its pledge had been motivated by the Tamiflu experience. He said Roche has provided data to “thousands” of researchers.

Page 3 of 3

Mr. O’Day said “there were probably errors on both sides” in how the Cochrane researchers and Roche communicated with each other, and said the relationship deteriorated after Dr. Jefferson refused to sign a confidentiality agreement. He said the company was trying to rebuild its relationship with the Cochrane researchers, but that it stood by the safety and efficacy of Tamiflu.

In 2010, Roche commissioned researchers at the Harvard School of Public Health to conduct a re-analysis of Tamiflu clinical data, which largely confirmed the positive conclusions of the Kaiser study.

Mr. O’Day asserted that the company’s transparency pledge had arisen from “the call from society in general for greater transparency of the clinical trials that we have.” But others say the Cochrane researchers are largely responsible for that call for transparency.

Andrew Witty, Glaxo’s C.E.O., said in an interview that his promise to provide detailed clinical data had grown out of a companywide effort, initiated soon after he became chief in 2008, that would “really ensure that we were more in step with where I thought, frankly, society and the world was moving.”

Glaxo, moreover, was in need of an image rehabilitation. Last year, it pleaded guilty to criminal charges and agreed to pay $3 billion in fines after the United States Justice Department accused the company, based in London, of failing to report safety data about its diabetes drug Avandia, and of publishing misleading information about Paxil, the antidepressant, in a medical journal. The settlement, which also included civil penalties over marketing of other drugs, was the largest ever involving a pharmaceutical company.

“We don’t see any reason for this information to be held out of the public domain,” Mr. Witty said, “provided that the people who are interrogating the information are legitimate researchers with a legitimate question to ask.”

In a twist, Roche now finds itself on the same side as the Cochrane researchers — and against many in its own industry — in a debate over what kind of data the European Medicines Agency should be making public. On Monday, the agency released a draft policy, expected to take effect next year, in which it would release clinical trial data whenever it approved a new drug. While Roche and Glaxo have supported the policy, the Pharmaceutical Research and Manufacturers of America, a major industry group, and other drug companies have opposed it.

John J. Castellani, chief executive of PhRMA, said the industry had championed open-source efforts to develop better methods for testing cancer drugs, for example. But proposals like those from the Cochrane team and the European agency go too far, he said.

“If you dump onto the sidewalk all the data and you include commercially protected information,” he said, “then you’re essentially giving to competitors what we invested billions of dollars in.”

Others warned that such a policy could discourage drug companies from investing in Europe. “If you, on the other hand, say, ‘You guys are bad actors, we want to cut your prices, we want to take your confidential data and share it with any one of your competitors,’ you don’t get the same feeling of encouragement,” Christopher A. Viehbacher, C.E.O. of the French pharmaceutical company Sanofi, told reporters in Brussels on Monday, according to Reuters.

Industry officials and regulators in the United States say the public already has access to vast amounts of information about clinical trials. The basic results of all clinical trials must now be registered in afederal clearinghouse, for example, and the Food and Drug Administration publishes staff reviews and other documents when it approves a new drug. The F.D.A. has said that it is monitoring the developments in Europe but that federal laws in the United States restrict what types of information can be released, particularly data that could reveal personal or commercially confidential information.

Cochrane group members point to the Medtronic study as an example of the value of a neutral perspective.

In 2011, Medtronic awarded a $2.5 million grant to Yale and asked it to oversee a detailed review of trial data for Infuse, a bioengineered material in spinal fusions to treat back pain. The company was facing claims that it had published misleading information about the treatment, and it turned over its data in an effort to address those criticisms. Two teams that examined the data came to similar conclusions: Infuse appeared to be no better than an older treatment, and may pose added risks.

EARLIER this month, Dr. Doshi opened what he hopes will be a new chapter in his quest for greater understanding of clinical trials. He and several other researchers published what amounted to an ultimatum to drug companies: publish your data, or we’ll do it for you.

Under the plan, researchers would publish articles summarizing trial results in cases where the underlying data has already been released. In isolated cases, such information has been made public through litigation and Freedom of Information Act requests.

“It’s really neat to see a larger opportunity for a larger impact,” he said. “Tamiflu just happened to be the lever that opened that door.”

http://www.nytimes.com/2013/06/30/business/breaking-the-

seal-on-drug-research.html?pagewanted=1&_r=1&

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Gouging the patient - 1boringoldman explains

These are the modern Robber Barons, the Hospital Corporations who take over small community hospitals like ours and indenture their staff into fee churning at the expense of everyone involved. It’s a scam extraordinaire that needs nationwide atention. It’s painful to watch!

http://1boringoldman.com/index.php/2013/06/27/the-modern-robber-barons/

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Deen dumped

Jun 27, 2013 2:53pm

By Andrea Dresdale

The list of corporate sponsors backing away from Paula Deen continues to grow. Target, Home Depot and diabetes drug maker Novo Nordisk are the latest companies to ends their relationships with the celebrity chef after she admitted to using a racial slur in the past.

The embattled TV chef, who appeared on TV yesterday to assure fans that she is not a racist, was previously dropped by Wal-Mart, Caesars Entertainment, and Smithfield Foods, a pork producer that services Deen’s restaurant. In addition, the Food Network announced last week that her contract would not be renewed.

How much does Paula Deen stand to lose?

A spokesperson for Target tells ABC News Radio, “We have made a decision to phase out the Paula Deen merchandise in our stores as well as on Target.com. Once the merchandise is sold out, we will not be replenishing inventory.”

According to US Weekly, Home Depot said Wednesday that it would stop carrying Paula Deen products in its kitchen and cookware departments. Pharmaceutical company Novo Nordisk also dropped Deen, 66, as a spokesperson for their diabetes drug Victoza. Deen has type-2 diabetes.

“Novo Nordisk and Paula Deen have mutually agreed to suspend our patient education activities for now, while she takes time to focus her attention where it is needed,” the company said in a statement. “Novo Nordisk would like to acknowledge Paula’s involvement in our ‘Diabetes in a New Light’ campaign, where she has helped make many people aware of type 2 diabetes and the lifestyle changes needed to control this serious disease.”

Deen was widely criticized when, in announcing her Novo Nordisk deal, she revealed she’d been diagnosed with type 2 diabetes three years earlier. High-fat, high-calorie recipes, such as those that are Deen’s trademark, have been shown to contribute to the illness.

A spokesperson for Random House, which is publishing Deen’s upcoming book Paula Deen’s New Testament: 250 Favorite Recipes, All Lightened Up, similarly told People magazine it is “monitoring the situation closely.” The book is due out in October.

Paula Deen released a video last week: “I beg for your forgiveness”

The controversy was sparked by a lawsuit filed by a former employee at Deen’s Savannah, Ga., restaurants, who claims racial and sexual harassment by Deen and her brother, Bubba Hier, while working for them. Deen’s attorney denies the claims, but in a suit-related deposition in May, Deen responded “I’m sure I have” when asked if she’d also used the n-word since being robbed, adding, “but it’s been a very long time.”

(Photo credit: Peter Kramer/NBC via AP Photo)

http://abcnews.go.com/blogs/entertainment/2013/06/paula-deen-fired-by-target-home-depot-and-more/?

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FDA shuts down 1,677 online pharmacies

The prices may look tempting, but ordering from an online pharmacy is often a bad deal, according to Interpol and the U.S Food and Drug Administration, announcing a crackdown Thursday on thousands of websites.

The FDA said it has shut down 1,677 sites for selling counterfeit or substandard medication, or for selling drugs without appropriate safeguards. Other sites received regulatory warnings. Officials said they also arrested 58 people and seized more than $41 million worth of illegal medicines.

Several sites had sleek interfaces and names that could easily be confused with legitimate pharmacy retailers. For example, the FDA shuttered Walgreens-Store.com; the well-known drugstore chain's website is actually Walgreens.com.

"It impacts consumers every day," FDA Commissioner Margaret Hamburg told CNN's Dr. Sanjay Gupta. "These products can have none of the active ingredient that people need for the treatment of their disease. They can have too much or too little (of the ingredient); they can have toxic ingredients, and they can prevent patients form getting the actual medications that they badly need to treat their disease."

The most common scams advertised popular drugs such as Viagra, Levitra, Celebrex and Avandaryl. The recent crackdown, labeled Pangea VI, involved the cooperation of more than 100 countries, according to Interpol.

http://www.abc15.com/dpp/news/national/fda-shuts-down-1677-online-pharmacies?

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Treasure Ireland contd.

The ESRI (Economic and Social Research Institute) today published a report on the prices of drugs/ pharmaceuticals. Last year, the Organisation for Economic Cooperation and Development (OECD) reported that in 2010, at €528, Ireland spent more on pharmaceuticals than any other European country on a per capita basis. This is 50% above the average across EU member states of €349.

http://www.finfacts.ie/irishfinancenews/article_1026195.shtml?

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SEC charges medical imaging firm CEO for lying on conference call

The U.S. Securities and Exchange Commission has filed fraud charges against a medical imaging firm and its CEO, charging that the CEO made misleading comments about a scanner rejected by the U.S. Food and Drug Administration during a shareholder call.

The SEC said Wednesday that during a November 2010 conference call with shareholders, Dean Janes, founder, chairman and CEO of Burbank, Calif.-based Imaging3 Inc., misled shareholders about the FDA's view of the company's medical device.

According to the complaint, in addition to selling, renting and servicing remanufactured or refurbished mobile imaging devices, the company has made repeated unsuccessful attempts to obtain FDA approval for a medical imaging device known as the Dominion Volumetric Scanner to produce 3D medical diagnostic images in real time.

http://www.businessinsurance.com/article/20130626/NEWS07/130629879?

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Sleepy Seroquel

http://1boringoldman.com/index.php/2013/06/25/all-i-see/

More here:

This possibility appears to have also come up before in a much more off the cuff way:
http://thelastpsychiatrist.com/2010/03/swallow_this_how_seroquel_xr_w.html#c007813

Some of the postings out there make the point that at 25mg doses Seroquel is essentially a different drug than at the higher doses, that the terms “antipsychotic” isn’t a meaningful guide at these low doses:

http://thelastpsychiatrist.com/2009/01/treating_insomnia_with_less.html#c003392

http://thelastpsychiatrist.com/2010/03/swallow_this_how_seroquel_xr_w.html#c007812

http://thelastpsychiatrist.com/2009/01/treating_insomnia_with_less.html

http://thelastpsychiatrist.com/2007/07/the_most_important_article_on.html

Do you think the idea of 25mg Seroquel primarily being an antihistamine is a fair one? And not necessarily more dangerous than other antihistamines at that dosage is the concept that seems to drive a lot of the primary care use. 1BOM, thoughts?

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Federal lawmakers urge FDA to change rules to allow design-flaw lawsuits against generic drugmakers

In the wake of Monday's Supreme Court decision that blocked the ability of patients to sue generic drugmakers for design flaws in their medicine because it would conflict with Food and Drug Administration rules, members of Congress and consumer groups renewed their plea to the FDA to change those rules.

A link to Tuesday's Inquirer story is here.

Three senators and four representatives - all Democrats - sent a letter to FDA Commissioner Margaret Hamburg, urging her to make the changes happen so that patients who think they are harmed can seek redress in state courts.

Karen Bartlett was the plaintiff in the case that was decided Monday. The New Hampshire woman took a generic painkiller made by Philadelphia's Mutual Pharmaceutical Co., which is now part of Sun Pharmaceutical Industries, Ltd. Her adverse reaction included terrible skin reactions, near blindness, 12 operations and the need for a medically-induced coma.

Mutual had argued that FDA rules prevent a generic manufacturer from changing the composition of, or official label for, a drug once it is approved by the FDA because it is based on the brand-name drug.

Rep. Henry Waxman (Calif.), who was among the authors of the transformational legislation passed in 1984 that helped boost the generic drug industry, joined Congressmen Chris Van Hollen (Md.), Bruce Braley (Iowa), and Matthew Cartwright (Pa.) in signing the letter. Cartwright's 17th district runs from Pottsville to the Delaware River, then shifts north to touch Wilkes-Barre and Scranton. The senators were Tom Harkin (Iowa), Patrick Leahy (Vermont) and Al Franken (Minn.)

"We write to urge the Food and Drug Administration (FDA) to expedite its consideration of revisions to the FDA’s drug labeling regulations to enable manufacturers of generic drugs to update patient safety labeling in appropriate circumstances," the letter to Hamburg said in part. "These changes are critically important to ensure that the public is adequately informed of the risks and benefits of prescription drugs, and that consumers who are injured by generic drugs have the same legal rights as those who are injured by the brand-name versions of the same drugs."

Waxman and Harkin had filed an amicus brief in the case, Mutual Pharmaceutical Co., v. Bartlett, 12-142, urging the court to find in favor of Bartlett.

Monday's decision mirrored an earlier Supreme Court decision that said generic drugmakers can't be sued in state court over failure to adequately warn patients because changing the official label for a drug would violate FDA rules. Those rules say generic products have to follow the official label of the brand-name drug.

Allison Zieve of the consumer advocacy group Public Citizen was the lead attorney who wrote the brief and she was dismayed by Monday's decision.

“This creates situation in which generic manufacturers have no responsibility or accountability for product design or labeling, a unique and disturbing situation for a consumer product in our country,” Zieve said.

Meanwhile, Mira Desai, a spokeswoman for Mumbai-based Sun Pharma said in an overnight email that the company was pleased with the ruling.

The decision, she wrote, "preserves the exclusive authority of the FDA’s scientific experts to determine the safety and efficacy of pharmaceutical products. We are pleased that the Supreme Court has recognized the importance of ensuring that affordable generic drugs remain available to citizens in all 50 states."

A link to the Supreme Court decision is here. Justice Samuel Alito wrote the majority opinion.

http://www.philly.com/philly/business/consumer_news/Federal-lawmakers-urge-the-FDA-to-change-

rules-to-allow-design-flaw-lawsuits-against-generic-drugmakers.html

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#UMNProud

http://www.healthnewsreview.org/2013/05/questions-journalists-should-ask-about-a-psych-drug-trial-suicide/

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Nemeroff in London - let's see the slides

http://hcrenewal.blogspot.co.uk/2013/06/professor-nemeroff-goes-to-london.html

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Pfizer still on the asbestos hook

he U.S. Supreme Court refused to shield Pfizer Inc. from some asbestos lawsuits connected to its Quigley Co. subsidiary, a bankrupt unit that stopped most operations in 1992.

The justices today rejected Pfizer’s appeal of a ruling that opened the New York-based drugmaker to some claims related to Quigley, which made asbestos-containing products for the steel industry from the 1940s to the 1970s. Pfizer acquired Quigley in 1968. Asbestos, once widely used an insulator, was later shown to cause cancer.

http://www.insurancejournal.com/news/national/2013/06/24/296464.htm?

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Meet the new Mr NICE Guy

Biography

Professor David Haslam is chair of the National Institute for Health and Care Excellence (NICE).

He is also National Clinical adviser to the Care Quality Commission, immediate past-president of the British Medical Association, past-president of the Royal College of General Practitioners, and visiting Professor in Primary Health Care at de Montfort University, Leicester.

He was a GP in Ramsey, Cambridgeshire, for many years and has been chair of the NHS Evidence Advisory Committee, co-chair of the NHS Future Forum Information subgroup, an expert member of the NHS National Quality Board, chair of the NQB Quality Information Committee, and National Clinical adviser to the Care Quality Commission.

He is a fellow of the Royal College of GPs, a fellow of the Faculty of Public Health, a fellow of the Academy of Medical Educators, and a fellow of the Royal College of Physicians.

David was chairman of Council of the RCGP from 2001 to 2004, and was also a member of the NHS Modernisation Board, vice chairman of the Academy of Medical Royal Colleges, a member of the Postgraduate Medical Education Training Board, a member of NHS Medical Education England, and co-chair of the MMC Programme Board from 2006-9.

He has written 13 books, mainly on health topics for the lay public and translated into 13 languages, and well over a thousand articles for the medical and lay press.

He was awarded the CBE in 2004 for services to Medicine and Health Care.

http://www.pharmafile.com/news/179780/david-haslam-new-chairman-new-nice?

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Of the 86 drugs in the industry's diabetes pipeline, how many agents are truly innovative and how many are simply me-toos?

http://www.fiercebiotech.com/story/innovation-not-imitation-

needed-diabetes-drug-development/2013-06-23?utm_source=rss&utm_medium=rss

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Sometimes it is best to do nothing. A "must read " by Dr Justin Coleman

The Naked Doctor: an indepth look at the pitfalls of “cutting edge” medicine

The Naked Doctor is an ongoing project at Croakey that aims to encourage discussion and awareness of the opportunities to do more for health by doing less.

In this latest edition, Dr Justin Coleman suggests that an equitable health system does not mean trying to give everyone the very best, if that means “the most tests, the most expense, the most treatments”.

“Not only will that aspiration require others to miss out on even the second-best treatment, but it too often also actively harms the recipient,” he says.

Perhaps one area where more intervention is needed is in tackling overdiagnosis and overtreatment – Dr Coleman suggests that if the ‘medical market’ is left unchecked, the balance naturally tips towards overtreatment.

He concludes with a powerful call to action:

“As a GP, I am a gatekeeper to a most powerful, expensive, superb and dangerous health system and I must never forget that sometimes my job is to shut the gate.”

The article below is based upon his plenary address to the Qld RACGP Annual Clinical Update in Brisbane last month.

It is dedicated to the late Professor Gavin Mooney, whose philosophy was that we must “judiciously apply what we know works, rather than enthusiastically embrace what we wish would work”.

***

The ethical imperative to tackle overdiagnosis and overtreatment

Justin Coleman writes:

Two years ago my good friend Gavin Mooney gave me a signed copy of his latest—and, as it turned out—last book, Evidence-Based Medicine in its Place. 

Professor of Health Economics at Curtin University, Gavin was an irascible Scot, and his book detailed his work with another great Scotsman, Archie Cochrane,who of course pioneered the science of Evidence-Based Medicine.

According to Mooney, after their first meeting, Cochrane informed him that he had revised his opinion of economists.

On the basis of the evidence of an afternoon with Mooney, he now placed them second bottom, with sociologists at the bottom. This merely confirmed for Mooney that there was much on which they agreed.

Mooney told me the story, repeated in his book, of how Archie Cochrane first gained notoriety as a very junior staff member at the massive Department of Health in London.

The young Archie presented slides from an RCT on outcomes after heart attacks following rehabilitation, either while remaining a hospital inpatient or after early discharge home.

London’s ‘Who’s Who’ of learned physicians nodded sagely as Archie showed the crucial slides where the hospital outcomes—represented in red—outdid the blue columns of home-based outcomes across nearly every parameter. A couple of supportive comments, no questions.

Then the young epidemiologist pretended to look flustered. ‘I’m terribly sorry. I seem to have mixed up the red and the blue!’

He had deliberately switched the labels. All the better outcomes were in fact in the home-based, early discharge group.

Needless to say, chaos ensued as suddenly a hundred disgruntled audience members grilled him on every possible dubious aspect of the study design!

Best practice or common practice?

Until that time, there had been no reason for a London physician to doubt that an intensive, expensive, high-tech hospital stay would improve health outcomes.

It made perfect sense, and a whole bunch of highly intelligent, caring physicians had spent their careers ensuring that such a system existed. Where it wasn’t affordable, public and charity funds were sought to ensure more people could get longer hospital stays.

This was best-practice care, in the same way that bed rest for back pain, monthly breast self-examinations, and antibiotics for sore throats have been understood by clever and well-meaning people to be fairly obvious best care. More about Archie—and Gavin—later.

In the brilliant Mitchell and Webb parody of a Homeopathic Emergency Department, Webb attempts to save a trauma victim’s life by drawing on his palm in pen to extend his life line. He justifies it by asking ‘Have you got a better idea?’

Luckily, the answer is ‘yes’.

There are some things that do work better than a pen mark, or a homeopathic vial of water, even a vial where the water molecules somehow retain the memory of a herb they once knew, while conveniently forgetting they were once flushed down a toilet.

And there are some things that do work better than our mainstream medical interventions, even when tens of thousands of medical practitioners believe they are doing the right thing.

This has always been true, and will ever be so. Our mistakes from the past remind us that we are making mistakes right now. Full credit to all those anonymous doctors and researchers who unwrapped these anomalies.

The art of discovering nothing

History rightly lauds those who discovered ‘something’; Alexander Fleming and penicillin.

But I also dips me lid to those who discovered ‘nothing’. Bloodletting doesn’t work. Arsenic doesn’t work. Keeping kids with polio in hospital back straighteners for six months of their lives doesn’t work.

In many cases, our patients would be better off if we chose not to act.

There’s a minimum standard in the medical profession—not the gold standard, but let’s call it the bronze.

The bronze standard is that the patient is no worse off as a result of seeing us. The bronze standard is probably achieved by enthusiasts who light ear candles and discover people’s chakras. Let’s at least stop doing things which fall below the bronze standard.

We must balance the important and exciting work of discovering new stuff with the un-sexy hard-slog science of analysing those times where we have over-reached and over-enthused.

The best of our medical predecessors started this process and we must continue it; this is why we are a science and not merely a tradition.

Two hundred years ago, the French physician Phillipe Pinel cared enough about the damage his colleagues were doing to his psychiatric patients to observe:

“It is an art of no little importance to administer medicines properly: but, it is an art of much greater and more difficult acquisition to know when to suspend or altogether to omit them.”

It took a young epidemiologist Archie Cochrane to highlight the flaws in obstetric practice that should ideally have already been obvious to the world’s leading obstetricians and their institutions.

And these were not minor flaws. Obstetrics units in one part of the world were teaching methods which had already been shown in another part of the world to kill women and babies, and vice versa.

Cochrane didn’t do the research himself; his genius was to inspire others—in this case, Iain Chalmers— to collect, collate and analyse all the available evidence and, importantly, reject the shoddy stuff: the anecdote and the meaningless trial, so that obstetricians and their departments could make informed decisions as to how to get the best outcomes.

Continues at:

http://blogs.crikey.com.au/croakey/2013/06/23/the-naked-doctor-an-

indepth-look-at-the-pitfalls-of-cutting-edge-medicine/

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Evidence Based Medicine - Why we can’t trust clinical guidelines (BMJ)

Evidence Based Medicine

Why we can’t trust clinical guidelines

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f3830 (Published 14 June 2013)

Cite this as: BMJ 2013;346:f3830

• Guidelines
• Injury
• Neurological injury
• Spinal cord
• Trauma
• Trauma CNS / PNS
• Competing interests (ethics)
• Contraception

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1. Jeanne Lenzer, medical investigative journalist

Author Affiliations

1. jeanne.lenzer@gmail.com

Despite repeated calls to prohibit or limit conflicts of interests among authors and sponsors of clinical guidelines, the problem persists. Jeanne Lenzer investigates

On 13 April 1990, in an unprecedented action, the US National Institutes of Health faxed a letter to every physician in the US on how to correctly prescribe a breakthrough treatment for acute spinal cord injury. Many neurosurgeons were sceptical of the evidence that lay behind the new recommendation to give high dose steroids, yet when two respected organisations released a review and a guideline recommending the treatment, they felt obliged to give it. Now, over two decades later, new guidelines warn against the serious harms of high dose steroids. This case and others like it point to the ethical difficulties that doctors face when biased guidelines are promoted and raise the question: why do processes intended to prevent or reduce bias fail?

Doctors who are sceptical about the scientific basis of clinical guidelines have two choices: they can follow guidelines even though they suspect doing so will cause harm, or they can ignore them and do what they believe is right for their patients, thereby risking professional censure and possibly jeopardising their careers.1 2 34 This is no mere theoretical dilemma; there is evidence that even when doctors believe a guideline is likely to be harmful and compromised by bias, a substantial number follow it.5

Disturbing precedent

In the early 1990s, high dose steroids became the standard of care for acute spinal cord injury,6 reinforced by a Cochrane review. The Cochrane Collaboration, is widely known to have strict standards concerning conflicts of interest, yet in this case the collaboration permitted Michael Bracken, who declared he was an occasional consultant to steroid manufacturers Pharmacia and Upjohn, to serve as the sole reviewer.7 He was also the lead researcher on the single landmark study, published in the New England Journal of Medicine,8 used to support the Cochrane review.

Neurosurgeons were not convinced. Many expressed concern about high rates of infection, prolonged hospital stays, and death with high dose steroids.9 10 One expert estimated that more patients had been killed by the treatment in the past decade than died in the 9/11 World Trade Center attacks.5

A poll of over 1000 neurosurgeons showed that only 11% believed the treatment was safe and effective. Only 6% thought it should be a standard of care. Yet when asked if they would continue prescribing the treatment, 60% said that they would. Many cited a fear of malpractice if they failed to follow “a standard of care.”5

That standard was reversed this March, when the Congress of Neurological Surgeons issued new guidelines. The congress found that, “There is no Class I or Class II medicine evidence supporting the benefit of [steroids] in the treatment of acute [spinal cord injury]. However, Class I, II, and III evidence exists that high-dose steroids are associated with harmful side effects including death.”11

Manufacturing consensus

Guidelines are usually issued by large panels of authors representing specialty and other professional organisations. While it might seem difficult to bias a guideline with so many experts participating under the sponsorship of large professional bodies, a worrying number of cases suggests that it may be common.

A recent survey found that 71% of chairs of clinical policy committees and 90.5% of co-chairs had financial conflicts.12 Such conflicts can have a strong impact: FDA advisers reviewing the safety record of the progestogen drospirenone voted that the drug’s benefits outweighed any risks. However, a substantial number of the advisers had ties to the manufacturer and if their votes had been excluded the decision would have been reversed.13

Biased guidelines can have powerful and wide ranging effects. Thousands of guidelines have been issued,14 and, when promulgated by highly respected professional societies, they sometimes serve as de facto “standards of care” that may be used to devise institutional protocols, to develop measures of physician performance, and for insurance coverage decisions. Guidelines may influence the medicines selected for inclusion on drug formularies and may be used as a “reliable authority” to support expert testimony in malpractice suits.4 Eighty four per cent of doctors say they are concerned about industry influence over clinical guidelines,12 yet the fear of malpractice suits puts many in an untenable position of following guidelines they believe are flawed or dangerous to patients.

Despite repeated calls to prohibit or limit conflicts of interests among guideline authors15 16 and their sponsors, most guideline panellists have conflicts,17making the guidelines they issue less than reliable.

Exuberant claims for alteplase in stroke

A similar scenario may be playing out for the use of the thrombolytic drug alteplase in acute stroke. Earlier this year, the American College of Emergency Physicians with the American Academy of Neurology (jointly)18 and the American Heart Association,19 separately, issued grade A level of evidence guidelines for alteplase in acute stroke. The simultaneous recommendation by three respected professional societies would seem to indicate overwhelming support for the treatment and consistent evidence. However, an online poll of 548 emergency physicians showed that only 16% support the new guidelines.20 Although the poll was not scientific, other surveys show substantial scepticism among emergency physicians and the treatment remains contentious.21 22 23 24 25 26 27

Guideline authors say that opposition to the guidelines is insubstantial. Andy Jagoda, a member of the guideline committee and professor and chair of emergency medicine at Mount Sinai School of Medicine, said that “almost all” resident physicians “believe in tPA [alteplase] for stroke.” Another guideline author, Steven R Messe, assistant professor of neurology at the Hospital of the University of Pennsylvania and the Pennsylvania Hospital, told the BMJ that “only a small, vocal minority [of emergency physicians] are opposed.”

An earlier survey claimed that emergency physicians don’t oppose alteplase for stroke. At a glance, the claim seemed justified: the poll found that 83% of the doctors surveyed said they would give the treatment.21 However, when asked whether “the science supports the use of tPA [alteplase],” only 49% agreed.

Alteplase was approved for acute stroke after the 1995 National Institutes of Neurologic Diseases and Stroke (NINDS) trial showed a 13% absolute reduction in disability.28 Advocates quickly began to promote the treatment with exuberant claims. The American Heart Association said it could “save lives,” a claim the organisation was forced to withdraw in 2002 when it was pointed out that no study had shown a mortality benefit.29 In 2007, leading stroke experts with industry ties repeated the “saves lives” claim in the New York Times, suggesting that far too few stroke patients were receiving the drug, largely because of resistance among emergency physicians. The newspaper later published a brief correction stating there was no evidence to support the claim that the drug saved lives.30

But as with steroids for acute spinal cord injury, claims of benefit rest on science that is contested. Sceptics say that baseline imbalances, the use of subset analyses, and chance alone could account for the claimed benefit.24 26 31 32 33 They also note that only two of 12 randomised controlled trials of thrombolytics have shown benefit and five had to be terminated early because of lack of benefit, higher mortality, and significant increases in brain haemorrhage.33

In addition, the guideline committee did not include the largest study of the treatment to date in its analysis. Messe, who was one of the guideline’s authors and a spokesperson until April 2011 for Boehringer Ingelheim, Genentech’s European marketing partner, told the BMJ that the joint panel did not include the International Stroke Treatment-3 (IST-3) Trial because the outcome “showed a benefit” among subgroups and because the patients treated were not the same population as in the NINDS trial. However, the effect on the primary outcome in IST-3 (treatment of stroke from 0-6 hours) was actually negative, and the claimed benefits were based on secondary, exploratory analyses. When this was pointed out, Messe acknowledged that the primary outcome was negative and said, “No one has claimed, nor do we recommend, treatment up to 6 hours.”

The new grade A recommendation by the American College of Emergency Physicians is seen as particularly surprising because emergency physicians have been the strongest critics of the treatment. In a survey of 1105 emergency doctors, 40% said they were “not likely to use” alteplase for acute stroke even under the ideal conditions recommended by the NINDS protocol.34 Two thirds of those doctors cited the risk of symptomatic intracerebral haemorrhage as the factor that most concerned them. A quarter cited the lack of clear treatment benefit.34 Their concerns seem understandable in light of a Cochrane review of pooled effects that showed alteplase increased fatal intracerebral haemorrhage nearly fourfold, and that thrombolytics overall were associated with a significant increase in mortality by the end of follow-up, representing an extra 30 deaths per 1000 treated patients.35

Curt Furberg, a prominent methodologist and former Food and Drug Administration adviser, told the BMJ: “The most powerful evidence comes from the Cochrane pooled analysis.” Furberg objected to the use of subgroup analyses to prove benefit, saying, “When clinical trial results are heterogeneous, it’s important to look at the totality of evidence. You should never draw firm conclusions from post hoc analyses. You can’t just select data that supports the thesis you like by asking, ‘How do the results look at 2 hours? How about 2 hours and 10 minutes? How about 3 hours?’ By chance alone you will find something that supports your bias.”

Best guidelines influence can buy: how it happens

Proponents of alteplase have launched projects to ensure uptake of the guidelines in the US, such as the development of “stroke certified hospitals,” which require hospitals to commit resources to enable rapid administration of alteplase to eligible stroke patients. Since ambulances divert patients with suggestive symptoms to stroke certified hospitals, the project has substantial financial ramifications. These efforts, and others like the “Brain Attack” campaign, have been actively supported by the American Heart Association and American Stroke Association, which “partnered” with the Joint Commission (a quasi-governmental agency that accredits hospitals) to promote hospital stroke certification. Genentech, Boehringer Ingelheim and Novo Nordisk, which market alteplase, have contributed tens of millions of dollars to the associations.

In its newly released guidelines, the American Heart Association states that it “makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of . . . a business interest of a member of the writing panel.” However, according to their conflict of interest disclosure statements, 13 of the 15 authors had ties to the manufacturers of products to diagnose and treat acute stroke; 11 had ties to companies that market alteplase.19 In 2010, two years after the association launched this guideline panel, it revised its financial conflicts policy; in the future, neither committee chairs nor the majority of its guideline writing members may have any relevant ties to industry.

Concern about the credibility of guidelines led the Institute of Medicine to recommend that ideally no guideline authors should have financial conflicts of interest.14 If individuals who have professional conflicts that can’t be divested (for example, specialists whose career depends on treating a certain condition) are included, the institute recommends that they “should represent not more than a minority” of the panellists.14

In the guidelines issued jointly by the American College of Emergency Physicians and the American Academy of Neurology, three of eight panellists disclosed ties to the manufacturers. However, seven had either direct ties to the manufacturer or indirect ties, knowingly or not, through affiliations with the Foundation for Education and Research in Neurological Emergencies (FERNE), which provides unrestricted continuing medical education grants (table⇓). Guideline readers were unlikely to know that according to its 2008 tax return, 100% of the $97 000 donated to the foundation that year came from drug companies, including $50 000 from Genentech. The foundation president and founder, Edward P Sloan, is an outspoken advocate of alteplase for stroke.36

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Competing interests of authors of American College of Emergency Physicians and the American Academy of Neurology guidelines on alteplase

For all guidelines, the overwhelming majority of committee chairs and cochairs have ties to industry,12 and selection of panellists with desired viewpoints can make a wished for outcome a foregone conclusion. Committee stacking may be one of the most powerful and important tools to achieve a desired outcome. Seven of the eight panellists had previously published or lectured on the merits of alteplase for stroke. The eighth panellist, Robert Wears, described himself as an “agnostic” but added that he was “surprised” that he was named as an author since he had resigned from the committee six years earlier. Not one sceptic was included on the panel. In response to a question about whether any known sceptics were invited to be on the committee, a spokesperson for the American Academy of Neurology said, “A potential panel member’s opinion on a topic does not determine eligibility for participation on an American Academy of Neurology guideline author panel. The guideline development process is evidence based.”

Wears, a highly respected methodologist and professor of emergency medicine at the University of Florida Health Sciences Center, had been the methodologist for the committee. He told the BMJ that he resigned in part because he was growing increasingly “disillusioned” with the guideline process. When asked why Wears’ name appeared as one of the committee members, Rhonda Whitson, clinical practice manager for the college told the BMJ, “He may have thought his role on the tPA panel ended sooner than it did . . . However, he did participate throughout the project as needed for his role.”

A spokesperson for the Annals of Emergency Medicine, which published the clinical policy, explained how Wears’ name was able to appear in the journal. She told theBMJ that it does not peer review the college’s clinical policies; nor does it vet the authors or members of the development panel.

Widespread problem

Many other conflicted guidelines have come to light in recent years. In 2006, the New England Journal of Medicine published an article warning against aggressive treatment of anaemia with erythropoietin in patients with kidney disease. Patients treated aggressively had increased rates of heart failure and need for dialysis.37Yet guidelines issued in 2007 by the National Kidney Foundation, which received multimillion dollar donations from companies that make erythropoietin, recommended aggressive treatment that would increase the number of patients receiving the drug.38

In 2004, newly issued cholesterol guidelines greatly expanded the number of people for whom treatment is recommended. A firestorm broke out when it was learnt that all but one of the guideline authors had ties to the manufacturers of cholesterol lowering drugs.39

Yet these and other guidelines continue to be followed despite concerns about bias, because as one lecturer told a meeting on geriatric care in the Virgin Islands earlier this year, “We like to stick within the standard of care, because when the shit hits the fan we all want to be able to say we were just doing what everyone else is doing—even if what everyone else is doing isn’t very good.”

Notes

Cite this as: BMJ 2013;346:f3830

Footnotes

• Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare.
• Provenance and peer review: Commissioned; not externally peer reviewed.

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