Petition by Professor David Healy - please sign if you agree

Let us see Drug Data! Drug hazards are not “trade secrets”!

Drug companies maximize the sales of new drugs by hyping their benefits while downplaying significant risks. In 2010 the European Medicines Agency began releasing patient-level data from the clinical trials used to approve new medicines in Europe – a development hailed by American, and European researchers and researchers around the world as a major step towards drug safety.

This process has been shut down by a lawsuit taken by two American corporations – AbbVie, makers of Humira, the number one selling medication in the world with projected sales of $10 billion in 2013; and InterMune, whose pulmonary-fibrosis drug Esbriet has recently been approved in Europe at a cost of over $40,000 per year.

AbbVie and InterMune have filed suit to deny access to the data from their trials on the benefits and harms of these drugs, claiming these vital facts are “trade secrets” whose release would harm their profits. Their action has led to the shutdown of the entire public-access program, leaving millions of patients worldwide, and their doctors, in the dark.

We call on AbbVie and InterMune to drop their European Union lawsuit and release all patient level data on Humira, Esbriet and their other products. Vital data on drug safety should never be hidden as a “trade secret.” By copying this petition to President Barack Obama and members of his Cabinet we call on them to ensure that meaningful public access to clinical trial data becomes the policy of the FDA and is written into any international trade agreements governing the sale of prescription drugs and devices.

Copies to: 
President Barack Obama; 
Margaret Hamburg, M.D., Commissioner, Food & Drug Administration; 
Secretary General Ban Ki Moon, United Nations; 
World Health Organization Director Dr Margaret Chan.

To: 
Richard Gonzalez, c/o Gregory Miley, Group Head, External Communications, AbbVie 
Daniel Welch, c/o Jim Goff, VP Corporate Communications

Please drop your legal action blocking access to EMA clinical trial data. 

Sincerely, 
[Your name]

http://www.change.org/petitions/richard-gonzalez-of-abbvie-and-daniel-w

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The book addresses, in great, evidence-based detail, a general system failure caused by widespread crime, corruption, bribery and impotent drug regulation in need of radical reforms.

About the Author

Peter C Gøtzsche, Professor of Clinical Research Design and Analysis, and Director, The Nordic Cochrane Centre, and Chief Physician, Rigshospitalet and the University of Copenhagen, Denmark

http://www.amazon.co.uk/Deadly-Medicines-Organised-Crime-healthcare/dp/1846198844

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1boringoldman explains data transparency

http://1boringoldman.com/index.php/2013/09/14/a-bottom-line/

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AllTrials Update

Dear Friends

Support for AllTrials around the world is growing and we need to keep it that way as we reach some crucial debates.

The European Medicines Agency’s proposed policy on publishing and sharing information from clinical trials is open for comment until 30^th September. Many of you have been involved in getting your organisations to sign up in support of AllTrials for all trials registered and all results reported. The EMA’s proposals will help to make that happen. But organisations that want to slow or restrict transparency are already making their views known. Please send comments to the EMA before the deadline. Even if you can only comment briefly, please do. It is vital that they hear from the range of bodies and individuals who want an end to hidden trials. We will publish our response next week and share it with you in case that helps.

Last month we published the AllTrials manifesto, which sets out challenges that regulators, companies, researchers, professional bodies, journals and others are addressing (or should be) to make sure that all trials are registered and results reported. There have already been meetings, discussions and documents enlarging on some of the points in there, such as how registries can work together to cross reference registered trials and what journals, funders and ethics committees can do to check up on registration.

We’re going to link these into the document and map out progress in different parts of the medical research system. Meantime, here is some of the news:

• In the UK, the Health Research Authority is about to implement its new policy to ensure all UK clinical trials are registered in a publicly accessible database. From 30th September it will be a breach of good research practice to fail to register a clinical trial.

• PLOS Medicine announced that it will now consider retrospectively registered trials for publication.

• The British Pharmacological Society and the American Society for Pharmacology and Experimental Therapeutics have announced their support for the publication of negative findings from early clinical trials.

• A new paper in the BMJ shows that only 28% of medical journals require a clinical trial reported in their pages to be registered.

• Trial registries around the world are going to work together to identify practicable ways to complete missing trial information.

We put campaign news onto our website at www.alltrials.net every day. We are just about to move on making the website, which we put up in a rush at the start, a more rapid and comprehensive way to keep up with the campaign developments across the world. If you have been visiting it and have suggestions please email in the next few days.

Best wishes                                                                        

Síle

  
www.alltrials.net

Please donate at https://www.justgiving.com/alltrials

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Ketamine, A Darling of the Club Scene, Inspires Next-Generation Antidepressants [Part 3]

Recent experimental research showing that ketamine, an anesthetic and club drug (Special K), can relieve depression quickly has intrigued a number of major pharmaceutical companies. Depression, it goes without saying, affects huge numbers and a fundamentally new and effective pharmaceutical approach to treating the disorder hasn’t emerged in decades.

The enthusiasm for ketamine is such that physicians, often working out of small clinics, have already started prescribing low doses of the generic anesthetic off-label for fast relief of le cafard—and drug companies are contemplating whether to get into the act by creating new drugs based on ketamine’s biochemistry  (Read part 1 and part 2).

A Johnson & Johnson subsidiary in Europe has gone as far as midstage clinical trials for a ketamine nasal spray. The trial there uses a slightly altered version of ketamine (esketamine, the “s” isomer for techies), which omits part of the molecule and leaves the most pharmacologically active portion in place, enabling less of the compound to be administered, perhaps then lessening any club-drug side effects. “You can get away with a 30 to 40 percent lower dose,” says Husseini Manji who leads neuroscience research at Johnson and Johnson.

The U.S. Food and Drug Administration has put Johnson & Johnson’s version of esketamine on a fast track for approval, although, even if all goes well, patients may still have to wait a few years to get a script. Esketamine, already used as an anesthetic in Europe, is not the only idea on the table. Ketamine appears to work (details still coming in from labs) by blocking a docking site, or receptor, on a neuron—in this case a spot where the essential signaling molecule glutamate attaches. The blockade triggers a complex chemical cascade that ends up restoring an impaired neuron’s ability to communicate with other brain cells.

If that process is multiplied over millions of neurons in two critical brain regions—the hippocampus and the prefrontal cortex—drugmakers hope the blues will lift like a cloud. Johnson & Johnson is working on other projects that tap into ketamine research—one of which is  looking at a wholly new drug that targets selected portions of this glutamate receptor in the hope of fine-tuning the antidepressant effects further. Other large pharmas, including AstraZeneca Merck and Roche, are pursuing similar strategies.

If a formal FDA imprimatur is forthcoming, the issue of off-label prescribing may persist. One issue, which must be resolved through clinical trials, not by trial and error at ketamine clinics, is whether a spray works as well as intravenous infusions. The generic non-isomer form of ketamine is already used off-label as a nasal spray and not all reviews are positive. “It helped but not as much as the infusion,” says Dennis Hartman, a patient with depression who sought help from ketamine-prescribing physicians, one of whom provided a spray.

A ketamine-like drug, if approved, will inevitably be more expensive than the generic anesthetic deployed in upstart depression clinics. Esketamine or one of its FDA-sanctioned cousins will probably be covered via a health insurance plan, but insurers’ love of low-cost generics may mean that consideration could still be given to covering plain-vanilla ketamine, even if it hasn’t run the clinical-trial gantlet. In fact, Carlos Zarate, a leading ketamine researcher who works at the National Institute of Mental Health, has even fielded calls from insurers wanting to know more about the generic drug to determine whether to put it on their formularies.

It is also still unclear whether the medical establishment, with a helping hand from law enforcement, may have to come to terms with what might be described as off–off-label prescribing—the depressed patient without insurance who learns about the possibility of a mood-altering quick fix and engages in the unsupervised self administration of Special K purchased in a club or on the street.

Hartman knows someone who went this route. “This personal friend received a ketamine infusion [from a physician],” Hartman says. He achieved very strong relief, very similar to mine. After he relapsed, he went and sought this illegal form and he did not get the same effect.” If Johnson & Johnson’s esketamine trials result in a salable drug, the company has  plans to safeguard it from the hands of those who want to divert it for recreational use.

What to do about ketamine is a question being posed everywhere, not just stateside. A New Zealand government official issued a report in July that instructed health boards throughout the country to scrutinize off-label prescribing more closely after a complaint lodged against a ketamine-supplying physician.

Inevitably, the grassroots appeal of an old drug with a new use that might provide hope for the deeply depressed is starting to generate its own social networks. As many as 20 physicians involved in prescribing ketamine interact on the Linked-In group called Ketamine for Psychiatry. Hartman is involved with setting up a new Web site, The Ketamine Advocacy Network, to foster activism among patients—another echo of medical marijuana’s legacy.

The desperation to find new antidepressants means that ketamine will remain an object of fascination for mental health professionals and their patients. In the next five years, regulators and physicians are going to have to figure out how, if at all, the drug fits into the psychiatrist’s pharmacopoeia. In the meantime, doctors and patients are increasingly adopting their own home-grown solutions.


About the Author: Gary Stix, a senior editor, commissions, writes, and edits features, news articles and Web blogs for SCIENTIFIC AMERICAN. His area of coverage is neuroscience. He also has frequently been the issue or section editor for special issues or reports on topics ranging from nanotechnology to obesity. He has worked for more than 20 years at SCIENTIFIC AMERICAN, following three years as a science journalist at IEEE Spectrum, the flagship publication for the Institute of Electrical and Electronics Engineers. He has an undergraduate degree in journalism from New York University. With his wife, Miriam Lacob, he wrote a general primer on technology called Who Gives a Gigabyte? Follow on Twitter @@gstix1.

http://blogs.scientificamerican.com/talking-back/2013/09/13/ketamine-a-darling-of-the-club-scene-inspires-next-generation-antidepressants-part-3/

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Shouldn’t Hip & Knee Replacements Come With Warranties?

(Great Beyond)

Most new products, from cheapo wristwatches to new cars, often come with manufacturers’ warranties. But that isn’t the case for most hip and knee implants, meaning that a growing number of Americans are having expensive devices put in their bodies without any written assurance from the manufacturers.

More than 4 million Americans currently have knee implants, and that number is expected to grow as life expectancy rates improve. In 2011 alone, there were 711,000 knee replacements performed. That same year, around 500,000 Americans received hip replacement implants. The combined annual demand for these two surgeries is expected to reach 4 million by 2030, and more than half of those patients will be under 65 years old, meaning they will likely be living with the implants for quite some time.

Yet, of the six major manufacturers of knee replacement implants — Biomet, DePuy, Smith & Nephew, Stryker, Wright, Zimmer — only one (Biomet) offers any sort of warranty, and that’s only on one partial knee implant model.

According to our coworkers at Consumers Union, between 2003 and 2013, these manufacturers recalled 709 different devices and components. During that same time period, these companies recalled 578 different recalls related to hip implants.

In both types of implant, the overwhelming majority of recalls were considered Class II recalls, which the FDA describes as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”

But more than 10% of all hip implant recalls were categorized as Class I, described by the FDA as “a situation in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death.” Most of the Class I hip implant recalls were for products made by Stryker.

Some patients with metal-on-metal hip implants have experienced debilitating symptoms — including cardiomyopathy and neurological problems — from debris that flakes off the device over time. The FDA has thus proposed a more rigorous review process for metal-on-metal hip implants.

As we’ve mentioned in the past, FDA approval process for many new implanted devices is streamlined so that each new product need not undergo individual review it the manufacturer can demonstrate that the device is “substantially equivalent” to one that’s already on the market. This is similar to the process FDA uses for giving the go-ahead to cigarettes, which implies the agency holds cancer-causing products to the same standards as implanted medical devices.

Given that most new hip and knee implants are very similar to what’s already being used, the devices are fast-tracked without ever being tested to see if they are safe and effective.

In a 2012 poll, the overwhelming majority of American consumers said they believed in a rigorous review process for new devices, and Consumers Union was one of several patient safety groups that urged Congress to require more pre-market testing of implanted devices during last year’s reauthorization of the Medical Device User Fee Act. Alas, patient advocacy once again lost out to the deeper pockets of the well-heeled medical device industry lobbyists.

You may not care about people with implanted devices and you may say that warranties are unwarranted because many patients are not going out of pocket for these surgeries (or the seemingly inevitable replacement surgeries), but for every failed implant that hits the market, there is an impact on the average consumer.

Even if the patient isn’t paying for the surgery, someone is footing the bill — and it’s often quite a big bill. This is compounded each time there is a replacement, as it often costs more to remove and replace an implant than it did to put it in initially. Patients often end up in the hospital for a longer period of time following these later surgeries.

Consumers Union estimates that revisions to hip and knee replacements cost hundreds of millions of dollars a year. Insurance companies aren’t going to shrug that much money off, especially when it seems likely to increase in the coming decade.

“Patients have a right to know how long medical device manufacturers are willing to stand by their products,” said Lisa McGiffert, director of Consumers Union’s Safe Patient Project. “While patients may be told by their surgeon how long a device can be expected to last, they rarely get a guarantee in writing since most hip and knee implants do not come with a warranty.”

“Medical device companies claim that current law provides adequate protection for patients and that their implants are dependable and safe,” said McGiffert. “If that’s the case, they should have no objection to offering warranties to back up those claims. Patients and taxpayers shouldn’t be on the hook for the cost of replacing devices when they fail.”

CU has already written to the manufacturers, urging each to provide a 20-year warranty with their products. The letters also clarified that an ideal warranty would:

*Cover the full cost of replacing the flawed device, including the device, surgeon and hospital costs as well as related patient out-of-pocket costs.

*Establish a clear system for patients to use, including a toll-free phone line and a registration number to track the claims process, with physicians charging the device company, not the patient.

*Not eliminate the patient’s right to sue if they use a warranty.

*Provide the patient with a full explanation if a warranty claim is denied and an appeals process for denials.

*Not disqualify patients across the board if they have specific diseases or illnesses that are not related to the failure of the device.

For those who believe that manufacturers should include warranties with their implanted medical devices, the folks at CU’s Safer Patient project have put together this handy online form to let you voice your opinion to these companies’ chief executives.

http://consumerist.com/2013/09/12/shouldnt-hip-knee-replacements-come-with-warranties/?

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Wise words

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GlaxoChinaGate contd. - German drug giant Bayer latest target of graft probe | South China Morning Post

The German pharmaceutical firm Bayer is the latest target of the mainland's ongoing investigation into malpractice in the pharmaceutical industry.

The All-China Federation of Industry and Commerce contacted a Bayer office on the mainland in relation to an investigation into anti-trust offences, Bayer's spokesman Guenter Forneck told theSouth China Morning Post in an e-mailed statement.

"We assume that this contact is related to a wider investigation into the pharmaceutical industry in China," he wrote.

The German company is the latest pharmaceutical giant to be drawn into an investigation that first came to light two months ago when police in Changsha, Hunan province, began an investigation into alleged "economic crimes" by employees of the British drug firm GlaxoSmithKline.

US firm Eli Lilly, the French firm Sanofi, the Danish firms Novo Nordisk and H. Lundbeck, the British firm AstraZeneca and the Belgian firm UCB have also said that they were contacted by investigators.

In July, the National Development and Reform Commission said it was extending its investigation to cover 60 international and domestic drugmakers.

Mainland health officials say rampant corruption in the health sector is driving up costs for patients. The investigation is aimed at cracking down on illegal practices among suppliers of pharmaceutical products on the mainland as part of a wider series of measures aimed at reforming the struggling public health care system.

Bayer said it was co-operating with the mainland authorities in the investigation. The company had strict compliance regulations in place and encouraged its employees to report violations, it said, adding that it would look into allegations of misconduct.

China is increasingly important to the firm, making up 19.5 per cent of its total global revenue in the last fiscal year.

Last week the European Union Chamber of Commerce in China's pharmaceutical working group called the industry-wide probe "unfair".

http://www.scmp.com/news/china/article/1308951/german-drug-giant-bayer-latest-target-graft-probe?

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Winning friends

Eli Lilly sues Canada for $500 million

INDIANAPOLIS - Eli Lilly and Company has filed a $500 million international lawsuit against the Canadian government.

Lilly says Canada unfairly shortened the life of patents for its best-selling drugs.

The case was filed Thursday under the rules of the North American Free Trade Agreement.

Lilly says Canadian courts unfairly threw out the patents when challenged by the generic drug manufacturers.

The legal fight will move to the next stage after the two sides failed to settle their differences during a 90-day consultation process which ends Friday.

Doug Norman, general patent counsel for Lilly, released the following statement Thursday:

“Patent decisions in Canada over the last decade not only fly in the face of long-established international standards, but they’re subjective and completely unpredictable. The standard seems to be that there is no standard. The Notice of Arbitration (NOA) is the next natural step in Lilly’s continuing efforts to address financial losses from improper invalidation of our Strattera® and Zyprexa® patents under Canada’s ‘promise utility doctrine.’ 

http://www.theindychannel.com/news/local-news/eli-lilly-sues-canada-for-500-million?

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Richard Smith: Is the pharmaceutical industry like the mafia?

The piece that follows is my foreword to a new and fascinating book by Peter  Gøtzsche, the head of the Nordic Cochrane Centre, entitledDeadly Medicines and Organised Crime: How Big Pharma Has Corrupted Healthcare. I hope that this piece might prompt you to read the book. I was not paid for my foreword and will not receive any payment from the book.

There must be plenty of people who shudder when they hear that Peter  Gøtzsche will be speaking at a meeting or see his name  on the contents list of a journal. He is like the young boy who not only could see that the emperor had no clothes but also said so. Most of us either cannot see that the emperor is naked or will not announce it when we see his nakedness, which is why we badly need people like Peter. He is not a compromiser or a dissembler, and he has a taste for strong, blunt language and colourful metaphors.  Some, perhaps many, people might be put off reading this book by Peter’s insistence on comparing the pharmaceutical industry to the mob, but those who turn away from the book will miss an important opportunity to understand something important about the world—and to be shocked.

An emotional debate at the Danish Society for Rheumatology

Peter ends his book with a story of how the Danish Society for Rheumatology asked him to speak to the theme “Collaboration with the drug industry. Is it THAT harmful?” The original title was “Collaboration with the drug industry. Is it harmful?” but the society thought that too strong. Peter started his talk by enumerating the “crimes” of the meeting’s sponsors. Pfizer, for instance, had been fined $2.3 billion in the United States for  promoting offlabel use of four drugs, while Merck, the last sponsor, had, said Peter, been responsible for the deaths of thousands of patients with its deceptive behaviour around a drug for arthritis. After this beginning to his talk he launched into his condemnation of the industry.

You can imagine being at the meeting, with the sponsors spluttering with rage and the organisers acutely embarrassed. Peter quotes a colleague as saying that he felt “my direct approach might have pushed some people away who were undetermined.” But most of the audience were engaged and saw legitimacy in Peter’s points. In the following year all but one of the companies declined to sponsor the meeting.

Right about mammography

The many people who have enthusiastically supported routine mammography to prevent breast cancer might empathise with the sponsors—because Peter has been critical of them and published a book on his experiences around mammography. The important point for me is that Peter was one of few people criticising routine mammography when he began his investigations but—despite intense attacks on him—has been proved largely right.

He did not have any particular view on mammography when he was asked by the Danish authorities to look at the evidence, but he quickly concluded that much of the evidence was of poor quality. His general conclusion was that routine mammography might save some lives, although far fewer than enthusiasts said was the case, but at the cost of many false positives, women undergoing invasive and anxiety-creating procedures for no benefit. The subsequent arguments around routine mammography have been bitter and hostile, but Peter’s view might now be called the orthodox view. His book on the subject shows in a detailed way how scientists have distorted evidence in order to support their beliefs.

I have long recognised that science is carried out by human beings not objective robots and will therefore be prone to the many human failings, but I was shocked by the stories in Peter’s book on mammography. Much of this book is also shocking and in a similar way: it shows how science can be corrupted in order to advance particular arguments and how money, profits, jobs, and reputations  are the most potent corrupters.

Some benefits from drugs, but this book is not about benefits

Peter does acknowledge that some drugs have brought great benefits. He does so in one sentence: “My book is not about the well-known benefits of drugs such as our great successes with treating infections, heart diseases, some cancers, and hormone deficiencies like type 1 diabetes.” Some readers may think this insufficient, but Peter is very clear that this is a book about the failures of the whole system of discovering, producing, marketing, and regulating drugs. It is not a book about their benefits.

Many of those who read this book will ask if Peter has over-reached himself in suggesting that the activities of the drug industry amount to organised crime. The characteristics of organised crime, racketeering, is defined in US law as the act of engaging repeatedly in certain types of offence, including extortion, fraud, federal drug offences, bribery, embezzlement, obstruction of justice, obstruction of law enforcement, tampering with witnesses, and political corruption. Peter produces evidence, most of it detailed, to support his case that pharmaceutical companies are guilty of most of these offences.

And he is not the first to compare the industry with the Mafia or mob. He quotes a former vice-president of Pfizer, who has said:

“It is scary how many similarities there are between this industry and the mob. The mob makes obscene amounts of money, as does this industry. The side effects of organized crime are killings and deaths, and the side effects are the same in this industry. The mob bribes politicians and others, and so does the drug industry …”

Falling foul of the US Department of Justice

The industry has certainly fallen foul of the US Department of Justice many times in cases where companies have been fined billions. Peter describes the top 10 cases in detail, but there are many more. It’s also true that they have offended repeatedly, calculating perhaps that there are large profits to be made by flouting the law and paying the fines. The fines can be thought of as “the cost of doing business” like having to pay for heat, light, and rent.

Many people are killed by the industry, many more than are killed by the mob. Indeed, hundreds of thousands are killed every year by prescription drugs. Many will see this as almost inevitable because the drugs are being used to treat diseases that themselves kill. But a counter-argument is that the benefits of drugs are exaggerated, often because of serious distortions of the evidence behind the drugs, a “crime” that can be attributed confidently to the industry.

The great doctor William Osler famously said that it would be good for humankind and bad for the fishes if all the drugs were thrown into the sea. He was speaking before the therapeutic revolution in the middle of the 20th century that led to penicillin, other antibiotics, and many other effective drugs, but Peter comes close to agreeing with him and does speculate that we would be better off without most psychoactive drugs, where the benefits are small, the harms considerable, and the level of prescribing massive.

Systematic corruption

Most of Peter’s book is devoted to building up the case that the drug industry has systematically corrupted science to play up the benefits and play down the harms of their drugs. As an epidemiologist with very high numerical literacy and a passion for detail, so that he is a world leader in critiquing clinical studies, Peter is here on very solid ground. He joins many others, including former editors of the New England Journal of Medicine, in showing this corruption. He shows too how the industry has bought doctors, academics, journals, professional and patient organisations, university departments, journalists, regulators, and politicians. These are the methods of the mob.

The book doesn’t let doctors and academics avoid blame. Indeed, it might be argued that drug companies are doing what is expected of them in maximising financial returns for shareholders, but doctors and academics are supposed to have a higher calling. Laws that are requiring companies to declare payments to doctors are showing that very high proportions of doctors are beholden to the drug industry and that many are being paid six figures sums for advising companies or giving talks on their behalf. It’s hard to escape the conclusion that these “key opinion leaders” are being bought. They are the “hired guns” of the industry.

And, as with the mob, woe be to anybody who whistleblows or gives evidence against the industry. Peter tells several stories of whistleblowers being hounded, and John Le Carré’s novel describing drug company ruthlessness became a bestseller and a successful Hollywood film.

So it’s not entirely fanciful to compare the drug industry to the mob, and the public, despite its enthusiasm for taking drugs, is sceptical about the drug industry. In a poll in Denmark the public ranked the drug industry second bottom of those in which they had confidence, and a US poll ranked the industry bottom with tobacco and oil companies. The doctor and author Ben Goldacre, in his book Bad Pharma raises the interesting thought that doctors have come to see as “normal” a relationship with the drug industry that the public will see as wholly unacceptable when they fully understand it. In Britain doctors might follow journalists, members of Parliament, and bankers into disgrace for failing to see how corrupt their ways have become. At the moment the public tends to trust doctors and distrust drug companies, but the trust could be rapidly lost.

Some solutions

Peter’s book  is not all about problems. He proposes solutions, some of which are more likely to happen than others. It seems most unlikely that drug companies will be nationalised, but it is likely that all the data used to license drugs will be made available. The independence of regulators should be enhanced. Some countries might be tempted to encourage more evaluation of drugs by public sector organisations, and enthusiasm is spreading for exposing the financial links between drug companies and doctors, professional and patient bodies, and journals. Certainly the management of conflicts of interest needs to be improved. Marketing may be further constrained, and resistance to direct to consumer advertising is stiffening.

Critics of the drug industry have been increasing in number, respectability, and vehemence, and Peter has surpassed them all in comparing the industry with organised crime. I hope that nobody will be put off reading this book by the boldness of his comparison, and perhaps the bluntness of the message will lead to valuable reform.

Richard Smith was the editor of the BMJ until 2004 and is director of the United Health Group’s chronic disease initiative.

http://blogs.bmj.com/bmj/2013/09/10/richard-smith-is-the-pharmaceutical-industry-like-the-mafia/

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Another day, another J&J recall ... Mold found in schizophrenia drug forces Johnson & Johnson recall

By Bloomberg News 

on September 11, 2013 at 5:25 PM, updated September 11, 2013 at 5:27 PM

Johnson & Johnson has recalled 5,000 vials of its long-acting drug for patients with schizophrenia. Bloomberg  

Johnson & Johnson is recalling 5,000 vials of its Risperdal Consta, a long-acting drug for patients with schizophrenia, after testing found the medicine was no longer sterile.

Routine analysis showed one lot of the injected drug was contaminated with alternaria alternata, a common mold found in the environment, said Robyn Reed Frenze, a spokeswoman for the New Brunswick-based company’s Janssen unit.

There haven’t been any reports of complications among patients who received the medicine, though injection site reactions are possible, she said.

J&J, the world’s biggest seller of health products, has been plagued by recalls for several years. The company last week withdrew about 200,000 bottles of concentrated Motrin Infants’ Drops and is facing thousands of lawsuits following the recall of 93,000 ASR model hip implants in August 2010.

“The risk to patients is low,” Frenze said. “We don’t want to create unnecessary concern,” though the company thought it was important to provide the information to doctors and others who may still have the medicine on hand, she said.

The recalled 5,000 vials are those remaining from about 70,000 originally manufactured and are mainly with wholesalers, distributors or in pharmacy or doctor’s officers, Frenze said in an interview. The medicine, approved for patients with schizophrenia and bipolar 1 disorder, generated $336 million in the second quarter. It is typically given every two weeks.

Risperdal Consta, which is refrigerated, is different from the company’s Risperdal medication, which is given orally. The recall doesn’t affect Risperdal.

http://www.nj.com/business/index.ssf/2013/09/mold_found_in_schizophrenia_dr.html?

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Hurrah!

Press Release
11 September 2013

FOR IMMEDIATE RELEASE

The HRA is now implementing its plans for ensuring that UK trials are registered in a publicly accessible database.

The HRA has a commitment to promote transparency in research, and has worked in consultation to develop plans to implement a set of practical and proportionate measures to improve transparency of research in the UK and to improve patient and public confidence in health research. It is now implementing the proposal to make trial registration a condition of the favourable ethical opinion. Janet Wisely, Chief Executive of HRA, commented: “We are fully committed to the principles of transparency in health research. Including a requirement for registration as a condition of the favourable ethical opinion is a significant step towards this.”

Requirements

From 30 September 2013 registration of clinical trials in a publicly accessible database will be a condition of the favourable ethical opinion. Failure to register will therefore be a breach of good research practice and managed through standard operating procedures for RECs (Research Ethics Committees) in line with other breaches.

The studies for which registration is mandated will initially be determined by the IRAS filter question. It will include the first four categories on the Integrated Research Application System (IRAS) filter question number 2, namely:

•   Clinical trial of an investigational medicinal product

•   Clinical investigation or other study of a medical device

•   Combined trial of an investigational medicinal product and an investigational medical device

•   Other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice 

  http://www.hra.nhs.uk/EasysiteWeb/getresource.axd?AssetID=179321&type=full&servicetype=Attachment

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Pain drugs will need new warnings to alert patients and doctors about their dangers.

Each year, 16,000 people in the US die of overdoses that include prescription opioids— and the extended-release and long-acting drugs such as Oxycontin or methadone are disproportionately responsible for such deaths. While currently labeled to treat moderate to severe pain, the drugs will now carry warnings that indicate the drugs are to be used only “for the management of pain severe enough to require daily, around-the-clock opioid treatment and for which alternative treatments are inadequate.” New warnings about the withdrawal syndrome that can affect newborns exposed during pregnancy, which can be life-threatening if not managed properly, will also be included.

The Food and Drug Administration’s (FDA) action is in response to the growing number of overdose and abuse cases related to opioid use; by restricting approval to the most severe cases of pain, the agency hopes to limit access to the drugs, since more prescriptions can lead to wider usage and to dependence or addiction. “The FDA is invoking its authority to require safety labeling changes and postmarket studies to combat the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs that have harmed too many patients and devastated too many families and communities,” FDA commissioner Dr. Margaret Hamburg said in a statement.

While a citizen’s petition by a group called Physicians for Responsible Opioid Prescribing (PROP), had called for limiting the drugs’ use to 90 days or less, the agency rejected that idea.  “What we’ve concluded is that we need more information about where risk begins,” said Dr. Douglas Throckmorton, the deputy director of regulatory programs at the FDA at a press conference, explaining that existing data doesn’t suggest a particular dose or duration at which risk becomes problematic. The FDA is also requiring that manufacturers conduct post-marketing studies to try to answer these questions.

“I would hope that [the new label] would help improve careful appropriate prescribing of these medications, which have unquestioned value in appropriately chosen patients,” Throckmorton said.

http://healthland.time.com/2013/09/10/long-acting-pain-drugs-no-longer-approved-for-treating-moderate-pain/?

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Trials. 2012; 13: 136.

Published online 2012 August 13. doi:  10.1186/1745-6215-13-136

PMCID: PMC3439687

Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin® litigation

S Swaroop Vedula,¹ Palko S Goldman,² Ilyas J Rona,² Thomas M Greene,² and Kay Dickersin¹

Author information ► Article notes ► Copyright and License information ►

This article has been cited by other articles in PMC.

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Abstract

Background

Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin®, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain.

Methods

We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (seehttp://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court’s findings).

We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom.

Results

We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of study results was delayed; and the role of ghost authorship.

Conclusions

Taken together, the extracts we present from internal company documents illustrate implementation of a strategy at odds with unbiased study conduct and dissemination. Our findings suggest that Pfizer and Parke-Davis’s publication strategy had the potential to distort the scientific literature, and thus misinform healthcare decision-makers.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439687/?report=classic

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GlaxoChinaGate contd. - GSK affirms China plans, despite scandal - BUSINESS - Globaltimes.cn

British drug maker GlaxoSmithKline (GSK) said it remains "committed to China for the long term" in a statement e-mailed to the Global Times Tuesday, despite recent reports that the company is considering pulling out of China. 

GSK is considering leaving China as it is facing a penalty of 20 billion yuan ($3.27 billion) for bribing doctors, China National Radio reported Monday, citing an unnamed company executive. 

With the continuing development of China, the need for healthcare and medicine will increase so it is not likely that GSK will leave a market with such great potential, said Lu Jinyong, director of the China Research Center for Foreign Direct Investment at the Beijing-based University of International Business and Economics. 

Lu also said it would be a dishonorable move for GSK to retreat from China amid such a widely reported bribery scandal. 

China welcomes foreign enterprises that obey local laws and regulations, He Manqing, director of the Institute of Foreign Investment under the Chinese Academy of International Trade and Economic Cooperation, told the Global Times Tuesday.

GSK should learn from its mistakes, Lu said. According to UK laws, the country's firms are forbidden from offering bribes when conducting business overseas, and GSK should have internal control to avoid such practices. But the scandal shows that GSK has not effectively implemented this in its branch in China, Lu noted. 

Lu and He both said it would be difficult to predict what kind of fine the company will face before the investigation is completed. 

The Department of Justice in the US is also investigating GSK over whether it violated US laws against overseas corruption, as the company is listed on the New York Stock Exchange, Reuters reported Friday.

http://www.globaltimes.cn/content/810250.shtml#.Ui_8Tny9KK1

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Dementia campaign could lead to over-diagnosis, say experts

The current prevalence of dementia is thought to be 10-30% in people over the age of 80. Photograph: John Stillwell/PA

Two-thirds of people aged 80 or over could be diagnosed with dementia in future because doctors are subjecting patients to needless investigation for and potentially damaging treatment of the disease, experts say.

The specialists in dementia, geriatric medicine and public health claim the growing trend towards older people having their risk of dementia assessed could lead to considerable over-diagnosis.

"The current prevalence of dementia is thought to be 10-30% in people over the age of 80, but the adoption of new diagnostic criteria will result in up to 65% of this age group having Alzheimer'sdisease diagnosis and up to 23% of non-demented older people being diagnosed with dementia," say the British and Australian experts, writing in the British Medical Journal.

They criticise government moves to increase the early diagnosis of dementia by identifying more people as soon as possible with mild cognitive impairment, or pre-dementia, which can be a precursor of the condition, such as through cash incentives to GP surgeries and establishing a network of memory clinics.

They claim the "political drive" in the UK and US towards early diagnosis is not backed by evidence of benefit and is part of a pointless "war against dementia" that is producing more commercial opportunities for firms that sell testing tools rather than helping patients at risk of developing the condition.

"Only 5% to 10% of people with mild cognitive impairment will progress to dementia each year, and as many as 40%-70% of people do not progress or their cognitive function may even improve," write the authors, who include Carol Brayne, professor of public health at Cambridge University.

In addition, "the neuropathology of mild cognitive impairment does not support the concept that most people with this condition are in the early stages of Alzheimer's disease," they say.

Supporters of the drive towards early diagnosis say foreknowledge that someone may develop dementia can let them draw up instructions for their future care, put their financial affairs in order and make lifestyle changes, such as eating healthily and taking more exercise, that will slow the disease's progress.

But the authors claim that an early diagnosis can lead to patients taking unproven therapies such as gingko biloba to try to delay the onset of dementia, suffering stress, distress and possible stigma, or even contemplating suicide or euthanasia.

http://www.theguardian.com/society/2013/sep/10/dementia-over-diagnosis

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Of Conflicts and Clinical Trials: Researchers Report New Results

CHICAGO, ILLINOIS—This week, the International Congress on Peer Review and Biomedical Publication here drew researchers from around the world to discuss ways to “improve the quality and credibility of scientific peer review and publication.” ScienceInsider attended and covered some of the more intriguing presentations. Today: a look at studies of problems in how researchers report the results of clinical trials and potential conflicts of interest.

Published Trial Results Often Differ From Those Initially Posted

Deborah Zarin, director of the database ClinicalTrials.gov at the National Library of Medicine, likes to say that her website is “a window into the sausage factory”—a view that we usually don’t get of how clinical trials work and how they don’t.

Six years ago, ClinicalTrials.gov was tasked by Congress to embark on a new experiment: In addition to trial registrations, many trial sponsors were required to deposit their results in the public database for anyone to access. At the congress, a group from Yale University School of Medicine explored how well the results posted on ClinicalTrials.gov match up with what’s published. What they found was not particularly encouraging.

Jessica Becker, a medical student, described how she and her Yale colleagues—Harlan Krumholz, Gal Ben-Josef, and Joseph Ross—identified 96 trials published between July 2010 and June 2011, all of them with a ClinicalTrials.gov identification number. They focused on studies that appeared in high-profile journals. Almost three-quarters of the trials analyzed were funded by industry.

All but one trial had at least one discrepancy in how trial details, results, or side effects were reported.

One big question was whether the same primary endpoints and secondary endpoints appeared in both the final publication and the ClinicalTrials.gov results database. A primary endpoint represents the main goal of a study and the question or questions it was designed to answer. Secondary endpoints are often added to squeeze as much information as possible out of what’s collected, but statistically they can be weaker because the trial wasn’t created with them in mind. Primary endpoints in 14 trials appeared only on ClinicalTrials.gov, while primary endpoints from 10 others were only in the publication. The results described were also different in some cases: For 21% of the primary endpoints, what appeared in the journal wasn’t exactly the outcome described on ClinicalTrials.gov, and in 6%, the Yale group suggested that this difference influenced how the results would be interpreted.

For secondary endpoints, the difference was even more dramatic: Of more than 2000 secondary endpoints listed across the trials, just 16% appeared the same way in both the public database and the published article along with the same results. Results for dozens of secondary endpoints were inconsistent. “Our findings raise concerns about the accuracy of information in both places, leading us to wonder which to believe,” Becker said.

The group hasn’t probed why this is happening: There could be innocent errors on ClinicalTrials.gov or typos in publications. Or authors may promote “more favorable stuff” in what’s printed, she speculated.

“There are many, many microdecisions” that come with writing up a publication, Zarin says. The uncomfortable results presented by Becker are “part of what motivates the desire” for anonymized information on individual patients, Zarin suggests—exposing that might be the only way to reconcile the discrepancies. Zarin also speculates that researchers might add positive secondary endpoints after the study is completed—a big no-no in the trials world—to give it a rosier hue, and thus they don’t appear on ClinicalTrials.gov when the study is first registered. Zarin is conducting her own analysis of the ClinicalTrials.gov results database, which now includes results from almost 10,000 trials. (150,000 trials are registered on the site.) She says she’s reaching similar outcomes as the Yale group.

One question that the Yale team didn’t explore was whether researchers had inputted their results on the site before submitting their paper—something that would allow journal editors or reviewers to play detective and see whether the document they have matches up with what’s in the database.

Potential Conflicts Still Going Unreported

Clinical trial authors still aren’t reporting their conflicts of interest, despite years of conversations and new policies encouraging them to do so. That’s the bottom line of a study presented here at the International Congress on Peer Review and Biomedical Publication, where Kristine Rasmussen from the Nordic Cochrane Centre in Copenhagen presented a new study tackling this question.

In most countries, it might be tough to determine whether authors who don’t disclose conflicts actually have them. But Denmark is unusual, because all Danish physicians are required by law to fill out forms if they collaborate with industry, and those forms are publicly available. (The United States is beginning to implement a similar rule as part of the Affordable Care Act.) The Danish system made it straightforward for Rasmussen and her Cochrane colleagues—Jeppe Schroll, Peter Gøtzsche, and Andreas Lundh—to compare disclosures of industry associations in published papers with the forms filed by doctors.

They looked at journals that follow recommendations from the International Committee of Medical Journal Editors (ICMJE) and searched for trials that had at least one Danish physician author who did not work at a company. They selected 100 recent studies. About half the doctors had some financial conflict of interest with a drug company, though not necessarily the company sponsoring the published research, they found.

Although most of the doctors disclosed relationships they had with the firm funding the published research, fewer than half shared relationships they had with industry competitors. And despite all the talk in recent years about conflicts, 16% who had a financial tie to a sponsor or drug manufacturer leading the study didn’t report it. One example cited by Rasmussen: a physician who was an advisory board member and speaker for AstraZeneca, maker of the drug being covered by the paper, who declared he or she had no conflicts.

“I was actually very disappointed” by this, says Vivienne Bachelet, editor-in-chief of the journal Medwave in Santiago, who was not involved in the study. In her country, she says, the “level of awareness is just nil” about conflicts of interest. Medical societies in particular get substantial funding from drug companies but almost no one—the societies themselves, drug regulators, or the individual doctors—see this as something that should be disclosed, Bachelet says. “If they’re not disclosing over there,” in Denmark, “what’s to be expected in Chile?”

Rasmussen noted that one issue might be vagueness in the ICMJE conflict of interest form: While it’s specific about the expansive nature of conflicts that might arise, such as travel paid by a company or fees for expert testimony, it suggests that authors disclose only those that are “relevant.” Says Rasmussen, “authors are left to decide” what falls into that category.

http://news.sciencemag.org/scientific-community/2013/09/conflicts-and-clinical-trials-researchers-report-new-results?

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Slumdog Clinical Trials contd - Kenyan patients being used as guinea pigs by researchers

By PETER ORENGO

Thousands of desperate Kenyan patients are being used as guinea pigs in a thriving multibillion-drug industry with some trials contravening the country’s laws and the international drugs-trial protocols.


A Dutch NGO, Somo, has released a report, Clinical Trials in Kenya, which says some of this research is conducted by individuals, especially university researchers working on their theses. The experiments conducted   often raise ethical issues, especially when safety protocols are ignored.

The specialists say the problem is being compounded when desperate Kenyans diagnosed with cancer or HIV volunteer for trials solely to gain access to medicine and treatment.

Those carrying out the trials include poorly-paid university researchers and doctors who willingly use new drugs on patients upon being promised   money, or an agreement for further studies in elite institutions outside the country.

The major risk factor here is bio-terrorism where the country could be exposed to harmful substances or even diseases worse than Aids. Those involved include renowned Kenyan professionals, who apart from working for drug companies, authorise the smuggling of medical samples such as blood and body part organs for study outside the country. The cartel is said to include high-level government officials.

“I know that a lot of our doctors and researchers participate, either knowingly or through orders of their superiors, in administering unapproved drugs on patients,” said a lead researcher who accepted to talk so long as he was not named.

  “Also, Kenyans, especially those with HIV, are signing up for clinical trials because they think they may somehow end up being cured. Research is big business in this country.”

Moses Otsyula, now head of virology at Kenya’s Institute of Primate Research, raised the red flag a few years ago when he filed a lawsuit against Oxford University and eight British scientists, alleging fraud and theft of samples and research materials, which were ferried outside the country.

MORE:

http://www.standardmedia.co.ke/?articleID=2000093238&story_title=Kenya-kenyan-patients-being-used-as-guinea-pigs-by-researchers

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