Garden State crackdown on drug marketing

Any doctor wanting to practice medicine in New Jersey may soon have to refuse lunches from drug industry representatives and any gift worth more than $200 (US), if new rules proposed by the state's attorney general are adopted.

The proposals were among 22 recommendations included in a Dec. 3 report to Attorney General Anne Milgram

While a handful of states have fought financial conflicts in medicine by regulating drugmakers and threatening hefty fines, the proposals would make New Jersey the first to make doctors the targets of enforcement.

The proposed regulations "are designed to ensure that patient care is guided by the unbiased exercise of doctors' best judgments," Milgram said in endorsing the report's proposals. "It is critical to minimize the potential for conflicts, and it is critical that patients are made aware of any financial relationship between a physician and a pharmaceutical company or medical device manufacturer. Such relationships could bias medical decision-making."

The report calls on the state medical board to require that 25 per cent of continuing medical education credits come from "evidence-based educational programs" that refuse industry grants. The report also targets ghostwriting, a widespread practice in the drug industry, by recommending that doctors be barred from claiming authorship for articles they did not write. The report also aims to stop doctors from misrepresenting their financial interests on disclosure forms.

On the industry side, the report recommends tight controls on what is known in the pharmaceutical industry as “data mining,” or tracking physician prescription information. All physicians would have to be notified when renewing their licenses that they can opt out of having information about their prescriptions sold by pharmacists to healthcare information organizations, which collect information on prescriptions for pharmaceutical company marketing.

As well, the report recommends that pharmacies be required to maintain documentation that doctors have consented to the sale of their prescribing information. The report calls for legislation to restrict the use and sale of prescriber information for commercial purposes.

 

 

The video Pfizer doesn't want you to see

Pharmaceutical giant Pfizer has asked a judge to order that a video be take off YouTube, saying it could prejudice juries in upcoming court cases.

It's the latest twist for a company caught for months in allegations of ghostwriting.

The video, entitled Prempro News Segment, was made by the law firm behind a $78 million (US) court-ordered settlement in the fall of a lawsuit brought against the company. The Philadelphia jury found that Wyeth, a division of Pfizer, failed to warn women that taking its hormone drug Prempro could cause breast cancer.

“Plaintiff’s counsel should be compelled to remove this video from the Internet and refrain from making any further inflammatory and prejudicial public statements” until the litigation is resolved, Pfizer’s lawyers said in a motion filed yesterday in Philadelphia Common Pleas Court.

More than 6 million women have taken hormone-replacement medicines to treat menopause symptoms such as hot flashes, night sweats and mood swings. Until 1995, many patients combined Premarin, an estrogen-based drug made by Pfizer’s Wyeth unit, with progestin-laden Provera, made by Upjohn, another subsidiary of Pfizer, the world’s largest drugmaker.

Wyeth scientists later combined the two hormones in its Prempro pill. The drugs are still on the market. New York-based Pfizer completed its $68 billion purchase of Wyeth in October.

The video was produced by lawyer Zoe Littlepage, who had her staff post it to YouTube. It is made to look like a TV news segment. In it, she accuses Wyeth of hiding the drug's dangers.

“Wyeth chose to not do studies, and even worse, chose to downplay and suppress any evidence of breast cancer and these drugs,” Littlepage says on the video, which doesn’t include a response to the allegations from Pfizer.

The video also features a man identified as a jury foreman in an already-concluded trial over the menopause drugs who calls Wyeth “despicable” and declares that the company is more concerned about profit than about the health of patients.

Documents in the case, filed by Connie Barton, a medical office assistant in Peoria, Ill., have now been unsealed, and used by the New York Times to track the marketing of hormone replacement therapy to women.

The documents that have surfaced in the Wyeth cases offer a rare glimpse inside the file cabinets and hard drives of a major drug company. And the cases demonstrate the importance of litigation in detailing exactly how drug makers operate their businesses, says Dr. Jerome L. Avorn, a professor of medicine at Harvard Medical School who has written about the subject in The Journal of the American Medical Association.

“The information coming out in litigation helps us understand how a belief in a ‘protective benefit’ of estrogens on the heart was able to spread like wildfire through the medical community,” says Dr. Avorn, who is not involved in the Wyeth litigation.

“Thousands of doctors prescribed the drugs for millions of women on that basis,” he says, adding that studies later contradicted the belief. “It will be very interesting to see whether the courts are able to connect the dots and make it clear whether this was a kind of medical ventriloquism on Wyeth’s part.”

Chris Loder, a Pfizer spokesman, says Wyeth acted responsibly by including a clear warning about a breast cancer risk on Prempro labels and by updating the warning as new evidence emerged. He said Pfizer plans to appeal every product-liability case on menopausal drugs it loses, including Barton’s.

 

 

 

Paxil costs Glaxo $1 billion or more: report

Settling lawsuits over its controversial anti-depressant Paxil has cost Glaxo SmithKline some $1-billion in court-ordered and out-of-court settlements, Bloomberg News reports.

“I don’t think this is within the boundaries of current assumptions for analysts.” Navid Malik, an analyst at Matrix Corporate Capital in London, is quoted as saying.

Another analyst, Savvas Neophytou, a Panmure Gordon analyst in London, says a $1.5 billion liability is possible.

The settlements result from suits in which people taking the drug caused them to contemplate suicide or birth defects in their children. In each of the cases, the plaintiffs allege that Glaxo knew of the dangers.

As part of the total, Glaxo, the U.K.’s largest drugmaker, so far has paid $200 million to settle Paxil addiction and birth-defect cases and $400 million to end antitrust, fraud and design claims, according to the people and court records.

The $1 billion “would be worse than many people are expecting,” said Navid Malik, an analyst at Matrix Corporate Capital in London. “I don’t think this is within the boundaries of current assumptions for analysts.”

The London-based company hasn’t disclosed the settlement total in company filings. It has made public some accords. Glaxo’s provision for legal and other non-tax disputes as of the end of 2008 was 1.9 billion pounds ($3.09 billion), according to its latest annual report. This included all legal matters, not just Paxil. The company said 112 million pounds of this sum would be “reimbursed by third-party issuers.”

The drugmaker has reduced its insurance coverage to contain costs, “accepting a greater degree of uninsured exposure,” the annual report states. “Recent insurance loss experience, including pharmaceutical product-liability exposures, has increased the cost of, and narrowed the coverage afforded by, insurance for pharmaceutical companies generally,” Glaxo said.

Glaxo declined to confirm the $1 billion figure. “Paxil has been on the market in the U.S. since 1993. Like many other pharmaceutical products, it has been the subject of different kinds of litigation over the years,” said Sarah Alspach, a spokeswoman for Glaxo, in an e-mailed statement. “It would be inappropriate and potentially misleading to aggregate payments in these various types of litigation.”

Chief Executive Officer Andrew Witty has moved to replace revenue lost to generic versions of drugs such as Paxil. Worldwide, Paxil generated about 514 million pounds in sales last year, or 2.1 percent of the total. Glaxo closed up 5 pence to 1,303 pence in London trading Dec. 11, down 8.8 percent from a year ago.

About 450 suicide-related Paxil cases were settled. Only about a dozen haven’t been, the people said. The $1 billion total doesn’t include more than 600 claims that Paxil caused birth defects.

A Philadelphia jury on Oct. 13 found the drugmaker should pay $2.5 million to the family of Lyam Kilker, a 3-year-old boy born with a heart defect after his mother took Paxil while pregnant. Based on that outcome, an analyst estimated the company may potentially face additional verdicts in birth-defect cases waiting to be tried in Pennsylvania.

“A liability totaling $1.5 billion is possible,” wrote Savvas Neophytou, a Panmure Gordon analyst in London, in a note to investors the day after the Kilker verdict. He still recommended buying Glaxo shares because a likely appeal may reduce the amount paid by the company.

 

Pfizer conflict controversy continues

The controversial appointment of Pfizer Canada executive Bernard Prigent to the Canadian Institutes of Health Research was the lead item on the CBC's national morning radio show, The Current.

A podcast of the show is available.

In the show, Francoise Baylis, Canada Research Chair in bioethics at Dalhousie University, says it is impossible for Prigent to avoid a conflict of interest in the new posting because his job as a Pfizer vice president is to sell as many drugs as possible. The job of the CIHR, however, is to ensure public safety. The two are not always the same thing, she said.

Dr. Jean Rouleau, dean of medicine at the University of Montreal and a member of the CIFR's governing council told the CBC's Anna Maria Tremonti that the group needs to hear from people in the pharmaceutical industry.

Baylis said such input, when needed, could be had by calling Prigent and other industry executives to make submission to the CIHR, without giving them a voice in the decisions made by the group.

Meanwhile, a former member of the CIHR, Saskatchewan researcher Steven Lewis lashed out at the appointment, citing the industry's past marketing scandals and saying the appointment gives Pfizer a competitive advantage over other companies.

"The industry's greatest innovations have occurred outside the lab," he wrote. "Expensive junkets for docs-for-hire to shill for their products to their peers; the purchase of previously distinguished academics to affix their names to ghostwritten papers; the suppression of unfriendly clinical trials and adverse effects data; the publication of the same data in different journals to bias systematic reviews and meta-analyses; etc. ad infinitum."

Lewis said it is "hardly irrelevant that the company to which Dr. Prigent owes his livelihood and his allegiance has owned up to sleaze that stands out even among its shady peers."

Since 2004, Pfizer, the world's largest drug company, has paid $2.75 billion in criminal fines and penalties, Lewis said. "Most recently (Pfizer paid) a whopping $2.3 billion for fraudulently marketing Bextra, a painkiller withdrawn from the market in 2005, and three other drugs."

He questioned how Prigent would respond if the council were asked to support research showing a Pfizer drug is dangerous or identifies the massive public subsidies that flow to drug companies.

As a member of the governing council, Lewis said Prigent will have access to information that his competitors do not and "he can exert a steering effect where they cannot."

CIHR president Dr. Alain Beaudet, who recommended Prigent for the appointment, has said he will bring a private-sector voice to the council and help ensure wise spending.

An online petition against the appointment has now collected almost 4,000 names.

 

 

Pfizer Canada facing two conflict fights

Drug giant Pfizer Canada finds itself at the centre of two conflict of interest controversies after one of its executives was appointed to the Canadian Institutes of Health Research and it signed a deal to provide $780,000 for the Canadian Medical Association to set up educational programs for doctors.

The controversies have also touched the Canadian Medical Association, which is coming under fire for taking $780,000 from Pfizer to set up the education programs.

“My feeling is that the pharmaceutical industry has no business at all educating doctors,” said Arnold Relman, professor emeritus at Harvard Medical School and former editor of the New England Journal of Medicine. “There's no question that if you're paying the piper, you influence the tune that the piper is going to play.”

Heather Bisset, Pfizer Canada's manager of corporate communications, said it simply wants to “improve education that's provided for doctors across Canada.”

Meanwhile, as of this writing, more than 3,100 people had signed an online petition against the appointment of Dr. Bernard Prigent, vice president and medical director of Pfizer Canada, to the governing council of CIHR.

Francoise Baylis, Canada Research Chair in bioethics at Dalhousie University calls Prigent's appointment "an intractable conflict of interest."

To quote from one of the signatories, “You don’t put the rooster in charge of the hen house.” The duty of pharmaceutical companies (e.g., Pfizer) is to make money for their shareholders. The duty of CIHR is to promote the public interest. The interests of shareholders and the interests of Canadians are not one and the same.

CIHR was created in 2000 as an arms-length federal agency responsible for funding health research in Canada. The 2009-2010 total budget for CIHR was just under a billion dollars. This is a lot of money and it is important that Canadians understand how their tax dollars are being spent.

CIHR president Alain Beaudet said Prigent's experience in innovation and commercialization will “fill a major expertise gap” on the board.

 

Researchers ask NIH to fund ethics research

In the wake of growing scandals over conflicts of interest and ghostwriting in medical research, more than 100 top researchers from around the world -- including several from Canada -- wrote to the U.S. National Institutes of Health this morning asking it to fund ethics research.

We are writing to ask NIH to fund studies on medical ethics, conflicts of interest in medicine and research, and prescribing behavior. NIH funds a substantial portion of the generation and dissemination of evidence, but the uptake of that evidence and its translation into clinical practice is strongly affected by the complex web of relationships that exists among industry, academicians, medical educators and clinicians.

There is growing evidence that each strand of this web is compromised by ethical lapses and financial conflicts of interest. The recent disclosure of ghostwritten articles, physician payoffs, and the use of academic opinion leaders to increase markets for FDA-regulated products indicate that ethical lapses may permeate biomedical research. A PLoS Medicine editorial in September called ghostwriting “The dirty little secret of medical publishing” and notes “the systematic manipulation and abuse of scholarly publishing by the pharmaceutical industry and its commercial partners in their attempt to influence the health care decisions of physicians and the general public.” An October 1 editorial in the Boston Globe called for a ban on industry speaker fees to physicians. Last month, a commentary in JAMA called for physicians to pay for continuing medical education (CME), citing a recent Institute of Medicine report4 that criticized physicians’ reliance on industry-funded education.

The letter to NIH director Francis Collins says the NIH "is the best place to launch and support a scientifically rigorous inquiry into the state of research ethics, industry-academic relationships, and the effect of these relationships on human health."

It notes, however, that there is currently no mechanism in place for the NIH to conduct such a study, but asks to meet face-to-face with Collins to discuss the issue.

The 10-page footnoted letter co-ordinated by PharmedIOut, a physician-run organization researching conflicts of interest, contains more than eight pages of signatures from top medical and ethics researchers from around the world.

Signatories include several Canadians, including Sharon Batt of Dalhousie University, Pierre Biron of the Université de Montréal, Alan Cassels of the University of Victoria, Carol Kushner a health policy consultant in Toronto, Joel Lexchin at York University, Barbara Mintzes at the University of British Columbia, David L. Sackett at McMaster University and Sergio Sismondo at Queen's University.

 

Research ethics need an overhaul: report

A report out this week calls for an overhaul of the way academic research is done in this country, and for an ombudsman to be appointed to oversee everything.

The report, the Montreal Gazette points out, was well underway before the question of academic integrity broke wide open in Canada last summer with a Toronto Star story about the use of ghostwriters by McGill University professor Barbara Sherwin in an academic article about hormone replacement therapy.

A university inquiry into Sherwin is still several months from completion, the schools says, and likely won't be finished until the new year. The school's provost office blames the long investigation on the huge repercussions for whatever it decides and the complexity and rarity of the case itself.

The new report, however, makes the point that academic misconducts are not all that rare -- though Canada is better than many. The drug sector is particularly bad.

Breeches of research integrity are a problem in some parts of the private sector, notably in the pharmaceutical industry. The existence of companies, including some in Canada, that “ghost write” papers for academic researchers is but one visible manifestation of research misconduct in the private sector. These companies craft research papers in support of a particular drug and seek out researchers willing to be listed as authors in exchange for money and other benefits.

The study, The State of Research Integrity and Misconduct Policies in Canada, prepared for the Canadian Research Integrity Committee by consulting firm Hickling Arthurs Low, says ghostwriting is only part of the problem.

The existence of companies, including some in Canada, that 'ghost- write' papers for academic researchers is but one visible manifestation of research misconduct in the private sector. These companies craft research papers in support of a particular drug and seek out researchers willing to be listed as authors in exchange for money and other benefits.

The report also looks at fabrication of data, falsification of data, plagiarism, conflicts of interest and abuse of power or retaliation towards colleagues and assistants. The 29 academic institutions surveyed, which represent about 60 per cent of the research done in Canada, reported investigating about 39 such incidents a year.

The report says that number is probably low.

This estimate should be treated with the appropriate caution given the challenges associated with collecting this information. In addition to research institutions having little incentive to share this information, there is a strong likelihood that misconduct cases go unreported by researchers due to an unwillingness to risk one’s own reputation or sour relationships with colleagues, or simply an unwillingness to engage a process that can lead to frustration and additional work stress. Under-reporting also comes about when allegations are reported but are then ‘swept under the carpet’ at some level of the institution. Anecdotes from interviews conducted for this study attest to all of these instances.

 

Top journals boost conflict standards

The top medical journals in the world, including the Canadian Medical Association Journal, will soon start demanding more stringent and uniform conflict of interest declarations from researchers than they have in the past.

The requirements will go beyond existing disclosure rules at many medical journals to include items such as financial relationships involving spouses, partners or minor children. Also required will be disclosure of nonfinancial conflicts, such as religious and political affiliations. Such disclosures are used in medical journals to alert readers to potential biases in research.

At least a dozen publications have agreed to use a new, standardized disclosure form, which will be phased in over the next several months.

By standardizing what researchers report to different medical journals, the editors are attempting to address complaints about the existing system for disclosing conflicts of interest. Researchers say medical journals' differing policies are confusing and lead to inadvertent omissions. Advocates for better reporting of financial conflicts say a researcher's potential conflict may be listed in one publication but not another.

The new standards are the products of the International Committee of Medical Journal Editors, and are signed by the editors of 14 leading medical journals around the world, including Paul Hebert, editor-in-chief of the CMAJ, as well of editors of such respected journals as the Lancet, The Britich Medical Journal, the Journal of the American Medical Association and the New England Journal of Medicine.

Under the new rules, researchers will have to fill out a form detailing their possible conflicts of interest. The ICMJE says the standardized form will make the process of disclosure simpler for all involved. "Our goal is to make the process of disclosure uniform and easy; the new form should eliminate the need to reformat disclosure information for specific journals," reads an association editorial on the new standards.

The Scientist magazine, meanwhile, has opened a discussion forum asking researchers what they think of the new form. The ICMJE says the form may be adjusted next spring, depending on how well it works out in the initial "beta" run.

A recent study in the New England Journal of Medicine found that up to half of researchers fail to properly discloe all potential conflicts of interest.

Glaxo loses Paxil lawsuit, more details

I have blogged about this verdict already today, but new details are beginning to emerge.

The $2.5 million (US) award granted by a Philadelphia jury in a verdict handed down this morning against GlaxoSmithKline in a lawsuit over its anti-depressant Paxil is more than twice what the plaintiff was seeking.

Michelle David, suing on behalf of her son Lyam Kilker, who turns four next week, had sought $1.2 million to cover future medical costs and other damages. The settlement granted by the jury in a 10-2 vote matches that awarded five years ago when the drug giant agreed to pay the state of New York $2.5 million to resolve claims that it suppressed research showing that Paxil may increase suicide risk in young people.

David's lawyer, Sean Tracey, hailed the verdict afterward, saying it was the first to "get a jury saying the drug caused the injury."

Business analysts following the company, however, were not so sure.

“I don’t think the link is proven, so there will likely be collective settlements which will keep costs low,” Navid Malik, an analyst at Matrix Corporate Capital in London with a buy rating on the stock, said in an e-mail. “If this was a threat to GSK, the first verdict might have been 100 times greater.”

Glaxo American depositary receipts, each representing two ordinary shares, fell 5 cents to $39.73 at 1:07 p.m. in New York Stock Exchange composite trading, after dropping as much as 1.4 per cent when the verdict was announced. Glaxo fell 14 pence, or 1.1 per cent, to 1,246.5 pence in London.

I have yet to see the full decision by the jury, but Bloomberg is quoting it as saying that the jury found that Glaxo officials “negligently failed to warn” the doctor treating Lyam’s mother about Paxil’s risks and concluded the medicine was a “factual cause” of the child’s heart defects.

On the other hand, the jury also found that Glaxo’s handling of the drug wasn’t “outrageous,” meaning the family couldn’t seek punitive damages against the British drug company.

In a statement after the verdict came down the company said it disagreed with the decision and will appeal.

GlaxoSmithKline disagrees with the verdict and will appeal. While we sympathize with Lyam Kilker and his family, the scientific evidence does not establish that exposure to Paxil during pregnancy caused his condition. Very unfortunately, birth defects occur in three to five per cent of all live births, whether or not the mother was taking medication during pregnancy.

I have called Glaxo for more comment, but have not yet heard back.

Glaxo spokesman Kevin Colgan called and read me the statement quoted above.
 

 

 

Glaxo loses Paxil lawsuit

Drugs giant GlaxoSmithKline was ordered this morning to pay $2.5 million (US) to the family of a young boy born with heart defects after his mother took the anti-depressant Paxil during pregnancy.

“The first win is always huge, especially when you get a jury saying the drug caused the injury,” Sean Tracey, Kilker’s lawyer, said in an interview after the jury reached its decision.

 It’s the first time a jury has considered claims that Glaxo, the U.K.’s largest drugmaker, knew Paxil caused birth defects and hid those risks to increase profits. The drug, approved for U.S. use in 1992, generated about $942 million in sales last year, or 2.1 percent of Glaxo’s total revenue.

“We’re disappointed with the verdict and I think we’ll be filing an appeal,” Joseph O’Neil, one of Glaxo’s lawyers, said in an interview.

Lyam Kilker, who turns four next week, was born with a rare heart deformity. During the trial, the first of some 600 filed against Glaxo, Tracey argued the company failed to warn doctors and patients about possible side effects to the drug.

Company lawyers presented studies and experts arguing that the drug is safe, despite warnings added to its label in 2005 (after Lyam was born) about the possibility of birth defects. Tracey countered by arguing before the jury that such researchers had close ties to the pharmaceutical industry.

The jury deliberated for seven hours. The Kilker case, brought by his mother Michelle David, was considered a test case for future lawsuits. The next will be heard in about a month -- also in Philadelphia, home to Glaxo's US headquarters.

Lawyers for many of those cases have been in Philadelphia monitoring the progress of the Kilker suit as part of their preparation for going to court.