Monday, May 31, 2010
Greek diabetic crisis - Novo's CEO speaks | Reuters
Novo Chief Executive Officer Lars Rebien Sorensen said he is in talks with the Greek government, which has ordered a 25 percent price cut on the Danish firm's insulins.
"What they propose right now is not acceptable," he said.
"It will have a rub-off effect on the European price level, and it has an effect on other markets outside Europe where the Greek prices are used as a reference price in negotiations with governments," Sorensen told Reuters.
FT.com - Drugmakers realise FDA has learnt to bite
Michael Druckman, a partner with the law firm Hogan Lovells in Washington DC and former FDA employee, says: “The new administration ... have set out pretty explicitly that the FDA would be more aggressive in enforcement and is putting more resources into inspections.
Scoop: No Free Pens But Pharma Influence Still Felt at APA
by Martha Rosenberg
New Orleans It was 95 degrees with 99 percent humidity. The Gulf had the biggest oil spill in US history. And attendees to this week's American Psychiatric Convention (APA) annual meeting in New Orleans had to brave 200 protestors chanting "no drugging kids for money" and "no conflicts of interest" to get into the convention hall.
Since 2008 when Congress investigated some APA psychiatrists for alleged pharma conflicts of interest, more light has shone between the two groups, historically almost indistinguishable.
Participants at this year's meeting, estimated at 14,000, saw conflict of interest slides before presentations and in their 240-page program book, fewer pharma funded classes and entertainment and no gifts or free meals at the 5-day event.
"They used to wine us and dine us," said one participant, a veteran of decades of annual meetings, ruefully.
"An SSRI maker flew my entire group to a Caribbean island," remembered a doctor from the East coast who did not want to be identified. Anymore.
But polarizing figures were still present. Sitting next to outgoing APA president Alan F. Schatzberg, MD, even as protestors chanted outside, was Charles Nemeroff, MD, former psychiatry chairman at Emory University who was investigated by Congress for unreported GlaxoSmithKline income and left his post in disgrace. Nemeroff was signing the Textbook of Psychopharmacology which he co-edited with Schatzberg, also investigated by Congress. Schatzberg, psychiatry chairman at Stanford, consults to seven drug companies, owns stock and patents with others and is on Sanofi-Aventis' Speakers Bureau according to the meeting's Daily Bulletin.
Heading a symposium about schizophrenia was S. Charles Schulz, MD, psychiatry chairman at the University of Minnesota who was investigated for financial links to AstraZeneca believed to alter his scientific conclusions.
Presenting a poster about the benefits of long acting risperidone was Wayne MacFadden, MD, AstraZeneca's US medical director for Seroquel until questions about his alleged sexual affairs with women doing research on the drug arose.
And a paper presented about attention deficit hyperactivity disorder (ADHD) was co-written by Harvard's Joseph Biederman, MD, also investigated by Congress for pharma financial links and considered the father of the pediatric bipolar disorder craze.
Despite the pharma thaw, exhibition displays were still pretty gee-whiz with Cymbalta, Seroquel XR, Abilify, Lunesta and Pristiq the most prominent. (A rep struggled to explain to a group from Columbia that Pristiq was not, repeat not, just a more expensive Effexor.) ADHD was also big. "Let's be as brave as the people we serve" said Shire's display, showing a patient's giant, valiant face; an entire children's bedroom was constructed by Bristol-Myers Squibb to sell INTUNIV.
But where take-one signs once existed, signs now warned health care providers they may be governed by no gift policies. And whereas glad-handing reps were still eager to answer questions --once they scanned badges for marketing data -- pharmacodynamic and patient care questions were referred to an information booth with a line to, well, see the doctor.
Nor was there a star of the show. The Next Big Thing was not a new drug at all but adjunctive therapy also known as adding existing drugs to existing drugs because they don't work right. Throwing good drugs after bad, popularized with the antipsychotic Abilify, has only been enhanced by a study in the January JAMA that found antidepressants don't work for mild depression at all. Antipsychotics are also being "enhanced" by adding drugs to offset weight gain and lethargic side effects.
No wonder panelists at a forum called "Is a Game Changing Psychotropic Too Much to Expect?" assailed pharma for issuing "me too" drugs and "seat of the pants" drug combinations, calling the industry nothing but a "marketing organization."
No wonder a Canadian physician castigated the FDA's Jing Zhang for approving drugs for "competitive reasons" not patient health in a symposium about comparative drug effectiveness. "In a recent transcript on your web site, Dr. Laughren [FDA director of psychiatry products] clutches at studies to try to approve a new drug on behalf of industry," he charged. "FDA's non-inferiority studies in which a drug can be less effective that an existing one and only beat placebo, present the 'patient risk' of a drug not working," he said.
But elsewhere drugs were given a better spin.
Ann Childress, MD, gave a veritable commercial for the ADHD drug Vyvanse, manufactured by Shire on whose Speaker's Bureau she serves. And the Wyeth funded C. Neill Epperson, MD, appearing with Wyeth Speakers Bureau member Claudio Soares, MD, actually told a clinician not to trust a pharmacist for a hormone preparation but to use pharma's drugs in a symposium called "Mood, Memory and Myths: What Really Happens at Menopause." Biodentical hormones, compounded by pharmacists, have been a revenue threat for Wyeth's menopause drugs. (The seminar devolved when breast cancer patients in the audience discussed their health status.)
If there were a take home message at the APA meeting about the blizzard of ADHD, bipolar and personality disorders threatening adults and children, it was don't wait. These dangerous conditions, likened to cancer and diabetes, won't go away.
Thanks to genetic advancements, psychiatric disease risks can now be detected and treated before symptoms surface, said presenters, fostering early treatment paradigms that are pretty Brave New World: People being told they have a disease they can't feel that needs immediate and lifelong treatment at hundreds of dollars a month or their health will suffer. Run that past me again? The National Institute on Drug Abuse is even working on vaccines to treat the specific genetic risks in opioid addicts. Good luck with that.
Not everyone agreed about early treatment. The very fact that bipolar disorder is a lifelong disease is reason to wait until you are sure said Mark Zimmerman, MD director of outpatient psychiatry at Rhode Island Hospital whose research, published in the June Journal of Nervous and Mental Disease, finds a link between unconfirmed, overdiagnosed cases of bipolar disorder and… the receipt of disability payments.
Not everyone agreed about multidrug combinations commonly called polypharmacy either. In between industry "research" in poster sessions extolling Seroquel, Vyvanse, Saphris, Geodon, Risperdal and Zyprexa was a study at Maimonides Medical Center in Brooklyn "Evaluating Antipsychotic Polypharmacy Regimens for Patients with Chronic Mental Illness."
When 24 patients on polypharmacy combinations of Seroquel, Zyprexa and other antipsychotics were reduced to only one drug -- monotherapy -- there was no worsening of symptoms or increased hospitalizations in 23. Not only did patients not deteriorate, their waist circumferences and triglycerides improved, say the researchers as drug interactions, side effects and cost of treatment declined.
"These are interesting data," said a young female psychiatrist viewing the poster. "Normally clinicians are afraid to take such patients off polypharmacy."So is pharma.
Related Stories on Scoop
- Do You Have Excessive Sleepiness? Pharma Hopes So 11/05/2010
- Pfizer's Ghostiwritten Journal Articles 22/02/2010
- "Naughty" Pharma Still Got Xmas Presents From FDA 05/01/2010
- New Year's Resolutions for the Drug Industry 27/12/2009
- Brochures Embarrass British Health Service 26/11/2009
Second Danish drug company pulls out from Greece over Government price cut | The Australian
Shroud waving!
Sunday, May 30, 2010
Doctors' role in drug studies criticized - JSOnline
Side Effects | Money, Medicine, and Patients
Doctors' role in drug studies criticized
Some recommend drugs, vouch for studies but don't see raw numbers
By John Fauber of the Journal Sentinel
Posted: May 30, 2010 |(17) Comments
Richard Page
Click to enlargeSide EffectsAn occassional series examining doctors, drug companies and conflicts of interest.
- Doctors' role in drug studies criticized (17)
- Cancer patient to get her medication (52)
- 69 Wisconsin doctors show up on Pfizer payroll (102)
- Woman's move triggers loss of coverage for cancer treatment (66)
- As universities tighten ethics policies, drug firms turn to private physicians (54)
- Journal editor gets royalties as articles favor devices
- Physicians' disclosures to UW, journals inconsistent
- Speaking fee ban riles UW doctors
- UW linked to ghostwriting
- UW tied to male hormone marketing
Richard Page thinks Multaq is an excellent new drug for treating atrial fibrillation, a type of irregular heartbeat that affects more than 2 million Americans.
And Page, chairman of the department of medicine at the University of Wisconsin School of Medicine and Public Health, should know. He co-authored a large, international study that led to the drug's approval by the Food and Drug Administration last year, a move that could mean hundreds of millions in sales for Sanofi-Aventis, the company that makes the drug.
But in putting his name on the influential paper, Page allowed Sanofi-Aventis to dictate the terms. He vouched for the accuracy and completeness of the study despite not seeing the raw data. The company, which paid for the study, collected that information and performed the analysis without an external audit for accuracy or completeness.
Page says it comes down to trusting the drug company.
"These companies, if they were falsifying data, wouldn't be kept in business if that were found out," he said. "I was satisfied and remain satisfied that the study was conducted in an appropriate way."
But more and more critics say there is something wrong with the way medical research is done in America. They point to a growing number of scandals in which drug companies have been accused of suppressing or manipulating research and skewing results to make their drugs look better and safer.
In the Multaq case, Page and all six co-authors had financial ties to Sanofi-Aventis at the time of the study.
Two authors worked for the company and owned its stock. Page and the four other authors moonlighted as consultants or speakers.
Questions are being raised about a finding in the paper that the drug reduced cardiovascular deaths - a claim that was disallowed by an FDA panel.
A spokeswoman for Sanofi-Aventis said the company conducts its clinical trials to the highest scientific standards with rigorous analysis and accurate reporting of clinical data. That includes the Multaq trial, spokeswoman Carrie Melia said in an e-mail to the Journal Sentinel.
Yet studies paid for by drug companies are much more likely to have positive results than studies paid for by nonprofit organizations with nothing to gain from a drug's success in the marketplace.
For instance, with cardiovascular treatments, 40% of trials paid for by nonprofit sources showed favorable results, compared with 66% among drug industry-funded studies, according to a 2006 study in JAMA, the Journal of the American Medical Association.
When outside authors don't have complete access and control of data and protocol, manipulation is easier, said Eric Campbell, an associate professor at Harvard Medical School who researches conflicts of interest in medicine.
"If data are cut and shaved and trimmed and manipulated to make a point and that doesn't represent truth or the way a drug behaves, science is harmed and, more importantly, patients are harmed," Campbell said.
Consider the case of the popular painkiller Vioxx, which was pulled from the market in 2004 by its maker, Merck.
A 2008 analysis revealed that while Merck told the FDA in 2001 that the drug did not increase the risk of death, the company's internal documents showed the death rate of patients using Vioxx was three times higher than that of patients taking a placebo.
Under the microscope
The conduct of the pharmaceutical industry continues to come under the microscope.
This month, a new analysis of illegal pharmaceutical company behavior that was exposed by whistle-blowers identified 18 major cases leading to investigations by the federal government. The cases, which were brought from 2001 to 2009, resulted in nearly $9 billion in settlements, according to the report in the New England Journal of Medicine.
Many of those cases involved the illegal and potentially dangerous promotion of drugs for purposes for which they were not approved, so-called off-label use.
While it is illegal for drug companies to promote off-label uses for drugs, once a drug is approved, doctors can prescribe it for purposes other than for what it was approved. Such off-label drug sales can substantially increase pharmaceutical revenues without the typical cost of proving that a drug is safe and effective.
Multaq is an expensive drug. At the dose used in the study, the drug costs $290 a month, or about $3,480 a year, at a Milwaukee Walgreens.
Before it went on the market last year, it already was linked to serious problems.
In 2003, a separate trial of Multaq was stopped because more patients on the drug were dying than those on a placebo. That study was published in 2008.
Even so, Multaq was described as an agent that significantly reduced cardiovascular deaths in Page's study, which was published in February 2009 in the New England Journal of Medicine.
Less than a month later, FDA advisory panel members criticized that claim, according to a transcript of their meeting.
Indeed, concerns about off-label use of Multaq were voiced at that FDA advisory panel meeting in March 2009.
"This is a drug that killed a lot of people in this first trial, and so there is a huge amount of concern," said panel member Sidney Wolfe, a longtime drug industry critic who became a member of FDA's Drug Safety and Risk Management Committee in 2008.
"We know this drug is toxic. We know this drug, in certain kinds of circumstances, has killed people, and we know, from every marketing experience we've ever looked at, that off-label use is guaranteed - and it's guaranteed all over the lot."
Melia, spokeswoman for Sanofi-Aventis, noted the trial had an independent data monitoring committee to keep tabs of deaths, hospitalizations and adverse events. The trial was designed by an independent steering committee along with the company.
She acknowledged that the company collected and managed the data but said both the steering committee and the data monitoring committee had access to analyzed data. They did not, however, have access to the raw data.
Neither Sanofi-Aventis nor Page has been accused of unethical conduct in the Multaq clinical trial.
Questionable methods
But critics are zeroing in on studies in which companies collect and control information from clinical trials, then disseminate it to researchers hired by the firms to write the studies.
Before the 1980s, drug industry money for clinical trial research at academic institutions gave complete control to university researchers, wrote Marcia Angell, a former New England Journal editor, in 2008. But now the companies often design the studies and do the analysis, sometimes without giving university researchers access to the original data.
Doctors must be able to trust what they read in published medical articles and know that the findings have not been manipulated, said Catherine DeAngelis, a physician and editor of JAMA, the Journal of the American Medical Association.
Studies in which drug companies control the data without an independent analysis open the door to manipulation, she said.
"Our primary role is to protect patients," she said. "If you can't trust what you are reading, then where are you?"
The Multaq trial is a good example of questionable studies, DeAngelis said.
At JAMA, such studies are no longer accepted for publication, she said. If drug company employees perform the data analysis, there must be an independent analysis by someone with no ties to the company before JAMA will consider it, she said.
DeAngelis instituted the requirement in 2005 after she received a clinical trial manuscript and asked for an independent analysis. The company refused. She declined to name the company or the product.
"It told me they were hiding something," she said.
The study later was published in another journal. Recently, she said, there have been reports of side effects with the product.
If regulators find that data was manipulated, she said, she will identify the case publicly.
The New England Journal of Medicine, which published the Multaq study, does not have such a policy.
Clinical trial data belong to the drug companies, said Gregory Curfman, executive editor of the publication.
"We are living in the real world here," he said. "They own it. It's their data."
He defended his journal's decision to publish the finding that Multaq reduced cardiovascular deaths 29%, calling it an exploratory finding, although no such wording is used in the article.
Before such a claim can be made, another clinical trial must be done, he said. He said doctors understand what the finding means.
But Campbell, of Harvard Medical School, said drug companies use such findings to increase sales of their drugs.
"Everyone has known for a long time that drug companies use publications in academic journals to stimulate off-label use (of a drug)," he said.
Campbell said it is inappropriate for academics to put their names on such studies.
Page said he and the other academic physicians were directly involved in protocol management and data analysis.
"Based on the direct involvement in design, management, analysis and manuscript preparation, it is appropriate for the steering committee to be authors on the report," he said.
A common practice
At the time of the Multaq study, Page worked at the University of Washington School of Medicine. He joined the University of Wisconsin in August.
Page said his work as a paid consultant to Sanofi-Aventis and other companies ended in May 2008 because he became president of a medical society that did not allow financial ties to industry.
"This partnership of physicians with industry serves the public by providing expertise and oversight in industry-sponsored trials," he said.
It is common for academic experts such as Page to sit on steering committees of drug company-funded trials.
In an interview, Page acknowledged that he and the other authors did not get the original raw data from the Multaq trial, which involved 4,628 patients with atrial fibrillation from around the world.
He did get reports of deaths that were provided in a blinded fashion, meaning that he did not know whether the person was getting Multaq or a placebo.
He said he and other members of the study's steering committee used the blinded data to make judgments.
"Furthermore, the FDA examined the original data and was satisfied with the conduct of the trial," Page said. "Any suggestion that the sponsor had any influence on the conduct of the trial interpretation is inaccurate."
Working on a clinical trial in which the drug-maker controls the data is not a problem if you trust that the company is going to do the right thing, Page said.
"We knew how it was analyzed," he said. "We just didn't do the analysis ourselves, and we didn't go out and hire other statisticians to do that. This was a trial sponsored by Sanofi-Aventis and they paid for the statisticians. There is a sense of trust that they won't falsify data."
FDA advisory panel members have raised questions, not about falsified data, but about how the study was conducted.
Data differences
Unlike the academic authors in the Multaq trial, published by the New England Journal of Medicine, the FDA got unanalyzed raw data for its later review and did its own analysis.
One FDA panel member questioned differences between the information included in the published February 2009 study and what was submitted to the FDA
The published paper concluded that the drug reduced cardiovascular deaths when in reality that benefit was not significant under the original study design, said advisory panel member Sanjay Kaul, who also serves as director of the vascular physiology and thrombosis research laboratory at Cedars-Sinai Heart Institute.
Determining the rate of cardiovascular death was a secondary measure of the study. The main measure was a combination of two things: hospitalization for a cardiovascular reason or death. On that count, there was 24% benefit with Multaq. It was on that basis that the drug was approved by the FDA.
Kaul said it worked like this:
The study was supposed to stop at 4,300 patients. At that number, there was not a significant benefit in reducing cardiovascular deaths.
But the study was extended beyond its planned cutoff date and an additional 328 patients were enrolled.
The expanded version of the study included five deaths among those in the placebo group and one in the Multaq group. The company and study authors determined that was enough to report a significant cardiovascular death benefit.
That's what was published in the New England Journal study.
But the FDA did not allow the claim.
"It is not proper to change the rules in the middle of the game," Kaul said.
Page declined to respond to Journal Sentinel questions about who made the decision to add additional patients. The lead author of the study, Stefan Hohnloser, a German doctor, also would not respond to those questions.
Some doubts
The claimed benefit of cardiovascular death reduction was not valid for another reason, Kaul said.
Cardiovascular deaths were part of a larger category of death from any cause. Because there was no significant difference in all-cause mortality on the drug or on the placebo, the claimed reduction in cardiovascular death also was not valid.
"These observations raise questions about the quality of the data and ultimately the reliability of the findings," Kaul said.
At the time of the FDA hearing, other panel members also questioned the claim.
"The cardiovascular death claim is on shaky ground," panel member William Calhoun, a physician with the University of Texas in Galveston, said at the March 2009 hearing.
In an interview, Kaul said Multaq was only modestly effective at best and had no clear safety benefit.
Kaul raised the questions after Sanofi-Aventis paid for a controversial lecture this year in which off-label uses for Multaq were touted by another doctor who has worked as a consultant to the company.
The lecture was posted on Afibprofessional.org, a site launched by the American College of Cardiology and the Heart Rhythm Society. UW's Page is the president of the society.
In the lecture, the doctor claims a dramatic reduction in cardiovascular deaths with Multaq.
But when the lecture initially was posted, it did not disclose that the doctor received undisclosed consultant fees in excess of $10,000 from Sanofi-Aventis, according to the CardioBrief blog by medical writer Larry Husten.
In March, the lecture was taken down and later re-posted, this time with the financial disclosure information.
Page said he supported the creation of the website but was not aware of its content, which was managed by the staffers.
Because of concerns raised about the lecture, his society now will include written disclosures for such activities, including verbal disclosures for audio programs.
Melia, spokeswoman for Sanofi-Aventis, said the doctor's comments were his independent view.
"Sanofi-Aventis U.S. does not engage in or endorse the off-label promotion of any product, including Multaq," she said.
John Fauber reported this story in a joint project of the Journal Sentinel and MedPage Today. MedPage Today provides a clinical perspective for physicians on breaking medical news at www.medpagetoday.com.
***
About this series
This article is part of an ongoing series about how money and conflicts of interest affect medicine and patient care.
BBC News - Novo Nordisk and Greece - "brutal capitalist blackmail".
Pavlos Panayotacos, whose 10-year-old daughter Nephele has diabetes, has written to Novo Nordisk's chairman to criticise the move.
"As an economist I realise the importance of making a profit, but healthcare is more than just the bottom line," he wrote.
"As you well may know, Greece is presently in dire economic and social straits, and you could not have acted in a more insensitive manner at a more inopportune time."
The Greek diabetes association was more robust, describing the Danes' actions as "brutal blackmail" and "a violation of corporate social responsibility".
Novo Nordisk pulls diabetes drugs from Greece over price cut
Copenhagen - Danish pharmaceutical group Novo Nordisk said on Saturday it was pulling 17 types of medication for treating diabetes from the Greek market after a government decree to lower prices of drugs.
"The products that are pulled from the market are the latest generation of insulin products in the pen system," said Mike Rulis, Novo Nordisk's head of corporate communications.
The company, the world's largest producer of insulin to treat diabetes, said it would not stop selling the 17 products but insisted on keeping its prices at the level before the Greek decree took effect on May 3, forcing it to lower prices by about 25 percent.
"That means wholesellers will no longer order these products, because they can only sell them to the pharmacies at a loss, because they will only be reimbursed at the minus 25 percent level," Rulis said.Novo Nordisk has, however, agreed to the price cut on its standard human insulin products, which diabetes patients take out of vials and inject with a syringe.
It will also make another product for diabetes sufferers, glucagon, available for free.
Rulis said about 50,000 people in Greece use the new generation products that the company will pull from the market, while another 40,000 use standard human insulin.
If Novo Nordisk complied with the 25 percent price cut on all products, its operations in Greece would become loss-making, Rulis said.
"The financial consequences for the company would be very significant," he said, adding "a price lowering of this magnitude in Greece would automatically trigger price reductions in other countries." - AFP
Curbing Drug Company Abuses: Are Fines Enough? - TIME
In late April, when the Justice Department announced its deal with AstraZeneca for the pharmaceutical company to pay a $520 million fine, as a result of the off-label marketing of its blockbuster anti-psychotic drug Seroquel, Justice officials called it a "historic settlement." Attorney General Eric Holder, Health and Human Services Secretary, Katherine Sebelius, and the head of the Food and Drug Administration held a press conference, trumpeting it as part of the administration's "top priority" fight against health care fraud. It was the largest ever civil-only fine imposed by the U.S. Government for an off-label marketing offense — promoting the drug for uses not approved because it has not been shown safe, necessary and effective.
Seroquel had FDA approval for use in short-term treatment of schizophrenia and acute bipolar 1, but according to Justice's complaint the company aggressively marketed the drug "as a long-term cure-all for a broad spectrum of psychiatric maladies, including...aggression and agitation in children" even though clinical studies have sometimes shown "serious and debilitating side effects," particularly among the elderly and children. Seroquel is typically prescribed by psychiatrists, but was being marketed to general medical practitioners, including staff at nursing homes, veterans hospitals and prisons, and to neighborhood pediatricians, making patients "guinea pigs in an unsupervised drug test," according to a prosecutor.
The company denied the allegations but agreed to settle to "avoid the delay, uncertainty, inconvenience, and expense of protracted litigation." That kind of outcome is not uncommon. A conviction in court can be crippling to companies. The government too has an interest in avoiding expensive court fights, particularly if it feels it can gain future compliance through fines and corporate integrity agreements [CIAs] that allow it to guide and monitor companies' compliance efforts.
But critics are starting to question these settlements, pointing out that even such large fines have yet to make a serious dent in recurring marketing abuses. AstraZeneca's fine represented just 16.5% of revenue earned from Seroquel during the years its off-label marketing was ongoing — $8.6 billion in the U.S. between 2001 and 2006. Just how much of this was due to improper marketing is unclear, but considering the limited primary market and the widespread use of the drug, it was bound to have been significant.
Since companies can roll the costs of such fines into future drug prices, the penalties become just another cost of doing business. That means Americans get whammied twice. The first involves hundreds of millions of dollars in unnecessary reimbursements paid out by Medicare and Medicaid for drugs that were surreptitiously being promoted for unapproved uses. "Healthcare fraud is not only illegal, it drives up the cost of medical care for all of us," noted Tony West, who directs Justice's civil division.
What's more, critics claim, the corporate integrity agreements that are part of many of these settlements have been too loose to curb future abuses. Indeed, AstraZeneca was already operating under such an agreement, dating back to 2003 when the firm pled guilty to criminal and civil charges related to marketing of Zoladex, its prostate cancer treatment. It paid a $355 million fine for fraud that took place over 12 years.
"You literally have a situation I think where the government pretends to go after these guys, the companies pretend to follow the law, but it's just a game for the consumption of the masses; so people will think that the wheels of justice are actually moving," says Peter Rost, a former senior Pfizer marketing executive turned industry gadfly.
If the government were more serious, Rost contends, it would double the funding for prosecutions so that Justice could go after more than a fraction of the cases and bring more companies to trial. "I think until that happens this game will go on," says Rost. "It's obviously great for drug companies, its great for the lawyers, it's great for the Justice Department to bring in a token scalp every now and then, so everybody involved wins, and that is why it continues."
But going to trial carries high risk for both companies and the government, so both have incentives to settle. "The government jumps through hoops to avoid [having to enforce] the law which would require the company to be actually be excluded from any federal health care programs [if there is a conviction,]" explains Michael Mustokoff, an attorney who represented the salesman-turned-whistleblower who first brought AstraZeneca's abuses to the government's attention.
Such exclusion is a virtual death sentence for drug firms, which derive an estimated 30%-40% of their sales from the government. "As much as the government wants the [settlement] money from these companies it does not want to put them out of business," says Mustokoff.
The government is beginning to share the critics' view. "These are legitimate concerns," concedes Lewis Morris, chief counsel for the Department of Health and Human Services' unusually powerful Inspector General's office, which is a key player in the search for ways to combat recidivism among pharmaceutical companies. He says the government is stepping up its enforcement and beginning to flex its considerable regulatory authority more robustly. This includes plans to target responsible executives — not just companies — by toughening the CIAs to require management and a board committee to certify company compliance.
Read more: http://www.time.com/time/business/article/0,8599,1990910,00.html?xid=rss-busi...
Saturday, May 29, 2010
Dan Carlat asks: Has psychiatry lost its soul?
NEW YORK, May 26, (RTRS): Psychiatry has lost its soul.
That’s how grimly Dr Daniel Carlat, a psychiatrist in private practice outside of Boston, characterizes the state of his profession.
“Over the last 20 to 30 years, psychiatry has really transformed itself from a profession in which we try to understand people and understand their psychology — and talk to them and help them that way — into a profession in which we diagnose diseases, and we medicate those diseases,” says Carlat.
“So over that time, we have in a sense, and this is really alarming to me, we’ve lost our sense of psychological curiosity,” he says. “And that’s kind of the very soul of psychiatry.”
Exactly what’s wrong, and how to fix it, was the topic of discussion last Thursday, when Reuters Health spoke to Carlat about his new book Unhinged: The Trouble With Psychiatry - A Doctor’s Revelations About a Profession in Crisis.
Prescriptions
The slide started, says Carlat, when psychiatric blockbusters like Prozac (fluoxetine), a so-called selective serotonin reuptake inhibitor, or SSRI, was approved in 1988. Thanks to Prozac and its cousins such as Zoloft and Paxil, and their relatively limited side effects, prescriptions grew to the millions.
Borrowing the words of late Harvard psychiatrist Dr Leon Eisenberg, psychiatry went from being “brainless” to being “mindless,” Carlat says. Today, psychiatrists spend 20 minutes with a patient every few months, in essence adjusting medications, compared to an hour or more each week trying to understand what was wrong.
Some argue that reflects a more mature science, one that pays off faster and more efficiently. But that’s not necessarily true, says Carlat. He cites an example from his clinic: He had been prescribing Ambien, a long-acting sleeping pill, to one of his patients for a while. At the same time, however, the patient was complaining to his therapist that he felt overly sedated and couldn’t get up in the morning.
“One of his psychological issues was that he had such low self-esteem that he felt that he wasn’t worth enough as a person to come to me — the more intimidating doctor figure — to ask me to do something about it.”
As a result of the gap between psychology and psychiatry, the man had nodded off at the wheel during a business trip, barely avoiding an accident.
With the change in psychiatry also came a shift in the way we think and talk about mental problems. In the case of depression, for instance, doctors often refer to a deficiency in the neurotransmitter serotonin. While this makes sense at first glance, all it means is that SSRIs can treat depression; it does not mean we understand what’s going on in the brain. In fact, nobody has ever found proof of a serotonin deficiency, according to Carlat.
“We do have a short-hand, “neurobabble” way of speaking to patients, and we usually use terms such as serotonin deficiency or epinephrine deficiency,” he says. “I basically ask, do we know what the heck we’re talking about when we even use those terms?”
While no one completely understands what’s going on in the brain of a depressed person, drug makers have been quick to take advantage of the medical model of mental illness, pushing their own expensive medicines in dubious ways, Carlat says.
Drugs
And he would know. In 2001, he was contacted by the pharmaceutical giant Wyeth, which offered him $750 to have a short lunch with primary care doctors. The basic idea: to tout the company’s psychiatric drugs, such as Effexor. Wyeth, later bought by Pfizer, gave him slides and took him to expensive conferences, where key opinion leaders in the field would lecture on the newest drug trials. And each time he did his talks, drug reps would listen in.
“I knew that if I wanted to get another gig, and another phone call, another invitation for another $750 check, I was going to have to say some pretty positive things about their drug, and I was going to have to downplay some of the negative side effects,” Carlat says.
Finally, after having made $30,000 and realizing he was just a hired gun, he started talking frankly about the side effects. The next day, he said, a drug rep came by his office and asked him if he’d been sick, as if that was the only logical explanation for such behavior.
“Doctors usually are going to think that other doctors aren’t going to try to deceive them about things, but unfortunately, that’s not true,” says Carlat, who later wrote about the experience in The New York Times Magazine. “Doctors are just as vulnerable to the allure of money, marketing and financial incentives as anybody else.”
For example, in 2006, one prominent psychiatrist, senior National Institutes of Medical Health scientist Pearson “Trey” Sunderland, was sentenced to two years’ probation for accepting about $300,000 in consulting fees from Pfizer without first obtaining approval and disclosing the funding. In response to this and other incidents, just last week, National Institutes of Health director Dr Francis Collins proposed new, more stringent rules about how to manage researchers’ financial interests in companies whose work is related to their own.
As part of the new proposal, NIH-funded institutions would be required to post conflicts of interest on a public website.
“The public may not always understand the intricacies of rigorous science, but most individuals quickly grasp the concept of bias,” Collins and a colleague wrote in the medical journal JAMA recently.
“Plain and simple,” they added, “Americans do not want financial conflicts of interest to influence the federally funded research they hope will yield better ways to fight disease and improve health.”
Diagnose
As important as minimizing conflicts of interest is, it isn’t going to give psychiatry back its soul. To start down that path, one of the solutions Carlat suggests in his book is a merger between talk therapy and psychiatry.
But there’s a problem: Today’s psychiatrists don’t have the time to do much more than diagnose and medicate their patients. In fact, they don’t even have time for that. Citing a new study, Carlat says 40,000 new prescribers of psychiatric medicine are needed in addition to the current 30,000 in order to fill the gap in US healthcare. Training that many psychiatrists would be hugely expensive.
The solution? Give psychologists a little extra training, and let them prescribe the most common drugs.
“We have something in the range of 80,000 to 100,000 psychologists in our country...who already know most of what you need to know to be a good psychiatrist,” Carlat said.
Louisiana and New Mexico have already approved psychologist prescribing, and according to Carlat there hasn’t been a single malpractice lawsuit there since 2002.
Not surprisingly, many psychiatrists are resisting the idea, says Carlat, adding that “this is just a good old-fashioned turf war and it’s all about money.”
But patients might benefit, such as the man who kept falling asleep because his sleeping pills were too strong. It almost took a car crash before he told Carlat, who immediately switched him to a lighter medication.
“If a therapist had been able to prescribe it, he would have gotten the drug right away and he wouldn’t have risked having a potentially fatal car accident,” Carlat says.
How Big Pharma has to change
By guest blogger Dan Hoffman:
Even casual observers of the pharmaceutical industry know that it is in a trough of new product development especially over the next three years. What remains unappreciated, even within the industry, is that pharma's entire customer base is undergoing enormous change. If the industry wants to adapt, its entire business model must change just as radically.
Pharma's historic customers -- the individual physicians -- have been consolidating into larger corporate entities. They are doing this to get a stronger hand in negotiating with insurers/payers, and to earn revenue from other sources such as clinical trials. And in an era when electronic medical records (EMRs) are becoming coins of the doctoring realm, larger practices possess the capital to make the change more quickly. This recent report in The New York Times shows that physicians now own less than 50% of private practices.
This trend holds several huge consequences for the pharmaceutical industry.
The sun will set on the gatekeeper system. Practices rather than individual physicians will make or constrain most of these decisions, and profits will represent the principal factor driving their choices.
Sales reps become obsolete. Pharma and others will have to conduct business-to-businss selling, not aim at individual docs. Reps will become as obsolete as buggy whip operators.
Niche products will be king. In the near future, the decision on which drugs to use will result from a dynamic of dueling electronic databases. Instead of a company being able to argue persuasively that its product is the most effective, larger practices will check the historical outcomes of each product among tens of thousands, and even millions of patients.
Until new blockbusters are found, most new, branded products will show better cost-effectiveness in only a small proportion of patients. That means pharma must learn to prosper by making profits on small, niche products. Until they can do that, the giant companies such as Pfizer, Merck and GlaxoSmithKline will operate with diseconomies of scale, the exact opposite condition of what favored the mergers and acquisitions that created those behemoth companies.
Friday, May 28, 2010
IndustryWeek : FDA Mulls 'Criminal Penalties' Against J&J Unit
FDA Staff Sees Allergic-Reaction Risk With AZ's motavizumab
Clinical trials - ain't they a bitch!
UPDATE 1-AstraZeneca won't file Recentin for colon cancer
LONDON, May 28 (Reuters) - AstraZeneca (AZN.L) dropped plans to file its experimental cancer drug Recentin as a first-line treatment for colon cancer on Friday after disappointing results from a second pivotal clinical trial with the medicine.The latest Phase III clinical trial, known as Horizon II, showed Recentin improved progression-free survival but there was no improvement in overall survival.
The drug, also known as cediranib, had already failed in another study comparing it head-to-head with Roche's (ROG.VX) blockbuster Avastin in March.
"Based on the results of these two trials, AstraZeneca does not intend to file regulatory submissions in first-line mCRC (metastatic colorectal cancer)," the company said.
The drug may still have a role in different cancer types, however. Results of a Phase III study evaluating in treating recurrent glioblastoma, a brain cancer, are expected soon and AstraZeneca is also examining whether it may have applications in a number of other tumour types. (Reporting by Ben Hirschler; Editing by Dan Lalor)
*We welcome comments that advance the story directly or with relevant tangential information. We try to block comments that use offensive language or appear to be spam and review comments frequently to ensure they meet our standards. If you see a comment that you believe is irrelevant or inappropriate, you can flag it to our editors by using the report abuse links. Views expressed in the comments do not represent those of Reuters.
Congress looks at ‘phantom recall’ of J&J’s Motrin - The Boston Globe
The new questions about J&J’s handling of quality issues came during a hearing about its latest recall involving over 100 million bottles of children’s medicine, some of which contained tiny metal particles.
But instead of sampling the product, the contractor began purchasing large quantities of Motrin and instructing its employees not to mention a recall.
A memo titled “Motrin Purchase Project,’’ distributed during the hearing states: “You should simply ‘act’ like a regular customer while making these purchases. There must be no mention of this being a recall of the product!’’
Thursday, May 27, 2010
Pulse - NHS London chairman steps down 'in Lansley protest'
NHS London chairman Sir Richard Sykes has resigned after the new Government scrapped the SHA’s plans to dramatically reshape the landscape of primary and secondary care in the capital.
UK's NICE backs Iressa after Astra sets fixed cost | Reuters
LONDON, May 27 (Reuters) - AstraZeneca Plc's (AZN.L) cancer pill Iressa has been recommended for use in Britain's state-run National Health Service (NHS) after the drugmaker agreed an unusual fixed cost deal.
The arrangement highlights the mounting pressure on firms to agree favourable "patient access schemes" in order to win approval from the National Institute for Health and Clinical Excellence (NICE), which decides if drugs are cost effective.
Iressa will be supplied at a fixed cost of 12,200 pounds ($17,560), irrespective of the duration of treatment, and there will be no charge for patients who are treated for less than three months.
"It has been designed to ensure value for money for the NHS and to enable the budget impact to be predicted more accurately," said AstraZeneca spokeswoman Abigail Baron.
While NICE does not negotiate or set prices, it does take special offers into account when deciding whether to recommend drugs for reimbursement on the NHS.
In future the watchdog could play a more direct role in determining prices under government plans to move to a system of "value-based pricing". [ID:nLDE64O1FW]
NICE said on Thursday its draft recommendation on Iressa, which is also known as gefitinib, was open to consultation before publication of final guidance later this year.
NEW PRICING
The agency had asked AstraZeneca in January for information on Iressa. This was provided along with the new pricing offer.
Lung cancer is one of the most common cancers in Britain, with around 38,000 people diagnosed every year. The most common type is called non-small cell lung cancer.
Iressa -- a once-daily pill -- was approved by European regulators last July for adults with locally advanced or metastatic lung cancer whose tumours have an EGFR mutation.
A mutation in the epidermal growth factor receptor (EGFR) is a characteristic occurring in around 13 percent of lung cancers in Europe, and studies have shown these types of tumours are particularly sensitive to Iressa.
The European regulator's decision effectively revived the fortunes of a drug that had been largely written off after it failed to show significant benefits in the overall population of lung cancer patients in a clinical tests five years ago.
In Britain, NICE has already recommended various injectable treatments for lung cancer, but Carole Longson, health technology evaluation centre director at NICE, said Iressa offered an advantage because it is taken in tablet form.
Separately, NICE said it had also recommended Roche's (ROG.VX) established cancer drug Xeloda as a first-line treatment for inoperable advanced gastric cancer, when used in combination with platinum-based chemotherapy.
Gastric, or stomach, cancer affects approximately 8,200 people in Britain every year. (Editing by David Holmes) ($1=.6947 Pound)
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JAMA -- Abstract: Reporting and Interpretation of Randomized Controlled Trials With Statistically Nonsignificant Results for Primary Outcomes, May 26, 2010, Boutron et al. 303 (20): 2058
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Reporting and Interpretation of Randomized Controlled Trials With Statistically Nonsignificant Results for Primary OutcomesIsabelle Boutron, MD, PhD; Susan Dutton, MSc; Philippe Ravaud, MD, PhD; Douglas G. Altman, DSc
JAMA. 2010;303(20):2058-2064.
Context Previous studies indicate that the interpretation of trial results can be distorted by authors of published reports.
Objective To identify the nature and frequency of distorted presentation or "spin" (ie, specific reporting strategies, whatever their motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results) in published reports of randomized controlled trials (RCTs) with statistically nonsignificant results for primary outcomes.
Data Sources March 2007 search of MEDLINE via PubMed using the Cochrane Highly Sensitive Search Strategy to identify reports of RCTs published in December 2006.
Study Selection Articles were included if they were parallel-group RCTs with a clearly identified primary outcome showing statistically nonsignificant results (ie, P
.05).
Data Extraction Two readers appraised each selected article using a pretested, standardized data abstraction form developed in a pilot test.
Results From the 616 published reports of RCTs examined, 72 were eligible and appraised. The title was reported with spin in 13 articles (18.0%; 95% confidence interval [CI], 10.0%-28.9%). Spin was identified in the Results and Conclusions sections of the abstracts of 27 (37.5%; 95% CI, 26.4%-49.7%) and 42 (58.3%; 95% CI, 46.1%-69.8%) reports, respectively, with the conclusions of 17 (23.6%; 95% CI, 14.4%-35.1%) focusing only on treatment effectiveness. Spin was identified in the main-text Results, Discussion, and Conclusions sections of 21 (29.2%; 95% CI, 19.0%-41.1%), 31 (43.1%; 95% CI, 31.4%-55.3%), and 36 (50.0%; 95% CI, 38.0%-62.0%) reports, respectively. More than 40% of the reports had spin in at least 2 of these sections in the main text.
Conclusion In this representative sample of RCTs published in 2006 with statistically nonsignificant primary outcomes, the reporting and interpretation of findings was frequently inconsistent with the results.
Author Affiliations: Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom (Drs Boutron and Altman and Ms Dutton); INSERM, U738, Paris, France (Drs Boutron and Ravaud); Assistance Publique des Hôpitaux de Paris, Hôpital Hôtel Dieu, Centre d’Épidémiologie Clinique, Paris (Drs Boutron and Ravaud); and Université Paris Descartes, Faculté de Médecine, Paris (Drs Boutron and Ravaud).
In this representative sample of RCTs published in 2006 with statistically nonsignificant primary outcomes, the reporting and interpretation of findings was frequently inconsistent with the results.
Icahn says Genzyme may need a new CEO - The Boston Globe
Billionaire investor Carl C. Icahn stepped up his campaign to gain partial control of Genzyme Corp. yesterday, suggesting the Cambridge biotechnology company could be broken up and calling on shareholders to consider replacing its longtime chairman and chief executive.
InterMune to Fire 40% of Workers After Drug Rejected
InterMune to Fire 40% of Workers After Drug Rejected (Update1)
By Drew Armstrong
May 26 (Bloomberg) -- InterMune Inc. said it will fire about 60 employees, or 40 percent of its workforce, to reduce costs after the U.S. Food and Drug Administration rejected the company’s lung drug earlier this month.
The firings will save the biotechnology company about $12 million a year, InterMune said today in a filing with the U.S. Securities and Exchange Commission. The Brisbane, California- based company said it expects to take a one-time charge of $2.4 million in the second quarter to pay for the cuts, which are expected to be completed by the end of June and will leave InterMune with about 85 employees.
The FDA rejected InterMune’s drug Esbiret as a treatment for idiopathic pulmonary fibrosis, a lung-scarring disorder. Analysts had forecast Esbiret would generate more than $1 billion in annual sales. The agency asked InterMune to conduct a new clinical trial to prove the medicine delays the progression of the disease, the company said in a statement on May 4.
InterMune tumbled 75 percent to $11.38 the day after the FDA rejection, the biggest drop since the company began trading on the Nasdaq Stock Market in March 2000. InterMune fell 3.5 percent to $8.57 at 5:55 p.m. New York time in extended trading after gaining 3 cents earlier today to close at $8.88.
To contact the reporter on this story: Drew Armstrong in Washington at darmstrong17@bloomberg.net.
Last Updated: May 26, 2010 18:21 EDT
Clinical trials - ain't they a bitch!
Pharma Giles writes ....
London-based AstraZubillaga has named Fulton McSly as its new President of Research and Development, a newly created position, effective from July 1. Two AZ executives who have led drug discovery and drug development, respectively, will now report to McSly, an AstraZubillaga spokesman said.
From 2007 to 2009, McSly was Head of Phoni's R&D operations where he presided over several billion-dollar failures, such as Phoni’s inhaled insulin debacle (Protubera) and the disastrous CETP blocker, Tellizanfib. Undeterred, McSly boasted of Phoni’s “wonderful database of failures”, whilst forcing Phoni into a death spiral of short-sighted site closures and head count reductions in an effort to make up for its losses.
But in October, Dry Prong Louisiana-based Phoni split its R&D organization into two after acquiring Whyus for $70 billion. Based on his track record, McSly was assigned to lead the "DeadLoss" research group, which focused on developing traditional synthetic small-molecules whilst Mike Doldrums, who had led R&D at Whyus, took over the "GreatWhiteHope" group which focused on large-molecule biologics, derived from living cells.
That split structure, however, proved to be short-lived. Phoni, which is the largest imaginary drug maker in the world by sales, said that with McSly's “resignation”--which is effective immediately--Doldrums will take over a unified R&D operation.
“Rats and sinking ships spring to mind, although you don’t often hear of them swimming from the Titanic to the Lusitania…”
AZ were equally positive about the appointment.
"Fulton has very clear and strong disaster management credentials," said AstraZubillaga CEO Max Headroom, "and we believe he can perform a very important role for us."
“It’s also a fact that most R & D programs end in failure. We feel that Fulton will therefore enable us to carrying on doing what R&D does best - failing. Fulton’s experience of failure is second to none in the industry. Long may he continue…”
In the real world, how long before another company-hopping R&D President winds up in his own wonderful database?
