Friday, September 23, 2011

My blog has moved to new Wordpress site

I have moved my blog to this Wordpress site here. You'll also be able to access the new blog via my website. Although I will no longer posting here, I look forward to hearing from you at my new location. Thanks for your continued interest and support!

Wednesday, September 14, 2011

Coverage of Rick Perry's vaccine misadventure misses the point

Recent media coverage of the heated debate over Texas Governor Rick Perry's endorsement of mandatory HPV vaccinations for school-age girls in his state seems to be missing a few crucial points. First, many of the medical groups who strongly endorsed the vaccine to prevent cervical cancer received funding from Merck, the maker of the vaccine in question, Gardasil. And two, Merck's aggressive marketing campaign to sell the vaccine as a preventative measure against a relatively rare type of cancer (cervical cancer) in middle-class teenage girls completely ignored poorer populations that are at much higher risk of developing this cancer.

Such concerns were amplified in a thoughtful 2009 paper in the Journal of the American Medical Association(JAMA), and reported by Gary Schwitzer's Healthnews blog and Gooznews.

As the JAMA researchers noted:
As marketing of this HPV (short for human papilloma virus) vaccine demonstrates, pharmaceutical company campaigns can undercut the most cost-effective and appropriate use of new agents to the detriment of adolescent health. By making this vaccine's target disease cervical cancer, the sexual transmission of HPV was minimized, the threat of cervical cancer to all adolescents maximized, and the subpopulations most at risk practically ignored.

Recent news reports do mention that Perry himself had substantial conflicts of interest when he signed an executive order mandating HPV vaccines for school-age girls, making him the only governor in the union to do so. As the San Francisco Chronicle notes, Perry has received at least $23,500 in campaign contributions from Merck, including $5,000 in 2006, the year before he ordered girls throughout the state to take the HPV vaccine. Merck also has donated about $500,000 to the Republican Governors Association, a group which Perry headed twice and has been among his most generous campaign donors. As the Chronicle and the New York Times also point out, Perry issued the executive order at a time when his former chief of staff was a lobbyist for Merck.

But the Times article fails to note the egregious conflicts of interest among key physician groups that strongly endorsed the vaccine for school-age girls. As the 2009 JAMA article pointed out, Merck provided educational grants to groups like the American College of Obstetricians and Gynecologists, the American Society for Colposcopy and Cervical Pathology (ASCCP), the Society of Gynecologic Oncologists (SGO), and the American College Health Association (ACHA), all of whom strongly recommended the vaccine in school-age girls.

The recent coverage also doesn't explore the public health costs and benefits of mandating vaccines for affluent school-age girls, which, as Gooznews notes, doesn't make a lot of financial sense. About 3,600 women die from cervical cancer every year -- compared to approximately 40,000 who die from breast cancer annually. Yet Merck itself estimated it would cost $1.4 to $1.6 billion to immunize young girls from the disease, which can be picked up fairly easily (and much more cheaply) with regular pap smears.

As the JAMA researchers were the first to note, it would make far more sense to spend the money paying for pap smears for poorer women who have multiple partners but no health insurance.

I have to say I find it ironic that Perry is being lambasted by his Republican rivals for mandating something they say should have been left up to families to decide, which is the primary focus of today's Times piece. But I wish the media would use this opportunity to explore the public health ramifications of allowing a drug manufacturer to aggressively target the wrong population for an expensive and possibly unnecessary vaccine.

Thursday, September 8, 2011

French lawmakers may mandate conflict of interest disclosures

At a time when our own government has stepped back from requiring true transparency about conflicts of interest in medicine, French lawmakers seem to be heading in a much bolder direction. According to Nature Medicine, the French national assembly is considering a bill that would require that conflicts are publicly disclosed by the country's regulatory agencies and made available to consumers.

In other words, instead of relying on the discretion of universities to disclose when their government-funded researchers get financial compensation from drug makers and other companies, as our own National Institutes of Health now does, the French would require their regulatory counterparts to publicly disclose all such conflicts of interest and face monetary sanctions if they don't.

This strikes me as a wonderful idea, since it takes the decision about disclosure out of the hands of academic institutions that are increasingly reliant on industry funding -- see here-- and puts it where it belongs -- in the hands of agencies like the NIH and FDA that use taxpayer money to fund and regulate research for the public good.

As has been widely reported, of course, the NIH recently tacked in the opposite direction under pressure from university lobbyists -- see here. Instead of requiring universities to disclose their faculty's conflicts of interest on a publicly available website, the newly announced rules gives schools the option to conceal financial conflicts of interest, according to Sheldon Krimsky, a professor of ethics at Tufts University School of Medicine.

Amazingly enough, most of France's nonprofit private health insurers appear to support that country's proposed new rules about disclosure. Etienne Caniard, president of Mutualité Française, a federation of these insurers, told Nature Medicine that:

“This proposal will help uncover the sectors where the state has given free rein to the pharmaceutical industry and where it should take its responsibility and regain control, such as continuous medical education,” he says.

Can you imagine the big for-profit health insurers in this country taking a similar stance? Dream on!

Wednesday, August 24, 2011

New NIH rules about conflicts of interest are a swiss cheese of loopholes

The newly announced rules on financial conflicts of interest among federally funded researchers are certainly an improvement on the existing regulations issued by the National Institutes of Health in 1995 (which were never enforced anyway). But as ethicists and consumer advocates note -- see here and here -- they fall short of true reform largely because they continue to leave the reporting and management of financial conflicts up to the discretion of institutions who are themselves increasingly dependent on private-sector funding and thus imprisoned by their own conflicts of interest.

Why is this a problem? As Greg Petsko, a researcher at Brandeis University who is studying Parkinson's and Lou Gehrig's disease, recently explained to me: "“If you are accepting any sort of reimbursement or personal funds from any organization that might benefit from what you’re doing scientifically or from public statements you’re making, you have a moral obligation to make that connection clear so people can decide for themselves how much weight they want to give what you’re saying.”

In other words, studies show that financial conflicts can sway the judgement of doctors and researchers who receive federal funding, and it is important that the public know just exactly what those conflicts consist of - so they can make up their minds about how valid the science conducted by these conflicted researchers is.

Yet the new rules promulgated by the NIH don't make it easy for consumers to find out about such conflicts of interest. When the revisions were first proposed, they contained a provision requiring universities to disclose their researchers' conflicts of interest on a publicly available website. But that provision has been dropped under pressure from university and industry lobbyists, and instead institutions can decide for themselves how they want to release conflict of interest information. The only requirement is that if someone inquires about a specific researcher's conflict, the institution has five business days to respond -- see here.

Under the new rules, institutions now have to disclose more information about their researchers' conflicts. Previously, each institution only has to report that there was a conflict to the funding agency and note that it was being managed, and there are many instances when universities didn't even do that and were never sanctioned for their failure to disclose. For example, Brown University School of Medicine never bothered to disclose to the NIH the hundreds of thousands of dollars in personal consulting and speaking fees that Dr. Martin Keller, then chief of psychiatry at Brown University, was receiving from drug companies each year, despite the fact that Keller was receiving millions of dollars in federal research funds from the National Institute of Mental Health -- see Boston Globe article I wrote here. But neither Brown nor Keller were ever publicly sanctioned for that failure to disclose.

Under the new rules, institutions are now supposed to disclose more information about the conflicts, including the specific holdings or financial interest, the value of the conflict, how this relates to the research in question and why it is deemed to be a conflict of interest. But again, how they disclose this information to the public is up to them, and if past history is any guide, there will be little enforcement of such rules by the NIH itself. As Sally Rockey, the NIH deputy director for extramural research, acknowledged in a brief teleconference about the rules yesterday, the federal agency has never terminated a grant because of non-compliance -- see here.

Dr. Bernard Carroll, writing in Health Care Renewal, points up another loophole with the new rules:
The revised regulations do not close the regulatory loophole through which Charles Nemeroff strolled when he moved from Emory to the University of Miami. We covered that incident several times on this blog last year. Though Nemeroff was under a 2-year sanction and banned from participating in NIH-funded research at Emory, his friend Thomas Insel, Director of NIMH, assured the dean of the medical school at Miami that Nemeroff was in good standing to apply for NIH funding when he moved from Emory. To underline the point, Insel displayed the bad judgment of appointing Nemeroff to 2 new NIMH review committees.Do today’s revised regulations prevent a repeat of this administrative travesty? No, they don’t. There is some mention of ensuring oversight if a sanctioned investigator wishes to transfer a grant to a new institution, but nothing to prevent the Nemeroff-Insel dance from being repeated.

One can't help but wonder if the weakened NIH regulations are part of the massive rollback in federal regulations by the Obama administration that I recently read about. What happened to our President's spine?

Wednesday, August 10, 2011

What's behind the growing rate of scientific retractions?

The retraction of studies in medical and scientific journals has surged in the last decade, according to separate analyses done by the Wall Street Journal and Retraction Watch.

In its page-one article today, the Journal noted that while just 22 retraction notices appeared in 2001, there were 139 in 2006, 339 last year and 210 so far this year. Retraction Watch, in a blog celebrating its one-year anniversary, said it has recorded 200 retractions over the last 12 months, compared to an annual average of about 80 over the previous 10 years.

Why are retractions on the rise? According to the WSJ, some journals argue that the increase indicates their rising vigilance in detecting errors. Others blame the increasingly competitive environment for research grants and career advances in science and medicine.

I would point to two other key factors. First and foremost, there's the pressure that the pharmaceutical and medical device industry exerts on researchers to come up with positive findings in clinical trials. (This starts with cherry-picking pliable researchers for specific studies and ensuring their cooperation with lucrative speaking and consulting gigs and then having the studies themselves ghost-written to make the drug or medical device in question look safer and more effective than it really is). This is known to have happened with clinical trials for Paxil (which Side Effects focuses on), Celexa, Zoloft, Vioxx and Avandia and several medical devices including a widely used bone growth product made by Medtronics (which The Spine Journal just devoted an entire special issue to).

This kind of industry-academia collusion, of course, has been going on for awhile. What's different now is the heightened scrutiny of scientific misconduct by the media and the steady drumbeat of blogs like Retraction Watch, POGO and Pharmalot. As a result, many journals are now adopting a tougher line and investigating errors more thoroughly. And that's exactly how it should be.

Wednesday, August 3, 2011

With Big Pharma on campus, who is looking after the public interest?

Medicare and social services for vulnerable Americans are not the only programs on the chopping block with Washington's deal to raise the debt ceiling and cut trillions of dollars in government spending. Looming ahead may be deep cuts in funding for medical and science research, and that raises the specter of growing collaboration between academic centers and industry, including pharmaceutical and medical device companies.

Even before the debt deal was reached, partnerships between Big Pharma and universities have been on the rise, according to an article in the current issue of Chronicle of Higher Education. The article, Big Pharma Finds a Home on Campus, details this growing collaboration and the "many new ethical and practice questions" it raises, including the increasing potential for conflicts of interest.

There may be some beneficial outcomes to these partnerships in the development of drugs to treat intractable diseases. But what concerns many is this: how can institutions that are increasingly reliant on funding from private companies do an adequate job of policing conflicts of interest among their own faculty? It's akin to having the fox guard the chicken coop.

"I'm not sure that universities can police conflicts of interest when they become so reliant on [private sector] funding," said Peter Conrad, Harry Coplan Professor of Social Sciences at Brandeis University and author of The Medicalization of Society. According to Conrad and others, academic centers are already doing a poor job of enforcing their own conflicts of interest policies. He points to the "slap on the wrist" Harvard Medical School gave Joseph Biederman for failing to disclose millions of dollars in financial ties to drug makers; see background here.

"Biederman used his name and position as a way of promoting the use of antipsychotics for childhood bipolar disorder," Conrad said. "He was basically an entrepreneur for the bipolar diagnosis in children and using drugs that have not been tested and approved for children."

Conrad believes such conflicts of interest will only worsen in the coming years as federal research money becomes scarcer and universities turn to industry to keep their science labs humming.

"I think this is just the beginning of the privatization of research," he says. "It's representative of the tilt in society towards business interests over public interests." Conrad cited the recent Supreme Court decision that allows corporations to give as much money as they want to political candidates an another example of that tilt toward allowing commercial interests to take precedence over public interests.

Indeed, university and industry lobbyists have already succeeded in convincing the federal government to drop a key provision in the proposed new NIH guidelines for conflicts of interest among federally-funded researchers. According to Nature, a cornerstone of the new guidelines — a series of publicly accessible websites detailing financial conflicts among academic researchers — has now been dropped.

Consumer advocates have roundly criticized the move. "It greatly diminishes the amount of vigilance that the public can exercise over financially conflicted research being funded by the NIH," said Sidney Wolfe, director of the Health Research Group at Public Citizen, in Nature.

My guess is that universities didn't want that much transparency out of fear it might embarrass their star faculty rainmakers and stifle lucrative partnerships with industry. After all, why bite the hand that feeds you?

Wednesday, July 20, 2011

Tougher NIH rules about financial conflicts in danger of being watered down

I realize this is the dead of summer and every journalist who isn't on vacation is captivated by the Murdoch phone-hacking scandal. But while everyone is looking the other way, the National Institute of Health's proposed new rules about the disclosure of financial conflicts of interest may be watered down.

The sticking point, according to the Project on Government Oversight (POGO), is a proposed rule that would require government-funded researchers to publicly disclose potential conflicts of interest to consumers. POGO officials say that the Office of Management and Budget (OMB), which has been reviewing the proposed changes for months, may weaken or eliminate the public disclosure requirement due to pressure from industry and university officials. In a letter to OMB July 11, POGO's executive director Danielle Brian and staff scientist Ned Feder called on the OMB to make sure that requirement remains in the new guidelines.

Why does this matter? Because it's vitally important for consumers to know if researchers and doctors' judgments are being swayed by industry largesse or other conflicts that could influence their work. One would think the federal agency that supports most medical research in this country (National Institutes of Health) would be playing a key role in making such conflicts of interest transparent. Think again. Even though current NIH guidelines calls for universities to report to the granting agency significant financial conflicts (more than $10,000 annually) among faculty who have NIH grants, neither the institutes nor the universities have bothered to adhere to these 16-year-old guidelines.

Case in point: Dr. Helen Mayberg, a neurologist at Emory University School of Medicine, and a principal investigator on five federally funded research projects. As I've blogged about before here and here, since she came to Emory in 2003, Mayberg has earned tens of thousands of dollars consulting for medical device companies and being an expert witness in death penalty cases, always on the side of prosecutors bent on execution. Mayberg was one of eight authors of a 2006 study who failed to disclose consulting ties with Cyberonics, the maker of the electronic device their paper touted as being effective in treating depression. Because of this egregious failure to disclose, the lead author of the study, Dr. Charles Nemeroff, then chair of psychiatry at Emory, was forced to step down as editor in chief of the journal Neuropsychopharmacology, which published the paper -- see background here.

Mayberg has also attracted notoriety for testifying (always for the prosecution) in more recent death penalty cases than almost any other doctor in the country. Mayberg's job in these cases is to raise doubts about the validity of scans that show brain damage in defendants on death row, and critics say her testimony often contradicts her own published research on brain scans. But she earns a pretty penny doing so. According to a psychiatrist who also testifies in such cases, Mayberg probably earns more than $50,000 per case. In 2009, she acknowledged testifying in at least five of these cases, which potentially adds up at least $250,000 in one year alone.

These are significant conflicts of interest that Emory should have reported to the NIMH, especially since Mayberg took over as principal investigator on two major studies that used to be led by Nemeroff: the mood and anxiety disorders initiative, a collaboration between NIMH (which put up $2.1 million last year alone) and GlaxoSmithKline, to develop a new generation of antidepressants, and another $1.8 million study called predictors of antidepressant treatment response. After Nemeroff stepped down from these NIH-funded projects in the wake of his own failures to disclose, the NIH instituted tighter rules on approving grants to Emory, including more documentation on researchers' outside activities and potential conflicts of interest, according to The Atlanta Journal-Constitution.

Yet according to NIMH records obtained under the Freedom of Information Act, "no financial conflicts of interest were identified to NIMH by Emory University about Dr. Helen Mayberg with regard to NIH-funded research projects in which she is listed as the principal investigator." It doesn't look like the NIH has enforced its own tougher requirements in the wake of the Nemeroff affair. All I could get out of an NIH spokeswoman was this: "NIH will neither confirm nor deny matters relating to compliance which may be under review." Does that mean the failure of Emory to disclose Mayberg's myriad conflicts is under review? The NIH won't say.

This is precisely why we need a public disclosure requirement in the new regulations governing scientific conflicts of interest. Taxpayers have a right to know what their publicly funded investigators -- in the case of Mayberg, someone who is in charge of millions of dollars in grants -- are up to.

Monday, July 11, 2011

UPenn President is urged to resign as chair of Obama's bioethics commission for ignoring scientific misconduct allegations

The Project on Government Oversight (POGO) has called on President Obama to remove Amy Gutmann, University of Pennsylvania's president, as chair of his presidential commission for the study of bioethical issues. The reason: Gutmann did nothing to sanction the chairman of UPenn's psychiatry department for publishing an editorial under his name that was ghost-written by a medical company that worked for the drug industry. The editorial, published in Biological Psychiatry, called for the aggressive treatment of bipolar disorder on the grounds that it was linked to a number of serious diseases. In a letter to NIH Director Francis Collins last November, POGO had disclosed the ghost-writing allegation, among other egregious ghost-writing examples, and called on Collins to curb this widespread practice in scientific research.

Now, Dr. Jay Amsterdam, a psychiatrist at UPenn, has filed a new complaint with the federal Office of Research Integrity (ORI), charging that Dr. Dwight Evans, UPenn's psychiatry chair, and four colleagues (including then psychiatry kingpin Charles Nemeroff) engaged in scientific misconduct by allowing their names to be appended to a manuscript that was drafted by the same ghostwriter for GlaxoSmithKline that wrote the editorial for Evans. Amsterdam also alleges the ghost-written paper misrepresented information from a study on the use of Paxil in bipolar depression. The study in question was funded by GlaxoSmithKline and a grant from the NIMH and published in the American Journal of Psychiatry in June 2001.

In his complaint, which can be found here, Amsterdam, who was one of study 352's principal investigators, alleges that the published manuscript did not acknowledge the medical ghostwriter's contribution or the extent of Glaxo's involvement in preparing the paper. The study itself, he says, made unsubstantiated claims about Paxil's effectiveness and downplayed some serious side effects. For example, study 352 suggested that Paxil was beneficial in the treatment of bipolar disorder, when in fact it failed to show efficacy over an older antidepressant on at least one primary outcome measure. The manuscript also did not report that Paxil may have induced mania in some patients, which is a well-known side effect not only of Paxil but other SSRI antidepressants.

Dr. Amsterdam also alleges that even though he was a principal investigator of the study, he was excluded from the final data review, analysis and publication of the paper by the ghostwriter, Scientific Therapeutics Inc (STI). STI has a longstanding history of ghostwriting medical articles under contract to GSK and other drug companies. STI was the same company that ghost-wrote the notorious Paxil study 329, as detailed in Side Effects. Indeed, study 329 was included as one of the egregious examples of ghostwriting in POGO's letter to Collins last November, which I blogged about here.

Back in 2001, when Amsterdam repeatedly complained about not being included in the publication of his own study, one of the junior psychiatrists who had been named as an author in his place apologized to him, explaining that "control of the paper had been taken away from him and that GSK published the paper without circulating the draft to all the participants..." Amsterdam continued to assert that some sort of reprimand was necessary to ensure that "plagiarism" of a colleague's data didn't happen again. But his complaints were brushed off by Evans and other colleagues at UPenn.

In his letter to ORI, Amsterdam's attorney notes that even though study 352 was published 10 years ago, it continues to be referenced in medical journals, most recently as this year. He called on the Office of Research Integrity to conduct a thorough investigation to ensure that similar misconduct never happens again and to prevent further use of study 352 "to support the dangerous prescription of Paxil to patients diagnosed with bipolar depression."

And now back to Amy Gutmann. As chair of the presidential commission on bioethics, UPenn's president is supposed to be working to promote ethical behavior in scientific and medical research. Last November, when POGO released its letter to NIH citing the ghostwriting incident involving UPenn's psychiatry chair, the university student newspaper jumped on the story. At the time, a university spokesman was quoted in the student paper saying that allegations of ghostwriting in Evans' editorial were "unfounded." Yet documents unsealed in a lawsuit show evidence that STI prepared a draft of the editorial for Evans. Amsterdam's attorney sent Gutmann a copy of his official complaint last week; see here.

In its missive to President Obama, POGO writes:
We do not understand how Dr. Gutmann can be a credible Chair of the Commission when she seems to ignore bioethical problems on her own campus. Until the University concludes a sincere and transparent investigation of these charges and takes decisive action to deter future ghostwriting, we feel that Dr. Gutmann should be removed as Chair of the Commission.

Stay tuned...

Tuesday, July 5, 2011

Biederman and colleagues at Harvard get a slap on the wrist

Harvard Medical School finally wrapped up its three-year-old investigation of Dr. Joseph Biederman and two colleagues accused of failing to disclose extensive financial conflicts of interest, with essentially a slap on the wrist.

In 2008, Congressional investigators accused the three psychiatrists -- Biederman, Thomas Spencer and Timothy Wilens -- of failing to disclose more than $1 million each in payments from the drug industry. As I blogged about here, most of Biederman's financial ties were with the makers of anti-psychotic drugs at the very same time he was promoting the use of these drugs in the treatment of childhood bipolar disorder. According to documents released in a lawsuit, Biederman also courted funding from Johnson & Johnson by promising that his work at Mass. General would promote the use of its anti-psychotic Risperdal in children. Johnson & Johnson gave the hospital $700,000 for a Biederman-led research center that did studies promoting Risperdal. All of which raises the question of whether Biederman helped the drug company illegally market the off-label use of its anti-psychotic drug in children

But rather than suspend or fire him for such unethical and possibly criminal behavior, Harvard and Mass. General let him and his two colleagues off easy. According to The Boston Globe, they required the three physicians to refrain from all paid industry-sponsored activities for one year and undergo unspecified additional training. A letter Biederman and his colleagues wrote to co-workers about the remedial actions also mentioned that they might "suffer a delay of consideration for promotion and advancement."

Wow, that's tough. As Dr. Jerome Kassirer, a Tufts University professor and author of On the Take, notes in The Globe article, Biederman already is a full professor at Harvard so it's unclear how a delay in promotion would affect him. This strikes me as one more example of how hospitals and medical schools are so compromised by drug company money themselves that they no longer care to impose ethical standards on their own faculty.

On a sadly related note, the mother of Iris Chang, a bestselling author and historian who killed herself in 2004, reveals in a new memoir that her daughter was taking psychoactive drugs that may have caused her suicide. Iris Chang was the author of The Rape of Nanking, a critically acclaimed history of the massacre of Chinese men, women and children by Japanese soldiers in the run-up to World War II. She was only 36 when she died and the mother of a two-year-old boy.

In her memoir, The Woman Who Could Not Forget, Ying-Ying Chang, reveals that Iris was taking Risperdal and the antidepressant Celexa, when she killed herself. Chang's mother writes that she believes Iris' suicide was caused by her medications. She calls attention to the extensive literature showing that SSRI antidepressants cause suicidal behavior in some patients (often in the days after they first start the drugs), and she notes that Iris had begun taking Celexa right before she shot herself in October 2004.

Her mother writes:
"[Iris] represented a classic case in which psychiatric medications change one's personality. I do not need to repeat the huge number of bizarre cases documented, in which an originally ordinary mildly depressed patient becomes violent and destructive after taking antidepressants...The tragic violent way she ended her life was not characteristic of Iris."
Ying-Yang said she hopes her memoir "will help people become aware of the possible danger of psychiatric drugs and to think twice before taking them."

Tuesday, June 28, 2011

Everything you wanted to know about ghostwriting but were afraid to ask...

Two quick notes: the Project on Government Oversight (POGO) has posted a helpful FAQ on corporate-funded medical ghostwriting. As POGO investigator Paul Thacker writes:
"We hope this [FAQ] will answer any questions you might have on this very disturbing practice that corrupts the medical literature, drives up healthcare costs, and puts patient safety at risk."

Also, my blog was recently listed on a popular pharmacy website as one of the 50 best blogs about pharmaceuticals, right up there with Pharmalot and BNET Pharma. I'm honored.

Monday, June 27, 2011

The real reason biotech industry opposes Medicare advisory panel

A page-one story in The Boston Globe today spotlights the Massachusetts biotech industry's effort to block a key piece of President Obama's health care overhaul: the creation of an independent payment advisory board (IPAB) that would make recommendations on how to trim wasteful and counterproductive Medicare spending.

The presidentially appointed board, to be comprised of representatives from hospitals, physicians, patients, drug and device companies and other health care constituencies, is supposed to recommend program changes that will hold Medicare spending increases to levels that are no greater than the pace of economic growth (GDP) plus one percent. As Merrill Goozner explains in gooznews, the board can recommend replacing fee-for-service with bundled payments or pay-for-performance schemes. It can penalize health care organizations for lousy care and give them incentives for higher quality care. Whatever the board recommends must be passed by Congress, which also has the option of substituting its own cost-cutting measures.

As Goozner, Paul Krugman and others note, the board will have much less power than comparable boards in Europe. Even so, the IPAB has come under attack from Republicans such as Paul Ryan (R-Wis.) and conservative columnists such as David Brooks. And now we see the biotech industry coming out against it.

Why? The Massachusetts biotech executive council says it's because the board would stifle innovation and hurt the state's economy. May I point out this is the same old canard the drug and medical device industry trots out whenever they don't like a particular regulation aimed at protecting American consumers? They trotted out the same argument when opposing Massachusetts' pioneering ban against gifts and free meals for doctors and then calling for its repeal -- see here. And they dusted it off again to pressure the FDA into backing down from its recent efforts to ensure that unsafe drugs and medical devices are kept from the market -- see here.

The real reason the biotech, drug and medical device companies are opposed to the creation of the independent board is because its recommendations that hospitals and doctors dispense effective but less expensive drugs and procedures would cut into industry's profit margins. Industry representatives don't seem to care that the board's decisions might actually improve the quality of patient care. Consider, for example, the metal-on-metal hip implants that Barry Meier wrote about in Sunday's New York Times. As it turns, these new implants, which were not fully vetted by the FDA, caused considerable pain and health problems for many patients.

If the independent payment advisory board had already been set up, it might have recommended that hospitals and doctors first consider older, safer hip implants for their patients. Likewise, as Meier points out, there are many older drugs that are just as effective, and in many cases, safer than the costly brand names. (Vioxx, Avandia, Seroquel and Zyprexa are just a few of the new drugs that were trumpeted as more effective and safer than existing meds but turned out to be the exact opposite). Yet the pharmaceutical industry does a masterful job -- through heavy marketing and lucrative doctor payments (some would call them kickbacks) -- of convincing physicians to prescribe costly new drugs instead of equally effective generic drugs. And as we can see from the soaring cost of health care, private insurers (the free market that Rep. Ryan is so fond of extolling) have done a lousy job of reining in these excesses.

The purpose of the independent advisory board is not only to cut such wasteful and counterproductive spending but to help doctors and hospitals reach more considered decisions about how to improve the quality of health care for Medicare patients. But the drug and medical device industry doesn't like that idea one bit.

Tuesday, June 14, 2011

New Pfizer deal with Boston-area medical schools dissected on WGBH-TV

I was planning to blog about Pfizer's new $100 million partnership with several Boston-area medical centers and its potential downsides. But before I could get around to doing that, I was invited to talk about the deal on WGBH-TV's Greater Boston show yesterday. If you're interested in what I have to say, you can watch here.

Wednesday, June 8, 2011

Is the credibility of Emory neurologist Helen Mayberg in question? You judge

A few weeks ago, I blogged about the strange case of Dr. Helen Mayberg, a neurologist at Emory University who has testified in more death penalty cases in recent years than almost any other doctor in the country. I highlighted Mayberg's lucrative and lethal (she always testifies for the prosecution who are pushing for the death penalty) sideline as an example of why the National Institutes of Health should adopt stricter conflict of interest guidelines that would require universities to more fully disclose the extent of their researchers' financial conflicts of interest.

At the time, I quoted a prominent neurologist who said that Mayberg goes to considerable lengths to rebut defense experts, often introducing inaccurate information and contradicting herself in the process. Since then, I have received additional information about her testimony in one particular death penalty case that appears to buttress such accusations. Indeed, critics say that her testimony indicates a level of hypocrisy and willingness to dissemble that should concern officials at the NIH, where Mayberg is principal investigator of several major multi-million-dollar research grants.

First some background. As I've blogged about here, Mayberg was recruited to Emory University by former psychiatry kingpin Charles Nemeroff and soon became involved in a major conflict of interest controversy with Nemeroff when they both failed to disclose significant financial ties to a medical device company in a positive paper they wrote about the company's patented technique. After Nemeroff was forced to step down as chief of psychiatry at Emory (for this and other failures to disclose), he departed Emory for the University of Miami. And lo and behold, Mayberg, who is not a psychiatrist and has never treated patients in clinical practice, became principal investigator of two major NIMH studies Nemeroff used to lead: the mood and anxiety disorders initiative, a collaboration between NIMH (which put up $2.1 million last year alone) and GlaxoSmithKline, to develop a new generation of antidepressants, and another $1.8 million study called predictors of antidepresssant treatment response.

As the principal investigator of such large, taxpayer-funded studies, Mayberg's credibility should be above reproach. However, according to transcripts, she has testified under oath in direct contradiction of her own statements in published research papers. In one particular death penalty case, a neurologist for the defense testified that PET scans taken of the defendant, a guy convicted of murder by the name of Erick Virgil Hall, showed that he had decreased functioning in an area of the brain associated with impulse control and aggressive behavior. Dr. James Merikangas, a clinical professor of psychiatry and at the George Washington School of Medicine, used the neuroimaging results, together with a comprehensive review of the defendant's social and medical history and a physical examination, to conclude that Hall had brain damage that should be allowed as mitigating evidence in his case. Merikangas was careful not to say that the decreased brain functioning found in the PET scan explained Hall's violent behavior, only that there was evidence of brain damage that may have impaired his judgment. (Such mitigating evidence is often introduced in an effort to take prisoners off death row and convert their sentence to a life in prison).

In her 2007 testimony in the Hall case, Mayberg derided the value of PET scans in showing brain damage, saying that "the use of PET scans for the clinical diagnosis and treatment of individual patients is extremely limited." She concluded that PET and functional neuroimaging scans cannot be used for diagnostic purposes or to quantify "residual effects of past traumatic brain injury."

However, Mayberg herself has used PET scans to diagnose depression and evaluate the response of depressed patients to deep brain stimulation, a surgical technique that she developed and patented and continues to promote as a valid treatment for depressed patients who have not responded to drugs; I've blogged about the controversial nature of her work here. In several papers Mayberg published about her research with deep brain stimulation, she discussed the value of using PET scans for this purpose. In one 1990 paper, for instance, she said that a PET scan "showed hypometabolism [decreased brain functioning] in the right lateral basotemporal region in all three patients." In another 2007 paper, she used PET scans to assert that "non-response to treatment and previous depressive episodes were associated with a higher degree of age-dependent hypometabolism in the rostral and anterior cingulate cortex." In yet another summary of one of her NIH-funded studies, she says she will use PET scans to assess the response of patients to different treatments. In these and other published articles, Mayberg herself is drawing cause and effect relationships between brain abnormalities and specific psychological conditions.

As Merikangas points out in his affidavit, Mayberg is well aware of the importance of neuroimaging in a forensic setting. In another 2007 paper, Mayberg concluded:
"In sum, neuroimaging evidence has become an increasingly important tool of proof in criminal and civil cases in the United States. Although subject to the constraints of reliability and relevance, results of neuroimaging scans can and do help courts to understand the nature, causes and behavior implications of injuries to the brain."
Indeed, a recent study cited in the New York Times affirmed that a highly sensitive functional type of magnetic resonance imaging found evidence of brain injuries in veterans injured in Iraq or Afghanistan that was too subtle to be detected by standard MRI scans.

To be fair, Mayberg testified in the Hall case three years before this new study came out. However, by 2007, plenty of research evidence existed showing that PET and other neuroimaging scans could detect key changes in brain functioning. In his affidavit, Merikangas cites three papers published in 2005 and 2007 indicating decreased brain functioning picked up by PET scans in areas implicated in aggressive and violent behavior.

Mayberg, Merikangas says, is simply ignoring the peer-reviewed literature on this subject. He concludes that her testimony in the Hall case is both misleading and deceptive. Now, Mayberg is at liberty to consult for and testify in whatever legal proceedings she elects to, as long as she fully discloses these conflicts of interest (which some would argue she hasn't). But as someone who is in charge of millions of dollars of taxpayer money, her word should be inviolate. It's kind of analogous to what's going on with Anthony Weiner and tweetgate. Given his sorry track record of lying to the American public, Rep. Weiner (NY) should probably resign his post in Congress, and in my view, we should hold federally funded researchers to the same high standard of credibility.

Footnote: Erich Hall is still on death row.

Tuesday, May 17, 2011

Helen Mayberg: A case study in why we need greater transparency about conflicts of interest

A year ago, the Department of Health and Human Services proposed new rules governing the disclosure and handling of financial conflicts of interest by medical researchers who receive federal funding. The more stringent rules were prompted by Congressional findings that prominent NIH-funded researchers had failed to disclose significant consulting and other income, violating the agency's own regulations. The new rules would, among other things, require universities to post on a publicly available website information describing the specific financial conflict of interests of their federally funded researchers, according to Sheldon Krimsky, the Tufts University ethicist who wrote about the new rules in an article for Ethics in Biology, Engineering & Medicine last year.

Why is this so important? Because the current system of disclosure has proven woefully inadequate in providing consumers with information about financial conflicts that can skew medical research and adversely affect patient care. According to a 2008 Inspector General's report, the vast majority (93 percent) of institutions reporting conflicts of interest to the NIH did not describe the nature of their researchers' conflicts; in addition, 90 percent of the universities relied solely on the researchers' discretion in reporting conflicts, which is why there was so much failure to disclose in the first place.

Here's an interesting case in point. Dr. Helen Mayberg, a neurologist at Emory University School of Medicine, has testified in more than 50 death penalty cases, always for the prosecution in an attempt to discredit any mitigating evidence of brain damage in defendants on death row. Indeed, in a 2009 transcript (State of Connecticut vs Richard Roszkowski), Mayberg acknowledged that she has probably testified exclusively for the prosecution in more recent death penalty cases than any other doctor in the country, except perhaps Park Dietz, known by some as Dr. Death for his decades of testifying on behalf of the prosecution in high-profile cases.

While Emory officials say Mayberg has reported her expert witness work to them, they are under no obligation to disclose the full range of her extra-curricular activities to the public under existing federal rules. As a result, very few of Mayberg's colleagues or patients know of her extensive testimony in death penalty cases. And Mayberg goes to some lengths to keep her lucrative sideline out of the public eye.

For example, she had a friend (David Dobbs)* scrub her Wikipedia page of any reference to her death penalty work or her previous failures to disclose other conflicts of interest; here's a more comprehensive earlier version of her wikipedia page pre-scrubbing. I blogged here about Mayberg's collaboration with former psychiatry kingpin Charles Nemeroff and her previous failure to fully disclose conflicts of interest involving her work with deep brain stimulation, a controversial technique for treating depression.

Also missing from Wikipedia is the fact that she has so angered other neurologists with her death penalty testimony that they tried to get her drummed out of the American Neuropsychiatric Association. As one prominent neurologist says, it's not just that Mayberg always testifies for the prosecution in death penalty cases -- in effect, "trying to kill people" -- but that she goes to considerable lengths to rebut defense experts, often introducing inaccurate information and contradicting herself in the process.

"She uses a lot of maneuvers to say that [defense] findings in brain scans are not valid, yet at the same time, she's written articles saying the brain scans are valid," says the neurologist in the Washington, D.C. area who has written extensively about brain damage. "In fact, she uses the same brain scans that she says are invalid in the courtroom to diagnose depression in people whom she then treats with deep brain stimulation."

According to Krimsky, Mayberg's death penalty work is considered a significant financial conflict of interest under both the old and new NIH rules. And if the new rules are adopted, she would not only be forced to disclose the extent of her death penalty work but also the money she makes from it. According to lawyers who do for this kind of work, Mayberg makes as much as $500 an hour testifying for the prosecution in death penalty cases. And since she travels all over the country to testify, including to notorious death penalty states like Texas and Alabama, those hefty hourly fees add up.

In response to my query about how many death penalty cases Mayberg has disclosed since she came to Emory in 2004 and how much money she's made from this sideline, all Emory officials would tell me is that "she reported five instances of expert witness activity in 2009." You do the math.

*Correction: David Dobbs did not scrub Mayberg's wikipedia page; he merely added a link to a feature he had written about her for the New York Times magazine.

Friday, May 13, 2011

A lesson in how not to run for public office -- in Canada or anywhere else

In his latest blog, Paul Thacker, an investigator for the Project on Government Oversight (POGO) and former aide to Senator Charles Grassley, struggles to understand how Dr. Stan Kutcher, a psychiatrist turned politician in Canada, could possibly say that Paxil study 329, which Kutcher co-authored in 2001, hasn’t caused any particular controversy. Thacker was at a conference in Toronto the night of the Canadian federal elections, and the talk at dinner that evening was all about how Kutcher, who was running on the Liberal Party ticket, had threatened to sue a Halifax newspaper, The Coast, for writing an article about his involvement in study 329.

In his blog, Thacker goes over ground covered in Side Effects -- how flawed the 2001 Paxil study is, how it was ghost-written by a medical contractor for GlaxoSmithKline, the maker of Paxil, and then signed off on by its many authors, including Dr. Martin Keller, the principal investigator from Brown University, and Stan Kutcher. Thacker notes that Side Effects isn’t the only detailed account of ethically questionable behavior in study 329. The BBC also ran an investigative report on its flaws, and several medical researchers have called for a retraction of the study; see here and here.

Rather than own up to his involvement in what many consider a mockery of empirical research, Kutcher threatened to sue The Coast for libel, forcing it to issue a retraction and remove the offending article from its website (it was promptly archived by another site, Scribd). And then, as Thacker and other bloggers note, Kutcher and his henchmen went on the attack and essentially accused me of being a Scientologist.

For the record, I am not and have never been a Scientologist. The more pertinent question is: does Canada want politicians who engage in these kind of ad hominen attacks? Apparently not.

Tuesday, May 3, 2011

Paxil study author and psychiatrist turned politician loses Halifax election

Stan Kutcher, the psychiatrist turned politician who threatened to sue The Coast newspaper in Halifax unless it issued a retraction on a story it did about Kutcher's involvement with Paxil study 329 (see retracted story here) and my blog about it), lost yesterday's election, along with the rest of his Liberal Party. See story here.

Sunday, May 1, 2011

Halifax newspaper buckles under to threat from psychiatrist turned politician

In recent years, experts (like Bill Kovach and Tom Rosenstiel) have warned that press freedoms are under increasing threat from economic pressures. As advertising and readers flee to the Web, they say, news outlets are more likely to cave in to pressure from corporate and political interests. Here's a disturbing example of this trend.

A few weeks ago, I was interviewed by a reporter for The Coast newspaper in Halifax, Nova Scotia. The reporter, Tim Bousquet, had discovered that the Liberal Party candidate in Halifax for the upcoming federal elections, Dr. Stan Kutcher, was one of the co-authors of Paxil study 329, a controversial clinical trial on the use of Paxil in treating depression in adolescent. When it was first published in 2001, study 329 purported to show that Paxil was safe and effective when in fact the actual data showed the opposite, as I reported in Side Effects and subsequent blogs. What New York prosecutors, several researchers and I found was that the study's authors manipulated and omitted data to make Paxil look safer and more effective in adolescents than it really was -- see background here. Given the study's serious flaws, researchers Jon Jureidini and Leemon McHenry recently called on the Journal of the American Academy of Child and Adolescent Psychiatry to retract the 2001 paper, according to the British Medical Journal.

Last Thursday, five days before the Halifax elections, which are being held May 2, Bousquet posted this article about Kutcher's involvement in study 329. Bousquet quoted me as saying that the researchers "essentially distorted the outcome measures." He also quoted Kutcher as saying that he stood by study 329 and didn't think it had caused any particular controversy. I thought the article was accurate except for two facts the reporter got wrong: he said that a secretary at Brown had leaked the information to me in 2003, when in fact the person who first blew the whistle on study 329 was the assistant research director in the department of psychiatry at Brown, and she first made me aware of some of study 329's flaws in 1996. As I explain in Side Effects, I was unable to pin down those particular allegations until 2004, when the New York State Attorney General's office sued GlaxoSmithKline for defrauding consumers by not telling them or doctors the full story about Paxil. In their lawsuit, the New York prosecutors found numerous flaws in the study 329, including the fact that the researchers had changed the primary outcome measures for the trial without disclosing that fact in the published paper. They also found that GlaxoSmithKline knew that the study 329's results were negative -- i.e. -- that the clinical trial didn't find Paxil more effective than placebo in treating depression -- but according to an internal memo, company officials decided to publish the study as a positive result anyway and indeed had it ghost-written by a medical contractor and then signed off on by all the co-authors, including Kutcher.

Kutcher's lawyers immediate responded to Bousquet's April 28 article by threatening to sue the newspaper for libel unless it immediately issued a retraction. Even though Bousquet backed up his article's assertions with documentation, the Coast decided to issue an apology and retraction anyway; see here. And then the newspaper simply removed the original article from its website; see here. So now readers of The Coast can see the apology but not why it was issued in the first place. Fortunately, a website called Scribd saved Bousquet's original piece along with a follow-up article about Kutcher's threat to sue The Coast if it didn't retract the piece.

As you can see from Scribd's follow-up piece, a blog here, and some comments on the original article (all of which were removed), Kutcher's hatchetmen are trying to paint me as a Scientologist in an effort to discredit me and the original story. That's a tactic as old as dirt; as a mental health reporter for The Boston Globe in the '80s and '90s, I remember when the drug industry and the psychiatrists on its payroll used that ridiculous canard to attack anyone who questioned their wonder drugs; indeed, in Side Effects, I write about how Eli Lilly, among others, attacked Dr. Martin Teicher, a respected psychiatric researcher at McLean Hospital, as a Scientologist when he first raised questions about the safety of Prozac in the early '90s.

All of this makes me wonder: where have The Coast and its editors been all these years? And do they really want to go down in history as an example of the not-so-free press buckling under to craven threats?

Monday, April 25, 2011

Serious flaws and conflicts skewed results of largest antidepressant study ever done

In 2006, researchers first published results from a $35 million NIMH-funded study of antidepressants known as STAR*D, claiming it proved the effectiveness of second-generation antidepressants used alone and in combination with each other. The NIMH chimed in with press releases extolling "new strategies" that help depressed patients become symptom-free, and the findings became the basis for American Psychiatric Association's guidelines calling for the open-ended use of antidepressants in treating depression.

But, as Edward Pigott, a Maryland psychologist, reveals in several published papers and his blog, it was all a big lie. Pigott shows how the STAR*D authors, 10 of whom had financial ties to antidepressant makers, played unethical games with the data to make all of the antidepressants in the study look far more effective than they really were. For instance:
       *The researchers changed the primary outcome measure from the Hamilton rating scale of depression (considered a gold standard in measuring depression) to a proprietary rating scale owned by the principal investigator, Dr. John Rush, a psychiatrist at the University of Texas (who by the way was investigated by Senator Grassley for failing to disclose extensive conflicts of interest). And they made the change even though the secondary rating scale had been used in clinical treatment, thus tainting it as an objective research measure. Furthermore, in the published results, Rush and his co-authors didn't bother to disclose this change (which skewed the results in favor of the drugs).
       * They failed to count patients who had dropped out as treatment failures, thus further skewing results in favor of the drugs.
       * Halfway through the study, they included patients with only mild depressive symptoms who had originally been excluded because they didn't meet the original criteria for being depressed, again making the results look better than they were.
       * They repeatedly rounded up percentages to make it look as if the antidepressants in the study were more effective than they really were. Yet they didn't round up any findings showing the percentage of negative side effects among patients taking these drugs.

After re-analyzing the data from STAR*D, Pigott found that in contrast to STAR*D’s published findings, only 108 of its 4,041 patients (2.7 percent) went into remission in the acute phase of the study. And of those initial patients, only 38 percent obtained remission after being dosed with other medications in three later phases of the trial. In every phase, more patients dropped out than were remitted, and this drop-out rate increased throughout the study. As Pigott says in a paper published this month in the journal Ethical Human Psychology and Psychiatry, "this reality directly counters the study's false claim that about 70 percent of those who did not withdraw from the study became symptom-free."

Three years later, in a review article for the Journal of Clinical Investigation, Dr. Thomas Insel, director of the NIMH in 2006 and today, pretty much acknowledged the inadequacy of second-generation antidepressants in treating depression. To quote Insel:
In 2007, the third and fourth most heavily purchased medications in the United States were antipsychotics and antidepressants, respectively, with a combined market of $25 billion. Remarkably, despite the heavy use of these medications, we have no evidence that the morbidity or mortality of mental disorders has dropped substantially in the past decades.
Instead, as Pigott points out in his most recent paper, "the morbidity and chronicity of mental disorders appears to be increasing with a twofold to threefold increase between 1987 and 2007 in the number of Americans receiving disability payments for such disorders." Robert Whitaker, of course, argues in his new book, Anatomy of an Epidemic, that it is the very overuse of so many psychoactive drugs with severe side effects that has led to this exponential increase in the number of Americans disabled by mental illness.

Whether or not you buy Whitaker's hypothesis -- and it certainly warrants further investigation -- the fact is that the STAR*D study, like Paxil study 329 was flawed in so many ways that its published results should be retracted.
Not only did most of the STAR*D authors including John Rush have financial ties to Forest Labs, the maker of Celexa, and other antidepressant makers who stood to benefit from the study's positive findings. But as Pigott reveals, the very same NIMH officials who were tasked with the oversight of this $35 million multi-center study were also allowed to put their names on STAR*D studies published in the New England Journal of Medicine and the American Journal of Psychiatry, an egregious conflict of interest that should never have been allowed.

Interestingly, while Insel acknowledges the inadequacy of current antidepressants in his 2009 review, there is nothing on NIMH's website that points to this more sober assessment, despite the existence of five meta-analyses that show "modest to no" advantage of antidepressants over placebo in clinical trials. Pigott concludes that it is hard to find any reason for this pro-drug bias "other than convention, ease to prescribe for physicians, and the success of pharmaceutical companies' relentless marketing efforts."

Friday, April 15, 2011

Let's fix the perverse financial incentives in Medicaid before hacking its budget

Medicaid and Medicare are in the news of late, as Congressional Republicans spar with President Obama and the Democrats on how best to rein in the ballooning costs of these entitlement programs, which make up a growing share of federal and state budgets. But what few policy makers seem to be talking about -- at least in public -- are the perverse financial incentives built into the system that allow the companies who manage Medicaid contracts on a statewide basis to make profits at the expense of quality health care for Medicaid recipients. As a result of these perverse incentives, many Medicaid patients, particularly those being treated for mental health problems, are either terribly under-served or in some cases, badly over-treated. The upshot, in many cases, is poorer health outcomes and higher Medicaid costs.

Allow me to explain. In most states, Medicaid contracts for mental health and substance abuse are separated out from medical services and handled by managed care companies that make their money from keeping patients out of expensive hospitals. As a result of the way many contracts have been drawn up, drug treatments for emotional and behavioral problems do not count as costs to the behavioral health managed care entity, but instead fall under the plan's general prescription drug coverage. However, hospitalizations and psychosocial treatments (such as different forms of therapy and family interventions) do fall under the managed care's costs. So to make a profit, managed care in almost every state has done a spectacular job over the last two decades of limiting hospitalizations and access to psychosocial interventions, according to a new Hastings Center Special Report, which focuses primarily on troubled children.

As the report concludes, it's much easier for "patients to obtain referrals for medication management and psychopharmacology." This perverse incentive goes a long way to explaining why so many Medicaid recipients, both children and adults, are prescribed expensive psychotropic drugs, which cause serious side effects, rather than alternative therapies, which might be more effective and less hazardous to their health. Managed care companies make more money that way.

As one top medical official for New York State told me, "If you're a managed care entity and the pharmacy benefit is not part of your budget, you're happy if a symptom can be controlled by someone prescribing a dubious and expensive drug. It's not your problem." Or, as the authors of the Hastings report put it,
"The country's mental health care system makes it difficult for children to access psychosocial care, but relatively straightforward to access medication treatments (even if those treatments are not monitored or reassessed as recommended)."
And the same, of course, holds true for adults.

Not only do individuals with mental health problems suffer as a result, but state governments actually end up spending more when these patients don't receive the most effective treatments and interventions. Some patients will inevitably "end up on the streets or in prison where the costs don't accrue to the managed care companies," the New York state medical official explains. The states, of course, still pick up the costs -- but out of separate budgets for prisons, homeless shelters and programs for troubled teens.

The plot thickens. In many states, large insurance companies such as United Health care, WellPoint and Blue Cross Blue Shield have joined large managed care companies such as Americhoice and Centene in managing Medicaid contracts, according to this article in The Washington Post. Some states have flat-rate contracts with managed care companies that are designed to balance the need to limit costs with providing appropriate mental and physical health care. But in other states such as Colorado, Florida and Tennessee, managed care companies have what is known as "at-risk contracts" -- contracts whereby they make a percentage profit based on how much is spent on each Medicaid patient. And with such contracts comes another perverse financial incentive that, in some cases, make patients sicker.

For example, some managed care companies actually benefit twice-over when patients are over-prescribed anti-psychotic drugs such as Seroquel and Zyprexa, according to Edward Knight, a former executive with a managed care company in Colorado and a recovery consultant. This is how: while the behavioral health arm of the company makes money by referring patients for drug prescriptions rather than more expensive psychosocial treatments, another arm of the company makes money by managing the diseases such as obesity and diabetes caused by the over-use of these drugs. The off-label use of anti-psychotics like Seroquel, Risperdal and Zyprexa is widespread in many states, with disastrous effects on some patients, as many bloggers, myself included, have already noted. To think that some companies managing Medicaid contracts are actually profiting from that over-use is indeed perverse.

Seems to me that until we do something about the conflicting financial incentives that are built into the Medicaid system, fighting over how to cut Medicaid funding to the states is a waste of time. As the New York medical official says, setting up contracts based on a specific dollar amount is fruitless. "If it's just dollars, [the managed care company] will cheat and figure out ways to get other entities to pick up costs, or they'll just deny care," he says. "We have to change the contract incentives so that these companies can earn X number of dollars when they improve health care. We have to get to risk-based contracts based on performance metrics rather than profits." Amen.

Monday, April 4, 2011

A tale of censorship and secrecy starring the American Psychiatric Association

Psychiatry is supposed to be all about disclosure, disclosing the dark secrets of one's past to a professional in an effort to heal or, at the very least, figure out why one is in such psychic pain. But given the recent actions of the American Psychiatric Association, the largest trade group for psychiatrists in the U.S., one might get the impression that the profession is really all about censorship and obfuscation.

Remember when the Project on Government Oversight (POGO), as part of an effort to get the NIH to crack down on ghostwriting, released documents showing that a psychopharmacology handbook for primary care doctors, authored by then psychiatry kingpins Charles Nemeroff and Alan Schatzberg, had actually been ghost-written by a company hired by GlaxoSmithKline, the maker of the blockbuster antidepressant, Paxil? The New York Times broke the story last fall, relying on internal Glaxo documents obtained in the course of a lawsuit against the drug giant, and a number of other journalists, including myself, blogged about it -- see here. The documents showed that Glaxo hired Scientific Therapeutics Information (STI) to prepare a draft of the textbook with the understanding that Glaxo could review the initial drafts before publication. The handbook itself, which was published in 1999 by the APA, essentially promoted Paxil, among other drugs, as a safe and effective treatment for anxiety and depression.

Sound familiar? As Side Effects reveals, that's exactly how the initial drafts of the notorious Paxil study 329 were prepared -- by the same company, STI, again under contract to Glaxo. In a remarkably similar arrangement, the authors of the Paxil study did not object to the draft's positive wording and made only minor changes to the paper, which concluded that Paxil was safe and effective in treating depression in adolescents even though the actual data showed quite the opposite -- see back story here. (In its later review of Paxil and other antidepressants before attaching black box warnings to them, the FDA labeled study 329 a "negative finding" because the study did not show statistical evidence of the drug's effectiveness and did not accurately represent the extent of Paxil's suicidal side effects among adolescents in the trial).

To get back to the story at hand, after the Times article was published, Nemeroff, who was drummed out of Emory for failing to disclose myriad financial ties to the drug industry and is now chair of psychiatry at the University of Miami, and Schatzberg, the dethroned chair of psychiatry at Stanford and a past president of the APA, called in their lawyers who insisted on several corrections to the Times piece, which I append here:
A headline on Nov. 30 with an article about SmithKline Beecham’s role in the publication of a book about treating psychiatric disorders overstated SmithKline’s actions. While documents show that SmithKline (now known as GlaxoSmithKline) hired a writing company for the book, they do not indicate that the company wrote the book for the authors, Dr. Charles B. Nemeroff and Dr. Alan F. Schatzberg. The article also described incorrectly, in some editions, events outlined in a letter from the writing company to Dr. Nemeroff. The correspondence proposed a timeline for the writing company to furnish the doctors and SmithKline with draft text and final page proofs for approval; the letter did not say that the company had already provided those materials for final approval. And the article misstated the context under which Dr. David A. Kessler, the former commissioner of the Food and Drug Administration, commented about the book’s production. The letter and other documents were described to him; he did not personally review the documents.

All well and good, but then the APA, probably in response to outraged queries from its members, wrote a self-serving and inaccurate piece about the whole affair in its news bulletin, Psychiatric News. Its bromide said the corrections "seemed to throw into doubt the central premises of the original article" and "seriously overstated the role of the writing company." Neither of these allegations, of course, are true -- the corrections appended to the Times article do not change the basic fact that the handbook was largely ghost-written by a company hired by Glaxo to promote Paxil and other antidepressants to primary care doctors.

Indeed, two prominent psychiatrists pointed that very truth out in a letter to the editor of Psychiatric News. While Ron McMillen, a spokesman for the APA, argued in the PN article that Nemeroff and Schatzberg were actively involved "in every stage of the book's development," the letter's authors note that McMillen did not venture to say that Nemeroff and Schatzberg "wrote the initial drafts -- or indeed any drafts." The letter notes:
"The released 49-page sample chapter draft provided by Diane Coniglio and Sally Laden, employees of Scientific Therapeutics Information (STI), is largely reproduced verbatim in the Handbook.

In their January 28, 2011 letter to the editor, Dr. Bernard Carroll, professor and chairman emeritus of the department of psychiatry at Duke University Medical Center, Dr. Robert Rubin, professor and vice chair of the department of psychiatry at the University of California, Los Angeles, and Leemon McHenry, a researcher at California State University, also called on the APA to release internal documents that might shed light how much influence Glaxo did have on the context and tone of the book and its role in approving drafts. The letter writers concluded, "This case highlights the need for disclosure if we ever are to understand the scale of corporate influence on academic publishing."

Here's where things really get absurd. After sitting on the letter for two months, Psychiatric News decided not to publish it. In an email to Carroll et al dated March 22, Cathy Brown, executive editor for the publication, wrote that the issue has been covered extensively already and "therefore, we will not be printing additional information about it at this time."

How sad. Can it be that the APA is so fearful of its members' reactions (or more likely, legal threats by Nemeroff and Schatzberg) that it cannot even run a short and well-reasoned letter to the editor? For an organization that represents a profession whose very modus operandi is based on disclosure and transparency, the APA's track record of censorship and secrecy is unacceptable.

Monday, March 28, 2011

New study finds corrosive influence of industry money on cardiology practice guidelines

In a finding that may stun heart patients but surprise few others, researchers have found that more than half of the doctors who wrote key clinical practice guidelines in cardiology had financial ties to medical device and drug companies that stood to benefit from those guidelines. The study, published today in the Archives of Internal Medicine, raises serious questions about the reliability of such clinical guidelines in treating heart disease.

In recent years, much of the attention on conflicts of interest in medicine has focused on how lucrative financial ties can influence doctors' ability to carry out unbiased research or give patients sound medical advice. But as the researchers who did the study note, "improper bias in the production of clinical practice guidelines can have a potentially more widespread adverse effect on patient care than individual practitioners' conflicts of interest." That's because such guidelines, which range from how to treat patients with various types of heart disease and stroke to how to do coronary bypass surgery, are often adopted as the standard of care throughout the field and taught in medical training programs at all levels.

As Dr. Steven Nissen, a noted cardiologist at the Cleveland Clinic who commented on the study in an accompanying editorial, put it: To allow individuals with financial conflicts of interest to write clinical practice guidelines "defies logic."

The authors of the study, physicians and bioethicists at the University of Pennsylvania, Thomas Jefferson Hospital and Massachusetts General Hospital, found that more than half of the doctors who wrote clinical practice guidelines in cardiology between 2004 and 2008 served as promotional speakers on behalf of industry, and a substantial number actually held stock in companies affected by the guidelines they wrote. Again to quote Nissen:
"No conceivable logic can defend the practice of including promotional speakers and stockholders on CPG writing committees. Participants in speaker's bureaus essentially become temporary employees of industry, whose duty is the promotion of the company's products."
Even more worrisome, the study found that the chairs of these guideline writing committees are significantly more likely (81 percent) than committee members (55 percent) to have a potential conflict of interest. As Nissen says, "Such findings are disturbing and suggest that the decision-making process for selecting chairs for cardiovascular [clinical practice guidelines] is seriously flawed."

Proponents of the status quo often argue that such guidelines are merely a synthesis of scientific evidence derived from randomized clinical trials. But as Nissen notes, research shows that nearly half of these recommended guidelines are based on expert opinion. "The subjective nature of the [guidelines] makes it even more essential that these documents be free of commercial influence," he says.

Nissen then poses the question as to why professional societies have allowed "such extraordinary levels of commercial influence to infiltrate CPG committees?" His answer:
"Professional societies and their leadership are often plagued by the same commercial relationships as the [guideline] committees. Pharmaceutical and medical device companies provide large amounts of financial support for the education and advocacy efforts of professional societies. Such relationships have created a dependency that is difficult to terminate because the leadership of professional societies is reluctant to antagonize their financial benefactors."
I'm glad to see Nissen, who has consulted for drug companies and received research funding from some of them in recent years, lay it on the line like this. Hopefully, his plainspokenness is a sign that change is coming. It's past time for doctors in all fields, not just cardiology, to recognize the corrosive influence of industry money on the practice of medicine and stop taking the dough. Only then can patients truly trust their doctors' medical judgments.

Monday, March 14, 2011

NESW posts video of informative blogging panel

Here is a link to the newly posted video of a blogging panel sponsored earlier this winter by the New England Science Writers, a local chapter of NASW. I moderated the panel, which featured a stellar group of health and science bloggers: Gary Schwitzer, who writes the Healthnewsreview blog, Daniel Carlat, of the Carlat Psychiatry Blog, Rachel Zimmerman, who curates WBUR's Commonhealth blog, and Ivan Oransky, who writes Embargo Watch and Retraction Watch. About 60 local health and science writers turned out for the event at the Harvard Faculty Club, and as you can see for yourself, it was an informative and entertaining evening.

Monday, March 7, 2011

Drug companies and psychiatry profession still singing the same old duet

The same drug giants paying millions of dollars to settle claims that they engaged in illegal and improper marketing of anti-psychotic drugs in the U.S. are even now looking for new worlds to conquer. Consider the study published today in the Archives of General Psychiatry. It surveyed more than 60,000 adults in 11 countries in Eastern Europe, Asia and South America and concludes that the treatment needs for people with bipolar disorder are "often unmet, particularly in low-income countries."

That may indeed be true. But I'd find this result a lot more believable if the study were not funded in large part by the same pharmaceutical companies who make the atypical anti-psychotics used to treat bipolar disorder: Eli Lilly (which makes Zyprexa), Janssen (the unit of Johndon & Johnson that brought us Risperdal), Pfizer (Geodon), Bristol Myers Squibb (Abilify), GlaxoSmithKline (Lamictal), and Novartis (Fanapt).

The fact that one of the study's primary authors is a long-time paid consultant for the drug industry also gives me pause, particularly since this researcher has been carrying water for the industry for years. I am referring to Ronald Kessler, an epidemiologist at Harvard Medical School, whose specialty is publishing alarmist studies about the increasing problem of mental illness among various populations -- a problem, of course, that can only be solved with drug treatment.

In 1999, for example, Kessler co-authored a widely publicized study showing that depression was afflicting more children than ever before; you may recall this was right around the time that Eli Lilly, Pfizer, GlaxoSmithKline and Forest Labs were ramping up their highly successful efforts to market antidepressants like Prozac, Zoloft, Paxil and Celexa to children and adolescents (and hiding the dangerous side effects of these drugs while doing so).

In 2001, Kessler (and coauthor Martin Keller of Brown University) struck again with a study purporting to show that a significant number of the world's population is plagued by chronic and excessive anxiety -- severe enough to require drugs. Like Keller, whose myriad conflicts I exposed in Side Effects, Kessler was a paid consultant at the time for GlaxoSmithKline and other companies who were also marketing their antidepressants as anti-anxiety agents. In 2007, he co-authored yet another finding declaring that one in four adults have symptoms of mental illness but only a third of them are receiving effective treatments (read drugs).

Then in 2008, in perhaps his most bizarre contribution, Kessler was among the authors of a controversial commentary in Nature that heralded a new era of "cognitive enhancement" -- the use of brain-stimulating drugs in healthy people. Kessler and his co-authors argued that competent adults should be able to freely indulge in such drugs and noted that this was already happening among undergraduate and graduate students trying to boost their academic performance with drugs like Adderall and Ritalin, which contain amphetamines. As one pediatrician who criticized the commentary told the San Francisco Chronicle, their arguments will only "fuel the fire of what we call prescribing pressure" even though the drugs in question have "very significant side effects." To its credit, the Chronicle article noted that Kessler and another co-author of the commentary were consultants to the same drug companies that stood to gain handsomely from their rhetoric.

Kessler currently serves on the board of an advocacy group for child mental disorders with none other than Joseph Biederman, the Mass General Hospital psychiatrist who was a major proponent of expanding the definition of childhood bipolar disorder so that more and more children could be diagnosed with it and treated with powerful anti-psychotic drugs. As I've blogged about here, Biederman came under fire from the Senate Finance Committee for failing to disclose his extensive financial ties to companies that make these anti-psychotics. (Biederman's failures to disclose have been under investigation for the past two years by Harvard Medical School, in what must be the longest investigation in that school's history).

But getting back to Kessler, if you read the fine print at the end of the latest Archives bipolar study, you can see for yourself the long list of drug companies whose generous payments have been padding his salary at Harvard over the years.

That list may help explain why I find the latest pronouncements about the unmet treatment needs of bipolar patients around the world so hard to swallow. What this study mainly indicates to me is that the psychiatry profession and its journal handmaidens are still singing the same tired old tune at the behest of drug companies.

To borrow a better tune (from Joan Baez), when will they ever learn, when will they ever learn?

Monday, February 21, 2011

New study dismantles myth of high drug development costs

I'm embarrassed to admit that when I was a medical reporter for The Boston Globe in the '90s, I (along with many other journalists) would unthinkingly use the $800 million that the pharmaceutical industry said it cost to develop a new drug product. Industry apologists routinely threw out that exorbitant figure whenever anyone complained about high drug prices, and they made sure to note that it was based on "real research," studies done by the Tufts Center for the Study of Drug Development.

What I didn't realize then was that the $800 million was a highly inflated cost estimate produced by a center that received substantial industry funding and has very little credibility. The same goes for the latest cost estimate of $1.3 billion per new drug bandied about by the same folks.

Now, in a newly published report in Biosocieties journal, researchers at Stanford and the University of Medicine and Dentistry of New Jersey have taken apart both of these inflated cost estimates and shown exactly where they are wrong. Don Light and Rebecca Warburton note, for instance, that neither the $800 million or $1.3 billion estimate includes the substantial contributions made by taxpayers through tax write-offs for research and development. As it turns out, taxpayers indirectly pay for about 39 of drug company R&D. In addition, the industry-based figures are based on clinical trials (and number of participants) much larger than actual trials reported by the FDA and the National Institutes of Health.

Perhaps most disingenous, half of the industry estimates are not real costs, but exaggerated estimates of profits that companies might have made if they had not developed the drugs but just put their money into the stock market. As Light and Warburton note, "even if one were to accept the argument that profits foregone should be included as a 'cost' (which no other industry does), US government guidelines call for using three percent, not the 11 percent used by (the Tufts group). Light and Warburton argue that the pharm industry "cannot have it both ways."
They cannot treat R&D costs as if they are a long-term capital investment when tax authorities do the industry the favor of treating them as an ordinary business expense, fully deductible each year.
In their report, Light and Warburton attempt to reach a more realistic estimate for drug development, which, as they acknowledge, is hampered by the fact that the pharmaceutical industry is exceedingly secretive about its R&D data. But building on some of the data gathered by the Tufts Center and research done by Merrill Goozner of gooznews among others, they conclude that the real cost per "self-originated" drug product is closer to $180-231 million, a big reduction from the estimates that continue to be thrown out by industry spokesmen whenever they want regulatory concessions or more government spending. The latest example of this can be found in Christoph Westphal's op-ed in The Boston Globe, which I blogged about here.

The myth of high R&D costs not only exerts a destructive influence on state and federal policy, but it provides drug companies with an excuse for focusing on high-priced me too drugs (like Paxil and Seroquel), instead of developing lower priced drugs that might really save lives -- such as vaccines and treatments for disease. As Light and Warburton note:
The mythic costs of R&D are but one part of a larger, dysfunctional system that gives us mostly new medicines that have few or no advantages and serious side adverse reactions that have become a leading cause of hospitalization and death.

I couldn't have said it better.