Tuesday, October 28, 2008

Exposing the drug industry's bogus $800 million cost estimate... and other sordid tales

In 2003. researchers at Tufts University published a study showing that it cost drug companies approximately $800 million to develop a new drug and get it approved by the FDA. In the intervening years, the drug industry has used that mind-boggling cost estimate to justify not only the high cost of new prescription drugs but also the need for expedited drug approvals and long patent protection once their drugs were approved.

Well, guess what? As it turns out, the study by researchers for the Tufts Center for the Study of Drug Development was deeply flawed and wildly inflated the actual cost of developing a new drug from start to finish. The study’s flaws and the undisclosed conflicts on the part of its authors were dissected both in a book by Merrill Goozner, the author of gooznews and in a paper that two bioethicists tried to get published in the Journal of Health Economics, which ran the original $800 million estimate.

In a tale that rivals anything out of Machiavelli, the editors of this supposedly respectable journal insisted on massive revisions and cuts in the bioethicists’ submission and only agreed to publish a milder version of their critique after the two threatened to sue the journal for violating academic freedoms. The JHE editors were particularly adamant about cutting from the critique the fact that authors of the $800 million estimate had failed to disclose in their study that they and the Tufts Center for the Study of Drug Development are heavily dependent on drug industry funding (although it didn't fund the cost estimate study).

The two bioethicists, Donald Light, a professor at the University of Medicine and Dentistry in New Jersey, and Rebecca Warburton, a health economist at the University of London, chronicle their convoluted efforts to publish their critique -- in an entertaining piece in the current issue of the Harvard Health Policy Review. They hold their experience up as an example of the need for higher ethical standards on the part of many conflict-ridden healthcare journals.

But wait – the story doesn’t end there. According to Gooznews, the editor of the student-run Harvard Health Policy Review yanked the entire issue of HHPR off the web last week after getting a steamed email from Richard Frank, one of the editors of JHE who also happens to be the Harvard review's faculty advisor and a big-time health economics professor at Harvard Medical School. In his email, Frank said he no longer wanted to be affiliated with the review. As the student editors now admit, “we panicked.”

The current issue is now back online along with an abject apology from the student editors for not having fact-checked the Light/Warburton critique to ensure the veracity of their claims. Apparently, what most incensed Richard Frank was that the HHPR didn’t contact the JHE editors for rebuttal before running the critique.

Funny how some powerful journal editors don't enjoy being on the receiving end of their own medicine.

Wednesday, October 22, 2008

New study of suicide rates reveals: the emperor has no clothes

A bewildered tone seemed to permeate the news reports this week that suicide rates among middle-aged Americans rose sharply from 1999 to 2005. Even the authors of the new analysis in the American Journal of Preventive Medicine said they had no idea why the suicide rate climbed 19 percent among white women ages 40 to 64 and 16 percent among white men of the same age during those six years. As Susan Baker, an epidemiologist at Johns Hopkins School of Public Health said in The Boston Globe yesterday, “I have no idea what’s going on with this age group.”

Could it be that some of the confusion stems from the fact that this new data puts the lie to the drug industry’s long-held contention that antidepressants known as selective serotonin reuptake inhibitors (SSRIs) lead to fewer suicides? After all, during roughly the same time period, antidepressant prescriptions in the United States rose 10 percent, according to a survey by the federal Agency for Healthcare Research and Quality. In a statistical brief published in June 2008, the AHRQ noted that the number of antidepressants purchased in the U.S. rose from 154 million in 2002 to 170 million in 2005. So if antidepressant prescriptions and suicide rates among middle-aged adults were both rising during the first five years of the 21st century, drugs like Prozac, Paxil, Zoloft and Celexa are obviously not stemming the tide.

So what does explain the sharp rise in suicide rates among folks that (unlike teenagers and the elderly) are not known for having a high risk of self-in jury? One explanation could be the economy. Research has shown that suicide rates tend to rise during periods of economic hard times and decline during good times. And as we all know, with the burst of the dot com bubble in 2000, the American economy slid into a recession for the next three or four years.

That correlation has prompted some observers to voice concerns about what might happen with the current financial meltdown. Newsday quoted Alan Berman, executive director of the American Association of Suicidology (AAS), saying he feared the struggling economy could accelerate the trend. “We know that unemployment affects suicide rates and that when people feel a severe economic strain, suicide rates tend to increase among people experiencing this trend,” Berman said.

I find it interesting that neither Berman nor any of the experts quoted in the news raised the issue of antidepressants and what role they may (or may not) play in the rising suicide rates. No one, it seems, least of all organizations like the AAS, which derives a lot of its funding from drug companies, are eager to call attention to the likelihood that the Emperor has no clothes.

Wednesday, October 15, 2008

Let the Sun Shine in on Research Conflicts

The Senate Finance Committee’s probe of physicians with extensive financial conflicts is gathering steam: first, Stanford University removed its psychiatry chief Alan Schatzberg as principal investigator of a federally funded study after Congressional investigators discovered that he owned $6 million of stock in a company whose drug he was studying and touting in medical journals (back story). Then last week, Charles Nemeroff, the dean of American psychiatry, was asked to step down as chief of psychiatry at Emory University after the same investigators found that he failed to fully disclose to Emory much of the thousands of dollars in consulting and speaking fees he was earning each year from companies whose drugs he too was promoting (back story). Most recently, the National Institutes of Health (NIH) has announced that it is freezing a $9.3 million, five-year grant to an Emory University center for research on treatments for depression, according to The Atlanta Journal-Constitution .

But while the NIH has finally been scolded into enforcing its own decades-old conflict of interest policies, legislation that would mandate the public reporting of such financial conflicts remains moribund. The Physician Payment Sunshine Act, introduced last year by Sen. Charles Grassley (R-IA), a ranking member of the Senate Finance Committee, would mandate the public reporting of payments (over $500 in a calendar year) to doctors and other health-care professionals by drug and medical device companies (back story).

Making public such information might make doctors think twice about accepting such large sums of money from the industry. Such disclosures would also make it harder for medical centers and federal agencies to ignore blatant financial conflicts, which, as I point out in my book, Side Effects, can spawn the publication of studies that are flawed and inaccurate. And finally, a payment registry would alert consumers to biases among doctors upon they rely for supposedly objective medical advice. As Grassley has said, “Making information about financial relationships open to scrutiny is the right thing to do.”

This landmark legislation was supposed to have been attached to a Medicare bill that passed this summer. In the process, however, it got watered down and then detached from the Medicare bill, says Dr. Peter Lurie, deputy director of the health research group at Public Citizen in Washington. He says the bill was altered to accommodate the concerns of the pharmaceutical industry and doctors’ groups.

Lurie notes, for example, that there’s a new clause in the bill pre-empting any state law that requires a similar public accounting of payments to doctors, as well as a new provision that delays the reporting of such payments for products under development.

“One could argue that those are precisely the kinds of conflicts we should be most interested in,” Lurie says.

Jill Kozeny, a spokeswoman for Sen. Grassley, said state law was pre-empted to ensure uniform nationwide reporting of financial conflicts. The provision to delay reporting for products under development was added to protect trade secret information. Drug companies had argued for the delay on grounds that they don’t want competitors to know what products they have under development.

Whether in its original or revised form, the bill isn’t going anywhere soon. As Lurie notes, “Congress is dealing with a few other pressing issues right now. Kozeny agrees. She says that "new legislation starting from scratch will be pursued by Sen. Grassley" in January. And it might actually have a chance of passage, Lurie predicts, especially if the country elects a Democratic president in November, along with more Democrats to the House and Senate.

Sunday, October 5, 2008

Conflict Allegations Force Dean of Academic Psychiatry to Step Down: Who's Next?

The academic kingpins who made so money at the trough of Big Pharma are starting to fall. This weekend, Charles Nemeroff stepped down from his post as chairman of Emory's Department of Psychiatry pending an investigation into allegations that he failed to fully disclose the millions of dollars he received in earnings from companies whose drugs he was simultaneously studying and promoting, according to The The Atlanta Journal-Constitution. Congressional investigators led by Senator Charles Grassley found that Nemeroff received $2.8 million in consulting fees from drug companies and failed to report a third of that amount to the university. If true, such failures to disclose would violate federal research rules and Emory's own ethics guidelines.

Nemeroff is just one of several prominent psychiatrists under investigation by the Senate Finance Committee. Others include Alan Schatzberg, chief of psychiatry at Stanford University), Martin Keller, (the psychiatry chief at Brown University) (back story here) and Karen Wagner (head of psychiatry at University of Texas Medical Brand at Galveston).

As Daniel Carlat says, Nemeroff is the creme de la creme of American psychiatrists. And his extensive ties to the drug industry go back for decades. In my book, Side Effects, I tell the story of how Nemeroff played a key role in quashing debate over the emerging suicidal side effects of Prozac and other SSRI antidepressants back as 1991. Indeed, some say it was his elegant presentation on behalf of Eli Lilly at the FDA's hearing that year that helped convince the FDA advisory panel to sweep concerns about the suicidal side effects of these antidepressants under the rug for another 13 years. At the 1991 FDA hearing, Nemeroff failed to disclose that he was earning lucrative consulting fees from Eli Lilly and even owned stock in the Indianapolis-based drug company.

While Nemeroff's conflicts of interest with Eli Lilly flew under the radar screen in the anything-goes decade of drug development in the 90s, Emory officials did raise concerns about his relationship with GlaxoSmithKline, the maker of Paxil, beginning in 2004. As first reported in The Wall Street Journal and The New York Times Friday, Congressional investigators found that between 2000 and 2006, Nemeroff was paid $960,000 by GlaxoSmithKline, yet he disclosed only $35,000 of those payments to Emory. During roughly the same period of time, Nemeroff was the chief investigator on a $3.9 million NIH study on five Glaxo drugs for the treatment of depression.

Yesterday, The The Atlanta Journal-Constitution reported that when Emory's conflict of interest committee first raised a red flag about the psychiatry chief's ties to Glaxo, he promised administrators in 2004 that he would earn less than $10,000 a year in drug company payments from then on. Yet according to documents entered into the Congressional record, Nemeroff went on to earn about $171,000 from Glaxo in 2004.

Emory officials seem finally to be losing patience with their doyen of psychiatry, who by the way brought in millions of dollars in research funding for the university (much as Martin Keller has done for Brown). In an interview with The Atlanta Journal-Constitution, a top Emory official said that "depending on the outcome of the university's own probe, the allegations could lead to the firing of Nemeroff."

Better late than never.