Researchers call on journal to retract notorious Paxil study

The retraction of questionable scientific papers seems to be on the rise, due in large part to increased media scrutiny of scientific misconduct and conflicts of interest among researchers who fail to disclose they have skin in the game, i.e. lucrative financial ties to the drug and medical device companies whose products they are studying. Indeed, retractions are becoming so common that Ivan Oransky, executive editor of Reuters Health News, has started a popular new blog called Retraction Watch.

Sad to say, actual retractions may be the tip of the iceberg. Consider the 2001 study of Paxil in adolescents, the subject of my book, Side Effects. According to a recent article in the British Medical Journal, two academic researchers have called on the journal that published the Paxil trial, known as study 329, to retract it because of the way its authors manipulated and omitted data to make Paxil look safer and more effective in adolescents than it really was. As I reported in Side Effects and subsequent blogs, Dr. Martin Keller, then chief of psychiatry at Brown University and the lead author of this study, miscoded several teenagers who had become suicidal as a result of taking Paxil as being noncompliant instead of as developing adverse side effects from the drug. In addition, Keller and his co-authors concluded that Paxil was effective in treating depression when in fact the drug was not more effective than a placebo on either of the two primary outcome measures of the study and most of the original secondary outcome measures.

As the BMJ article notes:

The drug only produced a positive result when four new secondary outcome measures, which were introduced following the initial data analysis, were used instead. Fifteen other new secondary outcome measures failed to throw up positive results.

It is important to note here that Keller, along with most of the co-authors of this paper, had lucrative consulting or speaking arrangements with GlaxoSmithKline, the maker of Paxil, the full extent of which they failed to disclose when the paper was published. Indeed, as I reported in Side Effects, the 2001 paper itself was ghost-written by Scientific Therapeutics Information (STI), a medical company hired by GlaxoSmithKline and the same one that helped the former psychiatry kingpins Charles Nemeroff and Alan Schatzberg write an entire psychiatric textbook promoting Paxil, according to the New York Times.

Even though peer reviewers for the Journal of the American Academy of Child and Adolescent Psychiatry said that the results of study 329 did not show efficacy for Paxil and had a host of other methodological problems, the journal accepted the study for publication anyway. One wonders whether the fact that one of the co-authors, Dr. Graham Emslie, was on the journal's board at the time had anything to do with its precipitous publication in July 2001.

Before making the decision to put black box warnings about increased suicidal risk of Paxil and antidepressants in children and young adults in 2004, the FDA looked closely at study 329 and concluded that its conclusions were indeed misleading and did not demonstrate the drug's efficacy over placebo; read about this here.

Two academic researchers, Dr. Jon Jureidini,associate professor of psychiatry at the University of Adelaide, and Leemon McHenry, lecturer in philosophy at California State University, are now calling for the retraction of this study, which was used by Glaxo to heavily market Paxil to doctors treating depression in children and adolescents.

As the BMJ piece notes, the Committee on Publication Ethics (COPE) recently advised journal editors to retract a paper if “they have clear evidence that the findings are unreliable.” If any published paper fits this category, study 329 does.

Hat tip to Neuroskeptic for making me aware of the BMJ article.

Panelists to share tips on how to become a health and science blogger

On Wednesday, Jan. 19, I'm moderating a panel on blogging about health and science, sponsored by the New England Science Writers. We are fortunate to have attracted some top-notch bloggers, including Gary Schwitzer, whose HealthNewsReview blog was named the best medical blog of 2009 by Epocrates; Daniel Carlat, of the Carlat Psychiatry blog (who blogged about the upcoming panel here); Ivan Oransky, executive editor of Reuters Health News, who blogs at Embargo Watch and Retraction Watch; and Rachel Zimmerman, who curates the CommonHealth blog for WBUR radio.

It promises to be a very stimulating evening of conversation. You can learn more about the event at the NESW website. And you can follow Tweets from the event by following the Twitter hashtag #nesciblog11.

One more reason why Genzyme might want to resist Sanofi's overtures

For weeks now, The Boston Globe has been running stories about Sanofi Aventi's hostile bid to acquire Genzyme, the Boston-based biotech giant. One recent story talked about how the CEOs of both companies attended the same conference in San Francisco without talking to each other. Genzyme has repeatedly rebuffed Sanofi's offer largely on the grounds that the share price being offered is inadequate.

But here's another reason why Genzyme might want to be wary of Sanofi's overtures: its new CEO, Christopher Viehbacher, comes from GlaxoSmithKline, where as head of its US operations, he presided over some less than savory business decisions. He was, for example, at the helm when top Glaxo officials ignored problems with a production plant in Puerto Rico, according to a former Glaxo employee turned whistleblower. (Glaxo recently agreed to pay a $750 million fine and plead guilty to a felony for manufacturing fraud that led to untold bottles of contaminated meds, mislabeled packaging and incorrect dosages at this plant, according to Pharmalot.)

Viehbacher also headed up the company's US operations during the tempest over news that its anti-diabetes drug, Avandia, increased the risk of heart disease in patients. Even though a meta-analysis done by Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, reported the increased heart risks in a major journal article in 2007, Glaxo executives kept insisting on the safety of their top-selling drug. It wasn't until an FDA advisory panel this past year recommended that Avandia either be pulled from the market or see its sales severely restricted that the company agreed to put black box warnings on the drug; read about this here. And Viehbacher was in charge when the New York State Attorney General's office sued GlaxoSmithKline for not telling doctors and consumers the full story about the suicidal risks of its blockbuster antidepressant, Paxil, and its lack of effectiveness in children and adolescents (which is the subject of Side Effects).

Viehbacher, of course, was not in charge in the late 1990s when company officials first decided to suppress data about Avandia and Paxil's risks. But since he became head of US operations in early 2003, there's a good chance that he was briefed about the dangers of these drugs and chose to do nothing about them, until forced to do so by regulatory officials. Indeed, according to the New York Times, after Nissen's study was published, Glaxo officials conceded that they had known of the drug’s potential heart attack risks for a number of years. But instead of pulling Avandia off the market, they reacted by defending the drug and threatening lawyers who were advertising on TV for patients who might have been harmed by taking Avandia; read about this here.

I have no idea whether Viehbacher was passed over for the top job at GlaxoSmithKline because of the less than ethical corporate behavior that occurred on his watch. But it is one more reason why Henri Termeer, the CEO of Genzyme, might want to think twice before handing over his company to Sanofi-Aventis.

More Americans harmed by prescription drug misuse than illegal drugs

Just last night, a friend of mine mentioned that an acquaintance of hers, a woman in her 50s who was taking prescription drugs for several conditions including diabetes and high blood pressure, died from an overdose of legally prescribed drugs. Which is why I was not surprised by today's story in the New York Times about new data showing that the number of emergency room visits in the U.S. from the misuse of prescription drugs has nearly doubled over the last five years. I was, however, surprised by the news that these prescription overdoses outstrip emergency care for people taking illegal drugs.

Perhaps we should all be shocked by such news -- shocked enough to do something about it. The reason for these latest statistics, which come from the Substance Abuse and Mental Health Services Administration, is obvious: the number of Americans taking prescription drugs has soared nearly 40 percent over the past 10 years and many of those people are imbibing multiple drugs, according to a Kaiser Foundation study. The impact on health care costs is well-known: spending on prescription drugs has doubled in the last decade, thanks in large part to the pharmaceutical industry's successful marketing of expensive drugs to a much wider segment of the American public than ever before.

We've also heard about the occasional celebrity who overdoses on legal drugs -- Heath Ledger and Brittany Murphy to name two, and I've blogged about the over-medicating of children with psychoactive drugs before; see here. But now we are seeing real evidence of the damage this pattern of overuse is wreaking on many people's lives.

There is no question that many health problems are treated or effectively managed through the use of prescription drugs and that some new drugs, particularly treatments for cancer and other diseases, are keeping people alive. But too many Americans are popping pills of questionable efficacy for conditions like high cholesterol, hypertension and depression. And because the drugs are "legally" prescribed by trusted medical professionals, consumers are much too sanguine about the side effects of these medications and how they interact with each other.

The best doctors closely monitor the drugs they prescribe to their patients and are very aware of possible drug interactions. The real danger comes when patients go to more than one doctor to get prescription drugs, a much too common occurrence. That, sadly, was the case with my friend's acquaintance: she had gotten her drugs from several caregivers and simply assumed they were safe.

The Times article today talks about a give-back program instituted by the Drug Enforcement Administration, where people have been able to drop off old or unused drugs at designated locations around the country. But I think health officials should be taking a more aggressive approach, perhaps by requiring patients to sign off with one primary caregiver before they fill their prescriptions. That's just one idea; I'll leave it to wiser heads than mine to come up with some workable solutions.

In the meantime, I hope the media keeps hammering home the message -- that just because the drugs you're taking are legally prescribed doesn't mean they're any safer than the drugs you might buy from the dealer down the street. If the latest finding is any indication, they can actually be more dangerous.