Side Effects: Merck is not the first pharmaceutical company to use ghost-writers

An article in The New York Times a few days ago about Vioxx almost makes it sound as if the ghostwriting of new drug studies by pharmaceutical companies is a new and relatively unknown practice. In fact, the ghost-writing of research by pharmaceutical companies eager to publicize positive results about their new drugs in prestigious medical journals has been a widespread industry practice for years.

David Healy, a psychiatrist and professor at the University of Wales in England, was among the first to write about the practice of ghostwriting by drug makers a number of years ago. In several scholarly articles, Dr. Healy drew attention to the fact that Pfizer had ghost-written a series of positive research studies for its blockbuster antidepressant, Zoloft. In a review of internal Pfizer documents unsealed in lawsuits, Healy found that just as Merck did with Vioxx, a Pfizer was preparing a number of Zoloft studies for publication before they had identified authors for the studies. On an internal list of these in-process studies, Pfizer had put question marks next to the line for possible authors.

As my forthcoming book reveals, GlaxoSmithKline resorted to a similar scheme in its effort to publicize the results of a study purporting to show the effectivenes of Paxil in treating depression in adolescents. Unsealed documents from a lawsuit against GlaxoSmithKline show that a consultant for Glaxo ghost-wrote the first draft of this research and then sent it to the principal authors for review and approval. The Paxil study was rejected by JAMA(in large part because its positive conclusion about the antidepressant was not backed up by the actual data in the study), but the study was eventually published in the Journal of the American Academy of Child Psychiatry.

The article in the http://www.nytimes.com/2008/04/16/business/16vioxx.html?ex=1366084800&en=ef29a5f6ea0a6e76&ei=5124&partner=permalink&exprod=permalink" based its news on a recent study in JAMA that looked at documents unearthed in lawsuits over Vioxx, which was pulled from the market in 2004. As these documents show, Merck also hired ghostwriters to draft Vioxx research studies, then the company found prominent authors who would be willing to attach their names to the studies for publication in medical journals. As David Egilman, an associate professor in community health at Brown University, tells Pharmalot blogger Ed Silverman, “By having no outside researchers look at data or be in control of a study allowed Merck to manipulate the trials. They were able to use spin to create the impression that the drug didn’t kill people, which it did."

As Dr. Joseph S. Ross, the lead author of the JAMA article says, this practice raises broad questions about the validity of much published drug research. Indeed, I would argue that it raises questions about the credibility of the entire system of drug testing and research. And now, finally, the mainstream media is paying attention.

Side Effects: Is the FDA making it easier to market drugs to doctors for unapproved uses?

You’d think that with Congress shining a spotlight on the financial ties between doctors and drug companies, the FDA might sense the prevailing winds and move toward restricting the marketing of drugs to doctors for unapproved uses. But no, the nation’s premier public health agency appears to be moving in the opposite direction. FDA officials recently announced proposed guidelines that would make it easier for drug companies to promote off-label uses to doctors without studying whether the drugs are effective or safe for such uses. Such a move would mean more off-label prescriptions of drugs that can cause dangerous side effects. Remember Paxil, Zoloft, Vioxx and Avandia? All of these drugs were approved for one condition and then widely prescribed off-label for other conditions. Such widespread usage ended up harming people, many of whom shouldn’t have been taking the drug in the first place.

Take Vioxx, as just one example. The heart problems associated with the drug became apparent only after it was widely prescribed off-label to patients who were unlikely to benefit from it. Similarly, the widespread prescribing of Paxil and other SSRI antidepressants for off-label uses spurred an increase in suicidal thoughts and behaviors among children and young adults taking these drugs. (With both these cases, there is evidence that the makers of the drugs knew about these potentially dangerous side effects but with-held the information from doctors and the general public for many years. www.sideeffectsthebook.com.) One would think the FDA would want to restrict such off-label usage, not promote a policy that would effectually expand it.

It is, of course, illegal for the pharmaceutical industry to market drugs for off-label uses to physicians and consumers. For the past decade, however, drug makers have been allowed to give physicians studies touting off-label uses that they themselves funded and got published in medical journals. But the drug companies could only hand out these studies to doctors if they gave the reprints to the FDA beforehand and promised to seek approval of the uses discussed in them. However, the law that instituted that requirement (the FDA Modernization Act) lapsed in 2006. In the latest proposed guidelines, the FDA has now abandoned the requirement that drug and device makers provide off-label studies to the agency beforehand or promise to seek approval of the discussed uses. In a recent article in the New England Journal of Medicine, Dr. Randall Stafford, an associate professor of medicine at Stanford Prevention Research Center, criticized the agency’s “backward shift,” noting that it “seems oddly incongruous with current pressures aimed at improving post-marketing drug evaluation.” http://content.nejm.org/cgi/content/full/358/14/1427?query=TOC

Stafford called on the FDA to do more to regulate off-label use, not less. The FDA is accepting comments on these draft guidelines through April 21. Let your voice be heard!