The August 2011 PLoS Medicine article, Legal Remedies for Medical Ghostwriting discusses legal approaches to combat the prevalent practice of published “academic” studies, which are actually ghostwritten at the behest of pharmaceutical companies. That is right, in many cases the so called “authors” never even see the manuscript before it is published. This troubling practice appears to be extremely wide-spread. It has given rise to a specialized industry of firms who ghostwrite academic studies for pharmaceutical companies.
In 2005, Adriane Fugh-Berman published an account of how an attempt was made to recruit her as the sham author of a paper promoting a pharmaceutical product, see: The Corporate Coauthor. “Drug marketing techniques include the sponsorship of articles signed by academic physicians or researchers and submitted to peer-reviewed medical journals. Some of these articles are authored or coauthored by ghostwriters who work for pharmaceutical companies or medical education companies hired by pharmaceutical companies. . . The true incidence of corporate ghost authorship or coauthorship is unknown; anecdotally, many of my colleagues who speak at national meetings have been approached with such offers. The arrangements made between drug companies or MECs and physicians are often discreet; negotiations are done over the phone, or in telegraphic e-mails. Paper trails are minimized; there are no invoices, no contracts, and no written scope of work. Payments may not be traceable to services rendered, or to the sponsoring pharmaceutical company.”
Lawsuits Reveal The Industry Secret
The true wide-spread nature of this practice has been more-fully revealed by documents obtained during the litigation discovery process of various lawsuits brought against pharmaceutical companies. Scientific Therapeutics International is one of the “medical education companies” discussed by Dr. Fugh-Berman.
STI was revealed to have ghostwritten studies promoting Vioxx for Merck.(ref) In the case of Vioxx, it turns out that Merck was involved in practically all published studies either directly, or indirectly through front “scientific” organizations, like STI, which sent drafts of studies to Merck for approval and revisions, even though the prestigious academics, listed as principal authors in publications, often never saw any manuscripts. According to the NY Times, “In some cases, Merck’s marketing department was involved in developing plans for manuscripts. . . In 16 of 20 papers that reported on clinical trials, a Merck employee was designated as the author of the first draft of the manuscript. But an outside academic scientist was listed as the lead author when the study was published. . . One paper involved a study of Vioxx as a possible deterrent to Alzheimer’s progression. The draft of the paper, dated August 2003 identified the lead writer as “External author?” But by the time the paper was published in 2005 in the journal Neuropsychopharmacology, the lead author was listed as Dr. Leon J. Thal, a well-known Alzheimer’s researcher at the University of California, San Diego. The second author listed on the published Alzheimer’s paper, whose name had not been on the draft, was Dr. Ferris, the New York University professor.” Dr. Ferris admitted to USA Today that although he reviewed whether subjects had AD, he played no role in analyzing the study’s data, and never saw a manuscript.
STI emails show that when one of the Vioxx “authors” returned a payment to STI saying “I really do not feel it is appropriate to be paid for this type of work,” the STI employee asked supervisors, if he should offer to reissue the check as a “research grant”. See Grassley.
CASPPER, the Unfriendly Ghost
According to the Associated Press, discovery in the Paxil birth defect litigation revealed that GlaxoSmithKline actually named a ghostwriting program “CASPPER”, which recruited medical scientists to be the “authors” of studies promoting their best-selling drug, Paxil. Between 2000 and 2002, articles from the CASPPER program appeared in five medical journals. The CASSPER ghostwriting brochure shows that the intent of CASSPER was to flood the market with ghostwritten information. It stated: “Paxil Product Management has budgeted for 50 articles for 2000.”
From Ghostbusting in Paxil Birth Defect Litigation: Expert witness, Dr. David Healey testified at the Paxil trial, “at least half, maybe more, of the articles that appear in major journals under the names of the best known people in the field, are ghostwritten when they have to do with pharmaceutical drugs,” he told the jury. “If they have to do with the drugs that are being sold at the moment, the ones that are fashionable at the moment, then these articles are highly likely to be ghostwritten even when they appear in the very best journals,” Healy said.
Who actually wrote many of the Paxil studies?
While testifying, Healy told the jury that he was familiar with companies that Glaxo hired to ghostwrite literature and put other doctors’ names on it. “I think the leading firm in the field was one called STI,” he said. “This stands for Scientific Therapeutics Information.” In a December 14, 2009 report on Pharmalot, Ed Silverman noted that Glaxo had published a list of fees paid out to US healthcare professionals for speaking and consulting services for the three month period of April 1, 2009 to June 30, 2009. “By its own tally, Glaxo paid $14.6 million to approximately 3,700 US docs and other healthcare professionals,” he reported. Those figures are direct payments by GSK, and do not include payments made by contracted firms, like STI.
GSK ended up settling the birth defect and other lawsuits last year for $1 billion, which is a pittance compared the the many billions it makes from sales of this dangerous product. See: GSK settles Paxil suits for reported $1B
NIH Funds STI Ghostwritten Study: Last month, a University of Pennsylvania psychiatry professor, Jay Amsterdam accused several colleagues (including the chair of his own department) of professional misconduct by allowing a study funded by the NIH to actually be written by STI working for GSK. “The published manuscript was biased in its conclusions, made unsubstantiated efficacy claims and downplayed the adverse-event profile of Paxil.” According to U Penn investigator, Dr. Karl Rickels, the so-called authors “never had a chance to review or even just see the manuscript.” Despite, Dr. Amsterdam’s complaints, and Dr. Rickels report, U Penn president, Amy Gutmann took no action. Ironically, Dr. Gutmann is the chair of US President Barack Obama’s bioethics commission. For this reason POGO (Project on Government Oversight) has called for her removal. “If Dr. Gutmann cannot deal with bioethical concerns on her own campus, with her own faculty, then how can taxpayers trust her to advise the President of the United States?”
Paxil Is a Dangerous Drug
Besides causing birth defects, Paxil is addictive, causing severe withdrawal effects, and can lead to suicide, especially in adolescents.
From ABCNews: “New documents uncovered by ABC News suggest GlaxoSmithKline, the maker of the popular antidepressant Paxil, failed to disclose important information about the possibility of an increased risk of suicidal behavior in some children taking the drug, as well as serious withdrawal symptoms when some patients stop taking Paxil — While Congress and the FDA have held hearings questioning GlaxoSmithKline and other drug manufacturers about suppressing studies that cast their products in a negative light, “Primetime Live” has obtained actual copies of GlaxoSmithKline reports from its own internal studies. In these studies, some children showed the same types of suicidal thoughts and behaviors that parents had for years claimed their children were exhibiting. According to these documents, internal studies by GlaxoSmithKline concluded that Paxil had little or no effect in treating depression in children and adolescents. And as far back as 1997, the company was aware of studies reporting suicide-related behaviors in young patients taking the drug. In spite of this information, GlaxoSmithKline distributed a memo to its sales force in 2001 touting the drug’s “remarkable efficacy and safety in the treatment of adolescent depression.” See the memo. Additionally, the internal documents reveal GlaxoSmithKline had scientific evidence Paxil could cause mild to severe withdrawal symptoms in some patients when they abruptly stopped taking the drug. A document the company distributed to sales staff referred to “withdrawal symptoms” and said they included problems like dizziness, nausea, fatigue, insomnia and nightmares, but advised the sales representatives to use the less-alarming term “discontinuation symptoms.” The documents suggest GlaxoSmithKline’s sales strategy was to downplay this information in order to maintain its share of the billion-dollar antidepressant market. “This is about money,” said Rep. Henry Waxman, D-Calif., who is on a congressional committee investigating antidepressant manufacturers. “This is not about science, because what they’re doing is withholding the scientific information, suppressing the studies that could have a negative impact on their sales and their profits.”
“In addition to the investigation by Congress, the New York attorney general’s office in June of this year leveled charges of consumer fraud against GlaxoSmithKline. The lawsuit alleged that the drug giant repeatedly concealed information about Paxil from doctors. The attorney general’s lawsuit noted that GlaxoSmithKline conducted at least five studies of Paxil’s use in children and adolescents, but the company only published one of these studies — a decision at the heart of the controversy. In 2005, a federal judge ordered GSK to cease all advertising that Paxil was not addictive. GSK has settled thousands of addiction related lawsuits, and hundreds of suicide-related cases. These settlements are very small compared the the amount of money that GSK continues to make by selling this dangerous drug.
Does Paxil Work?
GSK’s own internal documents show they knew it was ineffective at treating adolescents. They also knew it was addictive, and could lead to suicide, yet they decided to market the drug to adolescents anyway. What about adults? Are Paxil and similar drugs are effective at treating adult depression? A meta-analysis published in the JAMA last year concludes that Paxil and similar antidepressants are only effective at treating very severe cases of depression. In the majority of patients being prescribed the drugs, with milder symptoms, they are no better than a placebo. Despite this fact, the rate of prescribing antidepressants for patients with no diagnosis for depression has skyrocketed. In 2007, 73% of patients prescribed antidepressants by primary care physicians had no diagnosis for any type of depression! See: Proportion Of Antidepressants Prescribed Without A Psychiatric Diagnosis Is Growing. Previous meta-analyses of data obtained from published trials (mostly funded by pharmaceutical companies) have similarly failed to find any benefit from taking antidepressants.
From the 2005 publication Efficacy of antidepressants in adults:
1. Recent meta-analyses show selective serotonin reuptake inhibitors have no clinically meaningful advantage over placebo.
2. Claims that antidepressants are more effective in more severe conditions have little evidence to support them.
3. Methodological artifacts may account for the small degree of superiority shown over placebo.
4. Antidepressants have not been convincingly shown to affect the long term outcome of depression or suicide rates.
5. Given doubt about their benefits and concern about their risks, current recommendations for prescribing antidepressants should be reconsidered.
Pharma Spends More on Promotion than R&D.
Accurate information on promotional expenditures cannot be readily obtained from public financial disclosures, like annual reports, because the accounting category of “marketing” includes many other operating expenses. Also, pharma companies are multinational with multiple subsidiary entities, etc. Still, most conservative estimates show that pharma spends (in the U.S.) at least twice as much on promotion as on R&D, clearly demonstrating that it is a marketing-driven, rather than a research-driven industry. See: The Cost of Pushing Pills
These estimates surely understate the true promotional expense, since they don’t include ghostwriting, off-label promotion, and many other hidden expenses. Fees of “research” firms are usually for promotional purposes, not research. As mentioned, phase IV trials (a large percentage of R&D) are done mainly for their promotional value, not true research purposes, etc. See, also: Pharmaceutical Marketing – Time for Change.
Disease Mongering (2008): “Disease mongering is the selling of sickness that widens the boundaries of illness in order to grow markets for those who sell and deliver treatments. It is a process that turns healthy people into patients, causes iatrogenic harm, and wastes precious resources . Disease mongering is the contemporary form of “medicalisation.” It is a process now driven by both corporate and professional interests, and it has become part of the global debate about health care. International consumer groups now target drug company–backed disease mongering as a wasteful threat to public health , while the global pharmaceutical industry has been forced to defend its promotion of “lifestyle” medicines for problems like slimming and sexual difficulties .” See PLoS Medicine Disease Mongering Collection.
Does Pharmaceutical Promotion Improve Patient Outcomes?
The pharmaceutical industry justifies the enormous amount spend on promotion, claiming that it provides valuable information to both patients and practitioners. However, a recent study found that pharmaceutical promotion does not improve patient outcomes. The 2010 report Information from Pharmaceutical Companies and the Quality, Quantity, and Cost of Physicians’ Prescribing: A Systematic Review relates “Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians’ prescribing. With rare exceptions, studies of exposure to information provided directly by pharmaceutical companies have found associations with higher prescribing frequency, higher costs, or lower prescribing quality or have not found significant associations. We did not find evidence of net improvements in prescribing, but the available literature does not exclude the possibility that prescribing may sometimes be improved. Still, we recommend that practitioners follow the precautionary principle and thus avoid exposure to information from pharmaceutical companies.”
Most Pharmaceutical Advertising Does Not Comply with FDA Guidelines.
In the U.S. all pharmaceutical marketing is regulated by the FDA, which establishes advertising guidelines. Unfortunately, these guidelines are seldom enforced. One 2009 sample of advertisements direct toward physicians found that only 18% complied with FDA guidelines, see the 2011 publication Adherence of Pharmaceutical Advertisements in Medical Journals to FDA Guidelines and Content for Safe Prescribing. Although the FDA should revise their advertising guidelines to be less subjective, this would still be little more than a symbolic exercise. Given the sheer volume of medical industry advertising, and current budgetary constraints, it is unlikely that any guidelines would be adequately enforced, or given serious consideration.