Covering Pharma Ghostwriting: Five Tips from PLoS Medicine's "The Haunting of Medical Journals"
Adriane Fugh-Berman has been leading the charge against the use of drug company-sponsored ghostwriters to craft scientific articles for publication in seemingly legitimate journals. She has been a paid expert witness on behalf of plaintiffs in the litigation over hormone replacement therapy drugs, and she directs PharmedOut, a project at Georgetown University that aims to scrub industry influence from medical training. As a result, she is very familiar with thousands of documents that were recently made publicly available through the Drug Industry Document Archive.
Her new "Policy Forum" piece in PLoS Medicine, published today, provides a richly annotated history of, as she puts it, "The Haunting of Medical Journals: How Ghostwriting Sold ‘HRT.'" Antidote recommends the entire piece for anyone interested in pharmaceuticals, but here are five great tips to be gleaned from it:
1. Choose your words wisely. The reason Fugh-Berman puts "HRT" in quotation marks is because "hormone-replacement therapy" is a concept created by the drug industry, not by clinicians. It's subtle, but the term implies that when women lose their ability to produce estrogen as they age that they are lacking something all normal women should have and therefore need to replace that hormone through drugs. Dr. David Orloff, the former head of the FDA division that oversaw hormone drugs, told an FDA advisory committee in October 2003 that hormone replacement therapy, was "a term we hold as now clearly inappropriate if not frankly misleading." As Fugh-Berman notes, the drugs are "now properly termed menopausal hormone therapy, or HT."
2. Name names. Fugh-Berman lists dozens of ghostwritten journal articles and includes the names of the researchers involved. Three names will be familiar to regular readers of Antidote:Dr. David Archer, Dr. Gloria Bachmann, Dr. Leon Speroff, and Dr. John Eden. Eden comes in for particular criticism for signing his name to a ghostwritten article "built around a single message" in 2003. "Notes from a publication planning meeting held in 2000 read: ‘ John Eden was suggested as the author of a breast cancer paper questioning the role of progestins as a causative factor'. Discussion points the ghostwriter was told to put in the paper included ‘why progestins may not be responsible for the incidence of breast cancer in hormone replacement therapy (HRT) users'. The published article states, ‘ results from epidemiologic studies are inconsistent and mechanistic studies have not provided a physiologic foundation to implicate progestin in the pathogenesis of breast cancer'.
3. Compare notes. Fugh-Berman shows side-by-side the marketing messages that the ghostwriting firm DesignWrite, working on behalf of Wyeth, attempted to implant in scientific journals to pump up the Wyeth drug Prempro and the final result. Here is one marketing message: "When compared to Prempro 2.5, the 0.45/1.5 HRT dose results in an improved rate of amenorrhea [vaginal bleeding], particularly in the early cycles.'' Here is what Archer wrote in the journal publication: "The increased rates of amenorrhea that we observed in women treated with lower doses of CEE and MPA compared with those taking the most commonly prescribed CEE/MPA regimen provide strong evidence that lower-dose HRT reduces vaginal bleeding.'' Take away message: if your patient is bleeding too much with Prempro 2.5, try our new improved low-dose Prempro!
4. Beware the loudest critics. In 1998, researchers involved in the Heart and Estrogen/progestin Replacement Study (HERS) found that hormone therapy did not prevent cardiovascular disease. As Fugh-Berman writes, "Soon after HERS found no evidence for cardiovascular benefit for HT, numerous articles attacking the trial appeared in the medical literature. A 2001 article authored by Thorneycroft states: ‘The results of HERS do not contradict the weight of epidemiologic study findings showing a primary protective CVD effect in longer-term HRT users. Indeed, because of possible serious flaws in the study, a protective benefit of HRT for secondary CVD prevention cannot be ruled out.' Some articles were ghostwritten. For example, a 2000 article authored by Mosca states, ‘‘Remarkable consistency among epidemiologic studies supports a cardioprotective role of ERT.'"
5. Watch for the next move. The benefits of HT for preventing cardiovascular disease were knocked down, as were the benefits of HT in preventing stroke or saving patients from Alzheimer's disease. But that didn't stop Wyeth, its ghostwriting firm and its pliant group of researchers. Fugh-Berman shows how the company never was truly defeated. If a HT was shown to be harmful or less than effective in one arena, Wyeth would pivot. If it can't save you from a stroke, it can at least make you look younger.
"Ghostwritten articles supporting this message included a 2005 article by Brincat that states, ‘Estrogen treatment in post-menopausal women has been repeatedly shown to increase collagen content, dermal thickness, and elasticity.' A 2004 article by Bachmann and Leiblum states, ‘Continual estrogen loss often leads to numerous signs and symptoms, includingchanges in the vascular and urogenitalsystems. Alterations in mood, sleep, and cognitive functioning are common as well.These changes may contribute to lower self-esteem, poorer self-image, and diminished sexual responsiveness and sexual desire'."