Medical Mischief 3: Ghost Written Medical Journal Articles
Posted: Fri Oct 01, 2010 3:27 pm
Uncovering how one drug company influenced doctors to prescribe HRT
Lorne Brandes September 22
By now, almost everyone knows that taking estrogen and progesterone (also known as hormone replacement therapy, or HRT) in the menopause significantly increases the risk of breast cancer, estimated at 800 additional cases per 1 million HRT users. Since 12 million North American women took HRT at the peak of its use in the late 1990’s, approximately 10,000 annual cases of breast cancer were directly attributable to taking the two hormones.
As an oncologist who has treated this disease for over 35 years, I was not at all surprised when, in 2002, the link between HRT and breast cancer was definitively proven in the Women’s Health Initiative (WHI) study. Wide dissemination of that finding by the press in June, 2003, quickly led to a 50 - 67% drop in prescriptions for HRT. By 2006, a 7 - 9% decrease was observed in the rate of breast cancer, the first reduction in many decades.
Looking back over the years prior to the WHI study, I well remember the many conversations I had with gynecologists about hormones and breast cancer. To say that they and I had differing opinions on the potential risks would be an understatement.
One colleague, in particular, who pushed my wife to "get on board" the HRT bandwagon, honestly believed that only benefit would follow. When my wife expressed her concern about a family history of breast cancer, he minimized any risk, telling her that he had reviewed the literature extensively and was satisfied that, despite widespread long-term use, there was no conclusive evidence of any link between HRT and breast cancer; indeed, some studies actually suggested lower overall mortality, including breast cancer, among users of the hormones.
"When you start having hot flashes and other unpleasant menopausal symptoms, you’ll phone and beg me for a prescription," he told her. Luckily, she followed her own intuition and never made that call.
Now, an article just published online in Public Library of Science (PLoS) Medicine by Georgetown University’s Adriane J. Fugh-Berman, has cast my colleague’s previous beliefs and statement in a whole new and highly disturbing context. Entitled, "The haunting of medical journals: How ghostwriting sold ‘HRT’’’, Fugh-Berman sets the stage for this story in the introduction to her paper:
"In recent litigation against Wyeth [pharmaceutical company], more than 14,000 plaintiffs brought claims related to the development of breast cancer while taking the menopausal hormone therapy Prempro (conjugated equine estrogens and medroxyprogesterone acetate). Some 1500 documents revealed in the litigation provide unprecedented insights into how pharmaceutical companies promote drugs, including the use of vendors to produce ghostwritten manuscripts and place them into medical journals.
"These documents became public when PLoS Medicine and The New York Times intervened in the litigation. Both interveners successfully argued that ghostwriting undermines public health and that documents proving the practice should be unsealed.
"In this Policy Forum article, I use these documents, which are available through PLoS at www.plosmedicine.org/static/ghostwriting.action , to show how industry uses ghostwriters to insert marketing messages into articles published in medical journals."
Fugh-Berman goes on to meticulously document how, between 1996 and 2004, Wyeth hired medical education and communication companies, foremost among them, Princeton NJ’s DesignWrite, to "promote the Premarin family of products". This was accomplished by publishing dozens of ghostwritten (i.e., pre-written) reviews and commentaries in medical journals and supplements. Here is how it worked:
Manuscripts written by DesignWrite were sent to certain "recruited" physicians, usually affiliated with prestigious academic institutions who, presumably to pad their reputations as "opinion leaders", were willing to serve as unpaid "authors".
These individuals were free to modify the manuscript to suit their "comfort level" as long as DesignWrite believed that the revised text still contained the "message" desired by Wyeth (among the main objectives of any review or commentary were "to promote unproven benefits and downplay harms of HRT…to cast competing therapies in a negative light…to mitigate the perceived risks of breast cancer associated with HRT, to defend the unsupported cardiovascular ‘‘benefits’’…and to promote off-label, unproven uses of HRT such as the prevention of dementia, Parkinson’s disease, vision problems, and wrinkles").
In one specifically egregious example provided by Fugh-Berman, a DesignWrite ghostwritten supplement, called Postmenopausal hormone therapy and breast health: A review for clinicians, that was widely disseminated to doctors, "cast doubt on the link between HRT and breast cancer, questioned whether HRT-induced changes in mammographic density were related to increased breast cancer risk, implied that use of estrogen after breast cancer was safe, and promoted the concept that HRT-associated breast cancers were less aggressive cancers".
After reading this exposé, I can only shake my head. While I have previously documented the bad behaviour of big pharma, I am especially appalled by this particular drug company masquerade, one that had terrible consequences for thousands of women, in many instances because their doctors were duped by ghostwritten medical literature, "authored" by experts, into believing that HRT was safe. Yet even more upsetting to me as a physician/oncologist is that it could not have succeeded without the willing participation of certain physicians/academicians of highly questionable moral integrity.
As Fugh-Berman herself concludes, "Medicine, as a profession, must take responsibility for this situation. Naïveté is no longer an excuse. Perhaps physician/investigators should create and uphold a standard where relationships with industry are regarded as unsavory rather than sought after. Academic institutions and medical journals should take a hard line on ghostwriting. Patient care will benefit if physicians draw together as a profession to denormalize relationships with industry and avoid the role of corporate pawns in the future."
I couldn’t agree more.
Lorne Brandes September 22
By now, almost everyone knows that taking estrogen and progesterone (also known as hormone replacement therapy, or HRT) in the menopause significantly increases the risk of breast cancer, estimated at 800 additional cases per 1 million HRT users. Since 12 million North American women took HRT at the peak of its use in the late 1990’s, approximately 10,000 annual cases of breast cancer were directly attributable to taking the two hormones.
As an oncologist who has treated this disease for over 35 years, I was not at all surprised when, in 2002, the link between HRT and breast cancer was definitively proven in the Women’s Health Initiative (WHI) study. Wide dissemination of that finding by the press in June, 2003, quickly led to a 50 - 67% drop in prescriptions for HRT. By 2006, a 7 - 9% decrease was observed in the rate of breast cancer, the first reduction in many decades.
Looking back over the years prior to the WHI study, I well remember the many conversations I had with gynecologists about hormones and breast cancer. To say that they and I had differing opinions on the potential risks would be an understatement.
One colleague, in particular, who pushed my wife to "get on board" the HRT bandwagon, honestly believed that only benefit would follow. When my wife expressed her concern about a family history of breast cancer, he minimized any risk, telling her that he had reviewed the literature extensively and was satisfied that, despite widespread long-term use, there was no conclusive evidence of any link between HRT and breast cancer; indeed, some studies actually suggested lower overall mortality, including breast cancer, among users of the hormones.
"When you start having hot flashes and other unpleasant menopausal symptoms, you’ll phone and beg me for a prescription," he told her. Luckily, she followed her own intuition and never made that call.
Now, an article just published online in Public Library of Science (PLoS) Medicine by Georgetown University’s Adriane J. Fugh-Berman, has cast my colleague’s previous beliefs and statement in a whole new and highly disturbing context. Entitled, "The haunting of medical journals: How ghostwriting sold ‘HRT’’’, Fugh-Berman sets the stage for this story in the introduction to her paper:
"In recent litigation against Wyeth [pharmaceutical company], more than 14,000 plaintiffs brought claims related to the development of breast cancer while taking the menopausal hormone therapy Prempro (conjugated equine estrogens and medroxyprogesterone acetate). Some 1500 documents revealed in the litigation provide unprecedented insights into how pharmaceutical companies promote drugs, including the use of vendors to produce ghostwritten manuscripts and place them into medical journals.
"These documents became public when PLoS Medicine and The New York Times intervened in the litigation. Both interveners successfully argued that ghostwriting undermines public health and that documents proving the practice should be unsealed.
"In this Policy Forum article, I use these documents, which are available through PLoS at www.plosmedicine.org/static/ghostwriting.action , to show how industry uses ghostwriters to insert marketing messages into articles published in medical journals."
Fugh-Berman goes on to meticulously document how, between 1996 and 2004, Wyeth hired medical education and communication companies, foremost among them, Princeton NJ’s DesignWrite, to "promote the Premarin family of products". This was accomplished by publishing dozens of ghostwritten (i.e., pre-written) reviews and commentaries in medical journals and supplements. Here is how it worked:
Manuscripts written by DesignWrite were sent to certain "recruited" physicians, usually affiliated with prestigious academic institutions who, presumably to pad their reputations as "opinion leaders", were willing to serve as unpaid "authors".
These individuals were free to modify the manuscript to suit their "comfort level" as long as DesignWrite believed that the revised text still contained the "message" desired by Wyeth (among the main objectives of any review or commentary were "to promote unproven benefits and downplay harms of HRT…to cast competing therapies in a negative light…to mitigate the perceived risks of breast cancer associated with HRT, to defend the unsupported cardiovascular ‘‘benefits’’…and to promote off-label, unproven uses of HRT such as the prevention of dementia, Parkinson’s disease, vision problems, and wrinkles").
In one specifically egregious example provided by Fugh-Berman, a DesignWrite ghostwritten supplement, called Postmenopausal hormone therapy and breast health: A review for clinicians, that was widely disseminated to doctors, "cast doubt on the link between HRT and breast cancer, questioned whether HRT-induced changes in mammographic density were related to increased breast cancer risk, implied that use of estrogen after breast cancer was safe, and promoted the concept that HRT-associated breast cancers were less aggressive cancers".
After reading this exposé, I can only shake my head. While I have previously documented the bad behaviour of big pharma, I am especially appalled by this particular drug company masquerade, one that had terrible consequences for thousands of women, in many instances because their doctors were duped by ghostwritten medical literature, "authored" by experts, into believing that HRT was safe. Yet even more upsetting to me as a physician/oncologist is that it could not have succeeded without the willing participation of certain physicians/academicians of highly questionable moral integrity.
As Fugh-Berman herself concludes, "Medicine, as a profession, must take responsibility for this situation. Naïveté is no longer an excuse. Perhaps physician/investigators should create and uphold a standard where relationships with industry are regarded as unsavory rather than sought after. Academic institutions and medical journals should take a hard line on ghostwriting. Patient care will benefit if physicians draw together as a profession to denormalize relationships with industry and avoid the role of corporate pawns in the future."
I couldn’t agree more.