Two new studies suggest drugmaker Merck and Co. manipulated data on its withdrawn drug Vioxx, was slow to disclose adverse events associated with the painkiller, and used academic researchers to enhance the credibility of scientific studies largely written by Merck employees. One Canadian researcher, Dr. Claire Bombardier of Toronto’s Mount Sinai Hospital, denied this week that she was involved in manipulating data.
The articles were based on company documents made public as a result of thousands of lawsuits levelled against Merck and Co. after it withdrew the former blockbluster medication from worldwide markets in September 2004 because studies revealed people who used it were at higher risk of heart attacks and strokes.
They were published Wednesday in the Journal of the American Medical Association, which also ran a damning editorial calling on everyone in the business of clinical research to pull up their socks, starting with doctors. “The profession of medicine in every aspect – clinical, education and research – has been inundated with profound influence from the pharmaceutical and medical device industries,” editor Dr. Catherine DeAngelis and deputy editor Dr. Phil Fontanarosa wrote. “This has occurred because physicians have allowed it to happen and it is time to stop.” DeAngelis and Fontanarosa said the Merck actions are not unique in the industry.
Merck responded immediately, denying that it had withheld data and insisting it was committed to high standards of scientific integrity and ethics.
Canadian rheumatologist Dr. Claire Bombardier, who was the lead author of a major Vioxx paper, insisted Tuesday she was not used to enhance the credibility of questionable studies. Bombardier was the first author of the Vigor trial, published in the New England Journal of Medicine in 2001. The study, as reported, suggested Vioxx caused significantly fewer gastric bleeds than the pain relieve naproxen.
The New England Journal later chastised Bombardier and her co-authors for failing to report three deaths that occurred after the trial stopped and for editing out other adverse events shortly before submitting the paper for publication.
In an e-mail, Bombardier insisted accusations of ghost writing could not be applied to the Vigor trial. “Let me dispel any doubt. Our paper was not ghost written. … Dr. Lane, Dr. Reicin and I worked diligently, along with our co-authors who were members of the Vigor steering committee,” Bombardier said. “We were, and remain, proud of the important contribution our article made to medical science.”
One of the recent studies, by researchers at Mount Sinai School of Medicine in New York City, lays out evidence of wide scale use of “guest authorship and ghost writing” of medical studies on Vioxx.
Articles about the drug were frequently written in-house, the authors suggest, but an academic not on Merck’s payroll would be lined up to serve as first author. The first author on a scientific paper is typically the person who led the work; having an external scientist take that role lent an “appearance of objectivity” to the studies, said Dr. Joseph Ross, first author of this piece in JAMA.
“We had the opportunity to essentially peer through a keyhole and see how physicians and a pharmaceutical company wrote articles that were then published in medical journals,” Ross, who was part of an expert witness team for plaintiffs in Vioxx lawsuits, said Tuesday.
That doesn’t surprise Dr. Muhammad Mamdani, director of the Applied Health Research Centre at Toronto’s Li Ka Shing Knowledge Institute of St. Michael’s Hospital. Mamdani briefly joined for drug giant Pfizer in 2006 before returning to an academic appointment the following year.
“I think people may underestimate how much the financial benefits of such a relationship can influence academic physicians,” Mamdani said. “In my experience in industry, it was not very difficult to find physicians who would be I guess susceptible to shaping their opinions with the right financial inducement.”
The JAMA editorial called on all players — drug companies, regulators, authors, journals and the scientists who assess or “peer-review” articles for medical journals — to address the problems.
The editor of the Canadian Medical Association Journal applauded the call. “Industry influence is pervasive and we know it’s there. We have to have mechanisms in place to mitigate it or at least make it transparent,” Dr. Paul Hebert said. “None of us is there to suppress information. We’re in the job of publishing the damned stuff. But what we’re hoping to do … is to get the messages out clearly, that the data be presented fairly and that it be interpreted properly.”
Arthur Schafer, director of the Centre for Professional and Applied Ethics at the University of Manitoba, said fixing the system is imperative.
“The issue of research integrity is the major crisis facing modern medicine,” he said from Winnipeg. “Doctors are taught that modern medicine is evidence-based and that’s what separates it from superstition and folk tales. And once the public comes fully to realize how skewed so much of the evidence is when the studies are funded by drug companies, I think we’re going to have a crisis of confidence of catastrophic proportions.”
-with a report from CP