April 16, 2008

Ethical Concerns over Ghostwriting in Medical Research

The painkiller Vioxx has been the concern of two new reports about how drug companies influence the interpretation and publication of medical research.

The recent reports say Merck & Co. used ghostwriting to publish several research articles on the drug. The report claims the company frequently paid academic scientists to take credit for the articles. They also contend Merck tried to minimize deaths in two studies that showed that the now withdrawn Vioxx didn't work at treating or preventing Alzheimer's disease.

The reports, published in the Journal of the American Medical Association, have been dismissed as false and misleading by Merck. Five writers of the articles were paid consultants for people who sued Merck over Vioxx's heart and stroke risks and the sixth testified about Merck and Vioxx's heart risks before a Senate panel. Merck maintains that those connections alone make the reports biased.

JAMA editors say Merck is being singled out for a practice that is not at all uncommon. In an editorial, they urge strict reforms, including a ghostwriting crackdown and requiring all authors to clarify their specific roles.

Dr. Catherine DeAngelis, editor-in-chief at JAMA, such policies are already enforced at JAMA but not at many other journals.

"The manipulation is disgusting. I just didn't realize the extent," she said.

DeAngelis says the practices outlined in JAMA can lead editors to publish biased research that can result in doctors giving patients improper and even harmful treatment and medical researchers and journal editors bear some responsibility for those harms.

"We're the ones who have allowed this to happen. Now we've got to make it stop," she said.

Formal drug studies include designing and performing the research, analyzing the results and writing them up for submission to a medical journal. Pharmaceutical companies sometimes pay for a study but have independent scientists perform all those steps. But the studies criticized in the JAMA reports are those where the companies and their own scientists are involved in some or all of these steps.

Vioxx was pulled in 2004 because of its heart and stroke risks. The articles are based on reviews of company documents from court cases over Merck where the company agreed to pay $4.85 billion last November to settle thousands of lawsuits.

One JAMA report says internal company data showed in 2001 that Vioxx patients in two Alzheimer's studies had a higher death rate than patients on dummy pills. The report claims Merck didn't publicize that "in a timely fashion" and provided information to federal regulators that downplayed the deaths.

However, Jim Fitzpatrick, a Merck attorney, said "it's completely not true" that Merck tried to minimize those deaths and that Merck analysis found the excess deaths were not related to Vioxx.

The other JAMA article says one Alzheimer study was designed and conducted mainly by Merck scientists, but when published, the lead authors listed were academic scientists not named in a study draft.

Peter Kim, head of Merck Research Laboratories, said those authors "were intimately involved in the studies." Steven Ferris, an Alzheimer's specialist at New York University, disputed the implication that he had little to do with the study. He said Merck paid him for his work.

Fitzpatrick acknowledged that Merck does use outside firms to write drafts of other studies that later list scientists as first authors, but the scientist are required to review and suggest changes in the manuscript before publication.

The Alzheimer study was published in 2005 in the journal Neuropsychopharmacology. The new editor of the journal, Dr. James Meador-Woodruff, said the journal's policies have been strengthened to ban ghostwriting.