For the third time in three years, a prominent medical journal has criticized Merck & Co. Inc. for misrepresenting research on its now-withdrawn pain reliever Vioxx.

Merck endangered patients in 1999 when it disguised a marketing program as a scientific trial of its now-withdrawn Vioxx, according to an article and an accompanying editorial published today in the Annals of Internal Medicine.

Merck responded that the study in question answered important scientific questions. The Whitehouse Station, N.J., company also noted that the Annals researchers had worked as paid consultants for lawyers representing plaintiffs who claimed Vioxx caused heart attacks or other problems. The litigation ended when Merck agreed to pay $4.85 billion to plaintiffs who reported suffering heart attacks or other problems while taking the drug.

The editors of the Annals of Internal Medicine, which is based in Center City, said the journal's findings may point to a broader problem in the pharmaceutical industry. Drug companies have long been suspected of enlisting doctors in trials solely to get doctors in the "habit of prescribing a new drug," the editors said in what they described as an unusual, if not unprecedented, editorial.

These are known as "seeding" trials.

The editorial says "seeding trials" pay doctors involved in them to consult with the drug company plus a fee for each patient they enroll.

"The physician becomes invested in the drug's future and praises its good features to patients and colleagues," the editorial says. "Unwittingly, the physician joins the sponsor's marketing team."

While the Annals editors describe the findings in today's article as "smoking gun" evidence that such trials occur, some of the Merck documents cited in today's study had previously been reported in the New York Times.

Dr. Kevin P. Hill, the study's lead author, said he and his co-authors analyzed about 2,000 documents submitted as part of Vioxx litigation. While Hill and his coauthors worked for plaintiffs' lawyers in the Vioxx litigation, the funding for this research came from the Robert Wood Johnson Foundation.

"I think patients sign on to trials to help themselves or, altruistically, to help others down the road," Hill said in an interview. "But in this case they were really risking their own health for marketing purposes."

He cited a memo from two top Merck executives nominating the study, called ADVANTAGE, for an internal marketing award.

Hill, now a psychiatry fellow at McLean Hospital in Massachusetts, also pointed to excerpts from an e-mail from Edward Scolnick, head of the research division at Merck Research Laboratories, who worried that the ADVANTAGE study risked disclosing data to the Food and Drug Administration that could cause problems for Vioxx.

"Small marketing studies which are intellectually redundant are extremely dangerous. . . .," Scolnick said.

Merck, however, said the ADVANTAGE (for Assessment of Differences between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness) study did answer new scientific questions. Those questions included whether Vioxx or Naproxen, an older pain reliever, caused fewer side effects such as abdominal pain, heartburn and diarrhea, said Dr. Jonathan Edelman, executive director of the global center for scientific affairs, Merck Research Laboratories. A previous study reviewed different gastrointestinal problems, such as peptic ulcers. Any use of ADVANTAGE data for marketing happened separately from the scientific study, Edelman said.

Gastrointestinal problems were central to the battle between Vioxx and rival Pfizer Inc.'s Celebrex. Both companies claimed that their drug caused fewer gastrointestinal side effects.

Edelman also said the ADVANTAGE study was "most emphatically not done by the marketing department" and was staffed by doctors and others with medical-research backgrounds.

In an editorial accompanying Hill's article, Annals editor Dr. Harold C. Sox said Merck did not tell his publication that ADVANTAGE was marketing-driven when it published the results of the study in 2003.

Dr. David Egilman, a coauthor with Hall, brought the evidence to Sox's attention. Sox said he could think of only one other instance in his seven years as editor that the Annals had published an editorial like today's. He said he did not believe the researchers' work as experts for plaintiffs' lawyers was likely to bias their work.

During spring, the Journal of the American Medical Association accused Merck of hiding the dangers of Vioxx while its employees ghostwrote papers praising the drug and giving credit to leading professors who did little work. In late 2005, the New England Journal of Medicine posted an "expression of concern" on its Web site, saying researchers had made Vioxx appear safer than it was by omitting three of 20 heart attacks in a study.

Vioxx, prescribed to reduce pain in arthritis and other ailments, was a blockbuster drug that rang up more than $11.2 billion in sales for Merck from 1999 to 2004, company reports show. The firm, which employs roughly 12,000 people at extensive operations around West Point, Montgomery County, voluntarily took Vioxx from the market Sept. 30, 2004, amid concerns over heart attacks.

Contact staff writer Miriam Hill at 215-854-5520 or hillmb@phillynews.com.