Merck’s ADVANTAGE trial misled patients, claim researchers
The allegations are made in a study published in the Annals of Internal Medicine (August 19), which concludes that Merck’s ADVANTAGE study of Vioxx “is an example of marketing framed as science.” AIM published the original results of the trial in 2003.
Studies that are dressed up as bone fide research but in fact market the test product to doctors are known as ‘seeding’ studies, and in the case of ADVANTAGE the researchers claim the trial was conceived by Merck’s marketing division.
The stated aim of the trial was to try to measure the gastrointestinal safety of Vioxx compared to naproxen, an older and cheaper pain reliever, in patients with osteoarthritis.
However, the researchers, led by Yale University’s Harlan Krumholz, maintain that ADVANTAGE did not pose a novel study questions, and was effectively designed to engage future prescribers at a time when the drug was just reaching the market.
They draw their conclusions after reviewing Merck’s internal and external correspondence, obtained by court order, as well as documentation used in two lawsuits brought against Merck in the wake of Vioxx’ withdrawal from the market in 2004 after being linked to cardiovascular side effects
“The execution of the study by the marketing division of a company and, most important, the failure to disclose the true objectives of the trial to patients, investigators, or institutional review board members is not in the best interests of patients, the profession, or society.”
For its part, Merck insists that “the authors appear to purposely fail to distinguish between the various departments of Merck's ... organization, including its scientific research and marketing departments.”
Executive Director for Global Center for Scientific Affairs at Merck Research Laboratories, Jonathan Edelman, said in an open letter that the trial answered an important clinical question by concluding that concomitant use of aspirin did not have an impact on the gastrointestinal toxicity profile of Vioxx and naproxen.
“ADVANTAGE was a double-blind, randomized, controlled clinical trial with a legitimate scientific purpose designed to answer previously unanswered questions about the use of Vioxx in osteoarthritis in a primary care setting. It was not a seeding study.”
Merck also points out that the researchers all represented plaintiffs in lawsuits filed after Vioxx was taken off the market, a fact that is disclosed by the researchers in the AIM report.
But the team maintain that it was during this legal process that they uncovered evidence that the trial was a seeding study whilst reviewing court documents.
An editorial accompanying the study, co-authored by AIM editor Harold Sox, suggests that seeding studies are common practice in the pharmaceutical industry.
“The company flatters a physician by selecting him because he is ‘an opinion leader’ and incorporates him in the research team with the title of ‘investigator.’ Then, it pays him good money: a consulting fee to advise the company on the drug's use and another fee for each patient he enrols,” says the editorial.
“The physician becomes invested in the drug's future.”