Merck’s ADVANTAGE trial revealed for its marketing motivation. Source: Nature

Merck’s ADVANTAGE trial was conducted as a seeding trial to promote Vioxx prescriptions when the anti-inflammatory drug came on the market in 1999, according to a case study in the Aug. 19 issue of the Annals of Internal Medicine.

Seeding trials are long-suspected to have been conducted by pharmaceutical companies to seem as if they answer a scientific question but primarily promote a new drug by getting physicians to use it as if they followed the protocol of a clinical trial.

Kevin P. Hill, MD, from McLean Hospital in Belmont, Mass., and colleagues found, upon a review of internal and external Merck correspondence, reports and presentations created between 1998 and 2006 elicited to inform legal proceedings of Cona v. Merck and McDarby v. Merck, that:

• The ADVANTAGE trial was designed by Merck's marketing division to fulfill a marketing objective;
  
  
• Merck's marketing division handled both the scientific and the marketing data, including collection, analysis and dissemination; and
  
  
• Merck hid the marketing nature of the trial from participants, physician investigators, and institutional review board members. Although the systematic review of the literature identified six articles that focused on the practice of seeding trials, none provided documentary evidence of their existence or conduct.

The authors acknowledged that the legal documents in the legal cases provide useful, but limited, information about the practices of the pharmaceutical industry. However, they discovered the depth of Merck’s marketing scheme through their analysis of internal documents revealed to the courts. Hill and colleagues concluded that “without access to internal documents, the intent of pharmaceutical companies in conducting clinical trials is nearly impossible to prove.”

The ADVANTAGE trial, (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness),claimed the painkiller Vioxx (rofecoxib) was easier on the stomach than an older drug and Vioxx became a blockbuster for Merck with annual sales of $2.5 billion. In 2004, the FDA ordered the painkiller off the market after it was linked to more than 27,000 heart attacks or sudden cardiac deaths in the U.S. from 1999 through 2003.

In April, Hill revealed that clinical manuscripts from the trial were authored by Merck employees. Hill first published some of their initial findings in the Journal of the American Medical Association (JAMA).

Jeffrey R. Lisse, MD, the first author of the primary publication resulting from ADVANTAGE, told The New York Times that he did not have a role in data collection or analysis, confirming Hill’s revelation that Merck's marketing division was responsible.

“Merck designed the trial, paid for the trial, ran the trial. Merck came to me after the study was completed and said, ‘We want your help to work on the paper.’ The initial paper was written at Merck, and then it was sent to me for editing,” said Lisse, an academic physician not employed by Merck.

Also, the investigators reported that Merck and its public relations corporation, Ogilvy, trained ADVANTAGE investigators for interaction with the media after the trial results were published. ADVANTAGE ‘authors’ were given an information package that included a sample pitch letter. For example, Merck emphasized the importance of having all aspects of their marketing program ready when the FDA approved Vioxx to help accomplish objective AAA, or Announce ADVANTAGE at Approval.

Based on their research, the AIM authors concluded that “Merck conducted a seeding trial to promote the prescription of Vioxx.”

Despite the danger of seeding trials, Hill and colleagues concluded that “without access to internal documents, the intent of pharmaceutical companies in conducting clinical trials is nearly impossible to prove.”