Seeding Trials: Taking ADVANTAGE

Seeding trials conducted by pharmaceutical companies are clinical studies that are primarily marketing tools but seem designed to answer scientific questions. The existence of such studies has long been suspected, but published information about them has been limited.

An insider’s view of a seeding trial sponsored by Merck & Co. is revealed in a review of confidential internal communications made public because of recent litigation. The ADVANTAGE (Assessment of Differences between Vioxx And Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness) trial was devised by Merck’s marketing division in January 1999, before Vioxx was launched. The stated scientific purpose of the trial was to measure the gastrointestinal safety of rofecoxib. About 2 months before the FDA approved the drug, 600 investigators began randomly assigning 2785 patients with osteoarthritis to receive Vioxx and 2772 to receive naproxen.

A slide set developed by Merck for internal use states that a goal of the study was for investigators to “gain experience with Vioxx prior to and during the critical launch phase.” Based on their review of these and other documents, the authors of this case study identified three key themes pertaining to the purposes and development of ADVANTAGE: (1) the trial was designed by Merck’s marketing division for marketing objectives; (2) Merck’s marketing division handled the collection, analysis, and dissemination of both the scientific and the marketing data; and (3) Merck hid the key role of the marketing division and the trial’s marketing objectives from participants, physician-investigators, and institutional review boards. After FDA approval, Merck closely tracked the number of prescriptions that participating physicians wrote for Vioxx and for a competing drug.