Caveat Medicus: The ADVANTAGE Seeding Trial

Medical education is a continuous process, with the most important lessons learned after the swearing of solemn oaths, certification by examining boards, and licensing. One important lesson is that physicians are essential to the financial success of the pharmaceutical industry. Physicians fulfill this role simply and directly by prescribing medications and medical devices. While physicians are dutifully learning to improve knowledge and skills, segments of the pharmaceutical industry are devising tactics that will induce physicians to prescribe their products. Industry provision of meals, tickets, books, seminars, travel, and emblazoned backpacks is a visible stratagem that has been so effective that medical societies and organizations are seeking to eliminate it. A less obvious, more insidious, and even more effective technique was brought into daylight when the Vioxx litigation opened access to internal documents of Merck & Company related to seeding trials.

Although seeding trials may appear scientific, they are created to fulfill marketing objectives by the early placement of new products into a large number of practices. The documentation shows that these studies — including the collection, analysis, and dissemination of the data — were the responsibility of Merck’s marketing divisions and that personnel at the highest scientific levels of the company considered such studies to be “intellectually redundant” and “wasteful.” The primary care physician investigators were to be trained to be on message with a communication strategy concerning the study results. Patients, their physicians, and institutional review boards were not advised about the true purpose of these studies, and many might not have participated had they known.

The critical physician can use these criteria to determine if a study is a seeding trial:

• Lack of scientific significance

• No attempt to evaluate a new indication

• Open-label design

• No control group

This circumstance was unusual. Internal company data and records illuminating the purpose of a clinical trial are usually not available, which could make it difficult to distinguish between a seeding study and a legitimate one.

The medical community now has information that received extensive press coverage, and we will be more aware of seeding trials and their purpose. The design of the next generation of marketing-related trials will be more sophisticated, and physicians will need to stay alert to determine whether the inducements and rewards for patient and physician participants are driven by science and patient care or by the desire to influence prescribing habits.