The ADVANTAGE seeding trial: a review of internal documents

Ann Intern Med. 2008 Aug 19;149(4):251-8. doi: 10.7326/0003-4819-149-4-200808190-00006.

Abstract

Background: Seeding trials, clinical studies conducted by pharmaceutical companies that are designed to seem as if they answer a scientific question but primarily fulfill marketing objectives, have not been described in detail.

Purpose: To describe a known seeding trial, ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness), through documents of the trial sponsor, Merck & Co. (Whitehouse Station, New Jersey).

Data sources: Merck internal and external correspondence, reports, and presentations elicited to inform legal proceedings of Cona v Merck and Co., Inc., and McDarby v Merck and Co., Inc. The documents were created between 1998 and 2006.

Data extraction: An iterative case-study process of review, discussion, and re-review of documents to identify themes relevant to the design and conduct of ADVANTAGE. To supplement the case-study review, the authors did a systematic review of the literature to identify published manuscripts focused on seeding trials and their conduct.

Data synthesis: Review of the documents revealed 3 key themes: The 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 6 articles that focused on the practice of seeding trials, none provided documentary evidence of their existence or conduct.

Limitations: The legal documents in these cases provide useful, but limited, information about the practices of the pharmaceutical industry. This description of 1 company's actions is incomplete and may have limited generalizability.

Conclusion: Documentary evidence shows that ADVANTAGE is an example of marketing framed as science. The documents indicate that ADVANTAGE was a seeding trial developed by Merck's marketing division to promote prescription of Vioxx (rofecoxib) when it became available on the market in 1999.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Clinical Trials as Topic / ethics*
  • Clinical Trials as Topic / standards
  • Conflict of Interest*
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Deception
  • Disclosure
  • Drug Industry / ethics*
  • Ethics Committees, Research
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Lactones / adverse effects
  • Lactones / therapeutic use
  • Marketing / ethics*
  • Sulfones / adverse effects
  • Sulfones / therapeutic use

Substances

  • Cyclooxygenase 2 Inhibitors
  • Lactones
  • Sulfones
  • rofecoxib