The ADVANTAGE seeding trial: a review of internal documents.
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.


OBJECTIVE
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).


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Hill
Kevin P
KP
McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. kphill@partners.org
Ross
Joseph S
JS
Egilman
David S
DS
Krumholz
Harlan M
HM
D002986:Clinical Trials as Topic / Q000941:ethics* / Q000592:standards; D016265:Conflict of Interest; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D008192:Deception; D030881:Disclosure; D004345:Drug Industry / Q000941:ethics*; D028744:Ethics Committees, Research; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D040541:Marketing / Q000941:ethics*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib