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The ADVANTAGE Seeding Trial: A Review of Internal Documents
- Kevin P. Hill, MD, MHS;
- Joseph S. Ross, MD, MHS;
- David S. Egilman, MD, MPH; and
- Harlan M. Krumholz, MD, SM
- From McLean Hospital, Belmont, Massachusetts; Mount Sinai School of Medicine, New York, New York; Brown University, Providence, Rhode Island; and Yale University School of Medicine and Yale-New Haven Hospital, New Haven, Connecticut.
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.
Article and Author Information
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Note: All legal documents used in the article are available at http://dida.library.ucsf.edu.
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Acknowledgment: The authors thank Leslie Curry, PhD, for her advice on our methods for review of the litigation documents and Greg Mulvey for his help in organizing the documents.
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Grant Support: Dr. Hill was a Scholar in the Robert Wood Johnson Clinical Scholars Program sponsored by the Robert Wood Johnson Foundation while working on this project. Dr. Ross is currently supported by the Hartford Foundation.
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Potential Financial Conflicts of Interest: All authors were compensated for participation in litigation against Merck at the request of plaintiffs.
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Reproducible Research Statement: Study protocol and statistical code: None. Data set: Available at http://dida.library.ucsf.edu.
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Requests for Single Reprints: Kevin P. Hill, MD, MHS, McLean Hospital, 115 Mill Street, Belmont, MA 02478; e-mail, kphill{at}partners.org.
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Current Author Addresses: Dr. Hill: McLean Hospital, 115 Mill Street, Belmont, MA 02478.
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Dr. Ross: Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029.
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Dr. Egilman: 8 North Main Street, Attleboro, MA 02703.
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Dr. Krumholz: Yale School of Medicine, 333 Cedar Street, I-456, SHM, New Haven, CT 06510.
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Author Contributions: Conception and design: K.P. Hill, J.S. Ross, D.S. Egilman, H.M. Krumholz.
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Analysis and interpretation of the data: K.P. Hill, J.S. Ross, D.S. Egilman, H.M. Krumholz.
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Drafting of the article: K.P. Hill.
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Critical revision of the article for important intellectual content: K.P. Hill, J.S. Ross, D.S. Egilman, H.M. Krumholz.
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Final approval of the article: K.P. Hill, J.S. Ross, D.S. Egilman, H.M. Krumholz.
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Provision of study materials or patients: K.P. Hill, D.S. Egilman.
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Administrative, technical, or logistic support: K.P. Hill.
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Collection and assembly of data: K.P. Hill, D.S. Egilman.
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