Clinical trial was a Vioxx marketing tool, researchers say.
"One of the features of a seeding trial," said Annals editor Harold Sox in an e-mail interview, "is that its scientific value to society at large is low relative to the risks that patients take when they agree to participate."
The study analyzed Merck's internal and external correspondence about ADVANTAGE in documents produced as a result of litigation brought by plaintiffs who alleged injury resulting from the drug. (McDarby v. Merck, 949 A.2d 223 (NJ. Super. App. Div. 2008).) Quoting Merck employees in internal documents calling ADVANTAGE a seeding trial and detailing its origins in the company's marketing division, the researchers concluded that the clinical trial "was actually a sophisticated marketing tool designed to allow optimal 'seeding' of positive experiences with Vioxx among customers--primary care physicians--before its approval." They also noted that this purpose was hidden from participants, investigators, and institutional review board members.
Approved by the FDA in May 1999, two months after ADVANTAGE began, Vioxx was withdrawn in September 2004 after another trial showed a heightened risk of cardiovascular problems in patients taking the drug. Subsequent reports identified results, omitted from the published reports of ADVANTAGE and another trial, that showed similar cardiovascular problems.
In an editorial accompanying the Annals study, Sox noted that "seeding trials can occur only because the company does not disclose their true purpose to anyone who could say 'no.'"
That includes not only the 600 doctors and their approximately 5,500 patients who participated in ADVANTAGE, but also Sox himself. Five years ago, Annals published the results of ADVANTAGE, showing that Vioxx was as effective as other medications in treating osteoarthritis and was less likely to cause stomach problems. Although an earlier study, VIGOR, showed similar results for treatment of rheumatoid arthritis, the Annals editors "thought [ADVANTAGE] had a useful message that would benefit some doctors," Sox said in an e-mail.
In his editorial, Sox noted that no one from Merck told the journal about ADVANTAGE's true purpose. Instead, the editors learned of it in 2006 through a doctor, David Egilman, who served as an expert for the plaintiffs in the litigation and is a co-author of the current analysis.
Jonathan Edelman, the executive director of Merck's global center for scientific affairs, wrote a letter in response to the Annals editors, claiming that ADVANTAGE had a "legitimate scientific purpose" and noting that the authors of ADVANTAGE's critique are "paid consultants to plaintiffs' lawyers in the Vioxx litigation against Merck."
Egilman said in an e-mail interview that no one without access to these litigation documents could have known about ADVANTAGE's marketing purpose. (The documents used in the study are now publicly available at http://dida.library.ucsf.edu.)
And, he said, "if there was a possible refutation [of the current study], Merck can use any documents it wants to make any point it thinks it can make. It didn't make any."
Last November, Merck settled with many Vioxx litigants who had claims of heart attacks and ischemic stroke. More recently, the Third Circuit allowed a consolidated securities fraud class action against the company to move forward: Judge Dolores Sloviter found that there was sufficient evidence that Merck had continued to reassure investors that Vioxx was safe, even as its safety was questioned by independent researchers. (In re Merck & Co., Inc., Securities, Derivative, and ERISA Litig., 2008 WL 4138476 (3d Cir. Sept. 9, 2008).)
Mark Lanier, a Houston attorney who represents Vioxx plaintiffs, said the Annals study marks the medical community's formal recognition of a practice that plaintiff lawyers have long known.
"We knew of this seeding study and made an issue of it to the jury in Ernst, the very first Vioxx trial. Merck persisted in trying to keep the information out of the general scientific domain, but it is now out there for the world to see. This will not affect the settlements in place, but it may affect future studies that have marketing as their point-while wearing the mask of science."