‘May Be A Seeding Study, But Let’s Not Call It That’
7 CommentsBy Ed Silverman // August 26th, 2008 // 1:30 pm
Last week, a report in The Annals of Internal Medicine alleged that a key Vioxx study, known as Advantage, was actually a seeding study, which is a common reference to a stealth marketing effort.
The report caused a stir, partly because being able to prove seeding accusations is difficult, but also because Merck has consistently been charged with placing marketing above science in touting Vioxx, which was withdrawn in 2004 over links to heart attacks and strokes. Merck has since settled most US lawsuits for $4.85 billion.
In an accompanying editorial, the editor of The Annals of Internal Medicine, stated the journal was not told the true purpose of Advantage, which compared Vioxx with an older, cheaper pain reliever, naproxen, when it published results indicating Vioxx was better tolerated.
Jonathan Edelman, head of scientific affairs at Merck Research Laboratories, tells the AP that “the ADVANTAGE study was primarily a scientific study” designed and executed by the drugmaker’s clinical research unit and that any later use of data for marketing was a separate operation. Here is an open letter from Merck, the amended protocol for the trial, and Merck’s synopsis of the study.
Meanwhile, an e-mail thread from March 1999, the year Vioxx was launched, captures a conversation among Merck marketing people as they decide how to handle the Advantage trial. Notice that one wrote: “I eliminated the reference to seeding. It may be a seeding study, but let’s not call it that in our internal documents.” So… was it a seeding study or not?
We asked a Merck spokesman for a response to the e-mail and this is what came back: “Some non-scientists in the company used the term ’seeding study’ to describe the fact that one aspect of the study was that it enabled a large group of investigator physicians to gain familiarity with the product in the context of a rigorous study. This does not change the fact that this study had a significant scientific purpose and a rigorous methodology.
“Merck disagrees with the characterization of Advantage as a ’seeding study’ and with the conclusions of the journal article. The company firmly believes there is great value in understanding questions physicians want answered and in conducting rigorous, scientific clinical studies to address those questions.
“The Advantage clinical trial was designed, conducted, analyzed, interpreted and published by the scientific arm of Merck’s US Human Health (USHH) organization, Clinical Development (CDP), in conjunction with participating investigators. CDP was part of medical and scientific affairs department of USHH and was a separate from the marketing department within USHH. Merck Research Laboratories’ Clinical Research Review Committee exercised oversight.
“The (Annals report) authors, consultants hired by plaintiffs’ lawyers, erroneously claim that the objectives of the Advantage study were not scientific, based on their limited selection of documents produced in the VIOXX litigation. They purposely fail to distinguish between the dual scientific research and marketing functions of USHH.”
In case you missed it, here is an interview with one of the authors of the Annals report.
Doug Bremner
It clearly is unethical to conduct ’studies’ when there is no benefit to society at large of the information obtained. Anyone who has sat on an IRB knows this. When the public learns that they were participating in studies whose purpose was to get physicians to prescribe their drugs they aren’t going to want to participate in real research, which will hurt those of us who do this for a living. ADVANTAGE was clearly performed for marketing purposes, whatever acronym you want to use. Why else would they have 600 ‘investigators’, each of whom would have recruited about 5 patients? It doesn’t make any sense. How can you coordinate 600 sites and get them all to do things the same way? A Merck exec was even quoted as complaining to the marketing people that they had done a study that exposed them to the risk of finding out a bad side effect, when the study wasn’t needed.
Dan A.
May be a pointless study with no scientific value regarding the acquisiton of additional knowledge, but let’s not call it that, either.
atlex
Just because a study was done for marketing purposes, doesn’t mean it wasn’t done for legitimate medical purposes, as well. I don’t work in Merck marketing so I haven’t seen all of the information. Thus, for all I know this study was designed, implemented and published by Merck’s marketers. If so, there is definitely a problem. However, I seriously doubt that there was NO scientific rationale for the study. Moreover, while the “seeding” aspect of the study is disturbing, has anyone demonstrated that good study practices were not followed?
In my experience, marketers often try to push the envelope on studies; their opinions should be counterbalanced by their peers from Medical and Legal/Regulatory. If everything works, robust studies get conducted that meet medical gaps and marketing needs. By only looking at the emails from marketers, I feel as though I am only seeing part of the story.
One more note…this study was conducted in the late 1990s. In most major pharma companies, a “seeding” study would be highly unlikely to pass internal scrutiny today.
Salmon
At the time of this study Merck was divided into several different business divisions. Including Merck Research Labs, Merck Manufacturing, and Merck Marketing. I can’t remember the names for each of them.
However the marketing division had it’s own independent physicians who designed and conducted studies for the express purpose of marketing and these were not designed for any regulatory purpose.
Studies that have no scientific merit are not uncommon in the pharmaceutical industry. FDA generally won’t object to unethical studies if an institutional review board signs off on it and IRBs usually won’t make waves because once you do you can kiss future studies and $ goodbye. If an IRB has a problem they might ask if it’s been reviewed by FDA but since most studies that are submitted aren’t reviewed and especially not marketing studies it’s a big farce.
Salmon
Dan A.
To complicate things further, Some if not many IRBs are for profit as well, just as the CROs.
Mike M
I remember a small seeding trial in 1960, which was orchestrated by the Marketing department of a company called Merrell located in Cincinnati, Ohio. Sound familiar? The purpose of this “trial” was to sign up as many doctors as possible in order to sell them on their new drug, Kevadon (thalidomide). We all know how this ended (but hey, I am sure this “trial” was partially devised on scientific merit, so maybe we are just picking on poor Merrell). Yet, we still have people defending the disgusting practices of this industry, even though it is clear they perpetually place profits before patients, and continuously contaminate legitimate science with promotional stunts.
S Silverstein
One must not forget the words of the former President of Merck Research Labs on this issue:
In e-mail messages on April 7, 2001, to … an executive vice president at Merck Research Laboratories, [President of Merck Research Labs] Dr. [Edward] Scolnick wrote that he was especially angry because the Advantage trial had no scientific purpose. In theory, Merck set up the trial to show that Vioxx caused fewer stomach problems than naproxen. But Merck had already demonstrated that with the Vigor trial, which tracked more than 8,000 patients for a year.
… [T]he reason we have resisted doing large marketing clinical studies is just this. It opens a lot of data to FDA that compromises the large clinically meaningful trials.” Small marketing studies which are intellectually redundant are extremely dangerous,” Scolnick wrote.
If a pharma company does not listen to its head of R&D, then who will it listen to?