In the latest bombshell over Vioxx, a report in the Annals of Internal Medicine concludes Merck conducted a so-called seeding study of the notorious painkiller. This type of trial, whether or not the design is scientifically sound, primarily serves a marketing purpose. And this raises a few key issues, such as the extent to which patients are properly informed of the objectives and whether they risked any harm. Given the links to heart attacks, the researchers hold up the Vioxx trial, known as Advantage, as an example of what a drugmaker should not do. For its part, we should note, Merck denies the accusations and calls the report biased and replete with errors (back story). We chatted with Kevin Hill, a former Robert Wood Johnson Foundation clinical scholar at Yale University and now an addiction psychiatry fellow at McLean Hospital in Belmont, Massachusetts, about his report.

Pharmalot: Why is there such a fuss over a seeding trial? Why does it matter:
Hill: The idea isn’t new. Physicians have been recruited to participate in marketing studies in order to allow them to become familiar with a drug. And that’s what happened here. This trial allowed physicians to have experience with Vioxx. But as far as I know, our paper is the first to show how a pharmaceutical company planned and executed a seeding trial. There are documents showing how Merck could have gained an advantage. But what’s troubling is that physicians and patients weren’t told of the objective of the trial. And that’s problematic, because patients risk their health when they are signed up for such a trial, instead of advancing the cause of science.

Pharmalot: Well, Merck says the trial was designed properly.
Hill: Most clinical trials have a legitimate scientific question. Now, if the Advantage trial was the only trial Merck had undertaken to look at the issue of GI (gastrointestinal problems), Advantage could have stood alone. But they had looked at this quesion in many other trials. And in that way, Advantage wasn’t necessary. They knew the answer to the questions. They looked at it in the Vigor trial (which was being run simultaneously). You know, the merits of Advantage as a clinical trial have been debated. I actually thought it was designed in a fairly good way, but the issue is they didn’t tell people the objectives.

Pharmalot: So, if the trial had an acceptable design, why does it matter if it’s for marketing:
Hill: Again, patients risk their health in clinical trials. They need to trust the science, and seeding undermines that trust. These people were taking a potentially harmful drug that was being studied, essentially, for marketing purposes. It’s a question of informed consent. If you look at Figure 1 in our report, it clearly attributes numerous marketing objectives to the study. The memo makes it appear that Merck is most interested in the prescribing habits of the investigators. The case could be made there was a scientific purposes, but GI tolerability had been looked at already. How many times do you have to look at that to know the answer? And patients weren’t given a chance to make an informed decision about their participation.

Pharmalot: You mention a memo by Ed Scolnick (formerly Merck’s chief scientist). Why was that significant?
Hill: Scolnick called the trial ’scientifically redundant’ and lamented the fact that the marketing branch had a very large trail and ran many trials with a marketing purposes, and called attention to Merck products in a way that could be problematic. I think he was afraid that if his department didn’t have any say in what was going on, bad things would happen.

Pharmalot: What do you think this paper will really accomplish? These events happened years ago.
Hill: Well, hopefully this will create a dialogue and create transparency between academia, physicians and pharma. The paper focuses on the evidence and we’re hoping readers will read the paper and draw their own conclusions. We didn’t steer readers one way or the other.

Pharmalot: There’s a conflict of interest issue raised - you and your co-authors consult for lawyers who are suing Merck. How do you answer accusations of bias?
Hill: The question of bias should always be asked and I welcome the question. We’ve been very transparent about the fact that we receive compensation with respect to the litigation. We were paid to analyze the data and we were hired for our collective expertise in reviewing clinical trials. But we went into this without pre-formed hypotheses. We weren’t looking to cherry pick evidence. And you can’t spin an article in a journal such as the Annals of Internal Medicine that way. Hopefully, readers can draw their own conclusions.