I don't think we have predictive animal models. It's hard to get mice to tell you how much pain they have. What we're left
with is an approach like the one NicOx is taking—basically, they're improving on the drugs we already have in some way, rather
than coming up with a brand new drug.
Merck recently inked a deal with NicOx. What's NicOx's approach?
NicOx takes the view that they're going to improve on the products by adding nitric oxide [NO]. It turns out that NO also
protects your stomach, or prevents the type of damage you get with nonsteroidals in your stomach. The goal here, initially,
was to look at that as an endpoint. In the process of the development program, it also became clear that it mitigated the
blood pressure response that you see with non-steroidals. So the goal of the program now is really to demonstrate, ideally,
a difference in the blood pressure response.
The Editors Respond
We called the editors at the New England Journal of Medicine. Though they weren't taking interviews, the publication answered a few questions by e-mail.
Pharm Exec: Where should have the VIGOR investigators included the cardiovascular information?
The VIGOR article should have covered both the gastrointestinal and cardiovascular adverse events in roughly equal proportions.
The cardiovascular information should have been presented and discussed in all sections of the article. Supportive data in
the form of one or more tables and a figure should have been included. The tables and figure that would have been most relevant
have been reproduced on our Web site as a supplement to our Expression of Concern Reaffirmed.
How would you counsel article authors to include information about risk—particularly when it's there but not represented in
In a study on the safety of a drug, it is mandatory to present all relevant data on risk. In the case of the VIGOR article,
the presentation on risk was unbalanced, and very little of the cardiovascular risk data were included. Authors are not permitted
to include only selected safety data. They are obligated to tell the whole story. Even unanticipated adverse events, if they
are clinically relevant, must be reported in the article.
When authors do not follow the principle of complete reporting of data, physicians get incomplete information and their patients
can be put at risk. Our expression of concern has reminded the research community about this important principle.
Did you follow the appropriate guidelines for running the first Expression of Concern?
We followed the guidelines for issuing an expression of concern set forth by the International Committee of Medical Journal
http://www.icmje.org/). Whenever we have issued an expression of concern, we have notified our readers of that concern at the same time we notified
the authors, and we have then followed up with a response from the authors or their institution.
Thomas Schnitzer, MD, has conducted clinical trials on drugs such as Vioxx (rofecoxib), Celebrex, and Prexige, and has been published in many top
journals. Currently, Dr. Schnitzer is the principal investigator for NicOx Pharmaceuticals' lead pain-control compound AZD3582,
currently in Phase II. He also is a professor of rheumatology and assistant dean for clinical research at Northwestern University
Feinberg School of Medicine. He graduated from Harvard University in 1971.