Q&A with Dr. Adriane Fugh-Berman: Ghostwriting sneaks past most journal editors

Dr. Adriane Fugh-Berman is the principal investigator of PharmedOut, an educational campaign aimed at showing physicians how marketing influences their prescribing decisions. Originally funded by the Attorney General Consumer and Prescriber Education Grant, PharmedOut, among other things, offers continuing medical education to doctors, allowing them to earn credits without taking courses funded by drug or device companies.

Fugh-Berman is serving as an expert witness for the plaintiffs in a lawsuit brought by patients against Wyeth over the adverse effects of hormone replacement therapy drugs. During the course of that lawsuit, the New York Times and the medical journal PloS Medicine intervened to persuade a judge to release documents detailing how Wyeth ghostwrote articles promoting its drugs and had researchers sign them to make it appear as if the articles were independent.

I reached her at her office at the Georgetown University Medical Center, where Berman is an Associate Professor in the Complementary and Alternative Medicine Master's program in the Department of Physiology and Biophysics. A recap of the first part of our conversation is below. It has been edited for space and clarity. The second half of our conversation is posted here.

Q: Ghostwriting has been getting a lot of buzz lately because of the lawsuit you were involved in, but it's been going on for a long time, right? Why does it seem like the scientific world is just now waking up to it?

A: It's gotten a lot more attention in the media than it has in medicine. Medical editors have only started to pay attention to it in recent years. I don't know if you have seen my piece on the Corporate Coauthor?

Q: Yes. I was going to ask you about that. You actually had one of these ghostwritten pieces sent to you asking for your signature.

A: Right. And when I called the Journal of Internal Medicine to say, "Don't accept this piece that was submitted for review because it was ghostwritten, I did not anticipate the reaction, which was a wonderful sense of outrage. And then they activated the World Association of Medical Editors. So there that initial outrage became a wonderful stream of outrage. But I was struck by the fact that they didn't seem to know that this had been going on.

Q: Why is that?

A: I believe that part of the reason is that most medical journal editors are not fulltime editors. Most of them are academics who are editors part-time. But that's not the whole reason. Even though I really appreciated the outrage among the editors, it was appalling to me that they weren't already being vigilant about this.

Q: Charlie Ornstein wrote about it in the Dallas Morning News in May 1999.

A: His piece was one of the first. I can't think of any reporting about it before then. It's been a major problem. It still goes on. It affects all kinds of medical literature. Not just studies, but even more importantly, in the area of research that I'm focusing on, is the issue of ghostwriting in reviews and commentaries and in continuing medical education.

Q: In the Wyeth case, which sparked this recent spate of coverage, most of the ghostwritten pieces were reviews. What is so important about the review?

A: Contrary to what people might think, physicians do not go home and curl up with the New England Journal of Medicine and read randomized controlled trials. It's just no one's idea of a good time. We depend on our experts to synthesize medical literature and give us a clinically relevant synopsis. And that's what reviews and commentaries are supposed to be. From the industry's point of view, reviews and commentaries can be used to promote off label uses, new categories of diseases and completely ridiculous opinions.

Q: What are some of the things that you have seen promoted that way?

A: A lot of what academics are used for both in continuing education and in authorship of ghostwritten articles is generally to push diseases as opposed to drugs. Every drug usually has 15 to 25 marketing messages that are associated with it. Some are about differentiating the drug from other therapies used to treat the disease state. A lot of the messages are about the disease state itself. If I were to characterize them generally it would be:

• Disease X is under-diagnosed, and it's a tragedy.

• Disease X is more widespread than clinicians know.

• Existing therapies are inadequate to treat Disease X.

• This previously unknown or thought to be unimportant mechanism is extremely important.

All these messages might be used in pre-launch promotion. Years before a drug comes up for approval, there are massive promotion efforts to generate interest in the disease and in the potential therapy. About three times as much is spent on promotion before a drug is released on the market than in the first year after it is released. Think about that. They are spending more to promote the idea of the drug than they are when they actually have a drug with a brand name.

Q: How can marketing without a brand name possibly be effective?

A: Since promotion can start seven to 10 years before a drug comes before the FDA, some of the messages might be that this mechanism of action is very important. For example, for years there were a lot of articles and talks that were sponsored by drug companies about the importance of the endocannabinoid system. Humans have cannabinoid receptors which are activated by marijuana and also endogonous substances. There is legitimate research in this area, but, suddenly, there was a lot more time and money being spent on cannabinoid receptors than ever before. Why? Because a drug maker was getting ready to ask the FDA for approval of an obesity drug called rimonabant. It had already been approved in other countries. The FDA ultimately did not approve it because it also increased the risk of suicide, but it's going to come back in the form of a smoking cessation drug. My friend John McPartland wrote about it in PLoS One. The fact that cannabinoid research is being used as a marketing tool for drug makers is not something that an editor at a medical journal is going to recognize. Some of the drugs for which marketing messages are being disseminated don't even have a name yet. They are XL17342, not rimonabant.

Q: When this ghostwriting company contacted you in 2004 on behalf of a drugmaker, were you surprised that they did not seem to know that you had written some very skeptical pieces about drug marketing, including a piece about bust-enhancing herbal products?

A: I thought, "Why don't they do a little homework?" But it was a UK company, and they didn't do their homework. Well, they did in one respect. I am an expert in herb-drug interaction. And that's why they contacted me. They wanted to promote the idea that warfarin interacts badly with herbs.

Q: Why didn't you just say, "I won't do it" right off the bat?

A: I totally led them on for a little while because I was curious about what they were doing. When I asked, they told me that what they were doing was sponsored by AstraZeneca. That was even more interesting because AstraZeneca doesn't make herbal products, and they don't make warfarin. So I said, "Send me more information." Then, several months later, they sent me the entire manuscript. After reading it, I wrote back and said "I'm curious why is AstraZeneca is funding this." And they said something like, "Not that this is meant to promote any drug, but AstraZeneca will be bringing up for approval ximelagatran which has fewer drug interactions than warfarin." So I made a note to self to watch medical literature about how terrible warfarin is.

Q: What did you find?

A: I knew there would be more manuscripts on how warfarin interacts with other drugs and herbs, and it does interact with drugs and foods and things. So I started to see articles about how ximelagatran, or Exanta, has fewer drug interactions. The FDA was not happy with the rate of liver toxicity and didn't end up approving it.

Q: Was it surprising that this company tried to steer you to a specific journal?

A: No. The author is just the person whose name decorates the article. They don't have any say. Let's say I changed the whole thing. They would say, "Thank you very much." And then they would find someone else who would agree to author the original version. They have embedded marketing messages in that original draft, and they don't want those marketing messages changed. The marketing messages would be that warfarin interacts with a lot of herbs and this can be dangerous to the public health. If I had said, "This doesn't happen very often, so don't worry about it," that article would not be published. David Healy has written about this. He's a psychiatrist in Wales who has done some ghostwriting. He changed several lines in an article that a drug company wrote for him. The changes disadvantaged the drug that the company made. They basically changed it back and submitted it to the journal anyway.

Q: Do these companies think that certain journals will be friendlier than others?

A: Definitely. I'm a paid expert in the case that prompted the documents being revealed. There are some incredible documents in there, and I'm trying to help get them out there. Some of the documents have publication plans in them. There is a plan for what articles on what subjects will be placed in what journals with what authors. Journals are chosen for a variety of reasons. It might be the target audience. It might be that the journal doesn't require conflict of interest disclosures. It might be that a journal publishes very quickly. It might be that the journal is prestigious. They will sometimes just take it to a journal that caters to the pharmaceutical companies and will publish anything that the industry brings them and charge them for it.

Q: Charge them for it? So the article is basically a paid advertisement?

A: Charging to publish an article is very common in basic journals, but not as common in medical journals. It's not necessarily a bad practice. It's a way for the journal to cover its costs. I'm in the physiology and biophysics department at Georgetown, even though I'm neither of the above, and this is common in basic science. What scientists do is include publication charges in their grant applications.

Next week: What drives doctors to sign their names to drug marketing?