Q&A with John Carey: Peeling back the label on cholesterol drugs

John Carey, a 20-year veteran at BusinessWeek, wrote a story that set the pharmaceutical world on its ear in January 2008. Titled "Do Cholesterol Drugs Do Any Good?," the article systematically broke down the many myths behind the so-called "miracle cure" for heart disease: statins. Carey's story won an award from the Association of Health Care Journalists at its conference in Seattle.

I reached Carey, 54, at his office in Washington, D.C. Here is a recap of our conversation, which has been edited for space and clarity.

Q: What prompted you to take a look at this?

A: A guy named Allen Roses who moved over to GlaxoSmithKline and who said in 2003 that the majority of drugs only work in a minority of patients. That percolated around and was always in the back of our minds to take a real in-depth look at drugs in general and how well they actually work. The media covers the safety questions really well, but very few people look at the efficacy questions. Most people think that drugs really work.

Q: And you had considered looking at other drugs first? Statins weren't your first choice.

A: I had done some stories on heart surgery and angioplasty, which showed that in most of the cases the outcomes were no better than not doing the surgery. And a reader said you ought to look at NNT, number of people needed to treat, in order to show a benefit from the drug. So I did. And I was astounded. Those numbers are a lot higher than most people realize. And then we had the controversy over Avandia, the diabetes drug, in 2007, where there was a slight increase in heart attacks and mortality. I had already done a bunch of reporting that questioned the whole idea of what the drug was designed to do, which is keep your blood sugar in a tighter range. There was a very tortuous manipulation of the data to show any benefit at all. I had reams of scientific papers and critiques by the time the Avandia thing hit the news. I was convinced that all the stories were missing the major point. Who cares what the safety profile is, the real question is: does the drug do any good?

Q: So why did you end up writing about statins and not diabetes drugs?

A: At BusinessWeek, as with most publications, before you spend a lot of time on a story, it always pays off to go and talk to a top editor about how he sees it. I went up to New York and met with Steve Adler, the editor in chief. I talked about how we should shape the story around Avandia. And he said, basically, he didn't have any interest in diabetes drugs and most of our readers don't, either . But our readers are keenly interested in cholesterol drugs because a lot of them are taking them.

Q: What was your initial response?

A: I said they do work. There's evidence that they do work with people who already have heart disease. And he said, that's OK. Let's see what we can find out about the cases where they don't work. The name of the game in magazines these days is to get noticed. He knew that a story that looked at cholesterol drugs would get noticed. And he was correct.

Q: What started to change your opinion about the drugs?

A: I was skeptical that the story would end up being as strong as it was. There's such strong conventional wisdom that this is the one intervention that works. But people came out of the woodwork with criticisms. One of the people I called was a retired professor who had done the Cochrane review of all the studies about whether statins had any effect on Alzheimer's disease. They concluded there was no evidence. Then it turned out he had taken statins and had gone from being an active tennis-playing person to a guy who couldn't get out of bed to a guy who became paralyzed. That helped me talk about people who decided the risk benefit ratio wasn't worth it.

Q: I noticed you compared the NNTs for Lipitor to a particular antibiotic. Why that drug?

A: I had a source that had compiled a whole list of NNTs. And there were a number of antibiotics that had low NNTs. You could have done any antibiotic. But we wanted to look back at the data to see how those numbers were calculated, and we were able to do that with that drug.

Q: How long did the project take you?

A: I don't' think I actually started working in earnest until sometime in September 2007, and I had it written by December. Then it sat around for a while. Luckily, the results of the Enhance trial came out in January. That became the perfect opportunity to slam it in the magazine.

Q: When did you start talking to Pfizer?

A: In October or November, I let them know exactly what we were doing. We danced around for weeks and then they agreed to an interview. An hour before the interview, they said they would only respond to written questions. I was surprised by that.

Q: Did their responses to the written questions surprise you, too?

A: They said on the NNT that the numbers are right. Then on the more important question of even if there is a slight decrease in heart attacks, the studies show there's no overall difference in mortality, they didn't challenge that. The responses were just sometimes like a sentence or two per question. I thought they would go into long arguments.

Q: So who did take up the statins cause?

A: Scott Grundy, who is quoted in the story. He clearly is a believer in the power of these drugs. He helped write the cholesterol guidelines.

Q: Did you meet any resistance internally at the magazine?

A: There's an amusing incident that happened. I had always wanted to do a story about how drugs don't work as well as people think, and one editor I brought it up to said, "That's not a story. Everyone knows that's true. It's not surprising. As long as he was in charge, the story was not going to get done. We had a mantra that every story had to be surprising. He left and wasn't in charge any more. Other than that the editing went amazingly smoothly.

Q: What sort of data sources did you use?

A: I eventually rounded up all the main clinical trials that had been used to get FDA approval and then to bolster the drug companies' claims. I found them mostly through the journals themselves. I built a stack of studies that was at least a foot and a half high. Then I rounded up the studies cited by the critics. It's the first time I had binders with sections to organize it all.

Q: Did you createdatabases with the NNTs and other numbers?

A: No. I did spend a lot of time looking at the actual data in the studies and trying to figure out how the conclusions came to be. It was frustrating, though, because there are so many issues with clinical trials. Publication bias, the rate people drop out of the study, differences between the control group and the experimental group.

Q: Was there anything that surprised you from the reaction?

A: My wife joked about whether we should move away from the house or watch for cars following us. There are a couple of other writers, Shannon Brownlee and Jeanne Lenzer, and Jeanne had been targeted by Eli Lilly after a story in the British Medical Journal about Prozac. I got reactions from them saying I should watch out. "The companies will come after you." So I was surprised when they didn't. The reaction from readers and the medical community that did respond was more positive to the story than I had expected. I had expected a lot more "You are going to kill people" kind of thing. I went through about 300 comments or so and the numbers were 80% positive.

Q: A number of publications, including the New York Times, have taken a similar approach to cholesterol drugs since. Do you credit your work for that change?

A: There's been a change in the mainstream view of cholesterol drugs. There has been a spate of stories after ours that acknowledged our stories or questioned the drugs. Most of them used the excuse of the Enhance trial to raise those questions rather than our stories. I don't care. It seems like a good thing just to raise the question.