(Update)

Steve Nissen, a vocal critic of inappropriate industry influence in medicine, does he have his own conflict of interest problem?

This week, Nissen, the chief of cardiology at the Cleveland Clinic, was widely quoted in reports about FDA advisory panels evaluating two very promising new cholesterol drugs from Amgen and Sanofi/Regeneron.

Nissen was largely in favor of drugs. Although he was a leading voice against the approval and use of drugs based solely on their effect on surrogate outcomes, he was much more liberal about these drugs than some other experts and many panel members. According to CNBC:

“I’m someone who generally opposes drug approvals based on surrogate endpoints without outcome data,” Nissen said by phone Wednesday, referring to the reduction in LDL cholesterol already shown by the medication. “However, in this case, I actually support the endorsement and I actually think the concerns of the committee are not targeted.”

On the NBC Nightly News program he was even more expansive:

These drugs are breakthrough drugs, they are blockbuster drugs that will most likely have a big impact.

But it wasn’t always clear in these and other reports that Nissen might not be an entirely objective observer. NPR reported that, “for the record, he’s leading a study of one of the drugs and is on the steering committee of a Pfizer clinical trial. He’s not taking any money from the companies.”

A New York Times report contained a fascinating detail. Prior to the FDA panel, Nissen, along with other leading cardiologists, participated in a mock hearing at Amgen’s offices. Nissen, writes Gina Kolata,

…said he felt a little uncomfortable accepting and refused compensation. But he said he wanted to push the company on the quality of its drug data.

“I asked the kind of tough questions that should be asked,” he said. He added that he and others have emphasized the effects of very low LDL levels. “We tortured them for this,” he said. In the end, he said he was convinced that, based on what was known to date, there was not yet proof of harm and reason to expect a benefit.

But it’s not clear in the Times article that Nissen is the president of a multi-million dollar study of Amgen’s evolocumab (Repatha). Nissen doesn’t receive money directly from Amgen, but his work earns the Cleveland Clinic millions of dollars.

I asked Nissen what their policy was regarding the disclosure of such conflicts. Here is his response.

I am always completely frank with journalists on these issues.

I have a simple rule. I simply do not accept income for advice or any other reason from “for profit” businesses.

All sites that carry out clinical trials, whether a coordinating center or a recruiting center, are reimbursed for their direct expenses related to the conduct of clinical trials. The Cleveland Clinic is a not-for-profit entity and is not permitted to engage in “for-profit” activities. I am not involved in the negotiation of services between industry and the Cleveland Clinic for the studies in which I participate. I don’t even see the budgets. I address myself exclusively to science.

But I think it deserves a closer look. In addition to his stance against surrogates, Nissen is well known for drawing attention to conflicts of interest in medicine. Over the years, Nissen has repeatedly stated that he does not receive money directly from industry and that when he consults or performs other services for industry, he directs the money to organizations non-profit. I think it’s worth pointing out that in the academic medical world, conducting clinical trials brings prestige, power, and, the ultimate academic currency, publications. I’ll leave it to finer minds than mine to determine how this weighs on the COI scale, but it seems to me that this is at the very least a COI that should at least be fully disclosed to journalists and that journalists should include this information in their stories.

I don’t want to be misunderstood here. I don’t want to attack Nissen or suggest that he shouldn’t play a role in the public drug debate. There’s a reason journalists look to Nissen for quotes. He is as smart as can be and he knows how to explain difficult scientific concepts in accessible language. I don’t think there’s a reason why journalists shouldn’t use it as a resource. But they should be aware that Nissen, like others, is not perfectly objective, and it is fair that readers are aware of the full context of his statements.

Update, June 14–

James Stein, a cardiologist at the University of Wisconsin School of Medicine and Public Health, sent the following comment in defense of Dr. Nissen. I’ll respond to Stein in a day or two, but in the meantime, I think his comments deserve immediate attention:

The academic literature has long recognized the existence of multiple forms of potential conflicts of interest (COI) beyond direct financial compensation. Other potential conflicts of interest include “institutional” conflicts (i.e. generating revenue for your institution or employer), “intellectual” conflicts (i.e. reluctance to accept opposing positions) and the possibility that certain activities may increase public or academic status or lead to future financial gain, among many others. Indeed, medical journals often focus on personal and institutional financial conflicts of interest through a disclosure process. While disclosure is laudable and a good first step, it is not a particularly effective tool for managing potential conflicts of interest.

The academic literature also suggests that not all potential conflicts of interest are avoidable, particularly the non-financial conflicts of interest above. discussion. This is NOT the same weak argument used to justify financial conflicts of interest, which are more serious and dangerous. Indeed, non-financial conflicts of interest, with the exception of the most extreme, are often not the “conflicts” of interest that they are perceived to be, but rather a “confluence” of interests.

However, this article questions the integrity of Dr. Nissen. His opening sentence sensationally asks if Dr. Nissen has a “problem”, and it implies guilt by association, which is unfair. The article presents no evidence to support the claim that it has a large (even non-financial) COI, that it has disclosed no information (which, limitations aside, is the current standard of assessment and management of potential COI), or that he has done anything questionable. On the contrary, the journalists who did not ask about his other forms of involvement in the pharmaceutical industry are the culprits for not having done their job in asking the questions that might interest people. Dr. Nissen is a man of great integrity who led the ACC. and other professional organizations to clean up their conflict of interest laws and inspired a generation of physicians to do the same. Because he’s outspoken, quotable, and interacts with academia, industry, and government, he’s an easy target, but that wasn’t a fair handling of the issue. Your praise at the end of the article does not compensate for the dislike expressed at the beginning. I would have written the article in the reverse order.

Click here for my response to Stein’s comments.

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