Steven Nissen, Conflicts Of Interest, And The New Cholesterol Drugs

(Updated)

Does Steve Nissen, an outspoken critic of inappropriate industry influence in medicine, have his own conflict of interest problem?

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

Nissen was broadly supportive of the drugs. Although he has been one of the leading voices against approving and using drugs based solely on their effect on surrogate outcomes, he was much more liberal about these drugs than some other experts and many of the panel members. Here’s what he told CNBC:

“I am somebody who generally is opposed to approving drugs on the basis of surrogate endpoints without the outcome data,” Nissen said by telephone Wednesday, referring to lowering of LDL cholesterol already shown by the medicine. “However, in this case, I actually support approval and I actually think the concerns of the committee are not on target.”

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

“These drugs are breakthrough drugs, they are blockbuster drugs that are very likely going to have a big impact.”

But it wasn’t always clear in these and some other news reports that Nissen may not be an entirely objective observer. NPR reported that, “for the record, he is leading a study of one of the drugs and is on the steering committee for a Pfizer clinical trial. He takes no money from the companies.”

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

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

“I asked the kind of hard questions that should be asked,” he said. He added that he and others pressed on the effects of a very low LDL level. “We tortured them over it,” he said. In the end, he said he was convinced that from what was known to date, there was no evidence yet of harm and reason to hope for benefit.

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

I asked Nissen for his policy about disclosing these conflicts. Here’s his response.

I am always completely candid with reporters about these issues.

I have a simple rule. I just don’t accept income for consulting or any other reason from “for profit” companies.

All sites that do clinical trials, whether they are a coordinating center or an enrolling center are reimbursed for their direct expenses in conducting clinical trials. The Cleveland Clinic is a non-profit entity and is not allowed to engage in “for profit” activities. I am not involved in negotiating services between industry and the Cleveland Clinic for studies in which I participate. I do not even see the budgets. I address the science exclusively.

But I think this deserves closer examination. In addition to his position against surrogate endpoints Nissen is well known for calling attention to conflicts of interest in medicine. Over the years Nissen has repeatedly stated that he doesn’t take any money directly from industry and that when he does consult or perform other services for industry he directs the money to nonprofit organizations. I think it should be pointed out that in the academic medical world running clinical trials confers prestige, power, and, the ultimate academic currency, publications. I’ll leave it to finer minds than my own to determine how this weighs on the COI scale but it seems to me that at the very least this is a COI which should at least be fully disclosed to reporters and that reporters 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 discussion about drugs. There’s a reason journalists turn to Nissen for quotes. He’s as smart as they come and he knows how to explain difficult scientific concepts in accessible language. I don’t think there’s any reason that journalists shouldn’t use him as a resource. But they should be aware that Nissen, like others, is not perfectly objective, and it is only fair for readers to be 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 will respond to Stein in the next day or so, but in the meantime I think his comments deserve immediate consideration:

The academic literature has long recognized the existence of multiple forms of potential conflict of interest (COI) beyond direct financial remuneration.  Other potential COIs include “institutional” conflict (ie, generating income  for your institution or employer), “intellectual” conflict (ie, an unwillingness to accept contrary positions), and the possibility that certain activities can increase one’s public or academic status or lead to future financial gain, among many others.   Indeed, medical journals often focus on personal and institutional financial COI through a disclosure process.  Although disclosure is laudable and a fine first step, it is not a particularly effective tool for managing potential conflicts of interest.

The academic literature also suggests that not all potential COIs are avoidable, especially the non-financial COIs above,  Indeed, avoiding them is not necessarily desirable, since their “harms” are unclear and their obviation may eliminate generation of knowledge, insightful review, and discussion. This is NOT the same weak argument used to justify the financial COIs, which are more severe and dangerous.  Indeed, non-financial COIs, except the most extreme ones, often are not the “conflicts” of interest they are perceived to be, but instead are “confluence” of interest.

This article however, impugns Dr. Nissen’s integrity.  Its opening sentence sensationally asks if Dr. Nissen has a “problem,” and its implies guilt by association which is unfair.    The article presents no evidence to support the contention that he has significant COI (even non-financial), that he did not disclose any information (which, limitations aside, is the current standard of potential COI evaluation and management), or that he did anything questionable.  If anything, the reporters who did not ask questions about his other forms involvement with pharma are the ones at fault for not doing their jobs by asking the questions people might be interested in.  Dr. Nissen is a man of high integrity who led the ACC and other professional organizations to clean up their COI acts and inspired a generation of physicians to do the same. Because he is outspoken, quotable, and interacts with academia, industry, and the government, he is an easy target but this was not a fair handling of the issue.  Your words of praise at the end of article don’t make up for the aspersions cast in the beginning.  I would have written the article in reverse order.

Click here for my response to Stein’s comments. 

Comments

  1. “Nissen doesn’t receive any money directly from Amgen but his work brings millions of dollars to the Cleveland Clinic,” who pays his salary and contributes to his power and position as the leading cardiologist in the world and a video clip on the evening world news.

    He has this holier than thou attitude and gets away with his self serving bias and not so obvious COI in different ways. Are we that stupid and naive not to see his bias if not vendetta, in the past, dealing with companies like Merck and GSK. I can not help, but to be blunt in expressing my criticism after following Nissen sagas closely for the last 30 years and I do apologise for it.

  2. John Tucker says:

    Guida Rasi made some interesting arguments along this line (PLOS 2012, 9,1)

    “Surrounding the ongoing debate over sponsor-independent analyses is an implicit assumption that “analysis by independent groups” is somehow free from CoIs. We beg to differ.Personal advancement in academia, confirmation of previously defended positions, or simply raising one’s own visibility within the scientific community may be powerful motivators. In a publish-or-perish environment, would the finding of an important adverse or favorable drug effect at the p<0.05-level be more helpful to a researcher than not finding any new effects? …We submit that analyses by sponsor-independent scientists are not generated in a CoI-free zone and, more often than not, ego trumps money.

    Non-financial COIs are ubiquitous and are not confined to those whose opinions happen to be convenient to large financial interests. It may be better to acknowledge these and manage them rather than to pretend that they can be eliminated.

  3. James Stein says:

    The academic literature has long recognized the existence of multiple forms of potential conflict of interest (COI) beyond direct financial remuneration. Other potential COIs include “institutional” conflict (ie, generating income for your institution or employer), “intellectual” conflict (ie, an unwillingness to accept contrary positions), and the possibility that certain activities can increase one’s public or academic status or lead to future financial gain, among many others. Indeed, medical journals often focus on personal and institutional financial COI through a disclosure process. Although disclosure is laudable and a fine first step, it is not a particularly effective tool for managing potential conflicts of interest.

    The academic literature also suggests that not all potential COIs are avoidable, especially the non-financial COIs above, Indeed, avoiding them is not necessarily desirable, since their “harms” are unclear and their obviation may eliminate generation of knowledge, insightful review, and discussion. This is NOT the same weak argument used to justify the financial COIs, which are more severe and dangerous. Indeed, non-financial COIs, except the most extreme ones, often are not the “conflicts” of interest they are perceived to be, but instead are “confluence” of interest.

    This however, article impugns Dr. Nissen’s integrity. Its’ opening sentence sensationally asks if Dr. Nissen has a “problem,” and its implies guilt by association which is unfair. The article presents no evidence to support the contention that he has significant COI (even non-financial), that he did not disclosure any information (which, limitations aside, is the current standard of potential COI evaluation and management), or that he did anything questionable. If anything, the reporters who did not ask questions about his other forms involvement with pharma are the ones at fault for not doing their jobs by asking the questions people might be interested in. Dr. Nissen is a man of high integrity who led the ACC and other professional organizations to clean up their COI acts and inspired a generation of physicians to do the same. Because he is outspoken, quotable, and interacts with academia, industry, and the government, he is an easy target but this was not a fair handling of the issue. Your words of praise at the end of article don’t make up for the apersions cast in the beginning. I would have written the article in reverse order.

Trackbacks

  1. […] In my last post I raised the possibility that Steve Nissen, a highly influential cardiologist who has been an outspoken critic of industry influence in medicine, might have his own conflict of interest (COI) problem. In response, another cardiologist, James Stein, said that my post was unfair in its treatment of Nissen and failed to consider important distinctions and subtleties in the academic literature about conflict of interest. […]

  2. […] Nissen, MD, que ha sido una animadora para los inhibidores de PCSK9 Pero quizás su conflicto de intereses otra declaración merece un vistazo Larry Husten de CardioBrief […]

  3. […] This is the context in which to understand the issue of conflicts of interest. Because like in so many other cases, the breathless excitement over PCSK9 inhibitors runs far ahead of what we know for sure, but the hope for large benefits for patients seems to be enough for many physicians to want to change the rules – even if it is “just this once.” And we find ourselves asking “why?”  Is this really a good way for a great nation to run public policy? Larry Husten notes that Steven Nissen, MD, a keynote speaker at our Road to RightCare Conference and a strong and passionate voice against overtreatment, is a prominent supporter of PCSK9 inhibitors, and is currently leading an industry-funded trial of the drugs. […]

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