Lisa Rosenbaum, MD, a cardiologist at Brigham and Women’s Hospital in Boston, caused quite a stir earlier this year when she challenged medical orthodoxy in writing a three-part series on conflict of interest issues that was published in the venerable New England Journal of Medicine.1-3 Rosenbaum argues that conflict of interest policies designed to detect and prevent bias in medical research have morphed into an “anti-pharma, anti-industry” mindset that stifles legitimate research collaborations that could lead to new treatments and advances.

A writer at the journal in addition to being a practicing clinician, Rosenbaum’s provocative series hit a central nerve. This was in part because the series was published in the prestigious journal that is generally seen as the standard-bearer of the conflict of interest movement since it called attention to the issue more than three decades ago.4,5 Given this history, Rosenbaum’s series was subjected to withering criticism by three former senior editors at the journal, who called it “a seriously flawed and inflammatory attack on conflict of interest policies and regulations. … [F]inancial conflicts of interest have repeatedly eroded the credibility of both the medical profession and journals.”6 On the other hand, an article in the Wall Street Journal said, “Rosenbaum’s measured, thoughtful essays call for a more rational approach to managing conflicts.”7

For her part, Rosenbaum dutifully notes the past damage caused by conflicts of interest in medical research, but argues the pendulum has swung too far — the medical profession has overcorrected and now harbors an anti-industry bias of its own. Rosenbaum agreed to an interview with IRB Advisor to discuss some of the issues raised and the ongoing debate that followed.

IRB Advisor: Could you comment on the implications of your series on conflict of interest for IRB boards? Some members may certainly fear this perceived taint of industry, even though as you note we are missing opportunities for collaboration and medical progress.

Rosenbaum: One of the big points of the series was that, yes, these financial conflicts engender bias but potentially so, too, do these anti-pharma, anti-industry agendas that are ideological and hard to measure — but really critical to pay attention to. The point is that as much as there may be an industry bias engendered by financial conflicts, there are other ideological biases including those that are anti-industry. And that was part of the main point of the series.

IRB Advisor: Is there common ground that allows appropriate skepticism without jumping to a guilty verdict at the first signs of some mutually beneficial relationship between industry and medical researchers? You really touch on this issue when you note: “Though I believe outrage over industry behavior has made reasoned regulation difficult, I don’t think we should excuse past wrongdoings or eliminate oversight. Rather, I think we need to shift the conversation away from one driven by indignation toward one that better accounts for the diversity of interactions, the attendant trade-offs, and our dependence on industry in advancing patient care.”

Rosenbaum: I wrote [the series] because I believe we can have more common ground. And I think the place we have to all begin is that we all want to treat disease. If we can just keep coming back to that and remembering that is what it is all about, I think we can establish that common ground. Do I think that it exists right now? Absolutely not.

IRB Advisor: You certainly got quite a reaction by raising this topic.

Rosenbaum: Yes, part of that is just because this was a different take. Before this, there has been sort of a steady tide in the tenor of what is written and published in this space [that said], “We need to manage conflicts better. We need to get the pharmaceutical industry away from our trainees, our medical students. People with pharma ties should not be on advisory panels, guidelines committees, etc.” The point is that much of what is written in the literature about this emphasizes the risks of academic/industry relationships. I wanted to put [this other view] on the table and start a discussion, and I think we did. The discussion is really just beginning. I know we wanted to get people talking and now we are still thinking about where we go from here.

IRB Advisor: You describe something almost akin to peer pressure in medical school to be a “pharmascold,” yet in many cases you reveal that perceptions of bias were flat wrong. The researcher wasn’t trying to get rich, a perceived bias toward a medicine was, in part, because it was better medicine, etc. Is this “the rest of story” that is not being told?

Rosenbaum: Exactly. First, I do think it’s important when we talk about these perceptions to make a distinction between marketing activities and those that revolve around research and dissemination of expertise. The research collaborations are so obviously important, but I think what’s hard is that the marketing practices drive the impression of what pharma is. But the way our market is set up — a free market — this [marketing] is just an inevitability. The drug companies, of course, seek a profit, but they are also seeking to make drugs and devices to help people. So I think a few things happen when we are so quick to dismiss pharma as evil, as far as medical students and trainees are concerned. One is that there is fear or a disincentive to collaborate. Another is that there is an increasing skepticism about any data funded by pharma — which we saw in the Kesselheim study8 I reference, even though the studies funded by pharma are often as well executed as any.

IRB Advisor: You concur with one of the researchers you interviewed that scientists who develop novel treatments should not be the ones testing them in humans, writing, “financial conflicts aside, the desire for the treatment to succeed, can cloud judgment.” Is that kind of decision currently being made on a case-by-case basis?

Rosenbaum: All of these rules are so nuanced and they depend on the institution and obviously the IRB board. Exceptions might occur for very rare diseases where there is one physician treating 12 people in the world. That, and some research with devices where [the designer] needs to be there to know how to put it in. But in most cases, my sense in talking with the investigators is that that [separation] was desired because it protected them.

IRB Advisor: You observe how many highly qualified people end up being replaced by those with much less expertise on advisory panels and specialty boards just to remove any hint of industry influence.

Rosenbaum: That’s a huge issue, actually, and not spoken about enough. What happens is the best researchers are asked to collaborate with industry, so then by keeping those people off advisory panels, you lose the people who know the most. I don’t support that.

IRB Advisor: Have you found IRBs are making these kind of decisions in order to be, like Caesar’s wife, above all suspicion?

Rosenbaum: Well, that’s what we see with the recent Campbell study9 that showed that, while the proportion of those on IRBs with industry ties is somewhat stable, they actually found evidence of anti-industry bias in terms of how protocols were presented. Indeed, the anti-industry bias was more common than the pro-industry bias, judging by their survey results. One point [my] series raised is whether by explicitly prohibiting those with industry ties, we are selecting for a group made up of people who have chosen not to work with industry, who may have an anti-industry bias. I think that was one of the findings of the recent Campbell study. Again, these are not biases that we are prone to scrutinize, but I think they are equally rampant and problematic.

IRB Advisor: Your closing comments note some of the consequences of our current system: effective therapies adopted more slowly; missed opportunities to understand complex medical topics; even life-saving therapies whose development requires the combined talents of clinicians and industry scientists. Yet even in recognizing these potential benefits, you describe being interested in an offer to work with industry, but reluctantly turning it down rather than risk the harsh judgment of the prevailing medical culture.

Rosenbaum: Yes, I have been asked and I want to, but I can’t. I can’t risk my credibility as a writer right now. But that’s absurd, right? We all have to play by these silly rules or else we risk losing our credibility. It’s really kind of bizarre.

IRB Advisor: Was there a moment when the possible consequences of the prevailing conflict of interest culture really hit you — inspired you to write your series?

Rosenbaum: It was the moment [when 2013 cholesterol guidelines expanded recommendations for statin drugs]. I was studying medication non-adherence and thinking a lot about the emotional factors that influence patient perceptions about medication and why they do not want to take them. It struck me that there was this sort of insinuation that the [statin] drugs were being recommended in order to make money for the docs involved or a drug company that may really weigh on patients. When I heard that articulated and these guidelines were really maligned for these conflicts that didn’t really exist, I thought, “This is crazy — this has gone too far. This is where we have to draw the line because if patients don’t want to take meds because they think [the system is corrupt] that is a big problem.”

REFERENCES

  1. Rosenbaum L. Reconnecting the dots: reinterpreting industry-physician relations. N Engl J Med 2015;372:1860-1864.
  2. Rosenbaum L. Understanding bias — The case for careful study. N Engl J Med 2015;372:1959-1963.
  3. Rosenbaum L. Beyond moral outrage: weighing the trade-offs of COI regulation. N Engl J Med 2015;372:2064-2068.
  4. Relman AS. The new medical-industrial complex. N Engl J Med 1980;303:963-970
  5. Relman AS. Dealing with conflicts of interest. N Engl J Med 1984;310:1182-1183
  6. Steinbrook R, Kassirer JP, Angell M. Justifying conflicts of interest in medical journals: a very bad idea. BMJ 2015;350:h2942
  7. Rago J. A Cure for ‘Conflict of Interest’ Mania. Wall Street Journal. June 26, 2015.
  8. Kesselheim AS, Robertson CT, Myers JA, et al. A randomized study of how physicians interpret research funding disclosures. N Engl J Med 2012;367:1119-1127
  9. Campbell EG, Vogeli C, Sowmya RR, et al. Relationships among academic institutional review board members: Changes from 2005 through 2014. JAMA Intern Med. doi:10.1001/jamainternmed.2015.3167. Published online July 13, 2015.