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Barmy ideas can gain a foothold just because of the prominence of the person voicing them.Photograph by Tamaki Sono / Flickr

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The first time I saw the term, I was mystified. “Hey, Dr S! We’re getting a few KOLs together to give us some advice about how to develop our new compound,” began the friendly e-mail from a pharmaceutical liaison, her return address reflecting her third employer in as many years. “Are you available to come to Atlanta next Saturday? We’ll give you an honorarium for your time.”

KOL? What was that? Because “Google” had not yet become a verb, I pulled out my old college dictionary, but its sole suggestion seemed implausible: the Knights of Labor, a nineteenth century workingman’s organization. In response to my puzzled reply, the liaison patiently explained that KOL in this context meant “Key Opinion Leader,” a respected person who can influence others’ beliefs and actions.

I was flattered: someone valued my opinions enough to pay real money for them? But I also found the term peculiar. Opinions seemed like a nebulous area in which to be a leader; much better to be recognized for expertise in scientific discovery, for development of new effective therapies, or for something else tangible and useful. I once had an uncle who was an opinion leader at family gatherings, always willing to share ill-informed viewpoints, half-baked ideas, and elaborate conspiracy theories with anyone polite or bored enough to listen. As Clint Eastwood crudely quipped in an early Dirty Harry film, “Opinions are like a**holes—everyone has one.”

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Later, I received other invitations that used a synonym for KOL, cribbed from public relations jargon: “thought leader.” This term, too, seemed strange when taken at face value, with its implied suggestion that if I could not lead in productivity, at least I might distinguish myself in thinking about being productive. In The Adventure of the Greek Interpreter, Sir Arthur Conan Doyle’s master sleuth Sherlock Holmes described his brother Mycroft as just such a leader: a brilliant deductionist who could have been a better detective than Sherlock, but who instead lived mostly in his own mind, rarely bothering to stir his ample backside from its familiar armchair in London’s stuffy Diogenes Club. Sherlock complained to his companion Dr Watson, “[Mycroft] has no ambition and no energy. He will not even go out of his way to verify his own solutions, and would rather be considered wrong than take the trouble to prove himself right.” Imagination without execution, like a hypothesis without supporting data, is vapor.

When I mentioned these stalkers to a senior colleague, he was horrified.

I went to Atlanta and enjoyed the meeting with other KOLs, each of whom had far more experience than me. (At the time, I still had a six-figure medical school debt, so I also appreciated the honorarium.) Because all the advisory board involved was thinking and talking—not frantically washing dishes to keep up with a busy restaurant, mowing lawns on a muggy August afternoon, dodging punches from angry drunks while moonlighting in an emergency room, or any of the other jobs I have taken to earn a buck—it felt like the easiest day’s work ever.

The company that had called that first advisory board was new to oncology, was planning a clinical trial to test a drug they had obtained in a merger, and needed some help from physicians who treated patients. I, in turn, appreciated hearing the perspectives of senior colleagues, especially views or interpretations of data that I had not considered before. It also felt good to be included in a “club” of active investigators in the area of diseases, even if only as a junior member—a tangible reward for long nights and weekends of work. The company asked us good questions and took our collective advice to heart. The advisory group’s recommendations largely coalesced, and the resulting clinical trial was successful, eventually leading to a US Food and Drug Administration approval.

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Over the years, I’ve participated in many other advisory committee meetings and, although many have been models of healthy and productive academic-industry collaboration, not all have been as enjoyable as that first one. In some cases, the panel seemed less a forum for exchange of opinion and instead just another way for a company to disseminate a marketing message—a chance to raise awareness of a drug’s profile or quell emerging fears on drug safety. Too often, a company’s representatives have already decided on a clinical trial design and drug development plan and seem to be simply going through the motions of soliciting external advice, unwilling to heed sensible recommendations of clinical advisors, even when a draft trial design is impractical or a proposed development program unwise. Were it not for patients put at risk and wasted time, I might indulge in a bit of schadenfreude when ill-considered trials from stubborn sponsors predictably fail.

I have also learned that this type of work is not quite as easy as it seemed at first. Many of the questions that arise in an advisory board setting are difficult, with no clear answer, such as those that involve attempting to read the minds of US Food and Drug Administration regulators. Companies decide which confidential data to share with advisory boards during their discussions, and if these data are incomplete or cherry-picked, the panel may not be able to provide the best possible advice. Advisory boards can be convened too early, before there are enough data to form meaningful opinions, or too late, after a key trial fails and a drug is already moribund. Peer pressure in advisory settings can be intense, and if a department chair at a major cancer center expresses a strong opinion, it takes a certain degree of courage for a second-year faculty member to speak up and disagree. And sometimes a loud-mouthed colleague just ruins the day for everyone.

Sociologist Elihu Katz observed a half-century ago that certain leaders are disproportionately influential in a variety of settings, and advisory boards are only one forum in which KOLs can be found. For drug companies, a widely respected senior expert who thinks a new molecule is a major advance and discusses it favorably at conferences is more valuable than hundreds of thousands of dollars of advertising or a flashy booth at an annual specialty society meeting. A friend who works for a large oncology pharmaceutical firm tells me that her company’s marketing teams spend a great deal of time discussing how to manage KOLs in diseases relevant to their product portfolio, cultivating opinion leaders like bonsai trees to keep them from growing in undesirable directions. Companies have valid reasons for concern: when a highly influential KOL goes on the warpath against a drug she feels is ineffective or unsafe (or that she just doesn’t like, perhaps because the drug’s sponsor passed her over as leader of a pivotal trial), it can become a public relations nightmare and harm the bottom line.

Insight does not always correlate with reputation or length of experience.

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I once witnessed a bold attempt at opinion control first hand when, as an uninfluential and unknown first-year faculty member, I made a comment in a regional continuing medical education (CME) session about the disappointingly low response rate of a cancer drug in development. I said that although the drug could be helpful for some patients, a complete remission rate of less than 15 percent was a sign that we still needed more research and better therapies for the disease. A representative of the drug’s sponsor was in the audience and took offense at my remark. After the session I overheard him complaining to the meeting organizers, arguing that because his firm helped sponsor the meeting, their product deserved “fairer” treatment than what he thought I had given. To the organizers’ credit, they reminded the representative that CME is meant to be unbiased and not influenced by meeting sponsors. When he refused to be placated, they told him to go fly a kite.

For months thereafter, at every conference I spoke at, the representative or one of his colleagues lurked in the audience and asked me aggressive questions that challenged almost everything I said about their drug. Naively, I thought this was part of how such meetings played out—just another one of the scraps that characterize academic life. But when I mentioned these stalkers to a senior colleague, he was horrified. He called a leader in the company immediately and threatened to report the behavior to a regulatory group, and my shadows suddenly vanished. (The company also eventually disappeared.) I wondered what might have happened if, instead of being a nobody, I was my mentor: a master teacher who drew large audiences at every presentation and received dozens of e-mails and calls each day asking for his clinical opinion.

A few years after the e-mail that first introduced me to the term KOL, a visiting salesman inadvertently left a confidential paper in my office with a list of colleagues’ names, which revealed that some companies maintain an informal taxonomy of KOLs: local KOLs who see many patients or influence hospital formularies, regional KOLs who frequently have patients referred to them by community oncologists, and national KOLs who write practice guidelines and journal editorials, are invited to speak at major conferences, and lead important clinical trials. This eye-opening list included almost every physician I knew working in the disease area, which made me feel rather less than exceptional.

Opinions are divided about just how influential KOLs actually are—how “key” are key opinion leaders. Insight does not always correlate with reputation or length of experience. Some great ideas have been treated skeptically and their acceptance delayed because the idea’s originator was an unknown person or considered an outsider by a field’s narrow cabal of KOLs—think Augustinian friar Gregor Mendel and the principles of heredity or polar explorer Alfred Wegener and continental drift. Conversely, concepts that are wrong, unsupported by evidence, or even barmy can gain a foothold just because of the prominence of the person voicing them.

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Still, human nature tends to value the opinion of famous faces above the proverbial man on the street. Only the credulous or foolish would uncritically accept actress Jenny McCarthy’s opinions on vaccines causing autism or respect Suzanne Somers’ arguments about the superiority of unconventional treatments for breast cancer. But far greater numbers might fall into the “Nobel laureate trap,” taking the musings of Nobel prize winners seriously when they venture far outside their field and into fringe beliefs (eg, Kary Mullis and AIDS denialism, Linus Pauling and megadose vitamin C, or Luc Montagnier and homeopathy).

Because failure is frequent in medicine, those physicians who have become known as opinion leaders, key or otherwise, should retain some humility. One of the most notable names in the field of chronic lymphocytic leukemia is Kanti Rai, whose 1975 staging system began a new era of research into the disease. Several years ago, Dr Rai began a “Meet-the-Expert” session at the American Society of Hematology annual meeting with a characteristically disarming comment, “I don’t like the name of this session, because no one is an expert in chronic lymphocytic leukemia. I have been studying this disease for decades, and still too many of my patients die. If I were truly an expert, the disease would have been cured by now.”

David P. Steensma is an associate professor of medicine at Harvard Medical School and an attending physician in hematologic oncology at the Dana-Farber Cancer Institute.

This article was originally published on Cancer Focus in June 2017.

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