Clinical guidelines have the power to make or break a medication. If a committee recommends against a particular drug, Medicare and Medicaid, and then, likely private insurers, will decline to pay for it. Approvals that do go through can mean millions of dollars in sales, if not more.

So, the guideline committees that make those decisions — and the people who sit on those boards — play an important role for both the companies and the clinicians who want to choose treatments based on science, not money.

That’s why the nonprofit National Comprehensive Cancer Network (NCCN) takes great care to keep those who have financial conflicts off its 56 guidelines panels, noted NCCN CEO Robert W. Carlson, MD, in an interview with Cancer Therapy Advisor.

“Transparency and high-quality development, it’s what we live and breathe,” said Dr Carlson. “We have really rigorous processes in place to assure transparency and rigor and minimizing conflicts of interest. That’s why our guidelines — people trust them.”

But with companies spending millions each year to change medical minds, and human nature being what it is, conflict-of-interest (COI) specialists say it’s tough to build a conflict-free system as long as anyone’s taking any money at all.

The field of oncology is rife with conflicts, says Vinay Prasad, MD, a hematologist-oncologist and associate professor of medicine at Oregon Health and Science University in Portland. “Compared to other fields, I believe it’s probably one of the worst offenders,” he said, because well over half the drugs under development today are in oncology.

The NCCN’s guidelines look attractive, he said, and seem to be preferred by most clinicians, so he said he expects that NCCN’s committee members would be under significant pressure to accept industry handouts.

There is no research looking at COI on guideline panels, but studies suggest that even a small amount of money from industry can have a big impact on an individual’s opinion of a company’s product. “You don’t have to get $100,000 a year to be conflicted,” Dr Prasad said. “It’s the same reason the Hare Krishna give you a flower in the airport before they ask you for a donation. They do it to affect your behavior.”

The concern about COI will never go away, Dr Prasad said, as long as drug companies offer doctors money for consulting and personal services.

“There must be return on investment for that money,” he argued, and said that more rigorous public disclosure of industry payments is warranted. “You can’t blame a tiger for being a tiger. I don’t blame the industry.”

Dr Prasad doesn’t agree with the distinction made by some physicians that research funding is irrelevant. “Some people act as if they don’t benefit at all from that money,” he said, because it doesn’t come directly to them. But having the extra funding clearly benefits their institution and their department, he added.

NCCN guidelines committee members — including their spouses and dependents — are not allowed to accept more than $20,000 in personal payments from any single company or $50,000 in total from industry, according to NCCN rules. That cap includes consulting fees, honoraria, stock ownership and patent royalties, but not money for participating in data-safety monitoring committees, Dr Carlson said, because the job of such committees is to police company activities.

Every year, fewer than 1% of doctors on NCCN’s guideline review panel members have to step down because they have accepted too much money, or perhaps married someone in the industry, Dr Carlson noted. Panel members have to disclose financial interests every 6 months, and must resign if their financial position changes in a way that puts them in violation of the organization’s standards.

There are no earnings caps for members of the NCCN Guidelines Steering committee, which appoints the other committees but does not make drug decisions on its own, Dr Carlson said. Those 30 members, with 28 appointed by the institutions that participate in NCCN, are not subject to the same financial review. Dr Carlson said that if anyone on that body had a conflict, it would be diluted by the perspective of other members.

An examination of the steering committee’s earnings from corporations, according to 2017 data from the federal Centers from Medicare and Medicaid, showed that while most of them easily met the criteria for financial review, 3 of the 30 members did accept more than $20,000 in general payments from a single company, and 1 of those 3 members accepted more than $50,000 from the industry. Another member who accepted payments totaling more than these listed amounts recently left the panel, although the NCCN would not reveal any reasons for this individual’s departure. Thirteen panel members accepted less than $500 total from the pharma industry, and 10 panel members received more than $10,000.

Even relatively small amounts of money may be enough to influence decision making, said Aaron Mitchell, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, New York, New York, who researches COI. He said this is because of human nature. “There’s also the interpersonal relationship and the friendship and the sense of like, a give-and-take and mutual responsibility to give something back to someone who’s given you money,” he said.

In a recent study, Dr Mitchell showed that doctors who get money from a pharmaceutical company tend to prescribe more of that company’s drug than similar drugs.1 “It does appear to be related not to just whether you got money but the amount of money,” he noted. Doctors who received more than $100 behaved differently than people who got less, the research showed, suggesting that even relatively small amounts of money can have an impact on decision making.

There is really no way to know if payments have an effect on any individual or guidelines panel, Dr Mitchell said, because there’s no comparison group of doctors who haven’t accepted any money.

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It could also be that only well-established doctors who are already major prescribers of the drug are singled out for payments, said Samir Grover, MD, an assistant professor at the University of Toronto and gastroenterologist at St. Michael’s Hospital, and Rishad Khan, a medical student at Western University, Ontario, Canada, who collaborate on COI research.

But they both said that there’s little doubt that payments to doctors have an impact — or companies wouldn’t make so many of them.

“Just as smoking is a risk factor for lots of things, having industry ties in the form of general payments — it’s a risk factor for prescribing, it’s a risk factor for physicians trying to add drugs to hospital formularies,” Dr Khan said. “We don’t actually know if it influences clinical guidelines.”

The research duo is presenting an abstract at an upcoming conference, showing that there is a “rather substantial return on investment for biologic medicines” in gastrointestinal therapies. A similar study in 2016 showed the same pattern for statin prescribing,2 and in a recent research letter in JAMA Internal Medicine, the duo found that the presence of financial conflicts of interest in clinical practice guidelines may affect the objectivity of the recommendations. 3

Khan also cited a survey that found that the majority of doctors interviewed thought pharmaceutical payments had an impact on their colleagues’ prescribing behavior — but not on their own.4

Dr Carlson said that any concerns about COI on NCCN’s guideline panels are misdirected. “It’s not an accurate concern, because we have so many checks and balances in place.”

References

  1. Mitchell AP, Winn AN, Lund JL, Dusetzina SB. Evaluating the strength of the association between industry payments and prescribing practices in oncology [published online February 6, 2019]. Oncologist. doi: 10.1634/theoncologist.2018-0423
  2. Fleischman W, Agrawal S, King M, et al. Association between payments from manufacturers of pharmaceuticals to physicians and regional prescribing: cross sectional ecological study. BMJ. 2016;354:i4189.
  3. Khan R, Scaffidi MA, Rumman A, Grindal AW, Plener IS, Grover SC. Prevalence of financial conflicts of interest among authors of clinical guidelines related to high-revenue medications. JAMA Intern Med. 2018;178(12):1712-1715.
  4. Korenstein D, Keyhani S, Ross JS. Physician attitudes toward industry: a view across the specialties. Arch Surg. 2010; 145(6):570–577.

This article originally appeared on Cancer Therapy Advisor