Dr. Samir Grover was taken aback when, early in his gastroenterology career, he saw one physician speak two times and present contradictory conclusions about the same medication. Each time, the speaker presented identical data on a drug used to treat inflammatory bowel disease. First, he recommended the pharmaceutical. A week later, he deemed it ineffective. “How could this exact same data be spun in two very different ways?” asked Grover, a professor at the University of Toronto. One fact did change — the drug manufacturer that sponsored and paid for the lecture.
“Simply following clinical practice guidelines could lead doctors — even those who shun all industry gifts — to unwittingly dispense financially tainted medicine”
It’s no secret that drug makers pay doctors to hype their products to other doctors. But few outside the halls of hospitals witness physicians bending a single set of facts in opposing ways. After watching similar acts of statistical wizardry throughout his nine years of medical practice, Grover set out to investigate a more sweeping question about conflicts of interest. Do they infect clinical practice guidelines? Professional societies produce thousands of these documents every year. They steer the decisions of health care professionals and insurance companies about how to prevent and treat an ever-widening range of conditions — from diabetes, hypertension, and heart disease to arthritis, hepatitis, cancer, and depression.
Grover and his colleagues’ paper and a companion study recently published in JAMA Internal Medicine suggest that simply following clinical practice guidelines could lead doctors — even those who shun all industry gifts — to unwittingly dispense financially tainted medicine. More than half of the authors of guidelines examined in the two studies had financial conflicts of interest. In many cases, the doctors who wrote the guidelines were paid by the same companies that produced the drugs they recommended. In addition, a significant portion of the doctors who took pharmaceutical money failed to disclose the payments, many of which amounted to $10,000 or more.
The consequences of financial entanglements can be profound, warned Dr. John P.A. Ioannidis, a professor at the Stanford University School of Medicine. “Writing guidelines is like prescribing something to millions of people,” he said. For their part, medical societies acknowledge the need for impartiality in the guideline-development process. Yet many view the task of disentangling industry from clinical practice guidelines as challenging, maybe impossible. Grover believes that panels can do better, particularly when it comes to disclosing conflicts. Still, he said, “it would be very hard to find experts, particularly for high-grossing medicines, to be completely devoid of conflict.”
Grover’s study examined financial conflicts of interest for the authors of 18 clinical practice guidelines that provided recommendations for the 10 highest grossing medications of 2016. The blockbuster drugs included treatments for hepatitis C, rheumatoid arthritis, and Crohn’s disease. Nearly one third of the authors declared receiving payments from companies marketing one or more of the top-revenue medications. A separate study underscored Grover’s findings. It examined industry payments received by the authors of 15 gastroenterology guidelines published from 2014 to 2016. More than half of the gastroenterology guideline authors received money from industry. In both studies, the payments could be funds for clinical trials, or they could be for travel, honoraria, or speaking fees.
The payments could bias guideline authors’ votes on prescription recommendations, and they could also prompt guideline authors to try to sway the votes of other committee members, said Matt Vassar, the study’s senior author and a professor at Oklahoma State University Center for Health Sciences in Tulsa. Prior research suggests that doctors who receive pharmaceutical money and gifts have different prescribing patterns than their peers who don’t. A 2016 study of nearly 280,000 doctors showed that those who attended a single industry-sponsored meal, with an average value of less than $20, were more likely to prescribe a brand-name medication promoted at the event than alternatives within its class.
“Doctors who take money from companies tend to prescribe drugs from these companies more — quite a bit more,” said Diana Zuckerman, president of the National Center for Health Research, a Washington, D.C. think tank. “We have to assume the same for doctors on guidelines teams.”
Nearly one third of the authors declared receiving payments from companies marketing one or more of the top-revenue medications.
Especially worrisome to Vassar was his finding that the vast majority of the gastroenterology guideline authors failed to disclose industry payments that were reported in a federal database. Grover, too, discovered a lack of disclosure among guideline authors in his study — more than a quarter with conflicts failed to report payments they took from companies marketing one of the top 10 drugs. The undisclosed payments ranged from $1,638 to $102,309. For Grover, “the issue is not the conflict,” he said. “The issue is the transparency and adequately and appropriately noting conflicts.”
For Dr. Daniel Brauner, a professor of medicine at the University of Chicago, simply disclosing conflicts isn’t a cure-all. A geriatrician, he regularly sees patients suffering from what he believes are the consequences of specialists with conflicts writing clinical practice guidelines. “It’s over-prescription and a lack of really looking out for patients,” he said. When doctors adhere to multiple clinical practice guidelines, “older patients end up being on ridiculous numbers of drugs that will interact with each other and cause harm.” Yet doctors feel compelled to follow the guidelines, Zuckerman said. If they don’t, and their patients fare poorly, they can be sued for malpractice.
Ioannidis argues for a barrier blocking industry’s participation in clinical practice. “It’s fine to do research with industry funds,” he said. But then someone else should write the clinical guidelines. How can you be objective, he asks, “when every sentence you write may affect your own revenue, your own success, your own reputation?”
In 2011, the Institute of Medicine (IOM), now the National Academy of Medicine, developed standards to try to rein in conflicts. The IOM standards call for all the chairs of clinical practice guideline committees and at least half the members to be free of conflict. None of the guidelines Grover studied complied fully with the recommended standards. Why hasn’t the medical profession been able to police itself?
When doctors adhere to multiple clinical practice guidelines, “older patients end up being on ridiculous numbers of drugs that will interact with each other and cause harm.”
For one thing, some doctors and professional associations refuse to consider industry-funded research a conflict. After JAMA Internal Medicine reported widespread conflicts of interest in guidelines for the use of novel drug treatments for chronic hepatitis C virus infection, representatives of the groups that sponsored the guidelines defended the choice to overstep the IOM standards.
“Inclusion of panel members with research grants was essential for providing credible guidance to match the rapid pace of availability of these new and complex HCV treatments,” the 2017 presidents of the two societies that issue hepatitis C management guidelines wrote in a JAMA Internal Medicine letter. Instead of complying with IOM standards, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America created their own standards, ignoring industry-funded research as a concern.
Akilah A. Jefferson and Steven D. Pearson, the doctors who first reported conflicts in the hepatitis C virus guidelines while they were working in the bioethics department at the National Institutes of Health, responded by saying that if every specialty society similarly dismissed the IOM standards, “A race to the bottom could easily ensue. Every specialty believes that its guidelines are addressing fast-moving areas where the greatest clinical expertise is lodged in the hands of those doing the latest research.”
Half a dozen guideline authors with disclosed conflicts of interest declined interviews for this article. A spokesperson for the American Association for the Study of Liver Diseases, which, together with the Infectious Diseases Society of America, issues guidelines for hepatitis C management, said no one had time to talk. The organization did, however, send an editorial published last year in the journal Hepatology.
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The editorial defends the panel that developed the hepatitis C guidelines. A majority of the panel members had conflicts, but the authors — physician researchers at Brigham & Women’s Hospital in Boston and the University of North Carolina at Chapel Hill — maintain that the clinicians and researchers who are ideally positioned to write guidelines are “‘content experts’ whose consultation is sought by industry for advice and participation in clinical studies.” The editorial concludes: “Although a strict policy of zero industry interactions can minimize the prospect of the guideline development process being ‘hijacked’ by external influences … it comes at the nontrivial risk of weakening guideline quality.”
Dr. Patrick J. O’Connor, who has been writing clinical practice guidelines for about 25 years, scoffs at the notion that guideline authors have no choice but to take industry money. “The assumption is it’s your God-given right to take soft money and to write guidelines,” said O’Connor, a senior clinical investigator at the nonprofit HealthPartners Institute. “It’s not like you have to change your height by 6 inches. It’s something you can do something about if you want to.”
The American College of Cardiology and the American Heart Association have found a way. All of the authors of the two groups’ 2018 cholesterol-management guidelines were deemed free of conflicts. While some individuals did receive industry payments, none received payments that the two organizations considered relevant to the guidelines. One author, for example, was paid a considerable sum to consult for a company that makes a diabetes drug but does not make a cholesterol-lowering drug.
Greg Donaldson, an American Heart Association spokesman, said his organization and the American College of Cardiology believe that requiring all guideline authors to be free of all relationships with industry would render it “impractical if not nearly impossible for qualified experts to ever serve on a clinical guideline writing committee — thereby excluding many of the very best and most appropriate scientists and clinicians.”
“The assumption is it’s your God-given right to take soft money and to write guidelines.”
Dr. Neil J. Stone, a cardiologist at Northwestern University’s Feinberg School of Medicine, served as vice chair of the committee that wrote the most recent cholesterol-management guidelines, as well as chairing the committee responsible for guidelines published in 2013. When the latter were published, Stone faced criticism from medical journals and the lay press because some academic papers with outdated disclosures made it appear that less than a year had passed between his relationships with industry and the beginning of his work on the panel. Stone insists that a year had passed and that he was unfairly targeted for criticism — but he also says he took the criticism to heart.
After 2007, he said he began rejecting any payment that might flow from industry. It hasn’t been easy. When Stanford invited him to give a talk, he asked for a letter stating that the money reimbursing his travel expenses had no connection to a corporate entity. When the University of Pennsylvania could not provide such a letter, he paid for his own airfare and arranged his own lodging. “I’ve spent thousands of dollars of my own money to assiduously avoid taking anything,” Stone said. “When they have a meeting sponsored by industry, I sit and eat alone.”
Now he believes all the authors of clinical practice guidelines should be free of conflicts. He described the authors of the latest cholesterol guidelines as “first rate” and believes a no-conflicts policy only helped the panel by ensuring its credibility. He believes it’s important that clinical practice guideline panels be free of conflicts for one simple reason: “We want people to have confidence that there’s no influence of industry.”
Still, Stone, 74, sees it as a challenge for researchers, particularly young researchers, to avoid taking pharmaceutical industry money for clinical trials. “It would be great if industry never had to fund a study,” he said. “But that doesn’t happen.”
And, he added: “Because we have industry-controlled studies on statins, we have lifesaving drugs.”
Ronnie Cohen is a prize-winning freelance writer in Northern California and has regularly contributed to The New York Times and Reuters Health.
Update: Due to an editing error, a previous version of this article incorrectly noted the year Dr. Neil J. Stone stopped accepting payments that may flow from industry. He began this practice after 2007.