Roughly 80% of ESC Guideline Writers Have Financial COIs

The vast majority of experts who write and review some of the major clinical guidelines issued by the European Society of Cardiology (ESC), including those for ischemic heart disease, valvular heart disease, atrial fibrillation, and heart failure, have financial conflicts of interest, according to a new analysis.

These entanglements, whether or not they affect the final product, could raise doubts among clinicians and patients that undermine the guidelines’ message, sources told TCTMD.

Breaking down the type of conflicts seen across the different ESC documents, receipt of a direct personal payment, either for industry-funded talks, consulting work, or payments for serving on an advisory board, a committee, or as a clinical investigator, largely outpaced payments made directly to the hospital or money for research funding.

“I knew it would be prevalent, but I didn’t know just how prevalent it was,” senior investigator Benoy Shah, MBBS, MD (Southampton General Hospital, England), told TCTMD. “Excluding the guidelines for pericardial diseases, pretty much four-fifths of the authors had a relevant financial conflict of interest.” And while the present study focused on just five guidelines, Shah believes the problem is widespread throughout cardiology and medicine in general.

“It exists for heart valves, TAVI, MitraClip,” he said, referring to payments from device companies. “I have no doubt it exists for coronary stents, for biventricular pacemakers, [cardiac resynchronization therapy], defibrillators, the works. It’s everywhere. It’s pervasive. When you read the literature, we know that [these types of studies] have been done in almost every field of medicine. There’s such persuasive data that shows this, and this is not old, historic data. It’s happening right now in 2021.”

Shah said he hopes the study, which was published this week in Clinical Medicine, the journal of the Royal College of Physicians, kick-starts a conversation that ultimately leads to changes.

“We’d love it if there was at least some acknowledgement that this is a problem and a desire to move toward a different model, one that doesn’t necessarily exclude people who have worked with industry,” he said. “They have something to contribute and their views should be heard, but for the sake of transparency, integrity, and faith in the guidelines, they shouldn’t be writing the final document.”

We’d love it if there was at least some acknowledgement that this is a problem and a desire to move toward a different model. Benoy Shah

Stephan Achenbach, MD (University of Erlangen, Germany), president of the ESC, acknowledged the issue’s complexity, pointing out that the ESC has been incrementally strengthening its rules and policies around competing interests, noting that all relevant conflicts from guideline task-force members are compiled and published alongside the ESC guidelines.

Still, Achenbach said it remains critical to have input from experts and leading medical professionals involved in industry-funded research to build the best possible guidelines for patients.   

“Simply taking into consideration financial conflicts of interest would fall short,” he said in an email. With respect to their current process, Achenbach said that all competing interests are scrutinized by the chair of the Clinical Practice Guidelines Committee, and by the chairs of the guideline writing task force, with any serious concerns investigated before a task-force member is allowed to participate in guideline development. The same process is in place for reviewers, he said.

“We believe that transparency, coupled with a robust writing and reviewing development process, can address the potential for bias following the principle of checks and balances,” said Achenbach.

Lots of Guidelines, Lots of Conflict

The idea for this study first emerged in 2012, when Shah attended a session at the ESC unveiling the focused update of the atrial fibrillation (AF) guidelines. At the time, the field was transitioning away from warfarin to non-vitamin K antagonist oral anticoagulants (NOACs), a drug class that had earned a more prominent role in clinical care following several landmark trials. However, it was the conflict of interest slides—those flashed ever so briefly before meeting presentations—that caught his attention.

“I was really astonished, as it was the first time I’d been to a meeting where every single speaker showed a conflict of interests slide,” said Shah. “I was astonished at how little attention was paid to it. It just seemed like a very token gesture. The slides were full of conflicts, and there definitely wasn’t enough time to read what they said before they were just summarily dismissed.”

To look a little more deeply at the issue, the researchers dove into five ESC guidelines, starting the project nearly 3 years ago. They evaluated the competing interests of the doctors who drafted guidelines for ischemic heart disease (IHD), valvular heart disease (VHD), AF, heart failure (HF), and pericardial diseases, the latter serving as control of sorts because many treatments for pericardial diseases, such as aspirin, nonsteroidal anti-inflammatory drugs, and colchicine, are off patent. The guidelines were the most recent versions from the ESC, with the exception of those for the management of AF, which were based on the 2016 recommendations.

We believe that transparency, coupled with a robust writing and reviewing development process, can address the potential for bias. ESC President Stephan Achenbach   

In total, they identified 220 contributors to the five guidelines, of whom more than 80% had a direct financial conflict of interest with industry. The most common conflict was receipt of a direct personal payment (speaker fees, honoraria, consultancy, or payments for serving on an advisory board, as an investigator, or as a committee member). For example, 68% of authors of the IHD guidelines received a direct personal payment from industry compared with 82% of the AF guideline authors. Guideline reviewers had a similarly conflicted relationship with the pharmaceutical industry. Such relationships were less common among authors/reviewers of the guidelines for pericardial diseases.   

Next, the researchers looked at the studies that formed the basis for the pharmaceutical recommendations in the guidelines. In total, 42% of these studies were funded by industry, ranging from 5% of studies in the pericardial disease guidelines to 65% in the IHD guidelines. Overall, the majority of authors leading these pivotal studies, most often the senior investigator, had a direct financial relationship with the drug manufacturer funding the trial. Additionally, when moving from recommendations with level of evidence A to C, the latter based more upon expert opinion than hard data, the extent of industry involvement increased, said Shah.

Changing Tides

James Kirkpatrick, MD (UW Medical Center, Seattle, WA), who investigated financial conflicts of interest in cardiovascular guidelines from the American College of Cardiology/American Heart Association (ACC/AHA), said he was somewhat surprised by the pervasiveness of competing interests in the ESC guidelines. In their study of the ACC/AHA guidelines, which was published 10 years ago, they didn’t observe the same degree of involvement. In their analysis, 56% of nearly 500 physicians involved in creating the 17 guidelines reported a conflict of interest.

“I wasn’t aware that some of the changes that have been happening in the United States, specifically in terms of cardiology specialty societies following the Council of Medical Specialty Societies [CMSS] practice recommendations in regard to limiting conflicts of interest in the production of guidelines, appears not to be more of a trend worldwide,” Kirkpatrick told TCTMD. “It seems this recent trend may not have made it across the pond.”

The ACC and AHA have each adopted tighter controls for physicians drafting the various guidelines. In line with recommendations from CMSS, the ACC and AHA policy is such that the chair or co-chair of a guideline-writing committee, and at least 50% of committee members, must be free of all relationships with industry. Additionally, committee members can’t draft or vote on any recommendation if it is relevant to their industry relationship.

“Many of the other subspecialty societies in cardiology have followed suit and are very careful about this,” said Kirkpatrick. “Things have become much more—you could use the word ‘stringent’—but I would say that societies are now erring on the side of full disclosure and attempting to limit potential influence of industry relationships.”

Defending the ESC approach, Achenbach said that any guideline task force includes roughly 20 to 25 writing members with relevant expertise and all documents undergo up to three rounds of peer review chaired by two coordinators who are not part of the writing group. Peer review involves more than 80 independent reviewers, including representatives from the national cardiac societies, all of whom have different views, opinions, and subspecialties. All involved are expected to abide by the principles of evidence-based medicine, said Achenbach.

“The risk of bias or prevailing views is addressed by ensuring that the guideline-development process is based on an intense and independent review of all available evidence, transparency, and the principle of checks and balances,” said Achenbach. “Based on reviewer comments, the guideline draft is revised by the writing group, sent out to review again, and the process is repeated until all involved agree on the final version. As a result, the contents are extensively scrutinized to eliminate any undue influence from a member of the guideline task force before they are approved by all task-force members, the ESC, and, in some cases, also by the collaborating societies.”

I would say that societies are now erring on the side of full disclosure and attempting to limit potential influence of industry relationships. James Kirkpatrick

Under the ESC Declaration of Interest policy, no employee of a pharmaceutical/device company can serve as a member on the guidelines committee, direct company support for guideline development is not permitted, and physicians with significant stock ownership, patents, or royalties from intellectual property can’t participate on a guidelines committee.

The ESC has also started to put hard caps on the amount of money committee members can accept as a direct personal payment. In 2018, they placed a €10,000 per year limit for direct personal payments to guideline task force chairs and this cap was extended to the physician coordinators involved in the review process. Starting next year, which will impact guidelines published in 2024, no member of a guideline-writing committee can take in more than €10,000 per year in direct personal payments from industry, said Achenbach.

The EACTS, ESC, EXCEL Example

To answer the obvious question—why does it matter—Shah said there is ample evidence that financial payments influence how physicians think, even if they don’t acknowledge such influence. None of this makes them bad people, he said, but it’s critical for the guidelines to remain above the fray.

“You don’t want anybody to say, ‘Could these guidelines have been influenced because so-and-so received $5,000 or $10,000.’ You don’t want anyone to even have that question,” he said. “I’ve received replies on Twitter from patients who have talked about how clinical guidelines have let them down. There’s a lot of suspicion emerging among patients, certainly among very aware patients.”

You can end up in a very difficult situation if our largest body issues guidelines but a significant portion of doctors are turning around and saying, ‘Hmm, I’m not sure I believe that.’ Benoy Shah

To TCTMD, Kirkpatrick made a similar argument for limiting financial relationships between guideline writers and industry. There are data, he said, showing that consensus statements drafted by physicians with more conflicts of interest tend to favor more-expensive interventions as opposed to those drafted by doctors without competing financial issues. Aside from that, though, the larger issue is one of perception. Guidelines may not be adopted by clinicians because of perceived bias, and this ultimately leads to problems in adherence to appropriate medical therapy.

“We already have a problem with adherence to guidelines, so I don’t think we want to put ourselves in a position where these good things that should be happening are questioned because of undue influence,” said Kirkpatrick.   

Trust in guidelines is not something that should ever be taken for granted, agreed Shah. He highlighted the fallout between cardiac surgeons and interventionalists for the treatment of left main CAD following the EXCEL controversy. After allegations of missing data and failure to acknowledge surgery’s mortality benefit in this Abbott Vascular-funded trial—allegations the trialists deny—the European Association for Cardio-Thoracic Surgery (EACTS) formally pulled their support for the ESC revascularization guidelines for left main coronary artery disease. With the controversy, some surgeons on social media professed to have lost faith in the current recommendations and have called for an independent review (the ESC is currently reviewing the left main recommendations with EACTS).

“You can end up in a very difficult situation if our largest body issues guidelines but a significant portion of doctors are turning around and saying, ‘Hmm, I’m not sure I believe that,’” said Shah. “That’s a very dangerous place to go. Patients rely on these guidelines to guide care, and if we have a significant body of doctors telling patients, ‘Hey, look, these guys say we should do this, but I’m going to tell you something you don’t know. Here’s the reason why they said this. They’re all conflicted, and we should do this instead.’ That’s a very dangerous slippery slope.”  

What Should Happen?

Shah thinks that experts in their field, including those who have financial relationships with industry and those who have led sponsored clinical trials, still have a role to play. He cited the American College of Physicians’ guidance for managing competing interests as a good approach. For physicians with an active relationship with a company that has a direct financial stake in the clinical recommendations, they must either sever that relationship or resign from the guideline committee. If they are unable to cut financial ties or quit the committee, they can’t be part of the writing process, participate in discussions, or vote on recommendations. In circumstances where a physician might have an intellectual interest relevant to the guidelines, such as holding an opinion on a drug or device because they’ve been involved in a trial, they can participate in discussions but can’t draft or vote on the recommendations.

“That’s a good first step,” said Shah. “We could acknowledge their expertise and the insights they bring, and we’ll allow them to present their views and thoughts to the people who draft the guidelines. But for obvious reasons they shouldn’t be involved in writing the guidelines.”

Or, the guideline-writing committees could turn to other people entirely, he said, noting that roughly 20% of people in their analysis didn’t have any financial relationships. The National Institute for Health and Care Excellence guidelines, for example, are very strict about the extent of involvement with pharmaceutical and device companies, and yet they manage to attract physicians willing to participate in the writing process.

“If you know up front that ‘I want to be one of the [people] that helps write the guidelines, I can’t work for industry, financially at least,’ then people will have to make a decision,” said Shah. “They might decide ‘I get paid enough as a doctor, I don’t need that financial relationship with industry, and it’s more important for me to be involved in drafting the guidelines so that I can influence patient care.’ That could happen, too.”

Kirkpatrick noted their ACC/AHA study also showed there were a large number of doctors without financial relationships who could, and do, participate in the guidelines. “There’s plenty of them to go around,” he said.