Mitigating Conflicts of Interest in Healthcare

Facts are not enough

Dominique Brossard delivered the meeting's first keynote address, presenting the perspective of someone who's spent a career in science communication and has also been deeply enmeshed in efforts to explain the COVID-19 pandemic to the public. While much of the scientific community has bemoaned the apparent rise in anti-scientific sentiment in recent years, Brossard explained that at least in the US, overall public trust in science remains quite high. "There's been a lot of talk recently saying that ... trust in science was declining," she said, but data from recent surveys show that over 90% of Americans still trust physicians and scientists either "a lot" or "some." Only the military enjoys higher trust among the general public.

However, these surveys also reveal disturbing trends. In particular, polarized national politics have led to significant gaps in trust on issues such as climate change, where Republicans are much more likely than Democrats to mistrust the scientific consensus. "Also, something that could be worrisome is that there is a small but increasing gap between rural and urban perceptions of scientists as a whole and science in general," said Brossard.

Traditionally, science communicators tried to close that gap with facts and explanations. If the public only understood the science, the theory went, they would reach the same conclusions as the scientists. However, as multiple studies have now shown, this "science literacy information deficit" model is wrong. "At the end of the day, information and knowledge matter in very different ways for different groups," Brossard explained. She added, "we shouldn't try to persuade our audiences that the experts are right, and their perceptions are wrong."

The central problem is that the different social and psychological contexts in which people interpret the modern deluge of information can lead them to draw radically different conclusions from the same facts. "We are social animals that cannot always think through things in a way that would put more mental cognitive load in our very complicated lives, so instead we're going to use heuristics and mental shortcuts to form judgments," said Brossard. Stories about conflicts of interest can provide one of those mental shortcuts, offering an easy, but not necessarily accurate, way to interpret a scientific claim.

While digital news sites and social media platforms didn't create this problem, they have amplified it to an unprecedented scale. Most people learn about new scientific issues through internet searches, which selectively amplify interpretations that draw the most attention. In this instantaneous feedback loop, stories about conflicts of interest abound.

Many of these reported conflicts have no bearing on the underlying science, but readers may latch onto them to justify their preferred conclusions and dismiss opposing views. "What matters is not what we think are conflicts of interest,” said Brossard, “what matters is what the audience's perception of that conflict of interest is.” She concluded, "trust in science and the medical community is strong ... but it could be easy to destroy."

Too many cards on the table

After Brossard's presentation, the meeting's first panel discussion began, with a broad focus on conflicts of interest in the healthcare system. Despite having diverse perspectives from different parts of medical and scientific research enterprises, panelists converged on a few major challenges and trends.

All of the speakers agreed that conflicts of interest are multifaceted, requiring a series of difficult decisions tailored to a specific case. "It's a very complicated ecosystem, and we need to make clear that we're talking about a lot of dimensions," said Bernard Lo. He also emphasized that the existence of a conflict of interest isn't automatically bad. "Conflicts of interest are just a risk of undue influence or bias, they're not the bias itself," said Lo.

While the group agreed that disclosing conflicts of interest is an important first step, "the biggest issue ... is relevance, and what's relevant to a [research paper's] author may be very different than what's relevant to the reader or to the journal editor or to the peer reviewer," Christine Lane said.

If researchers and physicians disclose everything, they must understand that those disclosures present unique challenges. As a conflict of interest officer for a major research university, Sonya Lawrence explained that her office has gone from processing a thousand or so disclosed conflicts a year to handling over seven thousand. Howard Bauchner, the panel's moderator, added that at the journals he supervises, the number of conflict of interest disclosures now numbers in the tens of thousands.

Diligent readers of the medical literature might study the authors' conflicts of interest on a paper, but in other parts of the healthcare ecosystem, the torrent of disclosures might do little good. Christopher Robertson cited a survey his team conducted on patients: "One of the questions we asked was, have you looked up your physician's financial relationships on the [medical center] website?" Less than 1% of the patients had done so.

Panelists agreed that while the field has progressed in recent years, disclosures and discussions of conflicts of interest must continue to evolve. "The more that we can do to refine and create trust among all the users of healthcare ... the better off we'll be," said Lawrence.

Everyone's a little bit conflicted

In the second panel session, speakers explored the boundaries of the meeting's topic by attempting to define conflict of interest and bias. They quickly agreed that the concepts defy simple good-versus-evil framing.

"When some people think about succumbing to a conflict of interest, for instance in the case of a physician, they think ... it's a matter of consciously putting other interests ahead of those of the patient," said Jason Dana. In the vast majority of cases, though, biases and conflicts of interest interact in more subtle ways. "[Everyone has] thought patterns that allow us to reach favored conclusions, and we do this without necessarily even knowing we're doing it," he said, adding that most conflicts stem from "unconscious and unintentional biases in our decision-making that we're all prone to having."

Panelist Donald Berry concurred, explaining that in clinical research and product development, "people become entrapped in what they've been doing, they learn to love their product and [think] it can do no wrong." The results can be disastrous, ranging from wasting money on technologies that should have been abandoned to continuing to treat patients with therapies that have objectively failed.

Even the data itself can encode hidden biases. "We think about things like selection bias or response bias, so who is opting into our study or our trial, and [are they] telling me the truth when I do a public opinion survey, are those biased results?" Andrea Jones-Rooy asked. Processing data into conclusions can compound those problems, as researchers often latch onto their favorite analytical techniques or algorithms, which may not be the best choices for every data set.

The problems of bias and conflicts of interest trickle down to journalists trying to explain new research to broader audiences. "People say 'we want just the facts,' as if that's a thing, as if ... even a straight news report isn't selecting which facts and in which order to present them," said panel chair James Hamblin. He argued that long-form stories that delve more deeply into the nuances of a problem can help, but current incentives in the media industry favor shorter, less analytical coverage.

Artisanal conflict management

Individuals' personal conflicts of interest are a major focus of discussion and policymaking, and the third panel explored the evolving strategies for addressing this issue. The conversation ranged across three broad areas: disclosure, financial conflicts, and non-financial conflicts.

"Clearly we believe that patients have the right to know the information that might be related to their treatment decisions, [and] it's also clear that clinicians have a wide

range of complex interests," said Katrina Armstrong. To address that, she favors public disclosure of physicians' and researchers' conflicts of interest through institutional and journal websites. However, she acknowledged that "providing the data is a long way from enabling patients to effectively understand those data and to decide how to use them in their decision-making."

Neil Powe and panel chair Heather Pierce agreed with the need for disclosure, and both added that besides needing more context and explanation, current disclosure methods are often cumbersome. "It's all managed locally by institutional review boards or committees at universities or other organizations, and [they're] all very different," said Powe.

Financial conflicts of interest have been the primary focus of most disclosure efforts in recent years because they're relatively easy to identify and have been shown to increase the risk of bias. In extreme cases, conflicts can even feed outright research fraud. "We've had really strong cases [of research misconduct] that indicated conflict of interest went into the mix," said Barbara Redman. Nonetheless, she and other panelists emphasized that the existence of a financial conflict of interest isn't a problem by itself, and that adequate safeguards can mitigate the risk of bias.

Non-financial conflicts of interest are harder to address, in part because they're so common. "We each engage in non-financial conflicts of interest all the time, every day in our lives, when we have to weigh different roles," panelist Paul Wolpe explained. Everything from career advancement to personal experiences can influence researchers' and physicians' decisions, often unconsciously. This complex web of interests is "not inherently manageable in the same way that financial interests are, and that's part of the reason why we focus on financial conflicts of interest," says Wolpe.

Show me the money

The meeting's fourth panel focused on what is often considered the bogeymen of conflicts of interest: for-profit institutions. "What has received the most attention in the last five plus years is the relationship between the biopharma company and the healthcare professional,” said Cynthia Patton, “and I think that the reason for this interest is a perception that perhaps the physician's autonomy or judgment is impaired [by the relationship]."

That perception carries over to policymaking. "If you look at the way conflict of interest policies by most academic institutions are framed, they have a kind of flavor of 'let's protect ourselves against the for-profit sector," said Michael Rosenblatt. He added that "they usually don't describe the benefits of what is often a confluence of interests."

George Demetri added that in the best cases, corporate-academic partnerships can lead to a "virtuous cycle" that ultimately benefits patients. Other panelists agreed. "We all need each other, and when we stop worrying so much about the perception of conflicts, and put whatever our perceived conflicts are on the table and work together, it's amazing," said Patton.

Nonetheless, many for-profit organizations have achieved decidedly less virtuous outcomes in their partnerships. Kathleen Bachynski pointed to the National Football League's conflict-ridden efforts to collaborate with public health organizations on preventing head injuries. As accumulating research shows, football poses a significant risk of head injury, a finding the League has long tried to bury.

"It's a really interesting transitional period right now where the industry is acknowledging concussion, trying to work with public health agencies, and the question is what are the conflicts that are coming now as a consequence of this?" said Bachynski. As an example, she pointed to an NFL donation to the CDC to address brain injuries, which the League restricted to a narrowly framed educational campaign.

Chair Paul Aliu and panelist John Rah pointed out that, at least in the biopharmaceutical industry, companies have been working hard to limit the risk that their support will bias research outcomes. Rosenblatt added that "most of these companies have a North Star [of] operating for the benefit of patients."

Laying down the law

James Sheehan began the meeting's second keynote presentation by highlighting an important feature of conflicts of interest. "Conflicts can influence action, but they're not acts, and they do not constitute a breach of duty," he said, adding that "it's a status in many ways, and the question we ask ourselves ... is what standards should govern it?"

Those standards, in turn, are a result of collective agreements that have evolved in different contexts throughout human history. As extreme examples, Sheehan pointed to the Palio di Siena, a semiannual horse race in Italy, and the Cardozo standard of fiduciary responsibility enshrined in American case law.

In the Palio di Siena, conflicts of interest are a celebrated part of the competition; jockeys are expected to take bribes to influence the outcome. "Clearly a jockey that is being paid off ... has a conflict of interest, but everybody understands that's how it works, and it's so much fun that people [have been] doing it for 600 years." The Palio di Siena acknowledges that breaking traditional societal rules can be fun, and makes that part of the rules. At the other extreme, many American businesses follow a standard cited by eminent jurist Benjamin Cardozo, who explained that partners in a corporation should be held to an inflexible standard of undivided loyalty, rejecting any relationship that could conflict with their fiduciary duty to that business.

Between these two poles, different organizations follow a range of standards. Many hospitals and academic research institutions prefer a middle ground that allows conflicts of interest, as long as they're disclosed and mitigated.

Simply having a policy, though, isn't enough. Sheehan looked at New York's Memorial Sloan Kettering Cancer Center, which in 2018 was the subject of a series of investigative reports by the New York Times and ProPublica documenting extensive violations of the hospital's conflict of interest policies by top executives. The scale of the violations, which involved physicians and researchers taking millions of dollars from industry while conducting clinical trials, drew widespread public opprobrium. In the wake of the scandal, Sloan Kettering's attorneys investigated, concluding that executives had repeatedly ignored the hospital’s established plan to manage conflicts of interest. "It is essential that you establish a policy and that you follow it," said Sheehan.

Sloan Kettering is far from alone. Sheehan also cited a prominent case in Baltimore, where the University of Maryland Medical System (UMMS) bought thousands of copies of a book self-published by Baltimore's former mayor, who also sat on the medical system's board. "After this came out, it turned out a third of the UMMS board received payments from the system through contracts with their businesses," Sheehan explained. In another example, prominent psychiatrists at several universities were forced to resign, after a Senate investigation revealed they'd taken much larger payments from pharmaceutical companies than they'd disclosed.

Enforcing conflict of interest standards is essential but unglamorous. "This is a job that's almost as much fun as credentialing in major teaching institutions, [but] it's a very important job and needs to be given to someone who's got sufficient status to require major people to complete it," said Sheehan.

Doing good or doing well

The fifth panel discussion of the meeting focused on conflicts of interest in nonprofit organizations. Panel chair Otis Brawley introduced the topic by explaining that "501(c)3 or non-governmental organizations are organizations that frequently have to raise money, and their fundraising can have some conflicts of interest; they also have a corporate culture where there can be emotional conflicts of interest." Besides wanting to avoid offending donors, nonprofits can also run into conflicts when they allow their names and logos to be used by companies as marketing tools, or begin making venture capital investments to fund their missions.

Matthew McCoy noted that patient advocacy organizations may drift into ethical gray areas when advocating policies and treatment guidelines. This "can raise concerns about...whether or not patient advocacy organizations' priorities and the messages that they're advancing are being inflected by these often substantial relationships that they have with the pharmaceutical industry," said McCoy.

"Our members are dealing with this every day," said Eleanor Perfetto, whose organization represents dozens of patient advocacy groups. The challenge of handling such conflicts has intensified during the pandemic, which canceled many of the traditional fundraising activities of these groups even as it increased patients' needs for their services. "They were hit by having more and more demand on what they provide, but less and less dollars to do it, and one of the things they turned to is probably sponsorship and industry funding," said Perfetto.

Alexandra Hall works for a rare disease-focused patient organization that takes careful steps to avoid and mitigate conflicts of interest. "Before we take on a new project...we always consider how might this impact our other work...and then of course it all comes back to serving our patient communities," explained Hall.

Panelists all agreed that regardless of the size of a nonprofit organization, it must not only establish conflict of interest rules, but follow them. "You have to have a structure, but you also have to have a process," said Susannah Rose, adding that "we can have all the policies we want, [but] if the culture and the process isn't aligned with those policies, then you have a real problem."

Fat wallets

In the sixth panel discussion of the meeting, experts in nutrition science discussed how tangled conflicts of interest combined with inadequate public sector funding have left their field in a precarious position. "We're confronting a terrible trifecta right now,’ said David Ludwig, “nutrition research is wickedly difficult, it's underfunded, and that situation is ripe for exploitation through conflicts of interest and industry manipulation.

Catherine Woteki explained the funding landscape for nutrition research, which in the US includes relatively modest investments by the NIH and a few other government agencies, whose focus is almost entirely on basic research. Funding for applied nutrition science, including such crucial issues as crop breeding, comes almost entirely from private industry. Jerold Mande noted that the NIH budget for nutrition research, around $1.9 billion, is less than 5% of the institutes' total budget. However, poor diet is the leading cause of illnesses such as heart disease and diabetes, which receive far more support. Food industry funding dwarfs the federal investment in nutrition science but often focuses on selling products that undermine public health rather than support it.

Session chair Kelly Brownell pointed out that industry influence extends beyond research funding. "The selection of people to the dietary guidelines committee could be heavily influenced by politics, enhanced by industry influences," said Brownell, adding that "if the process were perfect, what you'd find is a one-to-one relationship between what the scientific experts recommend and what actually occurs in the guidelines, and that's not always the case."

Simply disclosing researchers' conflicts of interest won't fix the underlying problem. "What's the purpose of disclosing? If the intent is to increase the quality of the research that's being done, it fundamentally has to address...that we are under-resourcing nutrition research," said Christine Cioffe. Mona Calvo argued that disclosures alone can help evaluate potential biases in the published literature.

Panelists agreed that regardless of disclosures, funding sources can bias findings. "Financial conflicts in nutrition are like a prevailing wind that blows in one direction,” said Ludwig, “they select for investigators with a priori biases toward one hypothesis, [and] fund the studies that are most likely to be favorable."

Alternative facts

The meeting's seventh session turned to one of the few areas more fraught with conflicts of interest than nutrition research: America's response to the COVID-19 pandemic. Panelist Rick Bright, who until recently led the US government's Biomedical Advanced Research and Development Authority, started the discussion. "We did have delays from political pressure,” he said, “we did have a lot of interference from politicians, current and past lobbyists, current and past high-ranking military officials, and current and past company officials from around the world trying from every angle to drive science through politics [and] press releases."

Session chair Arthur Caplan commented that understanding those political conflicts of interest was also challenging for citizens and journalists. Meg Tirrell agreed: "It's really trying to weigh whether something has scientific merit, and getting all of the information that you possibly can, and...when it is clear that something doesn't work, no matter how much powerful people are saying it might, if the science is clear, just making it clear in your reporting."

Some prominent researchers and physicians exacerbated the problem. "There were counterfactual scientists pushing a very different agenda, and I think none of us had planned for that in a pandemic,” said Deborah Birx. “[We didn’t anticipate] that there would be a whole group of credentialed Americans saying something completely opposite to epidemiologic insights that we all share.”

All of the panelists were keen to learn from the past year's missteps. Peter Honig emphasized the roadblocks the pandemic highlighted in the clinical trial process, and how innovations could help speed the development of therapies for a wide range of diseases in the future.

Others focused on the next pandemic. "It's never too late to do the right thing, and the right thing is to plan for it in a way that we haven't before," said Michael Osterholm, who advocates a comprehensive review of the successes and failures at all levels of government and industry during the pandemic. Derek Angus added that researchers in far-flung fields also need to come together. "We didn't really bring infectious disease epidemiologists together with economists, [so] we ended up having competing visions rather than an integrated academic vision to inform policymakers, and that's a huge failing," Angus said.

Abort, retry, ignore, fail?

In the meeting's final panel discussion, speakers engaged in a lively debate about one of the recurring topics from earlier presentations: the influence of private funding on academic and government research. While the group agreed that conflicts of interest are inherent to any human activity, panelists diverged on which types of conflicts are the most important in different contexts.

"The actual quantitative threats to the integrity of research and medicine are far greater from non-financial inducements and conflicts," than financial ones, according to Jeffrey Flier. He addressed the "reproducibility crisis" engulfing some psychological and clinical research fields, in which numerous results have proven impossible to replicate. "That comes from scientists on NIH grants, pursuing their careers and publishing research that is wrong and should never have been published to begin with," said Flier.

Vinay Prasad conceded that non-financial biases can affect research outcomes but argued that across a field, these types of influences may cancel themselves out. Referring to a class of anti-cancer compounds, he said: "I might be against PI-3-kinase inhibition, you might be for PI-3-kinase inhibition, you know, these biases go [in] different directions." Studies have shown that financial conflicts of interest, however, always favor the private company involved, which he compares to a documented carcinogen. "So it's like the tobacco of biases, it's the one that we could tackle first," said Prasad.

To do that, Prasad advocates a major overhaul of the clinical research process, including more direct government involvement in clinical trial management, measures to discourage former drug regulators from taking jobs in industry, and restrictions preventing industry-paid scientists from penning treatment guidelines or editorial articles.

Panel chair Lisa Kearns suggested keeping patients' interests at the center of the discussion. "Maybe we [should judge conflicts of interest] by whether there is actual harm, and to whom," she said.

Despite their differences, panelists agreed on the need for stronger protections against bias. "We are aligned in the end result, we want integrity and truth ... and the way to get there is to have smart people talking honestly about the areas where they might think they disagree," said Flier.