Conflicts of interest (COI), both intellectual and financial, are prevalent in clinical practice guidelines, according to multiple recent studies.1-3 “Financial relationships between guideline authors and industry can be problematic because they can create conflicts of interest that influence guideline recommendations – and, ultimately, patient care,” says Jonathan Alpern, MD, assistant professor of medicine at the University of Minnesota.
Alpern and colleagues analyzed the prevalence and types of COI among Infectious Diseases Society of America guideline authors.1 Of 10 infectious disease guidelines, 47.7% of authors disclosed a relationship with a pharmaceutical company. One-third of the authors had at least one COI or high-level COI.
“Our findings are especially meaningful considering the strict definition of a COI that we used. This was done in order to avoid overstating the significance of the disclosed relationships,” Alpern notes.
The authors narrowly defined COI as a disclosed relationship between an author or spouse and a pharmaceutical company if the company, at the time of the guideline’s publication, manufactured a guideline-recommended drug. The study findings “highlight the delicate balance that exists at the interface of healthcare and industry,” Alpern adds.
Subject matter experts do need to collaborate with the pharmaceutical industry to drive innovation. Such relationships are of particular importance in the infectious disease field, considering the need for novel antibiotics in the face of rising antimicrobial resistance. “On the other hand, we can’t ignore the strong profit motive that exists in the pharmaceutical industry,” Alpern stresses.
Even the appearance of bias in clinical practice guidelines is problematic, since it could diminish public trust in medicine. “Ensuring we have functioning systems in place to keep practice guidelines objective and free of this influence needs to be a priority,” Alpern says.
Inaccurate disclosure of financial COI could undermine the integrity of guidelines and diminish physician and patient confidence in their recommendations, warns Maryam Mooghali, MD, MSc, a postdoctoral associate at Yale University’s Center for Outcomes Research and Evaluation (CORE). “The high prevalence of COI among guideline authors raises significant ethical concerns,” Mooghali says.
For instance, the primary ethical obligation for physicians is to prioritize patients’ well-being and best interests. If clinician guideline authors have financial ties to industry, recommendations could be influenced in a way that prioritizes certain products or interventions over what truly is in the patient’s best interest. “Moreover, in these cases, patients and clinicians may not have access to complete and unbiased information for making treatment decisions, thereby undermining patients’ informed consent,” Mooghali adds.
Mooghali and colleagues analyzed the prevalence and accuracy of industry-related financial COI disclosures of 270 U.S. physician guideline authors of 20 clinical practice guidelines published in 2020.2 Some key findings:
- Most guideline authors had financial relationships with industry, but more than 90% did not completely disclose all financial COIs.
- Only 72 authors accurately disclosed their financial COIs.
- 37% of authors disclosed no financial COIs but were found to have received payments from industry.
- An additional 8.5% of authors had disclosed a financial COI, but underreported payments received.
- Most guidelines had panel chairs with COI, all of which inaccurately disclosed their COI.
“This runs contrary to the recommendations put forward by the Institute of Medicine in 2008 on how to best manage COIs — namely that most authors within a guideline committee and the committee chair should not have financial COIs,” Mooghali says.3
COI disclosure often relies only on an “honor system” approach (i.e., self-reporting by guideline authors). Medical societies might not verify the information against the publicly available Open Payments database. Instead, they might rely on the authors’ self-reporting. “Also, guideline development is a resource-intensive process. Medical societies may not have the capacity to adequately oversee and manage COIs,” Mooghali adds.
Financial relationships can be complex, involving various forms of payment, such as stock ownership, research funding, consulting fees, speaker honoraria, or fees for travel and lodging. Stock ownership in a pharmaceutical company that manufactures the drug under evaluation might be more likely to influence recipients’ decision-making than a free dinner. “Identifying and managing these relationships could be challenging,” Mooghali admits.
Guideline authors usually are expected to recuse themselves from developing specific clinical practice guidelines or recommendations when they have significant financial COI that could bias their contributions. “However, there is often a lack of clarity about the amount and nature of financial COI that necessitates recusal,” Mooghali says.
Many researchers have studied COI in healthcare in recent years — how prevalent it is, how organizations manage it, and how much it may affect physicians’ recommendations. “But almost all of that work has focused on financial COI. While financial COI is easiest to quantify, intellectual conflict of interest can still potentially represent as big of a problem,” says Henry Brems, MD, MBE, a pulmonary and critical care fellow at Johns Hopkins University.
As experts in the relevant field, guideline authors may be asked to review their own work. Thus, the authors’ pre-existing opinions and biases could affect objectivity, Brems explains.
It is difficult to pinpoint exactly what constitutes an intellectual COI. “However, the criteria we used in our study show that at least some intellectual COI can be defined,” Brems asserts.
Brems and colleagues defined intellectual COI as whether a panelist was an author on a reviewed study, whether they had written an editorial related to a guideline recommendation, and whether they authored a similar guideline.4 People may disagree as to when an intellectual COI rises to the level of impermissible or causing bias. However, the same is true for financial COI, Brems argues. “There is no cutoff for financial value when an individual becomes clearly influenced by the COI,” Brems says.
Brems and colleagues examined intellectual COI in 14 cardiology and 25 pulmonology clinical practice guidelines published in the United States, Canada, and Europe in 2018 and 2019. Of the 737 authors of the 39 guidelines, 64% had at least one intellectual COI. Prevalence of intellectual COI varied by specialty. COI was more prevalent in cardiology guidelines than pulmonology guidelines (84% vs. 57%).
“It is certainly possible to develop guidelines while limiting intellectual conflict of interest. Guideline developers may just need to be more cognizant of the issue,” Brems offers.
There was not a single recusal for intellectual COI in any of the guidelines.
“Guideline developers may want to consider recusing panelists from voting on a recommendation if it is based on that panelist’s own study,” Brems suggests.
Some organizations relied on individuals reporting COI; after that, it was up to the individual to recuse themselves. Other organizations created rules that defined allowable vs. non-allowable COI for which someone may need to be automatically recused.
“Only a minority of organizations even had a policy that considered intellectual COI. They may not be consistently asking panelists to even report intellectual COI in the first place,” Brems notes.
It is possible a COI could lead to a biased recommendation for a treatment or diagnostic test that is not truly evidence-based. A biased recommendation could lead to inferior care. Another ethical concern is the presence of intellectual COI could threaten the trustworthiness of guidelines.
“Even if the guideline offers the best possible recommendation, there may still be harm if clinicians or patients do not trust the guideline enough to follow it,” Brems says. Generally, clinical practice guidelines promote high-quality, evidence-based care. However, clinicians also should recognize not all guidelines are perfect, nor will every guideline recommendation perfectly apply to their patients.
“If a clinician is unsure about a guideline recommendation, they should feel empowered to look at the literature themselves and use their own scientific and clinical judgment to treat the patient in front of them,” Brems offers.
REFERENCES
- Ahiskali AS, Drekonja DM, Alpern JD. Conflicts of interest among infectious diseases clinical practice guideline authors and the pharmaceutical industry. JAMA Netw Open 2023;6:e238592.
- Mooghali M, Glick L, Ramachandran R, Ross JS. Financial conflicts of interest among US physician authors of 2020 clinical practice guidelines: A cross-sectional study. BMJ Open 2023;13:e069115.
- Institute of Medicine. Knowing What Works in Health Care: A Roadmap for the Nation. Washington, DC: The National Academies Press; 2008.
- Brems JH, Wagner T, Diamant J, et al. Intellectual conflicts of interest among cardiology and pulmonology clinical practice guidelines. PLoS One 2023;18:e0288349.
Even the appearance of bias in clinical practice guidelines is problematic, since it could diminish public trust in medicine. Ensuring there are functioning systems in place to keep practice guidelines objective and free of this influence must be a priority.
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