Conflicts of interest in clinical practice: lessons learned from cardiovascular medicine
- PMID: 39313866
- PMCID: PMC12017469
- DOI: 10.1093/ejcts/ezae296
Conflicts of interest in clinical practice: lessons learned from cardiovascular medicine
Abstract
Cardiovascular diseases represent a major burden worldwide, and clinical trials are critical to define treatment improvements. Since various conflicts of interest (COIs) may influence trials at multiple levels, cardiovascular research represents a paradigmatic example to analyze their effects and manage them effectively to re-establish the centrality of evidence-based medicine.Despite the manifest role of industry, COIs may differently affect both sponsored and non-sponsored studies in many ways. COIs influence may start from the research question, data collection and adjudication, up to result reporting, including the spin phenomenon. Outcomes and endpoints (especially composite) choice and definitions also represent potential sources for COIs interference. Since large randomized controlled trials significantly influence international guidelines, thus impacting also clinical practice, their critical assessment for COIs is mandatory. Despite specific protocols aimed to mitigate COI influence, even scientific societies and guideline panels may not be totally free from COIs, negatively affecting their accountability and trustworthiness.Shared rules, awareness of COI mechanisms and transparency with external data access may help promoting evidence-based research and mitigate COIs impact. Managing COIs effectively should preserve public trust in the cardiovascular profession without compromising the positive relationships between investigators and industry.
Keywords: Aortic valve replacement; Cardiovascular research; Conflicts of interest; Coronary revascularization; Randomized controlled trials; Transcatheter aortic valve implantation.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Conflict of interest statement
A COI is defined as “a set of circumstances that creates a risk that professional judgement or actions regarding a primary interest will be unduly influenced by a secondary interest” [2].
A recent review on COIs mapped medical industry ties to activities and parties in the healthcare ecosystem [7]. There is an extensive network involving the industry and research, health professional education, guideline development, clinicians and patients. These relationships flow directly and indirectly through financial and non-financial ties, and a lack of appropriate oversight and transparency characterizes this intricate network [7]. Therefore, the state of knowledge on COIs, primarily financial, is complex and potentially incomplete and should include not only individual investigators, but also their affiliated institutions.
A major tool necessary, but not sufficient, to contain COIs is the disclosure of interest [1]. Disclosures have been widely applied in the policies of medical journals since 1984, although criticisms of their inefficiencies have been discussed [1]. Transparency of COIs also depends on honest disclosures by investigators, which is unfortunately not always the case [8].
To limit the impact of COIs in research, the International Committee of Medical Journal Editors (ICMJE) has published serial recommendations from 1979 to 2021 [9]. Authors, reviewers, editorial staffs and journals should disclose all relationships that could be viewed as potential COIs in the peer-review and publication process. Editors could then use this information to guide editorial decisions. Also, the ICMJE requests information on financial relationships, e.g. grants, royalties, consulting fees, stock ownership.
Among other recommendations, the Institute of Medicine 2009 report recommended prohibitions to limit the extent to which the industry can involve researchers, such as bans related to speakers’ bureaus and events directly controlled by the industry [2, 10]. This report highlights the importance of engagement of the institutions in adopting, implementing and strengthening COI policies.
In addition to financial COIs, non-financial ones can also take different forms [11]. For example, an investigator with a reputation for having developed a specific procedure may have an interest in having studies of this procedure be favourable, further branding his reputation. These non-financial COIs are more difficult to mitigate and identify. Not only do direct financial COIs need managing, but indirect financial COIs, including unrestricted research grants and donations to respective institutions/universities or research organizations, also require monitoring.
Although many diverging interpretations and comments arose regarding the recent results of large RCTs about myocardial revascularization and the treatment of valvular heart diseases and their interpretation, the recent publications of the North American and European guidelines for myocardial revascularization and the treatment of valvular heart diseases, respectively, have underscored the methodological bases on which panels derive clinical recommendations [46, 50, 51].
Despite the lack of generally accepted methodological standards, COIs among CPG panel members represent a well-known matter officially addressed by every scientific society, although not uniformly established. For instance, whereas the European Association for Cardio-Thoracic Surgery adopted the Institute of Medicine standards, where members with COIs must be a minority and the chair must be free from COIs, also involving a clinical methodology expert, the European Society of Cardiology requires the completion of COI forms and considers stock ownership or patents relevant to the guideline incompatible with the panel, whereas direct or indirect payments from industries are allowed up to 10,000 € [52, 53]. However, as disclosure rules for COIs have progressed, some loopholes remain, because grants to taskforce members’ institutions are allowed, representing a potential unconscious bias. On the other hand, the American College of Cardiology and American Heart Association state that >50% of the members and the chair of the taskforce must have no relevant relationships with industries, and conflicted members are not allowed to vote on recommendations for which COIs exist [54].
When developing CPGs, it is crucial that a balanced proportion of all the professionals involved in treating the addressed condition have identified shared, reasonable and evidence-based recommendations [46, 55]. Such equilibrium is even more important when addressing controversial topics. For instance, when considering the CPGs for the valvular heart diseases, in the European panel, the members are equally distributed among clinical cardiologists, interventional cardiologists and cardiac surgeons, affiliated with both the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery. Conversely, the North American panel is disproportionately composed of a larger number of cardiologists [46, 50, 56]. This imbalance may per se generate an uneven decision on the recommendations due to intrinsic professional COIs related to each specialist’s competence. Moreover, the consensus required for issuing recommendations is also critical (e.g. simple majority versus 75% of votes).
Such methodological approaches might preclude the development of shared recommendations, as happened with the 2021 American Heart Association/American College of Cardiology/Society for Cardiovascular Angiography and Interventions coronary revascularization guidelines [51]. These guidelines have generated a considerable debate, where progressively more surgical societies worldwide expressed concerns with some recommendations, therefore preventing their endorsement and spoiling their trustworthiness [46, 57, 58].
Because different recommendations have been developed by different panels based on the same evidence, it would be essential to consider whether other factors influence such decisions, including some indirect COIs [46]. For instance, Lenzer
Although the focus is commonly on financial COIs, non-financial ones are sometimes manifest in CPGs. Even the role of scientific societies, at times representing a “union” in defence of their specialty and thereby having unmitigable COIs, has been questioned [59]. This aspect is further biased since CPGs represent an important driver for a journal’s impact factor. Therefore, scientific societies have an interest in producing the CPGs published in their affiliated journals. Perhaps a neutral, external approach, using methodologists without skin in the game, using a reproducible framework to evaluate the evidence (e.g. GRADE), could produce balanced recommendations and avoid many COIs. A further example of how scientific societies should support a rigorous methodology in research is represented by the recently published position statement regarding the VARC-3 definitions for aortic valve clinical research [60].
The ultimate goal is to provide comprehensive, rigorous, reproducible and widely accepted CPGs developed by groups of independent methodologists that present the relative strength and weaknesses of the available evidence to a balanced multidisciplinary group of stakeholders for recommendation drafting and further independent review. This approach would lead to wider endorsements by scientific societies, thereby improving the trustworthiness and appraisal of guidelines and extending the recognition of recommendations by an extensive base of clinicians belonging to different specialties, everything for the benefit of patient care.
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