Addressing Conflict of Interest and Bias in Research, Education and Clinical Practice.

Abstract

I start my morning routine by scanning the national and local newspapers while enjoying my cup of coffee. Hardly a day goes by without news stories and work-related issues that somehow bring up conflicts of interest and bias. Climate change and universal healthcare are just 2 examples of topics that inevitably engender a great deal of doubt about what are facts and what are opinions. The Oxford English Dictionary defines conflict of interest (COI) as a situation in which a person is in a position to derive personal benefit from actions or decisions made in his or her official capacity (1Oxford Dictionaries. http://www.oxforddictionaries.com/us/. Accessed May 31, 2015.Google Scholar). In the context of medical research, education and clinical practice, COI often conjures up financial interests involving industry that may influence our abilities to make impartial decisions and judgements. Indeed, the prevalence of financial COIs between physicians and industry have become a major concern for the public and the medical profession regarding the integrity and trustworthiness of physicians, researchers and academic institutions. Such COIs could potentially threaten the objectivity and quality of scientific investigations, professional education and, above all, patient care. Physicians, researchers and the pharmaceutical and device industries share the common goal of improving the health and wellness of all peoples through discoveries, their translations into innovative, effective therapies and the prevention of various diseases. However, relationships among physicians, researchers and industry carry both benefits and risks. Collaboration between physician-researchers and industry facilitate fundamental discoveries and the development of new drugs and devices. Over the years, the pharmaceutical industry has gradually scaled back its own expensive research enterprises in favour of acquiring small biotechnology firms dedicated to specific diseases or products or of harnessing the brain power of physician-researchers at universities and academic health centres through contract research. Research collaboration between universities and academic health centres and industry provides mutual benefits. Garnering financial support from industry greatly facilitates the academic health centres' missions by expanding their leading-edge research, education and training programs and by advancing patient care. On the other hand, industry partners benefit from accelerated pipeline development at lower costs, from greater profits through increased sales of products and devices, and from augmented credibility and reputation indirectly through their philanthropic association with the universities and academic health centres. Increasingly, leaders of universities and academic health centres are invited to serve on industries' company boards or to hold comparable leadership positions. Senior management in industry may also be invited by universities and academic health centres to provide informal or formal consultations concerning a variety of matters that advance the institutions' missions. These kinds of arrangements, in which senior leaders are serving 2 masters, can give rise to potential COIs because universities and academic health centres and industry do not share the same strategic paths and missions, and those may indeed diverge from each other. One aspect that has received increasing scrutiny is the financial compensation of senior academic leaders who are serving as company directors or advisors. There have been rare instances in which an industry's compensation for the academic leaders far exceeds the salaries provided by the universities or academic health centres, in which case fiduciary responsibility to the industry may outweigh that of the universities or academic health centres, thereby creating significant COIs (2Steinbrook R. Disclosure of industry payments to physicians.N Engl J Med. 2008; 359: 559-561Crossref PubMed Scopus (31) Google Scholar). In 2008, 3 prominent physicians failed to report to their Ivy League institution that they had received large proportions of their incomes from industry consulting fees (2Steinbrook R. Disclosure of industry payments to physicians.N Engl J Med. 2008; 359: 559-561Crossref PubMed Scopus (31) Google Scholar). These and other revelations of egregious physician-industry relationships led to the recent enactment of the Physician Payment Sunshine Act in the United States, which mandated public disclosure by drug and device companies all payments to physicians that were more than $10 (3Rosenthal M.B. Mello M.M. Sunlight as disinfectant: New rules on disclosure of industry payments to physicians.N Engl J Med. 2013; 368: 2052-2054Crossref PubMed Scopus (43) Google Scholar). The Institute of Medicine (IOM) released a report in 2009 concerning COIs that covers many aspects of medical research, education and clinical practice; they pertain to individual as well as institutional relationships with industry (4Institute of Medicine Conflict of interest in medical research, education, and practice. National Academies Press, Washington2009Google Scholar). The IOM defined COI as “circumstances that create a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest. Primary interests of concern include promoting and protecting the integrity of research, the welfare of patients and the quality of medical education.” Secondary interests “may include not only financial gain but also the desire for professional advancement, recognition for personal achievement, and favors to friends and family or to students and colleagues” (4Institute of Medicine Conflict of interest in medical research, education, and practice. National Academies Press, Washington2009Google Scholar). The IOM listed 16 wide-ranging recommendations, with the overall goal to “protect the integrity of professional judgment and to preserve public trust rather than to try to remediate bias or mistrust after it occurs.” A further attempt to enforce a more profound cultural change in the medical profession is to initiate changes in medical schools and teaching institutions. The Pew Charitable Trust convened a task force in 2012 to review the literature on COI policies and to make additional recommendations concerning best practices in medical education (5Korn D. Carlat D. Conflicts of interest in medical education: Recommendations from the Pew task force on medical conflicts of interest.JAMA. 2013; 310: 2397-2398Crossref PubMed Scopus (20) Google Scholar). The guiding principle is to balance appropriate boundaries in physician-industry relationships with the need to encourage collaborations that are crucial for improving medical care and practice. The sea change in COI policies is laudable in its scope and noble intentions. Most academic health centres have developed COI policies to govern relationships between their faculty members and drug and device companies. Almost all medical schools in North America have developed policies that mandate their faculty members to disclose relationships with commercial interests before delivering lectures to medical students. Unfortunately, these COI policies have also resulted in unintended consequences that could potentially undermine their utility. It is worthwhile to consider in greater depth how COI policies negatively influence medical research, education and clinical practice. COI policies typically focus on financial gain because it is more objective and more easily quantifiable. Financial gain can be controlled and regulated more effectively than other secondary interests. Leading academic physicians are often recruited by drug companies to participate in industry-sponsored clinical research trials and speaker bureaus. These individuals have sometimes been unfairly targeted by their peers, the public and the media as promoting biased research or presentations for financial gain and career advancement. Some medical students may view teachers who have any relationship with industry as being biased and lacking in objectivity. The drug and device companies that are involved in bringing investigational products to market or in promoting disease awareness and treatment are viewed by the public and the media as being evil predators interested solely in increasing their profits and rewarding investors. Some alarmists would go as far as accusing the “big pharmas” of promoting drugs and devices that cause more harm than benefit. The recent marketing debacles of drugs like Vioxx and off-label promotions and kickbacks further erode public confidence in pharmaceutical companies. The development of clinical practice guidelines (CPGs) is another contentious area in which COI policies can adversely influence the outcomes and recommendations. One of the IOM recommendations for clinical practice guidelines is to exclude or limit the number of expert panel members with COIs. A majority of experts have ties to industry, mostly in the forms of research support and speaker bureau or consulting fees, so it appears somewhat unreasonable to conclude that the recommendations are motivated by a desire for financial gain or furthering other secondary interests. This is particularly true for evidence-based CPGs, such as the 2013 Canadian Diabetes Association's (CDA's) Clinical Practice Guidelines for the management of diabetes, which was free of industry involvement and was the diligent work of a large number of dedicated and unpaid physicians and healthcare professionals. All panel members disclosed their COIs, which are available on the CDA website. Nonetheless, critics continue to voice the negative influence of pharmaceutical companies in promoting adherence to the guidelines' goal glucose, lipid and blood pressure targets through aggressive pharmacotherapies, especially the use of newer and more expensive drugs. They neglect to take into consideration that new drugs are developed and introduced to the market not just because of superior efficacy but also because of fewer adverse side effects and better tolerability. Yet they tout industry greed as an inherent process of the guidelines' recommendations and implementations, and along the way, the experts involved in writing, promoting and implementing the guidelines are also tarnished. Another equally important secondary interest that is not often talked about in CPG development and continuing health education is what has been referred to as intellectual COI (6Akl E.A. El-Hachem P. Abou-Haidar H. et al.Considering intellectual, in addition to financial, conflicts of interest proved important in a clinical practice guideline: A descriptive study.J Clin Epidemiol. 2014; 67: 1222-1228Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar). The term intellectual COI can be defined as academic activities that create the potential for attachment to a specific point of view that could unduly influence an individual's judgement about a specific recommendation. This is a form of bias that results in making recommendations that are not scientifically valid or supported by the weight of rigorous evidence. The term cognitive bias refers to the ability to make systematic decisions that are based on cognitive factors rather than on evidence. The bias blind spot is the cognitive bias of recognizing the impact of biases in the judgements of others, while failing to see the impact of biases in one's own judgement (7Pronin E. Lin D. Ross L. The bias blind spot: Perceptions of bias in self versus others.Personal Soc Psych Bull. 2002; 28: 369-381Crossref Scopus (626) Google Scholar). Confirmation bias is the tendency to give more credence to data that confirm what the individual believes to be accurate. Both cognitive and confirmation bias can occur as a result of limited expertise in the subject, methodologic shortcomings or simply poor judgement. It has been argued that in continuing-education programs, bias is more troubling than COI, which involves only an unacceptable probability of bias (8Lo B. Ott C. What is the enemy in CME, conflicts of interest or bias?.JAMA. 2013; 310: 1019-1020Crossref PubMed Scopus (43) Google Scholar). COI is easily quantifiable, whereas bias is not. On the other hand, anti-industry bias, which has become quite prevalent among academic health centres and teaching hospitals, can affect patient care by overstating the risks and understating the benefits of new products and devices. Disclosures of industry funding can significantly affect physicians' interpretations of clinical trial data. A randomized study of how physicians interpret disclosure of sponsorship of research funding concluded that physicians discount the results when the hypothetical clinical trial was tied to industry rather than to sponsorship by the National Institutes of Health (9Kesselheim A.S. Robertson C.T. Myers J.A. et al.A randomized study of how physicians interpret research funding disclosures.N Engl J Med. 2012; 367: 1119-1127Crossref PubMed Scopus (140) Google Scholar). This is an example of bias blind spot, where financial COI could negatively influence clinical judgement and practice. The effort by academic health centres and teaching institutions to remove their ties to industry may improve the impression they make but is somewhat misguided and may impede the drive to achieve their mission of world-class medical research, education and clinical practice. Likewise, individual physicians' attempts to free themselves of industry interactions do not make them more virtuous. It is unfortunate that failing to harness the strengths and support that industry partners can provide is a missed opportunity. Canadian Journal of Diabetes, for its part, relies mainly on advertising revenues and subscription dues to support its ongoing operation. It maintains editorial independence, and all of our editorial board members provide full disclosure of potential COIs in accordance with the International Committee of Medical Journal Editors Form for Disclosure of Potential Conflicts of Interest (www.icmje.org/coi_disclosure.pdf). The editorial board ensures that all submitted manuscripts adhere to the journal's COI policies and takes steps to identify potential COIs between the authors and manuscript reviewers. The New England Journal of Medicine recently published a 3-part series revisiting COIs and the interactions between academia and industry, which I strongly recommend to our readers (10Rosenbaum L. Reconnecting the dots: Reinterpreting industry-physician relations.N Engl J Med. 2015; 372: 1860-1864Crossref PubMed Scopus (92) Google Scholar, 11Rosenbaum L. Understanding bias: The case for careful study.N Engl J Med. 2015; 372: 1959-1963Crossref PubMed Scopus (69) Google Scholar, 12Rosenbaum L. Beyond moral outrage: Weighing the trade-offs of COI regulation.N Engl J Med. 2015; 372: 2064-2068Crossref PubMed Scopus (75) Google Scholar). As long as COIs and bias are properly addressed and managed, with clear boundaries relative to industry partners, the medical community can better align the common goals of physicians, universities and academic health centres, and peer-reviewed journals with those of industry so we can fight and prevent disease and improve the health and well-being of everyone.