Conflict-of-Interest in AnesthesiologyCHAPTER 1

Conflict-of-Interest (COI) is omnipresent in medical science and the field of Anesthesiology is no exception.^1,2 Though COI issues are known for a century and well entrenched in healthcare, its common understanding and awareness in Anesthesiology is severely limited.³ Like in Medicine, COI impacts almost every aspect of Anesthesiology: i.e. clinical practice; academics and research domains. So, in order to avoid conduct reprimand and legal retribution arising out of lack of awareness or ignorance, it is high time that we wake up to applied implications of COI and embrace it in a wholesome manner.

Conflict-of-Interest ‘is a set of circumstances that create a risk that professional judgment or action regarding a primary interest will be unduly influenced by a secondary interest’.⁵ In simpler terms, COI is a situation in which personal considerations or interests, primarily financial, has a potential to induce bias in professional decision-making that adversely affects objectivity. The core ethical element that connects different stakeholders (Box 1) with activities enshrined in a typical healthcare gamut (clinics, research, academics) is ‘trust’.⁶ Further, objective reflection of clinical practice; justification of the treatment cost; research conduct and evidence creation; application of new evidence/recent advances; and disseminating awareness about health and treatment options is central to creation and sustenance of trust in the general public (Flowchart 1). The generation of COI by extraordinary pursuit of secondary interest, especially which result in deficit of primary service, fuel public mistrust and attracts greater regulation by relevant authority (departmental, institutional, sub-specialty, organization, government, state).

Conflict-of-Interest in itself is a generic term applied inflexibly and inconsistently in context of medical healthcare. COI is a concept that situates a possibility that a particular set of circumstances may undermine the primary interest by secondary financial/non-financial interest.

COI typically follows a potential → apparent → actual continuum, is subject to evaluation and adjudication of context it relates to, and its severity is defined by the overall harm to the recipient stakeholder. Although COI may involve both individual professionals and/or institution, it usually emanates out of the use of positional authority to eke out personal secondary gains from the assigned primary work for which he/she is being paid or employed for. COI can be broadly categorized into ‘tangible’ (that involves direct or indirect financial gains and pecuniary relationships) and ‘intangible’ (involving academics/research activity leading to name, fame, and influence) (Box 2).⁸ Evaluation of COI situations is based on identifying and relating the primary interest to the secondary consideration and then analyzing ‘conflict’ between the two.

The COI policies are specifically designed to analyze and to enforce sanctity on secondary financial interest, not because other interests are less important or irrelevant, but because they are more amenable to objective quantification. Sometimes the financial secondary interests are acceptable to an extent and are even valid provided they do not have any undue influence on the related primary interest. Although it is almost impossible to exclude secondary interest from a set of circumstances, social science investigations suggest that even miniscule returns (gift, favor, acknowledgment) which does not cloud primary interest as such, can lead to behavioral changes without the professional being aware of it.¹¹ This, over a period of time, can lead to individual professional developing a habit of seeking secondary interests and creating neo-COI situations.

Ernest Hemingway, the noted noble laureate, in his literary classic ‘For Whom The Bell Tolls’ (1940), deciphered complex conflicts (-of-interest!) within his characters that led to dereliction from their assigned primary duty of blowing up a fascist-controlled bridge during Spanish civil war of 1937.¹² Little did he know that almost eight decades later, JAMA Surgery would draw inexplicable comparison with the literary epic for explaining controversy around the use of vena-cava filters in the article entitled ‘For Whom The Benefit Tolls’.¹³ The first seeds of COI can be traced back a century ago when individuals and institutions collaborated with industries for research, education and practice. In 1920s Eli Lily, with researchers of University of Toronto manufactured insulin in quantities enough for clinical use and President Woodrow Wilson requested National Academy of Science to raise money from companies for academic research. However, the real conundrum of COI circumstances in healthcare delivery as we know today started in the 1950s when an out-of-the-box rethink was utilized to defend tobacco industries that were almost on the brink of banishment by scientific evidence that smoking causes lung cancer. John Hill, considered the ‘father of inventing COI’, when invited to navigate the tobacco industry out from troubled waters, stormed into the very fabric of medical practice and healthcare research by engineering a COI inventory designed to systematically run down the contemporaneous scientific evidence.¹⁴ Interestingly, by not actually resorting to direct disapproval or denial of what scientific consensus asserted and tormented tobacco industry, he raked up controversy around the validity of prevailing evidence by cultivating a carefully designed strategy that appeared to be in consonance with public health6 and supported scientific research. Hill and Knowlton Co., as a part of their service to a consortium of tobacco industry which was reeling under reactive backlash from restive consumers and public, rode on the shoulders of cynical, skeptical, and critical scientists who revealed in questioning the hypothesis, methodological conduct, and the generated evidence that tobacco kills.¹⁵ In a matter of decade (1950 → 60), the service conglomerate were able to manipulate and control scientific research, media communication, legal framework, and even the contemporary polity to induce confusion, create doubt, and also, fuel hedonistic smoking rituals. Probably, this was the first instance where financial COI forayed into purist institutions. The COI due to money pumped in by tobacco industry cultivated general public health advocacy and diluted direct tobacco-lung cancer link. They effectively used financial might and public relations to suppress any opposing viewpoint like, isolated outcry, ‘new’ evidence, motivated litigations, and random opinions. More surprisingly, the COI was able to shift responsibility of decision-making on ill-effects of smoking to the discretion of smokers by instituting statutory warnings on the cigarette packs.¹⁶

Conflict-of-Interest can be personal, professional, prejudice, or financial. While financial COIs are dealt extensively,²³ the other three which are classified under7 ‘individual’ COI need elaboration. The following types of COI situations are common (Box 3):

Typically, anesthesia practice involves use of drugs, devices, and techniques.²⁰ Each one of them requires close decision-making to cohere the best possible combination to facilitate anesthesia for a particular surgical situation. It is the prerogative of the anesthesiologist to decide on anesthetic agents, airway/moni-toring devices, and the anesthesia technique for the perioperative course of a surgical patient. In anesthesiology, due to a relative lack of a patient-anesthesiologist relationship,²⁶ there is a potential for bias because neither the patient desires nor he/she questions the integrity of anesthesiologists’ choices.

Further, more often than not, the anesthesiologist does not possess the necessary motivation and time to explain intricacies and issues to the patient. The anesthesiologist being largely dry to patients’ subtle needs, rides on essential nature of anesthesia care delivery (one requires anesthesia for surgery anyway) to do whatever they want to do and not care about the specific implications, cost or possible fallout of their decisions. Over the years, because the rapidly evolving field of anesthesiology has given more impetus to development of mechanisms and machines, the culture of brewing patient-physician relationship has taken a back-seat. Therefore, the anesthesiologists who usually have short and transitory subjective exchanges with their patients, the real-time interaction with machines and drugs becomes a primary interest, and relatively, the anesthetized and still patient become secondary object of interest. This relative lack of a patient-physician bond in conjunction with general human tendency towards other interests gives rise to ground for complex secondary COI, which are difficult to perceive and identify, and the most difficult to investigate and manage. Moreover, in order to ensure a safe anesthesia sojourn and return to consciousness, even when resorting to a shared decision approach,²⁷ a fairly informed patient entrusts the anesthesiologist to go ahead with his/her plan on-the-go. The anesthesiologist, who is otherwise supposed to function within the ambit of clinical guidelines and standard of conduct, still gets enough leeway to activate conflicted decisions without getting marked as such (Box 4).

In anesthesiology, the major quantum of research involves drug, devices, and the use of different techniques. Since research in anesthesiology toes patient's need, investigator will, and finances, there is always a possibility that COI situations would arise. Therefore, handling clinical practice of anesthesiology and related research would always have a real-and-present chance that COI would situate itself and influence the research proceeds (hypothesis, objectives, conduct, evidence generation, publication) accordingly. Moreover, over-and-above the personal interests that the anesthesiologist may have, there may be other interests which may trigger a COI scenario.

The acute conflation of healthy professional interests (subspecialty inclinations, a preference for a particular drugs/devices/technique) with specific targeted interests like, promotion, recognition and awards, and financial returns, invariably results in a significant COI platform.

Like clinical medicine practice and research, anesthesiology training and education is not free from COI situations. An investigator is likely to give the thesis scholar a topic that involves his/her area of interest irrespective of the difficulties therein; he/she may not be forthcoming on feasibility issues and the scope of the study area. Many a times, the anesthesiology trainees are allowed to learn a general technique first-up on actual patients without the mandatory pre-training on simulators.²⁸ Sometimes, the postgraduate residents are instructed to attend lectures with free luncheon on topics content beyond the scope of their curriculum. There are also instances where the trainees are allowed to use patients as training models, especially when they belong to free-category, thus exposing them to risk of complications owing to wrong techniques (no-effect, LA/neurolytic agent toxicity), over-exposure to radiation (during fluoroscopy guided pain blocks), and from failure to establish invasive monitoring (failed arterial puncture, catching carotid artery during internal jugular vein cannulation).

A typical COI situation where financial and/or non-financial secondary interests runs over the primary interest, needs to be analyzed first for its existence, then for its quantum, the harm it entails, and how it can be limited, managed or eliminated. Financial COI, for its objective presence, is fairly amenable to interpretation and enforcement by policy instruments. The non-financial COI are not only difficult to identify and analyze; for management, they are too complex to be contained within a structural realm. However, they are no less important and may have consequences that are far-reaching and more damaging with a long-term reverberating impact. In Anesthesiology, whereas a financial COI which actualizes harm is considered significant, at present, the comprehensive assessment of non-financial interest seems to be out of bounds. The clinical and academic Anesthesiology institutions, fraternity, and professional stakeholders who are entrusted with primary interest servitude, apparently, have only a general know-how of COI and usually follow the policies derived from other branches of medicine. Therefore, dedicated COI policy(s) governing anesthesiology sciences (practice, academic, research) is the need-of-the-hour. For Anesthesiology, the following strategies to evaluate and manage COI may be considered.

The current scenario of practice of Anesthesiology is far from being non-controversial. Every-now-and-then the anesthesiologists are tapped on the wrist by surgeons’ accusations, litigating patients, and competitive fraternal peers citing inconsistency and conduct. Ethical analysis and legal recourse notwithstanding, whenever an awkward situation puts professionals’ and/or institutions’ decision-making into a spot, the investigation into a possible COI trigger lurks around. Therefore, the individual professional anesthesiologists and the specialty office10 bearers should possess comprehensive clarity on the nuances of COI evaluation to be able to withstand deliberations on the content and the line of scrutiny. In principle, evaluation of a COI circumstance is based on the following:

Whenever a COI situation is considered, first the expected benefit from secondary interest is valuated and then whether it outweighs the bias it entails. Sometimes, secondary COI could be allowed to an extent if it benefits the primary cause (valid-COI). Therefore, for every COI situation, it is important to evaluate and balance the risk: benefit ratio arising out of the secondary interest.

The size and value of secondary interest should always be analyzed for its influence over the primary interest. Even small gifts, when given frequently in order to create and sustain physician-industry relationship, may bring about insidious subconscious changes in individual behavior. On most occasions, the professionals are either oblivious or are unaware of the changes in their behavior. Further, undue influence should be considered in the light of duration and extent of relationship.²⁹ The duration and closeness of professional's relation with industry sponsor heightens the risk of COI. The negative effects of COI are more pronounced if the latitude and traction of the professional (because of high institutional position and reputation) influence practice or research proceeds.

The COI which has an amplification impact on a large number of patients are considered more serious. When compared to investigator-initiated studies, the scope of harm due COI in research is greatest with clinical trials.³⁰ Therefore, the evidence generated during different phases of clinical trials which ultimately are applied to population at large, require greater diligence and monitoring.

If the research investigator is allowed to be less accountable for his/her actions and decisions to patients, participants, peers, institution, and health mechanisms of the state, the probability of harm due to COI increases. Institutions should take initiatives for accountability of healthcare delivery and research by promoting the disclosure clause, investigating the disclosed content routinely, managing the disclosure, and if required, prohibiting the investigator to participate in research.⁹ Importantly, institution COI policy should reflect their responsibility towards public in responding to query and grievances; justify remedial actions; and adjudicate penalty or compensation in case ‘harm’ has occurred due to issues with observance and handling of COI policies.

The evaluation and management of COI in Anesthesiology is a labor-intensive, contentious, and sometimes, an investigative process. It involves three major aspects; First, to identify and situate COI in a particular context/circumstance; second, disclosure of the COI; and third, the management of COI. Any research, clinical procedure, or related activity in Anesthesiology that is funded by a private11 organization (pharmaceutical industry, device firms) should be looked into from the outset for the presence of financial secondary interest. Even if it seems to be clean, the designated process needs to be monitored through its course. Finally, the research outcome warrants diligent scrutiny to ensure that the substantiated evidence is free from the influence of secondary interests. While cornerstone of managing financial COI in Anesthesiology is ‘Disclosure’,³⁰ ethical evaluation of the research proposal, monitoring of conduct of ongoing research, participation of stakeholders in establishing validity (internal, external) of research, and analyzing results for framing evidence for publication, are key to prevention. A general framework of controlling governance and policy of handling COI within a research institution is presented (Fig. 1).

Disclosure (for financial COI): Disclosure is considered the best way to manage a financial COI.³¹ Since a research can be affected by COI at every stage of development (hypothesis, methods, result interpretation, evidence creation), a proactive approach to disclosure of COI is desirable. However, there are a few concerns to settle. First, there remains a sensitive ethical issue of confidentiality and that any disclosure as a part of self-report or by institutional arrangement, should get limited dissemination within the institution;³² second an adequate ‘disclosure’ should be presented in simple and understandable language, and open to critical interpretation; and third, the disclosure which usually depends on self-declaration and self-reports, is vulnerable to subjective manipulations. Further, disclosure only offers to limit financial COI and does not eliminate it completely. Marcia Angell's school of thought, though radical, aims at a ‘zero tolerance’ dictum, i.e. there should not be any financial COI whatsoever such that manipulations around controlling and/or filtering disclosure cease to exist.³³

Many research societies have now adopted the zero-tolerance policy (e.g. American Society of Gene Therapy [ASGT]).³⁴ Similarly, many Journals have now stopped manuscript submissions of research funded by tobacco industry.³⁵ Recently, the noted writer Arundhati Roy employed zero-tolerance policy to recuse herself from a literary fest because it was sponsored by mining industry.

There is a possibility that influence of an individual's position or institutions’ stance which the people rely on, affects decision-making. Generally, COI stands separated from general “interest” if:

‘Reflexivity’ as a tool for managing non-financial interest attempts to seek heightened ‘disclosure’ in addition to routine disclosure required for a financial COI.³⁷ ‘Reflexivity’ account for the possible influence of personal and professional identity and interest on decision-making process, direction of research, and the dissemination of evidence. The ‘heightened disclosure’ advocates greater information sharing on investigator's/clinicians’ personal and professional identity, researcher's position statement, favored area of interest, and views on particular concepts and the research question.

The final aspect of ‘reflexivity’ enables one to look into possible influence of the identity of the investigator and/or institutional position and policy on research. COI policy primarily targets to minimize influence of secondary interest by:

Individual clinical anesthesiologists and researchers should always exercise due care to identify potential COI and manage accordingly. Apart from the common approaches to managing COI, such as, disclosure, recusal, substitution or the termination of relationship, the following mechanisms should also be considered wherever applicable:

Conflict-of-Interest is a clear and present nuance that can hamper practice and research in Anesthesiology. COI in Anesthesiology may result in harm to the anesthesia care service ‘recipient’ (the patients); the public at large (loss of confidence/trust); the science (conflicted evidence); and the ‘provider’ clinical anesthesiologist, investigators, institution (legal implications). A comprehensive basic and applied knowledge of COI will help anesthesiology healthcare institutions and individuals to ward off unknown challenges outside the area and scope of their domain. Moreover, getting aware and oriented about COI presence and implications would place them on a solid foundation of moral high ground in regard to patient care, clinical research, and advancement of science.14