By Ethan Sim
Impartiality is a cornerstone of scientific inquiry (Lacey, 1997), and undergirds science’s ability to accurately inform human understanding and policy (Oliver & Boaz, 2019). Scientific impartiality is often juxtaposed against vested interests – secondary goals which diverge from the primary aim of elucidating truth (Babor, Miller & Edwards, 2010). When these interests pose a significant chance of interfering with research, a conflict of interest (COI) arises (Resnik, 2007). Although COIs were traditionally thought to stem from commercially funded scientific investigations (Smith, 2006), the debate surrounding COIs has since grown to encompass nonfinancial interests and the publication process. This expanded scope has in turn fuelled further discussion about the nature and extent of COI influence in research, along with the measures needed to limit it. Ultimately, holistic measures against COIs, which involve all stakeholders in the research process, will be necessary to preserve impartiality in science.
While financial interests often cause COIs (Galea, 2018), it would be an oversimplification to conflate the two: scientists may be influenced by a diversity of vested interests, both financial and nonfinancial. The primary aim of science is to improve human understanding of the natural world (Miller, 2007). Implicit in this aim is the notion of faithfulness to facts (Reiss & Sprenger, 2020) – scientists are expected to design experiments and report observations without bias to obtain accurate conclusions (Montuschi, 2017). However, the nexus between science and policy, a product of public trust in science, has led to powerful incentives to distort scientific research (Rosenstock & Lee, 2002). Such incentives arise because policy changes may serve financial interests (Bero & Grundy, 2016). A scientist may be an employee of, or receive funding from, an industry which stands to profit from policy changes, and may thus face pressure to obtain conclusions which support the adoption of such policies. For instance, reviews sponsored by the pharmaceutical or tobacco industry are more likely to express conclusions favourable to industry interests (Smith, 1998); these interests may include the adoption of a new therapeutic regimen (Stelfox et al., 1998), or stymieing government regulation (Barnes & Bero, 1998). Apart from financial interests, policy changes could also serve personal convictions; scientists aiming to influence policy through research (Evans & Cvitanovic, 2018) might be more likely to obtain conclusions which support their personal beliefs (Krimsky, 2006). Yet, even the absence of industry and policy influence, the tight link between scientific research and career advancement may lead to overzealous and unethical experimentation (Saver, 2012). For example, critics argued that the desire to achieve an important result led Landon et al. (2009) to expose control subjects to unnecessary harm in a study investigating diabetes mellitus treatment (Stell, 2010). Although financial and industrial interests are major causes of COIs among authors, it would be erroneous to diminish the influence of interests either nonfinancial or personal.
Although much attention has been devoted to authors’ vested interests, the interests of other stakeholders in the publication process merit greater scrutiny. Due to authors’ status as sources of information, their COIs have the greatest capacity to influence the conclusions of scientific research, and most journal COI policies have justly been focused on mitigating their impact (Ancker & Flanagin, 2007). However, there is growing awareness of the importance of peer reviewers’ and journal editors’ COIs in undermining the objectivity of scientific research. By identifying weaknesses in manuscripts, such as unsubstantiated claims or flawed design, reviewers maintain the high standards expected of scientific research (Kelly, Sadeghieh & Adeli, 2014). Reviewer comments are then used to inform editors’ decisions to accept or reject a manuscript for publication (Resnik & Elmore, 2016). In this sense, reviewer and editor impartiality are necessary prerequisites for accurate and rigorous science. However, such impartiality may be threatened when COIs, such as personal connections or financial interests, are present. For instance, some journals, such as the BMC series, permit authors to nominate peer reviewers for their manuscript, leading to concerns that authors may nominate colleagues who may give favourable reviews more readily (Wager, Parkin & Tamber, 2006). This sentiment was exemplified by a study which found that author-suggested reviewers were more likely than editor-suggested reviewers to recommend acceptance for publication (Schroter et al., 2006). While peer reviewers may be more susceptible to nonfinancial COIs, editors may be more vulnerable to financial COIs, due to their routine communication with financially motivated groups, such as advertisers and corporate sponsors (Desai & Shortell, 2011). The concern that such COIs could likewise influence the review process was justified by a study of 52 high-impact US medical journal editors, which found that more than half received personal payments from industrial sponsors (Liu et al., 2017). Far from being limited to authors and their primary investigations, the ability of COIs to weaken scientific impartiality may be mediated by all aspects of the publication process.
Given the harm that COIs may pose to the validity of scientific research, it is unsurprising that COIs are thought to be uniformly detrimental to scientific progress. However, this perception may be superficial, as the nature of COI influence may vary with the nature of the underlying vested interest (Hurst & Mauron, 2008). While there is widespread agreement that financial COIs are damaging to scientific progress (Fabbri et al., 2018) and public trust in science (Feldman & Mann, 2019), growing awareness of nonfinancial COIs and their potential harm has led to perceptions of equivalence with financial COIs (Mahajan, 2013). This in turn spurred efforts by journals, such as Nature (Nature, 2018), to require their disclosure alongside financial COIs. However, this paradigm of equivalence has been challenged, most notably by Bero and Grundy (2016), who argued that the focus on nonfinancial COIs could divert resources and attention from financial COIs, which are more influential and damaging. Furthermore, the same authors argued that the term “nonfinancial COI”, which incorporates personal beliefs and careerism (Galea, 2018), is itself merely shorthand for, and detracts from, the problematic context in which scientific research takes place (Bero & Grundy, 2018). Yet, this view has itself been challenged: financial interests may influence scientific research through nonfinancial routes, such as industry endorsement; ignoring nonfinancial COIs would therefore imperil scientific objectivity (Wiersma, Kerridge & Lipworth, 2018). A possible resolution could be that nonfinancial COIs exhibit greater variation in their influence on scientific research; such influence, however, pales in comparison to the detrimental impact of financial COIs.
While attempts to generalise the nature of COI influence have generated controversy, greater consensus exists regarding the extent of COI penetrance in scientific research. Financial COIs, often in the form of industry-sponsored research, tend to be especially pronounced when economic interests are at stake, such as when research into chemicals, pharmaceuticals, or consumer goods is conducted (Rosenstock & Lee, 2002). Critically, the ramifications of such COIs may extend well beyond the arena of scientific opinion, and cause detriment to public health and safety (Resnik, 2007). Coca-Cola, for example, indirectly funded research which showed that obesity was due to inactivity, rather than a poor diet (Barlow et al., 2018), potentially influencing obesity policy in America and China (Greenhalgh, 2019). Similarly, industry-sponsored trials of clozapine, a schizophrenia drug, tended to report more positive results than non-sponsored trials (Wahlbeck & Adams, 1998). In both cases, financial COIs may have compromised public health. Apart from primary research, financial COIs may also influence secondary research; opinion articles criticising the use of systematic reviews for policymaking were 2.3 times more likely to possess ties to industry (Forsyth et al., 2014), a worrying trend given that such reviews synthesize and evaluate the totality of evidence on a particular research topic (Sweet & Moynihan, 2007). Financial COIs therefore threaten the ability of science to accurately inform policy, and thereby its ability to translate understanding into tangible benefits. However, the ability of financial COIs to manufacture scientific consensus may be overstated, due to greater awareness: laypersons tend to scrutinise claims from biased sources more closely, which may provide support for disclosure-based policies (Gierth & Bromme, 2020). Furthermore, while data is lacking on nonfinancial COIs, available research indicates that at least some may be limited in extent; where personal religious beliefs are concerned, most scientists believe religion does not interfere with their work (Ecklund et al., 2016). By permeating research in key economic sectors, financial COIs pose a significant threat to the public interest, but this may be balanced by greater vigilance. Unfortunately, where nonfinancial COIs are concerned, the lack of evidence prevents reliable generalisations from being made.
The heterogeneity of COI causes and effects, and the recognition that current efforts are inadequate, has led to a diversity of proposals seeking to mitigate their influence. The adoption of COI measures has been almost universal, with over 99% of core clinical journals requiring authors to disclose financial COIs (Shawwa et al., 2016). However, such policies may be inadequate: only 57% of these journals require nonfinancial COI disclosure (Shawwa et al., 2016), while just 33.9% of public health journals explicitly require reviewers and editors to disclose COIs (Resnik, Konecny & Kissling, 2017). These policies are further weakened by their reliance on self-disclosure, and the lack of an effective enforcement mechanism – when individuals refuse to disclose their COIs, journals may be unable or unwilling to continue pursuing the matter (Ruff, 2015). Amidst this context, a multiplicity of solutions has been proposed. Beyond disclosure, oversight and prohibition are two other solutions which could alleviate the COI problem (Resnik, 2007). Proposals in the former category include the creation of institutional COI committees empowered to manage COIs and enforce punitive measures (Lo & Field, 2009), and the inception of an independent centre responsible for monitoring and publicly reporting COIs (Ruff, 2015). The latter category includes the explicit exclusion of conflicted individuals from specific activities, such as writing clinical reviews and editorials (BMJ, 2014), although Resnik (2007) cautions that such measures may hinder scientific progress. While most of these measures may be justly critiqued for their failure to address nonfinancial interests, reflexivity, an approach which uses scientists’ personal and professional biases to ensure fair representation on research teams and review panels, may provide insights in this regard (Bero & Grundy, 2016). Clearly, the COI problem demands a holistic and enforceable approach.
The stereotypical COI – industrial sponsorship of primary investigators in key economic sectors – has since given way to more nuanced discussion on COI causes and effects. As complex and diverse ethical issues, COIs will only be mitigated by the universal adoption of holistic solutions which can enforce penalties at all stages of the publication process. Such measures will prevent vested interests from impoverishing science, and will ensure that the latter remains true to its mission.
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