Research is becoming progressively complex and quality standards increasingly demanding.17–24 As a result, conducting clinical studies is becoming more expensive and the role of sponsors to ensure the viability of research projects is becoming critical. However, funding from different sources may directly affect investigators and COI may inappropriately influence their actions or judgement.17–24 Subtle biases in design and interpretation may arise when a sponsor stands to gain from the report.17

Pharmaceutical and technological companies are responsible for most important advancements in medical knowledge.17–24 Patients, doctors, and society as a whole benefit from this unique effort and should be grateful for the research commitment by the industry. More than 75% of all clinical trials are funded by drug companies.25,26 Likewise, the bulk of research has moved from academic centres to direct contracts between sponsors and private organisations.27,28 For profit, contract research organisations currently consume more than 60% of research funding from industry.25–28 This could be a result of their ability to complete trials more rapidly than academic institutions.8,25 This phenomenon explains the gradual loss of the academic establishment's influence on the ‘research agenda’.25–29 Although the most cited articles continue to be generated by authors with academic affiliations, the number of trials financed exclusively by industry has increased exponentially.30

This paradigm shift has major consequences.25–29 First, many scientifically relevant issues are decreasingly likely to be investigated (orphan studies). Second, many studies8,31,32 suggest that in comparison with non-sponsored research, sponsored trials are published less frequently, raising the concern of publication bias.29 Although the industry has been blamed for preferential publication of studies with positive outcomes, this problem also affects government-funded research.8,31–35 To reduce the effect of publication bias, trials must be registered in publicly accessible repositories.29 Industry-supported research has also been associated with multiple reporting of studies with positive outcomes.8,36 This practice might affect results of subsequent reviews, meta-analyses, and even clinical practice guidelines. Alternatively, industry sponsorship has been associated with publication delays or restrictions.8

Finally, industry-sponsored trials have a three- to four-fold greater probability of obtaining favourable results than their non-sponsored counterparts.8,31–33,37,38 Interestingly, all these differences do not appear to be related to inferior methodology in industry-financed trials. Bekelman et al.8 performed a systematic review of 1140 original studies demonstrating a statistically significant association between industry sponsorship and pro-industry conclusions. The study showed that financial relationships between industry, scientific investigators, and academic institutions were widespread and that COI arising from these ties might significantly influence biomedical research. It was considered possible, however, that given limited resources, industry became selective enough to fund only potentially ‘wining treatments’.8 More recently, in a provocative study that included 324 cardiovascular trials published in the three medical journals with the highest impact factors, Ridker and Torres39 analysed the probability of positive results according to the source of finance. Industry-financed trials more frequently obtained results favourable to drug or device than those financed by not-for profit organisations. This was particularly evident in trials using surrogate endpoints.39

In 1997, Krimsky and Rothenberg40 found that only 16% of journals across all scientific disciplines had COI policies. In addition, existing editorial policies were often not readily available to submitting authors.41 However, a substantial increase in the prevalence of

COI disclosure occurred over time. Initially, most journals only required authors to disclose potential COI. Subsequently, journals encouraged authors to sign COI disclosure statements. If signed statements are not obtained from all authors, it remains possible that only the first author has reviewed the COI policy of the journal, leading to systematic under-reporting.6 Interestingly, some journals that theoretically adhere to ICMJE recommendations do not have clear COI policies when critically analysed.6 However, the journals with highest impact factors are more likely to have published COI policies.6,41

To better characterise COI policies, in 2006, Cooper et al.7 performed a cross-sectional web-based survey of a convenience sample of 135 editors of peer-reviewed biomedical journals. The survey included questions about the existence of specific policies for authors, peer reviewers, and editors, specific restrictions based on COI and the public availability of these disclosures. Ninety-three per cent of journals reported having an author COI policy but only 82% of these required a written attestation. While 77% reported collecting COI information on all author submissions, only 57% published all author disclosures. Eleven per cent of journals reported restricting author submissions based on COI. A minority of journals reported having a policy on reviewers’ COI (46%) or editors’ COI (40%); among these, 25 and 31% of journals stated that they require recusal of peer reviewers and editors if they report a COI. Only 3% of respondents published COI disclosures of peer reviewers and 12% published editors’ COI disclosures, while 11 and 24%, respectively, reported that this information was available upon request. In this survey, estimates were directly provided by the corresponding editors, but no information was taken directly from the actual publications.7

Other studies were more critical and analysed the information available directly from the journals yielding a different perspective. Interestingly, some of these studies focused on COI disclosures in cardiology. Weinfurt et al.42 searched in PubMed for English-language articles published in 2006 that provided evidence or guidance about the use of coronary artery stents. As a premise, it was considered reasonable to expect that authors’ COI were disclosed in similar ways in articles on the same topic published around the same time. A total of 746 articles with 2985 authors published in 135 journals were analysed. Articles were examined to determine whether authors’ financial interests were consistently reported. Eighty-three per cent of the articles did not contain disclosure statements for any author, 72% did not identify any funding source, and only 6% of authors had an article with a disclosure statement. Additionally, author disclosure statements varied significantly from article to article. Notably, articles published in journals that endorsed the ICMJE guidelines were more likely to have disclosure statements for all authors. Similarly, articles in which all authors had disclosure statements were more likely to appear in journals with higher impact factors (median impact factor 11.6 vs. 3.1). These investigators concluded that even rarely disclosed financial interests were not disclosed consistently, suggesting that there are problems with transparency in the cardiac literature with potential implications for patient care. Data suggested that the observed inconsistencies were a result of both journals’ policies and authors’ behaviour.42 Many would argue that an inconsistent system of disclosure is more harmful than no disclosure at all.

More recently, Blum et al.6 analysed COI policies of the top 10% of medical journals according to their impact factor. Instructions to authors and manuscript submission documents were electronically searched for phrases relating to COI using a standardised form. A total of 262 journals were analysed. Of these, 85% requested COI disclosure in the instruction to authors and an additional 4% in other submission documents. Links to specific policies on COI were found within the instruction for authors in only 25% of journals. Although 77% of journals provided definitions on COI, signed disclosure statements were required by only 54% of journals. Travel grant disclosure was requested by 12% of journals. Interestingly, journal category influenced COI disclosure requirements. This request was higher for internal medicine journals than for speciality journals, for journals in the top quartile according to the impact factor, and for journals endorsing the ICMJE guidelines.6

Our data on ESC NSCJ COI policies and disclosure requirements suggest that this topic remains controversial and is not uniformly addressed by journals. We relied on self-reporting by journal editors. However, given the anonymous nature of our survey, we do not believe that there is any reason to question the accuracy of their reports.

In October 2009, the ICMJE proposed an electronic ‘uniform’ format for COI disclosure.11 Four main areas were addressed: authors’ associations with entities that supported the submitted manuscript (indefinite time frame), associations with commercial entities with potential interest in the general area of the manuscript (time frame 36 months), financial association of their spouse and children, and, finally, non financial associations potentially relevant to the submitted manuscript. Each author should disclose resources received directly, or via the corresponding institution, which were used to complete the investigation. Additionally, all sources of revenues relevant to the submitted work paid by any third party before the submission and any relevant long-term relationship, even if ended, should be disclosed. Financial revenues should be disclosed regardless of the amount. A guide for authors and a completed sample was provided in a PDF format. The reporting form was made available at www.icmje.org/coi_disclosure.pdf to be downloaded, completed, and sent to the journal.11 The form can be saved and used again—adding updated information—for a new manuscript. Each author should submit a separate form and is responsible for the accuracy and completeness of the submitted information.11

The ICMJE allowed a period of beta-testing until April 2010 when submission of suggestions was encouraged.12 As a result of the feedback comments, the form was modified. Concerns raised were mainly technical and ethical regarding inquiries about non-financial associations. Accordingly, clarity was enhanced for non-native English speakers (including a glossary of terms). Additionally, owing to the difficulties detected in defining non-financial COI, this section was also modified to be less intrusive (currently presented as an open query) while keeping its locus. Finally, queries about COI in family members were removed from the updated form.12

The idea behind this initiative was to facilitate and standardise uniform disclosure of COI and to make the process easier for authors and less confusing to readers. This uniform ‘universal’ vehicle allows authors to save the electronic forms that can be updated as needed and eliminates the need for reformatting disclosure information for each new submission. Finally, this will eliminate apparent inconsistencies in the report of COI as a result of different journal policies.11,12

Concerns about COI are not new. In his play, Le Malade Imaginaire ‘Moliere satirised the relationship between the doctor and the druggist as they exploited the hypochondriac Argan for their own economic benefit.21 Biomedical journals are particularly vulnerable to COI-related problems. Richard Smith, the former editor-in-chief of the British Medical Journal, stated that ‘the quality of the journal will bless the quality of the drug’.43 Therefore, it is easy to understand the extra scrutiny of industry-sponsored research by reviewers and editors.33 Some editors require that authors of industry-associated research have their data analysis confirmed by a different source and others even ask for the raw data to be analysed by an independent academic statistician.20,33 Some editors do not commission editorial or review articles from authors with potential COI as these may blur objectivity.19,44,45 These pieces rely especially on interpretation and objectivity. However, assessing the importance of COI in opinion articles may be challenging. The dilemma is obvious: those authors with the greatest expertise are usually those with clearer potential COI.44 Last, but not least, editors should also avoid the existence of marketing masquerading as education in their journals. Of note, industry support accounts for most of the funding of accredited continuing medical education (CME) programmes.19 Some suggest that CME has become an insidious vehicle for the aggressive promotion of drugs and medical devices (even with off-label indications). Others consider CME a marketing machine and a lucrative process—with concealed payments to doctors—that undermines the independence of medical societies.19,46

Sometimes medical literature is produced in obscure ways. Professional writers, hired by the industry, may act as ‘ghostwriters’ to produce papers for which credibility will be subsequently increased by inviting academic physicians to act as a ‘guest author’.33 Unfortunately, these guest authors rarely make significant contributions to the design, analysis, and data interpretation.33 Conversely, many deserving industry scientists may be removed from the byline directly by the sponsors. Affiliation with a drug company should not be viewed as evidence of wrongdoing because, as previously emphasised, most important medical discoveries are generated by the pharmaceutical industry.

Journals typically use two main weapons to deal with COI: disclosure and exclusion.44 However, as discussed, policies for COI vary widely among editors. Disclosure should not be considered as a panacea to deal with COI but, from an editorial perspective, casting daylight on the relationship between doctors and pharmaceutical companies represents the best way to untie this Gordian knot.44 Editors should decide whether to publish the information disclosed by authors about potential COI. Editors have the ‘discretion’ to decide whether the potential COI is important enough to be revealed.6 However, it is unclear how editors decide whether to publish disclosures. Moreover, the extent to which such ‘secret disclosure’ may affect the integrity of the journal or the published work remains unknown.7 Some journals systematically disclose all reported potential COI.6 However, this strategy consumes major editorial resources and has been blamed for introducing prejudice in the judgement of manuscripts by readers and for tainting the full content of the article. The value of an exhaustive systematic disclosure of all potential COI remains highly controversial. This practice does not guarantee that the readers will be able to determine whether COI are meaningful or not. Indeed, this practice may be misleading because bias may be perceived when not present and overlooked when relevant. Although COI do not imply any improper behaviour, a McCarthyesque reaction to the term would wrongly support the presumption of guilty until proven innocent.23,33,47 The pendulum is swinging towards increased oversight, but responsible editors should ensure that their readers enjoy the sweet spot in the middle, at least for the time being.

Editors are very busy and cannot conduct a forensic check on every submitted trial. Our survey is consistent with prior reports,7 suggesting that almost no journal has a formal policy of ‘verification’ of COI disclosures.7 Editors are not policemen but, at the same time, it becomes clear that some action is expected when misconduct is detected. Many times editors behave as a ‘toothless watchdog’ regarding COI. Alternatively, other editors suggest that allegation of under-reported COI should be rigorously investigated.9 However, editors do not have the resources required to conduct a full investigation to clarify elusive and multifaceted COI-related issues. In most cases, their final role is just to raise the issue with the corresponding dean. Notably, formal ‘corrections’ about COI are rarely published.

All authors of this review support the importance of disclosing potential COI when a scientific paper is submitted for consideration to any ESC NSCJ. Moreover, when in doubt, it is better to err on the side of over-disclosure and let the editors make the decision. The ICMJE Uniform Disclosure Initiative represents a milestone in this regard and paves the way for further transparency in biomedical publishing.11,12 Therefore, we encourage ESC NSCJ to progressively adapt their policies in order to be able to adhere to this editorial proposal. However, in this journey, some potential caveats should be carefully heeded. Firstly, exhaustive disclosure of multiple, minor, and vaguely related potential COI might ‘dilute’ the relevance of real major COI that most readers would be interested to know. Secondly, some relevant institutional COI are not openly disclosed to all corresponding researchers and, accordingly, these may be impossible to declare. Thirdly, many major journals frequently allow senior international opinion leaders with clear (definitive and well-known) COI to systematically declare the absence of COI in their papers. Young scientists may perceive this as confusing and disturbing while others will regard this inconsistency as evidence that the whole process is completely hypocritical. Finally, major sociocultural differences among countries should also be taken into account. Most European doctors (including most editors in the byline of this article) frequently receive occasional travel grants from diverse pharmaceutical companies to attend medical society meetings and, up to now, these have not been systematically disclosed as potential COI. The situation, however, is quite different on the other side of the Atlantic where such practices have been considered inadequate or even misconduct for a number of years. In North America, direct support (including travel) of CME programmes by industry is prohibited while this practice is considered acceptable in most European countries.19 NSCJ editors should be alerted to the need to deal with these vexing problems in their respective journals in line with local policies and practices.48 Progressive steps should be taken to ensure a systematic approach to these COI-related editorial issues. However, commonsense and reason should prevail in order to achieve a balance between the pragmatic and utopian.