INTRODUCTION

A conflicts of interest (COI) is ‘a set of conditions in which professional judgment concerning a primary interest (such as a patient’s welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain)’¹. COI occurs when authors, reviewers or editors have interests that are not fully apparent and that could influence their judgment on what they publish or review^2,3.

Efforts to provide transparency regarding COIs date back to 1984^4,5. In recent years, COI disclosure policies have become a regular part of biomedical research. The International Committee of Medical Journal Editors’ guidelines recommend that authors should disclose the study’s funding sources and any financial ties to core companies, such as pharmaceutical or tobacco companies⁶. In addition, since 2013 the Committee on Publication Ethics (COPE) established two levels of obligation for its members. The first is a Code of Conduct which Journal Editors are expected to practise (and will consider complaints against members who do not follow it), and the second is a set of Best Practice recommendations, which are voluntary, but are suggested to include into the journal’s policies and practices⁷. Among these practices, ‘Editors should have systems for managing COI by authors and reviewers, as well as their own COI, including their staff and editorial board members’⁷.

Nevertheless, evidence shows that tobacco research sponsored by pharmaceutical⁴ or tobacco companies may be biased^8-11 due to vested economic interests. In the 1970s, tobacco companies downplayed the harm of second-hand smoke, for example, by hiding damaging data and distorting research findings^9-12. Nowadays, the four major tobacco companies are involved in the manufacturing of electronic cigarettes (also called e-cigarettes). Considering that this electronic device resembles cigarette use, it is plausible that the same strategies could be used for manipulating the scientific evidence about the use of this relatively new product¹². In fact, some in the scientific community are concerned that publications on e-cigarettes may hide COI and thus their results could be biased^13-16. A systematic review of the health effects of e-cigarettes revealed that 34% of the 76 reviewed articles had declared COI, mostly funding from the manufacturers of e-cigarettes or authors who had acted as consultants for the manufacturers of smoking cessation treatments¹⁷. Another systematic review that addressed passive exposure to e-cigarettes showed that 30% of the 40 reviewed papers had potential COI¹⁸. One report on the ‘evidence update’ of e-cigarettes¹⁹ claimed that ‘e-cigarettes are 95% less harmful to health than normal cigarettes’; this claim was contested because its conclusions appeared to be biased due to COI^12,15. That report also raised serious questions because of its lack of a peer-review process, and thus several organizations put this issue in the spotlight^12,19.

Some journals do not accept manuscripts with links to tobacco companies²⁰. This decision has been criticised by some authors, who argue that these journals have passed a strong rule without enough evidence to justify it and that the journals themselves have some countervailing reasons to do so²⁰. Although full disclosure of financial ties is common in scientific journals when publishing an original report, it seems to be less a priority for other types of articles, such as commentaries, news items, etc⁷. There are hundreds of publications about e-cigarettes, but, considering its novelty, less than half are original articles or reviews, with the rest being mainly notes, editorials or opinions²¹.

Thus, our objective was to conduct an assessment of potential COI in the emergent scientific literature on e-cigarettes. Specifically, we aimed to analyse the declaration of potential COI in any type of publication (original and non-original reports), according to the criteria proposed by COPE.

METHODS

We performed a search on PubMed (www.pubmed. gov) to identify all publications on e-cigarettes listed in Medline and indexed until August 2014. We included all types of publications whose primary or secondary aim or topic was related to e-cigarettes.

The full search strategy used was as follows: (‘electronic cigarettes’[All Fields] OR e cig[All Fields] OR e cigar[All Fields] OR e cigarettes[All Fields] OR e cigarette[All Fields] OR e cigarette’s[All Fields] OR e cigs[All Fields] OR ‘electronic nicotine delivery system’[All Fields] OR ‘electronic nicotine delivery devices’[All Fields]) AND (‘0001/01/01’[PDAT]: ‘2014/08/31’[PDAT]). No other restrictions were established.

The search returned 445 publications. Five pairs of reviewers assessed the title and abstracts (if available) of about 90 publications each. Of the retrieved publications, 30 were not related to e-cigarettes, 2 were duplicate publications, and 2 anecdotally mentioned e-cigarettes. Thus, 411 publications were eligible for full assessment. After reading the full text, 7 were excluded: 1 was not related to electronic cigarettes, 3 mentioned them as a secondary topic with no specific comments, and 3 were unavailable to retrieve (including unsuccessful contact with the corresponding authors); thus, 404 publications were included in the final analysis (Figure 1).

Figure 1

PRISMA chart showing the selection of the publications included in the analysis.

Some tools were created to extract the information, including a protocol to guide the pull out of data, an algorithm (Supplementary Figure S1) to assess the publication’s disclosure status, and an ad hoc Excel spreadsheet to register the information for each publication. They were pilot-tested using 5 full-text publications that were assessed by all of the researchers. When there were any questions, the reviewers discussed the papers with the assigned partner until agreement was reached. If they could not come to an agreement, two other researchers were assigned and resolved the issue.

RESULTS

A total of 404 publications were analysed. The more recent the publication year, the higher the number of publications on e-cigarettes, with a tendency towards an exponential increase (Supplementary Figure S2). Of all publications, 36.9% were original articles (Table 1). Almost all (96.0%) were written in English; the first author was in North America in half of the publications (48.5% of all publications were from the USA and 2.2% from Canada), and in Europe in a third of them (11.9% of all publications were from UK, 6.4% from Italy and 3.5% from Greece). Information about the country could not be determined in 7.7% of all the publications. The most frequent topics were e-cigarette regulation and marketing (24.5%) and toxicology (13.1%); nevertheless, a high percentage of the publications focused on miscellaneous topics, i.e. covering a variety of topics in the same publication or not addressing specific topics (21.5%). Overall, 41.1% of the publications reported empirical data; in these publications, the most frequent study subject was humans (62.0%).

Table 1 shows the COI disclosures in the publications. Of the included publications, 150 (37.1%) did not include any disclosure related to COI, mainly those without empirical data, including all 42 of the news articles and 16 of the 25 editorials. Another 38.6% of the publications disclosed no COI at all; 6.2% stated that there were no COI, but some authors had potential COI in previous publications; while 4.5% stated that they had no COI, but they acknowledged financial support by PTEC_CO. Finally, 13.6% of the publications disclosed potential COI: 13.4% with pharmaceutical companies, 3.0% with tobacco companies, and 10.6% with e-cigarette companies.

Table 2 shows the tendencies of the conclusions regarding e-cigarettes for the publications that had empirical data, both overall and according to independent variables (n=164; 2 publications had no conclusions). Of these, 55.5% of the publications had conclusions that were neutral or unclear, and 22.6% had favourable conclusions about e-cigarettes. Most of the publications were original articles, so the conclusion tendencies were similar to those observed in the publications overall. Publications in which the main topic was related to smoking cessation were the most prevalent in terms of having conclusions favourable to the use of e-cigarettes.

Table 3 shows the distribution of the types of COI disclosures among all publications and among those with empirical data, according to the conclusion and the publication tendencies. Overall publications with conclusions that tended to favour the use of e-cigarettes, 36.7% disclosed having potential COI, whereas 40.8% of those with conclusions that tended to be neutral/unclear disclosed no COI. When we consider only the 166 empirical studies, 37.8% of those with conclusions that were favourable to the use of e-cigarettes disclosed COI, whereas the majority of those with conclusions that tended not to favour the use of e-cigarettes or that were neutral/unclear disclosed that they did not have COI (55.6% and 50.5%, respectively). Regarding the distribution of COI disclosures according to the publication tendencies, we observed that 20.5% of the overall publications supported the use of e-cigarettes as a harm reduction tool, 31.7% supported regulating e-cigarettes, and 17.6% supported their use for smoking cessation. Among the empirical studies, most that supported harm reduction or e-cigarette regulation disclosed no COI (40.0% and 52.3%, respectively), whereas those publications that supported smoking cessation mostly disclosed potential COI.

Table 4 shows the PRs of the publications with favourable conclusions about e-cigarettes and the publications’ tendencies, estimated from multivariate Poisson regression models, according to having a COI disclosure, the main topic of research, and the main subject studied. Publications with a COI disclosure were more likely to have favourable conclusions about e-cigarettes (PR=2.23; 95% CI: 1.43–3.46), to support its use as a tool for harm reduction (PR=1.81; 95% CI: 1.14–2.89), and to support its use for smoking cessation (PR=2.02; 95% CI: 1.26–3.23). Publications about e-cigarette toxicology/health effects or about smoking cessation/clinical advice were more likely to have conclusions that favoured the use of e-cigarettes. Furthermore, papers in which the main subject was e-cigarettes themselves were less likely to have conclusions that were favourable to e-cigarettes (PR=0.49; 95% CI: 0.29–0.85). Publications with COI related to pharmaceutical companies were more likely to have favourable conclusions about e-cigarettes (PR=1.59; 95% CI: 1.05–2.40); this association was not found for COI involving other types of companies (data not shown). Publications that addressed smoking cessation/clinical advice, and other or miscellaneous topics, were more likely to support smoking cessation (PR=3.10 and 2.71, respectively), whereas papers in which the main subject was e-cigarettes themselves were less likely to support the use of e-cigarettes for smoking cessation (PR=0.30; 95% CI: 0.15–0.60).

DISCUSSION

We examined the factors associated with reporting potential COI in the scientific literature on e-cigarettes. We found that over a third of the publications did not have any COI disclosures; these were mostly news, editorials and other types of publications. Authors who had COI (disclosed or not) and publications in which the main topics included toxicology/health effects or smoking cessation/clinical advice were more likely to report favourable conclusions about e-cigarettes. In contrast, studies in which the main subject was e-cigarettes themselves were less likely to have favourable conclusions about e-cigarettes. There are a few possible explanations for these findings. First, the authors who published studies with favourable conclusions about e-cigarettes could have some ties to PTEC_CO. These authors may have framed the research question, conducted the study, or reported the results and conclusions, either consciously or unconsciously with the interests of their sponsors in mind. Second, it is possible that the authors failed to disclose their sponsorship or research constraints, and the editors were not as strict as with studies that reported non-favourable conclusions.

We found that the conclusions of reports on e-cigarettes are associated with their authors’ COI. In addition, we observed that publications that supported the use of e-cigarettes for smoking reduction and smoking cessation were more likely to be from authors with COI with PTEC_CO. Our study shows that publications that report favourable conclusions about e-cigarettes come from authors who had received financial support from PTEC_CO. This pattern is seen in publications with both empirical and non-empirical data.

A systematic review of the prevalence of COI found that a third of biomedical researchers in academic institutions had COI¹. Studies measuring undisclosed COI suggest that between 43% and 69% of study reports and other publications fail to include disclosures of COI³. In our study, we found that 37.1% of publications did not include any disclosure about COI. Disclosure only reveals the possibility of bias, without providing any guidance for resolving it³. Biases introduced by COI are difficult to deal with and should be treated like any other confounder that could affect the results of a study³; however, treating COI as a confounder is challenging. The failure of the scientific community to effectively address COI has serious repercussions for public health policy⁷. The scientific community must provide transparency, supervision and accountability to help ensure that research is not biased by undisclosed COI⁷. Some suggested methods for improving the disclosure of potential COI include the introduction of clinical trial registries, public accessible registers for declarations of interest, and the creation of an Ethics Centre that monitors and reports the enforcement of ethical standards⁷. A compulsory detailed statement of COI, including some of the variables studied in this analysis, may disclose them in a more effective manner. This would not completely mitigate the risk of bias, but it would facilitate a better understanding of how COI are related to biases and how they can influence research consensus³.

We also found that the type of publication can influence its tendency to e-cigarettes. Practically all reviews were neutral in terms of the tone of their conclusions, but letters and other non-empirical publications were more likely to be either against or favourable to the regulation of e-cigarettes. The journal characteristics may also influence the results and conclusions of the studies, as the quality of their reporting may vary according to the journal’s standards²². Articles published in peer-reviewed journals are generally of higher quality than those published in non-peer-reviewed journals². However, we did not include this independent variable in our assessment. Additional research is needed to clarify possible associations between the journal’s quality and the disclosure of COI in e-cigarette publications.

There is evidence that financial COI lead to systematic bias^23,24. In our study, we observed that only publications in which the authors reported ties with pharmaceutical companies were associated with favourable conclusions on e-cigarettes. However, we did not find that authors openly reported COI in all cases; sometimes, this information was extracted based on the author affiliation, funding received in previous studies or from the acknowledgments section. We observed that some authors reported no COI but declared financial support from or even were employees of PTEC_CO (code 3 in our classification); thus, they did not acknowledge this potential COI. Whether non-reporting of COI was consciously done or not is beyond the aims of this study. Lack of transparency at the time of submission on these issues is likely to lead to a perception by readers and editors that the research is tainted²⁵, thus is must be avoided.

CONCLUSIONS

A third of the assessed publications about e-cigarettes did not have any COI disclosure, and this proportion was even higher in certain kinds of publications, such as news, editorials and other types of articles. Publications with favourable conclusions about e-cigarettes were more likely to include a COI disclosure. Furthermore, favourable conclusions about e-cigarettes were more frequent in publications that had COI declarations related to pharmaceutical companies. Journal editors and reviewers should consider evaluating publications, including the funding sources, to determine whether the results and conclusions may be biased and to determine whether there are any relationships with PTEC_CO.