Conflicts of interest in clinical practice: lessons learned from cardiovascular medicine.

Cardiovascular diseases represent a major burden worldwide, and clinical trials are critical to define treatment improvements. Since various conflicts of interest (COIs) may influence trials at multiple levels, cardiovascular research represents a paradigmatic example to analyze their effects and manage them effectively to re-establish the centrality of evidence-based medicine.Despite the manifest role of industry, COIs may differently affect both sponsored and non-sponsored studies in many ways. COIs influence may start from the research question, data collection and adjudication, up to result reporting, including the spin phenomenon. Outcomes and endpoints (especially composite) choice and definitions also represent potential sources for COIs interference. Since large randomized controlled trials significantly influence international guidelines, thus impacting also clinical practice, their critical assessment for COIs is mandatory. Despite specific protocols aimed to mitigate COI influence, even scientific societies and guideline panels may not be totally free from COIs, negatively affecting their accountability and trustworthiness.Shared rules, awareness of COI mechanisms and transparency with external data access may help promoting evidence-based research and mitigate COIs impact. Managing COIs effectively should preserve public trust in the cardiovascular profession without compromising the positive relationships between investigators and industry.

Association between conflicts of interest and favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: systematic review.

OBJECTIVE: To investigate the association between conflicts of interest and favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Studies that compared the association between conflicts of interest and favourable recommendations of drugs or devices (eg, recommending a drug) in clinical guidelines, advisory committee reports, opinion pieces (eg, editorials), or narrative reviews. DATA SOURCES: PubMed, Embase, Cochrane Methodology Register (from inception to February 2020), reference lists, Web of Science, and grey literature. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of the studies. Pooled relative risks and 95% confidence intervals were estimated using random effects models (relative risk >1 indicates that documents with conflicts of interest more often had favourable recommendations than documents with no conflicts of interest). Financial and non-financial conflicts of interest were analysed separately, and the four types of documents were analysed separately (preplanned) and combined (post hoc). RESULTS: 21 studies that analysed 106 clinical guidelines, 1809 advisory committee reports, 340 opinion pieces, and 497 narrative reviews were included. Unpublished data were received for 11 studies (eight full datasets and three summary datasets). 15 studies showed risk of confounding because the compared documents could differ in factors other than conflicts of interest (eg, different drugs used for different populations). The relative risk for associations between financial conflicts of interest and favourable recommendations for clinical guidelines was 1.26 (95% confidence interval 0.93 to 1.69; four studies of 86 clinical guidelines), for advisory committee reports was 1.20 (0.99 to 1.45; four studies of 629 advisory committee reports), for opinion pieces was 2.62 (0.91 to 7.55; four studies of 284 opinion pieces), and for narrative reviews was 1.20 (0.97 to 1.49; four studies of 457 narrative reviews). An analysis of all four types of documents combined supported these findings (1.26, 1.09 to 1.44). In one study that investigated specialty interests, the association between including radiologists as authors of guidelines and recommending routine breast cancer was: relative risk 2.10, 95% confidence interval 0.92 to 4.77; 12 clinical guidelines). CONCLUSIONS: We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. Limitations of this review were risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest influence recommendations. SYSTEMATIC REVIEW REGISTRATION: Cochrane Methodology Review Protocol MR000040.

Robotic-assisted versus standard unicompartmental knee arthroplasty-evaluation of manuscript conflict of interests, funding, scientific quality and bibliometrics.

PURPOSE: Robotic-assisted unicompartmental knee arthroplasty (UKA) has gained popularity over the last decade claiming enhanced surgical precision and better joint kinematics, with peer-reviewed publications about this new technology also increasing over the past few years. The purpose of our study was to compare manuscripts about robotic-assisted UKA to those about standard UKA in terms of industry funding, author conflict of interest, scientific quality, and bibliometrics. METHODS: A systematic search using PRISMA guidelines on PubMed and Google Scholar from 2012 to 2016 resulted in 45 papers where robotic technology was performed for UKA and 167 papers that UKA were performed without the assistance of a robot. Between the two groups, we compared (1) rate of manuscripts with reported conflict of interest or industry funding, (2) journal impact factor, (3) level of evidence, and (4) relative citation ratio. RESULTS: Fifty-one percent (23/45) of robotic UKA manuscripts were industry-funded or had authors with financial conflict of interest, compared to 29% ([49/167], p < 0.01) of non-robotic UKA papers. Significantly more robotic UKA papers (24% [11/45] vs 9% [16/167), p < 0.01) were published in journals that were not assigned an impact factor by the Journal Citations Report. There was no difference in regard to bibliometrics or level of evidence. CONCLUSION: Manuscripts in which UKA was performed with the assistance of a robot were more likely to be industry funded or be written by authors with financial conflicts of interest and published in less prestigious journals. There were no differences in scientific quality or influence between the two groups. Readers analyzing published data should be aware of the potential conflicts of interests in order to more accurately interpret manuscripts data and conclusions.

The Impact of Corporate Payments on Robotic Surgery Research: A Systematic Review.

OBJECTIVE: To quantify the influence of financial conflict of interest (COI) payments on the reporting of clinical results for robotic surgery. DATA SOURCES AND STUDY SELECTION: A systematic search (Ovid MEDLINE databases) was conducted (May 2017) to identify randomized controlled trials (RCTs) and observational studies comparing the efficacy of the da Vinci robot on clinical outcomes. Financial COI data for authors (per study) were determined using open payments database. MAIN OUTCOMES AND MEASURES: Primary outcomes assessed were receipt of financial COI payments and overall conclusion reported between robotic versus comparative approach. Quality/risk of bias was assessed using Newcastle-Ottawa Scale (NOS)/Cochrane risk of bias tool. Disclosure discrepancies were also analyzed. DATA EXTRACTION AND SYNTHESIS: Study characteristics, surgical subspecialty, methodological assessment, reporting of disclosure statements, and study findings dual abstracted. The association of the amount of financial support received as a predictor of reporting positive findings associated robotic surgery was assessed at various cut-offs of dollar amount received by receiver operating curve (ROC). RESULTS: Thirty-three studies were included, 9 RCTs and 24 observational studies. There was a median, 111 patients (range 10 to 6420) across studies. A little more than half (17/33) had a conclusion statement reporting positive results in support of robotic surgery, with 48% (16/33) reporting results not in favor [equivocal: 12/33 (36%), negative: 4/33 (12%)]. Nearly all (91%) studies had authors who received financial COI payments, with a median of $3364.46 per study (range $9 to $1,775,378.03). ROC curve demonstrated that studies receiving greater than $9557.31 (cutpoint) were more likely to report positive robotic surgery results (sensitivity: 0.65, specificity: 0.81, area under the curve: 0.73). Studies with financial COI payment greater than this amount were more likely to report beneficial outcomes with robotic surgery [(78.57% vs 31.58%, P = 0.013) with an odds ratio of 2.07 (confidence interval: 0.47-3.67; P = 0.011)]. Overall, studies were high quality/low risk of bias [median NOS: 8 (range 5 to 9)]; Cochrane risk: "low risk" (9/9, 100%)]. CONCLUSION AND RELEVANCE: Financial COI sponsorship appears to be associated with a higher likelihood of studies reporting a benefit of robotic surgery. Our findings suggest a dollar amount where financial payments influence reported clinical results, a concept that challenges the current guidelines, which do not account for the amount of COI funding received.

Assessment of Conflicts of Interest in Robotic Surgical Studies: Validating Author's Declarations With the Open Payments Database.

BACKGROUND: Accurate conflict of interest (COI) statements are important, as a known COI may invalidate study results due to the potential risk of bias. OBJECTIVE: To determine the accuracy of self-declared COI statements in robotic studies and identify risk factors for undeclared payments. METHODS: Robotic surgery studies were identified through EMBASE and MEDLINE and included if published in 2015 and had at least one American author. Undeclared COI were determined by comparing the author's declared COI with industry reported payments found in the "Open Payments" database for 2013 and 2014. Undeclared payments and discrepancies in the COI statement were determined. Risk factors were assessed for an association with undeclared payments at the author and study level. RESULTS: A total of 458 studies (2253 authors) were included. Approximately, 240 (52%) studies had 1 or more author receive undeclared payments and included 183 where "no COI" was explicitly declared, and 57 with no declaration statement present. Moreover, 21% of studies and 18% of authors with a COI declared it so in a COI statement. Studies that had undeclared payments from Intuitive were more likely to recommend robotic surgery compared with those that declared funding (odds ratio 4.29, 95% confidence interval 2.55-7.21). CONCLUSIONS: We found that it was common for payments from Intuitive to be undeclared in robotic surgery articles. Mechanisms for accountability in COI reporting need to be put into place by journals to achieve appropriate transparency to those reading the journal article.

Trial sponsorship and self-reported conflicts of interest in breast cancer radiation therapy: An analysis of prospective clinical trials.

PURPOSE: We aim to assess any association between study and self-reported conflict of interest (COI) or trial sponsorship in breast cancer radiation clinical trials. MATERIALS AND METHODS: We searched PubMed for all clinical trials (CTs) published between 09/2004 and 09/2014 related to breast cancer. We included only radiotherapy CTs with primary clinical endpoints. We classified eligible trials according to the funding source, presence or absence of conflict of interest, study conclusion and impact factor (IF). RESULTS: 1,603 CTs were retrieved. 72 randomized clinical trials were included for analysis. For-profit (PO), not for profit organization (nPO), none and not reported sponsorship rates were 9/72 (12.5%), 35/72 (48.6%), 1/72 (1.4%), 27/72 (37.5%), respectively. Present, absent or not reported COI were found in 6/72 (8.3%), 43/72 (59.7%) and 23/72 (32%) of the CTs, respectively. Conclusion was positive, neutral and negative in 57/72 (79.1%), 9/72 (12.5%) and 6/72 (8.4%) of the trials, respectively. Positive conclusion was reported in 33/44 (75%) funded trials (PO and nPO) and 5/6 (83.3%) CTs with reported COI. On univariate analysis no association with funding source (P=0.178), COI (P=0.678) or trial region (P=0.567) and trial positive conclusion was found. Sponsored trials (HR 4.50, 95CI-0.1.23-16.53;P=0.0023) and positive trials (HR 4.78, 95CI- 1.16-19.63;P=0.030) were more likely to be published in higher impact factor journals in the multivariate analysis. CONCLUSIONS: nPO funding was reported in almost 50% of the evaluated CTs. No significant association between study conclusion and funding source, COI or trial region was identified. Sponsored trials and positive trials were more likely to be published in higher impact factor journals.

Can a good tree bring forth evil fruit? The funding of medical research by industry.

BACKGROUND: Systematic reviews analysing the influence of funding on the conduct of research have shown how Conflicts of Interest (COIs) create bias in the production and dissemination of data. SOURCES OF DATA: The following is a critical analysis of current opinions in respect to COIs created by industry funding of medical research in academic institutions. AREAS OF AGREEMENT: Effective mechanisms are necessary to manage COIs in medical research, and to prohibit COIs that clearly affect validity of research conduct and outcomes. AREAS OF CONTROVERSY: While most hold that industry investment in university research is not a barrier to good science, there are questions about how securing funding opportunities might be prioritized over the risks of potential COIs. It is argued that COIs are inherent risks to research integrity, requiring the strengthening of current governance frameworks. GROWING POINTS: The focus on COIs, created by the ostensibly categorical actions of industry, challenges the evolving research priorities within academic institutions. AREAS TIMELY FOR DEVELOPING RESEARCH: Less well-defined COIs are equally culpable to financial ones, in terms of the systemic damage they do to science. So, are they appropriately managed as risks within university research settings?

Dependability of results in conference abstracts of randomized controlled trials in ophthalmology and author financial conflicts of interest as a factor associated with full publication.

BACKGROUND: Discrepancies between information in conference abstracts and full publications describing the same randomized controlled trial have been reported. The association between author conflicts of interest and the publication of randomized controlled trials is unclear. The objective of this study was to use randomized controlled trials in ophthalmology to evaluate (1) the agreement in the reported main outcome results by comparing abstracts and corresponding publications and (2) the association between the author conflicts of interest and publication of the results presented in the abstracts. METHODS: We considered abstracts describing results of randomized controlled trials presented at the 2001-2004 Association for Research in Vision and Ophthalmology conferences as eligible for our study. Through electronic searching and by emailing abstract authors, we identified the earliest publication (journal article) containing results of each abstract's main outcome through November 2013. We categorized the discordance between the main outcome results in the abstract and its paired publication as qualitative (a difference in the direction of the estimated effect) or as quantitative. We used the Association for Research in Vision and Ophthalmology categories for conflicts of interest: financial interest, employee of business with interest, consultant to business with interest, inventor/developer with patent, and receiving ≥ 1 gift from industry in the past year. We calculated the relative risks (RRs) of publication associated with the categories of conflicts of interest for abstracts with results that were statistically significant, not statistically significant, or not reported. RESULTS: We included 513 abstracts, 230 (44.8 %) of which reached publication. Among the 86 pairs with the same main outcome domain at the same time point, 47 pairs (54.7 %) had discordant results: qualitative discordance in 7 pairs and quantitative discordance in 40 pairs. Quantitative discordance was indicated as < 10, 10-20, > 20 %, and unclear in 14, 5, 14, and 7 pairs, respectively. First authors reporting of one or more conflicts of interest was associated with a greater likelihood of publication (RR = 1.31; 95 % CI = 1.04 to 1.64) and a shorter time-to-publication (log-rank p = 0.026). First author conflicts of interests that were associated with publication were financial support (RR = 1.50; 95 % CI = 1.19 to 1.90) and one or more gifts (RR = 1.42; 95 % CI = 1.05 to 1.92). The association between conflicts of interest and publication remained, irrespective of the statistical significance of the results. CONCLUSIONS: More than half the abstract/publication pairs exhibited some amount of discordance in the main outcome results, calling into question the dependability of conference abstracts. Regardless of the main outcome results, the conflicts of interests of the abstract's first author were associated with publication.

Ideology versus evidence: Investigating the claim that the literature on e-cigarettes is undermined by material conflict of interest.

A review of the health effects of e-cigarettes (EC) by Pisinger and Dossing concluded that any reassuring the evidence on the contents of e-cigarettes cannot be trusted because 'A substantial number of studies were funded or otherwise supported by manufacturers of ECs' and the relevant literature is influenced by 'severe conflicts of interest' (A). The review also asserts that 'Conflict of interest seems to influence the conclusions of these papers' (BC). These claims have been embraced and magnified by EC opponents. The Pisinger and Dossing review included 76 studies and considered 26 (34%) to be 'funded or otherwise supported' by the industry. As the review identifies the 'conflicted' studies, such a claim can be checked. In summary, only 10 (13%) of articles covered by the review were sponsored by the industry and only 5 are published studies. Claim 'A' is misleading. Regarding claim 'B', it appears to have been conceived independent of any empirical support. Recently, anti-EC activists and media started to use conflict of interest accusations to disparage the validity of empirical evidence showing that vaping is much safer than smoking. Evidence needs to be considered on its merits rather than from the perspective of preconceived ideological positions.

Financial conflicts of interest and their association with outcome and quality of fibromyalgia drug therapy randomized controlled trials.

AIMS: To evaluate the association of financial conflicts of interest (FCOI) with the characteristics, outcome and reported methodological quality of fibromyalgia drug therapy randomized controlled trials (FM-RCTs). METHODS: A cross-sectional study of original, parallel-group, drug therapy FM-RCTs published between 1997 and 2011 from Medline and Cochrane Central Register of Controlled Trials was conducted. Two reviewers independently assessed each RCT for funding source, authors' FCOI(s), study characteristics, reporting of methodological measures important for internal validity and outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or non-positive). RESULTS: Forty-seven RCTs were eligible with funding source as: 26 (55.3%) industry; eight (17%) non-profit source(s); five (10.6%) mixed; and eight (17%) unspecified. Industry-funded RCTs were more likely to be multicenter and enroll greater number of patients. Reporting of key methodological measures was suboptimal; however, industry and non-profit funded RCTs did not differ in their reporting. Thirty (63.8%) RCTs had ≥ one author who disclosed an FCOI (receipt of research grant [21, 44.7%], industry sponsor employee [20, 42.6%], receipt of consultancy fee/honorarium [16, 34%] and stock ownership [11, 23.4%]). Although industry funding and certain authors' FCOIs (employment and receipt of consultancy fee/honorarium) were univariately associated with positive outcome, such association was not observed after adjusting for study sample size. CONCLUSIONS: The majority of FM-RCTs were industry-sponsored, and had at least one author with an FCOI. Reporting of key methodological measures was suboptimal. After adjusting for study sample size, no association of industry funding or author's FCOI with study outcome was seen.