Example

“SYR reports grants from Amgen, Astellas, Daiichi Sankyo, Eisai, Merck, Roche, Zymeworks, Indivumed, MSD, Ono/Bristol Myers Squibb, AstraZeneca, BI, Taiho, Lilly, SN Bioscience. SRF has received honoraria as an invited speaker for Lilly, Eisai, Daiichi Sankyo, MSD, and Ono/Bristol Myers Squibb; has participated on advisory boards for Amgen and Indivumed; and has served as an advisor for Astellas, Daiichi Sankyo, Eisai, LG Biochem, Merck Sharpe Dohme, Ono/Bristol Myers Squibb, and AstraZeneca. D-YO reports grants from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, Merck Sharpe Dohme, and Handok; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, Bristol Myers Squibb/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, and Merck Sharpe Dohme. M-HR reports research grants from AstraZeneca; consulting fees from Bristol Myers Squibb, Ono, Lilly, Merck Sharpe Dohme, Novartis, Daiichi Sankyo, AstraZeneca, Sanofi, and Astellas; and has received honoraria for lectures, presentations, speakers bureaus, or educational events from Bristol Myers Squibb, Ono, Lilly, Merck Sharpe Dohme, Novartis, Daiichi Sankyo, AstraZeneca, Sanofi, and Astellas . . .

 

“LY, SB and PB report full-time employment by Merck Sharp and Dohme, a subsidiary of Merck (Rahway, NJ, USA), and stock ownership in Merck. LSW reports consulting fees from Amgen; and has received honoraria for lectures, presentations, speakers bureaus, or educational events from Novartis, Bristol Myers Squibb, Merck Sharpe Dohme, Roche, and Amgen.

 

“PY, YB, JLee, MGF, JLi, MAL, TC, SQ, SL, and HP declare no competing interests” [98].

 

Explanation

Disclosure of authors’ conflicts of interest provides important context for readers of a trial report when ascertaining the overall methodological rigor of a trial (eg, relevance of the type of comparator intervention and eligibility criteria for patients) and risk of bias (eg, selective reporting of favourable results). Conflicts of interest of all trial manuscript authors should be reported, along with any procedures to reduce the risk of conflicts of interest influencing the trial’s design, conduct, analysis, or reporting.

 

Conflicts of interest can be defined as “a set of circumstances that creates a risk that professional judgement or actions regarding a primary interest will be unduly influenced by a secondary interest” [108]. In the context of authors of a trial report, conflicts of interest imply a risk that investigators’ personal interests and allegiances, or ties with companies or organisations, have undue influence on the design, conduct, analysis, or reporting of a trial. The concept implies a risk of influence and is not indicative of actual wrongdoing.

 

Conflicts of interest are most often associated with the drug and device industries. Types of financial ties include salary support or grants; ownership of stock or options; honorariums (eg, for advice, authorship, or public speaking); paid consultancy or service on advisory boards and medical education companies; and receipt of patents or patents pending. An analysis of 200 trials from 2015 reported that 57% of trials had at least one author declaring financial conflicts of interests [109].

 

Conflicts of interest may also exist with support from or affiliation with government agencies, charities, and professional and civic organisations. Non-financial conflicts of interest include academic commitments; personal or professional relationships; and political, religious, or other affiliations with special interests or advocacy positions. An analysis of 200 trials found that 4% of trials had at least one author declaring non-financial conflicts of interest [109]. There is ongoing discussion on the association between a problematic non-financial conflict of interest and a reasonable point of view [110].

 

A cross sectional study of 190 randomised trials, published in core clinical journals, found that trials with authors’ conflicts of interest had more positive results than trials without. The presence of a financial tie was associated with a positive study outcome (odds ratio 3.23; 95% CI 1.7 to 6.1). This association was also present after adjustment for the study funding source (odds ratio 3.57; 95% CI 1.7 to 7.7) [111].

 

Although financial conflicts of interest are often declared in trials, [109] the declarations are generally imprecise, and undisclosed conflicts are common [112]. A systematic review of studies comparing financial conflicts of interest declared in medical publications or guidelines (not only randomised trials) with declarations in payment databases (eg, the Open Payments Database) found that the median percentage of authors with “non-concordant” disclosures was 81% [112]. A study including only randomised trials found that 35 (30%) of 115 authors from non-industry funded trials had undisclosed conflicts of interest whereas that was the case for 102 (50%) of 203 authors from industry funded trials [113].  For financial conflicts that cannot be tracked to public databases and for non-financial conflicts, the rate of non-disclosure is unknown but it is likely to be even higher.