The relationship between study sponsorship, risks of bias, and research outcomes in atrazine exposure studies conducted in non-human animals: Systematic review and meta-analysis

Abstract

Background A critical component of systematic review methodology is the assessment of the risks of bias of studies that are included in the review. There is controversy about whether funding source should be included in a risk of bias assessment of animal toxicology studies. Objective To determine whether industry research sponsorship is associated with methodological biases, the results, or conclusions of animal studies examining the effect of exposure to atrazine on reproductive or developmental outcomes. Methods We searched multiple electronic databases and the reference lists of relevant articles to identify original research studies examining the effect of any dose of atrazine exposure at any life stage on reproduction or development in non-human animals. We compared methodological risks of bias, the conclusions of the studies, the statistical significance of the findings, and the magnitude of effect estimates between industry sponsored and non-industry sponsored studies. Results Fifty-one studies met the inclusion criteria. There were no differences in methodological risks of bias in industry versus non-industry sponsored studies. 39 studies tested environmentally relevant concentrations of atrazine (11 industry sponsored, 24 non-industry sponsored, 4 with no funding disclosures). Non-industry sponsored studies (12/24, 50.0%) were more likely to conclude that atrazine was harmful compared to industry sponsored studies (2/11, 18.1%) (p value = 0.07). A higher proportion of non-industry sponsored studies reported statistically significant harmful effects (8/24, 33.3%) compared to industry-sponsored studies (1/11; 9.1%) (p value = 0.13). The association of industry sponsorship with decreased effect sizes for harm outcomes was inconclusive. Conclusion Our findings support the inclusion of research sponsorship as a risk of bias criterion in tools used to assess risks of bias in animal studies for systematic reviews. The reporting of other empirically based risk of bias criteria for animal studies, such as blinded outcome assessment, randomization, and all animals included in analyses, needs to improve to facilitate the assessment of studies for systematic reviews.

Scientific integrity issues in Environmental Toxicology and Chemistry: Improving research reproducibility, credibility, and transparency

“…What becomes particularly difficult to self‐regulate is the convergence of cognitive bias, a human nature to seek to please one's patron, and the interests of one's employer or client. For instance, studies funded by drug or medical device makers tend to find positive effects that favor the company funding the research (Lexchin et al ; Smith ), and the funding effect for studies of chemical toxicity may lean toward finding negative effects (Krimsky , ; Bero et al ). However, concordance between a funder's self‐interest and research findings does not alone indicate bias.…”

“…They termed this distortion of information to further what may be perceived to be righteous ends as "white hat bias" (Cope and Allison 2009). However, their conflicted financial backing from the soft drink industry and from manufacturers of baby formula contributed to countercriticisms of funding bias (Bes-Rastrollo et al 2014;Harris and Patrick 2011;Mandrioli et al 2016). Unresolved in the claims and counterclaims of bias and financial conflicts of interest was what advice was most credible.…”

“…One does not have to search hard to find plenty of published concerns about the credibility of science. These include overstated and unreliable results (Ioannidis 2005;Harris and Sumpter 2015;Henderson and Thomson 2017), conflicts of interest (McGarity and Wagner 2008;Stokstad 2012;Boone et al 2014;Oreskes et al 2015;Tollefson 2015), profound bias (Atkinson and Macdonald 2010;Bes-Rastrollo et al 2014;Cormier 2015a, 2015b), suppression of results to protect financial interests (Wadman 1997;Wise 1997), deliberate misinformation campaigns as a public relations strategy for financial or ideological aims (Baba et al 2005;McGarity and Wagner 2008;Gleick and 252 coauthors 2010;Oreskes and Conway 2011), political interference with or suppression of results from government scientists (Hutchings 1997;Stedeford 2007;Ogden 2016), self-promotion and sabotage of rivals in hypercompetitive settings (Martinson et al 2005;Edwards and Roy 2016;Ross 2017), publication bias, peer review and authorship games (Young et al 2008;Fanelli 2012;Callaway 2015;), selective reporting of data or adjusting the questions to fit the data (Fraser et al 2018), overhyped institutional press releases that are incommensurate with the actual science behind them (Cope and Allison 2009;Sumner et al 2014), dodgy journals (Bohannon 2013), and dodgy conferences (Van Noorden 2014).…”

Why Having a (Nonfinancial) Interest Is Not a Conflict of Interest

“…Pharmaceutical, tobacco, food, or chemical industry funding biases human research studies towards outcomes that are favorable to the sponsor’s product, even when controlling for other biases in the methods [7–8,10–11,17]. Thus, even when the methods meet high standards for internal validity, financial conflicts of interest may influence research results through other mechanisms, such as the framing of the question, how the study is actually conducted, and whether it is fully and accurately reported.…”

Conflict of Interest and Funding Disclosure Policies of Environmental, Occupational, and Public Health Journals

“…Articles have examined financial COIs and sources of funding in research on the safety of industrial chemicals, 16,17 pesticides, 18 genetically modified foods, 19 sugar-sweetened beverages, 20 endocrine-disrupting compounds, 4,21 and electronic cigarettes. 22 Friedman and Friedman recently conducted a study of 373 articles published in 17 highly-cited environmental or occupational health journals in 2012.…”