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.

Keywords: Animal research; Atrazine; Bias; Chemical; Conflicts of interest; Funding source; Meta-analysis; Research synthesis; Risk assessment; Systematic review; Toxicology.

Figure 1. Flow of Included Studies

Figure 2. Meta-Analyses of the Effect of Atrazine on Harm Outcomes Indicated by an Increase in the Effect Size

Figure 3. Meta-Analyses of the Effect of Atrazine on Harm Outcomes Indicated by a Decrease in Effect Size