Evidence-based toxicology

The discipline of evidence-based toxicology (EBT) strives to transparently, consistently, and objectively assess available scientific evidence in order to answer questions in toxicology,^[1] the study of the adverse effects of chemical, physical, or biological agents on living organisms and the environment, including the prevention and amelioration of such effects.^[2] EBT has the potential to address concerns in the toxicological community about the limitations of current approaches to assessing the state of the science.^[3][4] These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility.^[5][6][7] Evidence-based toxicology has its roots in the larger movement towards evidence-based practices.

By analogy to evidence-based medicine (EBM),^[8] the umbrella term evidence-based toxicology (EBT) has been coined to group all approaches intended to better implement the above-mentioned evidence-based principles in toxicology in general and in toxicological decision-making in particular. Besides systematic reviews, the core evidence-based tool, such approaches include inter alia the establishment and universal use of a common ontology, justified design and rigorous conduct of studies, consistently structured and detailed reporting of experimental evidence, probabilistic uncertainty and risk assessment, and the development of synthesis methodology to integrate evidence from diverse evidence streams, e.g. from human observational studies, animal studies, in vitro studies and in silico modeling. A main initial impetus for translating evidence-based approaches to toxicology was the need to improve the performance assessment of toxicological test methods.^[9] The U.S. National Research Council (NRC) concurs that new means of assessment are needed to keep pace with recent advances in the development of toxicological test methods, capitalizing on enhanced scientific understanding through modern biochemistry and molecular biology.^[10]

A key tool in evidence-based medicine that holds promise for EBT is the systematic review. Historically, authors of reviews assessing the results of toxicological studies on a particular topic have searched, selected, and weighed the scientific evidence in a non-systematic and non-transparent way. Due to their narrative nature, these reviews tend to be subjective, potentially biased, and not readily reproducible.^[1] Two examples highlighting these deficiencies are the risk assessments of trichloroethylene and bisphenol A (BPA). Twenty-seven different risk assessments of the evidence that trichloroethylene causes cancer have come to substantially different conclusions.^[11] Assessments of BPA range from low risk of harm to the public to potential risks (for some populations), leading to different political decisions.^[12] Systematic reviews can help reducing such divergent views.^[3] In contrast with narrative reviews, they reflect a highly structured approach to reviewing and synthesizing the scientific literature while limiting bias.^[3] The steps to carrying out a systematic review include framing the question to be addressed; identifying and retrieving relevant studies; determining if any retrieved studies should be excluded from the analysis; and appraising the included studies in terms of their methodological quality and risk of bias. Ultimately the data should be synthesized across studies, if possible by a meta-analysis. A protocol of how the review will be conducted is prepared ahead of time and ideally should be registered and/or published.

Scientists have made progress in their efforts to apply the systematic review framework to evaluating the evidence for associations between environmental toxicants and human health risks. To date, researchers have shown that important elements of the framework established in evidence-based medicine can be adapted to toxicology with little change, and some studies have been attempted.^[13][14][15] Researchers using the systematic review methodology to address toxicological concerns include a group of scientists from government, industry, and academia in North America and the European Union (EU) who have joined together to promote evidence-based approaches to toxicology through the nonprofit Evidence-based Toxicology Collaboration (EBTC). The EBTC brings together the international toxicology community to develop EBT methodology and facilitate the use of EBT to inform regulatory, environmental and public health.^[3][16][17]