Evidence-based toxicology

The emerging discipline of evidence-based toxicology (EBT) is a process for transparently, consistently, and objectively assessing available scientific evidence in order to answer questions in toxicology, 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 adverse effects. EBT has the potential to address concerns in the toxicological community about the limitations of current approaches to assessing the state of the science. These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility.The evidence-based methods and approaches now being introduced to toxicology are widely used in medicine, which is the basis for their nomenclature. The need to improve the performance assessment of toxicological test methods was the main impetus for translating these tools to toxicology. 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. These new test methods capitalize on the recent advances in biochemistry and molecular biology that have enhanced scientists' understanding of the nature and mechanisms underlying how chemicals cause adverse effects, and the tests have the potential to be much quicker and less expensive than the tests traditionally used to evaluate toxicity.EBT can be applied to literature reviews of chemical effects, as well as test method performance. Historically, authors of reviews assessing the results of toxicological studies 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, are potentially biased and cannot be reproduced. Two examples highlighting these deficiencies are the cancer risk assessment of two persistent, organic pollutants, polychlorinated biphenyls (PCBs) and trichloroethylene. Narrative reviews of PCBs published within a year of each other came to different conclusions about the cancer risk posed by these chemicals. Similarly, 27 different risk assessments of trichloroethylene have come to substantially different conclusions.A key tool used in evidence-based medicine that holds promise for EBT is the systematic review, which is a highly structured approach to reviewing and synthesizing the scientific literature while limiting bias. The steps to carrying out a systematic review include framing the question to be addressed; appraising and deciding how relevant studies will be identified and retrieved; determining if any studies need to be excluded from the analysis; and deciding how the included studies will be appraised in terms of their quality and risk of bias. Ultimately the data will be synthesized across studies, often by a meta-analysis. Typically, a protocol of how the review will be conducted is prepared ahead of time and is often peer reviewed.Scientists have made progress in their efforts to apply systematic reviews to evaluate the evidence for associations between environmental toxicants and human health risks. To date, researchers have shown that important elements of the systematic review methodology established in evidence-based medicine can be adopted into EBT with little change, and a limited number of such studies have been attempted. For example, an EBT-style systematic review responds to concerns in the pharmaceutical industry regarding why drug candidates recommended by animal studies have unexpectedly failed by identifying instruments that may ameliorate the problem. Researchers using systematic reviews to address toxicological concerns include a group of scientists from government, industry, and academia in North America and European Union (EU) who have joined forces to promote evidence-based approaches to toxicology through the nonprofit Evidence-based Toxicology Collaboration (EBTC). The EBT is applying systematic reviews to toxicological methods. This is just one of the avenues that the EBTC's members are researching to help toxicologists improve health protection and safety assurance.