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, 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. 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. Evidence-based toxicology has its roots in the larger movement towards evidence-based practices. The discipline of evidence-based toxicology (EBT) strives to transparently, consistently, and objectively assess 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 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. Evidence-based toxicology has its roots in the larger movement towards evidence-based practices. By analogy to evidence-based medicine (EBM), 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. 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. 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. 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. Assessments of BPA range from low risk of harm to the public to potential risks (for some populations), leading to different political decisions. Systematic reviews can help reducing such divergent views. In contrast with narrative reviews, they reflect 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; 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. 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. Evidence-based approaches were first conceived as a means of anchoring policy decisions, not to current practices or the beliefs of experts, but to experimental evidence. Evidence-based medicine (EBM) was launched slightly later. Its rise as a distinct discipline is generally credited to the work and advocacy of Scottish epidemiologist Archie Cochrane. The Cochrane Collaboration named in his honor was launched at Oxford University in 1993 to promote evidence-based reviews of clinical medical literature. More recently, EBM expanded to encompass evidence-based health care (EBHC). EBM/HC involves the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients taking patients' preferences into account. Prior to EBM, medical decisions about diagnosis, prevention, treatment or harm were often made without a rigorous evaluation of the alternatives. Research in the 1970s and 1980s showed that different physicians regularly recommended different treatments and tests for patients with ailments that were essentially the same, and that large proportions of procedures being performed by physicians were considered inappropriate by the standards of medical experts.EBM/HC supporters stress that while evidence always has been important to the practice of medicine, EBM/HC provides an enhanced approach of identifying, assessing, and summarizing evidence. EBT's supporters make a similar argument. The idea of translating evidence-based approaches from medicine to toxicology has been percolating for two decades, with proponents in both medicine and toxicology. Three research papers published in 2005 and 2006 catalyzed what eventually became known as EBT by suggesting that EBM's established tools and concepts might serve as a prototype of evidence-based decision-making in toxicology. The First International Forum Toward Evidence-Based Toxicology was held in 2007. The forum was organized by the European Commission and attended by 170 scientists from more than 25 European, American, and Asian countries. The goal was to explore the available concepts of EBT, and to launch an initiative to formally implement evidence-based assessment methods in toxicology. The starting point for the discussions were two research papers suggesting that the tools and concepts established in evidence-based medicine could serve as a prototype of evidence-based decision-making for evaluating toxicological data. Apparent fundamental differences between medicine and toxicology were carefully considered during these discussions. Forum participants attempted to bridge the two disciplines in order to make use of the accrued wisdom and apply this approach to toxicology. (See http://www.ebtox.org/resources/evidence-based-toxicology-explained/ .)