Kick-off meeting of the Evidence-Based Toxicology Collaboration (EBTC) Europe
In conjunction with Eurotox Congress 2012 (Stockholm, Sweden)
June 17, 2012
15:30h - 17:30h
Radisson Blu Royal Viking Hotel • Vasagatan 1, Stockholm, Sweden
The Evidence-based Toxicology (EBT) Collaboration:
An Overview
Toxicity testing serves to help safeguard public health from the potentially harmful effects of chemicals, pharmaceuticals, and other agents. Given this important role, the toxicology toolbox should keep pace with advances in science and technology. The toxicological toolbox was expanded over the course of the twentieth century but the new tests were mostly variations on the prevailing theme of relying on animal models and extrapolating the results to humans or the environment. In vitro tests made inroads, but only insofar as validation studies showed that they were able to predict the results of animal tests.
More far-reaching changes are underway in the twenty-first century. Toxicity testing has begun to undergo a paradigm shift away from its heavy reliance on both animal models and in vitro methods based on animal biology. The emerging paradigm emphasizes tests involving human “pathways of toxicity,” often using human cells in high-throughput platforms. This transformation is being driven by advances in science and technology, changes in chemical regulation (e.g., REACH), recognition of the limitations of current methods, and calls for reducing animal testing.
Traditional validation approaches are not well-suited to evaluating the emerging methods. The new methods and approaches are evolving too rapidly to be evaluated by a process that typically takes several years and considerable resources to complete. Moreover, the new vision outlined in the 2007 National Academy of Sciences report on Toxicity Testing in the 21st Century focuses on predicting human biology, not replacing data from animal tests. Consequently, we need a new, evidence-based way to assess the relevance and reliability of the new methods—21st century validation for 21st century methods.
To address these and related challenges, toxicologists working in industry, government, and academia have formed the Evidence-Based Toxicology (EBT) Collaboration. Modeled after the Cochrane Collaboration in Evidence-based Medicine (EBM), the EBT Collaboration aims to foster the development of systematic, objective, and transparent test method assessment and decision-making based on test results. Usually, such decision-making will quantitativly integrate existing with newly generated evidence in a consistent manner.
Such a process will be invaluable to regulators as they evaluate the new methods and the data generated from them.
The medical community developed EBM over the last two decades as a way of translating complex clinical information into effective medical practice, as well as minimising potential subjectivity and biases in decision processes. This approach has involved a strong focus on scientific evidence and its careful evaluation. EBM seeks to ensure that decisions relevant to the health of patients are based on the best evidence available. It comprises a suite of assessment methods and decision-aiding tools, as well as structures for their implementation in the decision-making process. The methods of EBM include systematic reviews of relevant literature, scoring tools to prioritize published reports and clinical events, and meta-analysis of data. These tools have been used successfully in the assessment of etiologies, diagnoses, prognoses, and therapies. Collectively they have served to strengthen significantly the scientific basis of medicine.
The EBM movement (through the Cochrane Collaboration) has engaged 27,000 physicians, scientists and health care providers to produce more than 5,000 guidance documents evaluating clinical practices. Because of the transparency, objectivity, and scientific rigor of the process, EBM guidance - where available - is considered the best available evidence for a given clinical question. A similar process in toxicology (EBT) can and should be developed to provide the best possible guidance on how to use the increasingly diverse toxicological toolbox to address risk assessment questions.
There are at least three different areas of toxicology to which the approaches of EBM could be applied: method assessment, weighting and integration of evidence, and causation of an adverse effect. The EBT Collaboration will emphasize method assessment. Approaches translated from EBM will extend the current means of evaluating and quality assuring new testing methods, and will also be used in critical and objective analyses of current methods. In addition, however, toxicology-specific approaches will need to be developed for EBT that, nevertheless, will adhere to the principles of EBM.
A steering committee has been established in the United States to advance the work of the EBT Collaboration, with the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) serving as secretariat. A similar group has been formed in the European Union. The two steering committees will work in parallel but be closely coordinated. Cross-cutting activities such as an EBT website, newsletter, and working groups will be carried out jointly.
In the US, the EBT Collaboration was launched publicly at a workshop on March 10, 2011 following the Society of Toxicology annual meeting in Washington DC.
In Europe, the first initiative dates back to 2007. In October of that year, the First international forum toward evidence-based toxicology was held at Como, Italy. The forum was organised by the European Commission in close collaboration with scientists active in toxicology, life sciences, biostatistics, modeling and medicine. However, momentum was lost. Activities will be re-started by officially kicking-off the EU branch of EBTC on June 17 in Stockholm, Sweden, in conjunction with the EUROTOX congress.
The EBT Collaboration will be pivotal in facilitating the incorporation of new methods into 21st century toxicology.
Recommended readings:
Hoffmann, S. and Hartung, T. 2005. Diagnosis: toxic!—Trying to apply approaches of clinical diagnostics and prevalence in toxicological considerations. Toxicological Sciences 85, 422-428.
Hoffmann, S. and Hartung, T. 2006. Toward an evidence-based toxicology. Human & Experimental Toxicology 25, 497-513.
Hartung, T. 2009. Food for thought… on evidence-based toxicology. Altex 26, 75- 82.
Straus, S.E., Glasziou, P., Richardson, W.S., and Haynes, R.B. 2011. Evidence-based medicine: How to practice and teach it (4th ed.). Churchill Livingstone Elsevier, New York.
Draft of 21 December 2011