Session 4: Integrating Evidence and Analysis

OpenTox USA 2015, Session 4: Integrating Evidence and Analysis

Integrating Evidence and Analysis
Session Chair: Thomas Hartung, Johns Hopkins

Thursday, 12 February 2015
from 9:00 to 11:00

Speakers Title
Martin Stephens, Director EBTC, Johns Hopkins Introduction to Evidence-based Toxicology
Michael Rosenberg, Agilent Evidence-integration from multi-omics in the Human Toxome project
Thomas Hartung, Johns Hopkins Constructing and evaluating Integrated Testing Strategies (ITS) for Safety Assessment
Nicole Kleinstreuer, ILS/NICEATM Combining Data Streams and Modeling Approaches to Develop Skin Sensitization ITS
David Dix, (US EPA) High Throughput Chemical Screening for Endocrine Disrupting Potential
Session 4 Summary

Evidence-based approaches have been popularized in health care, especially clinical medicine, by the Cochrane collaboration and the Evidence-based Medicine movement. Starting in 2005, we began to translate this approach to toxicology with a first conference in 2007 in Como, Italy, which called on the scientific community to establish Evidence-based Toxicology (EBT).

A series of publications laid the ground for the creation of the EBT Collaboration in the US in 2011 and Europe in 2012. The secretariat is hosted by the Johns Hopkins Center for Alternatives to Animal Testing, where the first chair for EBT was created. A first conference was held in 2012 in Research Triangle Park and the next one is planned on 21 November 2014 in Baltimore. EBT is guided by the themes of transparency, objectivity and consistency, to promote the use of evidence-based approaches to strengthen decision-making in safety sciences. The primary tool of evidence-based medicine (EBM) is the systematic review, which includes a variety of steps: framing the question to be addressed and deciding on how relevant studies will be identified and retrieved, which studies will be excluded from the analysis, how the included studies will be appraised for quality/potential for bias, and how the data will be synthesized across studies (e.g., meta-analysis).

Bringing new approaches to the assessment of test method performance will be particularly timely. As toxicology moves to pathway-based approaches (as exemplified by the National Academy of Sciences┬╣ 2007 report on Toxicity Testing in the 21st Century) and in the OECD AOP concept, the field will need new tools for assessing test method performance, especially as the focus shifts from animal to human biology. Similarly, as test methods are developed to assess effects at multiple levels of biological organization (e.g. organ on a chip), tools will be needed to synthesize such data in ways that are transparent, objective, and systematic. Ultimately, this effort will open up new approaches to hazard and risk assessment with the ability to flexibly integrate new evidence or adapt to it. A concept for mechanistic validation has been developed in this context.