Coursera open-source course on Evidence-based Toxicology
Scientific Liaison Course Webinars
Webinar 1: September 11, 2018: Introduction to Systematic Review and Their Application in Chemical Risk Assessment Across the Atlantic: US EPA and EFSA
The use of systematic review (SR) and evidence-based methodologies in toxicology and risk assessment have evolved from theory to practice. This webinar series seeks to provide general information about the systematic review and present case studies of the use of SR in regulatory decision-making in different domains. The presentations will focus on efforts specifically associated with risk-based practices, such as development of health-based benchmarks (e.g., acceptable daily intakes, reference doses, etc.), rather than characterization of potential hazard (e.g., likelihood to be a hazard to humans for a given health outcome). Tools and frameworks initially developed for the field of medicine have been adapted to apply to toxicological research questions, and in many cases, new tools developed. The presentations will describe how the regulatory practitioners have addressed the challenges of toxicological data relative to that of medicine. For example, address challenges in evaluating exposures vs. interventions, multi-endpoint vs. single endpoint outcomes, well-defined diseases or conditions, complex data that is often not in humans (but rather in experimental animal studies or in vitro studies) vs. randomized controlled trials in humans, and evaluation of mixtures vs. pure substances. And beyond evaluation of individual studies and qualitative characterizations of hazard, approaches to integrate data in the context of risk‒to be evaluated on a common metric, to develop health based-benchmarks – have been developed and applied. These concepts must be balanced with the rigor of a SR, a component which translates into time and resources. It is anticipated that these series will provide practical information for toxicologists and risk assessors and facilitate an understanding of how SR is being utilized in support of risk-based chemical assessments. Notably, speakers will also highlight how systematic review provides additional rigor and transparency, as well relevance of the process in decision-making for regulated chemicals.
Speakers: Katya Tsaioun, EBTC at Bloomberg School of Public Health; Kristina Thayer, Director, US EPA IRIS Program; and Elisa Aiassa, Scientific Officer, European Food Safety Authority
Systematic reviews (SR) help clinicians keep abreast of the medical literature by summarizing large bodies of evidence and helping to explain differences among studies on the same question. Used to inform medical decision-making, plan future research agendas, and establish policy, SR methods are ready to be adopted in risk assessment. A number of case studies on the application of the principles of SR will be presented related to the evaluation of preclinical animal studies conducted by SYRCLE and others. Challenges in conducing SRs in preclinical research will be addressed. Recent solutions to these challenges such as recently opened pre-registration of preclinical protocols, internal validity (risk of bias) tools, and external validity (generalizability of results) will be presented.
Speakers: Katya Tsaioun, EBTC at Bloomberg School of Public Health; Kim Weaver, SYRCLE at Radboud University Medical Centre; and Daniele Wikoff, Health Practice Leader, ToxStrategies
Integrating Mechanistic Evidence into Toxicology Systematic Reviews
EBTC and the GRADE Working Group collaborated on a workshop which explored how mechanistic information can be better organized and integrated into systematic reviews of health risks posed by exposure to chemical substances. The workshop preceded the annual GRADE meeting June 13-14th, 2019 in Hamilton, Ontario.
The goal of this workshop is to explore, via discussion of four related themes, how systematic review methods and AOP concepts can be combined to develop and use non-animal test methods for predicting the toxicity of chemical substances in an evidence-based manner.
1. How do we distinguish high quality in vitro studies from low quality ones?
2. What does a systematic approach to AOP development look like?
3. How does one distinguish spurious AOPs from plausible ones?
4. How can one use AOP information to develop non-animal toxicity assays?
Introduction (EBTC, GRADE - Katya Tsaioun, Holger Schünemann) 00:00
- Certainty in modelled data - Jan Brozek, McMaster University (18:19)
- Certainty in AOPs and AOP-based alternatives - Holger Schünemann, Chair and Professor, Department of Health Research Methods, Evidence, and Impact Director, Cochrane Canada and McMaster GRADE Centre (42:48)
- Systematic maps and literature-driven AOP development- Michelle Angrish, US EPA, IRIS (1:04:20)
- Risk of bias appraisal of in vitro studies - Andrew Rooney, NIEHS, National Toxicology Program, OHAT (1:20:16)
- Using AOPs to develop non-animal alternatives and IATAs - Patience Browne, OECD (1:41:43)
Open Discussion (2:03:33)