EBTC Scientific Symposium #4: Overcoming Data Availability Obstacles in the Way of Evidence-based Toxicology
June 25, 2021
This Symposium will discuss how the issues of selective publishing and closing of data gaps in toxicology might be addresses.
The first presentation is about obstacles that publication bias presents to systematic reviews (SRs), using as a case-study a recent EBTC SR of drug-induced liver injury, where large amounts of relevant evidence were inaccessible due to selective publishing practices.
The second presentation is about gaps in data submitted for regulatory approval, focusing on improving access to drug safety and efficacy data currently held back from public view as proprietary. The third presentation is about methods for understanding the toxicity of chemicals for which there is simply very little data. The importance of transparency in AI-powered, read-across computational tools is discussed.
EBTC Webinar: Application of US EPA IRIS Systematic Review Methods to Health Effects of Phthalate Exposures
February 2, 2021
Scientists at the US EPA IRIS Program recently finalised a series of systematic reviews investigating the human health effects of exposure to phthalates. In this EBTC Online Scientific Symposium, the scientists will be presenting the main findings from their SRs, highlighting novel uses of SR methods in dose-response modeling, and drawing out general lessons learned in the application of SR methods in chemical assessment.
1. Introduction to the US EPA IRIS methodology being applied in the systematic reviews
2. Methods used for systematically reviewing animal studies of phthalate exposures (Dr Laura Dishaw)
3. Summary of findings of the systematic reviews of animal studies (Dr Erin Yost)
4. Summary of findings of the systematic reviews of epidemiological studies (Dr Elizabeth Radke)
5. Methods used for dose-response modeling in the systematic reviews (Dr Todd Blessinger)
6. Panel session with audience Q&A
EBTC Webinar: COSTER
September 17, 2020
COSTER is the first comprehensive set of recommendations for conduct of systematic reviews which have been developed specifically for toxicology and environmental health research. This webinar describes how COSTER was developed, gives an overview of its recommendations, and discusses how COSTER should be used. There will be an extended Q&A to answer participants' questions. The presenter is Paul Whaley. He is the lead author of COSTER, Systematic Reviews Editor for Environment International (IF 7.58), and an experienced advocate of the use of systematic methods for reviewing evidence to support the development of environmental health policy.
You can read the COSTER manuscript here.
EBTC GRADE Pre-Meeting
June 15, 2020
How certain are we? Progress in adapting systematic review methods to environmental health assessments
Watch Now Session 1
Incorporating mechanistic data in environmental health systematic reviews
- Applying SR methods to the task of developing knowledge of biological mechanisms by which environmental exposures cause adverse health outcomes (Michelle Angrish, US EPA)
- Applying mechanistic frameworks to the problem formulation step (defining the problem and eligibility criteria) of the systematic review process (Nicolas Roth, Swiss Centre for Applied Human Toxicology)
- Incorporating mechanistic data in IARC carcinogenicity assessments using the key characteristics approach (Kate Guyton, IARC)
Thoughts and responses from GRADE Working Group experience
Holger Schünemann, Rebecca Morgan
Watch now Session 2
Assessing certainty of the evidence in environmental health contexts
- WHO experience in adapting the GRADE Framework to assessing certainty of the evidence in SRs of prevalence studies (Frank Pega, WHO)
- US EPA IRIS Program approach to assessing certainty of the evidence, as conducted in the recent SRs of human health effects of exposure to phthalates (Beth Radke, Dr Erin Yost, US EPA)
- Experience in integrating mechanistic data and use of the NTP OHAT certainty framework in systematic reviews of the effect of organochlorine exposure on risk of endometriosis (German Cano Sancho, INRA)
Thoughts and responses from GRADE Working Group experience
Holger Schünemann, Rebecca Morgan
American Association for the Advancement of Science (AAAS) Annual Meeting
February 14, 2020
Bioinformatics and AI: Innovative Approaches to Research and Data Storage
- Knowledge Systems for the Anthropocene
Paul Whaley, Lancaster University, Lancaster, United Kingdom
- AI in Environmental Health: From Data Poverty to Factfulness and Evidence
- The Virtual Physiological Human
Liesbet Geris, University of Liège, Liège, Belgium
The challenges of maintaining population health in a rapidly-changing environment are evolving faster than researchers can respond. Climate change, shifting disease patterns, population demographics, and environmental pollution present multiple interacting threats which require urgent, evidence-based responses. However, traditional models of research conduct, publication, and analysis can take years to provide policy-makers with decision-critical information.
This symposium presents three expert perspectives on how the AI revolution in bioinformatics is transforming our conception of how scientific research should be stored, published and accessed. They describe how next-generation knowledge systems will optimize the use of existing scientific data, vastly increasing the accessibility of scientific evidence for the development of effective health policy.
Session participants will learn about the following themes: how social media platforms and AI could revolutionize research and data storage; how big data allows scientists to better-anticipate health risks posed by an increasingly polluted environment, and an introduction to an in silico biological system for developing and testing medical treatments.
Advancing the Application of Evidence-Based Methods to Construct Mechanistic Frameworks for the Development and Use of Non-Animal Toxicity Tests
October 2-3, 2019
European Food Safety Authority
Systematic evidence synthesis methods and adverse outcome pathways (AOPs) are two relatively recent arrivals in the toxicologist's toolbox, which promise to bring toxicological research into the 21st Century.
During a GRADE Working Group satellite meeting on 12 June 2019 in Hamilton, ON, it was explored 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.
The goal of the current workshop is to deepen the discussions from the pre-meeting and work on concrete tools and papers to advance the field. The workshop will cover 3 related themes:
1. Assessing certainty in AOPs (topic leads: Rebecca Morgan and Paul Whaley)
2. Literature-based AOP development (topic leads: Michelle Angrish, Steve Edwards and Paul Whaley)
3. Integrating certainty in AOPs and non-animal evidence into decision frameworks (topic leads: Ingrid Druwe and Sebastian Hoffmann)
Integrating Mechanistic Evidence into Toxicology Systematic Reviews
June 13-14th, 2019
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)
Raising the Standard of Systematic Reviews Published in Toxicology and Environmental Health Journals
Workshop May 29-31, 2019
Research Triangle Park, NC
The ultimate objective is to significantly improve the quality of the systematic reviews we are publishing as journals in the environmental health and toxicological sciences.
The individual objectives of the workshop are to:
1. Develop a common understanding of the challenges we as editors face in ensuring that all published SRs meet an acceptable standard of scientific quality;
2. Articulate a set of strategic editorial interventions (actions taken by editors to improve publishing outcomes), which we believe would improve the standard of published SRs;
3. Identify and commit to approximately five actions which can be implemented short-term at our journals to immediately improve the standard of published SRs.
(2) does not imply any commitment to specific actions; it is intended as a comprehensive strategy which, if followed, would be considered by the participants as being very likely to make a substantial and lasting difference to the standard of SRs being published by a journal.
(3) is an ideal rather than expected outcome of the workshop, whereby participants will work together to identify a set of actions which they feel they can collectively undertake on a relatively short-term timeline. The hope is that we will be able to agree on approximately five actions and potentially even publish these plans in a joint editorial across multiple journals, in a fashion similar to that for the launch of the PRISMA reporting standard (see here).
Boundaries: In the interests of a focused discussion which will make a material difference to SR publishing standards, we acknowledge several issues which are of fundamental importance to the publication of high-quality research but are nonetheless not part of the agenda. These are:
- a. Interventions for improving review-type manuscripts which are not systematic reviews
- b. Interventions for improving study reports of primary research
- c. The defining of standards and expectations for conduct and reporting of systematic reviews
(a) and (b) are excluded because they require different interventions, engagement with different research methodologists and audiences, and therefore a different strategy, which would dilute the focus of this event. While agreeing to work on (c) could be an outcome of the workshop, the defining of such standards themselves is not an objective of the workshop – in the same way that agreeing to work on specifications for improved editorial management systems may be a workshop outcome, actually defining and making those improvements would not be a workshop activity.
Society of Toxicology (SOT) Annual Meeting
March 16, 2020
Katya Tsaioun (EBTC), co-chair
- Mechanisms and Multiple Exposures: Methods to Tackle Toxicology's Most Difficult Challenges Using Systematic Review Frameworks
- Mechanistic Safety Tests in Decision-Making in the Absence of Human Data: Using a Systematic Review Framework
Daniele Wikoff (ToxStrategies, In., EBTC Scientific Board)
- Case Study Applications in the Identification, Assessment, and Integration of Mechanistic Evidence in Human Health Assessments: Consideration of Exposure in Developing Weight of Evidence Conclusions
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