Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment. The workshop discussions were centered around three related themes: 1) assessing certainty in AOPs, 2) literature-based AOP development, and 3) integrating certainty in AOPs and non-animal evidence into decision frameworks. Several challenges, mostly related to methodology, were identified and largely determined the workshop recommendations. The workshop recommendations included the comparison and potential alignment of processes used to develop AOP and systematic review methodology, including the translation of vocabulary of evidence-based methods to AOP and vice versa, the development and improvement of evidence mapping and text mining methods and tools, as well as a call for a fundamental change in chemical risk and uncertainty assessment methodology if to be conducted based on AOPs and new approach methodologies (NAM). The usefulness of evidence-based approaches for mechanism-based chemical risk assessments was stressed, particularly the potential contribution of the rigor and transparency inherent to such approaches in building stakeholders’ trust for implementation of NAM evidence and AOPs into chemical risk assessment

Applying evidence-based methods to the development and use of adverse outcome pathways

The workshop “Application of evidence-based methods to construct mechanistic frameworks for the development and use of non-animal toxicity tests” was organized by the Evidence-based Toxicology Collaboration and hosted by the Grading of Recommendations Assessment, Development and Evaluation Working Group on June 12, 2019. The purpose of the workshop was to bring together international regulatory bodies, risk assessors, academic scientists, and industry to explore how systematic review methods and the adverse outcome pathway framework could be combined to develop and use mechanistic test methods for predicting the toxicity of chemical substances in an evidence-based manner. The meeting covered the history of biological frameworks, the way adverse outcome pathways are currently developed, the basic principles of systematic methodology, including systematic reviews and evidence maps, and assessment of certainty in models, and adverse outcome pathways in particular. Specific topics were discussed via case studies in small break-out groups. The group concluded that adverse outcome pathways provide an important framework to support mechanism-based assessment in environmental health. The process of their development has a few challenges that could be addressed with systematic methods and automation tools. Addressing these challenges will increase the transparency of the evidence behind adverse outcome pathways and the consistency with which they are defined; this in turn will increase their value for supporting public health decisions. It was suggested to explore the details of applying systematic methods to adverse outcome pathway development in a series of case studies and workshops

The Belgian experience with intravenous thrombolysis for acute ischemic stroke

Purpose: We report the Belgian results of the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register (SITS-ISTR). This prospective observational register evaluates the safety and efficacy of intravenous thrombolysis with rtPA (recombinant tissue Plasminogen Activator) for ischemic stroke in routine clinical practice. Methods: We compared the baseline characteristics, treatment delay, rate of symptomatic intracerebral hemorrhage and functional outcome at 90 days after treatment between patients enrolled in centres in Belgium and the non-Belgian SITS-registry population. We performed a multivariate analysis to adjust for differences in demographic and baseline characteristics. Results: 743 patients were enrolled in 42 centers in Belgium between December 2002 and December 2007. These patients were older, had more severe stroke were more frequently female and more frequently had hyperlipidemia and atrial fibrillation. The median stroke onsetto-treatment delay was 140 min vs. 145 min. More patients died and were disabled 3 months after the stroke. A slight, non-significant, increase of symptomatic intracerebral hemorrhage (SICH) as per SITS protocol was observed (2,4 vs. 1,6%, p = 0.15). After adjustment for differences in baseline characteristics, functional independence (mRS <= 2) at 3 months (OR 0.95, 95% CI 0.86-1.05, p = 0.31) was not different from non-Belgian patients, nor was the rate of SICH. However mortality at 3 months in Belgian patients was slightly higher (OR 1.15, 95% CI 1.02-1.29, p = 0.02). Conclusion: Intravenous thrombolysis for ischemic stroke is safe and effective in the routine clinical use in Belgium. The higher mortality we observed is not related to a higher rate of SICH

Assessing author willingness to enter study information into structured data templates as part of the manuscript submission process:A pilot study

Background: Environmental health and other researchers can benefit from automated or semi-automated summaries of data within published studies as summarizing study methods and results is time and resource intensive. Automated summaries can be designed to identify and extract details of interest pertaining to the study design, population, testing agent/intervention, or outcome (etc.). Much of the data reported across existing publications lack unified structure, standardization and machine-readable formats or may be presented in complex tables which serve as barriers that impede the development of automated data extraction methodologies. As full automation of data extraction seems unlikely soon, encouraging investigators to submit structured summaries of methods and results in standardized formats with meta-data tagging of content may be of value during the publication process. This would produce machine-readable content to facilitate automated data extraction, establish sharable data repositories, help make research data FAIR, and could improve reporting quality. Objectives: A pilot study was conducted to assess the feasibility of asking participants to summarize study methods and results using a structured, web-based data extraction model as a potential workflow that could be implemented during the manuscript submission process. Methods: Eight participants entered study details and data into the Health Assessment Workplace Collaborative (HAWC). Participants were surveyed after the extraction exercise to ascertain 1) whether this extraction exercise will impact their conducting and reporting of future research, 2) the ease of data extraction, including which fields were easiest and relatively more problematic to extract and 3) the amount of time taken to perform data extractions and other related tasks. Investigators then presented participants the potential benefits of providing structured data in the format they were extracting. After this, participants were surveyed about 1) their willingness to provide structured data during the publication process and 2) whether they felt the potential application of structured data entry approaches and their implementation during the journal submission process should continue to be further explored. Conclusions: Routine provision of structured data that summarizes key information from research studies could reduce the amount of effort required for reusing that data in the future, such as in systematic reviews or agency scientific assessments. Our pilot study suggests that directly asking authors to provide that data, via structured templates, may be a viable approach to achieving this: participants were willing to do so, and the overall process was not prohibitively arduous. We also found some support for the hypothesis that use of study templates may have halo benefits in improving the conduct and completeness of reporting of future research. While limitations in the generalizability of our findings mean that the conditions of success of templates cannot be assumed, further research into how such templates might be designed and implemented does seem to have enough chance of success that it ought to be undertaken