1. Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessmentEdward J. Perkins, Roman Ashauer, Lyle Burgoon, Rory Conolly, Brigitte Landesmann, Cameron Mackay, Cheryl A. Murphy, Nathan Pollesch, James R. Wheeler, Anže Županič, Stefan Scholz, 2019, review article Abstract: An important goal in toxicology is the development of new ways to increase the speed, accuracy, and applicability of chemical hazard and risk assessment approaches. A promising route is the integration of in vitro assays with biological pathway information. We examined how the adverse outcome pathway (AOP) framework can be used to develop pathway-based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual-based models and should be chosen according to the questions being asked and the data available. We discuss the need for toxicokinetic models to provide linkages between exposure and qAOPs, to extrapolate from in vitro to in vivo, and to extrapolate across species. Finally, we identify best practices for modeling and model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of qAOP models and ultimately their use in regulatory applications. Environ Toxicol Chem 2019;38:1850–1865. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Keywords: Quantitative Adverse Outcome pathways, TKTD modelling, alternatives to animal testing, predictive toxicology, species extrapolation, prioritization of chemicals
Published in DiRROS: 06.08.2024; Views: 153; Downloads: 116
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2. Lung cancer biomarker testing : perspective from EuropeErik Thunnissen, Birgit Weynand, Dalma Udovicic-Gagula, Luka Brčić, Malgorzata Szolkowska, Paul Hofman, Silvana Smojver-Ježek, Sisko Anttila, Fiorella Calabrese, Izidor Kern, 2020, review article Abstract: A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future.
Keywords: lung neoplasms -- diagnosis -- therapy -- Europe, lung cancer, predictive testing
Published in DiRROS: 21.09.2020; Views: 1956; Downloads: 1153
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