A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals

Vandenberg, Laura N.; Ågerstrand, Marlene; Beronius, Anna; Beausoleil, Claire; Bergman, Åke; Bero, Lisa; Bornehag, Carl‐Gustaf; Boyer, Carolyn; Cooper, Glinda S.; Cotgreave, Ian A.; Gee, David; Grandjean, Philippe; Guyton, Kathryn Z.; Hass, Ulla; Heindel, Jerrold J.; Jobling, Susan; Kidd, Karen A.; Kortenkamp, Andreas; Macleod, Malcolm; Martin, Olwenn; Norinder, Ulf; Scheringer, Martin; Thayer, Kristina A.; Toppari, Jorma; Whaley, Paul; Woodruff, Tracey J.; Rudén, Christina

doi:10.1186/s12940-016-0156-6

Cited by 97 publications

(71 citation statements)

References 75 publications

(93 reference statements)

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“…The critical step is to understand the strengths and limitations of our models, both in vivo and in vitro. The systematic assessment of study quality (Samuel et al, 2016) is a key step toward such analysis, favorably by systematic reviews (Stephens et al, 2016), as recently proposed for example for endocrine disrupting chemicals (Vandenberg et al, 2016). Then we can start combining them to move towards more meaningful results in integrated testing strategies Rovida et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

Opinion versus evidence for the need to move away from animal testing

Hartung

2017

ALTEX

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toxicology, animal models are as much misleading as they are helpful. Half of the results are wrong (Ioannidis, 2005) -we only don't know which half… But the statement "half are wrong" is probably rather optimistic. Evidence versus opinion in toxicologyI am a strong advocate of evidence-based approaches, not least because I was one of the initiators of Evidence-based Toxicology (EBT) and the respective Collaboration and hold the first IntroductionFor the 10 th anniversary of Food for Thought … in ALTEX, it seemed appropriate to summarize what we have learned on this journey with respect to the core subject of this journal: the need for alternatives to animal experimentation. The series has mostly focused on toxicology, but here the aspects that apply also to drug development and basic research shall be considered.Sure, we need animal models -when we want to study animals. For example, we have to test drugs for animals in animals. However, when studying human physiology, pharmacology and Food for Thought ... Opinion Versus Evidence for the Need to Move Away from Animal Testing Thomas HartungJohns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), Baltimore, MD, USA, and University of Konstanz, CAAT-Europe, Konstanz, Germany SummaryScience is based on facts and their discourse. Willingly or unwillingly, facts are mixed with opinion, i.e., views or judgments formed, not necessarily based on fact or knowledge. This is often necessary, where we have controversial facts or no definitive evidence yet, because we need to take decisions or have to prioritize. Evidence-based approaches aim at identifying the facts and their quality objectively and transparently; they are now increasingly embraced in toxicology, especially by employing systematic reviews, meta-analyses, quality scoring, risk-of-bias tools, etc. These are core to Evidence-based Toxicology. Such approaches aim at minimizing opinion, the "eminence-based" part of science. Animal experiments are the basis of a lot of our textbook knowledge in the life sciences, have helped to develop desperately needed therapies, and have made this world a safer place. However, they represent only one of the many possible approaches to accomplish all these things. Like all approaches, they come with shortcomings, and their true contribution is often overrated. This article aims to summarize their limitations and challenges beside the ethical and economical concerns (i.e., costs and duration as well as costs following wrong decisions in product development): they include reproducibility, inadequate reporting, statistical under-powering, lack of inter-species predictivity, lack of reflection of human diversity and of real-life exposure. Each and every one of these increasingly discussed aspects of animal experiments can be amended, but this would require enormous additional resources. Together, they prompt a need to engineer a new paradigm to ensure the safety of patients and consumers, new products and therapies.

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Section: Resultsmentioning

confidence: 99%

Opinion versus evidence for the need to move away from animal testing

Hartung

2017

ALTEX

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“…In order to guard against the effects of such biases, the details of the search procedure should be clearly presented (O'Connor et al 2011). This protects against the effects of bias by providing a transparent and reproducible literature search strategy (Vandenberg et al 2016).…”

Section: Refine Results Of the Searchmentioning

confidence: 99%

“…In particular, the PECO framework has been developed for non-interventional studies: Population, Exposure, Comparator, and Outcome (Vandenberg et al 2016). One can ask, for instance: is there a mechanism in human males (population) linking exposure to high levels of benzo[a]pyrene (exposure) rather than low levels of benzo[a]pyrene (comparator) to scrotal cancer (outcome)?…”

Section: Formulate the Review Questionsmentioning

confidence: 99%

Gathering Evidence of Mechanisms

Parkkinen

Wallmann

Wilde

et al. 2018

Evaluating Evidence of Mechanisms in Medicine

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In this chapter we put forward more theoretical proposals for gathering evidence of mechanisms. Specifically, the chapter covers the identification of a number of mechanism hypotheses, formulation of review questions for search, and then how to refine and present the resulting evidence. Key issues include increased precision concerning the nature of the hypothesis being examined, attention to differences between the study population (or populations) and the target population of the evidence assessors, and being alert for masking mechanisms, which are other mechanisms which may mask the action of the mechanism being assessed. An outline example concerning probiotics and dental caries is given. (Databases that may be helpful for some searches can be found online in Appendix A).In the next three chapters, we develop core principles for evaluating efficacy and external validity. In this chapter we put forward proposals for gathering evidence of mechanisms. Then, in Chap. 6 we discuss how to evaluate this evidence. In Chap. 7, we explain how this evaluation can be combined with an evaluation of correlation in order to produce an overall evaluation of a causal claim.In the case of efficacy, where clinical studies find a correlation between the putative cause and effect, the task is to determine whether this correlation is causal by looking for further evidence of mechanisms. In order to evaluate efficacy, it is necessary to determine the status of the general mechanistic claim, i.e., to ask whether the correlated putative cause and effect are also linked by a mechanism that can account for the extent of the observed correlation.In the case of external validity, the existing evidence may establish causality in a study population that differs from the target population of interest. Here the relevant general mechanistic claim that needs to be evaluated is that mechanisms in the study and target population are sufficiently similar.

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“…SYRINA is a framework that was put forward to evaluate the strength of evidence that a certain exposure is an endocrine disruptor (Vandenberg et al 2016). This approach first evaluates the evidence for an association between chemical exposure and (adverse) effect.…”

Section: Comparison To Syrinamentioning

confidence: 99%

“…The problem also occurs in assessing whether an exposure is an endocrine disruptor. In this context, Vandenberg et al (2016) introduced SYRINA, a framework for the systematic review and integrated assessment of exposures. In this chapter, we compare the approach to assessing exposures given in this book with these other prominent approaches.…”

mentioning

confidence: 99%

Assessing Exposures

Parkkinen¹,

Wallmann²,

Wilde³

et al. 2018

Evaluating Evidence of Mechanisms in Medicine

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An important problem in causal inference in medicine involves establishing causal relationships between environmental exposures and negative health outcomes. It is typically not possible to use RCTs to solve this problem, for ethical reasons. The approach outlined in this book is compared to two other prominent approaches: the procedures of the International Agency for Research on Cancer (IARC), and SYRINA, a framework for detecting exposures that affect the endocrine system.An important problem in causal inference in medicine involves establishing causal relationships between environmental exposures and negative health outcomes (Hill 1965). Experimental studies, e.g., randomized controlled trials, tend to provide relatively strong evidence for causal claims. However, when assessing exposures it is typically not possible to carry out such trials in human populations, because this would involve unethically intervening to expose individuals to factors that are suspected to have deleterious health effects. The only available epidemiological studies are observational. As a result, it is difficult to obtain epidemiological data that are sufficient to establish causality.This problem occurs, for instance, when assessing whether an environmental exposure is carcinogenic in humans. In such cases, different types of evidence are required. For example, the International Agency for Research on Cancer (IARC) attempts to determine whether particular exposures cause cancer in humans by looking at a variety of different types of evidence, namely, epidemiological studies, studies in experimental animals, and mechanistic and other relevant data (IARC 2015). The problem also occurs in assessing whether an exposure is an endocrine disruptor. In this context, Vandenberg et al. (2016) introduced SYRINA, a framework for the systematic review and integrated assessment of exposures. In this chapter, we compare the approach to assessing exposures given in this book with these other prominent approaches. First compare our approach to external validity to the approach endorsed by IARC, with reference to the example of establishing carcinogenicity of

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A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals

Cited by 97 publications

References 75 publications

Opinion versus evidence for the need to move away from animal testing

Opinion versus evidence for the need to move away from animal testing

Gathering Evidence of Mechanisms

Assessing Exposures

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