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Würbel, H.

Publications and source records attributed to Würbel, H..

5 recordsLinked to original sources

Researchers' perspectives on preregistration in animal research

Preregistration is arguably one of the most promising and impactful Open Science practices. Defined as the a priori registration of study designs and analysis plans, preregistration has long been established as standard practice in clinical human research and is increasingly taken up in other fields of science. Despite growing evidence suggesting that preregistration can mitigate questionable research practices, and the existence of two platforms targeting animal studies, preregistration remains uncommon in animal research. In light of the reproducibility crisis and calls for more transparency and rigor also in animal research, preregistration represents a potentially promising step forward. However, implementing such policies without understanding their impact carries potential risks. It is, therefore, essential to uncover the strengths, weaknesses, opportunities, and threats of preregistration before advancing its implementation in animal research. This current study addressed this need as part of a larger feasibility project on preregistration of animal experiments in Switzerland, and aimed to: 1) assess the researchers experiences with preregistration; 2) examine their attitudes, subjective norms, perceived behavioral control, intentions, motivations, and perceived obstacles regarding preregistration; 3) explore associations between these psychosocial constructs and relevant background characteristics; 4) identify perceived facilitators and barriers to preregistration; and 5) summarize researchers suggestions for improving preregistration. A preregistered cross-sectional online survey was conducted among all registered study directors of ongoing animal experiments in Switzerland. Of the 1,385 invited study directors, 418 completed the survey (30.2% return rate; 41% female; age M = 47.1, SD = 9.52). Among them, 39.2% had never heard of preregistration, and only 10% had preregistered studies before participating in the survey. Bureaucratic burden (77.6%), time costs (71.4%), and low flexibility (65.7%) were the most common reported barriers to preregistration. On average, participants described rather unfavorable attitudes towards preregistration, negative subjective norms, relatively low perceived behavioral control, weak intention, and limited motivation to preregister, along with high perceived obstacles. Participants who had never preregistered a study, as well as those with more research experience, showed more negative scores on all assessed psychosocial constructs related to preregistration. Our findings offer guidance on promising measures to enhance acceptance of preregistration among animal researchers, including raising awareness, offering education and training, and facilitating procedures, to enhance the acceptance of preregistration among animal researchers.

scientific communication and education↗

Reliability of Mouse Behavioural Tests of Anxiety: a Systematic Review and Meta-Analysis on the Effects of Anxiolytics.

Animal research on anxiety and anxiety disorders relies on valid animal models of anxiety. However, the validity of widely used rodent behavioural tests of anxiety has repeatedly been questioned, as they often fail to produce consistent results across independent replicate studies using different study populations or different anxiolytic compounds. In this study, we assessed the sensitivity of behavioural tests of anxiety in mice to detect anxiolytic effects of drugs prescribed to treat anxiety in humans. To this end, we conducted a pre-registered systematic review of studies reporting tests of anxiolytic compounds against a control treatment using common behavioural tests of anxiety in mice. PubMed and EMBASE were searched on August 21st 2019 for studies published in English and 814 papers were identified for inclusion. Risk of bias was assessed based on Syrcles risk of bias tool and the Camarades study quality checklist on a randomly selected subsample of 180 papers. Meta-analyses on effect sizes of treatments using standardized mean differences (Hedges g) showed that only two of 17 test measures reliably detected effects of anxiolytic compounds other than diazepam. Further, we report considerable variation in both direction and size of effects of most anxiolytics on most outcome variables, indicating poor replicability of test results. This was corroborated by high heterogeneity in most test measures. Finally, we found an overall high risk of bias. Our findings indicate a general lack of sensitivity of common behavioural tests of anxiety in mice to anxiolytic compounds and cast serious doubt on both construct and predictive validity of most of those tests. The use of animals to model human conditions can be justified only if the expected results are informative, reproducible, and translatable. In view of scientifically valid and ethically responsible research, we call for a revision of behavioural tests of anxiety in mice and the development of more predictive tests.

neuroscience↗

The ARRIVE guidelines 2019: updated guidelines for reporting animal research

Reproducible science requires transparent reporting. The ARRIVE guidelines were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved.\n\nHere we introduce ARRIVE 2019. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise the items and split the guidelines into two sets, the ARRIVE Essential 10, which constitute the minimum requirement, and the Recommended Set, which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers to verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document that serves 1) to explain the rationale behind each item in the guidelines, 2) to clarify key concepts and 3) to provide illustrative examples. We aim through these changes to help ensure that researchers, reviewers and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

scientific communication and education↗

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments.\n\nDespite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.

scientific communication and education↗

A Reaction Norm Perspective on Reproducibility

Reproducibility in biomedical research, and more specifically in preclinical animal research, has been seriously questioned. Several cases of spectacular failures to replicate findings published in the primary scientific literature have led to a perceived reproducibility crisis. Diverse threats to reproducibility have been proposed, including lack of scientific rigour, low statistical power, publication bias, analytical flexibility and fraud. An important aspect that is generally overlooked is the lack of external validity caused by rigorous standardization of both the animals and the environment. Here, we argue that a reaction norm approach to phenotypic variation, acknowledging gene-by-environment interactions, can help us seeing reproducibility of animal experiments in a new light. We illustrate how dominating environmental effects can affect inference and effect size estimates of studies and how elimination of dominant factors through standardization affects the nature of the expected phenotype variation through the reaction norms of small effect. Finally, we discuss the consequences of reaction norms of small effect for statistical analysis, specifically for random effect latent variable models and the random lab model.

developmental biology↗