Query: animal testing

title: The impact of precision uncertainty on predictive accuracy metrics of non animal testing methods.
abstract: The ability of non animal methods to correctly predict the outcome of in vivo testing in repeated applications is referred to as precision. Due to dichotomising continuous read outs into discrete "positive/negative" hazard data, non animal methods can reveal discordant classifications if results are sufficiently close to a defined classification threshold. This paper explores the impact of precision uncertainty on the predictive accuracy of non animal methods. Using selected non animal methods for assessing skin sensitisation hazard as case study examples, we explore the impact of precision uncertainty separately and in combination with uncertainty due to varying composition and size of experimental samples. Our results underline that discrete numbers of non animal methods' sensitivity, specificity and concordance are of limited information for evaluations of non animal testing methods' predictivity. Instead, information on the variability, and the upper and lower limits of accuracy metrics, should be provided to ensure a transparent assessment of testing methods' predictivity, and to allow for a meaningful comparison of the predictivity of non animal methods with that of animal tests.

title: Animal testing and its alternatives the most important omics is economics.
abstract: For a long time, the discussion about animal testing vs its alternatives centered on animal welfare. This was a static warfare, or at least a gridlock, where life scientists had to take a position and make their value choices and hardly anyone changed sides. Technical advances have changed the frontline somewhat, with in vitro and in silico methods gaining more ground. Only more recently has the economic view begun to have an impact: Many animal tests are simply too costly, take too long, and give misleading results. As an extension and update to previous articles in this series written a decade ago, we reanalyze the economic landscape of especially regulatory use of animal testing and this time also consider respective alternative tests. Despite some ambiguity and data gaps, which we have filled with crude estimates, a picture emerges of globally regulated industries that are subject to stark geographic and sectorial differences in regulation, which determine their corresponding animal use. Both animal testing and its alternatives are industries in their own right, offering remarkable business opportunities for biotech and IT companies as well as contract research organizations. In light of recent revelations as to the reproducibility and relevance issues of many animal tests, the economic consequences of incorrect results and the reasons for still maintaining often outdated animal test approaches are discussed.

title: Animal Testing

title: Animal Testing for Acute Inhalation Toxicity: A Thing of the Past?
abstract: According to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages 10 tons per year. Three OECD test guidelines for acute inhalation toxicity in vivo are adopted (TG 403, TG 436, and TG 433) Since animal testing is ethically, scientifically and economically questionable, adoption of alternative methods by the European Union and the OECD is needed. An in vitro system based on the study of lung surfactant function is introduced.

title: In silico methods Computational alternatives to animal testing.
abstract: A seminar and interactive workshop on "In silico Methods Computational Alternatives to Animal Testing" was held in Berlin, Germany, organized by Annemarie Lang, Frank Butt gereit and Andrea Volkamer at the Charite Universitatsmedizin Berlin, on August 17 18, 2017. During the half day seminar, the variety and applications of in silico methods as alternatives to animal testing were presented with room for scientific discus sions with experts from academia, industry and the German fed eral ministry  Talks on computational systems biology were followed by detailed information on predictive toxicology in order to display the diversity of in silico methods and the potential to embrace them in current approaches (Hartung and Hoffmann, 2009; Luechtefeld and Hartung, 2017) The follow ing interactive one day Design Thinking Workshop was aimed at experts, interested researchers and PhD students interested in the use of in silico as alternative methods to promote the 3Rs  Forty participants took part in the seminar while the workshop was restricted to sixteen participants.

title: Alternatives to animal testing: A review
abstract: The number of animals used in research has increased with the advancement of research and development in medical technology. Every year, millions of experimental animals are used all over the world. The pain, distress and death experienced by the animals during scientific experiments have been a debating issue for a long time. Besides the major concern of ethics, there are few more disadvantages of animal experimentation like requirement of skilled manpower, time consuming protocols and high cost. Various alternatives to animal testing were proposed to overcome the drawbacks associated with animal experiments and avoid the unethical procedures. A strategy of 3 Rs (i.e. reduction, refinement and replacement) is being applied for laboratory use of animals. Different methods and alternative organisms are applied to implement this strategy. These methods provide an alternative means for the drug and chemical testing, up to some levels. A brief account of these alternatives and advantages associated is discussed in this review with examples. An integrated application of these approaches would give an insight into minimum use of animals in scientific experiments.

title: How institutional logics hamper innovation: The case of animal testing
abstract: For radical innovation to become successful the substitution of established practices are essential. Nevertheless, in the innovation literature novelty is often at the center and only little attention is paid to the influence of established technologies and underlying routines. This paper aims to contribute to this gap by increasing the understanding about the effect of persistence of established practices on the innovation process. We do this by using a framework that combines the Technological Innovation System approach with an analysis of the institutional logics reinforcing the established practice. The studied case concerns the innovation process to animal free medicine development. Despite the fact that the substitution of animal tests is called for since the 1980s and animal free methods are available, animal tests are still being used in medicine development. This study shows that adding institutional logics to the innovation systems analysis creates a much better understanding of the speed and direction of radical innovation.

title: Validation of Alternative In Vitro Methods to Animal Testing: Concepts, Challenges, Processes and Tools.
abstract: This chapter explores the concepts, processes, tools and challenges relating to the validation of alternative methods for toxicity and safety testing. In general terms, validation is the process of assessing the appropriateness and usefulness of a tool for its intended purpose. Validation is routinely used in various contexts in science, technology, the manufacturing and services sectors. It serves to assess the fitness for purpose of devices, systems, software up to entire methodologies. In the area of toxicity testing, validation plays an indispensable role: "alternative approaches" are increasingly replacing animal models as predictive tools and it needs to be demonstrated that these novel methods are fit for purpose. Alternative approaches include in vitro test methods, non testing approaches such as predictive computer models up to entire testing and assessment strategies composed of method suites, data sources and decision aiding tools. Data generated with alternative approaches are ultimately used for decision making on public health and the protection of the environment. It is therefore essential that the underlying methods and methodologies are thoroughly characterised, assessed and transparently documented through validation studies involving impartial actors. Importantly, validation serves as a filter to ensure that only test methods able to produce data that help to address legislative requirements (e.g. EU's REACH legislation) are accepted as official testing tools and, owing to the globalisation of markets, recognised on international level (e.g. through inclusion in OECD test guidelines) Since validation creates a credible and transparent evidence base on test methods, it provides a quality stamp, supporting companies developing and marketing alternative methods and creating considerable business opportunities. Validation of alternative methods is conducted through scientific studies assessing two key hypotheses, reliability and relevance of the test method for a given purpose. Relevance encapsulates the scientific basis of the test method, its capacity to predict adverse effects in the "target system" (i.e. human health or the environment) as well as its applicability for the intended purpose. In this chapter we focus on the validation of non animal in vitro alternative testing methods and review the concepts, challenges, processes and tools fundamental to the validation of in vitro methods intended for hazard testing of chemicals. We explore major challenges and peculiarities of validation in this area. Based on the notion that validation per se is a scientific endeavour that needs to adhere to key scientific principles, namely objectivity and appropriate choice of methodology, we examine basic aspects of study design and management, and provide illustrations of statistical approaches to describe predictive performance of validated test methods as well as their reliability.

title: E cigarettes and the need and opportunities for alternatives to animal testing.
abstract: E cigarettes have become within only one decade an important commodity, changing the market of the most mass killing commercial product. While a few years ago estimates suggested that in the course of the 21st century one billion people would die prematurely from tobacco consumption, e cigarettes continuously gaining popularity promise 10 30fold lower health effects, possibly strongly changing this equation. However, they still are not a harmless life style drug. Acceptability simply depends on whether we compare their use to smoking or to not smoking. In the absence of long term follow up health data of users, additional uncertainty comes from the lack of safety data, though this uncertainty likely only is whether they represent 3 or 10% of the risk of their combustible counterpart. This means that there is little doubt that they represent a prime opportunity for smokers to switch, but also that their use by non smokers should be avoided where possible. The real safety concerns, however, are that e cigarettes expose their users to many compounds, contaminants and especially flavors (more than 7,000 according to recent counts) which have mostly not been tested, especially not for long term inhalation exposure. Neither the precautionary traditional animal testing nor post marketing surveillance will offer us data of sufficient quality or sufficiently fast to support product development and regulatory decisions. Thus, alternative methods lend themselves to fill this gap, making this new product category a possible engine for new method development and its implementation and validation.

title: The challenge of a ban on animal testing for the development of a regulated legal market for new psychoactive substances (NPS) 'legal highs' in New Zealand: Issues and options for resolution.
abstract: In mid July 2013, New Zealand passed the Psychoactive Substances Act (PSA) which allowed 'low risk' psychoactive products 'legal highs' to be approved for legal sale. In early May 2014, following public protest, the Psychoactive Substances Amendment Act (PSAA) was passed banning animal testing of psychoactive products, potentially making the new regime unworkable.  To investigate strategies to overcome the impasse created by the animal testing ban.  Solutions to the impasse were investigated using 'scenario' and 'stakeholder' analysis. Legislation, parliamentary debates, and regulatory statements related to the PSA and animal testing were reviewed. Strategies to resolve the impasse were discussed with stakeholders including the Psychoactive Substances Regulatory Authority (PSRA) officials, health officials, a legal high industry lawyer, and a leading legal highs manufacturer. This process generated six possible scenarios and five decision making criteria of key importance to major stakeholders. Scenarios were then evaluated based on feedback from the industry and regulators.  The six scenarios were: (1) pragmatic modification of the animal testing ban; (2) waiting until new non animal test models are internationally accepted; (3) use of non validated replacement test methods; (4) judicial challenge of the animal testing ban; (5) 'creative compliance' by only presenting human clinical trial results; and (6) philosophical re conceptualisation of the 'benefits' from psychoactive products. Options 1 and 5 appear to be the most attractive overall solutions. However, both rely on a new political consensus and astute framing of the issues by political communicators. Political decision makers may be happy to accept Scenario 2 which would impose significant delays.  A 'failed' pharmaceutical product with psychoactive effects may have the test data required to be approved under Scenarios 1 and 5. Ultimately, the pleasurable benefits from psychoactive products may need to be included in the debate.