Publication Database

Refinement on the way towards Replacement of animal experiments:
a retrospective review of the use of Refinement methods in German animal research applications (2020)

Art

Hochschulschrift

Autor

Herrmann, Kathrin (WE 14)

Quelle

Berlin, 2020 — 161 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/27310

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon animals. When applying the principles of the 3Rs (Replacement, Reduction and Refinement), first described by Russell and Burch in The Principles of Humane Experimental Technique six decades ago, animal use in science should decline through reducing numbers of animals used and by replacing them with non-animal methods. In addition, the use of the third R, Refinement, should lead to an improvement of the conditions that cause fear, distress, pain and suffering to animals who are still being used. It is estimated that more than 127 million vertebrates are being used in science annually. Thus, until animal subjects can be fully replaced with non-animal methods, research into the third R, Refinement, and its application in practice remains imperative. To ensure scientific rigor, avoid needless animal suffering and enable an accurate harm-benefit analysis, researchers using animals must be knowledgeable about Refinement methods and apply them effectively. Indeed, researchers are legally accountable and required to minimize pain and suffering caused to the animals by their research projects. The aims of this thesis were to evaluate if and how findings from Refinement research have been implemented in practice, to determine areas where further improvement is needed and to make recommendations for the implementation of current best-practice Refinement methods. To highlight the significance of the Replacement of animals in science for scientific and for ethical reasons, a brief overview of the use of all the 3Rs in practice has also been provided and issues of poor rigor, reproducibility and translatability of animal experimentations are discussed. The study focused on experimental Refinement methods designed to minimize animal suffering. Research in this area has increased significantly over the past two decades. However, the extent to which Refinement methods are applied in practice is uncertain. Due to poor reporting standards in animal research publications, especially of Refinement, this study used original animal research proposals to retrospectively review planned Refinement. For the scope of the study, all applications submitted to the participating German competent authorities in 2010, that included recovery surgical procedures in mice and rats and that obtained a project license, were selected. The first paper of this publication-based thesis summarizes the findings of the assessment on the efficacy of proposed anesthesia and peri- and postoperative analgesia in animal research applications. Postoperative analgesia was not proposed for 30% of surgeries. Following 10% of procedures, animals were to be given pain analgesics if the investigators decided this was necessary; however, information on planned pain assessments were generally absent. Consequences of unalleviated pain and omission of pain assessment techniques are discussed, and recommendations to improve anesthesia and analgesia are made. In the second paper, we categorized the severity of proposed surgical interventions by using the relevant guidance documents and compared our rating with the rating included in the proposals. Furthermore, we assessed the appropriateness of planned monitoring of the potential adverse effects on the animals (“health monitoring”). Analysis showed that severity and chronicity of pain, suffering and distress that were to be inflicted upon the animals were frequently underestimated by the researchers. Planned health monitoring generally appeared insufficient to ensure the welfare of animals in the studies. In the third paper, the appropriateness of proposed humane endpoints and killing methods was discussed. Following 55% of surgical procedures, the investigators proposed humane endpoints. These were mostly not clearly defined, and/or were considered to be at a late stage in the animal’s deterioration. In addition, the choice of killing methods could be improved in many applications, thereby reducing suffering. The findings of this series of studies highlight the need for improvement in the implementation of Refinement in scientific use of animals, to fulfill legal requirements, to improve animal welfare and to improve the quality of research data. This study was the first to review Refinement methods in research proposals. It would be important to repeat it to assess if the situation has changed since 2010, as well as to expand it to other countries. The final paper provides an overview of the various areas of Refinement, namely housing, husbandry, care, experimental refinements and also improvements in planning, conduct and reporting of animal studies, and their application in practice. Efforts to implement the other two Rs, Reduction and Replacement, are also briefly discussed. This paper highlights extensive shortcomings in all areas of Refinement. In addition, it supports the view that, even though we have the political goal to phase out animal experimentation, in reality, we are not close to widespread Replacement of animal models with non-animal models as not enough is done to work towards such a paradigm change.