The necessary know-how on reduction in animal experiments

Reduction means the maximum possible decrease in the number of animals used in an animal experiment. However, it is essential that the quality and the information content of the research results are not negatively influenced.

Important measures to ensure reduction are, on the one hand, precise research and planning of the experiment and, on the other hand, the creation of a suitable publication to convey essential information to the scientific community. The results of the research should be comprehensible and reproducible by other research groups.

The so-called PREPARE and ARRIVE guidelines, which can be found on the homepage of Norecopa, the well-known Norwegian 3R center, provide an overview of reduction possibilities and offer valuable support to researchers in the experimental process from day one. In order to obtain high quality, as well as reproducible research results and to act in the spirit of the 3Rs, both guidelines should be followed.

PREPARE Guidelines

PREPARE in this context stands for Planning Research and Experimental Procedures on Animals: Recommendations for Excellence. The PREPARE Guidelines originate from a collaboration between Norecopa and the RSPCA (Royal Society for the Prevention of Cruelty to Animals), the oldest and largest animal welfare organization in the world. As can be seen from the title of the guidelines, they deal with all factors that are necessary for the planning of an animal experiment. For this purpose, a two-page checklist is provided on the homepage, which is even available in different languages. Furthermore, a video is referred to, which illustrates the content of the PREPARE Guidelines and explains how compliance with them has a positive influence on the research. The individual contents of the checklist are again described in detail in extra points on the homepage. Further sources of information and references are linked to each point. The topics of the PREPARE Guidelines include:

Literature search
legal framework
ethical obligations (harm-benefit analysis, humane endpoints)
experimental design and statistics
planning/timing of the project involving all persons involved
evaluation and selection of an appropriate laboratory animal facility
preparatory training, hazard analysis
description of substances and procedures used
know-how on the selected animal species
quarantine and health monitoring
species-appropriate animal husbandry
experimental activities
humane killing methods/reuse/disposal
dissection and sampling

ARRIVE Guidelines

The ARRIVE Guidelines - Animal Research: Reporting of In Vivo Experiments - are intended to contribute to the standardized publication of research results. They are addressed to the publishing person himself and to those who are responsible for the peer review. The current version of the guideline, ARRIVE 2.0, is linked on the Norecopa homepage. The link is to a Web site titled "ARRIVE Guidelines" (https://arriveguidelines.org/). ARRIVE 2.0 is a product of Norecopa's collaboration with other international partners and researchers from academia and industry. The ARRIVE Guidelines homepage provides a checklist, available in several languages, for free download. One page of the checklist contains a brief introduction to ARRIVE, as well as an explanation of the positive effect on research that can be achieved by following these guidelines. The second page contains two lists titled "The Essential 10" and "The Recommended List." "The Essential 10" is a checklist of items that must be included in a study in order for readers and reviewers to make a judgment regarding the reliability of the results. The list includes the following items:

experimental design
sample size
inclusion and exclusion criteria
randomization
blinding
measurement parameters
statistical methods
experimental animals
experimental interventions or measures
results

"The Recommended List" is used to supplement the first checklist and adds more information to the study assessment. It lists the following items:

Abstract of the experiment
background
objectives
ethical statement
housing and husbandry
animal care and monitoring
interpretation/scientific implications
generalizability/transferability
protocol registration
data access
declaration of interests

One criticism of the current version of the ARRIVE Guidelines from Norecopa is that it makes no mention of the 3R concept. Norecopa recommends a 3-tiered system (PREPARE, Report, Flag) for conducting animal studies. First, an experiment should be planned according to the PREPARE Guidelines (=PREPARE). In the next step, researchers should follow reporting guidelines such as the ARRIVE Guidelines or others such as the Gold Standard Publication Checklist (=Report). This should enable publication of the conducted study in a reputable journal. The last step is to mention the 3Rs in the title or abstract of the publication to highlight them again (=flag).

Apart from the guidelines mentioned above, there are other possible sources for obtaining information and planning animal experiments. The following list provides a brief overview.

Sources:
https://norecopa.no/ https://arriveguidelines.org/ https://ec.europa.eu/environment/chemicals/lab_animals/3r/key_resources/databases_en.htm (access: 08.03.2023)

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