Consideration of Alternatives

“What is the literature search for alternatives and why do I have to do it?” is a frequent question asked by primary investigators.

The US Animal Welfare Act (AWA) regulations (specifically the 1985 Amendment), require the principal investigators to consider alternatives to procedures that may cause more than momentary or slight pain or distress to the animals, and provide a written narrative of the methods used and sources consulted to determine the availability of alternatives, including refinements, reductions, and replacements.

The search for alternatives refers to the three Rs described in the book, The Principles of Humane Experimental Technique (1959) by Russell and Burch. The 3Rs are reduction in the number of animals used, refinement of techniques and procedures to reduce pain or distress, and replacement of animals with non-animal techniques or use of less-sentient species.

3 Rs:

Refinement: The use of analgesics and analgesia, the use of remote telemetry to increase the quality and quantity of data gathered, and humane endpoints for the animals are examples of refinements.

Reduction: The use of shared control groups, preliminary screening in non-animal systems, innovative statistical packages or a consultation with a statistician are examples of reduction alternatives.

Replacement: Alternatives such as in vitro, cell culture, tissue culture, models, simulations, etc. are examples of replacement. This is also where you might look for any non-mammalian animal models – fish or invertebrates, for example – that would still give you the data you need.

Before you begin your search:

• Consider other possible animal or non-animal models (e.g., tissue culture, cell culture, fish, rats, etc.)
• Consider your objectives and endpoints
• Note any drugs or compounds used in procedures (e.g., anesthetics, analgesics, test compounds, etc.)
• Note methods and procedures using animals, paying particular attention to those procedures that may cause pain or distress to the animal.
• List any potential alternatives (all 3 Rs) of which you are aware (e.g., alternate models, modified techniques, housing modifications, modified restraint, in vitro methods, computer simulations, etc.)
• Develop a conceptual search strategy using the keywords and concepts you noted above. A search strategy is necessarily flexible, dependent both on the topic and on the database selected. If too many records are retrieved, additional relevant terms may made the results fewer and more useful; if too little is retrieved, fewer terms and a more conceptual approach may identify the relevant material. Use these terms and concepts as needed when searching in the following database.

The Medical Science Library at Texas A&M has trained staff available to assist with alternative searches.

Database selection:

• Choose those that are appropriate for the area of the study.
• Please visit the Animal Welfare Information Center (https://www.nal.usda.gov/awic), which lists a variety of useful search engines as well as other information on searching for alternatives.

• There are several databases that can be searched for alternatives:
  • Medline
  • BIOSIS or Biological Abstracts
  • EMBASE or Excerpta Medica
  • AGRICOLA
  • SciSEARCH or Science Citation Index
  • Animal Welfare Information Center (AWIC)
  • Current Research Information Center (CRIS)

• There are also useful sites that can be helpful when searching for alternatives:
  • ALTWEB – Alternatives to Animal Testing on the Web
  • ICCVAM – Interagency Coordinating Committee on the Validation of Alternative Methods
  • Model Organisms for Biomedical Research
  • NORINA Database – Norwegian Inventory of Alternatives
  • FRAME – Fund for the Replacement of Animals in Medical Experiments

For additional information:

https://www.nal.usda.gov/awic/why-conduct-literature-searches-alternatives