
The U-M’s Institutional Animal Care & Use Committee (IACUC) requires that all Principal Investigators (PIs)/Study Teams provide detailed justification(s) for the use of any vertebrate animal or cephalopod in research or instruction.
In addition to fulfilling its regulatory obligation(s), outlined in greater detail in the federal Animal Welfare Act & Animal Welfare Regulations (AWA/AWR), the IACUC also uses the protocol review and approval process to assess:
- Whether the proposed species/model is the most scientifically valid method of study;
- If thorough consideration has been given to relevant new approach methodologies/non-animal models (NAMs) such as computer-based modeling, organoids, and/or Artificial Intelligence;
- If steps have been taken to address the Three 3Rs:
- Reduce the number of animals used to the minimum required for the study,
- Replace animals with less sentient or non-animal models, if feasible; and
- Refine all practices to provide the best possible animal welfare.
Accordingly, PIs must include the following in their protocol:
- Consideration of alternatives for any procedure likely to produce more than momentary pain or distress to the animal;
- Description of the methods and sources used to determine that no such alternatives exist,1 and
- Written assurance that their activities do not unnecessarily duplicate previous experiments.2
To perform an effective alternatives literature search, Study Teams are strongly encouraged to use the guidance and best practices below, which have been adapted from the United States Department of Agriculture (USDA)’s Animal Welfare Information Center (AWIC) website.
Steps for Performing an Effective Alternatives Literature Search

Use AWIC’s series of questions (see Step 1: Questions to Help Get You Started) to help inform your alternatives literature search.
Questions cover a variety of topics pertaining to study design and methodology; replicability; selection of procedures, species, and drugs; analgesic/anesthetic regimens; and housing considerations.

Searches should always be conducted using multiple (three or more) different databases.
Database use will vary widely depending on the specific topic of interest and coverage/focus area of each database. For example, PubMed is primarily used for biomedical literature (e.g., medicine and health sciences), whereas AGRICOLA is largely focused on agricultural (e.g., crops and livestock) literature.
Grey literature, which refers to publications from non-traditional sources (e.g., conference abstracts, reports, theses/dissertations), can also be used to find information about the 3Rs.
A list of 3Rs organizations that routinely publish grey literature can be found on the AWIC website.
Unfortunately, different databases employ different search logic, parameters, and syntax.**
Use the following to help guide your search across sites:
- Utilize scientific terms (e.g., metabolism, immunology, gene expression)
- Include both scientific and common species names (e.g., Mus musculus and mouse)
- Many publications do not solely rely upon common 3Rs keywords. Expand your search by including variations‡ of the following –
- Replacement: non-animal model, cell culture, in silico, digital imaging, organoid
- Reduction: microsampling, sample size, computational, animal study registries
- Refinement: pain management, bedding, injection, noninvasive

**Check the ‘Help’ section of the database you are searching or review AWIC’s Database Search Operator Reference Guide for more information on database-specific search parameters.
‡Note: for additional examples, review AWIC’s Terminology for Replacement Alternatives List.
Literature searching is a trial-and-error process.

If your search has returned too few (or too many) results, consider refining your search by:
- Only searching the publication title and abstract fields
- Limiting publication year (please note: a comprehensive search should still span multiple years)
- Adding another search concept
It is possible that no suitable alternatives currently exist for a specific procedure, method, or technique, resulting in minimal or irrelevant results.
If you are concerned about the efficacy of your literature searches, review the curated resources provided on the U-M Library’s Laboratory Animal Medicine Research Guide.
Consultations may also be requested with Bioinformationist Marci Brandenburg ([email protected]) at the Taubman Health Sciences Library on an individual, case-by-case basis.
Keep a record of previous literature searches – including keywords, databases used, publication years, search strings, etc. – that can easily be updated for future searches.

Many databases have a feature that allows you to save your search string within the database to modify or run in the future.
You may also consider using a software system to manage citations and references. More information about citation management programs can be found on the Taubman Health Sciences Library’s Citation Management Research Guide.
Where to Learn More
Detailed instructions on how to complete each of the steps above can be found on the USDA’s Literature Searching: How to Find Animal Use Alternatives website.
The U-M Library has also developed a curated collection of resources that includes a list of literature databases, online journals, and Three Rs / Alternatives Resources.