UVA investigators whose research protocols require the use of animals must meet the information requirements of the federal Animal Welfare Act (AWA). The AWA regulations require principal investigators (PIs)/scientists to consider alternatives to procedures that may cause more than momentary or slight pain or distress to the animals. They must provide a written narrative to their Institutional Animal Care and Use Committee (IACUC) that describes the methods and sources (e.g. the Animal Welfare Information Center) used to determine that alternatives were not available (9 C.F.R. § 2.31 (d)(ii)(2022)). Additionally, PIs/scientists must also provide written assurance that their activities do not unnecessarily duplicate previous experiments (9 C.F.R. § 2.31 (d)(iii)(2022)).

Written Narrative

Your protocol must provide written narrative to demonstrate to the UVA Institutional Animal Care and Use Committee (IACUC) reviewers you have made a sincere effort to address each of the 3Rs as outlined below.

The 3Rs

 Alternatives or alternative methods are generally regarded as those that incorporate some aspect of replacement, reduction, or refinement of animal use in pursuit of the minimization of animal pain and distress consistent with the goals of the research.” (USDA AC Policy 12).

As described above, the “3Rs alternatives” refers to the replacement, reduction, and refinement of animals used in research, teaching, testing, and exhibition. 

• Replacement refers to technologies or approaches that directly replace or avoid the use of animals
• Reduction—minimize the number of animals used in the study through strategies such as appropriate experimental design, correct statistical evaluation, and sharing resources/animals.
• Refinement—explore techniques that minimize or eliminate animals’ pain and distress and improve their welfare

Literature Search as Documentation

To document your efforts to address the 3Rs, you will need to complete literature searches utilizing at least two scientific literature databases such as PubMed. 

For each search you will need to document:

• Database searched
• Years covered by the search
• Detailed search strategy
• Date the search was performed

Performing the Literature Searches

1. Select appropriate literature databases 

When searching for animal research alternatives, it is important to look in more than one database. Use the list below and choose at least two databases to search, one from the Core list, and one from the Additional list.

Core Database (choose one of these)

• PubMed Provides access to over 35 million citations for the biomedical literature from MEDLINE, online books, selected publishers, and the PubMed Central repository.
• MEDLINE (OVID) Provides access to over 35 million citations for the biomedical literature from MEDLINE and the PubMed Central repository.

Additional Suggested Databases

• Web of Science (WOS) Over 85 million records from life sciences, biomedical sciences, engineering, social sciences, arts & humanities. Select the All Databases option to include the Biological Abstracts and BIOSIS databases.
• AGRICOLA  worldwide literature citations for journal articles, monographs, proceedings, theses, patents, translations, audiovisual materials, computer software, and technical reports pertaining to all aspects of agriculture and related fields
• See 15+ literature databases in biomedicine

2. Identify search terms

The search strategy consists of two types of terms:

1. Scientific terms related to the research protocol
2. Alternative (3Rs) terms that are relevant to the protocol

For each, your goal is to identify keywords (“search terms”), i.e. words and phrases used to express the main concepts and ideas you are searching for. Make sure to consider plurals, alternative spellings, and synonyms.

• Plurals and alternative endings: most databases use a truncation symbol, *, to find alternative endings. For example, metabol* will find metabolic, metabolism
• Alternative spellings: Consider American, British and European spellings
• Synonyms
  • Consider alternative names for animals (e.g. mouse, mice, murine)
  • Consider alternative words and phrasing for your concept (e.g. cage, housing)
  • In PubMed/MEDLINE, consider using Medical Subject Headings (MesH terms)
• 3R Terms:
  For your 3R terms, do not limit your search to general keywords like "alternative". Consult this list for words for each of the 3R concepts:
  
  AWIC's 3R Search Terms

3. Construct Your Search

A. Assemble your search terms

Construct your database search for the example below:

List out possible synonyms or alternative terms for your concepts. You can utilize search "hedges", i.e. pre-made standardized strings of search terms that utilize keywords and also database Subject Headings when available. Search hedges for various laboratory animal species are available from AWIC and the Animal and Veterinary Information Specialists (AVIS) here.

B. Combine search terms

Use Boolean Logic to begin to construct your search. Separate synonyms with OR to include any of the terms:

Use parentheses around each of your "OR" strings, and combine with AND for your final search:

C. Refine your search

Your first search is never your best: searching is an iterative process. Use the tips below to narrow or broaden your search

Database Specific Guidance

PubMed

1. Consider using the truncation symbol * to search for a root word and any alternative endings (e.g. hamster* retrieves hamster or hamsters). The truncation symbol requires at least 4 characters; for shorter root words, supply your own plurals:
   (hamster* OR cricetinae) AND (environment* enrichment OR enriched housing OR nesting material* OR bedding OR cardboard tube* OR wheel* OR toy OR toys)

    

2. You may want to use the Advanced Search page to construct your search using the query box. PubMed will add the parentheses for you.
   1. Enter just the terms from your first concept in the box, then click Add:
      
       
   2. Enter your string of terms from your second concept. Notice the Add button now says AND:
      
      
       
   3. With your search terms properly structured in the Query Box, click Search to complete your search.
       
3. If you get too many results, refine your search by searching for some of your terms as specific phrases. Do this using quotation marks:
   (hamster* OR cricetinae) AND ("environmental enrichment" OR "enriched housing" OR "nesting material*" OR bedding OR "cardboard tube*" OR wheel* OR toy OR toys)

    

4. Refine to title/abstracts. Sometimes PubMed's translation of your search terms results in too many articles. To bypass this, you can limit your search to look for your terms specifically in the titles and abstracts, or just titles, of the articles. Do this from the Advanced Search:
   
   

5. When you find articles of interest, click on them, then scroll down to notice:
   1. Similar Articles or Cited References - these may be good citations for your topic, and may lead to other citations
   2. Medical Subject Headings (MeSH) terms - these "tags" on your article help your search by:
      1. Covering similar concepts under one MeSH term. For example, searching the MeSH term Housing, Animal can find articles on cage enrichment, bedding, running wheels and other similar topic.
      2. Covering narrower concepts under one MeSH term. Searching the MeSH term Bioengineering will retrieve results tagged with Cell Engineering, Tissue Engineering, Synthetic Biology, etc
          
   3. Always use keywords in addition to MeSH to maximize your retrieval: You can combine MeSH terms with your keywords. Here's an example of a possible search:
   (hamster*[Title/Abstract] OR cricetinae[Title/Abstract] OR cricetinae[mesh] AND ("Housing, Animal"[mesh] OR "environmental enrichment"[Title/Abstract] OR "enriched housing"[Title/Abstract] OR "nesting material*"[Title/Abstract] OR bedding[Title/Abstract] OR "cardboard tube*"[Title/Abstract] OR wheel*[Title/Abstract] OR toy[Title/Abstract] OR toys[Title/Abstract])

    

6. OPTIONAL: PubMed now offers Proximity Searching. If connecting terms with AND is too broad, and quotation marks are too narrow, you can use the Proximity Operator to require your terms to be within # terms of each other. The example below would find blood and collection with no more than three words between them in the Title or Abstract, so would retrieve citations with blood collection, collection of blood, collection of arterial blood, etc.
   "blood collection"[Title/Abstract:~3]

Web of Science

1. From Web of Science, choose All Databases to include the Biosis and Biological Abstracts databases:
   
   
    
2. Web of Science uses * as a truncation symbol, and actually has other truncation options called Wildcards.
3. Quotation marks for phrases work in Web of Science, and are recommended: the Web of Science search translation sometimes searches too broadly for terms.
4. Web of Science has Proximity Operators to help refine your searches when AND is too broad and quotation marks are too narrow. For example searching blood NEAR/3 collect* will find records with blood collection, collecting blood, collection of blood, etc.
5. Web of Science covers some Meeting Abstracts: you may wish to limit your results after searching by using the menus at left to Refine your results.

Evaluate and review relevant citations  

Principal investigators should:

1. Complete and review the search before completing the protocol.
2. Assess and evaluate the alternative possibilities and be prepared to support their use and non-use
3. Provide a written narrative to the IACUC including:
   • Search strategy
   • Databases searched
   • Years covered by the search
   • Date the search was performed
4. Keep a copy of the search strategy, databases searched, and years of search. TIP: Set up alerts for searches in commonly used databases.
   • Instructions for PubMed search alerts
   • Instructions for Web of Science search alerts

Additional assistance is available to UVA Health System faculty, staff, and students. Just Ask Us - we are happy to provide help via email, phone, or in-person.