91´ÎÔª

Literature Search for Alternatives to Animal Use and Painful or Stressful Procedures

Number: IACUC-POL-012 

Responsible Office: Office of Research and Creative Scholarship (ORCS) 

Applies to: All animal research and teaching protocols involving live vertebrate animals 

1. Purpose 

This policy outlines institutional requirements and investigator responsibilities regarding the performance of literature searches to identify alternatives to procedures that may cause more than momentary or slight pain or distress to animals, in compliance with the Animal Welfare Act regulations, Public Health Service (PHS) Policy, and the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. 

The 3 Rs of the alternatives to animal use proposed by Russell and Burch in 1959 are (1) Reduction: minimize the number of animals used; (2) Refinement: use techniques and procedures that reduce pain and distress; and (3) Replacement: substitute animal models with non-animal techniques or lower organisms.  

2. Policy  

Federal law and policy mandate that investigators consider alternatives to procedures that may cause pain or distress to animals. These include both replacement, reduction, and refinement (3Rs) principles and the requirement to search for scientifically valid alternatives prior to the initiation of such procedures. 

• Animal Welfare Act Regulations (AWARs): 9 CFR, Chapter 1, Subchapter A, Part 2, §2.31(d)(1)(ii) requires investigators to consider alternatives to procedures that may cause more than momentary or slight pain or distress to animals, and to provide a written narrative of the methods and sources used to determine that alternatives were not available. 
• PHS Policy IV.C.1.g: Requires that applications and proposals include a description of procedures designed to assure that discomfort, distress, or pain to animals will be limited to that which is unavoidable and that humane endpoints are used. 
• U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, Principle III: Requires that the PI consider alternatives to potentially painful or distressful procedures. 

3. Procedure  

The 91´ÎÔª IACUC requires that Principal Investigators (PIs) who plan to use laboratory animals conduct a literature search for alternatives to animal use as part of the Animal Use Protocol. Wildlife protocols are exempt from the requirement of a literature search for alternatives to animal use. Additionally, all PIs (lab animal and wildlife) using animals in USDA pain categories D and E are required to conduct a literature search for alternatives to painful or stressful procedures as part of the Animal Use Protocol.  

  A literature search must be conducted and documented in the following situations: 

• Any procedure that may cause more than momentary or slight pain or distress. 
• Reuse of previously approved procedures involving potential pain or distress in a new protocol or major amendment.  

Search Parameters 

The search must be thorough and should include: 

• Databases searched (e.g., PubMed, AGRICOLA, Web of Science, BIOSIS, Altweb, AWIC) 
• Date of the search 
• Time span covered 
• Search strategy or keywords used (including terms related to the procedure, species, and 3Rs concepts) 
• Results summary and conclusion stating whether any valid alternatives were identified. 

Databases and Resources 

Investigators are required to search a minimum of 2 databases for relevant sources including: 

• ALTWEB: Alternatives to Animal Testing Web Site (https://altweb.jhsph.edu/) 
• AWIC: Animal Welfare Information Center (https://www.nal.usda.gov/programs/animal-welfare-information-center) 
• PubMed/Medline 
• TOXNET and BIOSIS Previews
• Investigators may also consult with the institution’s animal welfare officer or veterinary staff when evaluating alternatives. 

Documentation in Protocol 

The IACUC protocol form must include: 

• Documentation of the databases used, dates covered in the search and date of search.  
• Documentation of the key words used for the search. 
• A narrative describing the alternatives considered.
• Justification if alternatives are not applicable or scientifically acceptable. 
• An explanation of how the selected method minimizes pain or distress, including analgesics, anesthetics, or humane endpoints. 

Training and Support 

The institution will provide access to training and assistance in conducting alternative searches through: 

• Research compliance or IACUC office consultations 
• Library or information specialist support 
• CITI training modules related to alternatives and 3Rs 

4. References  

1. Animal Welfare Act Regulations, 9 CFR §2.31(d)(1)(ii) 
2. Public Health Service Policy on Humane Care and Use of Laboratory Animals, IV.C.1.g 
3. U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training 
4. Guide for the Care and Use of Laboratory Animals, 8th Edition, NRC, 2011 
5. Animal Welfare Information Center (AWIC), USDA:   
6. Altweb – Alternatives to Animal Testing:   
7. Office of Laboratory Animal Welfare (OLAW):  

5. Review, Approval and Version History 

Review and approval version history for this policy

Version	Date	Description of Changes	Approved By
1.0	December 12, 2006	Initial policy creation	IACUC Committee
2.0	September 13, 2017	Review	Heivilin
3.0	June 4, 2025	Review and Rewrite	Hicks