Alternatives Search Guidelines

"The Three Rs"

Consideration of Alternatives

Required Documentation

Additional Resources


The PHS Policy and the USDA animal welfare regulations require research institutions to ensure that investigators have appropriately considered alternatives to procedures that can cause more than slight or momentary pain or distress in animals, consistent with sound research design1. Federal regulations require:

  1. A written narrative description of the methods and sources used to search for alternatives to procedures that may cause more than slight or momentary pain or distress (category D and E procedures); and 
  2. A written assurance that the animal activities proposed do not unnecessarily duplicate previous experiments.

"The Three Rs"

Alternatives are framed within the context of the "3 R's" originally discussed by Russell and Burch in 1959 (The Principles of Humane Experimental Technique). These include:

Replacement: Utilizing non-animal models. These may include living systems utilizing organ, tissue or cell culture techniques; non-living systems such as chemical techniques and mechanical models for training; and computer simulations. Wherever possible, use of invertebrates or vertebrate species lower on the phylogenic scale may be considered as a replacement alternative.

Reduction: Determining the number of animals used in a study by experimental design and/or statistical analysis to minimize the number of animals required to obtain meaningful data.

Refinement: Reducing or eliminating pain or distress in animals by use of anesthetics and analgesics, modification of procedures or technical enhancements that increase the quality or quantity of data gathered.

Consideration of Alternatives to Animal Use/Painful Procedures:

Alternative searches are required in the planning phase of the animal use protocol and are given equal consideration along with the overall experimental design and the appropriateness of the animal model to be used.

Additional alternative searches should be performed when a protocol is changed significantly by modification, and are required when the modification involves use of a new or more-invasive technique or procedure that would be classified as a Category D or E procedure.

The IACUC must review and assess the information provided in the protocol application in order to ensure that the Lead Researcher has made a good faith effort to determine the availability of alternatives and consider their applicability to the specific research project.

An animal use protocol will be returned to the Lead Researcher without approval if the application:

  1. Does not include appropriate search terms for the refinement, reduction and replacement of live animal subjects.
  2. Does not use at least two appropriate literature data bases.
  3. Does not provide a narrative description of the methods, sources and results of the literature search.
  4. Does not include a written assurance that the use of animal subjects does not unnecessarily duplicate previous experiments.
  5. Does not clearly indicate that the researcher has considered all alternatives to the use of live animals and to procedures that may produce pain, distress or discomfort.

Documenting the Consideration of Alternatives:

The USDA considers the performance of a computerized search of scientific literature databases to be the most effective and efficient method for demonstrating compliance with the requirement to consider alternatives and avoid unintended duplication. With that in mind, the UCI IACUC requires that at least two legitimate scientific databases be searched. The Lead Researcher or study designer must provide the following as part of the written protocol narrative:

  • The name(s) of the database(s) searched.
  • The date when the searches were performed (e.g., "9/25/05"). NOTE: This date may not be more than three months prior to submission of the application to the IACUC for review.
  • The date range over which the search was conducted (e.g., "1950 - present").
  • The keywords used to search the databases. Keywords used in the search must be representative of the scientific design, procedures to be used in the project, alternatives to use of live animals, appropriateness of the proposed animal model and selection of the species lowest on the phylogenic scale that is appropriate for the study.
  • A detailed narrative description of the results and findings of the searches, including an explanation for why any alternatives found but not used are not appropriate for the study.

In some circumstances, such as highly novel or specialized fields of research, the following may be employed in lieu of a database search:

  • Attendance and participation in scientific conferences and colloquia.
  • Consultation with subject experts.

In order to provide adequate documentation in the protocol file when such methods are used in place of a database search, the Lead Researcher must provide detailed information such as the date, location and name of the conference or colloquia attended or the consultant's name and qualifications and the date and content of the consult.

Additional Resources:

The UCI Libraries staff can assist you in the successful performance and documentation of literature database searches alternatives:


  • Institutional Animal Care and Use Committee Guidebook, 2nd edition, 2002  
  • United States Code Title 7, Chapter 54, Section 2143(d) and (e)
  • Code of Federal Regulations 9CFR Chapter 1, Subchapter A, Part 2, Subpart C, Section 2.31(d)(1)ii and iii.
  • USDA Policies 11 (Painful Procedures) and 12 (Consideration of Alternatives to Painful/Distressful Procedures)

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