Skip to content

Alternative Search Guidelines

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

  • A written narrative description of methods and sources used to search for alternatives to such procedures (category D and E procedures); 
  • A written assurance that animal activities proposed do not unnecessarily duplicate previous experiments

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: Using non-animal models. These might include living systems using 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.

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 the 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 to ensure a principal investigator has made a good-faith effort to determine the availability of alternatives, and to consider their applicability to the specific research project.

An animal use protocol will be returned without approval if the application does not include appropriate search terms for the refinement, reduction, and replacement of live animal subjects. Applications must:

  1. Show use of at least two appropriate literature databases; 
  2. Provide a narrative description of the methods, sources and results of the literature search; 
  3. Include written assurance that use of animal subjects does not unnecessarily duplicate previous experiments; 
  4. Indicate the researcher has considered all alternatives to the use of live animals and to procedures that may produce pain, distress or discomfort.


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. The UC Merced IACUC requires at least two legitimate scientific databases be searched. Each principal investigator or study designer must provide the following in the written protocol application:

  • Date when the searches were performed (e.g., "9/25/05"). Note: This date may not be more than three months before submission of the application to the IACUC for review;
  • Date range over which the search was conducted (e.g., "1950 - present");
  • 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;
  • 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

To provide adequate documentation in the protocol file when such methods are used in place of a database search, the principal investigator must provide detailed information including 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.

The UC Merced Library staff can assist you in the successful performance and documentation of literature database searches alternatives. 

Search for Alternative Resources

Numerous free searchable databases are available under the AWIC Database list.

Please contact Leslie Teixeira-Porto at 209-228-4613 with questions.