Performing Searches for Alternate Procedures

Investigators performing procedures that are painful or distressful to an animal need to demonstrate that alternatives to procedures, that may cause more than momentary pain or distress to the animals, have been considered and that activities do not unnecessarily duplicate previous experiments. 

A thorough literature search regarding alternatives meets this Federal mandate.

"Information Requirements of the Animal Welfare Act, Final Rules and Regulations," Federal Register, Vol 54 (168), August 31, 1989:

"The principal investigator must provide a written narrative of the sources, such as Biological Abstracts, Index Medicus, the Current Research Information Service (CRIS), and the Animal Welfare Information Center that is operated by the National Agricultural Library. We believe that in fulfilling this requirement Committee members will discuss these efforts with the principal investigator in reviewing the proposed activity. We also believe that considerations of alternatives will be discussed during Committee meetings where proposed activities are presented for approval, and made part of the meeting minutes..."

Initial submission. Alternative searches are required in the planning phase of the animal use protocol.

Amendments. 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.

Annual review. The availability of alternate procedures should be evaluated at annual review and the search updated.

TIP: Set up alerts for searches in commonly used databases.

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).

Replacement—substitute animals used in the study with non-animal methods or lower organisms

Refinement—explore techniques that would reduce pain and distress to the animals in the study

Reduction—minimize the number of animals used in the study

Step 1: Identify Key Terms and Concepts on the protocol

Collect information about:

1. The area of study, including species and organ systems
2. Important acronyms and international spellings
3. Names of hormones, enzymes, and trade names
4. Possible alternatives and other prominent scientists in the field

Step 2: Develop a search strategy and refine as needed

The search strategy consists of three types of terms:

1. Scientific terms related to the research protocol
2. Alternative (3Rs) terms that are relevant to the protocol
3. Search Logic: Boolean Operators, limits, truncations, etc.

General Search Tips

• Use truncation: Depending upon the database system being used, symbols such as the * or ? may be used at the end of a search term to retrieve many word variations to the original term.
• Use spelling variations: When searching multiple databases, include American, British and European spellings.
• Use Boolean Logic: By using connecting words (operators) such as AND, OR, NOT the search can be expanded or narrowed.

AWIC's Alternatives & Searches
AWIC's Sample Search Strategies

Step 3: Select appropriate Information Resources

When searching for animal research alternatives, it is important to look in more than one database. Use the list below to select at least two databases to search. PubMed, Ovid Medline and ALTBIB are considered synonymous databases (search Medline). You may use any ONE of these. For your second database, you may select Web of Science or a specialized database depending on your topic.

DATABASES (use only one of these)

• ALTBIB Offers resources for alternatives to the Use of Live Vertebrates in Biomedical Research and Testing. Contents are a subset of MEDLINE records
• MEDLINE (OVID) Provides access to over 28 million citations for the biomedical literature, covering biomedical research, clinical medicine, nursing, allied health, and health policy. Includes In-Process & Other Non-Indexed Citations
• PubMed Provides access to over 28 million citations for the biomedical literature from MEDLINE, online books, selected publishers, and the PubMed Central repository

DATABASES

• AGRICOLA (via Proquest) Is a bibliographic database created by the National Agricultural Library and its cooperators. It includes 3 million citations to articles, government reports, theses, patents, and technical reports on food and nutrition, agricultural economics, and parasitology
• Altweb Contains reference material and news about all aspects of alternatives in animal research. It includes general, educational, scientific, and regulatory resources. It also contains conference proceedings, books, and reports. Current Research Information System (CRIS) lists USDA-sponsored projects
• Biological Abstracts
• NORINA (A Norwegian Inventory of Alternatives)
• PsycINFO
• TOXNET Provides access to toxicology databases including Registry of Toxic Effects of Chemical Substances (RTECS) and Chemical Carcinogenesis Research Information System (CCRIS)
• Web of Science (WOS) Contains the Science Citation Index, Social Sciences Citation Index, and Arts & Humanities Citation Index. WOS offers multidisciplinary searching and seamless access to cited reference searching. WOS databases include bibliographic and citation information for articles from over 5,700 science and engineering journals, 1,700 social sciences journals, and 1,100 arts and humanities journals

ORGANIZATIONS

• UVA Institutional Animal Care & Use Committee (IACUC)
• Animal Welfare Information Center (AWIC) National Agricultural Library
• European Centre for the Validation of Alternative Methods (ECVAM)
• Fund for the Replacement of Animals in Medical Experiments (FRAME)
• Institutional Animal Care and Use Committee Training and Learning Consortium
• NTP Interagency Coordinating Committee for the Evaluation of Alternative Methods (NICEATM)
• Johns Hopkins Center for Alternatives to Animal Testing (CAAT)

Step 4: Conduct the search, 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. Sample documentation worksheet: USDA Worksheet. Keep a copy of the search strategy, databases searched, and years of search.

The following should be included in 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 the use of live animals, appropriateness of the proposed animal model and selection of the species lowest on the phylogenetic 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.

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, faithful 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:

• Does not include appropriate search terms for the refinement, reduction and replacement of live animal subjects.
• Does not use at least two appropriate literature data bases.
• Does not provide a narrative description of the methods, sources and results of the literature search.
• Does not include a written assurance that the use of animal subjects does not unnecessarily duplicate previous experiments.
• 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.