The 3 Rs
The idea of reduction, refinement, and replacement (the 3 Rs) originally comes from The Principles of Humane Experimental Technique by Russell and Burch.

The Animal Welfare Information Center (AWIC) outlines the 3 Rs as:

Reduction  Minimizing the number of animals used
Refinement   Using techniques and procedures to reduce pain and distress
Replacement  Substitution of animals with non-animal methods or lower organisms

The Legislation

Alternatives
The Animal Welfare Act 13(a)(3)(B) requires that "the principal investigator considers alternatives to any procedure likely to produce pain or distress in an experimental animal.”

Policy 12 of the Animal Care Resource Guide - Written Narrative for Alternatives to Painful Procedures explains:“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.”

The IACUC
Policy 11 of the Animal Care Resource Guide - Painful Procedures on the role of the Institutional Animal Care and Use Committee (IACUC) states that “The Institutional Animal Care and Use Committee (IACUC) is responsible for ensuring that investigators have appropriately considered alternatives to any procedures that may cause more than slight or momentary pain or distress.”

Title 9, Chapter 1, Section 2.31 (d)(1) of the Code of Federal Regulations says that the IACUC must ensure that the investigator:
(ii) “has provided a written narrative description of the methods and sources, e. g., the Animal Welfare Information Center, used to determine that alternatives were not available” and (iii) “has provided written assurance that the activities do not unnecessarily duplicate previous experiments.”

Meeting the Requirements
Further to this, Policy 12 of the Animal Care Resource Guide - Written Narrative for Alternatives to Painful Procedures
outlines that: “When a database search is the primary means of meeting this requirement, the narrative must, at a minimum, include:

1. the names of the databases searched;
2. the date the search was performed;
3. the period covered by the search; and
4. the key words and/or the search strategy used.”

It also stipulates that “in some circumstances (as in highly specialized fields of study), conferences, colloquia, subject expert consultants, or other sources may provide relevant and up-to date information regarding alternatives in lieu of, or in addition to, a database search.”

If an alternative is found, the policy explains that ”If a database search or other source identifies a bona fide alternative method (one that could be used to accomplish the goals of the animal use proposal), the written narrative should justify why this alternative
was not used.”

Compliance at NYMC

NYMC Office of Research Administration “Participates in the activities of the Institutional Animal Care and Use Committee to ensure institutional compliance with regulations regarding the care and use of laboratory animals. “

NYMC Policy & Procedure for Vertebrate Animals

Approval by the Animal Care and Use Committee is required before animals may be used in research or teaching; federal and other agencies require certification of this approval in applications. Completion of the vertebrate animal section of the College forms and preparation of a vertebrate animal statement is required before an application proposing the use of animals will be endorsed by the Office of Research Administration. Questions regarding PHS policy may be directed to Catharine Crea, Associate Dean, Director, Office of Research Administration (914-594-4480). Dr. Ellen Levee, Director, Comparative Medicine (914-594-4215), will assist investigators with preparing the vertebrate animal statement.

The vertebrate animal section of the College form reflects federal requirements, for example, information regarding an investigator's search for an alternative to live animals. Additionally, tumor-cell lines previously propagated in rodents must be certified free of contamination with infectious viruses or other agents before use in the central animal facility.

NYMC Office of Research Administration Internal College Forms

The Search for Alternatives

Search Tips
The Animal Welfare Information Center (AWIC)
outlines areas of concern and offers tips for what to include in a search:

AWIC Search Evaluation RED FLAGS (areas of concern)

• Only 1 database was searched
• Terms used were only for painful aspects
• The term “alternative” was used alone with no other alternative terms
• Keywords listed were not relevant to the protocol
• Keywords and concepts were linked in an incorrect manner
• Search doesn’t cover adequate time period (5-10 years)

AWIC suggests that the following information be included in your search strategies or provided to your librarian:

• Description of protocol and area of study
• Species being used
• Organ systems involved
• Acronyms (bovine somatotropin= BST)
• Alternate spelling (behavior/ behaviour, hemophilia/haemophilia)
• Names of hormones, enzymes, CAS#s trade names (xylazine=rompun), etc.
• Prominent authors in the field, including the investigator
• Is the investigator aware of any possible alternatives?
• Previous searches and keywords used

Sample Search Terms
*These terms can be combined with other terms that pertain more specifically to the anticipated research. The boxes [] represent the placement of truncation symbols. Note that databases vary on their choice of truncation symbol. Use each database’s help screen to determine the appropriate symbol.

Reduction and Refinement

advers[]pain[], distress[], stress[], welfare
anesthe[, anasthe[], anaesthe[] tranquiliz[] analges[] sedative, anxiolytic
reduc[], refin[]
restrain[], restrict[], immobil[]
technique, method[], procedur[],assay[]
handl[], hous[], cag[] husbandry, environment[], enrich[], environmental enrichment, environmental enhancement, monitor[], device
euthanasia, euthanize[]

Replacement

alternative, replac[], animal testing alternative, animal use alternative, surrogate,
algae, fungus, hydra, plant, fish, cephalopod, amphibian, reptile, insect, invertebrate, bacter[], microorganism, protozoan, yeast, isolated (cell, tissue, organ), culture (cell, tissue, organ), biopsy, autopsy, cadaver, mannequin] or manikin, model[], theoretical model[], artificial[], mathematical model[], QSAR, software, computer, expert system, video[], virtual (surgery, reality), simulat[], interactive, artificial intelligence, AI, digital imag[], technique, method[], procedur[], assay[], in vitro (AND method, model, technique)

*Search terms reproduced from the NIH, AWIC and FRAME

Databases

Other databases that are helpful in the search for reduction, refinement, and replacement methods are:

Agricola U.S. Department of Agriculture   citations to publications encompassing all aspects of agriculture and allied disciplines, including animal sciences. Use the companion Agricola Thesaurus for Animal Use Alternatives to search or browse over 200 subject headings.

ALTBIB: Bibliography on Alternatives to Animal Testing U.S. National Library of Medicine  a searchable bibliography designed to assist in identifying methods and procedures helpful in supporting the development, testing, application, and validation of alternatives to the use of vertebrates in biomedical research and toxicology testing.

Altweb Humane Endpoints Database The Johns Hopkins Center for Alternatives to Animal Testing  designed to help investigators find the earliest endpoint that is compatible with the scientific objectives of their research. An endpoint is "the point at which an experimental animal's pain and/or distress is terminated, minimized, or reduced by taking actions such as killing the animal humanely, terminating a painful procedure, or giving treatment to relieve pain and/or distress."

Altweb Pain Management (Anesthesia/Analgesia) Database The Johns Hopkins Center for Alternatives to Animal Testing  citations about anesthesia and analgesia for most commonly used laboratory animals collected from the databases MEDLINE, TOXLINE, AGRICOLA, and AGRIS.

CRIS (Current Research Information System) U.S. Department of Agriculture   the USDA’s documentation and reporting system for ongoing and recently completed research projects in agriculture, food and nutrition, and forestry.

CRISP (Computer Retrieval of Information on Scientific Projects) U.S. Department of Health and Human Services/National Institutes of Health   a database of federally funded biomedical research projects conducted at universities, hospitals, and other research institutions.

Invitroderm: Alternatives to Skin Irritation/Corrosion Testing in Animals Various   over 360 abstracts about alternatives to irritation/corrosion testing in animals.

Refinement and Environmental Enrichment for All Animals Kept in Laboratories  Viktor and Annie Reinhardt, Animal Welfare Institute    reference material on all aspects of the refinement of housing and handling conditions, and environmental enrichment for laboratory animals. Primates and non-primates can be searched separately or in a single database.

TOXNET  National Library of Medicine    a system of nine toxicology and environmental health databases. Search individually or across all databases.

Tip Sheets & Tutorials

These sites offer guidance on the process of searching for alternatives.

Altweb: Search for Alternatives  The Johns Hopkins Center for Alternatives to Animal Testing  designed to assist researchers with their literature searches for alternative methods, while facilitating compliance with regulatory agencies.

AWIC (Animal Welfare Information Centre) U.S. Department of Agriculture Tips for Searching for Alternatives to Animal Research and Testing AND the Animal Welfare Brochure   these documents outline the search process and provide concise, practical search tips.

Guide to Searching For Alternatives to the Use of Laboratory Animals FRAME (Fund for the Replacement of Animals in Medical Experiments) provides guidance on search basics, term and database selection.

Searching for Alternatives to Painful Procedures Used on Research Animals  U.S. National Institutes of Health Library
a two-page tip sheet that outlines the search process, suggests alternative search terms, and offers search evaluation tips.

Searching the Literature for Animal Testing Alternatives University of North Carolina a very good tutorial and quiz that covers query construction, database selection, and search evaluation.

University of California Center for Animal Alternatives  UC Davis  search tips, sample search strategies, and links to resources.

Things to Remember

• Use more than one database
• When searching on refinement, include terms for reduction of distress (housing, handling, euthanasia) not just reduction of pain
• Use search terms for reduction and replacement, not just refinement
• Include terms that pertain specifically to the anticipated research
• Record the names of the databases used
• Record the dates the searches were performed
• Record the time period covered
• Record the search strategies or search terms used
• If you need help, contact the Reference Librarians at the Health Sciences Library