Literature Search for Alternatives Worksheet

step-by-step approach to an alternatives search

Supporting Information: SEARCHING and DATABASES

Worksheet Guide and Information

This worksheet is a tool used to 1) familiarize the principal investigator with the procedure; 2) identify keywords and concepts that are important in the development of a search strategy; and 3) aid in the selection of appropriate topical databases or other on-line resources. Although this worksheet will help, it is not designed as a replacement for communication between information providers, investigators, veterinarians, and IACUC members.

Searching for possible implementation of reduction and refinement to the study is essential. The use of analgesics and analgesia, the use of remote telemetry to increase the quality and quantity of data gathered, and humane endpoints for the animals are examples of refinements. Use of shared control groups, preliminary screening in non-animal systems, innovative statistical packages, or a consultation with a statistician are examples of reduction alternatives.

Because reduction and refinement aspects of alternatives are broad and often are addressed in the methods section of studies, the search at this point is really a comprehensive look at the field of study. Keywords and concepts from the area of research are used. This in turn addresses whether the protocol unnecessarily duplicates prior research. This approach will result in a basic understanding of the research area, including the literature published in the particular field, the techniques used, and the commonly used species.


Considering replacement requires that you address potential alternatives such as cell culture, tissue culture, models, simulations, etc. This is also where you might look for any alternate animal models lower on the phylogenetic scale —fish or invertebrates, for example— that would still give you the data you need. In addition considering non-animal and alternative animal-models, the proposed animal species should also be searched.

Objectives and Endpoints:

As often required for the protocol, write-up a complete description of the proposed use of animals, including a succinct outline of the scientific plan and direction of the experiment. When doing a keyword search, the database system searches for words that appear in the title, abstract, and descriptor fields of the citation. Because the painful part of the procedure may be described in the materials and methods sections, the search should focus on the experimental endpoint or objective, in most cases. Exceptions are when methodology papers are common in the field of study (i.e., skin irritation tests, antibody production). Humane endpoints, such as indicators of pain, or euthanasia can be searched to determine when the animal should be removed from the study. While endpoints are not easily searchable, they are worth considering when reviewing the search results.

Drugs or Compounds:

List specific names of drugs you may be using for your study or as anesthetics or analgesics. (i.e. halothane, rompun, buprenorphine, etc.). Remember to include the scientific and generic name of the drugs. If you are using other compounds in your study, included them when you search the literature for drugs that may conflict or have contraindications with your area of study.

Methods and Procedures:

Providing the methods and procedures used in your animal study protocol will assist in addressing issues of refinement alternatives, such as handling techniques, restraint techniques, injection techniques, surgical procedures, etc. Identify any painful procedures, along with drugs or methods that will be used to relieve the pain. The law defines a painful procedure as one that would "reasonably be expected to cause more than slight or momentary pain or distress in a human being to which that procedure was applied." If a procedure involves pain or distress, the PI must search for an alternative and, also, consult with the attending veterinarian.

Potential Alternatives:

Listing terms to describe any potential alternatives you are aware of, such as in vitro, tissue culture, alternative procedures or alternative animal models, etc. is helpful in conducting the refinement alternative aspect of the search. It is also helpful in determining potential search terms to use, since these are terms outside the specific area of study.

Search Strategy:

Keywords, concepts and database selection determine the ultimate search strategy. These keywords are those that will likely be found in the title, abstract, and descriptor fields of the citation. Use as many synonyms as possible, such as "cardiac" and "heart." Include acronyms and complete spellings (i.e., "GH" and "growth hormone"). Also include all possible spellings of words. For example, "anesthesia," "anesthetic," and "anaesthesia." Include words that make the study different from other studies. This will help detect unintentional duplication as well as limit the scope of the search if the number of citations from a broader search is more than 200. All potential alternatives should be included as keywords, whether or not the researcher believes they will be useful. Using the keywords selected from your notes, put together brief strings of words so that each search set covers a separate concept. For example, the first set might include words relating to the experimental outcome, and the second set will contain words relating to the animal model. Short and simple search sentences are preferred. Considering reduction and refinement requires a search similar to the typical literature review done in preparation for a new project or scientific publication. Keywords used will help determine if there is unintentional duplication, how many animals are necessary using the proposed model, appropriate anesthetics and analgesics, and any other method of minimizing pain and distress. Since much of the refinement and reduction information will be found in the materials and methods sections, it is important for the researcher to review some of the articles that may be of interest.

Many people make the mistake of putting the term ";alternatives" in the strategy and expect to find all possible alternatives. Because alternatives is a complex concept involving refinement, reduction and replacement, this term is best used only in those areas of study where larger amounts of research have been conducted on alternatives, such as in toxicology or education. They might also end up with ";alternatives" that have nothing to do with the 3Rs.

Considering replacement requires a search that should include keywords for potential alternatives such as "vitro," "culture," or "simulation." The word "alternative" may also be included here. The selected animal model, other species, and the word "model" will help retrieve animal and non-animal models as potential alternatives.

Search strategies for research, teaching, or testing protocols differ. For example, a teaching protocol might include keywords such as "teach," "educate," or "instruct," while a testing protocol could include "safety," ";efficacy," or "test".

NOTE: It is very important to realize that stringing together keywords on one line (i.e., dogs or cats and cardiac or thoracic and stent or device and alternative) does not create a proper search strategy and results in a poor search with inaccurate results. Boolean operators and individual database vagaries require familiarity or professional librarian assistance.

Database Selection:

The worksheet lists many of the most useful databases for biomedical research topics. Although there is some overlap in journals and other publications covered by the databases, each database is unique; each indexes a unique set of informational resources. Several of the core databases should be searched in order to conduct a comprehensive literature search. Keep in mind the type of protocol when choosing databases. An education protocol, for example, should include ERIC; a protocol involving testing toxic effects of compounds should include TOXNET and RTECS. There are many other specific databases available online — both free and subscription based.

Years of Coverage

Years of coverage. When a database is chosen on CD-ROM, the World Wide Web, or on a multi-database system, the publication years covered are listed near the title of the database. The searcher should record the years included in the search based on database coverage or the years selected by the searcher within the search strategy (i.e., 1988-2005).

It is important to become familiar with the informational resources, databases, and services available at your institution in order to most effectively perform an alternatives search. The institution's librarian or information specialist can help with this and should be consulted.

Narrative Description:

A written narrative is required, one that evaluates the search results and assesses the alternative possibilities. It should support the decisions to both use and to not use available alternatives. Be sure to address refinement and reduction alternatives, not just replacement.

Information on databases

Agricola (
Published by the National Agricultural Library, the Agricola database describes publications and resources encompassing all aspects of agriculture and allied disciplines including: animal science; veterinary science; entomology; plant science; forestry; aquaculture and fisheries; farming, farming systems and crops; agricultural economics; extension and education; food and human nutrition; and earth sciences and environmental sciences.
Covers 1970s to present.
AltBib (
Bibliography on Alternatives to the Use of Live Vertebrates in Biomedical Research and Testing, National Library of Medicine. The intent of the bibliography is 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. This bibliography is produced from MEDLARS database searches, performed and analyzed by subject experts from the Toxicology and Environmental Health Information Program (TEHIP) of the Specialized Information Services Division (SIS) of the National Library of Medicine (NLM).
Covers 1980s to present.
AltWeb (
The Alternatives to Animal Testing website was created to serve as a gateway to alternatives news, information, and resources. Altweb is also now the U.S. home of the journal ALTEX: Alternatives to Animal Experimentation, which is the official publication of the Johns Hopkins Center for Alternatives to Animal Testing ( (CAAT)
ANZCCART ( – Australian and New Zealand Council for the Care of Animals in Research and Teaching.
Many useful resources including Fact Sheets, Newsletters, and publications.
Aquatic Sciences and Fisheries Abstracts ( (ASFA)
Includes information on the science, technology and management of marine, freshwater, and brackish water environments and organisms. Database consists of the following subfiles: ASFA 1: Biological Sciences and Living Resources; ASFA 2: Ocean Technology, Policy and Non-Living Resources; ASFA 3: Aquatic Pollution and Environmental Quality; ASFA Aquaculture Abstracts; and ASFA Marine Biotechnology Abstracts.
Covers 1970s to present.
Comfortable Quarters (
Provides access to several focused databases, including primate enrichment, lab animal refinement, rodent and rabbit enrichment, and species-specific housing and handling recommendations.
All life science areas, including agriculture, biochemistry, biomedicine, biotechnology, botany, ecology, environmental sciences, genetics, microbiology, veterinary medicine & pharmacology. Indexes over 6000 journals, serials and conference proceedings. 1969-present
Citations and abstracts to the international agricultural literature, including veterinary medicine, human and animal nutrition, rural development, as well as other related topics such as tourism and human ecology.
Covers over 11,000 journals & conference proceedings and selected books in agriculture, 1972-present.
CCAC is the national organization responsible for setting and maintaining standards for the care and use of animals in research, teaching and testing throughout Canada.
CRIS ( – Current Research Information System
The USDA's documentation and reporting system for ongoing and recently completed research and education projects in agriculture, food and nutrition, and forestry.
DTIC ( – Defense Technical Information Center
Provider of DoD technical information. DTIC links information among DoD personnel, DoD contractors and potential contractors and other U.S. Government agency personnel and their contractors.
Promotes the scientific and regulatory acceptance of non-animal tests which are of importance to biomedical sciences through research, test development and validations and the establishment of a specialized database service ( It is the leading international centre for coordinating the validation of alternative methods, providing advice on theoretical and practical aspects of the validation of new tests, the current state of validation of alternative methods for use in toxicology and the biosciences in general, in vitro test for topical toxicity, embryotoxicity, haematotoxicity, metabolism-mediated toxicity, metal toxicity, neurotoxicity and nephrotoxicity, and general animal welfare issues (scientific and ethical), such as the use of transgenic animals.
EPA EcoTox (
The ECOTOX (ECOTOXicology) database provides single chemical toxicity information for aquatic and terrestrial life. ECOTOX is a useful tool for examining impacts of chemicals on the environment. Peer-reviewed literature is the primary source of information encoded in the database. Pertinent information on the species, chemical, test methods, and results presented by the author(s) are abstracted and entered into the database. Another source of test results is independently compiled data files provided by various United States and International government agencies. ECOTOX is a unified interface providing access to three U.S. Environmental Protection Agency (U.S. EPA) ecological effects databases: AQUIRE (all aquatic species including freshwater and marine); TERRETOX (terrestrial animal mainly wildlife); and PHYTOTOX (terrestrial plant). Ecology, Toxicology.
ERIC ( – The Education Resources Information Center
Sponsored by the Institute of Education Sciences (IES) of the U.S. Department of Education, produces the world's premier database of journal and non-journal education literature. The ERIC Database indexes and abstracts education and education related journals, studies and reports, with links to full-text studies and reports from 1993 forward,
Fish, Fisheries & Aquatic Biodiversity Worldwide (,uid&profile=ehost&defaultdb=ffw)
Covers fish, fisheries and aquaculture, including biology, genetics, natural history, behavior, diseases, parasites, limnology and oceanography, habitat management, culture, propagation, fish processing, marketing, and fisheries management.
ICCVAM ( – Interagency Coordinating Committee on the Validation of Alternative Methods
ICCVAM Develop and validate new test methods; establish criteria and processes for the validation and regulatory acceptance of toxicological testing methods; generate, use, or provide information from toxicity test methods for risk assessment purposes.
Data bank of in vitro techniques in toxicology. The aim of INVITTOX protocols is to present precise and up-to-date technical information of the performance of the in vitro techniques currently in use and under development, their applications, advantages and drawbacks. The information is obtained directly from those scientists already employing such methods. Each protocol includes a detailed methodology sufficient to enable another researcher to carry out a procedure, experimental data, where available, the rationale for choice of technique and endpoint, and critical assessment comments about the accuracy of the system, its sensitivity, ease of implementation, shortcomings, etc.
JAX Resources (
Supports and provides access to a variety of tools: Mice Database, Mouse Genome Informatics, International Mouse Strains Resources, Mouse Resources, and Informational Resources.
NCI Mouse Models (
The NCI Mouse Models of Human Cancers Consortium (MMHCC) is a collaborative program designed to derive and characterize mouse models, and to generate resources, information, and innovative approaches to the application of mouse models in cancer research.In addition to the MMHCC initiative, the NCI sponsors numerous other projects to develop, analyze, and apply mouse cancer models. This site is intended to provide the cancer research community with information about mouse models and mouse research generated by the MMHCC and other NCI-supported projects
NIH Model Organisms for Biomedical Research (
This web site provides information about national and international activities and major resources that are being developed to facilitate biomedical research using the animal models listed here.
NORINA ( – Norwegian Inventory of Alternatives, Norwegian Reference Centre for Laboratory Animal Science and Alternatives.
Database of audiovisuals, computer programs, cd-roms, interactive videos, and other alternatives for use in the biological sciences
NTIS ( – National Technical Information Service
The central resource for government-funded scientific, technical, engineering, and business related information.
PubMed (
Citations and abstracts for articles published in approximately 8,400 journals in medicine, life sciences, health administration, veterinary medicine, molecular biology and genetics. PubMed is a service of the U.S. National Library of Medicine.
Covers 1950s to present.
PsycInfo (
PsycINFO is a department of the American Psychological Association (APA). It provides citations to articles in professional journals, conference proceedings, books, reports, dissertations and even important internet sites in psychology and related disciplines, most with abstracts.
Covers 1840s to present.
RePORTER ( – Research Portfolio Online Reporting Tools Expenditures & Results
A searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other research institutions. It is a biomedical database system containing information on research projects and programs supported by the Department of Health and Human Services
RTECS ( – Registry of Toxic Effects of Chemical Substances.
Provides toxicological information on over 140,000 chemical substances. Records include toxicological data and reviews, international workplace exposure limits, references to US standards and regulations, analytical methods and exposure and hazard survey data. RTECS is a compendium of data extracted from the open scientific literature. Six types of toxicity data are included in the file: (1) primary irritation; (2) mutagenic effects; (3) reproductive effects; (4) tumorigenic effects; (5) acute toxicity; and (6) other multiple dose toxicity. Specific numeric toxicity values such as LD50, LC50, TDLo, and TCLo are noted as well as species studied and route of administration used.
Network of databases on toxicology, hazardous chemicals, and environmental health. National Library of Medicine, Specialized Information Services cluster of databases on toxicology, hazardous chemicals, and related areas. Includes: Hazardous Substances Data Bank (HSDB), Integrated Risk Information System (IRIS), Chemical Carcinogenesis Research Information System (CCRIS), Developmental and Reproductive Toxicology and Environmental Teratology Information Center (DART/ETIC), GENE-TOX, TOXLINE, Toxics Release Inventory (TRI), International Toxicity Estimates for Risk (ITER), CHEMIDplus among others. New databases or services include Wireless Information System for Emergency Responders (WISER); Haz-Map, Household Products Database, and TOXMAP.
Web of Science (
Provides access to the three ISI (Institute for Scientific Information) Citation Databases: Science Citation Index; Social Sciences Citation Index; Arts & Humanities Citation Index. Multidisciplinary database, with searchable author abstracts, covering the journal literature of the sciences. Unique capability to search for articles that cite a known author or work
Wildlife and Ecology Studies Worldwide (,uid&profile=ehost&defaultdb=fzh)
Indexes literature on wild mammals, birds, reptiles, and amphibians; covering all aspects of wildlife and wildlife management
Responsible for documentation and information on alternatives to animals in research and testing. The ZEBET database AnimAlt ( is mainly designed to support the examination of the imperative nature of animal experiments by providing information on possible alternative methods. To this end, the ZEBET database offers validated information on alternative methods. Since February 2000 the ZEBET database on alternative methods to animal experiments has been accessible without license fees on the Internet in German and English through the German Institute for Medical Documentation and Information (DIMDI). The databank includes: description of specific methods; evaluations of those methods according to the 3R's, a description of the experiment that can be so modified, names of scientists who are experienced in the use of that method, and references to literature on the specific method and the experiment that can be replaced, reduced or refined.
Zfin ( – Zebra Fish Information Network
Addresses zebrafish genetics and development via an online database of information for zebrafish researchers. ZFIN serves as the zebrafish model organism database. The long term goals for ZFIN are a) to be the community database resource for the laboratory use of zebrafish, b) to develop and support integrated zebrafish genetic, genomic and developmental information, c) to maintain the definitive reference data sets of zebrafish research information, d) to link this information extensively to corresponding data in other model organism and human databases, e) to facilitate the use of zebrafish as a model for human biology and f) to serve the needs of the research community.
FishBase (
FishBase is a global information system with all you ever wanted to know about fishes. FishBase is a relational database with information to cater to different professionals such as research scientists, fisheries managers, zoologists and many more. FishBase on the web contains practically all fish species known to science.
Zoological Record (
Comprehensive coverage of zoology; including behavior, conservation and environmental science, ecology, evolution, genetics, habitat, marine and freshwater biology, nutrition, parasitology and disease, reproduction, taxonomy and systematics, veterinary studies, zoogeography and fossil records. Especially strong in new species reports and field studies.

Additional Resources

Other Lists of Databases

For additional information or assistance:

Sample searches, methods and guidelines, training and education, databases, organizations, and other resources that can assist in understanding alternatives, finding alternatives and completing the alternatives search.
Mary Wood
Librarian, UC Davis Center for Animal Alternatives (

Other Resources:

USDA/APHIS/AnimalCare (
Animal Care Policy Manual (
Policy #11: Painful Procedures (
Policy #12: Consideration of Alternatives to Painful/Distressful Procedures (
Alternatives and the AWA Brochure ( – AWIC
Alternatives Search Tip Sheet ( – NIH Library
The Principles of Humane Experimental Technique ( by Russell and Burch