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Alternatives to Painful and/or Distressful Procedures – A Reference Guide

The U.S. Department of Agriculture (USDA), Public Health Service (PHS), and institutional requirements dictate that every animal care and use protocol which employs procedures which have the potential to cause more than momentary pain and/or distress to the animals have a “Search for Alternatives to Painful Procedures” be performed. These are frequently identified as “D” and “E” procedures in the animal care and use protocol form.

This following information includes links which can help you determine the painful/distressful procedures in your protocol and how to perform a search for alternatives. This does not have to be a literature search (though the USDA maintains that a literature search remains the best way to fulfill the search for alternatives requirement).

The IACUC has a document entitled “Meeting the Information Requirements of the Animal Welfare Act” which could be helpful for you in your search requirements. Please contact the IACUC office to have a copy sent to you.

 

Brief Outline of Conducting Literature Searches

Most investigators have difficulty when trying to meet the requirements of the AWA and the institution with the search for alternative to painful procedures. However, if you break the literature search procedure down into 5 simple steps, done prior to filling our your animal care and use application, it makes the process a little easier. Use of the alternatives search worksheet may be helpful.

Step One: Understand the Legislation and Regulatory Intent. USDA policy #12 is clear in its requirement that ALL potentially painful and/or distressful procedures performed on the laboratory animals must have an alternatives search. This may mean that your protocol more than likely requires more than one alternative search. PIs should be aware that the IACUC and federal regulations require that protocols do not unnecessarily duplicate previous research and that may require the PI to do a literature search; however, this does not mandate a narrative and assurance of compliance with this regulation is documented in Section 19 of the Animal Care and Use Protocol Application. This is NOT the same as the search for alternatives requirement which requires a narrative to explain each potentially painful and/or distressful procedure being performed in the protocol.

Step Two: Know Your Protocol. You should gather information about the area of study, including species and organ systems; important acronyms and international spellings; names of hormones, enzymes, CAS#, and trade names; prominent authors in the field; knowledge of possible alternatives; and previous searches, including the key words and search strategy used. List all your potentially painful and/or distressful procedures that you are performing and make sure that each one has an alternatives search performed.

Step Three: Formulate a Search Strategy. This is most easily done in two phases: phase one covers the aspects of reduction and refinement and provides a comprehensive view of the field of study, including techniques and common species used, and may address unnecessary duplication. This may address issues such as availability of cell or tissue culture, different models or simulations available, ability to use animals lower on the phylogenetic scale, etc. Phase two addresses potential alternatives to the potential painful / distressful procedures (e.g., the use of chemical castration instead of surgical castration of animals). The PI should list all the potentially painful and/or distressful procedures being performed in the protocol. A search for alternatives to each procedure needs to be performed. Please be aware that a procedure is still considered to be a potentially painful or distressful procedure even if the procedure is done under complete anesthesia and is a non-survival procedure (e.g., terminal thoracotomy for chemical fixation of the animal) under USDA and institutional definitions.

Step Four: Select Appropriate Databases. If you are performing a literature search to satisfy the search for alternatives requirement- listed below are multiple choices of databases in which to do your search. Take the time to select the appropriate databases.

Step Five: Provide a Completed Animal Care and Use Protocol to the IACUC. Principal investigators should complete and review the search before completing the protocol; address and evaluate the alternative possibilities and be prepared to support their use or non-use in writing; check to make sure the terminology, strategy, databases searched (minimum of two) and dates of search are provided; and keep a copy of the strategy, databases search, and years of search for future use.

Reminder: the search for alternatives does not have to be a literature search, although the USDA considers it the best method of searching for alternatives. Other searches can include: information provided at workshops and conferences, consultation with acknowledged experts in the field of research, and information from standard reference books.

 

Documentation Required in the Animal Care and Use Protocol Form for Searches

Literature Search: key words and/or search strategy used, the names of the databases used (must be at least two), the dates searched (must be at least five years), and the date the search was performed must be included in the animal protocol.

Expert Consultation: type of communication (email, phone call), date(s) of communication(s), information given during the communication(s), and a brief description of the expert (name, affiliated institution, and what makes than individual an expert) must be included in the animal protocol.

Meetings/Workshops: type of meeting, date(s) of meetings, sponsoring organization(s), and information received during the meeting must be included in the animal protocol.

Standard Reference Books: title of book, author or editor, publisher, date of publication, pages, and information contained in the reference book must be included in the animal protocol.

 

Search for Alternatives Examples

 

Alternative Search Websites

Tips for Searching for Alternatives to Animal Research and Testing
View slides from the workshop given by the USDA on Meeting the Information Requirements of the Animal Welfare Act.

Sample Literature Searches for Alternatives
These examples are provided by the Animal Welfare Information Center (AWIC). AWIC also provides low cost or no cost literature searches.

Animal Use Alternatives Thesaurus
This site provides a list of search terms or synonyms for key words. For example, if you need to do an alternative search on “surgery”, this web site will give you a list of other key words to utilize in your search. It also has a link to the National Agriculture Thesaurus.

 

Databases

University of California Center for Animal Alternatives
This site, run by the University of California Davis veterinary school, has multiple links to web based alternatives databases.

Virginia Commonwealth University Research Animal Welfare
This site from the Virginia Commonwealth University has information on how to perform searches.

The Norwegian Reference Centre for Laboratory Animal Science and Alternatives – NORINA (A Norwegian Inventory of Alternatives)
This European-based site has an excellent database and search engine for alternatives.

European Resource Centre for Alternatives in Higher Education (EURCA)
This European-based site is devoted to providing alternatives in classroom teaching.

Fund for the Replacement of Animals in Medical Experiments (FRAME)
This United Kingdom-based web site has excellent alternatives and databases.

Animal Welfare Information Center (AWIC)
This web site, run by the United States Department of Agriculture, is designed to provide both information and searchable databases for information on alternatives.

Johns Hopkins Center for Alternatives to Animal Testing (AltWeb)
This web site has information and one of the best alternatives search engines.

Scientists Center for Animal Welfare (SCAW)
This web site, run by the non profit organization SCAW, is dedicated to improving the welfare of all animals, with multiple publications listed.

Animal Welfare Institute (AWI) Enrichment and Refinement Database
This non-profit organization is based in the United Sates and publishes the book “Comfortable Quarters for Laboratory Animals”. This site has information and a search engine entitled “Database on Refinement of Housing and Handling Conditions and Environmental Enrichment for Laboratory Animals.”

National Centre for the Replacement, Refinement, and Reduction of Animals in Research
The National Centre for the Replacement, Refinement and Reduction of Animals in Research provides a UK focus for the promotion, development and implementation of the 3Rs in animal research and testing.

Universities Federation for Animal Welfare (UFAW)
This non-profit organization is based in the United Kingdom. The site has information in the form of links and publications.

Bibliography on Alternatives to Animal Testing (ALTBIB)
This site, a consortium sponsored by the National Library of Medicine and National Institutes of Health, has an excellent data base for identifying alternatives in biomedical research.

The ERGATT/FRAME/ECVAM Databank of in Vitro Techniques in Toxicology (INVITTOX)
This site has a search engine to identify in vitro alternatives to toxicity testing with a brief description of each test and links to full protocols.

Alternatives to Skin Irritation/Corrosion Testing in Animals (Invitroderm)
This site, devoted to dermatologic testing, has a searchable database.

Interagency Coordinating Committee for the Evaluation of Alternative Methods (ICCVAM) and its supporting center, National Toxicology Program Interagency Coordinating Committee for the Evaluation of Alternative Toxicologic Methods (NICEATM)
This federal agency is part of NIEHS and is assigned the role of developing and evaluating alternative models in toxicology testing.

European Centre for the Validation of Alternative Methods (ECVAM)
This is the European agency akin to ICCVAM.

National Agriculture Library (AGRICOLA)
This site is funded by USDA and will have citations for books, articles, and conferences to help in your search for alternatives.

Computer Retrieval of Information on Scientific Projects (CRISP)
This site is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other research institutions. The database, maintained by the Office of Extramural Research at the National Institutes of Health, includes projects funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Health Care Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

The Defense Technical Information Center (DTIC®)
This site is the premier provider of DoD technical information. DTIC serves as a vital link in the transfer of information among DoD personnel, DoD contractors and potential contractors and other U.S. Government agency personnel and their contractors.

Scientific Information Search Engine (SCIRUS)
This site contains, they claim, the most comprehensive science-specific search engine on the Internet. It will search over 200 million science-specific Web pages.

PrimateLit
This site is updated twice per month (around the 3rd and 17th) and is dedicated to primate information. It is supported by an NIH grant and is a collaborative project of the Wisconsin Primate Research Center, the Washington National Primate Research Center, and the University of Wisconsin-Madison Libraries.

National Library of Medicine Gateway
This site contains a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing “one-stop searching” for many of NLM’s information resources or databases.

 

Subject Coverage of Commonly-used Databases

Agricola – general agriculture, animal science, chemistry and biochemistry, microbiology, cytology, human and animal nutrition, biotechnology, physiology, veterinary medicine, wildlife, zoology, entomology.

Biosis – general agriculture, aerospace biology, biochemistry and anatomy, bacteriology, cell biology, botany, anatomy, physiology, clinical medicine, pathology, biophysics, toxicology.

Cab – general agriculture, animal science and production, crop science, forestry, pest control, human nutrition, biotechnology, pesticides, veterinary medicine, machinery and buildings, ergonomics.

Medline – clinical medicine, experimental medicine, pharmacology, microbiology, administration, nutrition, anatomy and physiology, veterinary medicine, occupational medicine, toxicology and other medical topics.

Embase – clinical medicine, experimental medicine, pharmacology and drugs and potential drugs, biochemistry, developmental biology, forensic medicine, health economics, occupational health, toxicology.