Meeting the Information Requirements of the Animal

Welfare Act

Gongchao Yang, MD, MLS

IACUC

Academic Information Services

University of Mississippi Medical Center

April, 2008

Searching for Alternatives

• Why do we need to?

• How are we going to?

• When should we?

• What will the library do?

• The issues we are facing.

Searching for Alternatives

• Why do we need to?

To comply with the USDA’s Animal Welfare Act [9 CFR, part 2, Section 2.31 (d)(1)(ii) and (iii)] you must complete a written NARRATIVE of the sources you consulted to determine whether or not alternatives exist to procedures that may cause pain and distress. Likewise, this search will ensure that the proposed studies are not unnecessarily duplicative.

Assurances

Animal Care Policy #12Written Narrative for Alternatives to

Painful/Distressful Procedures: June 21, 2000

• •“..the performance of a database search remains the most effective and efficient method for demonstrating compliance with the requirement to consider alternatives to painful/ distressful procedures.”

http://www.aphis.usda.gov/animal_welfare/downloads/policy/policy12.pdf

Definition of the 3 Rs by Russell and Burch*

• Reduction Minimize the number of animals used.

• Refinement Employ techniques that reduce pain and distress.

• Replacement Substitute animal with nonanimal methods or lower organisms.

*Russell and Burch (1959) -The Principles of Humane Experimental Technique http://altweb.jhsph.edu/publications/humane_exp/het-toc.htm

Searching for Alternatives

• How are we going to?

Minimum 2 databases need to be searched

PubMed and MEDLINE are considered one database

Approach to Meeting the Information Requirements

• Approach the search in two phases. • Analyze the protocol to determine where alternatives

might be used.• Decide where to go for the information.• Databases.• Websites.• Link terminology appropriately for best search

results.• Evaluate the search results.

Coverage of Databases

DatabasesBiomedical and Biological

• AGRICOLA http://agricola.nal.usda.gov

• CAB Abstracts

• MEDLINE

• PubMed http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=

• ToxFile

• EMBASE

• PsycINFO

• ASFA

• Pascal

• SciSearch

• Current Contents

• BIOSIS

DatabasesPharmaceutical and Technological

• Pharmaceutical News Index

• International Pharmaceutical Abstracts

• NTIS (National Technical Information Service)

DatabasesFederally-funded Research

• CRIS (Current Research Information System) http://cris.csrees.usda.gov

• CRISP (Computer Retrieval of Information on Scientific

Projects) http://crisp.cit.nih.gov

• NTIS (National Technical Information Service)

• FEDRIP (Federal Research in Progress)

Additional DatabasesAvailable on the Web

• Scientific and Technical Information Network (STINET)

• http://stinet.dtic.mil

• Alternatives to Skin Irritation Testing in Animals • http://www.invitroderm.com/

• Altweb (Alternatives to Animal Testing Web Site) • http://altweb.jhsph.edu/

Additional DatabasesAvailable on the Web

• DoDBiomedical Research Database • http://www.dtic.mil/biosys/org/brd/

• Scirus-scientific information search engine developed by Elsevier Science

• http://www.scirus.com/

• Animal Welfare Institute Enrichment and Refinement Databases • http://www.awionline.org/lab_animals/index.htm

• PrimateLit• http://primatelit.library.wisc.edu/

How to Search for Alternatives

Use three types of terms:

1. Scientific terms related to the research protocol;

2. Alternative (3Rs) terminology; and

3. Search terminology: boolean operators (AND, OR, NOT), limits, truncations, years, types of materials…

Alternative Terms: Refinement and Reduction

Most search terms can be obtained from the protocol and area of study

• analgesic or analgesia or painkiller• technique or method or procedure• anesthetic or anasthetic or anaesthetic• monitor or evaluate or supervise• restrain or immobilize or restrict• positive reinforcement or animal training• housing or facility or caging

Alternative Terms: Replacement

• artificial or vitro or culture • tissue or cell or organ, alternatives• animal testing alternatives, animal use alternatives• insect or arachnid or invertebrate• fish or mollusca or cephalopod• simulation or digital image or interactive• mannequin or manikin or model

Animal Use Alternatives Thesaurus http://www.nal.usda.gov/awic/alternatives/alternativeanimalusethesaurus.htm

Search Strategy

Two Phases

• Phase I, a comprehensive search for Reduction and Refinement- citations pertinent to PI’s field of study.

• Phase II: Replacement- use of nonanimal or alternative animal models.

Phase I: a Comprehensive Search for Refinement and Reduction

• Refinement and Reduction aspects of alternative are broad and often are addressed in the methods of the studies. The search results will reveal the techniques used, commonly used species and whether the protocol unnecessarily duplicates previous research.

Search Example

• Topic:

Stem cell-based therapy for the treatment of Type 1 diabetes mellitus

Database: PubMed

• Database covered: 1950-present

• Date of search: April 17, 2008

• Search covered: Recent 10 years

Stem cell-based therapy for the treatment of Type 1 diabetes mellitus

PubMed

Stem cells

Embryonic stem cells

Fetal stem cells

Diabetes Mellitus, Type 1

Insulin-Dependent

Diabetes Mellitus

Type 1 diabetes

Phase I: comprehensive search

Progenitor Cells

Stem cell-based therapy for the treatment of Type 1 diabetes mellitus

PubMed

Stem cells

Embryonic stem cells

Fetal stem cells

Diabetes Mellitus, Type 1

Insulin-Dependent

Diabetes Mellitus

Type 1 diabetes

Phase II: Alternative search for replacement

Vitro or tissue or culture

animal disease models

Animal use alternatives

Animal model

Animal testing alternatives

Analgesic or analgesia

Anesthetic or anaesthetic

Progenitor Cells

Searching for Alternatives

• When should we?

Animal Care Policy #12Written Narrative for Alternatives to

Painful/Distressful Procedures: June 21, 2000

• Alternatives should be considered in the planning phase of the animal use proposal.

Searching for Alternatives

• What will the library do?

The Library will

• Assist PI with selection of the databases to search and search strategies.

• Reference staff will conduct searches upon request for your animal study protocol at no cost.

Search EvaluationThe PI Role

• Check terminology, strategy, sources, and dates of search.

• Review the search before completing the protocol.

• Assess and evaluate the alternative possibilities.

• Be prepared to support the use or non-use of any alternatives in writing.

• Keep a copy of strategy, databases searched, and years of search for future use.

Narrative and alternative searchmight include…

Statements such as …

• No satisfactory alternatives to painful procedures were found using the above listed search terms.

• Based on the current literature, we have selected the least painful or least stressful procedure(s) that is/are adequate to answer our question.

• While non-animal models are available to provide answers, they will be used in conjunction with animal experiments and , thus, can lead to a reduction in the number of animals needed for this project.

• Our study is not duplicative of other studies identified by the search.

Issues we are facing

Some databases are fee-based and the PI will be charged if a fee-based database is

selected. Not enough information in #16 provided by

some PIs. Timing, direct contact with the library early in the

process will be more efficient. Interpretation of the number of hits, and how to

narrow a search.

Search EvaluationRED FLAGS

• Search completed at the last minute.• Only 1 database searched.• Terms only for painful aspects.• The term “alternative” used alone with no

other alternative terms.• Keywords listed not relevant to protocol.• Keywords and concepts linked in an

incorrect manner (e.g. wrong boolean operators).

• Search doesn’t cover adequate time period (5-10 years).

ACKNOWLEDGEMENT

• Dr. Linda Fulton• Dr. Andrew Grady• Ms. Amanda Murray Kinslow• Dr. Susan Warren• Ms. Jean Garrett• Ms. Ada Seltzer• Ms. Susan Clark• Ms. Helvi McCall Price• Ms. Candace Vance• USDA Animal Welfare Information Center

For their support and comments.