1. Meeting the Information Requirements of the Animal Welfare Act Gongchao Yang, MD, MLS IACUC Academic Information Services University of Mississippi Medical Center April, 2008

2. 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.

3. Searching for Alternatives Why do we need to?

4. 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

5. Animal Care Policy #12 Written 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

6. 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

7. Searching for Alternatives How are we going to? Minimum 2 databases need to be searched PubMed and MEDLINE are considered one database

8. 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.

9. Coverage of Databases

10. Databases Biomedical and Biological AGRICOLA http://agricola.nal.usda.gov http://agricola.nal.usda.gov CAB Abstracts MEDLINE PubMed http://www.ncbi.nlm.nih.gov/si tes/entrez?db=pubmed&cmd= search&term= http://www.ncbi.nlm.nih.gov/si tes/entrez?db=pubmed&cmd= search&term= ToxFile EMBASE PsycINFO ASFA Pascal SciSearch Current Contents BIOSIS

11. Databases Pharmaceutical and Technological Pharmaceutical News Index International Pharmaceutical Abstracts NTIS (National Technical Information Service)

12. Databases Federally-funded Research CRIS ( Current Research Information System) http://cris.csrees.usda.gov 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)

13. Additional Databases Available 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/

14. Additional Databases Available 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/

15. 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…

16. 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

17. 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/alternativeanimalusethesaur us.htm http://www.nal.usda.gov/awic/alternatives/alternativeanimalusethesaur us.htm

18. 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.

19. 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.

20. Search Example Topic: Stem cell-based therapy for the treatment of Type 1 diabetes mellitus

21. Database: PubMed Database covered: 1950-present Date of search: April 17, 2008 Search covered: Recent 10 years

22. 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

24. 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

28. Searching for Alternatives When should we?

29. Animal Care Policy #12 Written Narrative for Alternatives to Painful/Distressful Procedures: June 21, 2000 Alternatives should be considered in the planning phase of the animal use proposal.

30. Searching for Alternatives What will the library do?

31. 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.

32. Search Evaluation The 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.

33. Narrative and alternative search might 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.

34. 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.

36. Search Evaluation RED 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).

37. 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.