VA Animal Research IACUC

1. VA Animal ResearchIACUC

2. IACUC(Institutional Animal Care and Use Committee) Charged with ensuring compliance • ACORP(Animal Component of Research Protocol) Official VA animal protocol form • AAALAC(Assoc. for Assessment & Accreditation of Lab Animal Care)Accrediting body for animal research recognized by VA • OLAW(Office of Laboratory Animal Welfare) PHS office that administers policy on animal use and care. • ORO(Office of Research Oversight) VA advising office on compliance and assurance

3. The Components of our Animal Research Program DIRECTOR Omaha Veterans Affairs Medical Center The lines of authority and responsibility for administering the animal research program and ensuring compliance. Research and Development Committee Subcommittee of Animal Studies IACUC Subcommittee of Animal Studies IACUC Associate Chief of Staff/Research Service ACOS/R&D • IACUC Coordinator: • 402- 995-3940 Administrative Officer Research Service Ellis G. Jensen, D.V.M. P.D. Westenburg, D.V.M. Veterinary Consultants DVM Veterinary Consultant ARF Supervisor Robert Wiegert ARF Supervisor Animal Caretaker TBA

4. IACUC Self-regulatory body for animal research • Responsibilities: • Perform review and oversight functions PHS Policy- The Guide VHA Handbook 1200.07 • Review and approval of animal research protocols • Perform semi-annual program & facility reviews, annual PAM audits

5. IACUC Members (2013) • Voting: • VA Scientist, Chair • VA Scientist, Vice Chair • Scientist • VA Scientist • Scientist • Veterinary Medical Officer • Non-Science Member • Non-Science Member • Unaffiliated Member • Veterinarian • ARF Supervisor • Non-voting: • Deputy ACOS, Research Service • IACUC Coordinator • AO, Research Service • ACOS, Research Service • Alternates: • Scientists (3) • A quorum must be met and maintained throughout the meeting. • Quorum is defined as a majority (more than 50 percent) of voting members.

6. Application to perform animal research

7. Animal specific forms:

8. Protocol Review Required submissions: • Initial – entire ACORP • Annual Continuing review • Triennial – entire ACORP • Optional submissions: • Amendment –entire ACORP with highlighted changes • Amendment to add new personnel: • expedited- DMR

9. Initial / Triennial– entire ACORP

10. Protocol Review Required submissions: • Initial – entire ACORP • Annual Continuing review • Triennial – entire ACORP • Optional submissions: • Amendment –entire ACORP with highlighted changes • Amendment to add new personnel: • expedited- DMR

11. Annual Continuing review

12. Protocol Review Required submissions: • Initial – entire ACORP • Annual Continuing review • Triennial – entire ACORP • Optional submissions: • Amendment –entire ACORP with highlighted changes • Amendment to add new personnel: • expedited- DMR

14. Protocol Review Required submissions: • Initial – entire ACORP • Annual Continuing review • Triennial – entire ACORP • Optional submissions: • Amendment –entire ACORP with highlighted changes • Amendment to add new personnel: • expedited- DMR

16. Protocol review • Overall, three Rs (Replacement, Reduction, and Refinement) • Scientific justification- initials that are not peer reviewed • Pain category • Training of personnel • Justification of animal numbers

17. Justification of Animals Required ElementsFrom IACUC ACORP, SOP andVHA Handbook 1200.7 Appendix D • Section j. Justification for Number of Animals Requested and Group Sizes.Describe how the estimated number of animals needed for the experiments was determined. When appropriate, provide the following: • the number of experiments planned • the number and type of experimental and control groups in each experiment • the number of animals in each group • The GUIDE also states that whenever possible, the number of animals requested should be justified statistically. A power analysis is strongly encouraged to justify group sizes when appropriate.

18. Protocol types when statistical justification is inappropriate • There are certain types of protocols for which statistical evaluation is ineffective. Often studies in which no analytical comparison between any of the groups can be made. Examples: • Pilot studies • Breeding protocols • Teaching protocols • Non-interventive studies, such as behavioral observations. • Justification from PI may include personal experience or reference to a comparable study in which the desired effect sizes were shown to be statistically significant.

19. When statistical justification is appropriateRequired information from PI’s • Clear hypothesis-driven description/outline of experimental design • (ACORP Section C2): • 1) How many experiments in each study (specific aim). • 2) How many experimental and control groups within a particular experiment. • 3) Number of animals needed per group. • 4) Total number of animals for the entire project (all specific aims). • Consideration for additional animals needed to account for experimental losses: (i.e. morbidity, mortality, or other difficulties with experimental procedures).

20. Power Analysis • Power analysis is a statistical rationale for the number of animals requested. • Power analysis is a declaration of estimates of minimum effect size: • -mean differences between groups • -variability • Description of how precise the analysis will be and what the significant limits will be for obtained values. (PI to determine) • Determination of the beta error rate (risk of missing a true effect or difference). (PI to determine) • Evaluation of experimental design and power analysis (IACUC responsibility)

21. Power Analysis ReviewQuestions to help IACUC reviewers • The following are questions that pertain to the statistical justification of animal numbers pertaining to Section K: • In the Power analysis table are the number of Specific Aims and Experiment numbers listed correlate to the experimental design described in Section C2? • Is a Representative Assay listed for each experiment and does the information correlate to what was given in Section C2 and does it seem to be the assay that would have the highest error in the data obtained? • Does the value for (N) equal “r x n” ? If the value of (N) is not equal to “r x n”, then is an explanation provided following the statistical table? • r = The number of experimental groups (including controls) planned for the experiment • n = Sample size per group determined from the “Statistical Power Table” • N = Number of animals per experiment

22. Go back to Full Committee Protocol Review- process Outcome choices: 1. Approval 2. Table/ Withhold Approval 3. Requires modification Minor: Administratively changed Modification: APPROVAL Go to Designated Member Review(DMR) Proceed by DMR APPROVAL

23. PAM(Required action- ORO) • Program to audit approved animal use protocols yearly • PIs will be notified by letter two months prior to deadline given audit form that will be used contacted by PAM team member to schedule visit • What is expected at the visit: All in PIs lab - have read IACUC protocol - familiar with approved procedures Visual inspection of lab, surgical and recovery areas Have records available

24. Guidance Documents • Research Service Internet Site- • IACUC Forms • IACUC/ARF Standard Operating Procedures (SOP) • http://www.nebraska.va.gov/services/Research/iacuc/iacuc_forms.asp • 1200.07- VHA Handbook- Use of Animals in Research- • http://www1.va.gov/vhapublications/ViewPublication.asp?pub_ID=2464 • PHS Policy -http://grants.nih.gov/grants/olaw/faqs.htm • Guide for the Care and Use of Laboratory Animals- http://grants.nih.gov/grants/olaw/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf

25. Questions?