Tips for Write and Reviewing an Institutional Animal Care and Use Protocol

1. Tips for Write and Reviewing an Institutional Animal Care and Use Protocol

2. U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training • Proper transport • Relevant to human/animal health or basic knowledge • Proper species and numbers • Avoidance of pain and distress • Proper analgesics and anesthetics • Painless death • Proper husbandry • Proper training of researchers • Exceptions approved by IACUC, rather than researcher

3. 3-Rs • Reduce the number of animals being tested • Refine the methodology used, this implies the notion of end-points • Replace the animal models

4. Protol Items1-5. Header items • 1. Contact Info • 2. Title – New or Replacement • 3. Project Support – Federal Grant, Industry project, in-house funding • 4. External Scientific Review • 5. Internal Scientific Review

5. 6. Training and 7. Occupational Health Program • 6. PI and those who touch animals • Trained for species • Trained for procedure • Occ Hlth Pgm by species • 7. For those who handle tissues and samples only • Occ Hlth Pgm

6. 8. Lay Summary and 9. Specific Aims • 8. Write Lay Summary in 200 words or fewer for an 8th grade audience. Used by • the lay committee member during review • Public Relations for talking points to the media • 9. Specific Aims – Helps orient reviewer

7. 10. Design and Grant Pages • 10. Simple description of experimental design • Basic details of animal expts • Clearly show the role for each experimental group of animals and the number of animals in each group • Be concise and complete • Use bullets, tables, short-hand, etc. to get to the point fast • Must provide grant pages: Key pieces of Research Plan and Vertebrate Animal section • ACUC must approve transport through public areas • Note use of core facilities, such as imaging.

8. 11. A-B Animal Use • 11.A. Animal Transfers • 11.B Animal Table • Breakdown by Group • Show animal transfers • Special cases • Replacement protocols: Remove animals already used and killed; transfer animals in house • Breeding colonies: Include breeders, animals culled but not used as experimental subjects, include culled preweanling animals • Pain/Distress categories • C, D, E – Watched carefully by the USDA

9. 11.C. Preweanling animals • Important for breeding colonies

10. 11.D. Animal Rationale and Species • Why must animals be used? • Bad Answers • ‘cuz I can • ‘cuz I always have before • ‘cuz it’s all that I can afford • Good Answers • The science requires an intact animal • No other means are available • Why this species? • Good Answers • It is the next natural step to goal • It is the best model

11. 11.E. Animal number justification • Do • Power Calculations • Cite similar studies • Note pilot work • Don’t • Base it on your years of experience • Replicate experiments already justified by power analysis (except in rare cases)

12. 11.F. Animal Study Areas • Non-ARP space where live animals are used • ACUC must visit

13. 12.1-3 Drug Tables • 12.1 – Anesthetic drugs • Additional intra-operative monitoring required when paralytics are used • 12.2 – Analgesic drugs • Indicate analgesic/euthanasia to guide emergency care • 12.3 – ALL other agents (drugs, biologicals, etc.) • RESOURCE: Drug formulary by species on ARP web site

14. 13. Dietary Manipulations • Important to USDA • Food and Water restriction policies require specific documentation • Body weight • Actual daily food and water intake

15. 14. Surgical Procedures -Key Concepts I • Survival vs. Non-survival • Animals awake after survival procedure • Major vs. Minor • Major surgery enters a body cavity or produces permanent impairment • Single vs. Multiple • MMSS must be approved by IACUC • USDA must approve MMSS in second protocol

16. 14. Surgical Procedures -Key Concepts II • USDA-regulated animals vs. Mice, rats & birds • Unique facility regs for operative areas • Peri-operative procedures • Pre-operative analgesics • Intra-operative monitoring • Post-operative care: Documenting stages of recovery and pain management • 15. Non-surgical anesthesia

17. 14. & 15. Stumpers • Frequency of animal monitoring • Magic words are on protocol form: Post-surgical monitoring of animals should occur every 30 minutes throughout stage 4 of recovery, 6-10 hours throughout stage 3, and then daily. • Signs of distress monitored • Be specific • Use signs of pain noted in ACUC policies • Demonstrate thoughtful preparation for pain management by setting clear triggers

18. 16. Pain/Distress • If an animal in this study were not anesthetized, would the animal feel more than momentary or slight pain or distress if exposed to the procedures proposed in the protocol? • Will the animal experience unrelieved pain as part of the study? • If yes, the rationale must be well documented. -Very important to the USDA. • Literature search required • Purpose of search is for alternatives to painful or distressing procedures • Examples: • Replace surgical observation with MRI • Replace production of antibodies via ascites with in vitro production • Replace indwelling vascular catheter for HR/O2 measurement with finger-tip pulse-oxymeter.

19. 17. Prolonged restraint • Prolonged restraint vs. Restricted activity • Prolonged restraint = More than 12 hours • AWA Exception • Example: small cage size • Restricted activity = partial immobilization for more that 20 minutes in awake animals • Must document behavioral methods of acclimation • Example: NHP chair for behavioral studies requires training of animal

20. 18. Criteria for removal • Demonstrate thoughtful preparation for excluding animals by setting clear triggers • Make reasonable effort to anticipate adverse events • Be specific, e.g., 25% loss of BW, hematocrit at 40%. • Removed animals do not return • Death is not a criteria for removal

21. 19. Euthanasia • Describe for planned and unplanned • Comply with AVMA Guidelines of 2007 • CO2 in rodents requires secondary method

22. 20. Animal Housing • Central vs. Satellite • Satellite is… • the responsibility of PI • held to same standards as ARP • approved by the ACUC • inspected by ACUC prior to use

23. 21. Hazardous Agents & 22. RadioisotopesKey Concepts • Bio v. Chem v. Rad • Biologicals – DNA, cells lines, viral vectors, etc. • Must consider risk to public, researchers, animal care staff and animal populations • Cell lines must be tested for animal and human pathogens • May require separate approval from biosafety, chemical safety committee or ‘Radionuclide in Live Animals’ form

24. 23. Environmental Enrichment • Nonhuman Primates • Separate form with specific requirements • Single housing of any animal requires justification and plan for enrichment

25. 24. Canines • Non-standard housing is AWA exception • Dogs must be exercised

26. 25. Source of Animals • Non-commercial sources • Special procedures for procuring animals from other schools or research facilities • Transgenic animals • May have special needs • Breeding colonies • Makes special demands on researchers and ARP • Purpose of vet signature is related to source and housing of animals, NOT review of entire protocol

27. 26. Signature & Conflict of Interest Disclosure • PI signature • Personal financial relationship with research sponsor or personal financial interest in research outcome must be disclosed here – and ultimately managed.