1. Responsible Conduct of Animal Research
December 9, 2016
M.A. McCrackin, DVM, PhD, DACVS, DACLAM, CMAR
Veterinary Medical Officer, Ralph H. Johnson VAMC
Associate Professor, Comparative Medicine, MUSC

2. Objectives Review the origin of US regulations for animal research
Discuss principles of ethical review of animal research applied at MUSC and the VA

3. Impetus for Animal Welfare Act August 24, 1966
Snatching of “Pepper” Lakavage from Pennsylvania farm in 1965 & death in research surgery by
Dr. Seymour Furman at Montefiore Hospital in the Bronx.
Voting Rights Act approved & Medicare added to Social Security same day “Pepper’s Law” introduced. Pepper’s Law got much more public engagement than the other 2 landmark bills.
Life magazine article on dog dealers in February 1966

4. Impetus for AWA Amendment: Health Research Extension Act 1985
Rhesus macaques with deafferented limbs
Plasticity of brain
Undercover PETA worker exposed lab conditions
Amendment required ethical review (IACUC)
Edward Taub – macaques at Institute of Behavioral Research in Silver Springs, MD

5. Scope of Authority OLAW IACUC USDA AAALAC Funding
Direct Animal Care
USDA
Employees, Affiliates
AAALAC
Animal Ownership

6. IACUC – Ethical Review Institutional Animal Care & Use Committee
Local, institutional
regulation
Ethical review of
proposed research
BEFORE starting work
Non-scientists & non-affiliated lay members required

7. IACUC Responsibilities
Oversee animal research program
Semiannual facility inspections & program review
Manage protocol review process
Review protocols & subsequent amendments
Review animal welfare concerns
Investigate concerns; no whistleblower retaliation

8. Aspects of Ethical Review
Living
conditions
Euthanasia
Mitigation pain or distress
Qualified personnel
Justification of animal use
Species
Genders
Strains
Numbers
Veterinarian consulted
Survival Surgery
Location
Preparation
Sterile equipment
Aseptic technique
Medical care available
Space
Enrichment
Humane endpoints
Timeline
Sample
collections

9. 3 Rs Replacement Reduction Refinement
Replacing the use of animals with non-animal techniques
Reduction
Reducing the number of animals used
Refinement
Refining (enhancing) experiments or procedures to reduce pain or distress

10. Shamoo & Resnick, RCR, 2nd ed, 2009
3 Rs + 2 More
Relevance
Research questions with scientific, medical or social importance
Benefits outweigh harm to animals
Redundancy Avoidance
No repetition of previously published work unless strong justification
Literature searches to show
No repetition or justification for it
No viable alternatives to animal pain & distress
Shamoo & Resnick, RCR, 2nd ed, 2009

11. Humane Endpoints
Animal experiment design  identify clinical parameters that
Allow collection of meaningful data
Eliminate death as an endpoint
Earliest possible time point to prevent unnecessary animal suffering
Genetically engineered animals
Phenotype may require early euthanasia

12. Steps for Ethical Review
Complete CITI training +/- surgical assessment
Participate in occupational health program
Consult with veterinarian about animal model, analgesia, anesthesia, monitoring
Consult with other specialists about hazards (e.g., biosafety, radiation, chemical)
Draft proposals for review – capture animal experience from start to finish of experiment(s)

13. Top Hints for Smooth Review
Lay summary – readability scoring
Scientific basis for species, genetics, gender choices
Power analysis to justify numbers
Describe clinical phenotypes needing special husbandry / veterinary care
Timeline, timeline, timeline

14. Aspects of Ethical Review: Animal Experience Start to Finish
Euthanasia
Arrival & Acclimation -5
3-5
13-15
27-29
41-43
Days
Survival Surgery
Blood collection 1
Drug treatment IP 1
Drug treatment IP 2
Drug treatment IP 3
34-36
20-22
9-11
Blood collection 2
Blood collection 3
Blood collection 4

15. Veterinary Clinical Care
IACUC OR
POLICE =
Consult
Facilitate
Collaborate
Anesthesia
Analgesia
Surgery
Endpoints
Treatment
Euthanasia

16. Summary Reviewed the origin of US regulations for animal research
Summarized steps & tips for ethical review before conducting animal research at MUSC and the VA

17. QUESTIONS?