Introduction to the IACUC and RICRO

2. Content Ethical Considerations and Historical Perspectives Regulatory and Institutional Factors Business Workflow Common Protocol Questions Who to Call

3. What ethical obligations accompany doing research with animals? Animal models as surrogates for humans Obligation to �use� animals appropriately Not to cause unnecessary pain and suffering Not to use more animals than scientifically justified Not to duplicate work unnecessarily

4. What makes compliance necessary for doing research with animals? Public need for transparency Compliance with the federal laws and granting agency regulations (APHIS/USDA Animal Welfare Act (AWA), PHS Policy) Maintenance of AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care) international accreditation

5. Historical Perspective Regulatory oversight as a means to facilitate the welfare of animals used in research has existed for more than 125 yrs. Mid 1800s on�Increased Use of Animals in Medical Education & Early 1900s Increased Use of Rats & Mice in Research 1876�Cruelty to Animals Act passed in England 1867-1908�Establishment of Antivivisection Societies in US

6. Historical Perspective Nazi Germany used humans in research, but banned vivisection on animals Post WWII�Nuremberg Code contained 10 Directives for Human Experiments Voluntary consent of human subject is absolutely essential The experiment should be so designed and based on the results of animal experiments Post-War Economic Boom Large Increase in Scientific Research Creation of NIH and Federally Funded Research

7. History of Animal Protection in the U.S. Scientists� Involvement 1950 Animal Care Panel 1952 Institute of Laboratory Animal Resources (ILAR) within Nat�l Acad. of Sci. 1963 Publication of the first edition of the Guide for Laboratory Animal Facilities and Care Government Involvement 1962 NIH Contract Laboratory Animal Welfare Act of August 24, 1966 Focus on Preventing Theft of Pets (Life Mag. Article Spring 1966)

8. History of Animal Protection in the U.S. Animal Welfare Act (AWA) August 24, 1966 Animal Welfare Act Amendments 1970; 1976; 1985; 1990; 2002 1970 Extended into laboratory animals 1985 Established requirement to have IACUCs to oversee research

9. History of Animal Protection in the U.S. 1971 NIH Policy Institution had to have Assurance (AAALAC) Annual Inspections Comply with AWA Follow Guide Later revisions of Policy required IACUC Included all live vertebrates U.S. Gov�t. Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training

10. Compliance=Price of Doing Research Perform ethical and humane research with animals Comply with the APHIS/USDA Animal Welfare Act (AWA) Comply with PHS Policy Maintain AAALAC International accreditation

11. Other Policies and Guidelines Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching AVMA Guidelines on Euthanasia (last revised in 2007)

12. What is an �Animal�? PHS��any LIVE, VERTEBRATE animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes� USDA� �any LIVE or DEAD dog, cat, nonhuman primate, guinea pig, hamster, rabbit, or any other warm-blooded animal which is being used or intended for use for research, teaching, experimentation, or exhibition purposes or as a pet. This term EXCLUDES birds, rats of the genus Rattus and mice of the genus Mus BRED for use in research and horses not used for research purposes and other farm animals�used for food or fiber� or for improvement of animal nutrition, breeding, management, or production efficiency�� Dogs = all dogs including those used for hunting, security, or breeding� AAALAC�includes care of INVERTEBRATES

13. How the Process Works: Self-Monitoring A trust relationship between: OLAW/USDA and CSU CSU and individual investigators Failure to self-regulate may: Jeopardize CSU�s Assurance Jeopardize CSU�s ability to receive federal funding. Result in fines PIs may have IACUC approval suspended Generate negative public perception Use of animals is not a right but a privilege

14. What is an IACUC? Federally mandated committee to monitor the care and use of animals in research, teaching, and testing Each institution which falls under authority of the Animal Welfare Act and/or receives PHS support for research and teaching must have an IACUC Specific to each institution�appointed by CEO of the Institution Bioethical committee

15. IACUC Responsibilities Review, clarify, modify and approve animal research protocols before initiation (also any changes to animal procedures), Serve as a liaison between the CSU animal research community and the public Oversee CSU research involving animals Inspect animal facilities and review animal care programs semi-annually. Provide appropriate training for CSU�s research community. Suspend activity on previously approved projects if not in compliance with PHS Policy, USDA regulations or IACUC guidelines.

16. IACUC Composition Federal Requirements: Membership appointed by the Institutional Official Minimum of 5 (PHS) or 3 (USDA) members Must include: DVM with lab animal medicine training/experience and has program responsibility Non-affiliated member (community representation) Non-scientific member (PHS only) Practicing Scientist

17. IACUC Composition CSU Requirements: Must follow federal guidelines, plus Must include a representative from each college that uses animals CVMBS, Ag Natural Resources Natural Sciences Applied Human Sciences Must include an ethicist, anesthesiologist and statistician

18. Activities Requiring IACUC Review and Approval Use of live, vertebrate animals in RESEARCH, TEACHING, or TESTING by anyone at CSU (even if conducted at another institution) regardless of funding source Use of dead animals/identifiable body parts (that do not go through CSU Necropsy Lab) Dead animals from local Humane Societies Any invasive, painful, or distressing procedures to animals ordered by CSU PI to be performed prior to CSU acquisition

19. Observational studies that may materially affect animal health and behavior Field Studies that materially affect animal health and behavior Client-owned animals used in clinical research studies Farm animals (�food and fiber�)

21. The Protocol Trail Intake Review Types Full Committee Review Designated member Review Determinations and Correspondence What�s Wrong With My Protocol? Renewals: Annual and Fourth Year Amending a protocol Closing a protocol

22. About the $$$ Sponsored Programs will not set up your account unless IACUC (IBC, IRB, or combination) has approved your protocol If A-100 form is not submitted at same time as your research proposal, research may be delayed Funding agencies have specific time requirements regarding evidence of IACUC approval The PI, not RICRO, is responsible for providing funding agencies with required documentation of IACUC approval

23. Submitting a Protocol Forms and instructions are on the RICRO website: http://www.research.colostate.edu/ricro Deadline�Second Tuesday of each month at NOON Submit signed original and 17 copies to RICRO

24. Before You Get Started Get Help!!! Review an accepted protocol in your field Ask your college IACUC representative to go over your draft Ask the University Veterinarian to pre-review your protocol Required for Pain Category D & E, and Non-LAR Care/Non-LAR veterinary Care Ask Bill or Laura to administratively pre-review your protocol

25. Review Types Full IACUC review Submission of original A-100 and 17 copies IACUC meets 3rd Tues. each month �face-to face� Requires a quorum of voting members Designated Review (DR) Must meet certain requirements set by CSU�s IACUC to be considered for DR Submission of original, signed A-100 (and memo requesting DR) May occur at any time during the month May get sent to full committee review

26. Designated Review Protocols that may be eligible for designated review include: No pain or distress to animals used in protocol Breeding/holding colonies Non-invasive: injections, tattooing, blood sampling by venipuncture, or terminal harvesting of tissues from animals with no surgical manipulations Terminal surgical procedures with appropriate anesthesia and AVMA approved euthanasia method Observational studies with no impact on animals/habitat Clinical assessment of animals during hospital evaluations

28. What you can expect? Possible Determinations Approved Requires Clarification/Modification most have post review questions Disapproved Tabled Pending Additional Information

29. What�s Wrong With My Protocol? Common reasons why the IACUC asks post-review questions of the PI

30. Outdated version of the A-100: Check the RICRO Website!! Q #3 Missing or incorrect Pain Category Any Pain Category D or E requires consult with University Veterinarian

31. Q #4 Project Activity Duration: Unless continuation of a previously approved project, start date should not be prior to the IACUC review date. Stop date should not be before IACUC review.

32. Q #5 Lay Summary: Frequently too technical, i.e. not in lay language. Ex. what would be released to a newspaper Must Address: purpose of research reasons for conducting/importance of the research reasons why animals must be used

33. Lay Summary Examples: Too Technical: The long term goal of this project is to ascertain whether�.acts either during development to sexually differentiate neural regions involved in the adult stress response�.. Revised: The long term goal of this project is to determine whether � is activated by estrogens during development to sexually differentiate brain areas involved in regulating the�.

34. Lay Summary Examples: Too Technical: This study will evaluate novel antigens for immunization against�. Revised: The object of this project is to develop an effective vaccine to protect humans from infection with� Remember � don�t use �jargon� that others won�t understand.

37. Literature Search is required to assure the following�.. Reduction - Minimize the number of animals used to obtain valid results�appropriate statistical analysis Refinement - Techniques to reduce pain and distress. Replacement - substitute animal with non- animal methods.

38. Considerations for the PI: Why Consider Alternatives? Regulatory Economic Social Humane Scientific

39. Question #9 Literature Search (cont): Databases searched or other sources consulted Date of the search Years covered by the search�Search period of at least 5-10 years Key words and/or search strategy used Check terminology, concepts and key words linked correctly (Boolean), Consultation with an expert in the field may be acceptable **Must include the following: -Name and qualifications as expert -Date of consultation -Substance of the consultation. Articles or citations may be used if pertinent. Attendance at conferences or workshops on analgesia or techniques may also be considered.

40. Q #11 Justification of Animal Numbers: Too many or too few animals used �must be able to get valid results. Requires a power calculation � if not provided, explain why this is not feasible. If multiple groups/treatments, table of animal numbers often useful Be sure the numbers justified in #10 agree with those in #3 and #22.

42. AWA 9CFR 2.31 (d) [The] IACUC shall determine that� (x) No animal will be used in more than one major operative procedure from which it is allowed to recover unless: (A) Justified for scientific reasons by the principal investigator in writing. (B) Required as routine veterinary procedure. (C) Approved by the Administrator of APHIS.

43. Question #17 Aseptic Technique: Often insufficient description of aseptic technique for invasive procedures. Include: Description of instrument sterilization. Instrument sterilization between animals. Prep of the surgical site. Use of sterile drapes. Describe surgical attire worn

44. AWA 9CFR 2.31 (d) [The] IACUC shall determine that� (iv) Procedures that may cause more than momentary or slight pain or distress to the animals will: (A) Be performed with appropriate sedatives, analgesics or anesthetics, unless withholding such agents is justified for scientific reason, in writing, by the principal investigator and will continue for only the necessary period;

45. Q #20 Adverse Effects: List all potential adverse effects � even if secondary effects are not expected. Q #21a Animal Monitoring: Clinical pain scoring system highly recommended for painful or distressful procedures. Q #22 Analgesia: CSU�s IACUC requires animals receive analgesia for 72 hours post surgery. List analgesia to be used and dosage Must scientifically justify in A-100 if cannot use analgesia due to nature of experiment

46. Q #27 Clinical Signs and Endpoints: Provide sufficient description of clinical signs used to determine need for euthanasia. How will you handle unexpected illness or injury? Q #28 Euthanasia Method/agent: Specify method of euthanasia even if project does not call for euthanasia (in case of emergency) Euthanasia method should follow the 2000 Report of the AVMA Panel on Euthanasia. Cervical dislocation only allowed under anesthesia. If using CO2 for euthanasia, training in its proper use is required. Contact LAR staff.

47. Other Considerations Biohazard Radioactive Controlled Substances Carcinogenic

48. Renewing a Protocol PHS and USDA requirements differ USDA: Protocols must undergo �annual review�. PHS: Protocols must be reviewed once every 3 years. CSU abides by both requirements for all species

49. Renewing a Protocol Purpose of annual review is to confirm no changes have taken place that may require further IACUC consideration. Annual review must be performed by the IACUC.

50. Renewing a Protocol A-100 submitted for initial review, fulfilling both USDA/PHS New A-100 submitted after every third project year (yrs. 4, 7, etc.) fulfilling PHS policy In intervening years (2,3) A-101 (abbreviated) submitted with basic info NOTE: RENEWAL NOTICE IS NOT THE A-101 PI reports number of animals used on A-101 at what pain level PI may request planned minor amendments/personnel changes on A-101 If significant amendment, need new A-100 must be submitted for IACUC review.

51. Amending a Protocol:Minor Amendments Minor changes are part of research, but require amendments to original protocol before implementation Must be submitted in memo form through RICRO office and include: Details of changes (procedures, animal numbers etc) Justification for change No change to an approved protocol may be initiated without IACUC approval.

52. Amending a Protocol:Major Amendments

53. Examples of Significant Changes Results in increased mortality levels (greater than those that were specified or presumed in original protocol) Results in significantly increased morbidity or pain/distress Results in change in the overall aims or objectives of the study

54. Closing a Protocol Act of Closing: Contact RICRO at any time and ask to close. Check the appropriate box in the annual reminder from RICRO and return. Once closed, must be re-submitted as A-100 to open. If the proposal will be re-submitted elsewhere without ANY changes to animal numbers or procedures, IACUC approval can be kept open and funding source changed (process as amendment).

55. Something Isn�t Right Here! Who to contact

56. If You Have Concerns Regarding Animal Care or Use Issues Contact Dr. James Owiny, University Veterinarian�(970) 491-5668 James.Owiny@.colostate.edu Dr. Terry Engle, IACUC Chair�(970) 491-3597 Terry.Engle@colostate.edu Dr. Bernard Rollin, University Bioethicist�(970) 491-6885 Brollin@lamar.colostate.edu Dr. Sue VandeWoude, Director, Laboratory Animal Resources�(970) 491-7364 Sue,Vandewoude@colostate.edu Dr. Bill Farland, Sr. Vice President for Research & Engagement�(970) 491-7194 Bill.Farland@colostate.edu Kathy Partin, Director, RICRO�(970) 491-1553 Kathy.Partin@colostate.edu Laura Martin, Senior IACUC Coordinator, RICRO�(970) 491-0236 Laura.Martin@colostate.edu Bill Moseley, IACUC Coordinator, RICRO�(970) 491-8060 Bill.Moseley@colostate.edu

58. Ask before initiation� IACUC approval may be required.