IACUC Member Training September 27, 2007

Training Objectives A Quick Overview of the Rules IACUC Member Standards Protocol Review Procedures

Animal Welfare Regulations, Policies & Guidelines Animal Welfare Act - 9 CFR Chapter 1 Originally the “Pet Protection Act”, 1966 USDA Regulations and Animal Care Policies PHS Policy (1986) The Guide (National Research Council - 5th Ed.)

U.S. Dept. of Agriculture Enforces and Administers the Animal Welfare Act Enforces the Act through the Animal Welfare Regulations 9 CFR Chap. 1, Parts 1-3 Provides clarification of the Regulations through the Animal Care Policies

USDA Regulations Cover all warm-blooded animals exclude rats, mice and birds Animal Care policies cover more than just research Routine inspections of facilities Specific performance standards for: veterinary care and animal husbandry animal transportation and other issues Set requirements for committee (IACUC) composition and function Regs and Policies cover many other activities – pet breeders, circuses, marine mammal programs, swim with the dolphins, etc. Not to be outdone, the US Department of Health and Human Services was working on their own policy and regulations…..

PHS Policy – NIH Office of Laboratory Animal Welfare (OLAW) Health Research Extension Act of 1985 is the legislative mandate for PHS Policy. Covers all vertebrate animals NIH-funded institutions must adhere to the PHS Policy Oversight - Office of Laboratory Animal Welfare at NIH Each institution that accepts PHS funds must have an approved Assurance of Compliance with PHS Policy – essential a description of the institution’s program. There’s a copy in the member binder and on-line.

PHS Policy Covers all vertebrate species Reptiles, aquatics, birds, mice and rats, etc. Applies to all institutions that accept money from the Public Health Service for research, testing and teaching. UCI received $132,789,355 in last fiscal year All animal related costs are unallowable during lapses in approval Requires negotiation of an animal welfare assurance with OLAW Detailed description of our animal care and use program Hold up the booklets – Difference between the red and the green – the newest version (red, 2002) includes the just-in-time policy, allowing IACUC approval for animal work to be delayed until after the study section review of a protocol and assignment of a fundable score. Animal Welfare Assurance – ours was just renewed, in March 2003. Good until February 2008. It’s a negotiated agreement with NIH spelling out exactly how we assess and protect animals in research, testing and teaching.

Key Elements of PHS Policy: Requirements for the submission of funding applications (e.g., description of the use of animals, grant-protocol match) More specific record keeping requirements Different reporting requirements than USDA (no regular inspections) Composition of the IACUC (somewhat different than USDA requirements) USDA regs require three members, PHS policy requires 5 (including a non-scientist and unaffiliated member) USDA regs and PHS policy are like overlapping spheres – some stuff is duplicated, but each has its own focus – USDA is all uses (including pets and displays like zoos and circuses), PHS covers all species but focuses on research.

Composition of the IACUC USDA requires: At least 3 members Veterinarian, Non-affiliated member PHS Policy requires: At least 5 members Veterinarian, Nonscientist, Community/Non-affiliated member, at least 1 practicing scientist

The “Guide” Performance Standards: Institutional policies and responsibilities Animal environment, housing, and management Veterinary medical care Physical plant (facilities) The Guide is considered to be the Gold Standard for performance standards relating to animal welfare. Lots more detail than the regulations – specifics about how to run a program Basis for AAALAC accreditation

The Guide First edition issued in 1963 by the Animal Care Panel (renamed ILAR) The 5th and most recent edition was published in 1985. Used by AAALAC to evaluate animal care & use programs Covers all aspects of the animal care and use program, including facilities. First “Guide” was issued in 1963, 3 years before the AWA and 10 years before PHS policy Group of scientists/members of the National Research Council were already thinking about animal welfare

Other References 2000 Report from the AVMA Panel on Euthanasia Humane euthanasia techniques Endorsed by USDA and OLAW NASA Principles Respect for life Societal Benefit Non-maleficence Principles and organizations supporting the work of IACUCs AAALAC – private organization – Association for Assessment and Accreditation of Laboratory Animal Care

Ethical Principles of Animal Use Principles of Humane Experimental Technique by Russell and Burch, 1959 Written a long time ago, resurfaced in the 90’s The Three Rs – Replacement Reduction Refinement Use of animals in research involves responsibility – society places expectations on the scientific community that the use of living animals is of value to the furtherance of science and the good of society Groups such as NASA’s scientific advisory board began to think about applying ethics to research involving animals

The Three Rs Replacement Reduction Refinement Use something other than a live animal if possible Reduction Use as few animals as possible to achieve scientific significance without increasing pain and distress Refinement Make the procedures as non-invasive and painless as possible

Protocol Review Project Overview Use of Live Animals Replacement/Reduction: Refinement: Project Overview Use of Live Animals Literature Searches for Alternatives Experimental Design Justification of Animal Numbers Procedural Description Pain, Distress and Discomfort Analgesia Euthanasia Training & Experience These are the federal criteria for approval Items on the LEFT are the basics that justify use of animals in research, testing and teaching; these elements need to carefully thought through. Include elements of 2 of the "R"s, replacement of animals and reduction of numbers The items on the RIGHT are the “nuts and bolts” of the animal use protocol; the details of how animals will be used and cared for. There's the third R - refinement

USDA pain category – What’s up with that? Letters refer to the columns on the USDA Animal Usage report we file once per year Column A = animal species is listed here (that’s why there’s no pain category A). Number of animals used in the preceding year are listed in columns B – E

USDA Pain/Distress Categories B = animals used only for breeding purposes (breeder moms, stud males, culled pups, etc.) C = momentary (or less) pain or distress Needle stick for blood draw or administration of euthanasia No anesthesia needed for a similar procedure in a human

USDA Pain/Distress Categories D = Some pain/distress, treated with anesthetic, analgesic or tranquilizing drugs Similar procedure in a human would require topical or systemic anesthesia Post-surgical pain treated with analgesia Anesthesia used for restraint Cardiac Perfusion? Maybe not…..

USDA Pain/Distress Categories E = Pain/distress for which the use of appropriate anesthetic, analgesic or tranquilizing drugs would adversely affect the research. Analgesic studies Death as an endpoint REQUIRES SCIENTIFIC JUSTIFICATION

Special Review Issues Multiple Survival Surgery Prolonged Restraint Food and Water Restriction Use of paralytic agents Category E procedures Space/resources - check with Guy or me during the prereview, see what we know. Scientific Merit - refer to the policy. Is the hypothesis worthy of the animals' lives Modifications Minor - refinement - new drug or procedure; small number of additional animals (10% of original allocation) Significant - new species or additional animals on the magnitude of 100-200% of original allocation Needs to stand alone - Major changes to the experimental design or research paradigm

Review of Scientific Merit Protocols involving animals should have a sound research design, the animals selected should yield valid results, and the project should have relevance and scientific value (i.e. merit) . (based on PHS Policy and USDA Regulations)

It’s your responsibility … IACUC review of merit is not just for unfunded projects; both USDA and PHS delegate much of the responsibility for protocol review, including the assessment of merit, to the institution.

PHS Policy on Scientific Merit “Procedures with animals will avoid or minimize discomfort, distress, and pain to the animals, consistent with sound research design.” - PHS Policy (IVC1a) “The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results.” - U.S. Government Principles III

The USDA on Scientific Merit “Rationale for…species” “Appropriate species…to obtain valid results” “Activities do not unnecessarily duplicate…” “Procedures… for the conduct of scientifically valuable research” - 9 CFR 2.31

Training Objectives A Quick Overview of the Rules IACUC Member Standards Protocol Review Procedures

IACUC Member Standards Attendance Confidentiality Participation Conflict of Interest Disclosure

Attendance Members are responsible for attending all convened meetings and staying until business has been completed. If you cannot attend a meeting, notify the IACUC Administrative Office as soon as possible so an alternate member can be contacted if necessary to maintain quorum. Official committee business, including protocol review, cannot be conducted without a quorum of voting members.

Confidentiality IACUC protocols may contain personal, confidential and proprietary information. Members of the IACUC are responsible for maintaining all committee proceedings and documents in strict confidence. Information discussed at IACUC meetings may not be disclosed without the prior written permission of the Vice Chancellor for Research.

Participation Attend the meetings, including the semi-annual Program Evaluation and monthly Business Meetings Participate in Semi-Annual Facility Inspections Keep track of email/subcommittee reviews and respond promptly Volunteer to serve on subcommittees Keep up-to-date with regulations, policies, etc.

Conflicts of Interest Examples of a conflict of interest: Members of the IACUC must disclose all potential conflicts to the IACUC Chair or Administrator Examples of a conflict of interest: IACUC member is the Lead Researcher, faculty sponsor or collaborator on the project IACUC member has a significant financial or management interest in the sponsor of a project under review. IACUC member believes existing circumstances may effect his/her objectivity.

Training Objectives A Quick Overview of the Rules IACUC Member Standards Protocol Review Procedures

The New Review Procedure Prior to the Meeting: Administrative and Veterinary Pre-review IACUC Pre-review LR revision period At the Convened Meeting: Final Discussion and Approval

Pre-review Timeline Deadline – 3 weeks prior to meeting Week 1 – Admin/vet pre-review and distribution to committee via CD Week 2 – IACUC pre-review Protocols will be assigned to a primary and secondary reviewer, but all members are encouraged to review and comment all protocols Members’ pre-review comments must be returned to Administrator as soon as possible Week 3 – LR revisions LR’s revised protocol will be emailed to primary and secondary reviewers prior to the IACUC meeting.

At the Meeting Primary/Secondary Reviewers will: Present a BRIEF synopsis of the project Summarize the issues raised in pre-review and confirm that required changes were made Recommend Approval, Resubmission or Table for further revisions Discuss the protocol with other committee members (other than primary/secondary) if it’s in their area of expertise. I try to match assignments with expertise, but it’s not always possible.

Prior to Approval… Before the final vote, it should be clear to all members: That the need for live vertebrate animals in research, teaching or testing has been clearly articulated by the researcher. That the committee’s decision is consistent with the humane care of animals … even if you’re not the primary/secondary

Committee Decisions Approved Tabled Administratively (M) Very minor non-scientific issues Tabled for Subcommittee Review (T) Review by Primary/Secondary Reviewers Resubmission Required (R) Complete rewrite – serious scientific or welfare issues M examples - minor clarification in animal numbers, incorrect dosage of analgesic. Written confirmation for the official record is all we need. T examples - number of experimental or control animals needs further justification or a power analysis. Additional details of procedures needed. Scientific stuff.

Tabled to Subcommittee – The Process LR submits a response to the IACUC’s review Revised application, appendices Cover letter addressing each point of the IACUC’s memo Response materials are emailed to IACUC Subcommittee Primary and Secondary Reviewers, plus others as appropriate

Tabled to Subcommittee – The Process (con’t) Subcommittee responds to Administrator: OK to approve Additional information needed Email response is filed as documentation in the official protocol record.

Designated Review of Modifications Described in our OLAW assurance Appropriate for modification requests of a less-significant nature: Increase in animal numbers (< 10% of approved allocation) Refinements in technique Minor changes in procedure Requires polling of entire committee It only takes one member to call for full committee review Volunteers required for the standing subcommittee!

Training Objectives A Quick Overview of the Rules IACUC Member Standards Protocol Review Procedures

Questions? IACUC Webpage Member Binder When in doubt, ASK! http://www.rgs.uci.edu/ora/rp/acup/index.htm “Especially for IACUC Committee Members” Member Binder You got one when you joined the committee When in doubt, ASK!