ILAR J
Volume 49, Number 4, 2008
Animal Use Oversight: Balancing Risk Management with Burden

Bayne and Garnett.  Introduction: Mitigating Risk, Facilitating Research, pp. 369-371

Domain 3: Research
Domain 4: Animal Care
Domain 5: Regulatory Responsibilities

SUMMARY: The authors introduce this issue of the ILAR Journal which addresses the need to mitigate risk associated with animal-based research and the different ways to achieve the delicate balance between regulatory burden and research conducted in a humane and responsible manner.  The authors provide a very brief summary of the relevant documents and oversight bodies for policies and the regulatory framework of animal welfare oversight in the U.S.

QUESTIONS:
1. 	What "risk" do the authors mention in this introduction?
2. 	What is post approval monitoring?

ANSWERS:
1. 	Noncompliance.  Real or alleged noncompliance can jeopardize research funding, the individual researcher's reputation, and the credibility of the institution. But the risks of noncompliance in a single program or institution have much broader implications, because all animal research institutions are interconnected.
2. 	Post approval monitoring procedures compare the practices described in approved protocols and SOPs against the manner in which they are actually conducted.

Van Sluyters.  A Guide to Risk Assessment in Animal Care and Use Programs: The Metaphor of the 3-Legged Stool, pp. 372-378

Task 5 Execute IACUC Veterinary Responsibilities 12±2%

Abstract: A high-quality contemporary animal care and use program (ACUP) is a multifaceted dynamic system with three distinct organizational entities—the institutional official (IO), attending veterinarian (AV), and institutional animal care and use committee (IACUC)—each of whose authorities and responsibilities are mandated by a complex set of laws, regulations, policies, and guidelines. The 3-legged stool is presented here as a metaphor for the properly constituted and functioning ACUP, with the legs of the stool representing the IO, AV, and IACUC: when one component is weakened, the stool remains standing but tilts—the ACUP remains in compliance with animal welfare standards but is at risk of failure [Figure 1]. 

Mechanisms for assessing an ACUP's strengths and weaknesses include both external evaluators, such as the US Department of Agriculture, Office of Laboratory Animal Welfare, and Association for Assessment and Accreditation of Laboratory Animal Care, and internal evaluators, such as the IACUC, AV, and IO. However, each of these evaluators primarily assesses whether aspects of the ACUP are in compliance with current standards; they do not necessarily cite weaknesses in a compliant program. This article stresses the need for ACUPs to undertake a self-assessment of risk and outlines a number of ways programs can recognize their risks, with examples for each of the three components, which are characterized as either "weak" or "overzealous" in meeting their mandates. I caution against the use of a legacy of compliance as the sole means for evaluating an ACUP's strength, and instead promote the value of rigorous risk assessment/mitigation to ensure that a program is both strong and resilient.

Recognizing Risks in an Animal Care and Use Program: An animal care and uses program (ACUP) is at risk of failure when any of its components usurps another’s authority or responsibility or fails to fulfill its own.  The three major components of the ACUP are the 1) institutional official, 2) attending veterinarian, 3) and the IACUC.  In this manuscript, the authors go on to give specific examples of weak or overzealous behavior by the IO (page 374-375), AV (pages 375-377), and IACUC (377-378).

SUMMARY: The structure of ACUP in some ways resembles that of the US government, with three distinct branches each with its own mandate, and with checks and balances.  As with three governments, there are significant areas of overlap in the responsibilities of three components of the ACUP.  ACUPs in which the IO, AV, and IACUC work in harmony to fulfill their individual responsibilities are models for risk resistance.

QUESTIONS:
1.	What does the metaphor of the three legged stool represent?
2.	What is the acronym ACUP stand for?
3.	What is the acronym AV stand for?

ANSWERS:
1.	Each leg of the stool represents a component of the ACUP and together they support the program.  See Figure 1 on page 374 for details.
2.	Animal Care and Use Program
3.	Attending Veterinarian

Lowman.  The Institutional Official and Postapproval Monitoring: The View from 10,000 Feet, pp. 379-387

Task 5- Execute Institutional Animal Care & Use Committee Veterinary Responsibilities ; K4- Facility Inspection and Program Review

SUMMARY: The Institutional Official (IO) is ultimately responsible for ensuring a high quality program for the care and use of laboratory animals at the institution. The IO delegates authority to the IACUC and the institutional veterinarian but is ultimately responsible for assuring compliance of the institution. The IO may or may not have a background in science, but this should not affect their ability to perform the job. The IO is an executive position and should function as such. The IO does not need to be involved with the day to day activities, but should be aware of any potential issues and should provide leadership and direction for the program. The article discusses 4 tools for good leadership by the IO- (1) vision, (2) commitment to quality and integrity, (3) planning and resource development, (4) accountability.

Post approval Monitoring (PAM) is essential for measuring performance against standards. PAM monitors the performance of the staff who are conducting the IACUC approved research. Without this process the article states that the IO cannot accurately evaluate the performance of direct reports or that the IACUC is maintaining high ethical and scientific standards of the protocols it approves. The PAM process provides quantitative and qualitative evidence that protocols are being followed. It also provides an opportunity for promoting best practices. The data generated from PAM also allows the IO to evaluate whether the resource allocations are adequate to sustain the laboratory animal care and use program and whether the institutional vision for the program is being met.

QUESTIONS: 
1. 	What does the acronym OLAW stand for? 
2. 	What does the acronym PAM stand for? 
3. 	According to the PHS policy, who is ultimately responsible for the compliance of a facilities animal care and use program?
a. 	IACUC 
b. 	Attending veterinarian 
c. 	Institutional Official 
d. 	All of the above 
4. 	According to the PHS Policy on Humane Care and Use of Laboratory Animals who signs the Assurance of Compliance? 
a. CEO 
b. Attending Veterinarian 
c. IACUC administrator 
d. IO
 
ANSWERS: 
1. 	Office of Laboratory Animals Welfare 
2. 	Post Approval Monitoring 
3. 	c 
4. 	d. 

Collins.  Postapproval Monitoring and the IACUC, pp. 388-392

Domain: 5, Regulatory responsibilities
Animal species: all

SUMMARY: PAM (postapproval monitoring) can be a valuable adjunct to the mandated self-regulation that is the responsibility of an IACUC.  

The functions of the IACUC according to the USDA’s Animal Welfare Act and Regulations (AWAR 1989) and the Public Health Service Policy (NIH
2002) are as follows:

1.	Inspect all the institution’s animal facilities at least every 6 months
2.	Review the research facility’s program for the humane care and use of animals, at least every 6 months
3.	Submit the reports of program review and inspection to the Institutional Official (IO).
4.	Review and investigate concerns involving the care and use of animals at the research facility
5.	Make recommendations to the IO regarding research facility’s animal program, facilities or personnel training
6.	Review, approve, require modifications to, or withhold approval of the components of proposed activities related to the care and use of animals.
7.	Review, approve, require modifications to, or withhold approval of the significant changes in ongoing activities related to the care and use of animals.
8.	If necessary suspend an activity involving animals.

Depending on the species used and the source of funding, most IACUC members are familiar with the Animal Welfare Act (9 CFR) and the PHS policy on Humane Care and Use of Laboratory Animals (PHS Policy).  Many are also acquainted with AAALAC International’s accrediting process, which relies on the Guide. 

PAM responsibilities could be:

1.	Review of  approved protocols and meet with investigators to discuss current research activities
2.	Oversee new procedures, new investigators or new procedures/investigators which IACUC has a concern
3.	Provide training and or retraining as needed
4.	Support process of science with confidence that the animals receive humane care
5.	Help investigators to determine what changes require protocol modifications and need to be submitted for the IACUC approval
6.	Help the attending veterinarian to closely monitor animal health at a facility
7.	Provide firsthand observations to the IACUC
8.	On behalf of the IACUC inform an investigator that unapproved work may not continue and will be reported to the IACUC 
9.	PAM cannot supersede or replace the IACUC

What skills should PAM personnel have?

1.	Communication skills, especially in adversarial situations
2.	Clear understanding of regulations
3.	Listening skills, especially when English is not the primary language
4.	Broad experience with laboratory animal care, especially invasive procedures

How do you know if PAM is adequate in your research facility?

If your veterinary and husbandry personnel know the laboratory staff, the protocols, and the animals, you have a successful PAM.  If the institution is confident that the inevitable errors and accidents associated with an animal program are communicated with veterinarian and the IACUC, the PAM is excellent.

QUESTIONS:  
1.	Which of the following statements are UNTRUE about a PAM staff?
a.	Provide training and retraining as needed. 
b.	Help investigators to determine which changes require protocol modifications
c.	They become automatically a voting member of the IACUC
d.	Assure animal receive humane care
e.	Serve as an adjunct to the mandated self-regulation that is the responsibility of an IACUC.  
2.	Your institution has PHS funded grants, AAALAC accreditation, using only purpose bred Mus musculus; which of the following regulation WILL NOT apply?
a.	The PHS policy on Humane Care and Use of Laboratory Animals (PHS Policy)
b.	The Guide
c.	AVMA Guidelines on Euthanasia 
d.	The Animal Welfare Act (9CFR)
3.	Which of the following publications AAALAC International relies on as its PRIMARY standard for evaluating laboratory animal care and use programs. 
a.	Guide to the Care and Use of Experimental Animals.
b.	The Guide for the Care and Use of Laboratory Animals, NRC 1996
c.	FELASA Guidelines
d.	None of the above

ANSWERS:
1.	c
2.	d
3.	b

Dale.  Postapproval Monitoring and the Role of the Compliance Officer, pp. 393-401

SUMMARY: The Institutional Animal Care and Use Committee (IACUC) and Institutional Official (IO) of animal research institutions is charged by multiple federal regulations to provide program oversight, including training of animal users and compliance with approved protocol procedures.  A well-administered Post Approval Monitoring (PAM) program is one way that the IACUC and the IO can meet this requirement.  The most frequent concern expressed by USDA inspectors has been inadequate post approval monitoring.  The monetary and public relations costs of noncompliance can far exceed the resources required to fund PAM.  Regrettably, many PAM programs are not funded until a serious, costly noncompliance has occurred.

PAM programs should be administered by a Compliance Officer (CO).  This person should be familiar with research procedures and animal care and use, but should not be, report to, or even share office space with the veterinary staff.  The CO and his or her quality assurance coordinators must be able to interact collegially with investigators and to present themselves as a resource rather than a dictator or police officer. The compliance office should interact with the IACUC (providing compliance reports at monthly IACUC meetings), should keep the IO apprised of noncompliance, and should also interact with the facilities and occupational health and safety staff, in addition to the veterinary and husbandry personnel, media relations, federal agencies and AAALACi.

PAM is best performed by face to face visits. The goal of PAM should be to ensure that animal use protocols are complete, up to date and being followed, to ensure appropriate training (and retraining where required), and to provide post-visit documentation to the PI, staff and IACUC (including findings and outcomes). Quality assurance officers should act as liaisons between investigators and other institutional groups to ensure follow-through.  Visits should include protocol and administrative review, observation of research procedures, postprocedural review (including the need for any protocol amendments). The compliance office must stay abreast of advancements in animal care and use and regulatory changes. When noncompliance occurs, the compliance office should facilitate the institution's efforts to work through issues.  
 
QUESTIONS: 
1.	True or False?  The best way to maximize the efficiency and effectiveness of PAM is to have a member of the veterinary staff be the CO.
2.	The most frequent concern expressed by USDA inspectors is
a.	Controlled drug violations
b.	Inadequate veterinary care
c.	Inadequate medical records
d.	Inadequate PAM
e.	None of the above
3.	True or False?  PAM is best performed using frequent telephone contact and e-mail.

ANSWERS:
1.	False. The CO should not even share office space with the veterinary staff.
2.	d. Inadequate PAM
3.	False. PAM is best performed with face to face visits.

Banks and Norton.  A Sample Postapproval Monitoring Program in Academia, pp. 402-418

SUMMARY: The primary goal of the Animal Care and Use Program (ACUP) is to ensure animal well being while fostering progress in science. Both Animal Welfare Act (AWA) and the Public Health Service (PHS) Policy require the Institutional Animal Care and Use committee (IACUC) to provide oversight of the animal program. Semiannual assessment is a snapshots and does not provide an opportunity to observe research procedures being performed and most of the IACUC members are volunteers and unable to dedicate sufficient time.  

Post-approval monitoring (PAM) is additional tool that can contribute to the IACUC oversight. PAM is not explicitly required by the regulations. The most successful ACUP programs are the one where researchers believe that they are partners in the IACUC and PAM can be used as a tool to foster this process.

Reasons for noncompliance are: dangerous species, infective and hazardous agents, reactive chemicals, personnel that fails to adhere to the protocol, experimental drift overtime insufficient funds among many others. There are three general organizations for PAM:
1.	Attending veterinarian (AV)
2.	IACUC members or staff performing PAM
3.	Compliance office-based PAM which is probably the best model as it is less likely for them to have conflict of interest, dedicated personnel to assist the IACUC, and the AV to focus on their duties.

Ensure complete PAM coverage such as Veterinary and Husbandry staff, species and locations, organization and management. Unannounced audits may be needed in case of allegations against the researcher or an IACUC concerns. Resources that are needed are: trained personnel, finances, computer resources and access to the Standard Operative Procedures. 

PAM Methods. The audit has to be base on the specific content of the approved IACUC protocol and the “performance approach” focusing on the outcome:
1.	Advanced review of an approved protocol 
2.	Comparison of animal numbers
3.	Entrance interview with researchers
4.	Inquiries about any unexpected deaths or other adverse events
5.	Review of procedure records  for consistency wit approved protocols
6.	Review of animal use areas to assess proper animal care
7.	Review of proper ;laboratory training records
8.	Confirmation of appropriate medical surveillance participation 

PAM Procedure observations:
1.	Observation for the presence and condition of necessary equipment and supplies. 
2.	Husbandry and care practices for animals before, during, and after procedure.
3.	Animal manipulations.
4.	Transport of animals between housing and experimental areas. 
5.	Personnel qualifications in the procedure performance
6.	Review confirmation

Surgical observations:
1.	Appropriateness of the physical plant
2.	Housekeeping procedures
3.	Drug inventory and use
4.	Personnel skills and training
5.	Emergency protocols for adverse procedural events
6.	Anesthetic equipment and scavenging, anesthetic and analgesic regimen
7.	Post-procedural monitoring, nursing, and supportive care
8.	Overall conduct of major surgeries
9.	Review confirmation

Animal and critical care:
1.	Room checklist, safety sheets, emergency call rosters, and other documents.
2.	Review of animal disease report for indication of animal distress
3.	Proper equipment and resources
4.	Enrichment records.

Tips: be a Liaison and not a animal police, partner for culture change when necessary, keep it simple and without bias
	
Examples of Communication Letters are included (Box 1-5 and Table 1): initial, post visit, oral report, post-IACUC meeting decision Memo, trend report. 

QUESTIONS:
1.	Is the semiannual inspection sufficient to provide adequate compliance monitoring?
2.	Name three organizational structures of PAM.
3.	Name few methods that can be used for PAM process.
4.	What are the few areas where PAM has to put emphasis on the Procedure observations. 
5.	What are the few areas where PAM has to put emphasis on the Surgical observations.
6.	What are the few areas where PAM has to put emphasis on the Animal and critical care.

ANSWERS:
1.	No. Semiannual inspection is representative of a snapshot inspection?
2.	See text for questions 2-6

Plante and James.  Program Oversight Enhancements: The Other PAM, pp. 419-425

SUMMARY
·	Federal animal welfare regulations and policies require compliance during animal research but the how is left up to the IACUC
·	Post-approval monitoring (PAM)
o	not federally mandated
o	audit ongoing animal use activities against their approved protocols
o	performed by trained and qualified individuals on behalf of the IACUC i.e. compliance officers or research liaisons
o	AAALAC has traditionally engaged in PAM during triennial site visits
o	successful in spot-checking compliance in the following areas: (1) protocol compliance, (2) research staff's familiarity with and participation in the OHSP; (3) scope and quality of investigator training, and (4) policy and procedure comprehension
·	Is PAM a value-added activity?  Depends on...
o	current level of compliance
o	institutional support
o	team dedication
o	program size and structure
o	financial and personnel resources
o	effectiveness of other mechanisms for ensuring compliance
·	Program Oversight Enhancements (POE) (2 categories)
o	Those that employ institutional and IACUC oversight mechanisms
§	Federally mandated mechanisms such as: 
§	the Institutional Official (strong support from the IO plays an important role in ensuring IACUC commitment and investigator compliance); 
§	the IACUC (selecting the right mix of individuals is a sound investment of time and effort); 
§	training programs (relevant publications, web-based tutorials, IACUC-sponsored information sessions, and internal and external training forums; 
§	IACUC policies and procedures (IACUC can promote compliance only as well as it can communicate to researchers and other animal care and use personnel) such as (1)Global information: Institution wide information applicable at all sites/satellite facilities, (2)IACUC internal information: secure information accessible only to IACUCs and their administration, (3)Site-specific information: Multisite institutions typically have different policies and procedures customized to their unique programs that must be communicated to researchers
§	Enhancing mandated IACUC oversight standards with:
§	Protocol review, 
§	Amendment review, 
§	semiannual program review and facility inspections, 
§	unexpected outcomes (i.e. unanticipated or unpredicted adverse events such as mortality, morbidity, or increases in pain and distress)
§	Investigative staff and veterinary and animal care personnel should clearly understand their obligation to recognize unexpected study outcomes and to alert the IACUC if they occur.
§	Mechanism for reporting animal welfare concerns    
§	hotline
o	Those that do not rely directly on the IACUC 
§	Clearly defined organizational chart
§	Can expedite the resolution of noncompliance issues by clearly indicating whom to notify
§	Research Personnel
§	All animal research staff should have access to and be familiar with both their assigned responsibilities and approved animal use protocols
§	Only when all team members are fully knowledgeable about animal use activities can compliance be ensured
§	Animal support staff personnel
§	A vigorous, diverse and well-trained animal support staff is one of the most vital components of the animal care and use program
§	Animals’ “first line of defense”
§	Provide appropriate training and education about animal husbandry, basic veterinary care, and the research being conducted and the approved animal activities in their areas of care
§	Inherent Safeguards
§	Animal use personnel must have a sound understanding of the IACUC approval process and must be proficient in the techniques they are approved to perform
§	Help to prevent unapproved activities and minimize animal use mishaps
§	Centralized Animal Ordering/Census
§	Animal procurement and census management software should be used to track animal usage back to the approved protocol
§	Safeguards: Blackout dates, approval expiration alerts, and cross checks with approved protocols
§	Medical records maintenance and review
§	Development, maintenance, and storage of medical records should be managed by animal support staff.
§	Centralized drug dispensing
§	Safeguard against the use of unapproved drugs
§	Restricted access to animal facilities
§	Centralized facilities
§	Limiting use of labs and areas outside of the centralized animal facilities will facilitate frequent daily monitoring of the animals and activities by animal support staff
·	Conclusion: a formal PAM process is not a regulatory requirement, but it can be a valuable tool for assessing overall program health as well as ensuring compliance with IACUC-approved activities, which is clearly mandated.

QUESTIONS:
1. 	The following are all federally mandated mechanisms regarding POE except:
a. 	Institutional Official
b. 	IACUC 
c. 	Non-scientist
d. 	Training programs
e. 	All of the above
2. 	PAM is successful in spot-checking compliance in what 4 areas? 
3. 	What are the two categories of POE?
 
ANSWERS:
1. 	c
2. 	(1) protocol compliance, (2) research staff's familiarity with and participation in the OHSP; (3) scope and quality of investigator training, and (4) policy and procedure comprehension
3. 	(1)Those that employ institutional and IACUC oversight mechanisms; (2) Those that do not rely directly on the IACUC

Haywood and Greene.  Avoiding an Overzealous Approach: A Perspective on Regulatory Burden, pp. 426-434

Role delineation : 
1	Domain 3: Research
2	Domain 4: Animal Care
3	Domain 5: Regulatory Responsibilities

SUMMARY: The authors discuss the impact of regulatory burden on the “oversight mosaic” inherent to animal care and use programs, identifying three sources of regulatory burden and evaluating how institutions often –and unnecessarily- over-respond and therefore over-burden their researchers in efforts to create the ideal program.  The three sources of regulatory burden are (1) specific requirements in law and regulation, (2) interpretive requirements or “guidance” by regulatory agencies, and (3) self-imposed regulatory burden resulting from institutional interpretations.  Institutions should recognize that some legally mandated regulations intended to protect animals may actually do little to contribute to the animals’ health and well-being, and some policies and guidance issued by oversight entities extend beyond the regulations, without any basis in law, and may or may not benefit research subjects.  As for self-imposed regulatory burden, many institutional administrative reactions to agency-promulgated policies and guidance are overzealous and lead to excessive internal procedures in the quest of establishing “best practices.”  Reference is made to the NIH Initiative to Reduce Regulatory Burden (undertaken about a decade ago due to Congressional mandate), and one of its recommendations that the research community consider that much of the burden was the result of its over-interpretation of regulations and policies.  Most institutions do not distinguish between “guidance” and “regulation,” so both become de facto requirements.  Latitude in the application of policies and regulations that guide oversight of animals in research, teaching, and testing leaves room for the implementation of best practices and professional judgment, but institutions should balance risk and regulatory burden.  However, because there is little tolerance for risk in the research community, few institutions take the time to weigh the risks associated with implementing best practices that are beyond requirements for compliance against the actual policies and regulations.  

Risks associated with self-imposed regulatory burden include:
1.	Alienation of scientists and attempts to avoid compliance
2.	Difficulty in recruiting new scientists to the institution
3.	Avoidance of using animals in research due to the increased cost of compliance
4.	Missed funding opportunities and failure to pursue potentially important research that must be done in animals
5.	Diversion of money available for the actual care of animals to compliance efforts that may have little if any impact on animal welfare

After explaining how overzealous approaches have led to an increased and unnecessary burden on animal care programs, the authors discuss how the appropriate assessment of risk factors can allay the burden.  Through presentation of case studies and specific examples (including a nice laundry list of self-imposed regulatory burden items), the authors offer suggestions to consider in assessing risk and burden in institutional animal care programs, including the suggestion that IACUC’s use the following three questions to assess the necessity of practices:  
1.	Why do we do this?
2.	Does it help the animals?
3.	Can the end be achieved in a more efficient, cost effective manner?

QUESTIONS:
1. 	Which of the following is not one of the three sources of regulatory burden identified by the authors?
a. 	Specific requirements in law and regulation
b. 	Interpretive requirements or “guidance” by regulatory agencies
c. 	Standards of care or best practices within the field 
d. 	Self-imposed regulatory burden resulting from institutional interpretations 
2.  	What was the NIH study undertaken approximately a decade ago to study the impact of regulations in five areas of research compliance, including animal care and use? 
a. 	The NIH Initiative to Reduce the High Cost of Research
b. 	The NIH Initiative to Reduce Research Redundant Paperwork
c. 	The NIH Initiative to Identify Best Practices
d. 	The NIH Initiative to Reduce Regulatory Burden
3. 	Which of the following is not one of the risks associated with self-imposed regulatory burden?
a. 	Alienation of scientists and attempts to avoid compliance
b.  	Difficulty in recruiting new scientists to the institution
c.  	Avoidance of using animals in research due to the increased cost of compliance
d. 	Missed funding opportunities 
e. 	Failure to pursue potentially important research that must be done in animals
f.  	Compromise of the scientific quality of research
g. 	Diversion of money available for the actual care of animals to compliance efforts
4. 	Which of the following is NOT one of the questions the authors suggest that IACUC’s use to assess the necessity of practices?
a. 	Why do we do this?
b. 	Does it help the animals?
c. 	Can the end be achieved in a more efficient, cost effective manner?
d. 	Is this a standard of care or best practice for this area?
 
ANSWERS:
1.  	c. 	Standards of care or best practices within the field 
2.  	d. 	The NIH Initiative to Reduce Regulatory Burden
3.  	f.  	Compromise of the scientific quality of research
4.  	d. 	Is this a standard of care or best practice for this area?