FOCUSONANIMALWELFARE IMPROVEMENT - CCAC · imon Authier, DVM, MBA, PhD By: S of Veterinary Science and Safety Pharmacology irector D April 2012 FOCUSONANIMALWELFARE IMPROVEMENT

By: Simon Authier, DVM, MBA, PhDDirector of Veterinary Science and Safety Pharmacology

April 2012

FOCUS ON ANIMAL WELFAREIMPROVEMENT

FOCUS ON ANIMAL WELFAREIMPROVEMENT

Focus on Animal Welfare Improvement

Anthropomorphism: Harms and Benefits

Evidence Based Ethical Review

Risk Assessment: Beyond categories ofInvasiveness

Adverse Event Reporting: New Generation of PAM

Conclusions

Presentation Plan

From the lab to bedside…

Focus on Animal Welfare Improvement

Diversity of IACUCmembership

CommunityRepresentative(s)

Facility team

Scientists

Veterinarians

Diversity of EthicalReview Concepts

• Moral Principles

• Consequentialism

• Evidence BasedReview (EBER)

Animal WelfareRisk Assessment

• Surgery, analgesiainvasive procedures

• Recurrent issues

• Program weaknesses

• Critical periods(night/weekends?)

Program Monitoringand… Support

Technical support

Sharingbest practices

Approval Monitoring

ImprovedAnimal Welfare

Ethical Review

Diversity of Concepts Applied to Ethical Review

As Animal Ethic Committee members, which approachshould we take to assess scientific or regulatory merita project:

Deontology: Judgement based on adherence to rules

Moral Principles or moral laws (Emmanuel Kant)

Regulatory testing is based on international guidelines

Ethical Review


As Animal Ethic Committee members, which approachshould we take to assess scientific or regulatory merita project:

Utilitarianism or “greatest happiness principle” (JeremyBentham and John Stuart Mill)

Weighing the benefit and cost (3Rs)

Medical progress and development of new therapieswith animal welfare as a priority

Ethical Review


Discourse ethics (Jürgen Habermas)

• An ideal speech situation occurs when:• 1. Every individual with the competence to speak and act is

allowed to take part in a discourse.

• 2a. Everyone is allowed to question any assertion whatever.

• 2b. Everyone is allowed to introduce any assertion whateverinto the discourse.

• 2c. Everyone is allowed to express his attitudes, desires andneeds.

• 3. No speaker may be prevented, by internal or externalcoercion, from exercising his rights as laid down in (1) and (2)

Ethical Review


Is anthropomorphism present during ethical reviewof animal use protocols?

Should ethical review concepts be universal oradaptated to local characteristics?


Anthropomorphism

Definition and Value

Merriam-Webster: Anthropomorphism: Interpretation ofwhat is not human in terms of human characteristics.

“There is quite a difference between the use ofanthropomorphism as a tool, to generate hypotheses andanthropomorphism that does little else than projecthuman emotions and intentions onto animals without anattempt at justification, explication or seriousinvestigation.” (Anthropomorphism, Anecdoctes andAnimals, Mitchell, Thompson and Miles, New York StateUniversity Press 1997)

Anthropomorphism

The Good and the Bad

Benefits:

• Helps to seek the highest standards for animal welfare

• Source of motivation and empathy

Bads:

• May divert IACUC team from efforts to understandspecies needs

• Could confine protocol revision into subjectiveconsiderations (personal point-of-view)

• May prevent progress if used as leading concept duringethical review of animal use protocols

Evidence Based Practice

Evidence-based practice (EBP) aims to apply the bestavailable evidence gained from scientific method todecision making (Wikipedia). EBP is formally included inmodern medicine programs around the world.

Can this concept be applied to animal research protocolreview?

Should this concept be applied to animal researchprotocol review?



IACUC committees work for continuous improvementof procedures and the animal care program.

• What is our process for periodically reviewing animalwelfare literature to summarize key concepts and betterinform IACUC members on essential topics?

• Is the scientific literature appropriately addressingethical questions and concerns of the IACUC?




Ifthe literature is imperfectly answering ethical questionsand concerns from the IACUC:

Can we conduct in-house animal welfare research toanswer specific animal welfare questions?

Each institution gains considerable experience with simpletrials related to animal welfare:

• Types of housing

• Enrichment devices

• Endpoints

• Food and water schedules

• Analgesia protocols

• Etc.


Could we share efforts and results from eachinstitution to address animal welfare concerns withother institutions and maximize resource utilization

What are the limitations to share local animalwelfare research experience?

Would a secure and anonymous IACUC socialnetwork be useful?

Could we foster animal welfare by sharing thesesimple local experiences with a national platform



Published literature review:•Abundant representation of the scientific perspective

•Modest representation of the veterinary perspective

•Scarce representation of the technical perspective

•Nearly Inexistant published documents from communityrepresentative

IACUC social network:

•Platform to share results of simple assessments

•Easier to publish (compared to peer reviewed articles)

•Scientists, community representatives, technicians, vets,etc.


Experimental Context and Ethical Considerations

–Context: Non human primates are social animalsnormally housed with cagemate(s).

–Should a non-human primate be singly-housed whenthe cagemate needs to be assigned to a project for ashort period?

–Hypotheses: 1) A new cagemate may increase stressfor the non human primate. 2) A new cage-mate maydecrease the separation anxiety.

Animal Welfare Research

Study Design

–Three (3) cynomolgus monkeys with telemetry EEGmonitoring (3-4 yrs old)

– Beta waves: anxious thinking

Day 1 Day 2 Day 3 Day 4 Day 5

housedknowncagemate(morethan 3months)

Single-housed Single-housedPair-housednew cagemate

Pair-housednew cage mate


5E-06

0.00001

0.000015

0.00002

0.000025

0.00003

19:00:00 21:24:00 23:48:00 02:12:00 04:36:00 07:00:00

mV

Time

EEG Beta power by telemetry in cynomolgus monkeys (n=3)

Pair-housed

Single housed

Anxiety


6E-06

0.000011

0.000016

0.000021

0.000026

19:00:00 21:24:00 23:48:00 02:12:00 04:36:00 07:00:00Time


Pair-housed known cage mate

Single-housed night first night

Single-housed second night

Reduction of anxiety at 2nd night


5E-06

0.00001

0.000015

0.00002

0.000025

0.00003

19:00:00 20:12:00 21:24:00 22:36:00 23:48:00

Time


Pair-housed known cagemate

Single-housed 1st night

Single-housed 2nd night

Pair-housed new cagemate 1st night

Pair-housed new cagemate 2nd night

New cagemate:limited anxiety


Conclusions

• For young and socially housed animals, it isgenerally preferable to introduce a new animalwhen the cage-mate needs to be temporarilyassigned to a study.

Beyond the project:

• There are exceptions and some animals may beless socially compatible.

• Careful monitoring when introducing a new cagemate is definitely warranted.

Milestones to Evidence Based Ethical Review

Literature Review: Are IACUCs sufficiently active?

Animal welfare literature is available.

Review of scientific literature by researchers istargeting experimental endpoints and specific toeach project.

IACUC committees (and consequently animals)benefit from active review of animal welfare literaturerelated to experimental procedures but also to theanimal care program with discussion amongstmembers.


Animal welfare research can help address ethicalquestions that cannot be solved with discussions only.

Animal welfare research can be very simple trials withnew enrichment devices or refinement to procedures andcan be formalized and possibly added as an item on theagenda for IACUC meetings.

Should we have an Animal Welfare Research Plan?

Milestones to Evidence Based Ethical Review

Are IACUCs worldwide spending too much time reviewingdetails from the same animal use protocols year after year

Could we establish an Institutional Animal WelfareResearch Plan:

•During the IACUC meeting: Identify areas of possibleanimal welfare improvements

•Propose modest trials to evaluate the impact on animalwelfare

•Mandate an IACUC member (vets, investigator ortechnician) to perform assessments (simple or complexe)

•Present results of the animal welfare research at the yearlyAnimal Care Program review meeting

Animal Welfare Research Plan

Animal Welfare Risk Assessment

Strategies for risk mitigation?


• Categories of invasiveness alert investigators,animal care committees (ACCs) and thoseresponsible for animal care to procedures wherethere is a risk of animals being exposed to painand distress. (Griffin, Dansereau and Gauthier,AATEX 14, Special Issue, 715-720, 2008)

• Categories of invasiveness are informative andessential… but how can we further assess andeventually mitigate the risk of animal welfarebreach?


How can we further assess and mitigate the risk ofanimal welfare breach?

Identification of higher risk areas:

Project specific (e.g. special technique or model)

Project independent (e.g. animal monitoring)

Key questions:

Where and When are we more susceptible to fail inpreserving animal welfare?

What can we implement to prevent failure?


Focus on higher risk areas

•Animal monitoring outside regular working hours

• Suggest early surgery for longer post-op monitoring?

• Discourage invasive procedure during weekend?

•On-call system: investigator, veterinarian or senior studentavailable by phone?

•Analgesia

• Pain is maximal shortly after surgery, normally with rapidattenuation:

• Add opioate once immediately after surgery?

• Local analgesia immediately at end of surgery?

A New Generation of PAM


•Adverse event reporting

• In the drug industry, postmarketing surveillance uses anumber of approaches to monitor the safety of licenseddrugs… (Wikepedia)

• Post-approval monitoring (PAM): Compliance withapproved protocols… but was the risk for animal welfarefully captured in the protocol?

• Breaches to animal welfare are unpredictable and mayemerge in presence of protocol compliance…


Adverse event reporting

•Should adverse events be reported at the animal useprotocol renewal? Will this be too late?

•Adverse events need:• Immediate reporting• Immediate corrective actions

•Do we have a formal procedure to report and manageindividual animal adverse event?

•Most institution have formal disaster recovery plans forpower failure, fires or flooding but individual animaladverse event reporting is often informal.



Do we have a formal procedure to report and manageindividual animal adverse event?

•Definition of animal adverse events

•Immediate notification to Veterinarian and IACUC Chair

•Investigation of the adverse event

•Identification of a sub-group to manage the adverse event(composition, authority, availability, etc.)

•Immediate corrective action plan as needed

•Communication to IACUC members at the next meeting

•Annual compilation of adverse events observed with analysisfor proactive improvements (to prevent reoccurence)


Evidence based ethical review

• Literature review: Stimulate IACUC participation

• Animal welfare research

• Trials to improve animal welfare

• Share results (need an IACUC social network

Risk assessment: Focus on higher risk areas(Monitoring, on-call system, analgesia, etc.)

Reporting of adverse event: Formal procedure,immediate response and proactive analysis

Presentation Highlights

Focusing on Animal WelfareImprovements!

Focusing on Animal WelfareImprovements!

Papers and emails can always wait…Papers and emails can always wait…

Documents

FOCUSONANIMALWELFARE IMPROVEMENT - CCAC · imon Authier, DVM, MBA, PhD By: S of Veterinary Science and Safety Pharmacology irector D April 2012 FOCUSONANIMALWELFARE IMPROVEMENT