How to Write an Animal Care and Use Protocol

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How to Write an Animal Care and Use Protocol

• David Lyons, Ph.D.
• Asst. Dir. Animal Care and Use

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(No Transcript)
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Why Animal Welfare?

• To protect creatures who cannot speak for
  themselves
• To uphold community standards
• For the best science

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Where do you stand?
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1960s The Animal Welfare Act (AWA)
Life Magazine, 1966
Pictures Talk
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AWA Protections for pets and more
MED SCHOOL ESCAPE. He Has no fancy bloodlines,
but to the Thomas Connolys of New- ton, Mass.
Lancer is the family pooch. The dog was picked
up and impounded one day after delivering the
Connolly children to school. After 10 das he was
sold to Harvard Medical School.
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National Oversight

• U.S. Department of Agriculture (USDA)
• U.S. Department of Health and Human Services,
  Public Health Services (PHS), NIH, Office of
  Laboratory Animal Welfare (OLAW)
• Association for the Assessment and Accreditation
  of Laboratory Animal Care International (AAALAC)

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Morphed into MMORP (Massively Multi-player Online
Role Playing)
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Regulatory Structure Alphabet Soup
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The Guide

• Primary How to book for animal research

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U.S. Government Principles for the Utilization
and Care of Vertebrate Animals Used in Testing,
Research, and Training

• Proper transport
• Relevant to human/animal health or basic
  knowledge
• Proper species and numbers
• Avoidance of pain and distress
• Proper analgesics and anesthetics
• Painless death
• Proper husbandry
• Proper training of researchers
• Exceptions approved by IACUC, rather than
  researcher

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3-Rs

• Reduce the number of animals being tested
• Refine the methodology used, this implies the
  notion of end-points
• Replace the animal models

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1-5. Header items

• 1. Contact Info
• 2. Title New or Replacement
• 3. Project Support Federal Grant, Industry
  project, in-house funding
• 4. External Scientific Review
• 5. Internal Scientific Review

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6. Training and 7. Occupational Health Program

• 6. PI and those who touch animals
• Trained for species
• Trained for procedure
• Occ Hlth Pgm by species
• 7. For those who handle tissues and samples only
• Occ Hlth Pgm

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8. Lay Summary and 9. Specific Aims

• 8. Write Lay Summary in 200 words or fewer for an
  8th grade audience. Used by
• the lay committee member during review
• Public Relations for talking points to the media
• 9. Specific Aims Helps orient reviewer

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10. Design and Grant Pages

• 10. Simple description of experimental design
• Basic details of animal expts
• Clearly show the role for each experimental group
  of animals and the number of animals in each
  group
• Be concise and complete
• Use bullets, tables, short-hand, etc. to get to
  the point fast
• Must provide grant pages Key pieces of Research
  Plan and Vertebrate Animal section
• ACUC must approve transport through public areas

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11. A-B Animal Use

• 11.A. Animal Transfers
• 11.B Animal Table
• Breakdown by Group
• Show animal transfers
• Special cases
• Replacement protocols Remove animals already
  used and killed transfer animals in house
• Breeding colonies Include breeders, animals
  culled but not used as experimental subjects,
  include culled preweanling animals
• Pain/Distress categories
• C, D, E Watched carefully by the USDA

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11.C. Preweanling animals

• Important for breeding colonies

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11.D. Animal Rationale and Species

• Why must animals be used?
• Bad Answers
• cuz I can
• cuz I always have before
• cuz its all that I can afford
• Good Answers
• The science requires an intact animal
• No other means are available
• Why this species?
• Good Answers
• It is the next natural step to goal
• It is the best model

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11.E. Animal number justification

• Do
• Power Calculations
• Cite similar studies
• Note pilot work
• Dont
• Base it on your years of experience
• Replicate experiments already justified by power
  analysis (except in rare cases)

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11.F. Animal Study Areas

• Non-ARP space where live animals are used
• ACUC must visit

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12.1-3 Drug Tables

• 12.1 Anesthetic drugs
• Additional intra-operative monitoring required
  when paralytics are used
• 12.2 Analgesic drugs
• Indicate analgesic/euthanasia to guide emergency
  care
• 12.3 ALL other agents (drugs, biologicals,
  etc.)
• RESOURCE Drug formulary by species on ARP web
  site

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13. Dietary Manipulations

• Important to USDA
• Food and Water restriction policies require
  specific documentation
• Body weight
• Actual daily food and water intake

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14. Surgical Procedures -Key Concepts I

• Survival vs. Non-survival
• Animals awake after survival procedure
• Major vs. Minor
• Major surgery enters a body cavity or produces
  permanent impairment
• Single vs. Multiple
• MMSS must be approved by IACUC
• USDA must approve MMSS in second protocol

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14. Surgical Procedures -Key Concepts II

• USDA-regulated animals vs. Mice, rats birds
• Unique facility regs for operative areas
• Peri-operative procedures
• Pre-operative analgesics
• Intra-operative monitoring
• Post-operative care Documenting stages of
  recovery and pain management
• 15. Non-surgical anesthesia

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14. 15. Stumpers

• Frequency of animal monitoring
• Magic words are on protocol form Post-surgical
  monitoring of animals should occur every 30
  minutes throughout stage 4 of recovery, 6-10
  hours throughout stage 3, and then daily.
• Signs of distress monitored
• Be specific
• Use signs of pain noted in ACUC policies
• Demonstrate thoughtful preparation for pain
  management by setting clear triggers

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16. Pain/Distress

• If an animal in this study were not anesthetized,
  would the animal feel more than momentary or
  slight pain or distress if exposed to the
  procedures proposed in the protocol?
• Will the animal experience unrelieved pain as
  part of the study?
• If yes, the rationale must be well documented.
  -Very important to the USDA.
• Literature search required
• Purpose of search is for alternatives to painful
  or distressing procedures
• Examples
• Replace surgical observation with MRI
• Replace production of antibodies via ascites with
  in vitro production
• Replace indwelling vascular catheter for HR/O2
  measurement with finger-tip pulse-oxymeter.

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17. Prolonged restraint

• Prolonged restraint vs. Restricted activity
• Prolonged restraint More than 12 hours
• AWA Exception
• Example small cage size
• Restricted activity partial immobilization for
  more that 20 minutes in awake animals
• Must document behavioral methods of acclimation
• Example NHP chair for behavioral studies
  requires training of animal

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18. Criteria for removal

• Demonstrate thoughtful preparation for excluding
  animals by setting clear triggers
• Make reasonable effort to anticipate adverse
  events
• Be specific, e.g., 25 loss of BW, hematocrit at
  40.
• Removed animals do not return
• Death is not a criteria for removal

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19. Euthanasia

• Describe for planned and unplanned
• Comply with AVMA Report of 2000
• CO2 in rodents requires secondary method

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20. Animal Housing

• Central vs. Satellite
• Satellite is
• the responsibility of PI
• held to same standards as ARP
• approved by the ACUC
• inspected by ACUC prior to use

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21. Hazardous Agents 22. RadioisotopesKey
Concepts

• Bio v. Chem v. Rad
• Biologicals DNA, cells lines, viral vectors,
  etc.
• Must consider risk to public, researchers, animal
  care staff and animal populations
• Cell lines must be tested for animal and human
  pathogens
• May require separate approval from biosafety,
  chemical safety committee or Radionuclide in
  Live Animals form

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23. Environmental Enrichment

• Nonhuman Primates
• Separate form with specific requirements
• Single housing of any animal requires
  justification and plan for enrichment

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24. Canines

• Non-standard housing is AWA exception
• Dogs must be exercised

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25. Source of Animals

• Non-commercial sources
• Special procedures for procuring animals from
  other schools or research facilities
• Transgenic animals
• May have special needs
• Breeding colonies
• Makes special demands on researchers and ARP
• Purpose of vet signature is related to source and
  housing of animals, NOT review of entire protocol

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26. Signature Conflict of Interest Disclosure

• PI signature
• Personal financial relationship with research
  sponsor or personal financial interest in
  research outcome must be disclosed here and
  ultimately managed.