Can Work Continue on an Animal Protocol Without Naming a New Pi

A. Changes in Scope of Grant

The terms "significant change" and "change in scope" have different meanings. According to NIH Grants Policy Statement (GPS), change in scope refers to a change in the direction, type of research or training from the aims, objectives, or purposes of the approved project. A change in scope requires notification to the NIH funding component. However, a significant change is not necessarily a change in scope.

GPS: In general, the PI may make changes in the methodology, approach, or other aspects of the project objectives. However, the grantee must obtain prior approval from the NIH awarding Institute/Center (IC) for a change in scope. The grantee must make the initial determination of the significance of a change and should consult with the Grant Management Officer (GMO) as necessary.

Potential indicators of a change in scope include, but are not limited to, the following:

• Change in the specific aims approved at the time of award
• Substitution of one animal model for another
• Change from the approved use of live vertebrate animals
• Shift of the research emphasis from one disease area to another
• Application of a new technology, e.g. changing assays from those approved to a different type of assay

B. Funding

Examples of internal funding include (but not limited to): departmental funds, startup funds, Howard Hughes Medical Institute (HHMI).

Examples of external funding include (but not limited to): NIH, American Heart Association, American Diabetes Association, etc.

C. Is this person performing surgery?

Surgery is defined as the disruption of any integumentary surface of a living animal by any means other than a hypodermic needle, biopsy needle, ear punch, or tail snip on rodents prior to weaning.A procedure is considered surgical when it involves cutting of a tissue or closure of a wound. Other procedures may be considered surgery if they involve "common" surgical procedure or settings, such as use of a sterile environment, anesthesia, analgesia,  aseptic conditions, typical surgical instruments and suturing, surgical adhesives or stapling. Techniques used for animal identification such as tattooing, tail snip, toe clip and ear punches will not be considered surgery.

D. Instructional Course

An instructional course is part of the University curriculum and does not include training of laboratory personnel for procedures to be used in the Animal Protocol.

E. Literature Search

A search of appropriate database(s) of published studies is one way to evaluate whether alternatives to animal testing are available. Guidance on performing a database search has been developed by librarians at the Hardin Library for the Health Sciences to assist animal users with performance of an appropriate search for animal testing alternatives.

A step-by-step worksheet for performing a literature search for alternatives has been compiled by the USDA, and is available here.

F. Overall/Program/Training Protocol Definitions

Overall Project:  When a large project grant gets funded, only a portion of it may involve animal work.  The money may come into a University Center or an individual PI (i.e. main awardee) who has  various PIs responsible for certain projects under the main grant.  The main grant (encompassing all projects) is typically tied to what is called an "Overall" Animal Protocol approval.  The Overall is a sort of landing-place for the grant, and does not outline any animal work.  The specific projects involving animal work are tied to separate Animal Protocol approvals under the corresponding PIs.

Center/Program project :  A grant for which there is a common theme (e.g. heart disease) but for which there are multiple projects that may be done by any number of Co-PIs under the main grant.  The grant typically has a Primary awardee and comes into the University as a "Center/Program grant".  The grant will have a "P" such as P01, P20, etc  in the grant ID number.  The main grant (encompassing all projects) is typically tied to what is called an "Overall" Animal Protocol approval.  The Overall is a sort of landing-place for the grant, and does not outline any animal work.  The specific projects involving animal work are tied to separate Animal Protocol approvals under their corresponding PIs. The PIs involved in this type of grant, should refer to the Center/Program grant and the PI named as the primary PI (so that the funds can be appropriately followed back to the main grant).

Training Grant :  A grant that geared to training students, post-docs, faculty, etc for which there is a common theme (e.g. heart disease).  Only a portion of the grant may involve animal work.   The money may come into a University Center and subsequently be distributed to the various PIs responsible for certain projects.  The grant will have a "T" such asT32 in the grant ID number.  The main grant (encompassing all projects) is typically tied to what is called an "Overall" Animal Protocol approval.  The Overall is a sort of landing-place for the grant, and does not outline any animal work.  The specific projects involving animal work are tied to separate Animal Protocol approvals under their corresponding PIs. The PIs involved in this type of grant, should refer to their protocol as a Training grant.

G. Animal Housing Location

Examples of other locations where animals may be housed include but are not limited to: Iowa State University, Marshall Farms and Exemplar Genetics.  Non-OAR satellite housing facilities are to be described in "Will animals be housed outside of OAR animal facilities for longer than 12/24 consecutive hours?"

H. Adverse Phenotype

Some examples of adverse phenotypes and common methods to humanely manage those phenotypes include (but are not limited to) the following:

• Frequent deaths around weaning age due to small size at normal weaning age (21 days old)
  • Delay weaning until 28 days old (or longer if needed)
  • Provide gruel in breeding cage for one week prior to weaning
• Paresis or paralysis
  • Separate affected animals from cage-mates that are unaffected (to reduce competition for food and water resources)
  • Provide gruel daily on cage floor for easier access to food
• Spontaneous tumor development
  • Gruel may be provided daily if tumors lead to cachexia (muscle wasting/decreased body condition)
  • Managed by increased monitoring and adhering to humane endpoint limits
• Ulcerative skin lesions (ulcerative dermatitis)
  • Provide daily supplement of Vitamin E and omega fatty acids (DermaForm liquid) provided on gruel in a dish on the cage floor – Recommended

Consult with Office of Animal Resources veterinarians for recommendations on how to manage other adverse phenotypes.

I. Drugs and Substances

Any experimental substance (drugs, test substances or compounds administered to an animal by any route) that IS NOT an anesthetic, analgesic, or used for supportive care (such as fluids post-operatively) should be listed and described in this table. Additional rows can be inserted into the table as needed to provide space as needed.

J. Will any special husbandry or housing conditions be required for this project?

Any special husbandry and housing conditions must be approved by the IACUC.  The Office of Animal Resources (OAR) must be contacted prior to the start of any experiment with special husbandry conditions.  Husbandry logs must be kept when special husbandry conditions are used.

OAR standard housing:

Lighting - 12 light: 12 dark cycle

Humidity – 30-70%

Examples of special husbandry or housing conditions include but are not limited to:

Environment

1) Deviation from standard lighting

a. Extending or shortening the light or dark cycle

b. Inverted light cycle

2) Deviation from standard temperature and/or humidity - refer to OAR housing standards above

3) Biohazard containment – Any Animal Biosafety levels greater than ABSL-1.

Husbandry

1) Nonstandard diet

a. Antibiotic feed

b. High fat diet

2) Water additives or change of water supply (e.g. water bottles)

a. Use of water bottles

b. Use of water bottles with antibiotic water

c. Use of water bottle with NaCl

3) Husbandry by non-OAR personnel

a. Lab feeding and measuring food consumption

b. Lab feeding and measuring water consumption

c. Lab changing cages with wheels

Enrichment

1) Exemption of non-human primates from the University of Iowa Non-Human Primate Enrichment Program

a. Animal needs to be singly housed

b. Animal exempted from any portion of the enrichment program

2) Exemption of dogs from University of Iowa Canine Enrichment and Exercise Program

a. Animal needs to be singly housed

b. Animal exempted from any portion of the enrichment and exercise program

Housing

1) Single housing of animals for experimental needs

2) Non-standard caging

a. Cages with running wheels

b. Metabolic caging

c. CLAMS unit

d. Telemetry

e. Suspended caging

3) Non-standard flooring and/or bedding

a. Grid flooring will be used in metabolic caging

b. Mice housed in corncob bedding

K. Surgical Plane of Anesthesia

Anesthesia has been described as a series of four Stages.

• Stage 1: the period between administration of an anesthetic and loss of consciousness.
• Stage 2: the period after loss of consciousness, which may include actions such as uncontrolled movement, delirium, vocalization.
• Stage 3: the level at which surgery can be performed. Stage 3 anesthesia is divided into four planes.
  • Plane 1: "light" anesthesia - the animal still has blink and swallowing reflexes, and regular respiration.
  • Plane 2: "surgical" anesthesia - the animal has lost blink reflexes, pupils become fixed and respiration is regular.
  • Plane 3: "deep" anesthesia - the animal starts losing the ability to use the respiratory muscles and breathing becomes shallow; may require assisted ventilation.
  • Plane 4: the animal loses all respiratory effort, and breathing may stop entirely.
• Stage 4: Irreversible Anesthesia—respiratory arrest, followed by circulatory collapse.

L. Death as an Endpoint

The OLAW Institutional Animal Care and Use Committee Guidebook (NIH Publication No. 92-3415) states, "Endpoints other than death must always be considered and should be used whenever the research objective makes it possible." Death as an endpoint does not include euthanasia at the end of a study. Death as an endpoint implies that the study results in death of the animal without investigator intervention.

When animals begin to show signs of pain or distress, they should be monitored at least once daily (including weekends and holidays).  When the animals show progression of pain or distress they should be monitored at least twice daily (including weekends and holidays).

M. Hazards

Guidance for identification of hazardous substances used in projects
Some hazardous chemicals or drugs fall into multiple classifications/categories.  List the substance in the category that, based on your review, fits best.  You may specify multiple categories if appropriate.  Include ALL substances that fit the categories below, regardless of containment status (inclusion in this list does not automatically require additional containment or special handling).

Human or non-human primate blood, blood products, tissues, tumors, and/or cells:
Include any cell, tissue, or blood product of human or non-human primate origin, including cells/tissues growing in culture.

Other animal blood, blood products, tissues, tumors, and/or cells:
Include any animal cell, tissue, or blood product which does not fall under the human or non-human primate category above.

Engineered Nanomaterials/Nanoparticles
Include any engineered nanomaterial/nanoparticle (size range 1-100 nanometers).  Include the name of the material, the particle size/dimensions, and the form of the material administered to animals such as aerosol, liquid suspension, etc.  Also include whether or not the materials is believed to be biodegradable. Limited examples include carbon nanotubes, titanium dioxide, polystyrene.

Toxic chemicals, including carcinogens

OSHA Hazard Classification	OSHA Hazard Category	OSHA Pictogram	Signal Word on Label or SDS	Hazard Statement on   Label or SDS
Carcinogenicity	1A, 1B		Danger	May cause cancer
Carcinogenicity	2		Warning	Suspected of causing cancer
Acute Toxicity, Oral	1,2		Danger	Fatal if swallowed
Acute Toxicity, Oral	3		Danger	Toxic if swallowed
Acute Toxicity, Dermal	1,2		Danger	Fatal in contact with skin
Acute Toxicity, Dermal	3		Danger	Toxic in contact with skin
Acute Toxicity, Inhalation	1,2		Danger	Fatal if inhaled
Acute Toxicity, Inhalation	3		Danger	Toxic if inhaled
Skin Corrosion/Irritation	1A, 1B, 1C		Danger	Causes severe skin burns and eye damage
Eye Damage/Irritation	1		Danger	Causes serious eye damage
Sensitization, Respiratory	1A, 1B		Danger	May cause allergy or asthma symptoms or breathing difficulties if inhaled
Sensitization, Skin	1A, 1B		Warning	May cause an allergic skin reaction
Germ Cell Mutagenicity	1A, 1B		Danger	May cause genetic defects
Specific Target Organ Toxicity, single exposure	1		Danger	Causes damage to organs (specific organs may be listed)
Specific Target Organ Toxicity, single exposure	2		Warning	May cause damage to organs (specific organs may be listed)
Specific Target Organ Toxicity, repeated exposure	1		Danger	Causes damage to organs though prolonged or repeated exposure
Aspiration hazard	1		Danger	May be fatal if swallowed and enters airways

Limited examples include heavy metals, PCBs, neurotoxins, pesticides, benzene, DMBA, cyanide compounds, urethane, isocyanates

Examples may be found in the following references (carcinogenicity):
California Proposition 65 List of Chemicals (known to cause cancer or reproductive toxicity)
National Toxicology Program (NTP), "Report on Carcinogens" (latest edition)
International Agency for Research on Cancer (IARC), "Monographs on the Evaluation of Carcinogenic Risks to Humans" (latest editions)
OSHA 29 CFR part 1910, Subpart Z, Toxic and Hazardous Substances

Hazardous drugs including chemotherapy/antineoplastic and investigational drugs
Using the NIOSH definition, drugs considered hazardous include those that exhibit one or more of the following six characteristics in humans or animals:

• Carcinogenicity
• Teratogenicity or other developmental toxicity
• Reproductive toxicity
• Organ toxicity at low doses
• Genotoxicity
• Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria

Examples may be found in the following references:

NIOSH publication NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014 or most current
OSHA Technical Manual "Controlling Occupational Exposure to Hazardous Drugs"

Appendix VI:2-1. Some Common Drugs Considered Hazardous

OSHA Hazard Classification	OSHA Hazard Category	OSHA Pictogram	Signal Word on Label or SDS	Hazard Statement on Label or SDS
Carcinogenicity	1A, 1B		Danger	May cause cancer
Carcinogenicity	2		Warning	Suspected of causing cancer

Limited examples include doxorubicin, bleomycin sulfate, streptozotocin, cisplatin, tamoxifen, paclitaxel

Note that certain pharmaceuticals used in their common pharmaceutical form may be exempted at the discretion of the IACUC although they may have hazards such as carcinogenicity or reproductive hazards associated with their use.

Additional examples may be found in the following references:
National Toxicology Program (NTP), "Report on Carcinogens" (latest edition)
International Agency for Research on Cancer (IARC), "Monographs on the Evaluation of Carcinogenic Risks to Humans" (latest editions)
OSHA 29 CFR part 1910, Subpart Z, Toxic and Hazardous Substances

Reproductive hazards

Include mutagens, teratogens, developmental reproductive toxicity

OSHA Hazard Classification	OSHA Hazard Category	OSHA Pictogram	Signal Word on Label or SDS	Hazard Statement on Label or SDS
Germ Cell Mutagenicity	1A, 1B		Danger	May cause genetic defects
Toxic to Reproduction	1A, 1B		Danger	May damage fertility or the unborn child
Toxic to Reproduction	2		Warning	Suspected of damaging fertility or the unborn child

Limited examples include BrdU, oxytetracycline hydrochloride, RU-486 (mifepristone), 5-FU (fluorouracil), ribavirin, bleomycin sulfate, tamoxifen citrate

Examples may be found in the following reference:
California Proposition 65 List of Chemicals (known to cause cancer or reproductive toxicity)

Note that certain pharmaceuticals used in their common pharmaceutical form may be exempted at the discretion of the IACUC although they may have hazards such as carcinogenicity or reproductive hazards associated with their use.

Other potential or known hazardous substance (chemical)
Air-reactive, water-reactive, self-reactive other highly reactive chemicals with OSHA Signal Word "Danger"
Explosive chemicals with OSHA Signal Word "Danger"
Organic Peroxides with OSHA Signal Word "Danger"
Flammable Gases, Liquids, Aerosols, Solids with OSHA Signal Word "Danger"
Oxidizing Gases, Liquids, Solids with OSHA Signal Word "Danger"

N. Amendment Summary

Provide a brief summary of the purpose of the Animal Protocol amendment to be submitted. For example: "This amendment is needed to add 2 new procedures." or "This amendment is to increase animal numbers to achieve statistical significance following a pilot study, and to add additional personnel."

O. Procedures for Analgesics

The procedures listed under Question #16 are populated from the "Non-surgical Procedures" and "Surgery" sections, respectively. Some procedures which are populated may not be those perceived to cause pain or distress. If a surgical or non-surgical procedure is not listed in Question #14, confirm that it has been entered under the appropriate section. If analgesia is to be administered for circumstances other than those populated in Question #14, describe it under Question #16.

P. Procedures for Anesthesia

The procedures listed under Question #12 are populated from the "Non-surgical Procedures" and "Surgery" sections, respectively. Some procedures which are populated may not be those perceived to cause pain or distress. If a surgical or non-surgical procedure is not listed in Question #10, confirm that it has been entered under the appropriate section. If anesthesia is to be administered for circumstances other than those populated in Question #10, describe it under Question #12.

Q. Age Definitions for Euthanasia

For the purposes of euthanasia, rodents are grouped into 3 different age groups: fetus, neonate, and adult. The requirements for performance and/or confirmation of euthanasia procedures will depend upon the age of the animal.  The age at which an animal moves from one group definition to another depends on the species.

Mice, rats, gerbils, and hamsters: ​

• Feti greater than 15 days' gestation require confirmation of euthanasia (See IACUC Guidelines on Confirmation of Euthanasia).
• Neonates up to 10 days post birth are treated as neonates for euthanasia purposes (See IACUC Guidelines on Euthanasia).
• Animals greater than 10 days of age are treated as adults for euthanasia purposes.

Guinea pigs:

• Feti greater than 35 days' gestation require confirmation of euthanasia (See IACUC Guidelines on Confirmation of Euthanasia).
• Animals are treated as adults for euthanasia purposes starting at birth (no "Neonate" classification for euthanasia purposes).

R. Housing at Animal Biosafety Level 1 (ABSL-1)

Standard OAR housing (under either barrier or non-barrier conditions) is considered ABSL-1. These animals are treated with standard universal precautions ; exposure to the animals and any agents which may be administered to them , is not known to cause disease in immunocompetent adult humans, and there is minimal potential hazard posed to personnel and the environment. This is in contrast to animals housed at ABSL-2, or -3, which are infected with agents capable of causing human or animal disease or are of unknown risk; these animals are handled with special measures, including procedures, equipment, and decontamination procedures , in order to control the risk of exposure. In the case of recombinant or synthetic nucleic acids, if you are unsure whether your rodents should be handled with increased containment measures, please contact the IBC at ehs-rdna@uiowa.edu or 353-5679.

S. Start New Animal Protocol

Clicking the "New Animal Protocol" button will create a new blank form to be completed for the purposes of describing animal research/teaching activities. Please see When is an Animal Protocol Required? and/or contact the IACUC office at iacuc@uiowa.edu if you need more information on the conditions which require an IACUC-approved Animal Protocol.

T. Find Existing Animal Protocol

You may wish to locate an existing Animal Protocol for the purposes of viewing the Animal Protocol, creating an Amendment, renewing or copying the Animal Protocol, or editing a draft version.  Animal Protocols may be located by entering one or more search terms in the appropriate box: Animal Protocol number, the PI name or the name of any personnel listed on the Animal Protocol, the Project Title (or portion thereof), and/or filter the Animal Protocols which you are authorized to view using any of the checkboxes or filter options available. Once you have entered the appropriate information, click the "Search" button to produce the Animal Protocol(s) which meet your criteria.

You may then select the appropriate Animal Protocol by clicking the blue Animal Protocol number on the left side of the table. Clicking this link will produce the Protocol Summary page, from which you may select subsequent actions (View, Edit, etc.)

U. Animal Protocol Actions

• View: This action allows a user to view all sections of the Animal Protocol. A printable pdf may also be produced by accessing the Animal Protocol using this action.
• Edit: This action allows an authorized user to make and save edits to any section of the Animal Protocol or Amendment currently in Draft or Revisions status.
• Compare: This action allows a user to compare the most recent version of the Animal Protocol to a previous version (Draft, Approved, etc.). This action may be useful for determining what changes have been made during an Amendment proposal.
• Amend: This action allows an authorized user to begin a Draft Amendment to an Approved Animal Protocol. This action is only available on an Approved Animal Protocol for which an amendment is not currently in Draft or under IACUC review. Any number of modifications can be made in a given amendment request; however, only one amendment request can be initiated/in review at a time.
• Renew: This action allows an authorized user to start a Renewal Animal Protocol from the currently approved version of an Animal Protocol. All pertinent information (including Project Title, Animal Protocol Number and funding information) will be transferred to the new draft. All appropriate edits may then be made in the newly created Renewal Animal Protocol prior to submission for IACUC review.
• Copy: This action allows an authorized user to start a new Animal Protocol by copying the majority of an existing Animal Protocol. All sections will be copied, except for pertinent information in the Project Information section (including Project Title, Animal Protocol Number and funding information). All appropriate edits may then be made in the newly created Animal Protocol prior to submission for IACUC review.
• Withdraw: This action allows an authorized user to withdraw a submitted Animal Protocol or Amendment currently under IACUC review. Withdrawing a submitted document will remove it from the review process entirely.
• Delete: This action allows an authorized user to delete a Draft version of an Animal Protocol or Amendment. Once an Animal Protocol or Amendment is under IACUC review, it cannot be deleted without first being withdrawn.

V. Personnel Experience

The following are examples of how to adequately address experience for personnel included in the Animal Protocol.

(Non-surgical experience question) - For each species used, describe training and experience with Non -surgical techniques and procedures, or explain how he/she will be trained and by whom.

• John has 5 years of experience conducting experiments with rats. He has experience with some of the non-surgical (or surgical procedures) in this protocol and will be trained by experienced lab members before conducting any of the other approved procedures.
• John has performed euthanasia of mice by microwave irradiation for 5 years and will train others in this technique.
• John has not worked with dogs and does not intend to do so at this time.

(Surgical experience question) - For each species used, describe training and experience with the proposed surgical procedure(s) or explain how he/she will be trained and by whom.

• John has been performing surgery in mice and rats for greater than 5 years and has experience with some of the surgical procedures in this protocol and will be trained by experienced lab members before conducting any of the other approved procedures.
• John is being trained to assist the surgeon with equipment during dog surgery but will not perform any procedures on dogs.

W. Training Animals

Training animals are used in cases where individuals need to develop skills and become competent in procedures, in addition to those used to refine a procedure.  Includes an animal carcass or an animla used in a terminal/non-survival procedure.

• An IACUC approved Animal Protocol is required to use training animals
• Training animals reach their humane endpoint when the training objective is complete; they are not used to collect subsequent data
• Different humane endpoints may be needed for training than for data collection

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Source: https://animal.research.uiowa.edu/help-animal-protocol-questions

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