IACUC Protocol and the Review Process

  • An animal use protocol is a written description of a planned research or teaching activity in

    sufficient detail to allow for a review of the proposed research activities by the IACUC. Research
    protocols submitted for IACUC review should be submitted on the most recent version of the
    IACUC protocol form and are asked to follow a particular outline, detailing just the information
    necessary for a proper IACUC review in clear and plain language. Incomplete protocols,
    protocols containing confusing or highly technical language, or protocols involving excessive
    and unnecessary detail are unacceptable.

    A. The Animal Care and Use Protocol Approval Form

     

    Forms, along with instructions for completing them, are available on-line at: my.francis.edu. The most current forms are required to be submitted prior to review by the IACUC. Other forms of submission are not acceptable. The forms have been specifically designed to provide the information required by regulations and by the IACUC. The protocol form should be used for all research projects as required.

    B. What Should Be Addressed in a Protocol?


    A protocol must be sufficiently detailed to permit the IACUC to evaluate the soundness
    of the procedures proposed and to determine appropriateness of the species, the proposed number of animals, and that alternatives to using animals have been completely searched. The protocol form and its associated appendices will guide the PI to provide the necessary information. PI's should, however, ensure that they give full and detailed answers and complete all relevant supplemental forms. Sketchy answers or missing appendices will lengthen the review process. As a general guide, the following special elements should be well justified in the protocol:

    • Pain code classification: to classify protocols according to the level of pain or unrelieved distress involved. Investigators who complete a protocol must select the pain code that applies to the proposed work. If more than one classification applies, then an investigator should specify the percentage of animals in each. The definitions of these categories, as described in the protocol form, are as follows: 
    • Classification A: No pain, distress, or use of pain-killing drugs. (i.e., behavior studies, post-mortem tissue harvest; and routine procedures causing only transitory discomfort such as venipuncture, injections, ear tagging)
    • Classification B: Pain/distress with appropriate analgesic/anesthesia/tranquilizers. Procedures involving accompanying pain or distress to the animals and for which the appropriate anesthetic (for surgery), analgesic (for inflammation or pain) or tranquilizing drugs are used.
    • Classification C: Pain/distress without appropriate analgesic/anesthesia/tranquilizers. Procedures involving accompanying pain or distress to the animals and for which the appropriate anesthetic, analgesics or tranquilizing drugs are not used.

    If all or a percentage of animals will experience either category B or C, the PI must complete appropriate appendix to document that alternatives to painful or distressful procedures in animals have been considered. The regulations of the Animal Welfare Act (AWA) require that the principal investigator consider alternatives to procedures that may cause more than momentary (more than a simple injection) or slight pain or distress to animals. PI's must provide a written narrative of the sources consulted to determine whether or not alternatives exist to procedures that cause pain or distress. The USDA, which is charged with enforcing the AWA, has promulgated two policies (Policy #11 and Policy #12) that assist investigators in understanding how to comply with these regulations. Policy #11 (http://www.aphis.usda.gov/animal_welfare/downloads/policy/Policy%2011%20Final.pdf) provides the definition of what is considered a painful or distressful procedure, and provides examples of both. In general, any procedure that would be expected to cause more than slight or momentary and/or distress in a human to whom the procedure is applied is considered to be painful and/or distressful in animals. Policy #12 (http://www.aphis.usda.gov/animal_welfare/downloads/policy/Policy%2012%20Final.pdf) provides guidance in what the minimal written narrative should include. In general, this requires a narrative describing a specific literature search for alternatives, including databases searched, time period covered, key words used, and the date of the search. If alternatives are described but will not be used, the principal investigator must describe why these are not adequate for the project described.

    • IACUC policies conform to the standards of the 2000 American Veterinary Medical Association Panel on Euthanasia, JAVMA, Vol. 218, No. 5 (https://www.avma.org/KB/Policies/Documents/euthanasia.pdf). The IACUC will evaluate each protocol on a case-by-case basis to determine whether the justification warrants approval of a non-standard method of euthanasia. Generally, animal care and use standards require that prior anesthesia or sedation be used in conjunction with a physical method of sacrifice (i.e., decapitation or cervical dislocation). In cases where a physical method of sacrifice alone is proposed, the PI must provide a scientific justification, which should include research references, to explain why anesthesia or sedation cannot be used. The justification must include documentation of the alternatives considered and a description of the methods and sources used to determine that alternatives to the use of physical sacrifice alone were not acceptable or available.
    • The IACUC has a responsibility to ensure that the number of animals used is the minimum number that is sufficient to achieve the scientific or teaching aims. Toward that end, the protocol asks that PI's justify the number of requested animals in detail. Numbers should be based in a statistically valid power analysis or other specific justification. Investigators may not use more animals than the number approved by the IACUC. As part of its review process, the IACUC considers the appropriateness of the proposed animal numbers for the work proposed. PI's are expected to limit the number of animals to the smallest number, which allows meaningful conclusions to be drawn from the research. In cases such as field research where the PI cannot provide precise numbers or species lists, an appropriate justification should be made including estimates. The IACUC is responsible for ensuring that PI's do not use animals in excess of the numbers formally approved by the IACUC. In the event that during the conduct of the research, a PI determines that more animals than originally anticipated are required for the research, the PI is responsible for submitting an amendment requesting to increase the number of animals. This request should include not only the number of animals requested, but also a scientific justification for the increase. Such an amendment may be eligible for designated review, but depending upon the number of additional animals and the justification, the IACUC might determine that the amendment should be reviewed at a convened meeting.
    • The protocol should outline in detail any proposed anesthesia (type of anesthesia, rate of administration, dosage, timing). The IO, Vet of Record, or Chair can provide assistance to PI's in determining the most appropriate anesthetic regimen for the species and for the type of procedures. Anesthesia of laboratory animals is an art as well as a science. It is also a serious responsibility. Significant animal pain and distress can result from poorly administered or inadequately monitored or inappropriate anesthesia. Only trained personnel should undertake animal anesthesia. The attending veterinarian is available, not only for consultation in planning an anesthetic regimen, but also for training in administering anesthesia. Anesthesia must conform to the method approved by the IACUC in the specific protocol. Records must be kept.
    • Analgesia is the relief or prevention of pain in the conscious patient. The IACUC can assist in determining the need for analgesia and the appropriate analgesic regimen. The protocol should outline the proposed analgesia to be employed if pain is anticipated. It should be generally assumed that any procedure that would cause pain in humans would also cause pain in laboratory animals, and arrangements must be made to minimize pain. Unrelieved pain or distress is NOT acceptable except in circumstances where they have been scientifically justified and approved by the IACUC. 

    PI's should note that even after analgesic drugs have been administered, animals must be
    monitored closely for the adequacy and persistence of analgesia. Protocols should describe the plan for monitoring animals and should indicate who on the research team will be responsible for monitoring animals. Contact information is essential; this should be kept up to date. As with anesthetics, it is critical to document the administration of analgesia.

    • Any proposed surgical procedures, both survival and nonsurvival, must be fully described in the protocol. Nonsurvival surgery is defined as a surgical procedure from which the animal does not awaken. Nonsurvival surgery must meet applicable standards (e.g., clean instruments, surgeon appropriately garbed, in a suitable environment). Survival surgery, where the animal recovers from anesthesia, must follow strict standards for aseptic technique FOR ALL SPECIES and can only be conducted in a suitable environment approved for survival surgery. It is essential that individuals performing surgical procedures be well trained to minimize animal pain and to ensure success of the procedure. Appropriate animal and surgeon preparation, aseptic technique, suitable environment, proper instruments, and knowledge of tissue handling and suturing are all essential components of good surgery. Individuals who need additional training in surgery should contact the IACUC consulting veterinarian. The IO and Chair also can provide training materials on the subject of aseptic surgical techniques. Multiple major survival surgeries on a single animal are not permitted unless scientific justification is provided or approved by the IACUC.
    • Physical restraint may be a requirement of the research. However, such restraint must be made as painless as possible for the animals, should be of as short a duration as practicable and should utilize the most animal-friendly restraint system possible. The need to restrain animals should be fully described and justified in the protocol. Justification is particularly important if the restrain is of a long duration or the restraint mechanism itself is non-standard.
    • Animal care and use standards require that animals receive food and drink consonant with their species and its natural needs. Any deviation from the standard diet of food or constant availability of water must be scientifically justified in the protocol and approved by the IACUC.
    • PI's and their staff bear much of the responsibility to prepare and maintain records of the many aspects of animal care and use that are required by regulation and practice. Such records include, for example, records of: animals received, animals used under each protocol, anesthesia, analgesia, post-procedural care, euthanasia method and date, controlled substance use, training, breeding, basic animal care, and clinical care records. Consult the IO if you have any questions about the record keeping requirements for documentation of animal use.  

    C. Review Process


    The IACUC will meet monthly, if needed, to review submitted protocols and other business of the IACUC. In order for a protocol to be reviewed at a scheduled IACUC meeting, it must be received by the Chair of the IACUC at least two weeks prior to the meeting date. Particularly complex or controversial procedures with multiple follow-up questions may need additional review time by the IACUC. Every effort will be made to assist investigators with extenuating circumstances requiring special consideration.

    1. Process for the Initial Review of Research Involving the Care and Use

    a. Research Investigator Completes a Protocol Approval Form
    The first step in obtaining IACUC approval for research involving animals is for the research investigator to complete the IACUC Protocol Approval Form and all applicable appendices. This form may be obtained from the IO or on the SFU web site in PDF format. Only university faculty or staff may serve as Principal Investigators for an IACUC animal use protocol. Student investigators must be named on the form as being a co-investigator, with the faculty or staff
    member providing appropriate direction to the student researcher. The Principal Investigator then signs the submission form attesting to the submission materials'
    correctness and agreeing to follow the procedures established by the IACUC. The signed submission form should be sent directly to the Chair of the IACUC. Incomplete or illegible submissions will be returned to the Principal Investigator for resubmission. To avoid the perception of conflict of interest, committee members who are participants in the protocol being reviewed do not participate in the review, deliberations and decisions on those protocols.

    b. Routing by Chair of the IACUC
    The Chair of the IACUC receives submitted protocols and reviews each protocol for completeness. Incomplete protocols are returned to the Principal Investigator with a short note indicating its deficiency. Complete protocols are given an IACUC tracking number and entered into a computer database. The Chair then routes the protocol to all IACUC members for review before the next IACUC meeting. For protocols submitted with an "A" pain classification, a designated review process may be used. The full IACUC committee would receive a copy of the protocol and are given the option of calling for a full review. If after a designated time period (3 working days), no committee member has requested full committee review, the IACUC Chair, or appointed designated member appointed by the chairperson, could approve or require modifications to the protocol. Regardless of pain classification, a full committee review is required to disapprove or deny an animal protocol.

    c. Full IACUC Review
    Protocols classified B or C must be reviewed at a meeting of the IACUC, defined as a quorum of the total membership. A majority of that quorum must vote in favor for it to be officially approved. All animal use protocols brought before the IACUC are: approved as submitted, withheld pending minor revisions, or denied with recommendations for major revisions.

    1) Approve
    The IACUC has determined that, for a particular animal use and teaching protocol, appropriate justification for animal use has been made, a search for acceptable alternatives to animal use has been demonstrated, and methods described are within standard and acceptable guidelines. The
    IACUC signifies its approval of a research protocol by issuing a letter to the Principal Investigator that the research protocol has been reviewed, approved, and may be conducted. Protocols involving little risk to the subjects may be approved even if the benefit to be gained is likewise small (e.g., class projects where the primary gain is for the student to experience a research process). Protocols having higher degrees of risk to the species must demonstrate both sound methodology and an importance to the information that would be gained.
    2) Withheld Pending
    Protocols with a review status of withheld pending are most typically in need of one (or more) minor corrections or clarifications. The Chair will write a letter to the Principal Investigator indicating that approval for the protocol is being withheld pending certain minor revisions that must be made to the protocol. The letter will detail the items or questions requiring attention and a time frame for submitting revisions. The Principal Investigator will be invited to submit these revisions directly to the Chair of the IACUC. In certain cases the Chair might also elect to contact the Principal Investigator directly, to insure that the needed revisions are understood or to discuss ways the Principal Investigator might meet the requirements of IACUC. If the Principal Investigator responds to these minor issues raised in the letter to the satisfaction of the Chair, the Chair, as designated reviewer, may approve the protocol as revised. If no revisions are made, or the revisions are not satisfactory to the Chair, the protocol will be maintained as withheld pending and will be scheduled for presentation and discussion at the next regular meeting of the IACUC committee. More substantive changes to a protocol with a status of withheld pending may result in a re-review by the IACUC. A protocol is most typically held in a withheld pending file for no more than 30 days, after which it is approved, sent out for additional review, or administratively denied due to insufficient information.

    3) Denial
    The IACUC has determined that, for a particular research protocol, the risks outweigh the benefits to be gained by conducting that research. Research protocols might also be denied because:

    • The protocol is overly confusing or convoluted and not understood by the IACUC (e.g., poorly written or excessive technical language or jargon);
    • Procedures described are not considered acceptable according to current standards and justification made was not sufficient to endorse deviation.
    • The Principal Investigator has not convinced the IACUC of his or her capacity (training and experience) to conduct the proposed research; or
    • The methods being proposed are inadequate for the research, lack sufficient rigor or merit, or are unlikely to provide data that would allow the Principal Investigator to answer the main questions driving the research.

    A protocol may also be administratively denied when a Principal Investigator has not responded to a request for additional information and/or modifications from the IACUC in a timely fashion (30 days).

     


    The Principal Investigator may enact research protocols approved under this procedure for a period not to exceed the approval period. The starting and ending dates of the approval period will be stated on the approval letter sent to the Principal Investigator. In certain cases the IACUC may require a shorter approval period and will require interim protocol status reports annually on the progress of the research and the status of the animals as a condition of approval. The exact period of approval, and any conditions, will be stated on the approval letter.

    d. Granting Agency Requirements and Protocol Submission
    Many agencies such as NIH, NSF, DOD and the American Heart Association will not review protocols involving animals unless formal notification of IACUC review and approval has been provided. Other agencies may review and score protocols, but they will withhold funding pending notification of IACUC review and approval. PI's are urged therefore to submit the IACUC protocol prior to the submission of a grant application. It is critical that the protocol must reflect all proposed animal use detailed in the corresponding grant application in regards to the use of animals. In the NIH application, for example, Section F of the Research Plan asks for specific information on the identification of the species and approximate number of animals to be used, rationale for the use of animals and appropriateness of the species and numbers as well as statements addressing steps to assure minimization of pain and distress, as well as euthanasia methods. Please refer to the grant application for a listing of all the points. The answers to these specific points should be fully reflected in the protocol.

    Proposals for funding that involve the use of animals are carefully reviewed prior to receiving institutional endorsement. The review ensures that if a protocol number is listed on the Protocol Approval Form that is the correct protocol, that it is active and the approval date listed is correct, and that the PI of the protocol is listed as either the PI of the protocol or as a member of the research team. If a protocol is submitted prior to receiving approval for the relevant protocol, the University will not process the award or provide a University account until the protocol is fully approved.

    e. Questions and Appeals
    Any PI may request an appointment with the IACUC Chair, or an opportunity to address the IACUC at a regular or special meeting, for any purpose related to the business of the IACUC. The two most common reasons for such an appointment or hearing are to answer questions concerning protocols in development or research in progress, or to resolve difficulties related to the approval of a protocol. Concerns should be brought to the IACUC Chair. If resolution cannot be reached with the Chair, the Principal Investigator may be scheduled to present his/her case before the IACUC at the next regular meeting or at a special meeting called by the Chair (if the situation warrants). The decision of the IACUC, however, is final.

    3. A Note About Revisions/Changes to Proposed Protocols

    Investigators should note that it is not uncommon for protocols received by the IACUC to
    require revisions. The goals of the process are to ensure humane care and use of animals,
    sufficient and accurate documentation in protocols, compliance with all applicable animal use regulations, and that the methods and practices proposed reflect the highest in current standards. To facilitate the protocol development and review process, it is highly recommended that investigators work closely with the consulting veterinarian and the IACUC Chair in advance of protocol submission. The protocol forms are also a useful guide to ensure that protocols are as complete as possible prior to submission. In addition, it is the IACUC's hope that the review process can facilitate research through education and through acting as a forum for discussion.