- 3.0 Protocol Review
- 3.1 General Scope of Review
- 3.2 Specific Types of Activities
- 3.3 Exemptions
- 3.4 Who can be a Principal Investigator?
- 3.5 Protocol Review Criteria
- 3.6 Protocol Review Procedures
- 3.7 Required Principal Investigator Certifications
- 3.8 Range of IACUC Actions
- 3.9 Review of Modifications to Approved Protocols
- 3.10 Weekly DMR Docket
- 3.11 Administrative Action on Termination of Reviewed (Pending/Not Yet Approved) Protocols and Amendments
- 3.12 Minimization of Pain and Distress
- 3.13 Guidance Documents
The IACUC is responsible for overseeing and evaluating all aspects of animal care and use, and is charged with reviewing proposals that involve animals to ensure that the criteria established in the PHS Policy and the Animal Welfare Regulations (AWRs) are implemented. In its review of proposals, the IACUC’s primary goal is to facilitate compliance with applicable laws, regulations and policies consistent with the performance of appropriate and productive scientific endeavors.
3.1 General Scope of Review3
The following kinds of activities involving animals are subject to review by the IACUC prior to initiation:
- Activities conducted by University faculty, staff, or students;
- Activities performed on the premises of the University;
- Activities performed with or involving the use of facilities or equipment belonging to the University;
- Activities satisfying a requirement imposed by the University for a degree program or completion of a course of study; and/or
- Activities certified by a dean or department head to satisfy an obligation of a faculty appointment at the University, including requirements for clinical or adjunct appointments.
3.2 Specific Types of Activities4
Many of the animals covered in IACUC review are used in research, including medical, biological, and behavioral research as well as agricultural research (such as the study of food and fiber production or diet manipulation). Most of these animals are acquired and housed by the Institution; some may include free-ranging wildlife.
The use of animals in educational settings is subject to IACUC review. Examples include using animals to teach agricultural techniques, animal husbandry, and medical or veterinary procedures.
Review is required even if the activity does not seem to qualify as “true research” (e.g. when the results are not intended for publication, will not advance work in another area, or will not contribute to generalizable knowledge).
- Research Conducted by “Affiliated Faculty”
Research conducted by “affiliated faculty”—those who hold clinical or adjunct appointments—is subject to the Institution’s guidelines for animal use and must be submitted for IACUC review.
Any research project that is conducted by or under the direction of any employee or agent of the institution, in connection with his or her institutional responsibilities, requires IACUC approval.
- Research Projects in Which the Investigator is a Consultant
In some instances, University faculty or staff may serve in an advisory capacity for a research project conducted outside the University community. IACUC review is required unless the investigator has a strict consulting relationship in which:
- The investigator is hired on his or her own time;
- The investigator holds no rights in the work; and
- Neither the investigator nor the University retains any data.
Unless all three of these criteria are met, the IACUC must review the project. Review by another institution or facility’s IACUC is insufficient unless a cooperative arrangement between that IACUC and the Institution’s IACUC is agreed upon prior to initiating the consultant relationship.
- Research in Foreign Countries
Research conducted by the Institution’s investigators in foreign countries falls under the Institution’s purview and guidelines. Regardless of the setting, the standards for ethical and responsible use of animals in research will not be relaxed even if different customs prevail.
All animal-based research conducted in foreign countries is subject to IACUC review. This includes the use of animals in foreign research institutions, and fieldwork involving either domestic or wild animals.
Research projects must be approved by the local equivalent of an IACUC before they are initiated. Where there is no equivalent board or group, investigators must rely on local experts or community leaders to provide approval. The IACUC requires documentation of this local approval, as well as documentation of any necessary permits, before granting final approval for the project.
With regard to activities supported by PHS funds, foreign institutions that serve as performance sites must also have Assurances on file with OLAW.
The following are exempt from IACUC review:
- Activities involving animals that perform tasks, participate in club activities, or appear in exhibits or demonstrations;
- Use of tissues, organs or other parts of dead animals if received as such; and
- Noninvasive observation of wild animals in their natural habitat. Field studies that involve killing, trapping, banding, darting, implantation of telemetry devices, or any other invasive manipulation require IACUC approval.
3.4 Who can be a Principal Investigator?5
All use of animals in research and/or teaching at The University of Texas at must be under the direct supervision of a tenured, tenure track, or research faculty with assigned research space at The University of Texas at Austin. Faculty are considered to be sufficiently knowledgeable to supervise and/or conduct research as determined by their appointment. The IACUC, however, may at its discretion, determine that a faculty member lacks sufficient expertise to carry out any particular research project based on their relevant training and experience.
Research conducted by non-faculty, academic support staff, post-doctoral fellows, staff appointments, graduate students or undergraduate students must be under the direction of a faculty member, as defined above. In such cases, the faculty member shall be considered the Principal Investigator. The PI may delegate the performance of any or all components of the research to non-faculty if they certify to the IACUC that the individuals are sufficiently trained to perform the functions assigned.
Individuals that do not meet any of the above criteria may, by demonstrating sufficient cause and necessary expertise, petition the Director of the Office of Research Support for permission to submit an application for approval of an IACUC protocol. Such agreement shall be in writing and require the individual to comply with all relevant IACUC and University policies for the conduct of research involving animal subjects.
In order to approve proposed research projects or proposed significant changes in ongoing research projects, the IACUC shall conduct a review of those components related to the care and use of animals and determine that the proposed research projects are in accordance with PHS Policy, AWRs, and the applicable US Government Principles. Since the PHS Policy further requires that the provisions of the Guide apply, there are many other aspects of research that an IACUC should review, such as food and water deprivation, use of noxious stimuli, and physical restraint. The Guide provides useful guidance on these and other practices.
If the IACUC does not have the scientific and technical expertise to evaluate all aspects of a proposal it may bring in outside expert consultants to provide information. Such consultants will not have a conflict of interest with the research activity and may not vote on any matters pertaining to the protocol. In all cases, the onus should be on the investigator to justify and explain his or her proposed experiments to the satisfaction of the IACUC.
The procedural review requirements of the PHS Policy or the AWRs take precedence even though they may differ from some commonly used parliamentary procedures. The Institution may develop its own meeting procedures as long as the procedures do not contradict or are not inconsistent with the requirements of the PHS Policy or the AWRs.
If a proposed activity may cause more than momentary or slight pain or distress to animals, the AWRs specifically require investigators to consult with the Attending Veterinarian (AV) or his or her designee during protocol development.
The PHS Policy and AWRs recognize two methods of protocol review: Full Committee Review (FCR) and Designated Member Review (DMR). The following pertains to review of initial protocols as well as to review of proposed significant changes in previously approved protocols.
Full committee review of protocols requires a convened meeting of a quorum of the IACUC members. The PHS Policy and AWRs are explicit that proposals reviewed by the full committee must receive the approval vote of a majority of the quorum present in order receive approval.
At least three (3) business days prior to a meeting, the Office of Research Support distributes copies of the protocols being presented or any other items of discussion to each IACUC member, including alternate and non-voting member(s). Protocols are assigned a primary reviewer, who at the meeting orally presents the protocol to the rest of the committee for review and discussion. In addition, each protocol is assigned to a veterinarian to conduct an in-depth review of the protocol. The Committee then votes on protocol approval. A simple majority vote of the members present is required for approval.
The Committee has the authority to approve, require modifications in (to secure approval), disapprove, or table (defer until future meeting) any proposed activity. In many cases, the Committee finds the protocols approvable on certain conditions and votes to allow the protocol to be reviewed, and approved, using the Designated Member Review (DMR) process, as described in Section 3.6.2. Approval of the change from FCR to DMR must be unanimous (of a quorum of members (Section 2.4)) and is recorded in the minutes. Committee members are given the opportunity to require that the requested modification(s) be brought before the next committee meeting. Under no circumstances will animal work be permitted to resume or begin until final approval is granted.
Primary reviewers can also take the initiative to contact the investigator prior to the meeting for clarifications, additional information, or in anticipation of questions the IACUC may raise. Primary review differs from designated member review (see Section 3.6.2.), which delegates authority to approve a proposal to one or more members.
To utilize designated member review (DMR), each IACUC member must be provided with, at a minimum, a list of the proposed research protocols or proposed significant changes to previously approved protocols prior to the review. Written descriptions of the research proposals must be made available to IACUC members upon request. Each IACUC member is provided a copy of the protocol document from the Office of Research Support. Committee members are given a five (5)-business day member consideration period to review the protocol document and respond either allowing the DMR to review the protocol or to hold the protocol for the next FCR. Members are reminded that failure to respond within the member consideration period is considered as approval to use DMR for review. These responses are sent to the IACUC Program Coordinator via email. The IACUC Program Coordinator tallies the votes to ensure that more than half of the voting members respond, then at the end of the member consideration period, the IACUC Program Coordinator sends the protocol to DMR for review. If any one member votes to hold the protocol until the next IACUC meeting, then the protocol is placed on the agenda for the next IACUC meeting. If all members vote to allow the DMR to review the protocol before the end of the member consideration period, then the IACUC Program Coordinator sends the protocol to DMR for review.
The IACUC Chair (and in his/her absence, the Vice-Chair) designates one or more qualified members to review the proposal (or proposed amendment or annual renewal). These designated member(s) have authority to approve, require modifications in (to secure approval), or request full committee review. A designated reviewer may not withhold approval; this action may only be taken if the review is conducted using the full committee method of review.
While Federal regulations allow for two types of review of animal use protocols (FCR and DMR), recent guidance from the Office of Laboratory Animal Welfare (OLAW) granted authority for a small number of items to be administratively approved.
Amendment/modification applications to existing protocols that involve certain changes not considered significant (see Section 3.9.2) can be reviewed (and approved) administratively.
The IACUC will notify investigators and the University in writing of its decision to approve or withhold approval of those activities related to the care and use of animals, or of modifications required to secure IACUC approval as set forth in the PHS Policy IV.C.4. The IACUC procedures to notify investigators and the University of its decisions regarding protocol review are as follows:
- Upon completion of the review process, each Principal Investigator receives a written notification of review decisions (approved, modifications required in (to secure approval), approval withheld, or tabled) and whether any special monitoring provisions will be required. Records of communication are maintained within the IACUC protocol files.
- Upon completion of the review process, a copy of the meeting minutes is provided to the IO. This informs the IO of all actions taken by the IACUC.
3.6.5 Appeal of an IACUC Decision6
Investigators shall have the right to appeal a decision of the IACUC within two (2) weeks of notification by the IACUC Chairperson. A Principal Investigator may appeal decisions made by the Institutional Animal Care and Use Committee (IACUC) by following the below steps:
- The appealer states in writing to the IACUC Chair specific points of disagreement with the Committee’s action, reasons for disagreement, and the desired outcome of the appeal.
- The IACUC Chair appoints at least one IACUC member (“the hearer”) to present the appeals to IACUC members at a convened meeting of a quorum of the IACUC.
- A quorum of the IACUC membership hears the appeal from the hearer and/or from the person appealing and determines an outcome. The appealer will in any case be invited to attend and provided comments to the IACUC regarding the appeal.
- All decisions of the IACUC regarding an appeal request will be conveyed to the appealer in writing and copied to the Institutional Official.
- If the person(s) appealing is not satisfied with the IACUC’s decision, he or she may appeal to the Institutional Official and thereby initiate further IACUC consideration if the Official so requests. Officials of the institution, however, cannot approve an animal activity that has not been approved by the IACUC.
In order to submit an animal utilization proposal (AUP), or protocol, to the IACUC for review, the Principal Investigator must certify the following:
- I assure that all students, staff, and faculty on this project are familiar with the Animal Welfare Act (AWA) and the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, the National Institute of Health (NIH) Guide for the Care and Use of Laboratory Animals, and recognize their responsibility in strictly adhering to approved protocols.
- I assure that all individuals listed on this project are qualified or will be trained to conduct procedures involving animals under this proposal, and that they have completed an approved UT-Austin Orientation Course [3198: Orientation] and received training in the biology, handling, and care of this species; aseptic surgical methods and techniques (if necessary); the concept availability and use of research or testing methods that limit the use of animals or minimize distress; the proper use of anesthetics, analgesics, and tranquilizers (if necessary), and procedures for reporting animal welfare concerns.
- I assure that all procedure will be conducted in accordance with The University of Texas at Austin safety procedures, including those pertaining to personal protective equipment.
- I assure that all individuals working on this proposal are participating in the Occupational Health Program-Laboratory Animal and Biomedical Services (OHP-LABS).
- I assure that ANY change in the care and use of animals involved in this protocol, including ANY change in the personnel listed on this protocol, that would affect their welfare will be promptly forwarded to the IACUC for review. Such changes will not be implemented until approval is obtained from the IACUC. Animals will not be transferred between investigators without prior approval.
- I assure that I have reviewed the pertinent scientific literature and the sources and/or databases and have found no valid alternative to any procedures described herein which may cause more than momentary or slight pain, distress, or generalized discomfort to animals, whether it is relieved or not.
- I assure that every effort has been made to minimize the number of animals used and reduce the amount of pain, distress, and/or discomfort these animals must experience.
- I assure that the activities described with in this document submitted for IACUC review are consistent with those described in any related grant, contract, or subcontract.
- I assure that the information contained in this application for animal use is accurate to the best of my knowledge.
- I understand that this application and/or my animal use privileges may be revoked by the IACUC if I violate any of the aforementioned assurance statements.
It is implicit upon submission of the protocol that the Principal Investigator has read and agrees to abide by the above obligations.
Upon review of protocols, the IACUC may take one of several different actions depending upon the findings of the committee: approval, modifications required in (to secure approval), and withhold approval. An IACUC may also defer or table review of a protocol. The PHS Policy and AWRs require the IACUC to notify investigators and the institution in writing of its decision to approve or withhold approval, or require modifications in (to secure approval) of a protocol. If approval is withheld the IACUC must provide the reasons for its decision and give the investigator an opportunity to respond.
When the IACUC has determined that all review criteria, based on the PHS Policy and AWRs, have been adequately addressed by the investigator, the IACUC may approve the project, thus granting the investigator permission to perform the experiments or procedures as described.
The IACUC-approved proposal may be subject to further appropriate review and approval by institutional officials due to financial, policy, facility, or other institutional or administrative considerations. Those officials, however, may not approve an activity if it has not been approved by the IACUC.
- Modifications required in (to secure approval)
The IACUC may require modifications to the protocol before granting approval. If the IACUC determines that a protocol is approvable contingent upon receipt of a very specific modification (e.g., receipt of assurance that the procedure will be conducted in a fume hood), or clarification of a specific point, the IACUC may handle these modifications or clarifications as administrative details that any member, such as the Chair, could verify prior to granting approval.
If a study is unusually complex or involves untried or controversial procedures the IACUC may wish to impose restrictions, (e.g., approval for the use of a limited number of animals as a pilot study with a written report of interim results, or close monitoring by veterinary or other qualified personnel). If such modifications represent significant departures, the IACUC can ask the investigator to revise the protocol to reflect the modifications imposed by the IACUC.
If the protocol is missing substantive information necessary for the IACUC to make a judgment, or the IACUC requires extensive or multiple modifications, then the IACUC can require that the protocol be revised and resubmitted. If the IACUC wishes to shift to the designated member reviewer mode for the approval of the modified protocol, that shift should be explicitly noted in the meeting minutes and the requirements for designated review must be met.
- Withhold approval
When the IACUC determines that a proposal has not adequately addressed all of the requirements of the PHS Policy and AWRs, as applicable, or the described activities represent inappropriate or unethical use of animals, the Committee may withhold approval. A designated reviewer may not withhold approval; this action may only be taken if the review is conducted using the full committee method of review.
As indicated above, a higher institutional authority may not administratively overrule an IACUC decision to withhold approval of a proposal.
- Defer or table review
If the protocol requires significant clarification in order for the IACUC to make a judgment, Committee members with certain expertise are not present, the IACUC wishes to seek external consultation, or any of a number of other reasons prevent the IACUC from conducting its review, then the IACUC may wish to defer or table review until a future FCR.
Significant changes to an IACUC-approved protocol must be reviewed and approved by the IACUC before they occur (PHS Policy IV.C.1., and AWR §2.31[d]). The Institution interprets significant changes to mean those that have the potential to impact substantially and directly on the health and well-being of the experimental animals. Examples of significant changes include, but are not limited to, changes:
- in the objectives of a study;
- from non-survival to survival surgery;
- resulting in greater discomfort or a grater degree of invasiveness;
- in the species or in approximate number of animals used;
- in Principal Investigator;
- in anesthetic agent(s) or the use or withholding of analgesics;
- in the method of euthanasia; and
- in the duration, frequency, or number of procedures performed on an animal.
Proposed significant changes require IACUC review (and approval) prior to initiation.
The University interprets non-significant changes to mean those that do not have the potential to impact substantially and directly on the health and well-being of the experimental animals. Examples of non-significant changes include, but are not limited to, changes:
- in the funding source;
- in personnel (other than the PI); and
- in the use of a new vivarium housing location.
Proposed non-significant changes require administrative review (and approval) prior to initiation.
The goal of the IACUC and Office of Research Support is to rapidly process protocols in an effort to provide faculty with the maximum amount of time possible to address Committee concerns and clarifications. In order to maintain an expeditious review process, proposed protocol modifications and annual renewal forms will be circulated to Committee members for one week (see Section 3.6.2) and only those items that are specifically asked to be reviewed at the FCR will be assigned to a meeting agenda.
3.11 Administrative Action on Termination of Reviewed (Pending/Not Yet Approved) Protocols and Amendments
The IACUC has the responsibility to require modification(s) to requests for animal use prior to approving a protocol or amendment to an existing protocol. To prevent the development of a collection of pending/not yet approved protocols or pending/not yet approved amendments, that results in slower service to all researchers, complicates the oversight process, and interferes with support of active research, the IACUC has established a process for protocol and amendment review and approval (and amendment review and approval). The goal of the IACUC and Office of Research Support is to rapidly process protocols in an effort to provide faculty with the maximum amount of time possible to address Committee concerns and clarifications. This policy specifically addresses the duration of time at which point the IACUC will administratively inactivate an application for failure to respond for further clarification and queries.
The Office of Research Support (ORS) staff will pre-review and process the proposed activity (protocol application or amendment application) within three (3) business days of receipt. The ORS staff will communicate the review status (as described in Section 3.6) within five (5) business days of the IACUC meeting or receipt of review comment(s) from the Designed Member Reviewer(s). ORS Staff will receive PI correspondence, when provided, and forward to the appropriate IACUC activity (Designated Member Reviewer(s), Chair, Vice Chair, Attending Veterinarian, etc.) within two (2) business days of receipt.
The process for PI notification of IACUC administrative actions is as follows (counting from the day of Full-Committee Review or the end of the Member Consideration Period as day 0):
Day 0-5 (Week 1): ORS staff will provide IACUC communication to Principal Investigator detailing the modifications required in (to secure approval), including specific IACUC clarifications, required training, etc. Email is the preferred method of communication. If there is no email address, then a facsimile or hard copy mailed letter may be used.
Day 10-15 (Week 3): If no response from the PI is received by this milestone, then the ORS staff will send a second correspondence to the PI requesting a response to the IACUC’s previous correspondence. Email is the preferred method of communication. If there is no email address, then a facsimile or hard copy mailed letter may be used.
Day 20-25 (Week 5): If no response from the PI is received by this milestone, then the ORS staff will send a third correspondence to the PI requesting a response to the IACUC’s previous correspondence. Email is the preferred method of communication. If there is no email address, then a facsimile or hard copy mailed letter may be used. A template letter is attached to this policy.
Day 30-35 (Week 7): If no response from the PI is received by this milestone, then the:
- ORS staff will send a fourth correspondence to the PI requesting a response to the IACUC’s previous correspondence. Email is the preferred method of communication. If there is no email address, then a facsimile or hard copy mailed letter may be used.
- ORS Staff will place a phone call to the PI, and if the PI is not available, a message will be left on the voice messaging system.
Day 40 (Week 8): If no response by the PI is received by this milestone, then the ORS staff will send an email (facsimile or hard copy letter) to the PI advising them of the termination action and advising them that a new protocol / amendment must be submitted to the IACUC if they wish to pursue this proposed activity.
In design of the research, training or educational activities, it is the responsibility of the PI to consider and include procedures that minimize animal pain or distress.
As required by the PHS Policy and the AWRs, and reiterated in the Guide, the IACUC is mandated to critically evaluate research protocols to ensure that pain and distress are minimized in laboratory animals and assure that appropriate steps will be taken to enhance animal well-being. The AWRs stipulate that the IACUC determine that the principal investigator has considered alternatives to procedures that may cause more than momentary or slight pain or distress to the animal and has provided a written narrative description of the methods and sources used to determine that alternatives were not available. The Guide states that the IACUC should ensure the protocol addresses:
- Appropriate sedation, analgesia, and anesthesia;
- Criteria for timely intervention, removal of animals from study, or euthanasia if painful or stressful outcomes are anticipated; and
- Details of post-procedural care.
The protocol must provide adequate information for the IACUC to assess the potential animal pain and/or distress resulting from the study and the effectiveness of the pain- and distress-relieving agents proposed for use. Criteria for re-dosing the animal should also be established. The AV must be consulted for any procedure that has the potential to cause more than momentary pain or distress.
Examples of procedures which the Guide suggests may have the potential to cause pain or distress, include:
- physical restraint,
- survival surgeries,
- food or water restriction,
- death as an endpoint,
- noxious stimuli,
- skin or corneal irritancy testing,
- tumor burdens,
- intra-cardiac or orbital sinus blood sampling, and
- abnormal environmental conditions.
Numerous references indicate that both laboratory animals and humans receive and process noxious stimuli using similar mechanisms. An animal’s response to pain is often adaptive to reduce movement to minimize re-injury and aid recuperation. This response, however, may lead to physiological and behavioral changes which impact negatively on both the animal’s well-being and the research results.
Fundamental to the relief of pain is the ability to recognize its clinical signs in various species of animals. Due to the inability of animals to verbalize, it is essential that animal care staff and researchers receive adequate training on how to recognize clinical signs of pain and distress. It is often useful to start with a general set of observations for assessing pain and distress such as change in body weight, physical appearance/posture or changes in unprovoked and provoked behavior. The assessment system should then be modified on a case-by-case basis using specific changes that may be anticipated in a particular study.
Accepted best practices for dealing with the possibility of unrelieved pain and distress should be considered and incorporated into protocols unless there is a sound scientific rationale for deviation from those practices. The investigator must also provide an assurance that unrelieved pain will continue for only the minimum period of time necessary to attain the study objectives.
Protocol methodology should be considered that decreases the potential for pain or distress. In addition to thorough searches of the literature, this can be done through the careful use of pilot studies to determine earlier endpoints or less invasive alternatives.
Pharmacologic treatment of pain or distress should be given as consistent with the type of pain/distress and the needs of the research question. The veterinarian must be consulted for all such protocols and should provide guidance to investigators and the IACUC. Non-pharmacologic treatments should also be employed. This may include special housing considerations, dietary and other environmental enrichments, adjustments and careful supportive care.
It is the responsibility of the investigator to show s/he has considered all the options for minimizing pain and distress that do not compromise the scientific validity of the experiment. The IACUC’s deliberations regarding the management of potential pain and distress in a protocol will be documented. Personnel should be trained in pain and distress management. The IACUC should ensure that there is a mechanism in place for prompt reporting of sick animals to the veterinary staff.
From time to time, the IACUC will issue guidance documents (a.k.a., Guidelines) to the University’s animal research community. These guidelines have been written to assist faculty, staff, and students in performing vertebrate animal procedures in a humane manner and complying with pertinent regulatory requirements. Under some circumstances deviations from these procedures may be indicated but such variances must be approved in advance by the IACUC.
A current list of available guidelines is available at: http://www.utexas.edu/research/rsc/iacuc/policies_index.html
3. This section contains content that was adapted from materials obtained from the University of Minnesota.
4. This section contains content that was adapted from materials obtained from the University of Minnesota.
5. Section 3.4 contains content that was adapted from materials obtained from the University of Pennsylvania.
6. Section 3.6.5 contains content that was adapted from materials obtained from Mississippi State University and Seattle Children’s Research Institute.