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Protocol Review Process
Under the AWRs and PHS Policy, the requirements of IACUC protocol review are as follows:
Pre-review
Prior to the review, each IACUC member must be provided with a list of proposed research projects to be reviewed. Written descriptions of research projects must be available to all IACUC members, and any member of the IACUC may obtain, upon request, full committee review of those research projects.
A best practice is to avoid literal interpretation that only a list of protocol names needs to be provided to IACUC members before the meeting. IACUCs routinely provide the actual protocols as well as an agenda listing the protocols scheduled for review.
Many IACUCs assign personnel to conduct a pre-review of animal use protocols before IACUC members review the forms. Pre-review can be limited to administrative issues, such as documentation of training, or can involve a veterinarian or other IACUC member(s). Pre-review often dramatically increases the efficiency of IACUC review because it results in fewer corrections and clarifications during actual IACUC meetings. For example, a pre-review might reveal that a protocol is missing information that would delay IACUC approval if not discovered until the IACUC meeting.
Designated Member Review:
If full committee review is not requested, at least one member of the IACUC, designated by the chairperson and qualified to conduct the review (the so-called designated reviewer) reviews those research projects and has the authority to:
o Approve;
o Require modifications (to secure approval); or
o Request full committee review of those proposed projects.
Sometimes more than one designated reviewer is used. If they do not agree on the review outcome, a full committee review would be required.
It is considered a best practice to have a detailed standard operating procedure (SOP) or policy for designated and full committee review to guide IACUC members and the Chair.
To secure approval and to comply with federal regulations, an animal use protocol should completely address the following:
o Relevance of the proposed study to human or animal health, the advancement of knowledge or the good of the society.
o Justification for why animals are needed in the study.
o Adequacy of the species, quality and quantity of animals requested for study.
o Proper husbandry and veterinary care for the animals.
o Ways to minimize pain and distress including alternatives to potentially painful and distressful procedures.
o Complete description of all procedures to be performed, including use of aseptic techniques during surgery, pre and post-operative monitoring and pain relief.
o Humane experimental endpoints and appropriate euthanasia.
o Training, qualifications and experience of all individuals involved in the study.
o Consideration for safety of individuals and animals involved in the study.
o Statement that the study does not unnecessarily duplicate previous studies.
NOTE: The term “designated member review” is sometimes confused with “expedited review.” However, “expedited review” refers to a process by which an Institutional Review Board (IRB) — which reviews human subjects research — Chair or an experienced reviewer may conduct reviews of human research protocols that meet certain minimal risk criteria without input from other IRB members.
This expedited review is not the same procedure as designated member review allowed for IACUC use. The difference is that designated member review can only occur if all IACUC members have the opportunity to decide that full committee review is not needed. IRB expedited review can occur without input from other IRB members.
Full Committee Review:
If full committee review is requested, approval of those research projects may be granted only after review at a convened meeting of a quorum of the IACUC and with the approval vote of a majority of the quorum present.
The full committee may:
o Approve;
o Require modifications (to secure approval); or
o Disapprove a proposed activity.
Again, to secure approval and to comply with federal regulations, an animal use protocol should completely address the criteria described above under Designated Review.
A common reason for disapproval of a study is insufficient information to proceed with a full-fledged study. In such cases, the IACUC may recommend a pilot study, or a limited study that utilizes a small number of animals, and can reveal important information that can ultimately reduce animal pain/distress and/or reduce animal numbers in a full study. Pilot studies can be used for many purposes, such as improving study design, determining the earliest and most humane experimental endpoints, minimizing the number of animals and ensuring appropriateness of the species, adjusting dose ranges, assessing the need for analgesics or anesthetics, and identifying other unanticipated or adverse events.
Minority Opinions:
Occasionally, IACUC members will not be able to agree on issues, and a member might want to file a minority opinion that disagrees with the vote of a majority of a quorum. Both the Animal Welfare Regulations (AWRs) and PHS Policyrequire minority opinions to be recorded in the IACUC report generated by the semi-annual program evaluation (Chapter 6/Week6). However, the AWRs and PHS Policy are silent on the issue of minority reports for protocol reviews.
It is considered a best practice by many institutions to give all IACUC members the opportunity to record minority opinions in the minutes for any type of business conducted. Not to do so can give the appearance of trying to suppress dissension, which can be damaging to the reputation and integrity of the IACUC, and prevent open and honest discussions of important issues.
Standard Operating Procedures (SOPs):
Animal use protocols often incorporate frequently used procedures that have become routine. By including such procedures into institutional standard operating procedures (SOPs), investigators can simply reference the procedure as described in the SOP rather than describe it in detail for every protocol in which the procedure is used.
Activities that might be included as SOPs are routine blood sampling procedures; species-specific pain regimens for commonly used drugs; and frequency and method of documenting animal observations.
Other common SOPs found in many institutions include contingency plans for emergencies (loss of power, flooding, etc.), and animal disease prevention and surveillance.
Conflict of Interest:
No member may participate in the IACUC review or approval of a research project in which the member has a conflicting interest (e.g., is personally involved in the project) except to provide information requested by the IACUC; nor may a member who has a conflicting interest contribute to the constitution of a quorum.
Consultants:
The IACUC may invite consultants to assist in the review of complex issues. However, consultants may not approve or withhold approval of an activity or vote with the IACUC unless they are also members of the IACUC.
Notification of IACUC Decisions:
The IACUC must notify investigators and the institution 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. If the IACUC decides to withhold approval of an activity, it must include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing.
Continuing Review:
The IACUC must conduct continuing review of each previously approved, ongoing activity at appropriate intervals determined by the IACUC. The AWRs require review at least annually, while PHS Policy requires de novo review of animal use activities at least once every three years.
As best practice, the IACUC (usually the IACUC coordinator or manager) sends a reminder and renewal form to the PI at least a month in advance of the anniversary of the protocol’s approval. The completed form must be received by the IACUC before the anniversary of the protocol’s approval to ensure review prior to the anniversary date.
Suspension of an Activity:
The IACUC may suspend an activity that it previously approved if it determines that the activity is not being conducted in accordance with the AWRs, the Guide, the institution’s Animal Welfare Assurance, or PHS Policy.
The IACUC may suspend an activity only after review of the matter at a convened meeting of a quorum of the IACUC and with the suspension vote of a majority of the quorum present.
If the IACUC suspends an activity involving animals, the Institutional Official — in consultation with the IACUC — must review the reasons for suspension, take appropriate corrective action, and report that action with a full explanation to OLAW, USDA, and to any other federal funding agency, if applicable.
Further Review:
Applications and proposals that have been approved by the IACUC may be subject to further appropriate review and approval by officials of the institution or by other committees (the Institutional Biosafety Committee, for example). However, neither those officials nor those committees may approve an activity involving the care and use of animals if it has not been approved by the IACUC.
Record Keeping:
The institution is required to document the presence of a quorum; adequacy of review; committee deliberations; and all IACUC decisions.