Modifications to Approved Protocols
The PHS Policy on Humane Care and Use of Laboratory Animals and Animal Welfare Regulations define the responsibilities of the IACUC regarding review and approval of proposed significant changes to animal activities. Changes to approved research projects must be conducted in accordance with the institution’s Assurance, the US Department of Agriculture (USDA) Animal Welfare Act and Animal Welfare Regulations, and must be consistent with the Guide unless an acceptable justification for a departure is presented. Additionally, IACUCs are responsible for assuring that the changes to approved animal activities meet the requirements described in the PHS Policy.
The IACUC has defined a Significant Change as any deviation from the protocol that substantially alters or affects the overall study objectives/rationale, specific approved procedures, or the potential for pain, distress and discomfort in the animals. Since changes to approved animal-use protocols vary in their potential impact on the welfare of the animals, the Office of Laboratory Animal Welfare (OLAW) has granted assured institutions some discretion in determining the level of review required for modifications to approved protocols. The IACUC has developed and approved standard guidance and procedures to determine the level of review required for each modification request in order to assure that the highest level of humane animal care is maintained while assuring that researchers are not unduly burdened by administrative requirements.
In general, the addition of a new procedure that increases the invasiveness or the amount of pain or distress an animal experiences requires review by the full committee, either at a convened meeting or via Designated Member Review. Additionally, if the study objective changes significantly, a new protocol may be required. Consultation with a ULAR Veterinarian or the IACUC Administrative Staff is recommended for assistance in determining appropriate levels of review.
Levels of Review
All requests to modify approved protocols are administratively assessed to determine the appropriate level of review:
A. Full Committee Review
Modification request of significant changes must be submitted for review at a convened meeting of the IACUC with a quorum present.
Examples of modifications that require full committee review:
- Additional Animals in Category E (unrelieved pain/distress)
- Major Changes in Scope or Experimental Design
- Invasive Procedures likely to increase pain, distress or discomfort
- Addition of a new species
- Departures from the Guide
B. Designated Member Review
Modification request of significant changes may be reviewed by a subcommittee consisting of at least two voting members of the IACUC, provided that no member of the IACUC calls for an elevation of the modification request to full committee during a 5-day electronic polling period (review of a written description of the request by all committee members via email).
Examples of modifications that may be considered for Designated Review:
- Additional experiments that fit within the scope/rationale of the originally approved protocol
- Substantial changes to experimental design
- Additional animals - approximately 25% of the originally approved allocation of research animals (categories C and D only; increases in category E require full committee review)
- Change in Lead Researcher
- Changes that may have an impact on the safety of research personnel
Note: A modification submitted for Designated Member Review may be elevated to Full Committee Review at the request of any single voting member of the IACUC.
C. Accelerated Review (Within Pre-Approved Categories)
Significant Changes that may be handled administratively in consultation with a veterinarian authorized by the IACUC are classified below (these categories are subject to review by the IACUC at least once per year):
- Changes in therapeutic agents listed in the ULAR Drug Formulary
- Changes in anesthesia, analgesia, sedation or experimental substances including new drugs of the same class (purpose), change of duration, frequency, route of administration, or dosage as long as the proposed changes are consistent with standard veterinary care.
- Change in euthanasia method, provided it is approved in the AVMA Guidelines for Euthanasia
- Changes to approved blood collection procedures in accordance with IACUC Guidelines for Blood Collection in Rodents.
- Changes between acceptable methods for collection of tissue for genetic analysis as defined in the IACUC policy/guidelines on Rodent Breeding Colonies (tail tip excision, ear punch, peripheral blood collection, distal toe clipping).
- Minor changes to duration, frequency, type or number of procedures performed on an animal; provided that, in the professional opinion of the veterinarian, the change will not increase the potential for pain, distress or discomfort.
D. Administrative Changes
The following changes are NOT considered "significant" and are subject only to administrative review and processing:
- Changes in funding source
- Changes/updates to non-key personnel
- Changes in lab area locations (where live animals are used or held)
- Contact information updates
- Increase in up to 100% of the originally approved allocation for category B animals
- Increase in animal numbers of not more than 25% of the originally approved allocation in pain categories C and D
- Reallocation of animal numbers between condition codes (NA, Pregnant, Dams w Litter)
- Additions of strains for a previously-approved species, including genetically-modified strains
Notes and Guidance
- Significant Changes (categories A-C above) require submission of the following:
- Completion of the Modification Tab in RMS
- Proposed changes incorporated into the protocol
- Refer to our Modification Submission Guidance page for advice on how to submit modifications.
- All modifications requests must be submitted by approved personnel who are listed on the protocol.
- See our Applications & Forms page for all document forms.
- All modification requests are subject to rigorous pre-review. The appropriate level of review will be assessed at the time of submission; any request may be forwarded for Full Committee Review for any reason at the discretion of the veterinarians and/or IACUC administrative staff.
- Requests for additional animals, regardless of strain, must include a brief explanation for why the additional animals are required.
- The addition of genetically modified animals must include:
- Justification for the new strain
- Description of any possible phenotypic abnormalities
- Creation/generation of genetically modified animals may require Institutional Biosafety Committee (IBC) oversight.
- Changes to therapeutic agents may be processed administratively with veterinary consultation provided the proposed agents, dosage ranges, etc. are consistent with the ULAR Drug Formulary. All proposed changes will be reviewed for potential hazards to research and vivarium/husbandry personnel and may require additional oversight from Environmental Health and Safety and/or the Institutional Biosafety Committee.
- Changes between methods of euthanasia may be processed administratively with veterinary consultation, provided that the new method is consistent with the AVMA Guidelines on Euthanasia.