Significant Changes to Approved Protocols

Changes to Approved Animal Use Protocols

Approved on October 16, 2014 (Download)

Background: Federal regulations require review and approval by the IACUC of Significant Changes in any activity involving the use of vertebrate animals; federal regulations also require administrative review and handling of some other changes that are not considered significant.  On August 26, 2014 the Office of Laboratory Animal Welfare at NIH released new guidance regarding changes to animal activities, specifically addressing how Significant Changes and Other Changes are defined, reviewed and approved.  The newly revised UW Policy on Significant Changes, as well as other changes to animal use protocols, is described below, and brings the University of Washington into alignment with the new guidance.  We recommend that you contact the Office of Animal Welfare (OAW) to inquire if there is any question about whether a requested modification to a protocol constitutes a Significant Change.

Principal investigators are responsible for ensuring that members of their staff who work with animals are familiar with all relevant procedures and details specified in the protocols.

In addition, supervision of work performed on animals must be adequate to ensure that approved protocols are being followed and that Significant Changes are not implemented prior to approval.

Policy: This policy defines three categories of ‘Significant Changes’ and outlines the procedures used to review and approve such changes.  This policy also identifies some changes that are not significant, and describes the procedures for handling these.  Based on current guidance there are 3 defined ways of approving a Significant Change to an animal use protocol depending on the nature of the Significant Change (Sections A, B, C).  Some changes are not significant but still require administrative approval (Section D).  Some changes are not significant and do not require administrative approval (Section E).  Each change will be assessed on a case by case basis, using the criteria below, to determine the appropriate category for approval.   

A. A Significant Change that must be reviewed and approved using the standard approval methods described in the PHS Policy IV.C.2.—i.e. full committee review or designated member review—includes any proposed modification of an IACUC-approved protocol that results in any of the following:

    1. changes in surgical procedures:
      • from not involving surgery to involving surgery;
      • from non-survival to survival surgery;
      • from minor surgery to major surgery;
      • from a single surgical procedure to multiple surgical procedures;
    2. changes resulting in greater pain, distress, or degree of invasiveness from what was either specified or presumed to occur when the protocol was originally reviewed;
    3. changes in euthanasia to a method not approved by the AVMA;
    4. changes in housing and or use of animals in a location that is not part of the animal program overseen by the IACUC;
    5. changes in species;
    6. changes in study objectives or overall aims;
    7. changes in Principal Investigator (PI);
    8. changes in animal numbers greater than specified in Section C below, or due to morbidity or mortality not described in the IACUC-approved protocol,or due to the addition of a new experiment or experimental group; and
    9. changes that impact personnel safety

B. A Significant Change that can be reviewed and approved by the University of Washington Attending Veterinarian, or designee, includes the following:

    1. changes in anesthesia, analgesia, sedation, or experimental substance that do not result in greater pain, distress, or degree of invasiveness;
    2. changes in euthanasia to any method approved in the AVMA Guidelines for the Euthanasia of Animals; and
    3. changes in duration, frequency, type, or number of procedures performed on an animal that do not result in greater pain, distress, or degree of invasiveness.

The veterinarian reviewing and approving such changes will confirm that the requested change is in alignment with this policy and does not change any of the items listed in Section A, is in alignment with all relevant IACUC policies (e.g., Analgesia in Research Animals), conforms with sound professional judgment, and should not require training that cannot be provided to the investigative group at or before implementation of the change.  Furthermore, the veterinarian, for any reason, may refer any Significant Change request to the IACUC for approval as described in Section A.  The veterinarian and PI are responsible for ensuring that the approval is routed to the OAW for inclusion in the PI’s animal use protocol.

C. A Significant Change in animal numbers can be reviewed and approved administratively by the OAW if:

    1. the animals are being requested to replace animals that could not be used (note that requests for additional animals for a new experiment that is not described in the approved protocol cannot be handled administratively); and
    2. the number of additional animals is not more than 10% of the number of animals initially approved, or not more than one animal, in the case of an experiment for which fewer than 10 animals were initially approved.

  If additional animals are needed due to unexpected morbidity or mortality associated with an IACUC-approved experiment, the adverse event(s) must be reported to the IACUC.  In this case, an increase in animal numbers requires IACUC approval as described in Section A.

D. Changes that may be handled administratively by the OAW include:

    1. correction of typographical errors;
    2. correction of grammar;
    3. contact information updates;
    4. changes in personnel, other than the PI, if such personnel meet the UW training requirements and are enrolled in Occupational Health and Safety programs; and
    5. changes in rodent strain if the new strain has no increased morbidity or mortality, and the new strain will require no additional monitoring.

E. Investigators may use fewer animals than approved. This does not require IACUC or OAW approval, notification, consultation, or administrative handling.