Sample Policy #2
Review of Significant Changes to Previously Approved Protocols
This policy is intended to clarify the process for determining what constitutes a “significant
change” to an approved ARC protocol, and to describe the process for review of these activities.
Statutory Basis
Federal regulations require that the Institutional Animal Care and Use Committee (IACUC) at
each institution “review and approve, require modifications in (to secure approval), or withhold
approval of proposed significant changes regarding the use of animals in ongoing activities”
(USDA AWRs §2.31(c)(7), PHS Policy IV.B.7).
PHS Policy IV.C.1 requires that when reviewing any “proposed significant change,” the IACUC
“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 [the PHS] Policy. In making this
determination, the IACUC shall confirm that the research project will be conducted in
accordance with the Animal Welfare Act insofar as it applies to the research project, and that the
research project is consistent with the Guide [Guide for the Care and Use of Laboratory
Animals] unless acceptable justification for a departure is presented.”1
IACUC approval of proposed animal activities or significant changes to previously approved
animal activities is generally only granted after full committee review (FCR) or designated
member review (DMR). However, thanks to new guidance from OLAW, the IACUC now has
some discretion to use local policies to define what it considers a significant change, or to
establish a mechanism for determining significance on a case-by-case basis in accordance with
the PHS Policy IV.C.1.a.-g.
According to OLAW, “…significant changes include changes that have, or have the potential to
have, a negative impact on animal welfare. In addition, some activities that may not have a direct
impact on animal welfare are also considered to be significant.” In an effort to reduce regulatory
burden, and acknowledging the roles of professional judgment and performance standards,
OLAW also allows institutions to develop policies to allow administrative handling of some
significant changes. See the OLAW Guidance on Significant Changes to Animal Activities
(http://grants.nih.gov/grants/olaw/significant_changes.htm) for more information.
ARC Review of Significant Changes
With the exceptions outlined by OLAW, the ARC must review all proposed significant changes
using either the Full Committee Review (FCR) or Designated Member Review (DMR) processes
(see http://oaro.research.ucla.edu/OARO/Pages/applications.aspx#reviewprocess).
Significant changes that must be reviewed by FCR or DMR include changes:
1
Specific criteria that must be considered are set forth in PHS Policy IV.C.1.a.-g., USDA AWRs §2.31(d)(1)(i)-(xi),
and USDA AWRs §2.31(e).
Approved 3/28/11
Significant Changes to Previously Approved Protocols
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a. adding one or more survival surgeries;
b. resulting in greater pain, distress, or degree of invasiveness;
c. in housing and or use of animals in a location that is not part of the animal program currently
overseen by the IACUC;
d. in species;
e. in overall study objectives;
f. in Principal Investigator (PI);
g. that impact personnel safety.
Investigators are advised to build flexibility into their protocols in order to minimize the
likelihood that significant changes must be made to the protocol (e.g., including a maximum
volume of blood to be collected, alternate methods of blood collection, a range of drug doses to
be administered).
If a proposed significant change does not appear on the above list of significant changes
requiring FCR or DMR, it may be eligible for administrative review. At the discretion of the
ARC Chair or Vice-Chair the specific changes described below may be handled administratively:
a. anesthesia, analgesia, sedation, or experimental substances;
b. euthanasia using any method approved in the AVMA Guidelines for the Euthanasia of
Animals;
c. duration, frequency, type or number of procedures performed on an animal.
d. increase in previously approved animal numbers.
The ARC Chair or Vice-Chair, in consultation with the authorized veterinarian2, is empowered to
review these changes.
Review of Non-Significant Changes
Changes that are considered not significant may be reviewed by the ARC Chair or Vice-Chair, or
authorized OARO staff3; these changes include:
a. personnel, excluding the PI;
b. contact information;
c. title of ARC protocol; and
d. funding.
In all cases, the PI must submit an amendment, in the regular manner, describing the
changes for review.
2
The authorized veterinarian was selected by the ARC to serve as a subject matter expert in this circumstance. The
individual designated to serve in this capacity is a matter of record in the ARC office.
3
The OARO staff authorized to perform administrative review of non-significant changes were selected by the ARC
at a convened meeting and is a matter of record in the ARC office.