Office of Laboratory Animal Welfare
Model For Performing Institutional Animal Care and Use
Committee: Continuing Review of Animal Research
GWENN S.F. OKI, MPH (1), ERNEST D. PRENTICE, PHD (2), NELSON L. GARNETT, DVM (3), DALE F. SCHWINDAMAN, DVM (4), and CAROL Y. WIGGLESWORTH (5)
(1) Director, Research Subjects Protection, Research Administration, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000; (2) Associate Dean for Research, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-6810; (3) Director, Division of Animal Welfare, Office for Protection from Research Risks, 6100 Executive Boulevard, Suite 3B01, MSC 7507, Rockville, MD 20892; (4) Deputy Administrator, United States Department of Agriculture, Animal and Plant Health Inspection Service, Regulatory Enforcement and Animal Care, 4700 River Road, Unit 97, Riverdale, MD 20737-1234; (5) Senior Policy Analyst, Division of Animal Welfare, Office for Protection from Research Risks, 6100 Executive Boulevard, Suite 3B01, MSC 7507, Rockville, MD 20892. [The Animal Welfare Division of OPRR was renamed Office of Laboratory Animal Welfare (OLAW) in 2000.]
Abstract: Although institutional animal care and use committee (IACUC) continuing review of ongoing animal related activities is a requirement imposed by the Public Health Service Policy (PHS Policy) and United States Department of Agriculture (USDA) animal welfare regulations, there is lack of uniform understanding and application of these federal requirements. This paper endeavors to clarify the purpose and substance of continuing review through exploration of the requirements of the PHS Policy and the USDA regulations. It proposes a model that incorporates a practical, meaningful, and reasonable method of performing continuing review which institutions can adopt or modify to suit their individual needs.
The PHS Policy at IV.C.5. states "the IACUC shall conduct continuing review of activities
covered by this policy at appropriate intervals as determined by the IACUC but not less than once
every three years (3)". The USDA regulations 9 CFR 2.31(a)(5) (4) use similar language, except
that continuing review must be performed not less than annually.
The OPRR has interpreted the PHS Policy provision for continuing review as a requirement for a
"de novo" review (5-7). In this context, "de novo" means that the criteria and procedures for
review of projects specified in IV.C. of the PHS Policy must be applied not less than once every
three years. The IACUC must make the determination that the project conforms with the criteria
at IV.C.1.a-g. of the PHS Policy. These criteria address such factors as pain and distress, pain
relief, animal husbandry, veterinary care, personnel qualifications and methods of euthanasia. In
addition to confirmation that projects are in compliance with the PHS Policy, the IACUC must
also determine that the project is being conducted in a manner consistent with the "Guide for the
Care and Use of Laboratory Animals" (Guide), unless departure is justified.
The preamble to the USDA regulations provides guidance on the USDA requirement for annual
continuing review as follows: "We are adding a provision to the Final Rule to require that the
Committee conduct continuing review of activities covered by the Animal Welfare Regulations at
appropriate intervals, and at least annually [Final Rule 2.31(d)(5)]. This review...is intended to
provide current information to the Research Facility regarding all ongoing activities so it can
remain in compliance" (8).
The USDA interprets the role and purpose of the annual continuing review as one form of
monitoring the use of animals. Monitoring can be accomplished by the use of a standard form
containing basic protocol information to be provided by the investigator (status of the project,
assurance that activities are being conducted in accordance with the approved protocol, and
proposed departures from the protocol in the upcoming year). It should be noted that the USDA
regulations [9 CFR Part 2, Subpart C, 2.31(c)(7); 2.31(d)] and the PHS Policy [IV.C.1] require
that proposed significant changes to the currently approved protocol be reviewed and approved
by the IACUC prior to implementation.
THE PURPOSE AND SUBSTANCE OF CONTINUING
|Species||Total # Approved||# Used to Date|
|[ ]||Survival (Chronic) Study||[ ]||Prolonged Restraint||[ ]||Inducement of a Disease State|
|[ ]||Terminal (Acute) Study||[ ]||Neuromuscular Blockers||[ ]||Inducement of Behavioral Stress|
|[ ]||Multiple Surgeries||[ ]||Antibody Production||[ ]||Blood/Tissue Collection|
|[ ]||Transgenic Breeding|
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Request Protocol Continuance
Request Protocol Termination
|[ ]||Yes:||Have there been any personnel/staff changes since the last IACUC|
|approval was granted?|
|[ ]||No:||If yes, please complete the following sections (Additions/Deletions).|
|For additions, please submit a completed Personnel Qualification|
|Statement with this Continuing Review Form and make arrangements|
|with the Animal Resources Center staff for inservice training on the|
|proper care and handling of laboratory animals.|
Additions: Name/Role/Responsibility for Project
[Please note that if the modifications are significant, you may be required to complete a new
application. If you have questions or require assistance in making this determination, please
contact the IACUC Office and/or the Attending Veterinarian.]
CERTIFICATION OF THE PRINCIPAL INVESTIGATOR.
Signature certifies that the Principal Investigator understands the requirements of the PHS Policy
on Humane Care and Use of Laboratory Animals, applicable USDA regulations and the
Institution's policies governing the use of vertebrate animals for research, testing, teaching or
demonstration purposes. Signature further certifies that the investigator will continue to conduct
the project in full compliance with the aforementioned requirements.
Signature of the Principal Investigator||
Section 1 would be completed by the IACUC Office via database generation of the report form.
The information captured in this section is considered to be basic protocol-identifying data, which
may be helpful to any designated reviewer, as well as to the Committee, in their assessment. In
addition, certain items, such as the pain category and nature of the protocol may prompt the
IACUC to look more closely at the continuing review update.
Item 4--Protocol Status; 5--Funding Status; and 6--Project Personnel. The status of the protocol,
funding source, and changes in project personnel are fairly standard questions to which the
investigator is expected to provide responses.
Item 7--Progress Report. The progress in achieving the specific aims of the protocol should be
described. The information in this section should be provided as an update to help the IACUC
document the continued approvability of the research. For example, if 50 dogs were used and the
investigator had no progress to report, in light of the specific aims of the protocol, it would be
reasonable for the IACUC to request clarification. It should, however, be recognized that
scientific inquiry may involve "blind alleys", and
failed experiments, thus resulting in little progress in the short- versus long-term.
Item 8--Problems/Adverse Events. Any unanticipated problems or adverse events that
have occurred should be reported, as well as an explanation of how these events/problems were
resolved. Depending on the information provided here, this response may also need to be factored
into the IACUC's assessment of the ethical cost-benefit justification.
Item 9--Alternatives to Animal Use. This section raises the question of whether any viable
alternatives to use of live animals have become available since the last IACUC review.
Item 10--Alternatives to Potentially Painful Procedures. This section asks whether there are any
alternatives to USDA Category D or E procedures that are potentially less painful and could be
used to achieve any of the specific aims of the research. The USDA Category D and E
procedures are defined as follows. Animal activities in Category D involve "procedures that may
cause more than momentary or slight pain or distress" for which appropriate sedatives, analgesics,
or anesthetics will be administered (12,13). Category E is similarly defined, with the exception
that sedatives, analgesics, or anesthetics cannot/will not be administered due to scientific
Item 11--Duplication. This section requests assurance that the animal activities do not
unnecessarily duplicate previous experiments, as required by USDA regulations.
Item 12--Future Plans. The investigator is asked to indicate future plans for continuation of
his/her project. This would include an indication as to whether the research would continue as
originally approved; or conversely, if changes are planned, an outline, description, and brief
justification of the proposed changes should be provided.
Finally, the investigator is asked to sign the Continuing Review Form, which contains a
certification of his/her understanding and responsibility for conduct of animal activities in
accordance with the PHS Policy, USDA regulations and the institution's (IACUC) policies.
Signature here also attests to the accuracy of the investigator's responses. Requiring completion
of this form, at least annually, indicates to the investigator the seriousness of the IACUC's review
and the importance of investigator accountability for his/her research activity; for reporting it
accurately; and for justifying continuance of the research project for another year. Accordingly,
the IACUC, through its designated reviewer mechanism, is also held accountable for appropriate
and responsible review of the IACUC protocol file, and for continuation approval of ongoing
animal research, if it is still justified.
Method of IACUC continuing review. All IACUC members would be
provided a copy of the completed Continuing Review Form, and would have access to the
corresponding IACUC protocol file on request. Any IACUC member could ask for a full
committee review of the Continuing Review Form and the protocol. Utilizing the "designated
reviewer" process, if none of the IACUC members requests full committee review, the IACUC
Chair would then designate at least one qualified member (i.e., designated reviewer) to conduct an
in-depth review of the current protocol in conjunction with the Continuing Review Form. This
review would include consideration of the previously described continuing review criteria in
accordance with PHS Policy IV.C. The designated reviewer would then review and be authorized
to approve, require modifications in order to approve, or require full committee review of the
protocol in question. By conducting such a comprehensive "de novo" review on an annual basis,
using this model, there is no further PHS Policy requirement for continuing review at three-year
The way in which an institution chooses to implement the PHS Policy and USDA regulations is
subject to change over time. Changes in IACUC membership may result in different perceptions
and judgements regarding animal use issues. These changes may affect the outcome of continuing
review, as will the evolutionary changes in protocol review forms, new regulations and guidelines,
and precedents set by ongoing regulatory compliance activities, internal and external to the
institution. Oki and Prentice, therefore, recommend that, in addition to the procedures outlined
previously, a complete new IACUC protocol review form (i.e., new IACUC application form) be
submitted if a project will extend beyond six years. There is, however, no federal requirement for
resubmission of a new application for IACUC review within any time frame.
In summary, the review process and report form described in this section meet the requirements of
the PHS Policy and the USDA regulations for continuing review. Use of this model for
performing IACUC continuing review would rely upon yearly comprehensive "de novo" reviews
for institutions desiring to comply with both sets of requirements (PHS Policy and USDA
The PHS Policy and USDA regulations were intentionally written to avoid a great deal of
specificity with regard to institutional procedures. This has provided institutions with a needed
degree of flexibility in designing, implementing and adjusting their own individual systems of
ensuring compliance with the PHS Policy and the USDA regulations. Many provisions of the
PHS Policy and USDA regulations are, therefore, open to variable methods of implementation.
Over the last decade, academicians, administrators and federal regulators have struggled with the
imperative to interpret and apply the PHS Policy and USDA regulations in a practical, meaningful
and reasonable way to ensure the highest possible standards of laboratory animal welfare while
facilitating valuable research for the benefit of humans and/or animals. As a result, our
understanding of what constitutes appropriate animal welfare in a research context has grown
tremendously. Today, the IACUC is a far more sophisticated and effective review body than it
was in 1985 when the PHS Policy was first promulgated.
It is not surprising that there has not always been agreement between the academic/research
community and federal regulators. Some have publicly criticized the OPRR and the USDA for
failing to provide "black and white" guidance on exactly how the PHS Policy and USDA
regulations should be interpreted and implemented. In response, however, it is our contention
that laboratory animal welfare is best promoted by engaging in a partnership of communication
and problem solving between the federal regulators of animal welfare, the IACUCs, and the
investigators who use animals in research and other activities. In addition, the philosophy and
message of animal welfare groups who oppose animal-based research should be given thoughtful
consideration as we struggle to achieve the appropriate balance between the needs of science and
fulfillment of our moral and ethical responsibility to animals and society. Our joint and mutually
accepted understanding of the meaning of the "letter" and the "spirit" of the PHS Policy and
USDA regulations has evolved and continues to do so in the interest of promoting animal welfare
and facilitating valuable research.
The model for continuing review presented in this paper represents a comprehensive approach and
should not be confused with a minimalist's approach to the task (i.e., compliance with only the
"letter of the law" without attempting to address "the spirit of the law"). To achieve the highest
possible standards of laboratory animal welfare, institutions should view the PHS Policy and
USDA regulations as establishing standards that serve as a platform on which to build as our
understanding of science, animal welfare and research ethics increases. We think the institution's
animal care and use program should be dynamic and evolving in nature as we identify ways in
which laboratory animal welfare can be improved. It is important to note that although the model
described herein by Oki and Prentice was designed principally to meet PHS requirements for
triennial review, it also complies with and, indeed, exceeds the USDA requirements for annual
review. Finally, we point out that institutions may adopt other models for performing continuing
review that may be equally acceptable from regulatory and ethical viewpoints.