The National Institutes of Health's (NIH's) Office for Protection from
Research Risks (OPRR) is responsible for developing, implementing, and
overseeing compliance with the Public Health Service (PHS) Policy on the Humane
Care and Use of Laboratory Animals (Policy). The PHS Policy, along with the U.S
Department of Agriculture's (USDA's) Animal Welfare Regulations, are the two
principal federal documents setting forth requirements for animal care and use
by institutions using animals in research, testing, and education. A primary
function of OPRR in assisting institutions in implementing PHS Policy is to
respond to policy-related questions.
The following represent a few of the most commonly asked questions from
institutions and the OPRR responses:
1. Are avian embryos covered by the PHS Policy, i.e., must their
proposed use be reviewed and approved by institutional animal care and use
committees (IACUCs)?
PHS Policy is applicable to proposed activities that involve live vertebrate
animals. While embryonal stages of avian species develop vertebrae at a stage
in their development prior to hatching, OPRR has interpreted "live
vertebrate animal" to apply to avians (e.g., chick embryos) only after hatching.
2. May our institution apply the requirements of the PHS Policy
exclusively to activities that are supported by the PHS? In other words, may we
apply different requirements for application and proposal review when the
proposed work is funded by another agency or is it to be conducted with internal
institutional funds?
Institutional adherence to PHS Policy is a requirement for all activities
supported by the PHS, most commonly through NIH grants or contracts, but also
including other forms of PHS support such as collaborations and postdoctoral
stipends. Since the 1985/1986 revisions to the PHS Policy, the vast majority of
institutions filing Animal Welfare Assurances with OPRR have chosen to apply the
Policy requirements to all activities involving animals at their institution.
Until 1989, dual mechanisms with PHS-supported and non PHS-supported
activities were theoretically possible. With the finalization in 1989 of Part 2
of the USDA regulations, which includes administrative requirements for proposal
review, veterinary care, and personnel qualifications, such dual systems are
impractical. Part 2 of the USDA regulations are virtually identical to the PHS
Policy. Thus, institutions using species covered by the USDA regulations (which
currently exclude mice and rats) must establish programs and follow procedures
identical to those required by the PHS Policy in order to meet USDA
requirements. A more pragmatic reason for having a uniform institutional policy
has to do with the public relations dilemma of trying to defend a double
standard of humane care for animals. Accordingly, institutional policies should
be designed with an emphasis on the desired outcome of appropriate humane care
and use of all animals at the institution.
3. Our institution requires that when the IACUC meets, not only must a
majority of the members be present, but that the quorum must include the
institutional veterinarian and a nonaffiliated member. Is this requirement in
keeping with PHS Policy?
Two issues are actually contained in this question: (1) Must the
veterinarian and/or nonaffiliated member be present for all formally convened
meetings of the IACUC? and (2) May an institution impose requirements more
stringent than the corresponding provision of the PHS Policy? The PHS Policy is
silent on the first question. OPRR has interpreted the Policy to provide that,
with respect to the IACUC, all members are equal. Thus there is no requirement
that the veterinarian and/or the nonaffiliated member be present for every IACUC
meeting. Attention should be paid by institutions to attendance at IACUC
meetings ensuring that an appropriate mix of members attends all meetings and
that frequent absences from such meetings by any member are avoided. No member
may be excluded from any IACUC function (e.g., semiannual reviews). A history
of nonattendance by IACUC members, especially those required by statute, will
always arouse the suspicion of a site visitor or inspector.
With regard to the second question, institutionally imposed requirements
that exceed those of the PHS Policy are not proscribed by the Policy.
Additional requirements may be imposed by the institution at its discretion,
bearing in mind that the spirit of the PHS Policy is to promote humane care and
use of animals, while facilitating the pursuit of legitimate scientific
objectives.
4. Is it permissible under PHS Policy to reimburse the nonaffiliated
member of the IACUC?
Meeting fully the letter and spirit of the PHS Policy (and USDA regulations)
requires that the nonaffiliated IACUC member be completely disinterested in the
institution's profit or benefit from proposed activities that involve animals.
While in the vast majority of instances effective nonaffiliated IACUC members
may be willing to serve without reimbursement, in other instances remuneration
may allow for participation by effective individuals that would not otherwise be
possible. Both OPRR and USDA maintain that nominal compensation is permissible
without jeopardizing a member's nonaffiliated status, if it is only in
conjunction with service on the IACUC. The level of reimbursement varies from
payment of travel and related expenses, such as parking and meals, to modest
monetary payments for participation in this capacity. The dollar amount of
compensation, if any, should not be so substantial as to be considered an
important source of income or to influence voting on the IACUC.
5. In fulfilling its requirements under PHS Policy and USDA
regulations, must the IACUC inspect every laboratory or other site where
investigators use animals?
When considering IACUC responsibilities for semiannual review, it is
important to keep in mind that the institution, usually acting through the IACUC
and/or the facility veterinarian, is responsible for all animal-related
activities of the institution, regardless of where animals are maintained or the
duration of their stay. The PHS Policy allows institutions some discretion
regarding specific methods to assure compliance, but the institution is clearly
responsible for what happens to animals in investigators' laboratories. The
degree, method, and frequency of IACUC oversight depends a great deal on the
nature of the activity. For example, satellite holding facilities or areas
where surgical manipulation is conducted should always be included in the
semiannual review. Other activities, such as routine dosing, weighing, or
immunization of animals in laboratories, may be monitored using other methods
such as random evaluation.
Inclusion of these laboratories in the semiannual IACUC review would be
another way to satisfy the PHS Policy requirements. In any case, the IACUC must
have access to all investigators' laboratories for the purpose of verifying that
activities involving animals are conducted in accordance with the proposal
approved by that committee.
6. The PHS Policy requires semiannual IACUC inspection of all
facilities where animals are held for 24 hours or more, while the USDA
regulations require such inspections of sites where animals are kept for 12
hours or more. How should our IACUC deal with this discrepancy?
The PHS Policy requires compliance with the Animal Welfare Act. The USDA
regulations apply to animal study areas where USDA-covered species are
maintained for more than 12 hours. These areas of the facility must be included
in the semiannual review. The PHS Policy definition of satellite facility and
duration of stay requirements remain unchanged, and may be applied to species
such as rats and mice that are covered by the Policy but not by USDA
regulations. The important point to remember is that the institution remains
accountable for all activities involving animals, regardless of any technical
differences in definitions and time limits. Again, institutional policies
should be designed with an emphasis on the desired outcome of appropriate humane
care and use of all animals at the institution.
7. To what extent, if any, is the IACUC responsible for assessing the
scientific merit of proposals it reviews?
Peer review of the scientific merit of a proposal is considered to be the
purview of the PHS funding component, acting through an initial review group
(IRG). The PHS Policy requires the funding component to verify that the IACUC
has reviewed and approved animal activities before the PHS awarding unit makes
an award. Additionally, the IRG has the authority to raise specific animal
concerns. The primary focus of the IRG is scientific merit, whereas the primary
focus of the IACUC is animal welfare. It is evident, however, that there is
some overlap of function between the two bodies.
Although not intended to conduct peer review of research proposals, the
IACUC is expected to include consideration of the U.S. Government Principles
for the Utilization and Care of Vertebrate Animals in Testing, Research, and
Training (PHS Policy) in its proposal review process. Principle II calls
for an evaluation of the relevance of a procedure to human or animal health, the
advancement of knowledge, or the good of society. Other references (sections
IV.C. I and IV.D. 1.) include language such as "consistent with sound
research design," "rationale for involving animals," and "in
the conduct of scientifically valuable research," which presumes that the
IACUC will consider in its review the general scientific relevance of the
proposal. The presumption is that a study that could not meet these basic tests
would be inherently invalid or wasteful and, therefore, not justifiable.
8. The PHS Policy requires that the IACUC "conduct continuing
review of activities" at least every 3 years, while the USDA regulations
require such review annually. How can our IACUC best meet both these
requirements?
The frequency of IACUC consideration of approved, ongoing activities is one
of the few areas in which the PHS and USDA have differing requirements, that is,
PHS requires it at least once every 3 years, whereas USDA requires it annually.
While USDA's exclusion of rats, mice, and birds allows for dual mechanisms of
IACUC monitoring of activities involving USDA- covered species annually and
activities involving all other species triennially, many institutions will
choose to establish uniform procedures that satisfy both of these federal
requirements.
It is helpful in considering this issue to refer to the evaluation of
ongoing activities by use of the term monitoring, as opposed to the function
that the IACUC performed at the outset of a new activity and at the expiration
of an approved activity, which may be called review. OPRR has interpreted the
PHS Policy to require an institutional process that provides review of proposed
activities, with committee approval for a specified period of time not to exceed
3 years. This review and approval may be accomplished by either convened
committee action or by a designated reviewer/expedited review process that meets
the PHS Policy requirements of Section IV.C.2.
During this period of approval, monitoring may be done on an annual basis to
meet USDA requirements. The purpose of monitoring is to ensure that no changes
have taken place inadvertently in the approved activity that might require
further review by the IACUC and that any new requirements of the PHS, USDA, or
the institution are transmitted to the investigator. Monitoring need not
require convened IACUC or designated reviewer/expedited action. A relatively
simple mechanism to meet both federal requirements is to circulate annually to
all investigators with IACUC-approved activities a standard form giving current
basic information, such as IACUC approval number, IACUC approval date, title of
project, and species used. The investigator then notes that either no changes
have taken place, or he/she describes any changes that have occurred. Responses
are reviewed by an IACUC-designee for assessment of the changes reported. Any
changes to the approved activity that are deemed of sufficient magnitude to
merit further consideration may then be presented to the IACUC. All of these
dispositions should be documented as official IACUC actions.