3. How to apply for review
3.1 The review process
Researchers initiate IACUC review by submitting an application
to the Research Subjects' Protection Programs. The IACUC assesses the
project's societal benefit and treatment of animals and communicates
its decisions and requests to the investigator in writing. Initial review
typically takes two weeks. If the IACUC requires explanations or revisions
of the initial proposal, it reviews the project again to see whether
its concerns have been adequately addressed. Sometimes a project must
be revised several times.
The IACUC must approve a project before investigators can begin work
on it -- even before the animals can be acquired, since acquisition
and housing are part of the review.
Each approved application receives a code number, called the "protocol
number." The number is located on the first page of the form and on
the "cage card" attached to animal's cage. Investigators must use this
number in placing an order
for animals through Research Animal Resources.
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3.2 Preparing the Application
To submit a project to the IACUC for review, investigators should
complete the Animal Usage Form and enclose
supporting material as requested on the form.
The following checklist can help ensure that the application is ready
for review. Investigators should:
- Use up-to-date form.
- Complete the application form.
- Obtain appropriate signatures.
- Enclose signed Animal Use Certification Statements.
- Make a copy for their own records.
- Enclose the correct number of copies for the IACUC.
Investigators should provide 12 copies if the project meets the
criteria for
- Category A (question 8 on the Animal Usage Form); or
- uses rodents and meets the criteria for Category B.
Investigators should provide 16 copies of the application if
the project meets
- the criteria for Category B but does not use rodents, or
- meets the criteria for Category C.
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3.3 What the committee assesses
What the committee assesses:
The IACUC's overall task is to determine
- whether a project's societal benefit justifies any animal pain and
suffering that it might cause, and
- whether whatever animal pain or suffering occurs will be kept to
a minimum.
The investigator must furnish the information that the committee uses
to make these decisions by completing all pertinent items and required
appendices in the Animal Usage Form. Each item is explained in the form.
In general, the committee's review covers six broad areas:
- the project's goals,
- the level of any animal pain or distress,
- the abatement of pain and distress,
- environmental health and safety,
- the potential for human consumption, and
- the investigators' preparation.
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3.3.1 The project's goals
The project must stand a reasonable chance of promoting human or
animal health, contributing to the good of society, or advancing the boundaries
of knowledge. As the likelihood of animal pain and suffering increase,
the likelihood of significant benefits must increase.
3.3.2 The level of animal pain and distress
Whether procedures cause pain or distress can be a more complicated
assessment. Following the definition of pain developed by the American
Physiological Society, the IACUC considers procedures painful if they
produce a stimulus that people would experience as painful, that elicit
escape behavior in animals, or that is capable of damaging tissue. In
accordance with the definition of distress developed by the National Research
Council, the IACUC holds that procedures cause distress if they involve
any disruption of physiologic equilibrium manifested by abnormal or maladaptive
behavior.
The Animal Usage Form asks investigators to classify a project's procedures
into three categories and to indicate which of the three categories
will apply to each species. The categories are:
- Category A
- procedures that cause little or no discomfort. Examples include
injections, ear tagging, restraint of less than 12 hours, and food
deprivation for up to 48 hours using well-nourished, healthy adult
animals.
- Category B
- procedures that cause pain, distress, or discomfort that is relieved
by anesthetics, analgesics, or tranquilizers. Examples include surgery,
cardiac or retroorbital blood collection, and trauma.
- Category C
- procedures that cause pain, distress, discomfort, or deprivation
that is not relieved by anesthetics, analgesics, or tranquilizers.
Examples include experimental induction of a debilitating disease,
certain testing procedures, and sampling procedures such as blood
collection by cardiac puncture.
A project may involve procedures in more than one category in which
case the project is classified in the most advanced category.
3.3.3 The abatement of pain and distress
The IACUC also determines whether the investigator has designed the
protocol so as to minimize any animal pain and suffering that occurs.
The IACUC can withhold approval from projects in which the pain and
suffering are not minimized, even if the project's benefits outweigh
the pain and suffering.
Some steps that investigators can take to minimize pain and suffering
are unrelated to the study protocol. For example, animals' living conditions
should be appropriate for their species. Sometimes, living conditions
can be improved by making minor changes, by placing them in rooms with
windows or providing enrichment, for example.
Other steps concern the protocol. These fall into three broad kinds:
- replacement: finding alternatives. The research model should be
whatever will involve the least amount of pain and suffering, within
the constraints of the project's goals. The most common kind of replacement
is to switch to a species that is lower on the phylogenetic scale.
Some replacements are innovative: for example, investigators are sometimes
able to avoid inducing a pathologic condition in subject animals by
using animals in which the condition occurs naturally. Occasionally,
computer simulation, chemical or mechanical models, or in vitro laboratory
studies can supplant an animal model altogether.
Suggestions for replacements are available to investigators in the
University's Animal Care and Use Manual, from the Johns Hopkins University
Center For Alternatives To Animal
Testing, and from the U.S. Department of Agriculture's Animal
Welfare Information Center.
- reduction: minimizing the numbers. The project should obtain the
most information possible from the fewest number of animals. The Animal
Usage Form asks investigators to give a scientific justification of
the number of animals they plan to study. Appeals to tradition or
to convenience are not acceptable.
- refinement: improving the protocol. Research procedures should
cause as little animal pain and suffering as possible and curtail
it when it arises. For example:
- Anesthetics can prevent pain during and after a procedure. Whether
animals are experiencing pain can vary with circumstances and
needs to be monitored. To assess pain, researchers should be alert
both to behavioral signs (based on the animal's normal behavioral
patterns) and to physiological parameters (such as plasma cortisol,
catecholamines, white blood cell counts, and cardiovascular parameters).
When in doubt, researchers should assume that the animal is in
pain and take steps to alleviate it.
The IACUC recognizes that anesthetics can compromise the scientific
validity of some research protocols. Researchers must explain
the benefit of these experiments more rigorously and explain why
anesthetics are inappropriate.
- Aseptic technique reduces the likelihood of infection.
- Physical restraints should restrain to the minimum extent necessary.
They should cause as little discomfort as possible and allow the
animal to assume normal positions as much as possible. Investigators
should also train or condition the animals to accept the restraint.
- Freund's adjuvant should be replaced with another type of adjuvant
if possible. If Freund's adjuvant is scientifically preferable,
it should be administered in the least painful manner. The University's
Procedures of Animal Care
contains guidelines for immunization techniques.
- An early endpoint for a study can reduce pain by curtailing
it. Sometimes, in fact, the information an investigator needs
can be gathered before the animal experiences any ill effects.
For example, a pilot study of the course of a disease or toxin
might reveal clinical signs that reliably predict eventual debilitation
or death. The full study can then be terminated as soon as those
clinical signs appear.
- Euthanasia is necessary for animals that would experience severe
pain when their study is complete. When necessary, investigators
should administer it as soon as possible, perhaps even during
the experimental procedure, and should choose the method that
causes minimal distress. The University's Procedures
of Animal Care contains guidelines for euthanizing techniques.
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3.3.4 Environmental health and safety
If a project involves a biohazard, the IACUC assesses the risk to
humans and the need for precautions.
Investigators must list biohazards in the application form and register
their work with the University's Institutional Biosafety Committee, using
an IBC form. Biohazards
include diseases transmissible from animals to humans, infectious agents
capable of causing disease in humans, biological toxins, radiation, and
recombinant DNA. Investigators can obtain more information on biohazards
from the Department of Environmental
Health and Safety.
3.3.5 The potential consumption by humans
If a project might introduce an animal or animal product into the
human food chain, the IACUC assesses the risk and the need for precautions.
3.3.6 The investigators' preparation
Those who carry out research procedures must be appropriately qualified
and trained. Before participating in the project, they must have completed
the occupational health program, and all employees working with animals
are required complete the tutorial
found on the Web. The seminar is offered bi-weekly and the schedule
is available by calling the IACUC office at 612-626-5654.
The University's environmental health and safety standards may require
that those who work with animals receive additional training, depending
on the species and materials used in the project. Training
is available from Research Animal Resources.
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Next Section: 4. Meeting IACUC approval requirements for sponsored projects
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