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UC Center for Animal
Alternatives School of Veterinary Medicine University of California, Davis |
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Nelson Garnett, National Institutes of Health Office of Protection from Research Risks (NIH/OPRR),
V Wensley Koch, United States Department of Agriculture, Animal and Plant Health Inspection Service/Animal Care(APHIS/Animal Care), Western Sector
James Serpell, Department of Clinical Sciences, School of Veterinary Medicine, University of Pennsylvania, and
William Stokes, National Institute of Environmental Health Sciences.
Refinements, responsibilities of the IACUC and the PI and the need for quality assurance of animal care. Discussions were lively and opportunities were given to all participants to express their concerns and discuss their problems. Solutions were found for some site-specific problems.
Each group was asked to bring recommendations or suggestions for the implementation and documentation of Refinements in animal care, and to attempt to rank them when reporting. It was apparent from the group discussions that not all suggestions were reported in the wrap-up session, or in the reporters' summaries, but those reported are listed here.
Education and Training follow it. It became quickly
obvious that the IACUC, the research faculty and the public do not adequately
understand the implications of Refinement as an alternative.
Pre-review. The protocol writer may be the one to
introduce alternatives into the process, but since the resident laboratory
animal veterinarian, or a consulting veterinarian, may be the first person to
advise the PI (principal investigator) about the possibilities, the veterinarian
may also have the opportunity to introduce alternatives, including Refinement,
into the protocol.
Some institutions regularly provide protocol pre-reviews.
Again, the veterinarian may be the contact, provide support, and be an ally to
the PI. This pre-review or short, early review may increase the investigator's
awareness of not only alternatives but also potential adverse effects of the
proposal on the animals. Such pre-review has reduced the amount of kickback from
the IACUC (Institutional Animal Care and Use Committee). Other IACUCs have
considered providing a distillation of information regarding refinement for
their PIs.
Literature searches for alternatives were documented in
various ways. Some relied on the PI to check the appropriate box on the form,
others requested the names of the database searched, dates of coverage (eg,
MEDLINE and all back files, current MEDLINE only, BIOSIS and MEDLINE), and
others requested a copy of the search statement and the search results attached
to the protocol.
The coordination of studies can reduce the numbers of
animals used by sharing tissues. It was suggested that a record of institutional
projects with these details be kept on an intra-net or on an internal web
site.
Some IACUCs have standard operating procedures (SOPs) for
particular needs or procedures to reduce the discomfort to the animal (eg,
production or procurement of MABs, monoclonal antibodies).
Some IACUCs are involved in animal husbandry
decisions--crowding, bedding, changes in housing-- which are intimately tied to
the welfare of the animals. In one case, the IACUC and veterinarian obtained
committee support for the use of low profile cages.
Role of veterinarians. At one institution all resident
veterinarians sit in on the IACUC meetings whether needed as consultants or not.
This provides them with tremendous insight into research needs and provides the
IACUC with substantial professional support.
Some IACUCs require substantive documentation for the number of animals, no matter how few. In other cases, retrospective studies have been made of the number of animals actually used compared with the argument for their support. The studies indicate that PIs characteristically overestimated the number of animals needed. It was suggested that pilot studies, with as few animals as possible, be recommended to the PI before substantiating the total number.
Stretching the IACUC's role. It was asked how IACUCs
determine whether work is relevant, whether the animal model is appropriate for
the study, and if the appropriate number of animals is selected. It was
recommended that IACUCs do quick literature searches. Participants suggested
including the use of the zoo literature for refinement issues and the upcoming
NIH web site links to alternative databases on the web.
We discussed how we could teach PIs to search for alternatives. They already are knowledgeable about searching databases for their area of expertise, but many do not search for alternatives. We noted that PIs search for alternatives and reply to the issue because they are required to do so.
The best way for IACUCs to convince investigators to
implement refinements is to demonstrate that they will lead to better scientific
results because the animals are under less stress. However, it must be
acknowledged that refinements can also increase variability, and thus have a
potentially negative effect on results. At present, there is a lack of
information about how refinements (e.g. environmental enrichment) actually
affect animals and the use of animals as models.
A funding commitment from the federal level will be
necessary in order to fully develop and evaluate the effects of refinements on
animal welfare and the validity of scientific results. The costs and benefits
(to both animals and investigators) of refinements need to be carefully
evaluated before they are recommended by ACUCs. For example, is there really a
net benefit from training an animal to give blood samples if that animal is only
going to be bled a few times?
Expertise will be necessary in order to implement
refinements. Training of animal care staff is important. However, institutions
should also consider hiring a resource person who can do "hands on" work
implementing refinements (e.g. training, socializing, and/or enriching animals
and training the animal care staff in these techniques; keeping abreast of the
latest literature on refinements). Smaller institutions could share a resource
person.
Training sessions for investigators should emphasize that
"alternatives" means more than just replacement with non-animal methods, but
also includes refinement. However, as the emphasis shifts to a broader
definition of alternatives, there will also need to be a new approach to
literature searches. Investigators tend to do disciplinary-based searches when
they look for alternatives to experimental methodology. However, searching for
the full range of refinements will require using new databases and search terms.
Access to a librarian experienced in conducting such broad-based searches will
be important.
Additional flexibility will be needed to deal with some
refinement issues. For example, if animals are to be shared, the IACUC might
need to expedite protocol approval to enable the animals to be transferred to a
new research project in a timely fashion. Sharing of animals also raises
interesting questions about multiple survival surgeries--if these would decrease
the number of animals used, this would be consistent with the goal of reduction.
USDA could be asked to approve more multiple survival surgeries.
Sharing of animals and information among investigators could be greatly facilitated by a good institutional database of ongoing research protocols. This database could also be used to identify investigators who are using particular techniques to notify them when alternatives to those techniques become available.
We should look at a gradual process for changing
equipment and making recommendations to PIs in regards to enrichment and
refinement. Money is a significant consideration in enrichment changes.
IACUCs and their campus's librarians can help PIs
identify and understand the resources available for alternatives
searches.
The UC Center for Animal Alternatives should provide
leadership by conducting workshops on the various campuses, including both PIs
and library personnel, on alternatives literature searches.
For reluctant PIs we suggested obtaining a copy of their
professional society's guiding principles.
Use the zoo and animal agricultural resources for
searching for Refinement alternatives.
Educate the scientific community that due to political pressures and social changes, expectations are shifting towards improved animal care and less intrusive procedures.
UC Center for
Animal Alternatives
