Summary of Points related to 2011 Guide
A previous public comment period yielded the conclusion that no Guide revision was
necessary, yet one was undertaken.
The rationale for having allocated funds to prepare this new Guide is not clear. In
November 2005, NIH Office of Scientific Affairs opened a public comment period
(NOT-OD-06-011) on the need to update the laboratory animal welfare standards of the
7th edition of the Guide, published in 1996. The results of that comment period were
reviewed by a working group of scientists and laboratory animal veterinarians who
concluded that there was “no evidence to warrant revising the performance standards of
the 1996 Guide. These standards have allowed individual institutions the flexibility to
adapt policies and procedures to their own institutional environments.” (NOT-OD-07016) The report indicated the Guide should become a web-based document that would
make it possible to revise the Appendix periodically with current references and reports
to be included after critical review for scientific validity. Despite this conclusion, a Guide
revision project was initiated in the fall of 2008. Rather than merely updating references
and providing new information on animal husbandry, however, the 8th edition is twice the
length of its predecessor. It contains new policies and requirements that impose
substantial financial and paperwork requirements on investigators, IACUCs, and animal
housing programs without commensurate benefit to the care and use of animals in
research. Furthermore, it strays further from its traditional domain of guiding institutions
on appropriate veterinary care, housing, and facility construction of vertebrates in
research into new policies that have the effect of imposing restrictions on research design
and on the exercise of scientific judgment by federally funded researchers.
Newly introduced policy on “Multiple Survival Surgical Procedures (p. 30) and advice
against multiple use of animals per se (Chapter 1)
Rather than use the definition of “major operative procedure” as defined in the
Animal Welfare Act Regulations,, the Guide now leaves that definition to “the
veterinarian and the IACUC.” It expands the AWA regulatory requirements for multiple
major operative procedures to “multiple survival procedures” for any vertebrate. This
may have been poor drafting that was not caught in revision, but it is an example of one
of the many sections in which the writing is imprecise and guidance being given is
inappropriate. Beyond that, however, is the more important point that a guiding principle
in PHS Policy as well as the Animal Welfare Act is the “avoidance or minimization” of
pain/distress/discomfort (U.S. Government Principls IV and V). The focus thus should
be on appropriate post-operative care for any surgery.
Instead, the policy in the new Guide against multiple surgical procedures appears to
advocate increasing the number and costs of animals in research rather than in making
maximum, productive, yet humane use, of any one animal. This echos a caution in
Chapter 1 in which investigators are strongly discouraged from advocating animal reuse
as a “reduction” strategy. Restrictions against using animals in multiple procedures most
certainly will increase the number of animals needed in research, but also indirectly
hampers the use of within-subject and single subject designs that are particularly
powerful for behavioral research.
Food and Fluid Regulation (p. 30-31)
paragraph 2: The statement that "the development of animal protocols that
involve use of food or fluid regulation requires evaluation of three factors: the necessary
level of regulation, potential adverse consequences of regulation, and methods for
assessing the health and well-being of the animals." indicates that an IACUC should
require that each protocol specifically address each of those factors and that we review
them. This adds to the paperwork burden of the researcher in writing the protocol and the
committee in review.
Also paragraph 2: A new sentence about the variables that determine the amount
of food or fluid restriction that can be used safely includes "prior experimental
manipulation." Some IACUC's could interpret it as an opportunity to restrict continued
use of an animal in a food restriction protocol. Note that Chapter 1 recommends against
animal “re-use” as a way to reduce the use of animals in research.
paragraph 3: Specific direction to record body weights at least weekly for food
restriction. That is, "Body weights should be recorded at least weekly. . . ." as an acrossthe-board-statement for either food or fluid restriction, rather than, as in the 1996 Guide,
"Precautions that should be used in case of fluid restriction to avoid acute or chronic
dehydration include . . .recording of body weight at least once a week." Weekly
recording is not a good general recommendation. In some protocols with rodents,
weighing should occur more often than weekly. In others, such as for non-human
primates, weekly recording of body weights may not be necessary under stable feeding
conditions, and is not desirable if the animal has to be anesthetized to be weighed. The
wording of the 1996 Guide focuses on maintaining the well-being of the animal without
being as prescriptive as the 2011 Guide as to exactly what must be done. Also in paragraph 3, there is a requirement to keep written records of daily food
and fluid consumption for animals in either food or fluid restriction experiments. The
'96 Guide has the requirement for recording daily fluid intake only for fluid restriction
experiments; it does not require this for food restriction. This seems to preclude the use
of automatic watering devices for either type of restriction, meaning that calibrated water
bottles be used for all such animals, and the amount consumed recorded daily. This
would be a terrific new expense and burden for many species. Consider: housing
facilities' buying the calibrated bottles, writing down amount consumed for individual
animals at the same time each day, for example; or having lab members do so 7
days/week. It also can be interpreted to mean that there be a record for each animal of
food consumption
(e.g., weigh the food given to animals on fluid restriction and then
weigh what is left). This is unnecessary micromanagement of food and fluid
restriction procedures, which generally are carefully worked out, based on needs of each
species, and the experience of the investigator.
The recommendation that “a highly preferred food or fluid be used as positive
reinforcement, instead of restriction” for “conditioned-response research protocols” is
made despite information provided in two of the papers they cite in this section that such
strategies do not work well to train behaviors. This is another example of inclusion of
citations that either do not support the point being made or are otherwise inappropriate.
Thus, the principle that scientific data will be used to support recommendations on
animal care and use.
Newly introduced policy on “Use of Non-pharmaceutical-Grade Chemicals and Other
Substances (p. 31)
The new section on “Use of Non-Pharmaceutical Grade Chemicals and Other
Substances” adds a policy that, on the surface, may sound reasonable, but is inappropriate
for basic research. Its apparent premise (based on its citation of an interpretive rule
guiding USDA inspectors regarding adequate veterinary care) that the use of commercial
drug solutions sold for clinical use in human or veterinary practice “ensures that toxic and
unwanted effects are not introduced into studies conducted with experimental animals” is
false. Not only do very few commercially available preparations exist that are suitable as
tools for experimental research, but also, commercial solutions themselves are subject to
formulation errors, as evidenced by recent recalls. Even with solutions that may be
useful for a particular project, the need to conduct dose-effect evaluations inevitably
means the commercial solution would need to be diluted in the laboratory to accomplish
this purpose.
A second point is that the requirement in the new Guide that “The use of nonpharmaceutical-grade chemicals or substances should be described and justified in the
animal use protocol and be approved by the IACUC,” further implies that any preparation
of drug solutions by the researcher can be assumed to be inferior to commercial
preparation. The further requirement that “In such instances, consideration should be
given to the grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route
of administration, formulation compatibility, and pharmacokinetics of the chemical or
substance to be administered, as well as animal welfare and scientific issues relating to its
use. . ” inappropriately defers the scientific judgment of the researcher to the IACUC.
This also presumes that the IACUC has expertise, or retains someone with such expertise,
to evaluate the details of formulations planned by the researcher.
Post-approval Monitoring
Newly introduced requirements for post-approval monitoring of IACUC-approved
protocols include direct observation of “laboratory practices and procedures and
comparisons with approved protocols”) and formal review of “unexpected outcomes” of
research. These are examples of items that require additional IACUC staffing to
accomplish as well as require additional time on the part of research team members.
Cage Sizes (Chapter 3)
Requirements for new cage sizes for some species and for rodent breeding situations
(apparently to conform to European standards) and mandatory requirements for social
housing of all species will require large expenditures of funds to accomplish. [Note:
More details are in the NABR letter to Dr. Collins.]
Constraints on Professional Judgment
The section on “non-pharmaceutical grade drugs” and the constraints against using
animals in more than one procedure along with multiple other sections of the new Guide
preempt scientific and professional judgment on the design and conduct of research. This
seems especially inappropriate for a document that will govern the research of scientists
whose funding has been granted based to a significant degree on the peer-reviewed
determination of their expertise and ability to carry out specialized research. The new
Guide goes significantly beyond the traditional value of this document for setting
standards for animal housing, husbandry, and veterinary care of research animals.
The 2011 Guide also introduces new policies that constrain the exercise of scientific and
professional judgment by laboratory animal veterinarians and others experienced in
laboratory animal management. One example is the new policy that social housing must
be the default for all species. Although exceptions include needs of research and welfare
of the animal, no provision is made for practical considerations, such as duration of
housing of a nonhuman primate in a facility compared to the time necessary to adapt the
animal to a social housing situation.
The many new requirements for IACUC oversight and review necessitate the researcher’s
devoting a great deal more time and effort in protocol preparation and also additional
review time and effort by IACUC personnel.