Guidelines for the design of experiments
Guidelines for the conduct of experiments
Factors that relate specifically to the conduct of vision and ophthalmology experiments
Investigators outside the United States
Animal use guidelines
Alternatives to animal research
Animal use resources
Organizations that promote proper and ethical use of laboratory animals
Research in vision and ophthalmology improves the quality of life. This improvement stems in part from progress in ameliorating human disease and disability, in part from advances in animal health and veterinary medicine, and in part from the enlargement of our understanding of human and animal life. Because so much of vision research is aimed at understanding the structure and function of complex and intricately connected biological systems, work with living animals is vital to continued progress in many areas of clinical and basic research on vision. The proper use of animals in research is an honorable and essential contribution to the improvement of human and animal lives.
Our concern for the humane treatment of animals obliges us always to establish that the potential benefits to human and animal health outweigh the cost in animal lives, and it is desirable for scientific societies such as The Association for Research in Vision and Ophthalmology to formulate guidelines for the humane use of laboratory animals in research.
The remainder of this document provides guidelines which are generally considered acceptable and reasonable by the biomedical research community. The guidelines are intended for the investigator who is responsible for the humane care and use of animals in research. The discussion deals mainly with warm-blooded vertebrates, but the principles can be applied generally. Ethical issues involving the use of any species should be considered in relation to the complexity of its central nervous system and its apparent awareness of its environment.
The fundamental principle is that animals must not be subjected to avoidable distress or discomfort. The investigator's first concern must therefore be to avoid the use of animals when possible.
When it is established that animals must be used, the investigator's obligation is to minimize the animal's distress or discomfort, assessed by anthropomorphic judgments made by reasonable and prudent human observers. Although most research on animals causes little or no distress or discomfort, certain important scientific questions may demand experimental studies that inevitably give rise to discomfort or distress.
In such cases discomfort or distress must be minimized by careful experimental design involving the use of analgesics and/or anesthesia. There is no difference between distress and discomfort that result from the design of a study and distress or discomfort that are its unintended side effects. The investigator must therefore identify and eliminate all avoidable sources of discomfort or distress, taking advantage of veterinary expertise when necessary.
When designing studies that cannot be undertaken without animals, the investigator must justify the use of animals and the species and number needed to provide reliable information. Experiments should be designed to minimize the number of animals used and to avoid depletion of endangered species. Although a few experiments have a risk of unreliable results, advances in experimental methods, within-subjects designs, and modern statistical techniques all help reduce the number of animals used without compromising scientific quality.
The quality of the information obtained through research depends in no small measure on the health and general condition of the animals used. Proper animal husbandry is fundamental to the success of any research effort that uses animals.
Research animals must be obtained and cared for in accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, the Public Health Service Policy on Humane Care and Use of Laboratory Animals, and in Canada, the Guide to the Care and Use of Experimental Animals by the Canadian Council of Animal Care (if conducting research in Canada).
Experienced investigators can contribute very valuable information about the care of animals rarely used in the laboratory and about the use of animals in particular experimental situations.
Investigators in the United States must comply with relevant local, state and federal laws, including the U.S. Animal Welfare Act, as amended, and its accompanying regulations. An Institutional Animal Care and Use Committee must review and approve the use of animals in vision research in the United States and Canada.
Surgery should be carried out or directly supervised by persons with appropriate levels of experience and training, and surgery performed on animals that will survive (for example, on animals intended for long-term studies) should be undertaken with careful attention to aseptic technique and prevention of infection. Major surgical procedures should be completed under anesthesia that will render the animal insensitive to pain. Muscle relaxants and paralytics have no anesthetic action and must not be used as a substitute for anesthesia. Postoperative care must include efforts to minimize discomfort and the risk of infection.
Some studies require surgical preparation of animals that are not intended to survive. In such cases the animals ordinarily should be maintained unconscious throughout the experiment. At the end of the experiment animals must be euthanized without recovering consciousness.
Where experiments require physical restraint and/or the withholding of food or water, the effects of which are not themselves the objects of study, care must be taken to minimize discomfort or distress and to ensure that good general health is maintained. Only when there is no alternative procedure should animals be subjected to immobilization or restraint to which they cannot be adapted readily. Whenever it is not inconsistent with good experimental design, the experimental schedule should include reasonable periods of rest and readjustment. In the rare cases where distress and discomfort are unavoidable attributes of a well-designed study, the investigator must, within the limits of the design, take all possible steps to minimize these effects and to minimize the duration of the procedure and the number of animals used.
ARVO will amend The Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research pending changes to US and EU guidelines (FELASA and EU legislation).
Besides the considerations generally applicable to all animal experiments, production of visual disability is a special animal welfare consideration that may apply to some vision research protocols. Visual disability of experimental animals may be either an intrinsic or an unplanned consequence of experimental design. In its definition of major survival surgery, the Guide to the Care and Use of Laboratory Animals includes any surgical intervention that has the potential for producing a permanent handicap in an animal that is expected to recover. Hence, any experimental procedure that results in, or has the potential to result in, a level of visual disability sufficient to disrupt an animal's normal daily activity should be considered a major survival procedure. Such procedures require appropriate justifications and suitable animal care accommodations.
Protocols involving bilateral survival ocular procedures require special consideration and justification, with particular attention to any visual consequences. Such procedures include bilateral ocular surgeries, whether performed simultaneously or sequentially, and any other experiments with the potential to affect vision bilaterally. The Guide to the Care and Use of Laboratory Animals recommends that animals not be subjected to multiple major survival surgical procedures unless they are related components of a particular research project. Accordingly, a visually disabling procedure should not be performed bilaterally unless the two procedures are related components of a specific project. As noted in the Guide to the Care and Use of Laboratory Animals, cost savings alone is not an adequate justification for performing multiple survival surgical procedures.
Vision investigators are encouraged to distribute unrelated tissues to investigators in other research areas and, where practical, to obtain suitable ocular tissues from investigators working on other organs. This recommendation applies to all species.
Inherited disorders of the visual system are significant health problems for both humans and animals. Even so, the breeding of animals with genetic disorders leading to blindness needs specific justification. Investigators who breed genetically impaired animals are encouraged to share such animals and tissues with qualified investigators having complementary expertise, including those outside their own institution.
Although the laws that regulate the care and use of animals in the United States are not directly applicable to citizens of foreign countries, ARVO endorses the policies in the Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy on the Humane Care and Use of Laboratory Animals (revised 2002), and the U.S. Animal Welfare Act, as amended. If ARVO is to support a vision scientist under scrutiny by animal activists, the vision science experiment involving animals must conform to the guidelines established in these documents, even though they are not necessarily enforceable by law in the country in which the experiment is performed.
In addition to these Guidelines, references in the following resources are recommended.
- Guide for the Care and Use of Laboratory Animals (NRC2011): Main resource used by Association for Assessment and Accreditation of Laboratory Animal Care's (AAALAC's) Council on Accreditation; also a primary reference on animal care and use (required if research is conducted with PHS funds). The Guide.
Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals
NIH Grants Policy Statement (2011)
Institutional Animal Care and Use Committee Guidebook
- 2008 Guidance for Researchers and Institutions: Good animal care and good science go hand-in-hand.
- A tutorial for new animal care and use committee members, institutional administrators, investigators, animal care personnel and veterinarians. OLAW PHS Humane Care and Use of Laboratory Animals Tutorial
- NIH Medical Research with Animals Website: The site contains information for researchers and institutions, as well as the general public, including a fact sheet on the benefits of biomedical research, and a Frequently Asked Questions section. NIH Medical Research with Animals website.
NIH iEdison: Helps government grantees and contractors comply with laws and regulations
- US Department of Agriculture (USDA), Animal Welfare Act and Regulations : a document with regulations to improve animal care and use in research, testing, teaching, and exhibition. See also, USDA Animal Welfare Information CenterFASS Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching
Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research, National Academies Press
- Canadian Council on Animal Care list of guidelines: Guide to the Care and Use of Experimental Animals
- Expectations of the major research council and charitable funding bodies: Medical Research Council guide for the use of animals. Responsibility in the use of animals in bioscience research.
- Bibliography on alternatives to animal testing: ALTBIB
- Global clearing house for information on alternatives to animal testing: AltWeb
- Center for Alternatives to Animal Testing (Johns Hopkins University): CAAT
- Animal use alternatives terminology (National Agricultural Library): USDA Thesaurus
- Office of Laboratory Animal Welfare (OLAW)
- Asian Federation of Laboratory Animal Science Associations. AFLAS.
- Canadian Association for Laboratory Animal Science. CLAS.
- American Association for Laboratory Animal Science. AALAS.
- Federation of European Laboratory Animal Associations. FELASA.
- International Council for Laboratory Animal Science. ICLAS.
- American College of Laboratory Animal Medicine. ACLAM.
- Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International: This site contains a listing of international regulations and resources by country. AAALAC Resources.