Federal Regulations for Animal Research

Author(s): Elysa Koppelman, Ph.D.

The following is explanation of the federal regulations concerning research with animals. This discussion focuses on regulations that focus on research design. There are other regulations that focus on the carrying out of animal research. These regulations are not discussed here. Links to all regulations concerning animal research, which include the Animal Welfare Act, PHS policy on the Humane Care and Use of Laboratory Animals, and the Report of the AVMA Panel on Euthanasia, are found in the Resources Maintained by Others section on the animal research page.

Understanding and following regulations is important. However, ethical behavior involves more than simple adherence to rules; it requires discretion and judgment. Regulations do not necessarily cover all the choices and they do not give a formula for complete and mature ethical decisions. For example, regulations might tell us that we should not perform research on animals if the research doesn't provide benefits to humans or animals or contribute to scientific knowledge. But this doesn't tell us how to determine if the anticipated outcomes of a particular research project are or will be beneficial, nor does it provide guidance for the subtle questions that arise concerning what constitutes a contribution to scientific knowledge.

Introduction

All serious researchers should demand that animals used in research be treated humanely. Concern for animal welfare should always be on researchers' minds when designing the research protocol. It is concern for animal welfare that underlies Federal Regulations. And it is concern for animal welfare that comprise the basic criteria for IACUC approval of protocols.

The basic criteria for IACUC approval are that the research (a) has the potential to allow us to learn new information, (b) will teach skills or concepts that cannot be obtained using an alternative, (c) will generate knowledge that is scientifically and socially important, and (d) is designed such that animals are treated humanely.

The underlying idea behind these regulations is that researchers should never unnecessarily burden animals in research. Therefore, it is the job of researchers to design and carry out research in a way that does not subject animals to unnecessary burdens. Doing research that does not promise to generate important knowledge, subjecting animals to unnecessary pain, doing experiments on animals when the objectives can be reached without doing so are all ways of unnecessarily burdening animals.

This discussion focuses on the main questions on the IACUC application and explains how to design research projects so that they meet regulations and ethical standards essential to performing humane animal research. Bear in mind that federal regulations require that people without scientific training serve on the IACUC. All IACUC members must understand your application. In answering IACUC questions, researchers should present concepts clearly, use a minimum of specialized terminology, and be as concise as possible.

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Rationale for Using Animals-- Benefits to be Gained

Researchers must show that animals used in their particular project are not being unnecessarily burdened. This means that any burden placed on experimental animals needs to be justified. One aspect of providing that justification is to show that the research is likely to bring benefits either by (a) improving medical care of humans or animals or (b) contributing to new scientific information.

Many IACUC applications ask researchers to provide this justification. Researchers should explain the purpose of their study, the hypothesis of the study, and the importance of the study. In providing this justification, researchers should think about what will be gained by doing the research they propose to perform. Why is this research project necessary?

Description of Procedures Involving Animals

IACUC members are charged with determining whether the protocol design researchers propose is acceptable. In order to do so, many IACUC applications ask researchers to provide a description of all of the procedures that will be performed on animals in the course of research. This description should be focused, detailed, and accurate.

This description should include all experimental procedures that will be done to animals (e.g., restraints to be used, fasting, blood volume to be drawn, drug dosage, and the euthanasia process). All procedures explained here should also be listed in the protocol or grant application (and later, in your lab notebook).

IACUC members will look at your procedures description and protocol to make sure that you have done what you can to reduce the burden on animals used in research. In other words, researchers need to justify using the research design they propose over other designs that might be less burdensome on animals.

Research Design

So, how can researchers design projects so that they do not unnecessarily burden animals? By keeping in mind Russel and Burch's Three R's: reduce, refine, and replace. Researchers justify their research design to the IACUC by showing that they followed the three R's in designing research.

Reduce (or Minimize) the Number of Animals Needed in Research

There are three aspects to reducing the number of animals needed in research that researchers should keep in mind when designing research.

  1. maximize the data gained from an individual animal (e.g., by using animals already being used in other experiments);
  2. avoid duplicating prior research unnecessarily;
  3. use sound statistical methods in design and analysis of the study so that the appropriate number of animals are used to accomplish the objective.

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No Unnecessary Duplication:

If research projects merely duplicates prior research and this duplication is unnecessary, researchers are failing to reduce the overall number of animals used in research. This subjects animals to many unnecessary burdens. The IACUC will ask researchers to prove that they are not unnecessarily duplicating research. Researchers need to either (a) prove that they are not duplicating prior research or (b) explain why duplication is warranted.

Unnecessary duplication occurs when researchers are unfamiliar with or fail to keep up with the literature in their field. Therefore, proving that one is not unnecessarily duplicating prior research involves showing IACUC members that one is up to date in one's field. Researchers should:

  • document literature/database searches (include words and dates searched);
  • reference their own published work;
  • communicate with colleagues;
  • contact the Animal Welfare Information Center;
  • attend meetings and conferences.

Justify Number of Animals Used:

Reducing the overall number of animals needed in research also involves using the appropriate number of animals needed to accomplish the objectives of the research. Researchers need to show IACUC members that they have used sound statistical methods in design and analysis of the study to determine the number of animals to be used. This is, perhaps, the hardest question on the IACUC application to answer. A sample too small will not provide a meaningful answer to the question posed. However, a sample too big unnecessarily burdens animals. Many institutions have a department of biostatistics that can help in this regard.

Replace animals with in vitro models or computer models. Replace vertebrate animals with less sentient animals whenever possible

Doing research on animals when objectives can be reached without doing and doing research on vertebrate animals when objectives can be reached using less sentient animals are two more ways of unnecessarily burdening animals. Research should be designed with these facts in mind.

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Alternatives to Animal Use

Researchers should replace animals with in vitro or computer models when possible. Researchers need to determine whether doing research on intact animals is necessary; that another model cannot be used to accomplish the objectives of the proposed research.

Law mandates that researchers document the source and keywords used to search for alternatives to the use of intact animals. Researchers should do a literature search and list:

  • resources searched;
  • keywords checked and inclusive dates;
  • the results

Some IACUC committees require a similar literature search when applying for an extension of the approval period.

Species Justification

Doing research on animals when the objectives can be reached with a less sentient animal also unnecessarily burdens animals. Researchers should replace vertebrate animals with less sentient animals in their research design when possible. Researchers will need to provide IACUC members with adequate justification for the species their design incorporates.

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Refine experiments procedures to minimize pain and distress

Procedures used during experiments may cause pain and/or distress to animals. Regulations require that researchers refine experiments to minimize pain and distress. This is accomplished by requiring researchers to classify all animal usage in terms of amount of pain and distress and, for animals that fall into a particular classification, to justify subjecting them to pain and distress. (Pain and distress is also the usual cause of animal bites, scratches and kicks sustained by researchers. This gives researchers another reason to be concerned with the amount of pain and distress their research design will inflict on animals.)

There are three steps to following the regulation to refine experiments to reduce pain and distress:

  1. understand the definitions of pain and distress;
  2. use this understanding to classify procedures in terms of the amount of pain and distress and their possible relief;
  3. research ways to refine procedures to minimize the amount of pain and distress research animals bear.

Step One: Understanding definitions of pain and distress

The first step is to understand the meaning of pain and distress so that animal use can be classified.

  • Pain: awareness of acute or chronic discomfort occurring at varying degrees of severity resulting from injury, disease, or emotional distressed and evidenced by biological or behavioral severity or both.
    • Acute Pain: pain that results from a traumatic, surgical, or infectious event that is abrupt in onset, relatively short in duration (days to weeks) and generally relieved by analgesics. Associated distress may be relieved with tranquilizers.
    • Chronic Pain: pain that results from a long standing physical disorder or emotional distress that is usually slow in its onset, has a long duration, and is generally not relieved by analgesics, but frequently responds to tranquilizers combined with environmental manipulation and behavioral conditioning.
  • Distress: undesirable physical or mental stress resulting from pain, anxiety, or fear. Acute distress can be relieved with tranquilizers. More sustained distress requires environmental change and behavioral conditioning.

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Step Two: Pain/Distress Classification

The second step is to use the understanding of what constitutes pain and distress to classify experimental procedures. The USDA requires that all animal usage be classified according to one of four types. It is important that researchers understand this classification, because procedures that fall under classification E requires special justification. The four classifications are:

  1. Animals being bred, conditioned, or held for use in teaching, testing, experiments, research, or surgery but not yet used for such purposes.
  2. Animals upon which teaching, research, experiments, or tests were conducted involving no pain, distress, or use of pain-relieving drugs. Procedures that are performed in the normal practice of veterinary medicine fall under this classification.
  3. Animals upon which experiments, teaching, research, surgery, or tests were conducted involving accompanying pain or distress to the animals and for which appropriate anesthetic, analgesic, or tranquilizing drugs will be used. Drug or radiation toxicity tests, surgery or manipulation of bones, biopsy, and branding generally fall under this classification.
  4. Animals upon which teaching, experiments, research, surgery, or tests were conducted involving accompanying pain or distress to the animals and for which the appropriate anesthetic, analgesic, or tranquilizing drugs would have adversely affected the procedures, results, or interpretation of the teaching, research, experiments, surgery, or tests.

As the definition of 4 suggests, researchers need to provide an explanation of the procedures producing pain and distress in these animals and the reasons drugs were not used to relieve the pain and distress.

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Step Three: Provide justification if procedures fall under classification E

Providing justification can include searching databases for less painful/stressful alternatives and reporting the detailed results. If less painful or stressful alternatives are not available, researchers may want to describe the measures they will take to help alleviate the pain and distress in lieu of tranquilizers or anesthetics/analgesics.

Euthanasia

Finally, in designing research investigators need to determine the endpoint. In most cases, death is not an appropriate endpoint of research. This means that some animals will need to be euthanized and researchers need to specify how this will be done. The Report of the AVMA Panel on Euthanasia sets the standards for acceptable means of euthanizing animals.

Cite this page: "Federal Regulations for Animal Research" Online Ethics Center for Engineering 9/11/2006 National Academy of Engineering Accessed: Wednesday, December 17, 2014 <www.onlineethics.org/Resources/TeachingTools/Modules/19237/resethpages/regan.aspx>