'…And Mice.' (Or Tips for Dealing with the Animal Subjects Review Board)
EDITOR'S NOTE: Part one of this two-part feature ran in the May/June 2001 Observer. Special thanks to Gopakumar Venugopalan for his help on this issue.
If you do any research involving humans, as described in the accompanying article, you must submit your protocols to the Institutional Review Board (IRB). If you do any research involving animals, the process is much the same. All of the advice on preparing and submitting proposals to the IRB will apply to submitting and preparing proposals for animal research with some particular differences. I will try to address those particular differences since the general requirements for proper preparation of protocols for review have already been covered outstandingly.
The institutional committee responsible for the oversight of animal research at a particular institution is called the Institutional Animal Care and Use Committee (IACUC). The IACUC is constituted and follows the regulations as promulgated by the Office of Laboratory Animal Welfare of the National Institutes of Health. However, there are several overlapping sets of regulations followed by any particular IACUC. These include the Public Health Service Policy on the Humane Care and Use of Laboratory animals, the U.S. Department of Agriculture's Animal Welfare Regulations, the National Academy of Science's National Research Council's, the Guide for the Care and Use of Laboratory Animals, the Food and Drug Administration and Environmental Protection Agency requirements for "Good Laboratory Practices," the Marine Mammal Conservation and Protection Act, and the Lacey and Endangered Species Acts. In addition, some institutions take part in a voluntary program of evaluation conducted by the American Association for Accreditation of Laboratory Animal Care.
One major difference among these sets of regulations and guidelines is the definition of exactly to what animals they apply. This is not a problem faced by the human IRB since everyone can normally agree on whether or not humans are involved in any particular research program. However, that is not the case with the IACUC. Some regulations do not apply to cold-blooded animals, or to mice and rats. Others, in the words of the Public Health Service Policy, apply to "all live vertebrate animals used or intended for use in research, research training, experimentation or biological testing or for related purposes." It is always safer to assume that what you are doing needs IACUC approval. As with "exempt status" in the use of human subjects, only the IACUC can make the decision of whether or not your project requires IACUC approval. That decision, in turn, can only be made after a careful review of your protocol. I will, therefore, assume that your research does require the approval of the IACUC and concentrate on the steps needed to obtain that approval.
The key to the preparation of a protocol for IACUC approval is R and D (research and documentation). The members of the IACUC will be looking at several key elements before they begin reviewing what you plan to do. The first is whether or not the proposed work is needed. To the researcher, intimately involved in their work, this seems obvious. However, you must spell out the objectives of the research in simply lay terms. If you can't explain why you are doing something to your grandmother, you shouldn't be doing it. The second component in deciding if the research is needed is the availability of acceptable non-animal systems. You must document that there are no such systems that could provide equivalent data. The IACUC will not simply take your word for this. You must document that you have tried to find acceptable non-animal alternatives. Such documentation should include literature database searches listing the databases searched and the search parameters. Further you must show that what you are proposing has not been done before. Repeating a previous study will generally not win approval unless you can provide substantial evidence that the outcome will be different. Again, literature searching is expected. Finally, you must justify the appropriateness of your choice of species and that you will use a minimum number of animals to provide statistically significant results. This should include the statistical model that you are using to determine the power of your analysis.
Now, finally, you are ready to describe the work that you wish to do. Again, simple clear descriptions are needed. You need to describe exactly what will be done to each animal and the amount of pain and discomfort that can be expected from the experiments. The level of pain and discomfort is broken down into three categories. The first is a level to be expected from procedures that might be used to decrease pain and discomfort. That is a procedure similar to injection of drugs. The second category includes procedure that could be expected to generate greater levels of pain and discomfort but are alleviated by administration of appropriate drugs, for example, surgery with anesthesia and analgesia for reduction of post operative pain. The final category includes all procedures in category two but not alleviated by drugs. This category of experiments requires extraordinary justification for why the pain or discomfort cannot be adequately treated. A key function of the IACUC is to determine into which of these categories the proposed experiments will fall. The committee will not simply take your assessment. It will make its own decision. It has been my experience as a member and chair of our IACUC that most requests for modifications or for further information center on this evaluation. Once it is determined that the research requires the use of animals, the overriding concern of the IACUC is to reduce the level of pain and discomfort to a minimum.
Once you have all of the information and documentation that you think you will need to contact your Director of Animal Resources or the veterinarian in charge of your animal facilities. Discuss your plans with her or him and seek their advice on standard procedures used within the animal facilities and whether or not they will impact on your study. In particular, you need to discuss the particular drugs and dosages to be used. Remember, each species is different and may react differently to particular drugs.
Now obtain the protocol submission forms either from the Director of Animal Resources or the chair of the IACUC. Fill them out completely and carefully. Submit them along with all additional documentation. Remember the IACUC is composed of researchers involved in animal research, researchers not involved in animal research, and members of the community that are not employees or relatives of employees of the institution. These last are the ones that you must convince. They serve unpaid and unrewarded except for our thanks. They are our reality check. They are your grandmothers!
PAUL LEBLANC is a professor in the Department of Biological Sciences at the University of Alabama. He has been chair of the IACUC for past 2 years and member for last 15.
If you're interested in learning more about IACUC issues, go to www.iacuc.org. This is a website written with comprehensive information for IACUC boards that is likely to have answers to questions you may have about ethics issues you may encounter.