ANIMAL USE PROTOCOL REVIEW FORM
INSTRUCTIONS
Note: These are the "official" instructions that accompany the March 1998 version of the Rutgers Animal Use Protocol Form. Expanded "unofficial", line-by-line instructions are available for the Laboratory Animal Services Word97 version of the protocol form. |
Instructions
Sample Narratives
Checklist
According to the Animal Welfare Policy for Rutgers University (October 11, 1994), before any work with live vertebrate animals commences, all procedures using live vertebrate animals whether new or on-going, or proposed for funding, and irrespective of source or present funding, whether conducted at the University or elsewhere by faculty in the discharge of their University duties and responsibilities must be reviewed by the Animal Care and Facilities Committee. This shall include use of animals for research, instruction, or demonstration purposes (with the exception of farm animals utilized for demonstration purposes by Rutgers Cooperative Extension).
Procedures described in the protocol must conform with those prescribed by the U.S. Public Health Service Policy (PHS), Animal Welfare Act Regulations, The Guide for the Care and Use of Laboratory Animals and the University's Assurance.
REVIEW PROCEDURE: All Animal Use Protocol Review forms are examined and approved at a monthly meeting of the Animal Care and Facilities Committee (ACFC). In order to obtain approval, the ACFC conducts a review of procedures involving animals and determines whether the activities are in accord with the University and Federal policies. The ACFC determines whether the activity conforms with the University's Assurance and meets the following criteria set forth in, and excerpted herein, the U.S. Government Principles Regarding the Care and Use of Animals:
The transportation, care, and use of animals should be in accordance with the Animal Welfare Act (7 U.S.C. 2131 et seq.) and other applicable Federal laws, guidelines, and policies.
Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society.
The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results. The use of statistical models and proper experimental design can help determine the numbers of subjects needed to produce required statistical power. Following such good scientific practice might actually increase the total number of animals used in a project. Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered.
Proper use of animals, including the avoidance or minimalization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures which cause pain or distress in human beings may also cause pain or distress in other animals.
Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents.
Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure, or if appropriate, during the procedure.
The living conditions of animals should be appropriate for their species and contribute to their health and comfort. Normally, the housing, care, feeding, and care of all animals used by biomedical purposes must be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. In any case, veterinary care shall be provided as indicated.
Investigators and other personnel shall be appropriately qualified and experienced for conducting procedures on living animals. Adequate arrangements shall be made for their in-service training, including the proper and humane care and use of laboratory animals.
Where exceptions are required in relation to the provision of these Principles, the decisions should not rest with the investigators directly concerned but should be made, with due regard to Principle 2, by the Institutiona Animal Care and Use Committee (at Rutgers, the Animal Care and Facilities Committee). Such exceptions should not be made solely for the purposes of teaching or demonstration.
AMENDMENTS: In cases of an amendment to a previously approved protocol, an investigator should submit a letter detailing the change. In describing the amendment, the animal protocol review form should be used as a guide to discuss species, number of animals, surgery, anesthesia, analgesia, prolonged restraint, pathological conditions, death as an endpoint, dietary manipulations, experimental stress, final disposition and use of hazardous agents.
NOTIFICATION OF APPROVAL: Investigators will be notified in writing of the committee’s decision concerning their protocol.
TERM OF APPROVAL: The period of approval will be for one to three years unless otherwise specified by the ACFC.
ASSISTANCE: For further information on completing the animal protocol review form, planning of alternatives, modification of protocols or for discussion of problems arising in particular studies contact Robert L. Harris, D.V.M. or Stephen Curtis, D.V.M., Office of Laboratory Animal Services, Phone: (732) 445-4168. Contact Karen M. Janes, Office of Research and Sponsored Programs, Phone: (732) 445-2883, for information on administrative matters.
NOTIFICATION TO FUNDING AGENCIES: Investigators who wish to have ACFC approval communicated to funding agencies will complete the form which accompanies the Notice of Approval.
Sample narratives are provided as an example of the type of information that the committee is looking for in reviewing the project. A brief description of the overall aims of the project is helpful in placing the animal use procedures in context. While it may be sufficient to reproduce portions of grant proposals, this practice often gives too much information about non-animal aspects of the study and not enough information about the procedures involving animals.
Sample narrative One is a study involving a procedure that may cause pain or discomfort. It involves the use of general anesthesia and drugs to relieve pain, non-rodent survival surgery, euthanasia and validation of a non-animal alternative. Sample Narrative Two, which is much simpler from the animal use standpoint, is a typical study involving euthanasia and harvesting of animal tissues in vitro work. The narrative for such a study can be quite brief.
Note that both narratives discuss considerations given to reduction of the number of animals used and the replacement of animals with lower species or non-animal alternatives. Because Narrative One includes procedures which may result in more than momentary or slight pain, it also includes a description of sources and means used to determine that alternative procedures were not available.
| SAMPLE NARRATIVE ONE | |
Bacillus cereus is a widely distributed bacterium commonly found in soil and isolated from a variety of foods. This food-poisoning organism produces a toxin, known as an enterotoxin, which reacts in the gastrointestinal tract and causes diarrhea. It is known that this enterotoxin is composed of at least two separate proteins, both of which must be present in order to cause biological activity in test animals. In our studies to further characterize this toxin we have isolated two proteins with biochemical characteristics very similar to those that have been reported to be the enterotoxin components from B. cereus. When combined, these two proteins cause hemolysis (they break open red blood cells in culture media). A two-component hemolysin is unique and not previously reported by other investigators. We strongly believe that the two-component hemolysin and the two-component enterotoxin are one and the same. In order to prove this, however, it is necessary to perform the ileal-loop-fluid-accumulation test in rabbits. This test is the basic procedure used by public health and other laboratories to establish that a microorganism is able to produce enterotoxigenic activity. Once we have established that the hemolysin and the enterotoxin are identical, we can then use a simple in vitro test for blood hemolysis to further study the toxin. In addition to providing a better understanding of the nature of this toxin, a primary result will be the development of an in vitro test that will make it unnecessary for investigators throughout the world to require animals for testing of toxin. |
Background
information puts animal procedures in context of overall aims. Does not have to be a
justification or rationale.
Note lay language.
|
Female New Zealand White rabbits will be used for the ileal-loop-fluid-accumulation assay. Buprenorphine (Buprenex) will be given pre-operatively to provide post-operative analgesia. Under general anesthesia, and using aseptic technique, the small intestine will be exposed through a 2 inch midline incision. The intestine will be tied off into six sausage-shaped test loops, each separated by a smaller interloop. Test loops will be injected with 2 ml of solution: each of the two protein components, alone and in combination with one another; a negative saline control; and a blank (0 ml) control. The abdominal incision will be closed in a routine manner and the rabbit allowed to recover from anesthesia. The rabbit will be observed continuously for 5 hours post-injection and then euthanized with an overdose of pentobarbital. A positive response is defined as a volume/length ratio (ml/cm) greater than or equal to 0.5 in 50% of the test animals. |
A detailed step-by-step
description of the use of animals. Drugs, dosages, and other details are described in answers to questions on the form.
Description of "final disposition" of animals. |
As explained above, this procedure is currently the definitive test for identification of enterotoxins, and it is one goal of this project to validate a non-animal alternative. Several modifications have been made to minimize pain and discomfort. The procedure as described in the literature, was originally done on a conscious rabbit using local anesthesia. We will use general anesthesia and provide analgesia throughout the post-operative period. The post-operative period has been reduced from 24 hours, as described in the original procedure, to 5 hours. Rabbits will be observed continuously for 5 hours. If rabbits exhibit evidence of pain, additional analgesic will be administered. Discussions with investigators experienced with the technique suggest that a minimum of 6 rabbits is required for statistical significance. Careful surgical technique is reported in the literature to be critical to a successful outcome. Although a simple procedure, all surgery will be performed by an experienced surgeon to assure proper surgical technique. |
The information in the next four
paragraphs is also asked for in Section XI, Justification of Animal Use. In some studies
it may be helpful to the committee to include discussion of these items in the narrative. Consideration given to minimize the number of animals, and to minimize pain and discomfort. |
Since it is our intention to validate an alternative to an assay considered the standard for defining enterotoxins, it is necessary to use rabbits. Although there is one report of using mice to test for Bacillus cereus enterotoxin, the rabbit remains the most widely used species. |
Consideration given to use of lower species or non-animal alternatives. |
The proposed project is not unnecessarily duplicative of previous work, as the proteins in question were isolated in our laboratory. |
Required statement that proposed activities are not unnecessarily duplicative. |
In determining that applicable alternative procedures are not available, the following sources were consulted: 1) Lab of Dr. Meriones Unguiculatus, the Oat Bran Institute, Wobegon University (author of a 1989 review article, personal communications), and 2) Index Medicus (headings: Bacillus cereus, enterotoxin). The study of this enterotoxin has been a major focus of our laboratory's efforts for the past five years. We communicate with leaders in this field throughout the world and review the literature on the subject on a continual basis. |
Required statement giving the sources and means used to determine that alternatives were not available. |
SAMPLE NARRATIVE TWO |
|
Our laboratory develops drug delivery systems such as skin patches that allow drugs to be administered to patients by being absorbed through the skin rather than by other means such as pills, injections, etc. Transdermal drug delivery is convenient, can be used in patients who cannot take oral medication, and can deliver drugs slowly over a defined period of time. |
Background information puts animal procedures in context of overall aims. Does not have to be a justification or rationale. |
Genetically hairless rats are euthanized with CO2. A piece of skin is removed from the back of the rat and placed in a permeation chamber which allows us to study how drugs cross through skin. |
Description of procedures using animals, including a description of "final disposition" of animals. |
Full-thickness mammalian skin is necessary for studies of how drugs penetrate skin. The permeation chamber is ideal for studies where we are not interested in how drugs are distributed throughout the body. Those studies require the use of live animals. The permeation chamber has a very small skin surface area which reduces the number of animals needed. These studies are used to select those drugs that will be studied further in live animal systems. |
The information in the next two paragraphs is also asked for in Section XI, Justification of Animal Use. In some studies it may be helpful to the committee to include discussion of these items in the narrative. Consideration given to minimize the number of animals. |
The proposed project is not unnecessarily duplicative of previous work, as the compounds we are studying are synthesized in our laboratory. Comparable drugs are not available for use in transdermal drug delivery systems. |
Required statement that proposed activities are not unnecessarily duplicative. |
(Note: As this study does not involve procedures which may cause pain or distress, it is not necessary to include a statement giving the sources and means used to determine that alternatives were not available.)
ANIMAL PROTOCOL FORM CHECKLIST This form is for use by the principal investigators and need not be submitted.
Type responses.
| For assistance on clinical matters contact: | |
Robert Harris, D.V.M. or |
Stephen K. Curtis, D.V.M. Associate Director Laboratory Animal Services Nelson Biology Labs 604 Allison Road Phone: (732) 445-4168 FAX: (732) 445-4841 E-mail: curtis@orsp.rutgers.edu |
Complete Appendix A.1 and A.2 - if the protocol involves use of a chemical hazard.
Complete Appendix B - if the protocol involves use of transplantable cell lines and tumors.
Attach a copy of the animal care and use sections of the relevant grant. For example: PHS application form 398 - section F.
Sign - page 2 section D.
If the protocol is for a course, the departmental chairpersons must sign page 2 - section E.
Keep a copy of the protocol for further reference.
For assistance on administrative matters and submission, contact:
Karen M. Janes
Sponsored Programs Administrator
Rutgers University
Office of Research and Sponsored Programs
Administrative Services Building, Annex II
58 Bevier Road
Piscataway, New Jersey 08854-8010
Phone: (732) 445-2883
FAX: (732) 445-3257
E-mail: janes@orsp.rutgers.edu