9. Form of application for ethical review |
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9.1 Written proposals
These should provide the ECRA with sufficient information to enable the committee to perform an ethical analysis and to conclude that the proposed use of animals is unavoidable, and that:
9.1.1 the use of animals is justified by a harm/benefit assessment;
9.1.2 the applicants are competent to perform the proposed studies;
9.1.3 the resources supporting the project (competent qualified/registered staff, and facilities) are adequate and that procedures reserved for Veterinarians and members of the Para-Veterinary Profession will be conducted only by persons registered with the SA Veterinary Council;
9.1.4 the project will be conducted in a responsible manner and at its conclusion will be formally reported on to the ECRA by the principal investigator; and
9.1.5 the application of the 'three R' principles of replacement, reduction and refinement will be evident in the proposed design and conduct of the study.
9.2 Form of proposal
Written proposals should be presented in a form that allows the ECRA easy access to information which is essential for ethical analysis, and written in such language and form that they can be comprehended by non-scientists who serve on an ECRA.
9.3 Checklist of information required for ethical analysis
Written proposals should contain the following information.
9.3.1 Project title
A short project title using keywords that best describe the study.
9.3.2 Applicants' profiles
The names, qualifications, institutional and departmental affiliations of persons applying for clearance to conduct the animal experiment together with background information on their past experience in animal experimentation should be given to provide some assurance of competence.
9.3.3 Co-workers
The names, qualifications and affiliations of all other co-workers involved with the proposed study are to be stated.
9.3.4 Declaration of principal investigator/educator
The signature of acceptance by the principal investigator of the pro forma MRC policy statement on: i. the moral philosophy that supports animal experimentation; ii. the recognition and acceptance of animal interests; iii. the principles (the 'three Rs') of humane experimental technique; iv. a requirement for relevance of the proposed research in the context of the MRC's objectives of advancing education, science, and human and animal welfare; and v. the assumption of responsibility on a personal basis for ensuring that the highest levels of welfare shall be maintained and that animals shall be protected from abuse and any unnecessary violation of their interests; and vi. a personal declaration of understanding and acceptance of the principles detailed above (i-v), an undertaking not to deviate from experimental protocol if and when it is approved by the ECRA, and an undertaking to report on the progress of the study at 6-month intervals once it has been started, as well as on its outcome when it has been completed.
9.3.5 Peer review statement
The application is to be supported by a peer review statement from either a Departmental, Faculty or Institutional Scientific Committee, indicating that in the opinion of the reviewers the proposal has been judged in accordance with accepted scientific practice and norms, and is likely to be successful in achieving its objectives.
9.3.6 Categorisation of the project
The proposed project is to be categorised in terms of its purpose, either to educate or train students/staff or to do research. If animals are to be used for training purposes, the nature of the course and number of students to be trained is to be given. The proposed dates for starting and completing the study are to be given to indicate the required duration of the proposed study.
9.3.7 Background Information
A brief introductory statement (non-scientific summary) that explains what problems, questions, needs or new ideas have led to the planning of the experiment. A few key journal references may be included to substantiate viewpoints or premises. 9.3.8 Aims/objectives of the proposed study
The aim/s should be stated in brief sentences or as bullet points. 9.3.9 Potential benefits of the research findings or teaching exercise
Benefits arising from potential results or the expected outcome of animal studies should be stated in terms of how they may contribute to either new knowledge or knowledge that will be useful for the treatment or protection of either man or animals or the environment. This enables the ECRA to weigh the 'harms' to the animals against the potential benefits which may arise from the results of the experiment. This procedure constitutes the formal 'cost (harm)/benefit analysis' which is central to the ethical review process. The term 'cost/benefit analysis' can be misleading if it is not understood in the context of ethical analysis. The 'cost' refers to the harm done to the animals and not to any financial cost. Parallels with cost/benefit analysis in a financial context may also suggest that the assessment is quantifiable, whereas in practice it is really a question of professional judgement. This assessment should rather be called a 'harm/benefit analysis' to promote a better understanding of what evaluation is being carried out. 9.3.10 Statement of hypothesis
If the proposed research project is of an explanatory nature rather than for gathering descriptive data, it is likely that an hypothesis is being tested. If this is so, the postulate should be simply and briefly stated (in non-scientific terminology) to assist the reviewers in following the rationale of the experimental design. If no hypothesis is being tested, this should be stated. 9.3.11 Animal requirements
The species, strain, gender, body mass, age and health (microbial) status of the proposed experimental animals and the total minimum number required for the experiment should be detailed. This information is important for defining the 'quality' of the proposed experimental system. 9.3.12 Justification of the need to use sentient animals and the species selected
Applicants should state why a non-sentient experimental system cannot be used for their study, what non-sentient model/s were considered, and on what grounds they were rejected.
The use of the selected animals should then be justified in terms of their biological appropriateness for use as a test system in the proposed study, i. e. in what way will they approximate man or other animal species in terms of the question being asked or problem being addressed in the study. A brief explanatory statement should be given.
9.3.13 Reduction of the number of animals to be used to a minimum
An explanation of how the minimum number of animals required to achieve the scientific objective of the study was arrived at. This could be by either calculation (statistical design) or specification (i. e. use of a validated test protocol).
9.3.14 Animal caging and care
State where the experimental animals are to be housed, what provisions will be made for their physical and psychological (behavioural) well-being, and who will care for them on a daily basis.
9.3.15 Experimental design
Describe how the animals will be allocated by random selection to experimental and control groups, what experimental treatments will be assigned to each group, and at what frequencies these treatments will be applied.
9.3.16 Experimental procedure
Describe briefly in short numbered sentences all the steps to be performed in conducting the experiment, including operative procedures, collection of samples (give frequencies, blood volumes to be drawn, routes of collection) and any other measurements to be performed during the study. Describe also what will be measured in the samples and why this is being done. A non-scientific summary is required.
9.3.17 Physical restraint of the animals
If the animals are to be physically handled, describe what situations are likely to involve physical and chemical methods, describe the restraint methods to be used, state who will be restraining the animals and what steps will be taken to minimise stress in the animals.
9.3.18 Severity of the experimental procedures
Experimental procedures can cause fear, deprivation, illness, distress and
9.3.12 Justification of the need to use sentient animals and the species selected
Applicants should state why a non-sentient experimental system cannot be used for their study, what non-sentient model/s were considered, and on what grounds they were rejected.
The use of the selected animals should then be justified in terms of their biological appropriateness for use as a test system in the proposed study, i. e. in what way will they approximate man or other animal species in terms of the question being asked or problem being addressed in the study. A brief explanatory statement should be given. 9.3.13 Reduction of the number of animals to be used to a minimum
An explanation of how the minimum number of animals required to achieve the scientific objective of the study was arrived at. This could be by either calculation (statistical design) or specification (i. e. use of a validated test protocol). 9.3.14 Animal caging and care
State where the experimental animals are to be housed, what provisions will be made for their physical and psychological (behavioural) well-being, and who will care for them on a daily basis. 9.3.15 Experimental design
Describe how the animals will be allocated by random selection to experimental and control groups, what experimental treatments will be assigned to each group, and at what frequencies these treatments will be applied. 9.3.16 Experimental procedure
Describe briefly in short numbered sentences all the steps to be performed in conducting the experiment, including operative procedures, collection of samples (give frequencies, blood volumes to be drawn, routes of collection) and any other measurements to be performed during the study. Describe also what will be measured in the samples and why this is being done. A non-scientific summary is required. 9.3.17 Physical restraint of the animals
If the animals are to be physically handled, describe what situations are likely to involve physical and chemical methods, describe the restraint methods to be used, state who will be restraining the animals and what steps will be taken to minimise stress in the animals. 9.3.18 Severity of the experimental procedures
Experimental procedures can cause fear, deprivation, illness, distress and pain in varying degrees. All of these conditions can be caused singly or in various combinations or, by the nature of the experiment, be absent altogether.
Applicants are required to state briefly what the physical and psychological effects of their experimental treatments are likely to be on a single animal in each of their experimental groups in terms of frequency, severity and duration, e.g.
The severity of the proposed procedure should be rated as minimal, intermediate or high on the basis of the criteria detailed below (adapted from the British Laboratory Animal Science Association's report on this aspect13).
SEVERITY SCALE OF PROCEDURES:
0- 8 Minimal
9-20 Intermediate
> 20 High
Notes: Any procedures which are likely to cause severe deprivation, fear, illness, distress and pain that will endure or are likely to endure will ordinarily not be approved by the ECRA. Components of severity considered in this scale: Conscious - anaesthesia - preparation - restraint - duration - tissue sensitivity - organ risk - mortality - pain - distress - deprivation. Numerical values are for single applications - multiple and more frequent applications over short periods of time may increase severity.
9.3.19 Fate of animals and their disposal at the end of the study
If this information has not been given earlier in the application, briefly state what the fate of the group of experimental animals is to be at the end of the study (rehabilitation, release or euthanasia). Also indicate what method of euthanasia is to be used, what humane rationale supports this choice, and how the animal carcasses are to be disposed of.
9.3.20 Administration of scheduled medicinal (Medicines Control Act) and other experimental substances
Detail of the route of substance administration and its dosage (mass or volume per body mass). The volumes of doses to be administered are also detailed for all medicinal and experimental substances.
If scheduled substances (Schedules 3-6) are to be administered by any person other than a registered medical, dental or veterinary practitioner then the registered person who is legally responsible for supervising and directing such use must be named, and this responsibility be accepted by appending that person's signature to the application form.
9.3.21 Statistical design and analysis
Briefly describe the basis of the statistical design of the study (in terminology comprehensible to non-scientists) and state how the statistical analysis of data obtained from the study will be processed for descriptive analysis (calculation of mean, standard deviation, standard error) and statistical evaluation (calculations of probabilities, tests of significance, determination of associations and correlations, etc.). If this analysis is to be done in collaboration with a statistician, state who that person is and what their institutional affiliations are.
9.3.22 Refinement of methodology to promote humaneness
Briefly and pertinently describe what steps have been taken to refine the experimental procedures to reduce the potential severity of harm to a minimum (i. e. gentle handling/restraint, use of chemical restraint, use of appropriate anaesthetics, use of aseptic procedure, postoperative care and analgesia, improvisation of methods to bypass stressful treatments, etc.).
9.3.23 Assurance of technical support and competence
Describe who will be responsible for the pre-, intra-, and postoperative/experimental treatment care of the animals. Detail their experience, qualifications and competence in monitoring the well-being of the animals. Briefly state what behavioural and other criteria will be used to assess the well-being of the animals during the pre-, intra-, and post-operative phases of the study.
9.3.24 End-points for animal experiments that may cause illness and death of the animal
In studies in which illness or death of an animal may be an end-point (i. e. regulatory toxicology, diagnostic toxicology, acute toxicity studies in research, infections, disease studies, micro-organism virulence studies, vaccine efficiency trials, cancer research and cancer treatment, evaluation, etc.), discomfort should be alleviated by choosing the earliest end-point that is compatible with the scientific objectives of the research. 12
If end-points are given, the applicant must submit a brief explanatory statement of why an end-point has been specified and what the humane basis for the selection of the end-point is.
The specification of end-points may have to be done in consultation with a laboratory animal veterinarian and the animal care committee.
The specification of end-points should also be supported by a statement of what detailed observations will be performed on the animals during the experimental period, together with a list of the most significant predicators of deterioration of the animal's condition and how these will be responded to by the investigators in deciding when to end observations and kill the animal.
It is expected that researchers will have reviewed the literature on this aspect in their field of study, and will be able to provide an observational protocol with a defined end-point which can be considered to be humane in terms of both the objective of the study and its potential benefit to humans, animals and the environment.
9.3.25 Biohazard statement
If the proposed study poses any hazards to either other laboratory animals or institutional staff arising from the handling and/or administration of infective agents, parasites, toxic or carcinogenic agents, or ionising radiation, a brief protocol for containing these hazards is to be provided. This should be supported by an approval statement from the Animal Unit Manager and Institutional Safety Officer, to provide assurance that the proposed project can be safely conducted. This statement should be signed by both of these officers.
9.3.26 Repetition
If the experiment or part of it is a repetition of previous work performed by the applicant or other persons, this is to be stated. If so, details are to be given and an explanation provided as to why the experiment or part of it that has previously been done is to be repeated to produce significant new knowledge.
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