1. What is the South African Medical Research Council's ethics policy?

1.1 General policy
The MRC recognises injustices in our past and subscribes to the values enshrined in the Constitution of the Republic of South Africa Act, No 108 of 1996: human dignity, the achievement of equality and the advancement of human rights and freedoms.

The ethics policy of the MRC is clear. All research sponsored by the Council must be of the highest ethics standard. No research will be sponsored without ethics clearance from a Research Ethics Committee recognised by the Council and operating in accordance with MRC ethics guidelines.

1.2 For whom are these Guidelines intended?
The MRC Guidelines are concerned with research on human participants and animals. The Guidelines consider all forms of research on individual persons, whether they be volunteers or patients, and include the study of treatment which might benefit the individual patient (therapeutic research) and the acquisition of knowledge that may be of no immediate benefit to the healthy volunteer (non-therapeutic research). These Guidelines apply also to non-clinical research on humans. Guidelines on ethics in the use of animals in research are dealt with in Book 3 of the current MRC Guidelines series.

What follows in the chapters of this Book 1 of the series Guidelines on Ethics for Medical Research is extensively based on three previous editions and on international documents1-9 (see also Appendices V - VII) but is adapted for South African conditions and law.

1.3 Ethics principles
1.3.1 The MRC promotes the four principles of biomedical ethics:

• autonomy (respect for the person - a notion of human dignity)
• beneficence (benefit to the research participant)
• non-maleficence (absence of harm to the research participant)
• justice (notably distributive justice - equal distribution of risks and benefits between communities)

There is considerable debate about whether one or more of these principles require or deserve preference when ethical problems are considered. For example, the trend in most Western countries seems to emphasise autonomy over beneficence. This counters the alleged danger of paternalism in the practice of medicine, and emphasises the importance of the consent and freedom of patients in making decisions about their own health and well-being. Such views are questioned in the context of many developing countries, where solidarity within communities is valued together with respect for individual choices, and where there is increasing concern about conflict between personal autonomy and public safety in the face of, for example, infectious diseases such as tuberculosis and, particularly today, the HIV/AIDS pandemic. Concern for distributive justice in developing countries also enjoys a higher priority than in some wealthy Western nations.

The MRC is convinced of the importance of adherence to the four classical principles of biomedical ethics, and of the importance of human rights and individual dignity, but it takes no prejudicial position in debates on the ranking of these principles. The MRC also does not commit to any one approach to moral reasoning or to any one strategy for the resolution of complex ethical dilemmas. It seems clear that, in most disputes in biomedical ethics, some balance between the four principles should be pursued. In maintaining commitment to the classical principles, the complexities of each case must be understood and taken into account in any effort to make justified moral judgements. Of more importance than the consistent adherence to a specific approach or strategy for the resolution of moral dilemmas, is the willingness and ability to justify whatever position is taken, through sound moral reasoning.

1.4 Conclusion
Application of ethics standards requires a critical evaluation of the relative merits of each of the four principles of ethics to produce a harmony appropriate to a particular research project.

2. What is research?

2.1 What constitutes research on humans?
2.1.1 Clinical practice
When an activity is undertaken with the sole intention of benefiting an individual patient, and where there is a reasonable chance of success, that activity may be considered to be part of clinical practice. The progressive modification of methods of investigation and treatment, in the light of a clinician's experience, is a normal feature of clinical practice and should not be considered as research.

2.1.2 Research
Research is a systematic investigation, including research development, testing and evaluation designed to develop or contribute to generalisable knowledge. Any such investigation raises ethical issues. The issues themselves may be small, but because studies may involve subordination of at least the immediate interest of the individual participant to the objective of the advancement of knowledge, they must be subject to ethics review.

2.1.2.1 Therapeutic research
The aim of therapeutic research is to benefit the individual research participant or patient by treating or curing their condition.

2.1.2.2 Non-therapeutic research
The aim of non-therapeutic research is to benefit people other than the research participant. The participant or healthy volunteer may unexpectedly become a direct or indirect beneficiary of non-therapeutic research. The acquisition of knowledge may be of no immediate benefit to the participant or healthy volunteer.

2.1.2.3 Intervention research
This is always invasive and interferes with the research participant's mental or physical integrity by, for example, the removal of bodily material, the introduction of (contrast) fluids into the body or the use of a procedure or method that has not been adequately tested. It always involves risks, the magnitude of which may be unpredictable.

2.1.2.4 Observation research may be:

1. non-invasive, involving no risk and no interference with the mental or physical integrity of the human being; for example, the unlinked and anonymous gathering of information about the person by means of a questionnaire or from clinical records, the unlinked and anonymous examination of a specimen taken from a patient for a clinically indicated intervention; measuring; observing.
2. invasive of mental or physical integrity, but involving no risks or only negligible risks which are known from routine medical experience; for example, the taking of one blood sample, the collection or urine or of slightly more bodily material than is strictly necessary for a normal, medically indicated intervention.

2.1.3 Clinical practice and research
The distinction between clinical practice and research is often less clear than is suggested above, because both may be practised simultaneously on the same person. Any activity aimed at obtaining knowledge affecting a person in any way, and which is additional to ordinary clinical practice, is to be regarded as research (see also 7). A useful rule of thumb8 is that if this new knowledge is generalised or transferred to others, or presented at a scientific meeting, or submitted for publication or for a higher qualification, it is research. Clinical audits through examination of patient records; observation of activities of individuals; health systems research to improve efficiency, cost-effectiveness and equity in health care, all are recognised as valid research.

2.1.3.1 Non-clinical research
This type of research includes studies of anatomy, physiology and laboratory investigations not involving patients.

2.1.4 Innovative treatment