Written by
Nivedhna Singh
Expert advice
Adv. Ann Strode, (UKZN) & Dr. Joanna Bourke-Martignoni (UNINE)
Supervised by Prof. Douglas Wassenaar (UKZN)
Sponsored and Funded by a Medical Education Partnership Initiative from the Fogarty International Centre of the US National Institutes of Health FIC Grant number 1R24TW08863 to the University of KwaZulu-Natal. PI : Prof. U Lalloo
Please select a theme from the left pane to see the corresponding references.

1. Type of Research

South Africa has developed a comprehensive legal and ethical framework to regulate health research. This framework is primarily established in the National Health Act (No. 61 of 2003), which consolidates most of the law relating to health and creates a number of statutory institutions and regulatory bodies for the oversight of health research. These different structures include :

  1. Statutory institutions, which set the policy agenda, adopt binding norms and standards, and review and monitor research studies;
  2. Legally enforceable norms and ethical guidelines which establish substantive and procedural standards; and
  3. Monitoring and enforcement mechanisms through, amongst others, Research Ethics Committees (RECs), the Medicines Control Council (MCC) and the National Health Research Ethics Council (NHREC).

The field of ‘health research’ is defined in section 1 of the National Health Act as :

(A)ny research which contributes to knowledge of – (a) biological, clinical, psychological or social processes in human beings; (b) improved methods for the provision, of health care services; (c) human pathology, (d) the cause of disease, (e) the effects of the environment on the human body, (f) the development or new application of pharmaceuticals, medicines and related substances, and (g) the development of new applications of human technology. There are two key elements to this definition. First, the research activity must aim at knowledge production. The national ethical guidelines issued by the NHREC define research as a ‘systematic investigation to establish facts, principles or knowledge’ (Department of Health, 2004). Second, the research must fit within the ambit of one of the fields mentioned in (a) – (g) of the definition.

Obligations relating to health research apply to studies that include human and non-human participants. The term ‘health research’ is used in the following sections of the National Health Act which deal with the regulation of research :

  1. (i)Sections 69 and 70 require the National Health Research Council (NHRC) to determine the health research priorities for all state funded research;
  2. (ii)Section 72 describes the role and functions of the NHREC with regard to the ethical issues involved in health research; and
  3. (iii)Section 73 places an obligation on a wide range of institutions conducting health research to set up or have access to a registered REC.

The implications of this broad definition of health research are that any research which comes within the definition must (a) reflect national research priorities (if it is done using state funds), (b) be regulated by the NHREC and (c) be submitted for ethics review to a registered REC.

The second important category of research that is addressed in section 71 of the National Health Act is ‘research or experimentation on a living person’. There are additional obligations placed on researchers and institutions when this type of research is carried out.

The third term that delimits particular health research obligations is ‘health service for research or experimental purposes’. Again, this is a particular type of health research, namely, therapeutic research or a type of experimental health service. The term health service is defined in section 1 of the National Health Act as ‘(a) health care services, including reproductive health care and emergency medical treatment, contemplated in section 27 of the Constitution; (b) basic nutrition and basic health care services contemplated in section 28(l)(c) of the Constitution; (c) medical treatment contemplated in section 35(2)(e) of the Constitution; and (d) municipal health services’. It requires additional steps to be taken when patients or persons using health services are enrolled in a research study. These are set out in sections 11 and 16 of the National Health Act. There is one notable exception which relates to record reviews done for research purposes by health care providers at a health establishment. In these cases, section 16 of the National Health Act provides that no consent is needed from the patient.

  • Constitution of the Republic of South Africa, 1996 s 12 (2)(c), 27, 28(l)(c),35(2)(e)(d)
  • National Health Act, No. 61 of 2003, s 69, 70, 72, 73, 71,11,1
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004

1.1.Biomedical research

Biomedical research refers to clinical trials, research on human biological materials, epidemiological studies and certain health-related social science research. This is a term used in various ethical guidelines in South Africa; however, there is no special mention of the term biomedical research in the National Health Act. This type of research falls within the definition of health research and researchers must :

  • Ensure the objective of the study fits within national research priorities, if state funded/sponsored
  • Submit to the authority of the NHREC, through a registered REC
  • Submit the study for ethics review to a registered REC

If the study has human participants, it must also comply with the additional obligations outlined in sections 11, 16 and 71 of the National Health Act.

If blood, blood products, tissues or gametes are used from humans, researchers must further comply with sections 55 and 56 of the National Health Act and the Regulations Relating to the use of Human Biological Material.

  • National Health Act sections s11,16, 73, 55, 56
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, (2006), Preamble
  • Regulations Relating to the use of Human Biological Material, Government Gazette No. 3599, 2 March 2012

1.1.1. Clinical trials

A clinical trial is a research design and method aimed at developing a treatment or procedure known as an intervention. Clinical trials are used to determine the usefulness of drugs, surgical or other procedures, therapeutic and diagnostic devices.

The South African Good Clinical Practice guidelines (2006) were created with the South African context in mind, to ensure that research is scientifically sound and adheres to the four main ethical principles : respect for the dignity of participants, beneficence, non-maleficence and justice.

The National Health Act does not refer to or use the term ‘clinical trials’.However, clinical trials are a form of health research and must therefore :

  • Fit within national research priorities, if funded/sponsored by the state
  • Submit to the authority of the NHREC, through a registered REC
  • Submit the trial for ethics review before submitting to the MCC
  • Apply to the MCC for approval to conduct the trial and comply with its monitoring requirements
  • Register with the South African National Clinical Trials Register

Clinical trials must also adhere to the obligations laid out in sections 11, 16 and 71 of the National Health Act.

If blood, blood products, tissues or gametes are used from humans, researchers must further comply with sections 55 and 56 of the National Health Act and the Regulations Relating to the use of Human Biological Material.

Principal investigators (PIs) responsible for conducting clinical trials are governed by a code of professional conduct as well as specific legal and ethical guidelines. It is the duty of the PI and research staff to ensure that research is conducted ethically before, during and after the trial. Ethics and regulatory review and approval must be obtained prior to the recruitment of participants into a trial. Trials must be reviewed annually. There are four phases of such trials :

  • Pre-clinical trials : involve research using animals in laboratory settings.
  • Phase I : as the risks of a product or drug are not known, during this phase the candidate product is primarily tested to assess safety
  • Phase II : during this phase, studies are conducted to further assess safety, dosages and preliminary efficacy.
  • Phase III : involves large scale studies aimed at assessing the efficacy of the candidate product.
  • Phase IV : if the product or drug is found to be effective, this phase involves post-marketing studies as well as post-marketing surveillance.
  • National Health Act sections s11, 16, 71;55,56
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, Section 6
  • SA Medicines Control Council Regulations, 2012
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, Section 2.5. Section 3.4, Section 6
  • South African National Clinical Trials Register

1.1.1.1. Clinical drug trials

All clinical drug trials in South Africa must be reviewed and approved by the South African Medicines Control Council (MCC), which operates under The Medicines and related substances control act (Act 101 of 1965).

“The Medicines Control Council (MCC) is a statutory body that regulates the performance of clinical trials and registration of medicines and medical devices for use in specific diseases. The MCC is responsible for ensuring that all clinical trials of both non-registered medicines and new indications for registered medicines comply with the necessary requirements for safety, quality and efficacy.

Applications for clinical trials and for registration of medicines and medical devices are reviewed by an MCC expert committee, which considers amongst other issues the scientific aspects of the applications. Reports on the progress of the study are sent to the MCC on a regular basis. Proof of safety, quality and efficacy must be submitted when applying to the MCC for approval and registration of a medicine for use in South Africa” (South African National Clinical Trial Registry).

Clinical Trials must also be reviewed by a registered REC following the principles from the Department of Health “Guidelines for good practice in the conduct of clinical trials with human participants in South Africa(2006)” and South African National Health Research Ethics Council “Guidelines on ethics in health research : principles, structures and processes” (2004).

  • The Medicines and Related Substances Control Act 101 of 1965
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section, 1.5.1
  • South African National Clinical Trial Registry

1.1.1.2. Other clinical trials

South Africa is known for its involvement in HIV prevention trials including those aimed at the development of vaccines, microbicides and voluntary medical male circumcision. All these studies are considered health research and are regulated by the framework described above.

The development of an HIV vaccine is a long and challenging process which includes following a step-by-step methodology determined by the South African Medical Research Council (2003) (SA MRC) and the MCC.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, Section 8

1.1.2. Research with human biological material

1.1.2.1. Biological research

Biological research often forms part of public health research and health services. Biological research can be experimental or observational. Biological research is conducted through studies of the whole body, tissues or bodily fluids.

Biological research is a form of health research and must comply with all obligations regarding health research set out in the National Health Act. The definition of health research includes studies with deceased persons or with tissues, blood or body fluids. If living human beings are enrolled in a biological study, the obligations in sections 11, 16 and 71 of the National Health Act must be complied with.

Researchers engaged in biological research also have to comply with the Regulations Relating to the use of Human Biological Material.

  • National Health Act, No. 61 of 2003, s11, 16, 71
  • Regulations Relating to the use of Human Biological Material, Government Gazette No. 3599, 2 March 2012
  • South African Medical Research Council, Book 1 : Guidelines on Ethics for Medical Research, 2003, Section 4.1.1, p.14; Section 4.2.3

1.1.2.2. Genetic Research

Genetic research aims at understanding how human genes interact with environmental factors to influence the health status of individuals in various communities. Genetic research is extremely important since this type of research generates knowledge that can be used to improve the health of individuals. Genetic research helps scientists and researchers examine individual susceptibility to disease and inform steps towards interventions.

Section 57(1) of the National Health Act prohibits any activities involving research into the reproductive cloning of human beings. Section 57(5) of the National Health Act defines the reproductive cloning of a human being as the ‘manipulation of genetic material in order to achieve the reproduction of a human being and includes nuclear transfer or embryo splitting for such purpose’. However, a written application may be made to the Minister of Health for permission to research ‘stem cells and zygotes which are not more than 14 day olds (s 57(4)).

Written consent from the person concerned is required for the removal of tissues, blood and gametes and there are further conditions laid down in relation to these products in section 56 of the National Health Act.

The Regulations relating to the use of human biological material provide that the following genetic research is permissible :

  • Research into excess embryos obtained from in vitro fertilisation. These may be used to produce embryonic stem cell lines provided that written informed consent has been obtained from the embryo donor or cord blood donor (Regulation 7)
  • Research on primordial germ cells obtained from aborted foetuses provided that the prior written informed consent is obtained from the donor of the aborted foetus (Regulation 8).

The Regulations relating to the use of human biological material, provide further that when genetic health research is undertaken the following conditions must be complied with :

  • Only a ‘competent person’ may remove the biological material (a competent person is someone registered with a statutory Health Professions Council of South Africa)
  • Written consent is obtained. If the person is a child they may give their own consent to the removal if they are over the age of 12 and have sufficient maturity
  • The research has been approved by a registered REC.

If tissues are being removed from a deceased person for research purposes. It must be established :

  • Whether they consented to the removal before their death, or
  • Request written consent from to ‘the spouse, partner, major child, parent, guardian, major brother or major sister of a deceased person, in the specific order mentioned’.
  • National Health Act, No. 61 of 2003, s 57, 57(5), 57(4)
  • Regulations Relating to the use of Human Biological Material, Government Gazette No. 3599, 2 March 2012

Genetic research requires adherence to ethical guidelines. Ethical issues in genetic research are unique because genetic material is used in research protocols and numerous issues arise when genetic material (which is kept anonymous) is shared with family members and unrelated individuals in the population. Genetic research sometimes requires the participation of groups of family members as opposed to individual. The results gained from genetic research are useful and may be shared amongst blood relatives and other individuals in the population. Information produced from genetic research could affect life decisions and provide methods to improve health and wellbeing. On the other hand, some individuals might not wish to know the outcome of the research and their potential health risks. This information, however, could be valuable to relatives and individuals not related by blood, such as spouses or partners, because of health concerns regarding offspring. There are several ethical issues that arise in genetic research such as harm in the form of stigmatisation and unfair discrimination or the implementation of exclusionary policies.

It is the responsibility of researchers to ensure that special care is taken to protect the privacy and confidentiality of genetic material. RECs need to ensure that researchers consider whether the research could lead to potential harm and implement methods to counteract foreseeable harm. It is important to note that results from genetic testing could potentially be used by third parties (such as insurance companies and employers) to make decisions about participants and their relatives. Participating in genetic research should not affect an individual’s access to benefits that are readily available to other members of the community.

Genetic research and resultant findings are socially significant. Researchers are expected to consider the social and cultural significance of their research, especially in areas characterised by complex socially significant identities/traits and the genetic characteristics of collectivities. When genetic characteristics are being investigated, RECs need to ensure that ethical principles and guidelines are stringently maintained in the research. During ethical review of protocols for genetic research, RECs should ensure that there is a balance between the generation of knowledge and possible harm to participants or communities. The REC reviewing the protocol needs to determine from the researcher if there is a possibility of impact on local policies.

  • Regulations Relating to the use of Human Biological Material, Government Gazette No. 3599, 2 March 2012
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, Section 9, 9.1

1.1.3. Epidemiological studies

Epidemiology is “the study of the distribution and determinants of health-related states or events in specified populations and the application of the study to control health problems” (NHREC, 2004, p.43). “The study” in this context refers to research such as “surveillance, observation, hypothesis testing, analytic research and experiments” (NHREC, 2004). “Distribution refers to analysis by time, place and class of persons affected”. “Determinants refer to all physical, biological, social, cross-cultural and behavioural factors that influence health”. “Health related states and events include diseases, causes of death, behaviours such as use of tobacco, reactions to preventative regimens and provision and use of health services”. “Specified populations” are those with identifiable characteristics such as precisely defined numbers. “Application of data to control health problems makes explicit the aim of epidemiology – to promote, protect and restore health.” (Dictionary of Epidemiology (2001, cited in NHREC, 2004, p.43).

Epidemiological research can range from groups of individuals to entire populations and is part of public health and health services research. Public health, generally, is concerned with improving health systems planning, health care services and is usually carried out with human participants. Data (biological samples) and demographic information are usually collected from human participants as it is the only means to gain knowledge about human health. Many epidemiological studies are thus non-interventional and rely on policy makers to implement findings into public health policies.

Epidemiological research is a form of health research as described above. It must comply with all the obligations relating to health research as described above.

  • National Health Act, No. 61 of 2003, s 1, 71
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, Section 7

1.2. Research involving humans other than health research

1.3. Health related social science research

Health related social science research refers to observational and interventional studies aimed at generating knowledge and/or implementing experimental behavioural and/or social change. Social science research might not provide instant benefit to participants and communities but produces useful knowledge.

There is only one special requirement that applies to social science research conducted by the Human Sciences Research Council. Section 14(6) of the Human Sciences Research Council Act provides that when research is being conducted in areas under the jurisdiction of traditional leaders, notice of intention to do such research must be sent, in writing, to the House of Traditional Leaders.

  • Human Sciences Research Council Act No. 17 of 2008, s 14
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, Appendix E
  • Wassenaar, D.R., & Mamotte, N. (2012). Ethical issues and ethics reviews in social science research. In M. Leach, M. Stevens, G. Lindsay, A. Ferrero, & Y. Korkut (Eds.) The Oxford handbook of international psychological ethics (pp. 268- 282). New York : Oxford.

2. Ethics Review

2.1. Research Ethics Committees (RECs)

Section 73 of the National Health Act places an obligation on all institutions, agencies or health establishments conducting health research to set up or have access to a registered REC. This is an institutional obligation to establish and have access to an REC. There is a direct obligation on the institution to ensure all health research is reviewed. This means that indirectly researchers are under a legal obligation to obtain ethical clearance from a registered REC. If they fail to do so the institution that employs them or has funded them to do the research or which is allowing them to conduct the study on their premises could take disciplinary action against them.

In South Africa, RECs are found in most tertiary academic and research institutions and in large service-rendering health institutions. RECs are usually responsible for ethical review of protocols. At the time of writing this module, there were more than thirty-four RECs based at various institutions in South Africa (see National Health Research Ethics Committee Guidelines for a list of RECs (see also researchethicsweb.org).

According to section 73 of the National Health Act the function of RECs includes :

  • Reviewing research protocols and proposals to ensure that the research will be conducted according to the relevant guidelines and principles and will ultimately promote health and prevent or cure disability and disease;
  • Approving research protocols that meet the ethical standards of the committee.

The role of RECs includes :

  • Ensuring that prospective participants are treated fairly and with dignity, such that the wellbeing of both animal and human participants is not jeopardised;
  • Informed consent must be obtained when human participants (including children) are involved in the study
  • National Health Act, No. 61 of 2003, s 73
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 3.1, p.12; section 4
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section, 1.5.4

2.1.1. Jurisdiction of the REC

The jurisdiction of RECs is not geographically defined within South Africa but instead depend on institutional policy i.e. some are local, some are national, some are private for profit.

  • National Health Act, No. 61 of 2003, s 72.
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 3.2

2.1.1.1. National Health Research Ethics Council

The National Health Research Ethics Council (NHREC) is a regulatory body established by section 72 of the National Health Act. The NHREC does not conduct ethics reviews. The National Health Act creates four roles for the NHREC specifies :

  1. Norm setting. NHREC must issue guidelines on the functioning of RECs and on ethical norms/standards
  2. Oversight over RECs. The NHREC must ensure that RECs are carrying out functions as described in the National Health Act
  3. Enforcing ethical norms and standards. The NHREC must adjudicate complaints, refer violations to statutory professional councils and institute disciplinary action when needed
  4. Advise the government on ethical issues.

The NHREC consists of approximately 15 members and elects its own chairperson. It meets four times per annum, submits annual reports and advises the Minister on policy.

The NHREC has the power to establish ad-hoc committees to monitor or investigate the following :

  • Policy standards and standard operating procedures (SOPs);
  • Training and capacity building;
  • Appeals;
  • Sub committees.

The NHREC is sustained by the Department of Health (DOH) which ensures that a database on health research ethics activities is available in South Africa. Qualified inspectors are employed to oversee the functions of the NHREC. These functions include “training, assessment and accreditation and ad-hoc visits” (NHREC, 2004, p.13). National Health Research Ethics Council advises the Department of Health (DOE) on health research ethics matters and is responsible for registering and auditing RECs and is not involved in ethical review of protocols. The NHREC may make public statements on ethical issues.

The NHREC is responsible for advising the DOH on health research ethics issues in South Africa. The NHREC cannot substitute for other committees or RECs but regulates research ethics.

All RECs in South Africa must be registered in accordance with NHREC requirements. RECs are audited by the NHREC. REC members must receive initial and ongoing training to ensure current acceptable standards of research are met and satisfied.

  • National Health Act, No. 61 of 2003, s 72
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 3.2

2.1.2. Independence of ethics review/RECs

The REC is an independent body and functions to protect the rights and welfare of individuals participating in research. The REC remains independent of all “political, institutional, professional and market influences”. The National Health Act, 2003 (Act No. 61 of 2003) specifies the legal status of RECs in South Africa.

  • National Health Act, No. 61 of 2003, s73
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4, Glossary

2.1.2.2. Independence of members

All REC members are required to sign conflict of interest declarations and these signed documents should be kept on file.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.3
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, Section 8.2, notes 37

2.1.3. Composition of the REC

The NHREC and South African ethical guidelines stipulate the following composition of all South African RECs. The REC should comprise of members who have suitable qualifications and experience to review and evaluate the scientific, clinical and ethical dimensions of research protocols. It is proposed that an REC consists of :

  • A chairperson;
  • A minimum of nine members, with 60% representing a quorum;
  • The committee should aim for equal numbers of males and females; however there should not be more than 70% of one gender;
  • The committee should include two lay persons who have no attachment to the institution and preferably from the community/population under investigation;
  • Members who have up-to-date knowledge and experience in different fields of research that will likely be repeatedly considered by the committee;
  • A member who has knowledge and current experience in “professional care, counselling or treatment of people (e.g. medical practitioners, psychologists, social workers, nurses” (South African Good Clinical Practice guidelines, 2006, p.59);
  • At least one member should have a comprehensive background in qualitative and quantitative methodologies;
  • One member with legal training and experience;
  • Members that have the ability to evaluate all categories of research;
  • Members that are demographically representative of the local community;
  • A signed list of appointments specifying the term of appointment of each member.

Appointment of committee members might differ at various institutions; therefore, each institution should determine its own specified recruitment process. It is imperative that appointment of members is made through formal notice. Members must be indemnified should any legal action be taken against the member when he/she is carrying out his/her respective duties for the REC.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.1
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 8.2

2.1.4. Functioning of the REC

It is mandatory that RECs establish and maintain procedures in a written format for the following, including :

  • Frequency of meetings;
  • Preparation of agenda and minutes;
  • Distribution of papers prior to meetings;
  • Presentation of research protocols;
  • Presentation of all documents and other materials used to inform potential research participants;
  • Quorum and methods of decision making;
  • Requirements for submission of research projects for ethical approval;
  • Registration of applications;
  • Timely review and notification of decisions to researchers;
  • Decisions made by the committee and reasons for decisions must be recorded in writing.
  • Each REC is required to ensure that a procedure is in place for the disposal of confidential information and documents such as agendas and the minutes of committee meetings.
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.3

2.1.4.1. Organisation of the REC

Health research has a considerable impact on the welfare of the population. During the establishment of an REC, terms of reference are developed. The terms of reference specify the level of responsibility and accountability of the committee, relationships to unrelated researchers, and the procedure for reporting possible remuneration. The organization must ensure that there are sufficient resources available to establish and maintain the REC.

The NHREC makes provision for two levels of REC :

  1. Level one RECs may only review minimal risk research
  2. Level two RECs may review all types of health research including clinical trials.

The NHREC is responsible for ensuring that all RECs comply with relevant legislation and guidelines. The REC must be registered with the NHREC and provide a list of their members before commencing with ethical review of protocols. The NHREC may request records from any REC. All institutions and RECs must report to the NHREC annually about the following :

  • Membership and membership changes;
  • The number of meetings held;
  • Confirmation of participation by required categories of members;
  • The number of protocols presented, the number approved and the number rejected;
  • Monitoring and related problems;
  • Complaints procedures and number of complaints received and handled (SA DOH, 2004, p.19).
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.1.3; 3.3.3.1; 4; 4.10

2.1.4.2. Decision-making process within the REC

The REC is expected to keep a record of all research protocols received, including details of the sponsors or institutions funding the research, specific project details, details of the principal investigators/researchers and any documents participants will receive. The REC must keep records of complaints from PIs whose protocols were rejected and if protocols were approved (including terms and conditions of approval). Terms and conditions may refer to expedited review, opinions from other RECs and “any actions taken by the ethics committee to monitor the conduct of the research” (Department of Health, 2006, p.61).

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.1, 4.6

2.1.4.3. Transmission of REC decisions

RECs have the authority to grant approval, propose modifications or reject protocols on ethical grounds. RECs are required to document and keep written records of all correspondence with applicants. It is suggested that RECs maintain a standard format when communicating with PIs. Researchers are expected to engage and think critically about the ethical issues in their protocol instead of merely repeating and including the basic ethical guidelines that govern research with human participants. Assistance from ethical experts is permissible; however, it is imperative to ensure no potential conflicts of interest between the expert and the subject under investigation.

RECs must ensure that when members of an REC are directly involved in a research protocol their role and opinions as committee members are excluded to avoid conflicts of interest. An investigator managing a protocol is required to divulge in writing specific details of all and any contractual affiliations related to the trial under ethical review. It is the responsibility of the REC to ensure that the protocol addresses and considers the context in which the research is taking place. In particular, research protocols carried out in community settings need to specifically stipulate how the community will be involved in, and benefit from, the research and how the information will be disseminated.

The PI remains the communication link between the sponsor and the RECs (however, in the private sector the PI is often an employee of the company sponsoring the study). It is essential that all documents that form part of the protocol, such as letters of informed consent, advertisements and questionnaires, are reviewed and approved by the REC before data collection commences.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.3

2.1.5. Ongoing review of research

The REC is permitted to request amendment to or terminate a study on ethical grounds if there is evidence of unethical practice or serious harm to research participants. Data and safety monitoring committees (DSMBs) monitor and evaluate clinical trials. Regular unblinded assessments are made of the safety of participants, the efficacy of treatment and usefulness of data. If DSMBs report that participants are being harmed, the REC may terminate the trial. DSMB reports must routinely be forwarded to the REC. RECs are obliged to ensure that trials are monitored once they are approved. The frequency and type of monitoring is dependent on the level of risk to research participants. RECs should at the very least request detailed reports from PIs on the progress of the trial. The suggested time frame is at least annually on issues such as :

  • The progress of the trial and any outcomes or findings of the research;
  • Information about how records will be stored and kept;
  • Evidence that protocols were followed or any amendments were approved and adhered to the protocol.
  • Occurrence and severity of adverse events experienced by participants;
  • Any changes to the protocol;
  • Any unexpected incidents that affect the ethical approval of the study.

The REC should provide feedback to the PI on decisions after progress reports have been reviewed. The REC may propose additional methods for monitoring a clinical trial/research study such as visits to trial sites; examination of data collected and signed consent forms.

Once ethics approval for a study or trial is obtained, the PI is required to provide reasons and details if, for any reason, the clinical trial/research is closed or discontinued.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.6, 4.7

2.1.6. Responsibilities of the REC

The legal obligations of RECs in terms of section 73 of the National Health Act specify two roles for RECs :

  1. To review research to make sure that it is relevant to institutions that promote health and prevent disease.
  2. To grant approval when the research is ethical in terms of guidelines used by that committee.

The main ethical responsibilities of RECs in South Africa are to :

  • Ensure protection and respect of research participants by preserving their rights, safety and welfare.
  • Assure the public that research with human participants is independently reviewed and approved and that individuals conducting research are experienced and appropriately qualified and the research methods safe.
  • Ensure research is ethical and scientifically valid; RECs are required to assess and evaluate the scientific merit of proposed research protocols. Although the primary role of RECs is to protect the dignity, rights and safety of research participants, each member on the REC is obliged to autonomously evaluate the ethical and scientific merit of the research protocol. Most research institutions are expected to establish and maintain RECs. Terms of reference must be developed when the REC is established and must clearly stipulate the scope of the REC, responsibilities, roles of members, and remuneration, if applicable.
  • Implement these responsibilities guided by South African ethical guidelines, standards and codes of practice such as :
  • National Health Act, No. 61 of 2003, s 73
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section, 4
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 8.1

2.2. Ethics review criteria

Ethics review ensures that research proposals are independently and critically evaluated because research may impact on the rights and wellbeing of people and on the continued development of health care resources. In South Africa the following bodies are involved in the ethical review of research :

REC : a group of professionally qualified and experienced individuals, such as medical practitioners, scientists, lawyers, social scientists and community representatives. The National Health Act provides in section 1, read with section 73, that RECs must review and approve all health research protocols regardless of whether they involve human beings. All South African RECs must be registered with the SA NHREC see 2.1.1.The National Health Act provides further in section 73(2)(b) that RECs must ‘grant approval for research by the relevant institution, agency or establishment in instances where research proposals and protocols meet the ethical standards of that health research ethics committee’ (p.77). It is submitted that as the NHREC is mandated by the National Health Act to issue ethical guidelines, any norms set by them would be the ‘ethical standards’ referred to in the Act.

The Medicines Control Council (MCC) is a statutory body established under the Medicines and Related Substances Control Act (1965 as amended). The MCC reviews all clinical trial protocols and is responsible for assessing the safety, quality and efficacy of new drugs entering the pharmaceutical market. However, the MCC is not accredited to conduct ethical review. This must be done by a registered REC.

  • National Health Act 73(2)(b)
  • National Health Act 72(6)(g)
  • Medicines and Related Substances Control Act 101 of 1965 (as amended in 2007)
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2

2.2.1. Social value of the research project

The research must have social value to the community, population or country under investigation, such that it justifies the use of resources and subjecting participants to inconvenience, discomfort or potential harm.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, preamble, section 2

2.2.1.1. Medical relevance of the research project

Section 69 of the National Health Act creates the National Health Research Committee (NHRC; not to be confused with the NHREC described above). This body is tasked with the following functions :

  1. (a) Determine the health research to be carried out by public health authorities;
  2. (b) Ensure that health research agendas and research resources using state funding focus on priority health problems;
  3. (c) Develop and advise the Minister on the application and implementation of an integrated national strategy for health research; and
  4. (d) Coordinate the research activities of public health authorities

Section 70 of the National Health Act requires the NHRC to consider the following 5 factors when setting national or provincial health research priorities :

  1. (a) The burden of disease;
  2. (b) The cost-effectiveness of interventions aimed at reducing the burden of disease;
  3. (c) The availability of human and institutional resources for the implementation of an intervention at the level closest to the affected communities;
  4. (d) The health needs of vulnerable groups such as women, older persons, children and people with disabilities; and
  5. (e) The health needs of communities.

Priorities established by the NHRC are only applicable to state funded research. However, ethical principles require research to be relevant and address health concerns of the population under investigation.

  • National Health Act, No. 61 of 2003, s 70, 69
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2

2.2.1.1.1 Relevance for the target population

In South Africa, researchers are responsible for ensuring that the research they conduct is pertinent to the health and developmental needs of the context and to those populations under investigation. The goals of the research must ideally be translatable into solutions for improving the health of South Africans. State funded research must fit within national priorities set by the NHRC. See section 2.2.1.1 above.

  • National Health Act, No. 61 of 2003, s 70, 69
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.2, p.5

2.2.1.1.2. Relevance for public health

Studies should ask relevant questions and generate findings that can be translatable into solutions for improving the health status in a country. In line with the best possible standards of clinical research, protocols should be based on priority of research and research questions that need to be developed in line with the context. The research questions should address the problems faced by local and regional populations in South Africa. The rationale of a study needs to identify the problem area and indicate how research can address this area of concern and indicate how findings could be locally implemented.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.3

2.2.2. Scientific validity of the research project

The research must have a sound scientific rationale and methodology to answer the research questions posed. Valid research questions provide answers to research problems. Individuals who are experienced and qualified should be involved in the collection and analysis of data to ensure knowledge produced is valid and reliable. The scientific validity of the study should be assessed by the REC. Some researchers argue that scientific considerations are not for an REC to consider. Most international ethics guidelines, including the South African (2004) guidelines make it clear, however, that consideration of scientific validity is an integral component of the ethics review process.

  • South African Medical Research Council, 2003 : HIV Preventive Research, section 9.12.1, section 9.12.2.3
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 7.9

2.2.2.1. Method/design of the research project

Appropriate study designs ensure that valid results will be obtained. The study design must show how the questions will be answered. Justification must be provided for the use of certain methods, the choice of population being sampled, size of sample and analysis. The design of the study must not undermine a participant’s current treatment.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.3

2.2.2.1.1. Pre-clinical data

Pre-clinical data emerges from research in a laboratory and research with animals and must be summarised by the researcher when relevant (e.g. clinical trials).

  • South African Medical Research Council, 2003, Book 5 : HIV Preventive Research, section 8.1.1

2.2.2.1.2. Scientific literature review

In addition, proposals should include systematic review of literature from previous research (National Health and Medical Research Council, 1998 cited in NHREC, 2004). The research protocol must be open to review and critical discussion from experts in the field.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.3

2.2.2.1.3. Research design

Studies that have been properly designed should enable scientific questions to be answered and the design must be appropriate for the research questions. Details and rationale for the study sample and population must be provided. If the sample includes a vulnerable group¸ justification must be provided for using that particular group and how the research is likely to benefit this population. In clinical trials a participant’s current care and treatment may not be compromised because of the care and treatment under investigation.

HIV preventative research is common in South Africa. For this to be ethical the research protocol should have scientific merit and the benefits of the research should accrue to the participants and relevant populations (see TRREE Module 3.3).

  • South African Medical Research Council, Book : 5 HIV Preventive Research, 2003, section 4.2; 4.3; 4.4

2.2.2.2. Investigator’s brochure (for clinical trials)

The purpose of an investigator's brochure is to document information about the investigational product. Information compiled in the brochure contains elements of the investigational product as well as data and findings from previous studies. The investigator's brochure should contain justifications of the length of the trial and assessments of safety and strategies for avoiding risks/harm. The investigator’s brochure must be updated by an appropriate person when new information about the investigational product becomes available.

  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, Appendix F

2.2.3. Investigator’s qualifications

PIs should be adequately qualified to conduct research on a large scale. The investigator’s competence is usually assessed by their competence in research and their educational qualifications, knowledge, experience and certification through training. S/he will be directly responsible for the ethical management of the research/study. Technical competence of the investigator also includes having interpersonal and management skills. Ideally, each study should have a local PI who is a permanent resident of the host country and be registered with the Health Professions Council of South Africa.

  • Health Professions Council of South Africa, Book 6 : General Ethics Guidelines for Health Researchers, 2008, section 8.1

2.2.4. Compensation for damages

Before commencement of a trial the REC must ensure that provision has been made for compensation should a participant be injured during the trial. Compensation is paid based on the probability that injury arose as a direct result of the product or intervention under investigation. Compensation is only paid for serious and permanent injuries and not for temporary discomfort or less serious injuries.

South Africa has adopted the “no-fault insurance” principle. This principle intends to provide compensation to clinical trial participants, without proof of fault, in the event that they suffer research related injury. No fault insurance applies to clinical trials. No fault insurance intends to provide compensation to clinical trial participants, without them having to prove that the researchers or sponsors were negligent.

  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 4.11
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.5, 6
  • Mamotte, N., Wassenaar, D., & Singh, N. (2013). Compensation for research-related injury in NIH-sponsored HIV/AIDS clinical trials in Africa. JEHRHE, 8(1), 45-54

2.2.4.1. Cover for damages

Compensation is also recommended for unborn foetuses (in-utero) injured in research due to maternal participation. Compensation for injuries is usually paid when injuries are permanent and of an enduring disabling nature. In addition, compensation is payable when procedures developed to deal with injury result in further injury. If this occurs, participants should be compensated as though injury occurred as a direct result of the drug under investigation. Sponsors are strictly liable if the product under investigation leads to injury. The Guidelines for Good practice in the conduct of clinical trials with human participants in South Africa provide that participants may have a claim for compensation if it can be shown that :

  • A trial product or procedure was administered that caused serious bodily injury
  • The bodily injury was serious and of an enduring character
  • The injury would not have occurred but for participation in the trial

In other words in a clinical trial compensation may only be claimed for physical harms that are enduring in nature.

Compensation for injury is not payable when :

  • The product under investigation fails to provide any benefit to the participant;
  • Injuries occur due to other licensed drugs used as a comparison for the product under investigation;
  • The control group receiving placebo fails to benefit;
  • Injuries occur through the following :
    • Considerable departure by the researcher from the research procedure;
    • Default act of a third party;
    • any negligence of the participant.
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 4.11

2.2.4.2. Extent and nature of damage

The amount payable for compensation should be based on the “nature, severity and persistence of the injury” (South African Good Clinical Practice Guidelines, 2006, p.42) and should be equivalent to an amount deemed acceptable for similar forms of harm by the South African courts. The Guidelines for Good Practice (2006) provide that participants will only have a claim for compensation if they suffer bodily injury that was serious and of an enduring character. Compensation will not be paid for psychological harms, or harms that are not serious or not enduring.

Payment of compensation for research-related injury depends on individual circumstances.

  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section, 4.11

2.2.4.3. Persons responsible under the cover for damages

When disputes arise between sponsors and participants, it is advisable that an independent third party is employed to assess whether compensation is payable and the amount. When an incident of research related injury occurs, the study PI is first notified, the REC, MCC and the study sponsors. It is the sponsor’s duty to take responsibility for any injuries that occur during the trial. Injuries that occur due to treatment administered after the research remains the responsibility of the treatment personnel i.e. medical team.

  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section, 4.11

2.2.5. Selection of research participants

Research must be carried out on participants based on appropriate selection methods.

Based on the principle of Justice, the selection of participants should be fair and justified based on scientific and ethical principles. There should be strict selection criteria specifying which participants will be included and excluded.

The research protocol should clearly discuss which population is likely to benefit from the research and how they will be selected. The methodology section of the research will provide a justification for the selection of participants, discussing why they are appropriate.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.17; 2.8; 6
  • South African Medical Research Council, Book 1 : Guidelines on Ethics for Medical Research, 2003, 7.1

2.2.5.1. Selection criteria

The ethical principle of Justice requires that there be fair mechanisms in place when participants are selected to participate in research. Justice becomes relevant to the selection of participants at social and individual levels. On the individual level, there should be fair and transparent procedures in place during the selection of participants. Research that is potentially beneficial should be offered to all persons and not just to a select few in the population; especially those who are easily available or identified as ‘disadvantaged’ for high-risk research. Socially, high risk research should not include individuals who are likely to be exploited or identified as ‘burdened’. The selection criteria should consider individuals belonging to all socio-economic statuses unless the research applies specifically to such groups. If a population is selected to participate in the research and will not benefit, their inclusion must be justified.

  • Belmont report, 1979, section 3
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.17

The selection of research participants should be justified by the research topic being investigated. Every individual in the population of interest should have an equal and fair chance of being included in the study. Criteria should be devised when recruiting participants into a study to ensure that the findings are valid and representative of the population under study.

If prospective participants are excluded from a study, a referral process needs to be set up for them, enabling them to access necessary local facilities. A clear risk-benefit ratio needs to be determined and an assessment of vulnerability factors that might affect prospective participants should be conducted. The research protocol must contain safety mechanisms to protect participants from harm during the research process.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.3
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 2.7

2.2.5.2. Vulnerable participants

Many research participants and research communities in South Africa may be considered vulnerable as a result of factors including; limited economic development; inadequate protection of human rights and discrimination on the basis of health status; inadequate community/cultural experience with the understanding of scientific research; limited availability of health care and treatment options and limited ability of individuals in the community to provide informed consent.

  • UNAIDS/WHO Ethical considerations in biomedical HIV prevention trials, 2012

2.2.5.2.1. Populations or communities with limited resources

Research often includes vulnerable communities. In some cases, communities that are ‘developing’ or ‘underdeveloped’ are deliberately excluded from early phases of research/trials because of perceived vulnerability to harm or exploitation. When a vulnerable group is included in the study the researcher must make an effort to address the vulnerability of the community and ensure participants are protected. Strategies for addressing vulnerability are capacity building initiatives, collaborative partnerships between community and researcher, on-going informed consent and fostering support and sponsorship. If participants are drawn from a vulnerable population the research process must be carefully designed and RECs must require the following :

  • Justification for including a group is needed to explain why other less vulnerable groups cannot be used;
  • Justification for how this research will benefit the vulnerable community and addresses any problem in collaboration with the community;
  • Explanation to research participants of their rights and roles as participants so maximise their ability to make an informed decision about participation. The research process needs to be tailored to the characteristics of the community.
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 7.1
  • UNAIDS Joint United Nations Programme on HIV/AIDS, Good Participatory Practice : Guidelines for biomedical HIV prevention trials, 2011, section 3.13

2.2.5.2.2. Communities with insufficiently well-developed systems for the protection of the rights and welfare of research participants

Participants may be from poorly-resourced communities or may be dependent on welfare programmes. Research should address the needs of the community and ensure that their welfare is protected. It is imperative that there be on-going informed consent and that a decision to participate is made after careful consideration of the consequences of participation and counselling. A trial monitor or independent authority may be necessary to assess the consent process. An assessment should be made of the negative consequences of participating in research and providing access to necessary facilities, such as psychological, legal and health care, should the need arise.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 7

‘Collectivities’ are groups of individuals who are distinct from other groups because of their beliefs, values, and social structures and who are usually influenced by tradition or custom. Approval should be sought from RECs when disagreements occur between collectivities, ownership of data collected, distribution of benefits and harms and obtaining informed consent. Researchers working with collectivities are encouraged to collaborate with collectivities at all stages of research.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.12
  • UNAIDS Joint United Nations Programme on HIV/AIDS, Good Participatory Practice : Guidelines for Biomedical HIV Prevention Trials, 2011, section 3.

2.2.5.2.3. Individuals with limited capacity or freedom to consent or to decline to consent

Participants with impaired capacity to communicate

Impaired capacity refers to individuals who receive medical care and are in non-acute states. Acute impairment refers to difficulties with cognition and requires alternative expressions while non-acute states inhibit expressions.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.13

Participants with mental disabilities

Mental disabilities include psychiatric and cognitive disorders and conditions arising from substance abuse. Research involving these groups is required to assess the social value of the research, risk/benefit ratio and individuals ability to provide informed consent (or gain consent from any relevant party who has legal responsibility). Research with mentally disabled individuals is only permissible when the research question applies to this population of individuals. The research should be in the interest of the participant and benefit the participant’s condition. In the event the person with the disability refuses to participate this should be respected.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.13

Unconscious participants

Research with unconscious participants is problematic because of participants’ inability to provide informed consent. Informed consent is obtained on behalf of these individuals from others who are either legally responsible for them or who care for them. Research protocols involving unconscious persons should avoid any procedures that are risky and should be limited to observational research.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.13

Special groups

Special groups are defined as individuals who have suffered trauma, terminally ill persons, elderly patients, marginalised groups, students and employees.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.13

2.2.5.2.4. Junior or subordinate members of a hierarchical group

Research involving junior or subordinate persons occurs when consent to participate in research depends on another individual's approval. RECs are required to ensure that consent to participate is voluntary and informed for each individual.

It is difficult to identify all relationships of this nature; however, they occur when individuals occupy junior or subordinate positions within the hierarchy. Examples of these kinds of relationships are between :

  • ‘Old or aged individuals and the persons responsible for their care and wellbeing;
  • Terminally ill patients and the persons responsible for their care and wellbeing;
  • Patients under the care of their medical practitioners;
  • Learners and Educators;
  • Prisons and relevant authorities;
  • Managers and workers;
  • Wards of state and guardians’ (NHREC, 2006, p.30)
  • Military seniors and subordinates.
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.4
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 7.8

Research with women

There is a relative lack of data on women’s health interventions because women were previously excluded from research because of potential pregnancy and harm to the foetus. This exclusion needs to be adequately justified and RECs are required to assess whether this justification is legitimate. Researchers have an ethical duty to conduct research that avoids discrimination against women by unfairly excluding them from research protocols.

In some instances, women belong to communities where their independence and autonomy are not recognised and might be susceptible to the influence of others.

It is essential to consider the special needs and additional health risks of women who are, or plan to become, pregnant while participating in research to avoid harm to the foetus. Exclusion of women should be based on scientific grounds and avoidance of risk.

Ethically, research involving pregnant women and foetuses is only permissible if :

  • Preliminary studies have been carried out on animals and non-pregnant women;
  • The rationale for the research is to meet urgent health needs of the mother and the risk is minimal to mother and foetus;
  • There is specification of timing, methods and procedures to be used if the pregnancy is terminated;

No procedures for terminating pregnancy may be introduced into the protocol for investigational purposes.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.5
  • Macklin, R. (2010). Enrolling pregnant women in biomedical research. The Lancet, 375, 632-633

2.2.5.2.5. Persons who have serious diseases

Research with persons requiring medical care

Section 11 of the National Health Act deals with the situation when a ‘health service; is offered ‘for research or experimental purposes’’. In such a situation, a number of additional steps must be taken including ensuring consent is obtained from the :

  • Patient
  • Health care provider primarily responsible for their treatment
  • Head of the health establishment concerned and
  • The relevant REC , or any other person to whom this authority has been delegated

Ethically, special attention is needed for research targeting individuals highly dependent on medical care. Due to their medical condition, research participation might involve increased risk. Researchers need to be aware of the impact the medical condition and medication might have on the participants' ability to voluntarily consent to research and communicate their decision. Participants need to be informed that refusal to participate will not affect their treatment.

  • National Health Act 61 of 2003 s11
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.13

The following types of research are different and warrant discussion and assessment by RECs :

Emergency care research

Emergency care research is different from other research because it commences quickly at a time when participants and their families are most vulnerable. Observational research is often conducted with these groups. The difficulty with this research is that obtaining informed consent from the participants leads to time delays in treatment which can decrease potential benefits.

Intensive care research

Individuals receiving intensive care are those connected to life support and under sedation. Ideally, informed consent for intensive care research should be obtained before patients are admitted to this type of care. If research is conducted on these patients it should be observational research.

Neonatal intensive care research

Research involving neonates is conducted according to the child’s best interests. Protocols for neonate research require careful examination and assessment because of the vulnerability of infants.

Terminal care research

Terminal care research involves participants who are terminally ill and are vulnerable because they are unlikely to benefit from the research. It is the responsibility of researchers to ensure that the potential benefits to the participants are not used to pressure individuals to participate in research or rationalise the increased risk inherent in the research. The needs and wishes of participants should be respected at all times.

  • National Health Act No 61 of 2003, s 5
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5, 8, p.32; section 5.13

2.2.5.3. Recruitment process

During the recruitment process researchers will need to consider restraints evident in both the research team and potential participants. The recruitment of research participants must be justified and fair based on scientific and ethical principles. The methodology section of the protocol will discuss how participants will be recruited and what methods will be used to obtain informed consent.

  • South African Medical Research Council, Book 1 : Guidelines on Ethics for Medical Research, 2003, 7.1.2
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.8; 6
  • Guidelines for Good practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 2.2

2.2.5.3.1. Recruitment process in general

During the recruitment stages of research, participants should be free from undue stress and coercion. Initial recruitment may occur through advertisements, community meetings, or by approaching participants personally. The method used to recruit participants should be outlined in the protocol and approved by the REC. The protocol should also show how participants will be recruited and the time frame in which recruitment will take place.

  • South African Medical Research Council, Book 1 : Guidelines on Ethics for Medical Research, 2003, 7.1.2
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 3.2

2.2.5.3.2. Recruitment process by advertisement

Any advertisements or other public information materials designed to inform potential participants about research must be reviewed by the appropriate REC.

    Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.3

2.2.5.4. Community Consent

The process of gaining community access occurs firstly (where relevant) through a process of consultation with the head of a community or with relevant representatives, investigators, research ethics committee members, sponsors and relevant bodies/stakeholders. They collaborate to devise a plan to obtain community support and preparation for decisions about research participation. Strategies for building capacity and addressing factors such as illiteracy, confidentiality, anonymity, autonomy, language barriers, cultural norms and beliefs need to be discussed collectively. Attempts must be made to ensure that the research process and terminology are understood which will foster informed and voluntary decision-making concerning participation. Consultations of this nature create an avenue for questions to be answered about the impact of trial participation on the wellbeing of individuals and their families. Note that under South African guidance, that this process entails community engagement rather than formal community consent.

  • South African Medical Research Council, Book 5 : HIV preventive research, 2003, section 5
  • UNAIDS Joint United Nations Programme on HIV/AIDS, Good Participatory Practice : Guidelines for Biomedical HIV Prevention Trials, 2011, section 2.6

2.2.6. Informed consent

Section 71(1)(b) of the National Health Act provides that written consent must be obtained from all participants in health research. Furthermore, consent can only be lawfully obtained if the research participant has been ‘informed of the objects of the research or experimentation and any possible positive or negative consequences for her or his health’. Given the very broad definition of health research set out in section 1 of the National Health Act which provides that health research is research which contributes to knowledge in various health-related fields, it means that the flexibility that existed in the past has fallen away as written consent is always required if human participants are involved in the study (see Section 1 above for the full definition). Furthermore, in terms of section 11 of the National Health Act where research involves experimental health services, written consent must also be obtained from the :

  • Patient
  • Permission must also be obtained from :
  • Health care provider primarily responsible for their treatment
  • Head of the health establishment or a person to whom this responsibility has been delegated
  • REC approval is also required

The only form of health research which does not require written consent is a record review which is being conducted by a health care provider. Consent is not required in this instance if the health care provider does not obtain any information on the identity of the patient or research participant (s 16(2), National Health Act). Review by an REC is required.

In terms of section 71(2) and (3) of the National Health Act, if minors are to participate in the study, consent must be obtained from their parents or guardians. They (the minor) will consent alongside the person giving proxy consent if they have ‘understanding’. In other words minors will provide consent to research but not independently as there is a dual consent process.

  • Given this framework, RECs can no longer approve a study if the researchers want :
  • Consent to be waived
  • Verbal consent to be obtained.

Independent consent is required from minors or children. In other words, written consent is required for all health research except record reviews by health care providers. If minors or children are being used in the study consent must be obtained from both the child and their parent or guardian.

In a clinical trial, or other forms of health research, biological material may need to be taken from the research participant for genetic research. The Regulations relating to the use of Human Biological Material provide that this may only be done if :

  • The person removing the biological material is competent, in other words they are a registered health professional
  • The research participant gives written consent to the withdrawal or removal of the biological material

In terms of section 71(3) of the National Health Act if non-therapeutic research is to be conducted with minors, consent for the study must also be obtained from the Minister of Health. At the time of writing this module (2013) how such consent would be obtained was unclear as regulations dealing with this issue have not been published.

Ethical principles on informed consent require it to be obtained before the research begins. Informed consent means that participants are aware and understand the possible risks and benefits without being influenced by coercion and undue incentives. Consent is obtained verbally and in writing unless the participant is unable to give consent, such as in special cases discussed previously.

It is the responsibility of the investigators to ensure that participants consent voluntarily to research and that refusal to participate will not have any negative consequences. Every attempt to ensure voluntary informed consent must be made. Participant consent should be based on information that is accurate and representative of the research to be conducted. The rationale for informed consent is to stimulate decision-making about participation in research. Decision-making by the participant should be assisted by the researcher who should encourage the participant to make a decision that is compatible with his/her belief systems, values and needs. Details about the number of participants, nature and assignment of participants into groups or treatments/procedures must be made explicit to all participants. Participants should also be informed of potential reasons that could lead to termination of participation.

Each context creates difficulties and requires attention. Many South Africans are particularly vulnerable due to socio-economic factors such as limited access to health care facilities and low literacy levels. Documents given to research participants need to be written in language that is clear, easily understood, simple and culturally appropriate to the participants. If participants are unable to understand the documents an appropriate participant engagement process must be initiated by the PI. The following guidelines are used to judge whether a participant is capable of consenting to research :

  • Has an understanding of what the research aims to do;
  • Has an understanding of the duration of their involvement in research;
  • Has an understanding of the procedures, treatments and medication involved in the research;
  • Has given consent to participate either verbally or in writing;

In some situations it is necessary for participants to be assisted to make an informed choice about their participation in research. This occurs by using culturally appropriate language, selecting an environment that participants feel comfortable in and having counselling facilitators available for questions, queries and discussion.

  • National Health Act 61 of 2003, s 7
  • Regulations Relating to the use of Human Biological Material, Government Gazette, No. 35099, Regulation 3
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.5
  • UNAIDS Joint United Nations Programme on HIV/AIDS, Good Participatory Practice : Guidelines for biomedical HIV prevention trials, 2011, section 3.9

Information that participants must be provided with includes :

  • Investigators' qualifications;
  • Participants' responsibilities during the research process;
  • An explanation of the potential risks or harms;
  • An explanation of the potential benefits to the participants and others during and after the research.
  • It must be emphasised that the participant is free to withdraw from the study at any time without any negative consequences;
  • Clear statements that participation is voluntary
  • Description of alternative treatments and medication available;
  • Explanation of how anonymity and confidentiality will be guaranteed;
  • Description of who will have access to patient records, files and results;
  • Statements verifying that ethics approval has been obtained by an authorised REC;
  • Contact details of the REC;
  • Explanation of how research-related injury will be managed with regard to treatment and whom to contact if injury occurs.
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.5

In some cases, there are risks that cannot be predicted beforehand but as soon as researchers become aware of any risks, they are obliged to disclose the nature and extent of such risks to RECs and participants. Participants must understand their rights to the information generated in the research and the consequences of withdrawing from the research.

Informed consent ensures that research is both ethical and legal. It should not be viewed as legal indemnification for the research team. Researchers have an obligation to protect participants which is not limited to these stipulations. Research staff and assistants should receive training about their ethical and legal responsibilities to participants before, during and after the research.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.5
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 12

2.2.6.1. Capacity

Capacity refers to the ability to make decisions about actions to be taken. An adult is a person over the age of 18. All adults are presumed in law to have the capacity to consent to research unless the contrary is proved. There are, however, legal conditions that need to be met when establishing a participant’s capacity to consent. Capable persons are individuals above the age of 18 years, who display mental and psychological stability and are judged as capable of making informed decisions about participating in research. When an individual below the age of 18 is requested to participate in research, permission must be obtained from a parent or legal guardian for all forms of health research. In terms of ethical guidelines there are special circumstances where individuals under the age of 18 can consent to health research without obtaining permission from their parents or legal guardians. However, these have been superseded by the introduction of section 71 of the National Health Act. There is a degree of inconsistency with South African law regarding the age at which capacity of consent is presumed to be obtained. Various laws stipulate different ages.

  • National Health Act, No. 61 of 2003, s 71
  • Children’s Act No. 38 of 2005, s 17
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 12.7

2.2.6.1.1. Adult

Capacity has legal and medical connotations. There is a difference between the legal and medical meaning. The legal connotation implies that an individual has or lacks capacity to engage in activity. In a medical sense, capacity refers to the clinical evaluation of a person’s ability to make decisions about his/her life. In a legal sense, someone considered incapable requires a third party to make judgements about the person’s best interests.

  • South African Law Commission, Assisted decision-making : Adults with impaired decision-making capacity, 2004, Discussion paper 105
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 12.7
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.1.1.Note 8

2.2.6.1.2. Capable adult

Capacity is defined as “someone’s ability to do something. In the legal context it refers to a person’s ability to perform a specific juristic act (a voluntary human act to which the law attaches at least some of the legal consequences willed by the party or parties performing the act – such as for instance entering into a contract granting a power of attorney, or making a will)” (South African Law Commission, 2004, p.45).

In legal terms, capacity ensures that all persons have the right to make decisions about their life. A capable or autonomous person is someone who is able to make their own decision about issues that affect them. Ethical research respects autonomous persons and allows them to deliberate about issues that concern them, unless their actions suggest otherwise.

  • South African Law Commission, Assisted decision-making : Adults with impaired decision-making capacity, 2004, Discussion paper 105
  • Belmont report, 1979, principle B1

2.2.6.1.3. Incapable adult

“Incapacity, or the inability to enter into a transaction, is either imposed by the law for policy reasons (usually since the individuals concerned need to be protected from their own inexperience and imprudence and from exploitation by others e.g. as in the case of children); or arises by reason of mental disorder” (South African Law Commission, 2004, p.45).

An adult is considered incapable or legally incompetent when they are unable to make decisions due to physical or mental impairments. In such cases, the PI is required to obtain consent from the person’s legal representative and fulfil all other rules according to the law.

  • South African Law Commission, Assisted decision-making : Adults with impaired decision-making capacity, 2004, Discussion paper 105
  • Declaration of Helsinki, 2000, principle 24

2.2.6.1.4. Legal representative

There is no South African law which provides that a child or a person lacking legal capacity must have a legal representative to protect their interests in research.

Legal minors, however, require the consent of their parents or legal guardians to participate in health research. Section 71 of the National Health Act mandates active written consent from a parent or legal guardian for all research conducted with subjects under the age of 18.

  • National Health Act, No. 61 of 2003, s 71
  • Zuch, M., Mason-Jones, A.J., Mathews, C. and Henley, L., (2012), ‘Changes to the law in consent in South Africa : implications for school-based adolescent sexual and reproductive health research’, BMC International Health and Human Rights 2012, 12 :3

2.2.6.1.5. Minor

A minor refers to a person who lacks legal capacity. Generally, this is a child under the age of 18. However, the term also includes adults who lack legal capacity because, for example, they are mentally disabled.

A child may become a legal major before the age of 18 if they marry (in terms of the civil or customary law). In such a case the child will remain a major even if the marriage ends due to death or divorce before the age of 18. A child may also become a legal major before the age of 18 if they are emancipated from their parent or guardian. Emancipation can occur if the minor is acting without the assistance of their parent or guardian in juristic acts, for example, they are running their own small business. In this rare situation the minor can apply to the High Court to be emancipated. If the emancipation is granted they will be regarded as a major or an adult in certain aspects of their lives before the age of 18. Becoming a parent before the age of 18 does not change a child’s legal status. If they are unmarried they remain a child until they are 18 and their child falls under the guardianship of its maternal grandmother. Note that same sex marriages are not legal if either or both parties are below the age of 18.

In South African law there are special obligations on research involving minors. These are different for therapeutic and non-therapeutic research.

Section 71(2) of the National Health Act provides that if the research is therapeutic in nature and it is to enrol minors then the following obligations exist :

  • The research must be in the best interests of the minor
  • Consent must be obtained from the minor’s parent or legal guardian
  • Consent must be obtained from the minor if they have understanding.

Section 71(3) of the National Health Act provides that if the research is non-therapeutic in nature and it is to enrol minors then the following obligations exist :

  • Consent must be obtained from the minor’s parent or legal guardian
  • Consent must be obtained from the minor if they have understanding
  • Consent must be obtained from the Minister of Health

At the time of writing this module (2013) it was unclear what process ought to be followed in obtaining consent from the Minister of Health as no regulations has been published with these details. Regular updates will be posted on this website to advise researchers should there be a change in this situation.
  • National Health Act, No. 61 of 2003, s 71
  • Children’s Act No. 38 of 2005, s 17
  • J Heaton The South African Law of Persons (3rd ed) (2008) Butterworths Lexisnexis, Durban, South Africa

Ethically, the inclusion of minors in research is only permissible when their participation is essential for the research and when the research is in their best interests. Participation in research must be beneficial to the child’s interests and well-being. A child’s decision to not participate in a study needs to be respected in all instances. Finally, the research protocol must be relevant to the situation/condition faced by the children being invited to participate in the study.

  • Children’s Act No. 38 of 2005, s 17
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.1

Even though children and minors always require parental or guardianship consent to participate in research, they may be able to consent independently to certain therapeutic or research elements of the study including :

  • Medical treatment if the child is over the age of 12 child has ‘sufficient maturity’
  • Condoms, contraceptives and contraceptive advice from the age of 12
  • HIV testing if the child is 12 years old or below the age of 12 if they have ‘sufficient maturity’
  • Male circumcision if the boy is 16 years or older
  • Termination of pregnancy, at any age
  • Removal of biological material for genetic health research, if they are over the age of 12 and have ‘sufficient maturity’.
  • Children’s Act, No. 38 of 2005, s 129,134,130, 12
  • Choice of Termination of Pregnancy Act, No. 92 of 1996, s 5
  • Regulations relating to the use of Human Biological Material, Government Gazette No. 3599, 2 March 2012, Regulation 3
  • Zuch, M., Mason-Jones, A.J., Mathews, C. and Henley, L., (2012), ‘Changes to the law in consent in South Africa : implications for school-based adolescent sexual and reproductive health research’, BMC International Health and Human Rights 2012, 12 :3

When children are included in research consent must be obtained from :

  • Parents/legal guardians. Although ethical guidelines allow consent to be waived for example, in emergency cases or where parental consent would adversely affect the child’s wellbeing the law requires proxy consent in all instances, see section above 2.2.6.1.1. In other legislation, such as the Children’s Act, care-givers of children, for example, grandparents may give proxy consent for a child to receive medical treatment. However the National Health Act does not recognise care-givers as being competent to give proxy consent for a child to participate in health research.
  • The Minister of Health, if is non-therapeutic research.

Assent is obtained from the child, as long as he/she is judged competent to participate in the research.

  • Children’s Act, No. 38 of 2005, s 129
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.1.1
  • Zuch, M., Mason-Jones, A.J., Mathews, C. and Henley, L., (2012), ‘Changes to the law in consent in South Africa : implications for school-based adolescent sexual and reproductive health research’, BMC International Health and Human Rights 2012, 12 :3

The REC must assess if the research can be carried out with adults. If it is found that the research can be carried out with adults, a specific justification will be required for the inclusion of minors in the study.

RECs should only approve research protocols involving children/minors when :

  • The child is exposed to no or minimal risk;
  • The risk of research is outweighed by the potential benefits (the risk must be justified by the benefits);
  • The risk of research is greater than minimal and there are no direct benefits but the research is likely to generate generalisable knowledge about the research problem (IRB, 1996 cited in NHREC, 2006).
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.1, note 8

2.2.6.1.6. Capable minor

Ethically, minors are considered capable when they display competence to make decisions about their situation. A minor may assent to research participation. However, parental or guardianship consent is required for all forms of research participation. If a minor refuses to participate in research, that decision must be respected irrespective of whether parents/legal guardians have provided consent for the minor to participate in the study.

Legally, a minor will be considered to ‘capable’ if they have married below the age of 18 of they have been emancipated. See section 2.2.6.1.5.

  • National Health Act, No. 61 of 2003, s 71
  • Children’s Act No. 38 of 2005, s 17
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004 section 5.1, note 8
  • Heaton, J. The South African Law of Persons (3rd ed) (2008) Butterworths Lexisnexis, Durban, South Africa

Child assent and parental consent

It is the responsibility of the REC to ensure that the correct steps are described in the protocol to obtain assent from the child when the child is judged competent to give assent. If and when assent is required for child participation the protocol must specify how assent will be documented.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.1.2

2.2.6.1.7. Incapable minor

All minors are regarded as being incapable of being able to consent independently to health research. Consent must be obtained from parents or legal guardians

  • National Health Act, No. 61 of 2003, s 71
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 5.1.1; note 8

2.2.6.2. Participants’ right to information

In order to give consent to participate in research, individuals have the right to know what the research entails and what the potential benefits and risks are of participating in the research. The National Health Act states that participants must be told of the ‘objects of the research or experimentation and any possible positive or negative consequences for her or his health’. Participants have the right to information that will affect their ability to make a decision and to information discovered during the research as it will enable them to decide if they wish to continue participating. Furthermore if the research is part of a health service participants must be told that the health service is experimental or part of a research study.

  • National Health Act, No. 61 of 2003, s 11, 71
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.5
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 3.1; section 12.6

2.2.6.2.1. Form of the information

The ethical principle respect for persons requires that appropriate and relevant information be given to all participants in plain language and in their own language, to ensure voluntary participation in the research. Participants must receive information about the study, such as risks, as part of the informed consent documents or as an information sheet. It is the PI’s responsibility to ensure that the participant reads and understands the information given. An interpreter may be present during discussions and informed consent. The interpreter should be independent of the research team and conversant in the language of the participant, if the research is minimal risk, a relative or friend may be present (See 2.2.6).

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 4.3; 4.4; 6.1.
  • Belmont report, 1979, B1
  • South African Medical Research Council, Book 1 : Guidelines on Ethics for Medical Research, 2003, 9.12.4.3.3.

2.2.6.2.2. Scope of the information

Information sharing is a bilateral process between the PI/researchers and participants.

Researchers should make an effort to learn more about the participant’s life circumstances, expectations and reasons for participating in the research. This will allow for potential misunderstandings to be discussed and resolved. Information should be transmitted through a medium that is appropriate and culturally sensitive. This will ensure that participants understand the aims, rationale, and length of participation, potential risks and benefits and consequences of their participation. Their rights as participants need to be clearly understood. Procedures should be adopted to access understanding, such as discussions based on case studies and checklists. Procedures can be developed by researchers and community members.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 12.5

2.2.6.3. Freedom of consent

Freedom of consent implies that participants have the right to decide for themselves whether they wish to participate in research having understood all the details explained to them.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes 2004, section 9.3

2.2.6.3.1. Compensation to participants

The payment of incentives during research requires careful deliberation. Incentives in research should not be so extreme as to unjustly compel individuals to participate in research. Compensation for transport and food should be fair and reasonable allowing the individuals to decide independently whether they wish to enrol in the study after weighing up the risks and benefits. Information about incentives must be explained in the study protocol and in the case of multinational studies the payment of incentives in all sites must be included in all protocols submitted for review. Differences in the amounts of incentives must be justified. All incentives and reimbursement to participants must be approved by the REC.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section, 9.4, section 9.5; section 10.1, point (iv)
  • Payment of trial participants in South Africa : Ethical considerations for Research Ethics Committees, (2012)
  • Mamotte, N., Wassenaar, D., & Singh, N. (2013). Compensation for research-related injury in NIH-sponsored HIV/AIDS clinical trials in Africa. JEHRHE, 8(1), 45-54

During the study, research participants should benefit from activities relating to the research. These include the following :

  • Participants should have access to and contact with health care facilities and psychological services;
  • Participants should receive information or training on how to protect themselves against further infection/disease;
  • Participants should have continual access to treatment and medication;
  • Participants should receive compensation for time, travel and any inconvenience relating to participation in research;
  • When participants incur any expenses as a result of their participation in research, they should be reimbursed for that expense. Payment for discomfort and inconvenience is justifiable.
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 10.1
  • Payment of trial participants in South Africa : Ethical considerations for Research Ethics Committees, (2012)

2.2.6.4. Form of consent

Consent must be given verbally and in writing. In some circumstances where participants are illiterate consent may be given and documented with a thumbprint in the presence of others. If the participant is unable to consent for various reasons, permission is obtained from persons legally responsible for the participant witnessed consent may also be approved by an REC in special circumstances.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 12.9.2
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 2.5

2.2.7. Risk to benefit ratio

The risk to benefit ratio should be assessed by the investigator and the REC prior to the commencement of the research. The risk-benefit analysis should provide comprehensive information about the possible risks and benefits during and after the research, especially if the condition under investigation is enduring and severe. Individuals who are likely to be at greater risk should be excluded from the study. The researcher is expected to evaluate alternative ways of providing benefits to participants.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.5, section 2.8

2.2.7.1. Risks of the research

Risks refer to any injuries and harm that might occur during research participation. Risks can be psychosocial, physical, legal, social and financial. Researchers are obliged to minimise risks in research and inform participants of risks involved in participating in the research.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.5; section 2.8, section 6.1
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 9.2

2.2.7.1.1. Harm

Harm is defined as an adverse event (AE) that affects the wellbeing of an individual or a group. Harm can be experienced physically, psychologically or financially. Potential adverse reactions resulting from any current treatment as well as injuries related to the research must be explained in the protocol and discussed with prospective participants during the informed consent process. The protocol must specify what medical treatment will be provided if injury occurs as well as whether compensation is payable for harm that results from research-related activity and what guidelines will be utilised to ascertain if compensation is payable. Participants must be fully aware of the potential level of harm related to research participation in order to make an informed decision about their participation in the study. All misconceptions and misunderstandings must be clarified to ensure the participants understand what the research entails and are not mistaken about how they will benefit from the research.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.8
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 9

2.2.7.1.2. Nature of harm

The Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa (2006) state that participants may have a claim for compensation if it can be shown that :

  • A trial product or procedure was administered that caused serious bodily injury
  • The bodily injury was serious and of an enduring character
  • The injury would not have occurred but for participation in the trial.

In other words in a clinical trial compensation may only be claimed for physical harms that are enduring in nature.

  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 4.11

2.2.7.1.3. Extent of harm

Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa (2006) provide that participants will only have a claim for compensation if they suffer bodily injury that was serious and of an enduring character. Compensation will not be paid for psychological harms, or harms that are not serious or not enduring.

  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 4.11

2.2.7.1.4. Measures to minimise risks

Risks in research should be reduced to a minimum. The protocol and informed consent document must explain all the risks in the study and what measures have been taken to minimise them.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.8

Risk minimisation measures include :

  • Counselling participants about what the study is about and clarifying any misunderstandings about what the study findings can and cannot do;
  • Continually assessing the risks of research participation;
  • Providing supportive counselling during and after the trial;
  • Developing strategies to counteract stigma and discrimination;
  • Ensuring participants have access to support services once the trial is over;
  • Ensuring the research location enables maintenance of participant confidentiality;
  • Contracting third parties to represent the interests of participants when the need arises, i.e. an ombudsman;
  • Non-therapeutic research – healthy participants should only be exposed to minimal risk even if there is considerable benefit to other individuals and communities;
  • RECs should assess whether the level of risk is justifiable and whether the benefits outweigh the risks;
  • Consultation with community representatives to discuss risks and benefits is necessary before research begins.
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section, 9.7

2.2.7.1.5. Monitoring

An ethical requirement of research is to ensure that the safety of participants is monitored. This requires prevention strategies, on-going monitoring, punctual reporting and efficient management of adverse events (AEs), including post-study events. The protocol must specify how AEs and serious adverse events (SAEs) will be reported and managed. All South African RECs must have a policy on how and when PIs will report AEs and SAEs to the REC.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.12; section 4.7; Appendix D

2.2.7.1.6. Quality assurance

Quality assurance is "all those actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with these guidelines … and the applicable regulatory requirements" (Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, p.33). Quality assurance is attained through monitoring, auditing and thorough inspection.

The research sponsor is responsible for quality assurance. Particularly, sponsors are responsible for quality control systems with standard operating procedures (SoPs). SoPs specify how research should be conducted; data is collected, recorded and reported, so that it meets the necessary requirements of the protocol, Good Clinical Practice (GCP) guidelines and other regulatory guidelines. The sponsor must ensure that trial sites, research documents and results are easily accessible for monitoring and auditing purposes. The process of quality control can occur at any stage of data collection and analysis to assess the reliability and security of the data and whether it has been processed accordingly. Any agreement relevant to the research must be formal and in writing as part of the protocol or separately.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.10, section 4.3, section 7.10
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 3.6

2.2.7.1.7. Appropriate resources

  • Appropriate resources are needed to conduct safe and effective research. To ensure the availability of appropriate and adequate resources the principal investigator must be able to show the following :
  • Appropriate participants can be selected according to the planned recruitment period;
  • An adequate amount of time is allocated for data collection;
  • Suitable and experienced research staff are employed and appropriate research equipment and supplies are available;
  • All research staff trained and have comprehensive knowledge about the research process, treatments and their roles and responsibilities;
  • All research budgets should be adequate for the planned scope and duration of work.
  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 3.3

2.2.7.1.8. Competent personnel

Competent personnel are needed for research as they interact with participants, collect data, analyse data and report findings. Personnel selected for research should have good interpersonal skills as they interact with the participants in the study. Personnel are required to have appropriate scientific and ethics training and expertise as they counsel participants to ensure they understand the research procedures and make informed decisions about participating in the research. Personnel are the communication link between participants and the principal investigator/researcher and are able to inform investigators of changes and/or improvements that need to be made and in so doing assist in managing queries, questions and concerns.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 4.5

2.2.7.2. Benefits of participants including control groups research

A risk-benefit analysis precedes the commencement of the research. The analysis will consider both the risks and benefits during and after the research. Ideally, the research should provide benefits to the participants and this should continue after the research has been conducted. Individuals at high-risk of exploitation should not be included in the study. The benefits of the research should be directed to those who participated in the research and the community they belong to. Furthermore, the findings of the study should be made available to the community and participants in an appropriate form.

  • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, 1.2.4; footnote 22
  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 10

2.2.7.2.1. Direct benefits

The clinical trial must maximise benefit to the individuals participating. Researchers should be aware of the following :

  • A communication link must always be open between participants and researchers to ensure that participants are able to receive support during the research;
  • In health research, researchers should provide assistance and impart knowledge that can be useful in managing the health problem under investigation and maximise benefits for the individuals;
  • Ensure that participants have access to health facilities as required;
  • In health research, if the intervention, treatment or medication under investigation is found to be effective, participants must have post-trial access to the intervention, treatment or medication if indicated.
  • Expected benefits need to be discussed with community representatives if participants are recruited from communities. These benefits must be explained during the informed consent process but the presentation of these benefits must not influence decisions to participate.
  • Study results must be made available to the participants in appropriate formats using appropriate processes.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 10
  • UNAIDS Joint United Nations Programme on HIV/AIDS, Good Participatory Practice : Guidelines for biomedical HIV prevention trials, 2011, section, 2.6; 3.5D

2.2.7.2.2. Indirect benefits

Results from research must be presented appropriately to participants and their communities. The community should benefit from the research process and findings, including through capacity building initiatives, training opportunities, access to effective treatments/medication.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 10

2.2.7.2.3. Minimal risks

Minimal risks refer to the likelihood and level of harm/discomfort that can be experienced in the research which should be similar to the level of harm/discomfort experienced in everyday life. Minimal risk also refers to a slight chance of serious injury and/or harm.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 9.8
  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, Appendix E

2.2.7.2.4. Upper threshold of risk

The South African guidance is silent on the upper threshold of risk. However, the benefits of the research should outweigh risks to communities and individuals who are at risk of exploitation. Benefits should always outweigh known and foreseeable risks. When decisions are made about the choice of intervention, the use of placebo may require consideration of several factors, but the well-being of participants should be considered first. The REC should review the ethical and scientific justification for the control arm and assess whether it poses any risk in relation to benefits. The scientific design of the study should yield valid and reliable results.

The potential benefits of research should outweigh potential risks or harms to vulnerable individuals and communities.

  • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004
  • South African Medical Research Council, Book 1 : Guidelines on Ethics for Medical Research, 2003, 2.13; 2.15.

2.2.8. Conflicts of interest

Researchers are required to disclose to participants and RECs who the sponsors are and the amount of funding. Researchers must disclose conflicts of interest with other associates, participants and sponsors when findings are reported, when research protocols are devised and when protocols undergo ethics review. All current, potential and apparent conflicts of interest must be disclosed.

Sponsors must develop policies to deal with conflicts of interest. All research staff must be aware of the policies and disclose any conflicts of interest prior to the research. If there are limited resources available to conduct the research, the sponsor is required to develop necessary facilities and resources before the research begins.

In preventative trials conflicts of interest may arise between risk-reduction and meeting scientific goals. Researchers have an ethical obligation to ensure that the generation and production of knowledge is secondary to protecting the wellbeing of participants. A possible solution is to co-opt a monitor to evaluate the consent process and develop strategies to reduce risks, simultaneously ensuring that the anonymity and confidentiality of participants are protected.

REC members are required to disclose any conflicts of interest when their own protocols are reviewed and may not use their position to influence the decision made by the committee. The REC will assess whether the conflicts of interest can jeopardise the scientific reliability of the study.

  • South African Medical Research Council, Book 5 : HIV Preventive Research, 2003, section 15.5

2.2.9. Protection of privacy and confidentiality

The South African Constitution states that “everyone has the right to privacy, which includes the right not to have-

  • their person or home searched;
  • their property searched;
  • their possessions seized; or
  • the privacy of their communications infringed”
  • Both the privacy and confidentiality of research participants must be protected at all times. Privacy refers to limiting the access of patient records while confidentiality is defined as utilising participants' information anonymously once they have disclosed information to the researcher (Bergulund, 1990 cited in NHREC, 2004).

    • Constitution of the Republic of South Africa, 1996, chapter 2, s14
    • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.7
    • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa 2006, section 1.2.6
    • South African Law reform commission : Privacy and date protection, 2005, discussion paper, introduction

    2.2.9.1. Privacy

    Everyone has a constitutional right to privacy. This is the right to be apart from company or observation by others. This includes the right a person has to ensure privacy of their personal communications. In other words it protects confidential disclosures made to researchers or information obtained by researchers from being disclosed or distributed without express consent.

    • Constitution of the Republic of South Africa, 1996, chapter 2, s 14

    When personally identifiable information is collected from research participants or communities, it must be collected in a manner that respects their privacy and confidentiality. Any agreements or arrangements made with communities and participants must be honoured and remain private. Procedures for protecting research participants and communities must be outlined and discussed in the protocol and informed consent, such as the use of electronic records and limited access of staff to records. Guidelines must be formulated to deal with failure to protect the confidentiality and privacy of research participants.

    • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006 , section 2.7

    2.2.9.2. Professional secrecy

    The term professional secrecy is not used in South Africa but is referred to as confidentiality. Health care providers are under an ethical-legal obligation to keep all information that arises in the doctor-patient relationship confidential. This principle also applies within the context of a researcher-research participant relationship.

    All participants’ confidentiality must be protected. All personal and identifiable information collected must be collected, stored and destroyed in a manner that protects the participants and their communities. With epidemiological research, personal details of individuals are used and the protocol must specify how data will be protected i.e. de-identifying personal details from the participant. The REC must be satisfied that the research complies with the law and relevant legislation, only relevant people should have access to the information/documents/human materials and there should be a scientifically and legally justified process for the disclosure of information and dissemination of research results.

    • Jansen van Vuuren v Kruger 1993 (4) SA 842 (A).
    • Guidelines for Good Practice in the Conduct of Clinical trials with Human Participants in South Africa, 2006, Glossary
    • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 2.7 ; 7.2 ; 7.4 ; 8.2 ; 8.6, definition
    • International Conference on Harmonisation - Guideline for Good Clinical Practice, 1996, point 2.11.

    2.2.9.3. Data protection

    Upon completion of the study the PI and sponsors are required to keep the data collected for safety reasons, auditing and inspection. Data is kept according to the time frames set out in the South African Constitution and must satisfy the requirements of privacy legislation. All documents pertaining to the study must be kept in a safe, secure place.

    • Constitution of the Republic of South Africa, 1996, Chapter 2
    • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 6.5

    2.2.9.4. Rights of access to data

    In South Africa a participant may seek access to their clinical trial records under the provisions of the SA Promotion of Access to Information Act (Act 2 of 2000) which stipulates that all persons have “ the constitutional right of access to any information held by the State and any information that is held by another person and that is required for the exercise or protection of any rights; and to provide for matters connected therewith” (Promotion of Access to Information Act (Act 2 of 2000), p.2).

    • Promotion of Access to Information Act, 2 of 2000, introduction
    • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 1.2.5

    2.2.10. Ongoing respect for research participants

    Research participants must be respected throughout the research process. Participants' wellbeing and rights must be protected before the research begins and after it has ended. Respect for research participants entails valuing and recognising their cultural beliefs, language, individual opinions and traditions and their privacy and confidentiality.

    • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa (2006) 2004, section 5.8

    2.2.10.1. During the research

    Every effort must be made to protect the research participant’s needs and wishes. The study must not compromise the participant’s mental and physical wellbeing during the study.

    The autonomy of participants must be respected and strategies for ensuring autonomy are essential. This may involve discussing the research with community representatives and ensuring participants understand that they are free to withdraw from the study without having to give a reason.

    • Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa, 2006, section 5.15

    Adverse events

    It is the responsibility of RECs to check if protocols have appropriate processes in place for reporting AEs and SAEs. During pre-clinical trials, the safety of products is assessed. It is important that all adverse events are reported. It is the ethical duty of all researchers and health care professionals involved in a study to refer all adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) to relevant authorities (REC, MCC and sponsors).

    Once researchers have established AEs, SAEs and SUSARs it is the duty to inform potential participants of these. Should AEs, SAEs or SUSARs occur, the PI is expected to collect relevant information regarding them and inform the study sponsor and the REC. PIs are required to make provision for dealing with any AEs, SAEs and SUSARs that might occur.

    • Guidelines on Ethics in Health Research : Principles, Structures and Processes, 2004, section 6.1

    2.2.10.2. After the research

    Research findings should be reported to participants, communities and populations under investigation in a manner that is appropriate to each specific audience and outlined in the research protocol. The monitor is required to ensure the following :

    • Documents are transferred for safekeeping;
    • All relevant parties are informed that the study has ended;
    • The relevant standard operating procedures have been followed for supplies that were not used;
    • Records are kept of personnel who were involved with the investigational product/treatment.
    • Guidelines for Good practice in the conduct of clinical trials with human participants in South Africa, 2006, section 5.1.6