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findings, controversy arose. A major concern was the use of deception and invasion of privacy (Lenza, 2004).
The current section has described some examples of controversial and unethical research involving humans that led to the development of modern day research ethics. While most of these scandals were in biomedical research, the literature review has also shown that there were also examples of unethical social science and behavioural research involving humans that caused ethical controversy (see 2.1.6 and 2.1.7). The next section describes some of the key
international codes, declarations and guidelines that were developed as a result of the unethical research scandals described above.
2.2 Key international research ethics codes and guidelines
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1. “The voluntary consent of the human subject is absolutely essential.
2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
3. The experiment should be so designed and based on the results of animal
experimentation and knowledge of the natural history of the disease or other problem under study, that the anticipated results will justify the performance of the
experiment.
4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
5. No experiment should be conducted, where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.
6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death 8. The experiment should be conducted only by scientifically qualified persons. The
highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.
9. During the course of the experiment, the human subject should be at liberty to bring the experiment to an end, if he has reached the physical or mental state, where continuation of the experiment seemed to him to be impossible.
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10. During the course of the experiment, the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgement required of him, that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject” (Nuremberg Code, 1947, pp. 181-182).
Although the Nuremberg Code was published in 1947, there were other ongoing and later scandals and unethical medical research involving human beings carried out at leading research institutions and hospitals in the US (Beecher, 1966). The Nuremberg Code did not have a great impact on the way in which clinical research was being carried out in other countries as it was seen as only being of direct application to the physicians that were on trial. According to Faden, Lederer and Moreno (1996), some researchers were against the Nuremberg Code for three main reasons namely 1) discrepancies between what investigators had come to know in real practice in research with patient-subjects and what they read in the lofty, idealized language of the
Nuremberg Code, 2) others simply were not in agreement with some elements of the Code and 3) others decried the notion of a “one-size-fits-all” standard to guide research in such a complex landscape of human experimentation.
Therefore, after it was established, the Nuremberg Code had little effect in curbing unethical research practices in other developed countries such as the US (Faden et al., 1996). This was evident from the fact that despite the publication of the Nuremberg Code in 1947, many
instances of unethical research conducted on vulnerable persons in other countries continued or
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were initiated, often without their knowledge and voluntary informed consent (Beecher, 1966), which subsequently led to the creation of a number of key international ethical guidelines which are discussed in the next section. The Nuremberg Code enshrined voluntary informed consent above anything else. This later proved to be an unworkable impediment to research on certain populations (e.g. unconscious patients, psychotic patients and children). Emanuel et al. (2003) importantly point out that most codes were drafted driven by a scandal, causing them to be flawed in some way to prevent that particular scandal from recurring.
2.2.2 Declaration of Helsinki (1964)
The World Medical Association (WMA) published the Declaration of Helsinki in 1964, outlining ethical principles for medical research involving human subjects, including research on
identifiable human material and data. This declaration, with very similar guidance to the Nuremberg Code, mainly focused on medical research intended for therapeutic purposes.
Although the Declaration of Helsinki (1964) had many similarities to the Nuremberg Code (1947), the feature that distinguished it from the previously promulgated Nuremberg code, was the need for independent ethical review by RECs. Key issues addressed in the Declaration of Helsinki included:
• Research with humans should be based on laboratory and animal experimentation
• Research protocols should be reviewed by an independent committee
• Informed consent is necessary
• Research should be conducted by medically/scientifically qualified individuals
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• Risks should not exceed benefits
Since 1964, the Declaration of Helsinki has gone through several revisions (1975, 1983, 1989, 1996, 2000, 2008) and most recently in 2013 during the 64th WMA General Assembly in Brazil (WMA, 2013). Briefly, the Declaration of Helsinki (2013) provides guidance on the following ethical issues: risks, burdens and benefits; vulnerable groups and populations; scientific
requirements, research ethics committees; privacy and confidentiality; informed consent; use of placebo, post-trial access; public and dissemination of results; and unproven interventions in clinical practice (WMA, 2013).
2.2.3 US National Research Act (1974)
When the Tuskegee Syphilis study, which began in 1932 (described in section 2.1.1) was publicised and there was public outcry in 1972, the US Congress passed the National Research Act in 1974 (Emanuel et al., 2003). Subsequently, the National Research Act established the National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research to identify the basic ethical principles that should underpin the conduct of biomedical and behavioural research involving human participants and to develop guidelines governing studies involving human participants to ensure the protection of human research participants. To that end, the US National Commission developed the Belmont Report (1979) (see next section), a foundational document guiding the ethics of human participants research in the United States.
The National Research Act required prior IRB approval of biomedical and behavioural research (Williams, 2005).
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2.2.4 The Belmont Report (1979)
The Belmont Report is a statement of basic ethical principles and guidelines that provide an analytical framework to guide the resolution of the ethical problems arising from research with human subjects (Belmont Report, 1979). It was developed in 1979 by the US government appointed National Commission for the Protection of Human Subjects in Biomedical and Behavioural Research. The three basic ethical principles (respect for persons, beneficence and justice) and their applications are summarized in Table 1 below:
Table 1: Belmont Report (1979) basic ethical principles and their application
Principle Application
Respect for persons Informed consent
• Persons should be treated as autonomous individuals
• There should be protection for persons with diminished autonomy.
• Participants must freely choose whether or not to participate in research
• The essential elements of the consent process are:
• Information disclosure,
• Understanding, and
• Voluntariness.
Beneficence Assessment of risks and benefits
• There should be no harm to human participants
• Proposed research should ensure that possible benefits are
maximized possible harms minimized.
• There should be systematic
assessment of risks and benefits to ensure favourable risk/benefit ratio
Justice Selection of participants
• There should be fair distribution of research benefits and risks.
• Selection of participants must be unbiased such that there is fair distribution of research benefits and risks
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2.2.5 US Code of Federal Regulations “Common Rule”
In 1981, the Department of Health and Human Services (DHHS) and the Food and Drug
Administration (FDA) issued their regulations based on the Belmont Report. DHHS issued Code of Federal Regulations (CFR) Title 45 (public welfare), Part 46 (protection of human subjects).
The US Federal Policy for the Protection of Human Subjects, also known as the “Common Rule”
was published in 1991 (DHHS,1991; Williams, 2005). The regulations, 45 CFR part 46, (45 CFR 46) consists of four subparts: subpart A, basic HHS policy for protection of human research subjects; subpart B, additional protections for pregnant women, human foetuses, and neonates;
subpart C, additional protections for prisoners; subpart D, additional protections for children and subpart E, registration of IRBs (45 CFR 46). The Common Rule led to the proliferation of IRBs to provide independent review of research involving human participants and requirements for obtaining and documenting informed consent (Emanuel et al., 2003).
The current section has highlighted the key international ethics codes and guidelines that were developed as a result of research scandals such as the Tuskegee Syphilis study (see 2.1.1) and Nazi medical war crimes (see 2.1.2). In conclusion, the Nuremberg Code (1947), Belmont Report (1979), Declaration of Helsinki (1964) and Common Rule (1981) formed the foundation for modern day research ethics guidelines. Today, several international and national ethical guidelines have been developed. Examples of other international ethical guidelines include the CIOMS (1993) guidelines and later revised in 2002 (and currently under revision), the
International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines (1996), Nuffield Council on Bioethics (2002) guidelines on the ethics of research related to
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healthcare in developing countries and WHO (2011) standards and operational guidance for ethics review of health-related research with human participants.
Having described the development of research ethics from an international perspective, the focus of the next section is to highlight the history and development of the South African research ethics system. This is important considering that the current thesis was aimed at analysing ethical issues raised by two South African biomedical RECs.