1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonable to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment.
The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.
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 a 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.
Box 4.9 (continued)
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 seems to him to be impossible.
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 judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject. From Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol. 2, pp. 181–182. Washington DC: U.S. Government Printing Office, 1949.
Beneficience – do good;
Non-maleficence – do no harm; in practice this has to be balanced against the
principle of beneficience – the potential benefits should outweigh the possible risks;
Respect for autonomy – respect the rights of the individual; this includes the
right to privacy and the right to make informed decisions and thus the need for study participants to give their ‘informed consent’ before enrolling in a study;
Justice – equity, impartiality and fairness.
These principles were first codified in a practical form after the Nuremburg trials of German medical researchers at the end of World War II. The result- ing ‘Nuremburg Code’, which underpins all subsequent codes of health research ethics, is shown in Box 4.9. However, this Code was largely ignored at the time and formal statements outlining requirements for the ethical conduct of research did not start to appear until the late 1970s after continuing reports of disquieting ethical practices such as the Tuskagee Study (see Box 4.8) and the Willowbrook Study (1963–1966) where children in an institution for the mentally handicapped were deliberately infected with hepatitis virus to study the course of the infection (http://iris.uwaterloo.ca/ethics/human/resources/index.htm).
Tensions continue today between the need to protect the rights of individu- als (often via strict privacy laws) and the public need for good quality informa- tion to improve health. Rigid application of privacy laws can make some forms of epidemiological research almost impossible. As discussed above, this is espe- cially true for record linkage studies where it may be impractical or even impos- sible to obtain consent from individuals to access their information. The costs of complying with human research guidelines can also drive up the costs of research, with studies often needing to obtain approval from, and report back to,
Questions 121
multiple different ethics committees. However, as the historical examples cited above emphasise, we cannot ignore the need for real autonomy in relation to participation in research.
If you are interested in learning more about research ethics the US National Institute of Health (NIH) Office of Extramural Research has developed a free on-line tutorial (http://phrp.nihtraining.com/users/login.php). Although it is designed primarily for NIH grant holders who are subject to US Department of Health and Human Services regulations, the majority of the content is generic and applicable to all.
Summary
Experimental studies like those described above are theoretically the ideal way to look for associations between exposure and disease or health outcome. They do, however, have to be designed, run and reported rigorously to realise this poten- tial in terms of providing convincing evidence concerning causality. Unfortu- nately, they are often inappropriate (for ethical reasons), not feasible or unaf- fordable. Furthermore, since they are often conducted in highly selected groups of volunteers, it can be challenging to generalise their findings and we will come back to this problem in Chapter 11. The non-experimental study designs, par- ticularly cohort and case–control studies, are therefore of central importance in public health and, as you will see when we discuss causality in Chapter 10, other designs such as ecological studies can also provide valuable information. The fundamental importance of descriptive studies in monitoring the health of a population and for identifying emerging health problems should already be apparent, and you will see further examples of their essential role in evaluating the effects of population interventions when we discuss prevention in Chapter 14 and screening in Chapter 15. Each design thus has an important role to play and, as you have seen, different designs will be more or less appropriate in dif- ferent situations. It is also essential to recognise the strengths and limitations of each; we will consider these further in Chapter 7 when we look at some of the sources of bias in epidemiological studies.
Questions
1. Complete Table 4.1 to show the relative strengths and limitations of the main study designs, scoring each one on a scale from 1= poor (e.g. not good to investigate a rare disease or very expensive) to 5= excellent (e.g. very good to investigate rare exposure or very quick to do).
2. Look back to Box 4.9 and identify which of the four fundamental moral prin- ciples apply to each of the 10 statements in the Nuremburg Code.
Table 4.1 Comparing the strengths and weaknesses of different study designs.
Ecological Cross-sectional Case–control Cohort
Randomised controlled trial
Nested case–control Investigation of rare disease or
outcome
Investigation of a rare exposure Testing multiple effects of an
exposure
Study of multiple exposures Establishing temporalitya
Give a direct measure of incidence
Explore exposures which change over time
Time required Costs
Ethical problems
ai.e. that the exposure came before the outcome.
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