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|Date:||Monday, 11 December 2023, 1:57 PM|
Table of contents
- 1. Introduction
- 2. The Evolution of Research Ethics
- 3. Nuremberg Code
- 4. The Emergence of Rules Specific to Research
- 5. The First Requirement for Independent Review
- 6. The Development of International Guidelines
- 7. Questionable Research Practices
- 8. The Emergence of Formal Requirements for Ethics Evaluation
- 9. Publication of the Belmont Report
- 10. Why Research Gets Evaluated
(This section is organised in the form of a book, please follow the blue arrows to navigate through the book or by following the navigation panel on the right side of the page.)
Medicine, like other health and social sciences, is not an exact science. For example, ‘established treatments’ might not be suitable for some patients, might not work well for others and some patients simply cannot access them.
This means that research is important, because:
- Established treatments need to be monitored and evaluated to find out when they are effective, i.e. when they work well.
- We are always looking for new treatments.
- medicine is ‘experimental’, i.e. we learn as we go by using new ideas and techniques.
- New diseases and conditions emerge and we need to find out how to treat them.
- Financial investment - more money is put into health research.
- Diversity - more and more areas are considered and studied, including:
- the factors that might affect health in defined populations (epidemiology),
- genes (genetics),
- humans and social behaviour (anthropology and sociology),
- the factors that might affect access to health care (health systems research).
Research ethics aims to promote high standards of behaviour in the conduct of research involving humans. It does this through an awareness of relevant values, principles and rules.
2. The Evolution of Research Ethics
Research involving humans has been part of medicine for centuries. In the nineteenth century, the adoption of the experimental method in both science and medicine generated significant progress in research involving humans. However, when animal experimentation became current practice, some scientists, mainly physicians, began to question whether research on humans was needed. Various ethical debates arose within the scientific community regarding the appropriateness of such research.
By the beginning of the twentieth century, the idea of conducting research involving humans was becoming more acceptable as long as extensive studies were first conducted on animals. With the development of bacteriology (the study of bacteria) and the rise of pharmaceutical companies, the number of animals and humans used in research increased significantly.
Research in bacteriology at the end of the nineteenth century and the beginning of the twentieth century involved some ethically unacceptable practices. For example, infectious agents were injected in orphans, mentally disabled persons and prisoners without their consent or knowledge. Various other experiments were reported involving use of electric shocks on vulnerable individuals.
There had been some attempt to regulate human experimentation. For example:
- The Prussian Minister of Religious, Educational and Medical Affairs circulated a guideline on human experimentation in 1900.
- The German Reich Ministry of the Interior issued regulations on new therapy and human experimentation in 1931.
3. Nuremberg Code
The Nuremberg trials in 1946 brought the issue of inhuman treatment of some individuals included in 'research' to the attention of the public. In one of the subsequent trials, twenty-three Nazi doctors and administrators were held responsible for the deaths of thousands of concentration camp prisoners who died during and after horrific experiments. The judges' verdict in 1947 included a section entitled 'Permissible Medical Experiments' which described ten principles to be followed in conducting research on humans. Known today as the 'Code of Nuremberg', it states as its first principle that 'the voluntary consent of the human participant is absolutely essential'.
Please take a few minutes to read the Nuremberg Code, Available at:Ethical Codes & Research Standards | HHS.gov
4. The Emergence of Rules Specific to ResearchMore revelations about the inappropriate treatment of humans in research followed the Nuremberg trials and Code. This continued to raise the importance of research ethics and the need for some form of public oversight of research involving humans.
5. The First Requirement for Independent Review
In 1953, the United States (US) established a federal funding requirement for institutional review by an independent committee of proposed research projects involving humans. This rule was limited to research conducted directly within the facilities of the National Institutes of Health (NIH) at Bethesda, Maryland, USA.
Yet, the lay membership on these committees showed that biomedical research is an activity of public interest and the public has important views to share on its ethical aspects.
6. The Development of International Guidelines
The World Medical Association (WMA) published its first version of the Declaration of Helsinki in 1964, which has been revised several times since (last revision 2013). The first revision of the declaration in 1975 stated that protocols for clinical research should be sent to a ‘specially appointed committee for consideration, comment and guidance’.
This was the first international statement on the concept of review of research where the review is independent from the researcher, the sponsor or any other influence. However, under the Declaration of Helsinki, the ultimate duty to ensure the protection of human participants remains with doctors.
7. Questionable Research Practices
During the latter half of the twentieth century, questionable research practices were reported in many different parts of the world. Some events were especially significant since they prompted regulatory activity and increased public scrutiny.
In 1966, Henry Beecher, an American doctor and researcher, described 22 cases of American researchers conducting ethically dubious research involving humans. He concluded that ‘it must be apparent that [participants] would not have been available if they had been truly aware of the uses that were made of them’ [Henry Beecher, Ethics and Clinical Research, 1966]. This was followed by other revelations of misconduct, most notably:
The Willowbrook case - the hepatitis virus was given to institutionalised mentally retarded children in an attempt to understand the natural history of the disease and to test the effect of a protein called ‘gamma globulin’ [US, Advisory Committee on Human Radiation Experiments, Report Chapter 3].
8. The Emergence of Formal Requirements for Ethics EvaluationSome events in research ethics are historically significant because they prompted concrete actions. In the Tuskegee syphilis study [US, Advisory Committee on Human Radiation Experiments, Report Chapter 3], researchers observed the effects of untreated syphilis in black men. Started in 1932, it was not until 1972 that revelations about the conduct of the study exposed the need for clearer guidance. A flurry of regulatory activity followed and a US federal statute (National Research Act, 1974) was adopted. This is still in force today. It formally requires research institutions to establish independent, local, multidisciplinary institutional review boards (IRBs). The purpose is to protect human research participants. These institutional review boards in the US have the same role as research ethics committees (RECs), as they are called in the EU and many other countries.
9. Publication of the Belmont Report
During the 1970s, a presidential commission was established in the US. Its aims were to identify ethical principles to guide research on humans and to develop guidelines for researchers and institutions. Its 1979 report, commonly called the Belmont Report, identified three basic principles of research involving humans:
- Respect for persons - this requires respecting people’s autonomy (capacity to make informed, independent decisions) and protecting people with diminished autonomy (people who are less able to make informed, independent decisions on their own).
- Beneficence - ‘doing good’, where the welfare of the research participant should be the goal of any clinical trial. In order to maintain this, harms should be minimised and benefits should be maximised.
- Justice - Who ought to receive the benefits of research and bear its burdens? This is a question of justice, in the sense of ‘fairness in distribution’ or ‘what is deserved’. An injustice occurs when some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly. These three principles form the fundamental requirements for ethically acceptable research.
In the past few decades, a number of countries have developed legislation that regulates research involving humans. In many countries, clinical trials with investigational medicines or other products are tightly regulated through specific legislation.
The increase in rules and guidelines internationally has resulted in varying requirements that researchers and sponsors must meet. The International Conference on Harmonisation (ICH) was initiated (April 1990) to develop a process to harmonise requirements, Within the clinical trial field the work aimed specifically for international multi-centre clinical trials (i.e. trials held at more than one centre or clinic). This resulted in the Good Clinical Practice (GCP) guideline. The GCP guideline aims to:
- Avoid the duplication of studies by making data generated in trials in one country admissible in other countries,
- Speed up the medicines development process.
10. Why Research Gets Evaluated
There have been a number of examples of ethically questionable research. In some rare cases, significant violations resulted in criminal sanctions. These latter cases aside, many of the former unethical situations were rooted in the ‘dual-role’ of doctors who were also researchers.
In addition, it is generally accepted that participation in research may expose individuals to harm that they would not otherwise experience. This is one of the reasons why research involving humans requires review and approval by an independent REC according to accepted standards. This review serves to assess the ethical acceptability of research studies and helps researchers improve the quality of their projects.
The doctor’s role [that can be extended to other healthcare providers] in the doctor-patient relationship is different from the researcher’s role in the researcher-participant relationship, even if the doctor and the researcher are the same person. The doctor’s primary responsibility is the health and well-being of the patient, whereas the researcher’s primary responsibility is the generation of knowledge, which may or may not contribute to the research participant’s health and well-being. Thus, there is a potential for conflict between the two roles. When this occurs, the doctor role must take precedence over the researcher.
Medical research is a well-funded enterprise, and study centres are sometimes offered considerable rewards for participating. These can include cash payments per research participant enrolled, equipment such as computers to transmit the research data, invitations to conferences to discuss the research findings, and co-authorship of publications on the results of the research.
This dual-role is relevant to all healthcare providers who have a relationship of trust with patients and who also conduct research. The potential conflicts between the two roles are minimised by the development and implementation of appropriate legislation and guidelines.
In the context of international collaborative research, there are often inequalities in resources between developed countries, which often sponsor research, and developing countries that host the research. This raises important ethical concerns, including the potential for exploitation. Given the need for research in developing countries, awareness of the risk of exploitation reinforces the need for robust evaluation of research by RECs.