A short history of modern health research ethics

The 1964 Declaration of Helsinki by the World Medical Association was a seminal global event in the development of research ethics principles and processes. The Declaration was an elaboration and development of the 1947 Nuremberg Code (World Medical Association 2008). The Code was a response from the judges at the Nuremberg War Crime Trials to the cruel and harmful research projects that had been undertaken in World War II. It specifies basic principles that should govern the conduct of medical research. Most contemporary research ethics codes across the world draw heavily from the Helsinki Declaration and the underpinning Nuremberg Code.

The Declaration has been elaborated a further eight times by the World Medical Association at various meetings since 1964, with the most recent changes being in 2008. The amendments have related to drafting improvements and changes in technology and knowledge. In particular the responsibilities relating to publication and dissemination of research have now been specified.

Although the Declaration is now quite lengthy, it is worthwhile to reproduce the basic principles within the declaration as they provide a clear and definitive guide to the ethics principles that drive ethics processes globally. The language in the guidelines is oriented towards physicians, as it is, after all, a statement made by the World Medical Association, but the content is directly applicable to all research involving humans and it has been used extensively in the design of human research ethics procedures more broadly. The Declaration is the foundation for most ethics statements and procedures throughout the world.

There have been numerous codes of medical ethics published in various countries and professional bodies for guiding health and medical research (Emanuel et al 2000). The Helsinki Declaration has been very influential in the development of ethics codes in different countries. Thus while the codes vary somewhat from country to country they have essentially the same foundation. The Declaration is built upon certain key and basic ethics principles and concepts. These principles and concepts are now discussed.

Key principles and concepts

There are many principles and concepts in ethics processes but some are fundamental. We will now discuss some of the basic ones.

A key ethics principle is that of informed consent and self-determination, i.e. freedom of choice to participate or not. That is, the research participants must be fully informed about the purposes of the research, any risks associated with their participation and the uses to which the collected research data will be put. Their participation must be fully voluntary and made with full knowledge of any potential benefits and costs. Special arrangements are implemented where the researchers may have undue influence upon the research participants such as if they are also their patients or have some form of dependent relationship with the researcher.

As discussed later in this chapter, this principle is frequently protected through the use of explanatory statements sometimes called plain language statements. In this statement the researcher explains in plain language to the participants the goals of the research and exactly what is going to happen to them if they agree to participate in the research. The participant’s agreement to participate with full information and knowledge about the study is recorded in an informed consent document which they normally sign. In this document they state they have understood the purpose of the study, its risks and the nature of their participation in the research.

Another key ethics principle is scientific excellence and quality. Most research ethics committees take the view that the proposed research has to be of high scientific quality and address research questions that have not already been answered. This is safeguarded through the ethics review process where the evaluators consider whether the researchers have the qualifications necessary to conduct the work and whether the scientific rationale for the work is sound. The view is taken that it is unethical to conduct work that is not going to add to the scientific body of knowledge because of its poor quality or a high degree of overlap with existing work. This is a waste of resources and involves participants in unnecessary activities and potential risks.

Another key ethics principle is minimizing risk and harm to participants. Of course, most scientific work and indeed all human activities involve some degree of risk and the possibility of harm but this needs to be minimized. The Helsinki Declaration and all ethics processes that derive from it centrally consider the risk of harm to the participant. They seek to see that all risks have been minimized and that the participant is fully aware of such risks before they have agreed to participate. In animal research, discussed later in this chapter, minimization of harm to animal research subjects is also a high priority in ethical review.

A further key ethics principle is that of confidentiality and right to privacy. This principle is concerned with ensuring that people’s private information is not disclosed as a result of their participation in the study. In most ethics processes this involves quite a lot of attention concerning how people’s information is to be obtained, stored, processed and disseminated. So the researcher is often asked detailed questions about how the information is to be obtained and handled and how it is to be retained and ultimately disposed of when the project has been completed. Further detail is required of how the work is to be published and disseminated. Many countries also now have privacy legislation that informs the local ethics procedures because any work within that country needs to comply with the local laws.

The risks of identifying individuals in research are increased in the study of small, specialized sub-populations and in qualitative studies where direct quotation of the words of the research participant may be used in the publications. One of the authors of this text was once asked to participate in a study of staff who had left a university with the assurance that the results would be anonymous. However, he was the only male professor who had left over a five-year period in his faculty. With any basic cross-tabulation of the data based upon appointment level and gender, he would be the only respondent in that category, so the chances of being identified would be very high. In qualitative studies involving the direct reporting of the statements of participants the risk is also increased. People have distinctive manners of expression and experiences such that, while there may be no names mentioned, people who know them may be able to identify the person through their language and the experiences they are describing. We know of numerous examples where research participants have been identified by others when their responses have been directly quoted in research reports and publications with the promised protection of anonymity. So given that most researchers promise to maintain anonymity of their research participants, the possibility of ‘outing’ through publication must be taken seriously and guarded against.

In this discussion we have used the terms confidentiality and anonymity interchangeably as is now common usage in research discussions. However, they actually mean different things. Anonymity means that the identity of the research participant is not disclosed and in some cases may not even be known to the researchers. Confidentiality, however, means that whatever is being maintained as confidential is not revealed to a third party. While some researchers promise confidentiality of the research findings and the participants, what they often really mean is anonymity. A literal interpretation of confidentiality would mean that they could not publish their research results!

A further key ethics principle is lack of conflict of interest. Conflict of interest occurs when an individual or an agency is potentially able to exploit their involvement in research in some way for their own personal or agency benefit. Some commentators argue that all researchers have an intrinsic potential conflict of interest in that they are directly impacted by the findings of their research in some way or another. For example, the outcomes for the researcher may be quite different if they identify that a new therapy is effective versus if it does not work. The positive result may mean more support for their work, professional acclaim, press coverage and so on, but a negative or null result may result in de-funding and little prospect of acclaim or favourable publicity. Similarly, a government agency or institution may have a vested interest in showing that a disease or problem within the community is low or even high to legitimize their existence.

The relationship between researchers and research funding bodies is also an area of potential conflict of interest. This is why many journals and professional and scientific bodies require full disclosure of such arrangements. The researchers are required to disclose their funding sources, memberships and relationships that may impact upon their independence and perceived bias. In ethics review, a high standard is imposed upon researchers. Thus for many the appearance of potential conflict of interest is just as important as whether it is an actual conflict. Some researchers, for example, will not accept funding from tobacco companies, or alcohol or gambling interests or pharmaceutical companies or government because of a perceived conflict of interest for them. There is always the fear that the results obtained in such research may be biased in some way either through direct influence or a desire on the part of the researchers to please the funding agency. To address this issue some of these funding agencies have ‘arm’s length’ funding arrangements where they donate to a third party foundation, but some are intricately involved in the approval and conduct of the research. Although government is generally not categorized with tobacco interests, government officials and ministers still have identifiable conflicts of interest and through ‘contract research’ can potentially exert considerable influence on the conduct and outcomes of the research they fund.

In some instances the pressure upon researchers to produce exciting and fundable research findings results in misconduct whereby the researcher may cut corners through use of low-cost or non-standard protocols or even directly falsify their research findings. There have been a series of celebrated examples in history and modern day of such lapses. The case of Sir Cyril Burt is one such figure. It is claimed by some that Burt falsified some key data sets for his research (a claim hotly contested to this day). Typing the search terms ‘medical research fraud’ into any Internet search engine brings up hundreds of reported cases of misconduct and fraud, often involving data falsification. However, it must be remembered that this is a very small proportion of the studies that are conducted. For example, in the UK it is typical to exceed more than two million animal study notifications annually. Interestingly some methodologists claim that poorly conducted research and researcher incompetence, notwithstanding ethics approval, is a much more serious threat to science than outright fraud!

Finally, a key principle in ethics protocols is independent review. Researchers and funding bodies are not in a good position to independently evaluate the ethical implications of their own work or the work they may wish to fund. They have an intrinsic conflict of interest. This is why most medical research councils and funding bodies, while enunciating the principles and processes for ethical review, do not directly participate in such review. Of course, the independence and expertise of reviewers is in itself an issue in terms of potential conflicts of interest. Expert reviewers in many fields may have friendships or enmities with the person or research group whose work they may be reviewing. Even if they don’t know them some professional jealousies may exist. This is why there are particularly detailed guidelines for reviewers to attempt to address these issues. In small, specialized fields obtaining independent review is particularly problematic because ‘everyone knows everyone’. A second option is to use reviewers that do not work in the field but the problem then is that it is easy to obtain reviews that are misinformed about important technical details of the research.