Research ethics in real world research

My interest in research ethics began more than 20 years ago when I was a doctoral student seeking research ethics approval for my grounded theory study exploring what it was like to live with normal pressure hydrocephalus. To cut a long story short, my application was rejected on two occasions primarily because the Research Ethics Committee (REC) did not understand what I was trying to do or how I was going to do it. This experience motivated me to get myself more involved in the ethical review of research, and now, more than 20 years later, I spend considerable amounts of my time thinking about research ethics and the ethical conduct of research, as a researcher, as a research ethicist and as the Chair of an NHS REC. Research ethics is something all researchers have to think about but in most instances this will only be for a very short time at the beginning of a research project when there is a requirement to seek the necessary research ethics approvals or opinions. During this encounter, if the Committee immediately offers a favourable opinion then ethical review is usually treated as a useful part of the research process. But when the REC says “no,” asks challenging questions or seeks changes to what is planned then the REC is often condemned for causing delays to the start of “important research” and I have never heard of a researcher describing their own research as anything other than “important.” When someone has identified an important research question, why can't they simply begin their research and why do they have to spend time thinking about the ethics of what they are planning to do? Furthermore, why do they need to seek the opinion of an independent group of individuals formed as a REC? To put it bluntly, the main reason we take research ethics so seriously is that when we don't, people are at risk of being harmed. The history of research ethics includes repeated cycles of harm, where an unethical research event has occurred, someone has been harmed as a result of that event and there is then often a response seeking to prevent that event, or any similar event, from happening again. Unfortunately, these multiple responses have repeatedly failed to halt unethical research and it is only a matter of time before the cycle of harm is repeated. It seems that in the world of research ethics we sometimes find it hard to learn from past mistakes. Prior to 1800, there was very little consideration of research ethics when conducting experimentation or research with human participants (probably better described as “subjects” at the time) but as we moved into the 19th century, researchers began to spend much time considering the ethical implications of their research. An early example of the cycle of harm was the research undertaken by Dr Albert Neisser in Prussia. In seeking to find a vaccine for syphilis, Dr Neisser injected small amounts of syphilis-infected blood into healthy individuals who all developed syphilis, suffered terribly and died. There was a public outcry, so the Prussian government published the Prussian Directive in 1900, which was the first ethical guidance for researchers in which they highlighted the needs to seek informed consent. Unfortunately, this response to harmful research had little impact on ending unethical research. Given the growing insight into the importance of research ethics in central Europe, the events occurring during the third period (1939–1947) were all that more astonishing. There are well-documented accounts of the unethical and harmful research happening before and during this period in many parts of the world. This time the response was the Nuremberg Code written by the lawyers at the Nuremberg Trials and published in 1947, which again emphasised the need to seek “voluntary consent” and that possible suffering should be avoided. Unfortunately, the Nuremberg Code was not widely adopted and again did not have a significant impact on ethical conduct in future research. In the years following the publication of the Nuremberg Code, unethical research continued and was captured in Henry Beecher's paper in the New England Journal of Medicine (Beecher, 1966) and in Maurice Pappworth's book “Human Guinea Pigs” (Pappworth, 1967). Pappworth (1967) detailed 78 examples of unethical research conducted in the UK and the subsequent harm to participants involved in that research. The next response came from the World Medical Association who published the Declaration of Helsinki at their meeting in Finland in 1964. The Declaration, which has now been updated on several occasions, is still widely used today and is frequently referred to in protocols for clinical trials of new medicines. The Declaration should leave researchers in no doubt about what is expected of them when seeking to recruit participants to their research. Whilst the Declaration has undoubtedly been influential, it has certainly not put an end to unethical and harmful research. In recent years, it has been easier to find information about unethical research because such events are more readily reported in the professional and popular press. In addition, many more people are aware of the need to undertake research in an ethical manner and what the consequences might be when this does not happen. Despite this, there have still been further examples of the cycle of harm. One of the most obvious examples of unethical research conduct resulting in harm in recent years is the event occurring at Alder Hey Children's Hospital. Between 1988–1995, many children and babies who died and had postmortems had their organs retained for research purposes without first seeking informed consent from parents or guardians. When this was discovered, sometimes many years after the death of these children, this caused considerable further distress and upset for parents. There were two responses to events at Alder Hey. First, the Department of Health published the “Research Governance Framework for Health and Social Care” which provided a clear summary of who in the research team, and outside the research team, was responsible for what (Department of Health, 2001). More important, however, was the implementation of the Human Tissue Act 2004 which put in place a clear legal framework for the collection, storage and use of human tissue. Researchers are now left in no doubt about the ethical and legal requirements when using human tissue in research. In this editorial, it has only been possible to highlight just a small number of examples of the ethical cycle of harm but there are many more examples, from all disciplines, continue to be widely reported. What is clear is that when researchers do not give due regard to the ethical implications of their actions, there will be a risk that participants will be harmed. So in today's world of complex interventions and multiple research methodologies, how should researchers be guided when planning and undertaking their research? I would argue that the answer is the same as it ever has been; they should be guided by a set of principles that can be applied to all forms of research, from the large pharmaceutical company-sponsored clinical trials to undergraduate student projects, and can also be applied wherever that research is being conducted around the world. These principles can offer important guidance to both those undertaking research and to those undertaking ethical review. If both groups are applying the same principles, then how difficult can it be for there to be agreement about what is right and what is wrong? Unfortunately, the interpretation of these principles can vary widely. Much has been written about the ethical principles that should guide researchers, and I suggested seven ethical principles in a paper published 20 years ago (Gelling, 1999). My thinking about how these principles might be applied to the real world of research might have developed over the past two decades, but the principles themselves are as relevant now as they were when I first wrote about them. It has not been possible to explore these ethical principles in great depth in this editorial, but a brief consideration of just one will highlight their complexity and will emphasise their importance to researchers and RECs. Nonmaleficence requires that researchers seek to minimise the risks to which research participants and themselves might be exposed. RECs spend much of their time considering risks and benefits and seek to ensure that balance exists between them. There may, however, be occasions where it might be considered ethical to allow someone to participate in research where the risks might be greater than the possible benefits. For example, when someone with advanced cancer has been through all the possible treatment options and might be dying, should they be allowed to participate in research of a new medicine where there is greater uncertainty about the efficacy and safety of the drug? More importantly, who should make that decision? Should the REC decide or should they seek to ensure that potential research participants have adequate information to make a decision for themselves? Such situations are often discussed in REC meetings, but the answer is still not clear. Judging the risk of harm can be complicated because possible harm comes in so many forms. Physical harm is often more obvious and sometimes easier to anticipate and plan for. Psychological harm, however, can be harder to predict but can be no less traumatic for participants. Social harm might occur in research exploring hereditary conditions. For example, if research needs blood samples from a child and both parents there is a danger of causing social harm if the father is not the blood father of the child and this is discovered during the research. Avoiding economic harm is about ensuring that participants do not incur a financial burden when participating in research, especially in large pharmaceutical company-sponsored studies where it should be possible to meet all participant expenses. To complicate matters further, there are also degrees of possible harm which can be hard to predict. No research involving human participants is without risk, and at the other end of the continuum, no REC anywhere in the world would approve a study where there is certainty of permanent harm. So, all research can result in one of the three degrees of possible harm: temporary discomfort, unusual levels of temporary discomfort or risk of permanent harm. The difficulty can be in predicting where on the continuum harm might occur and therefore what precautions should be put in place when planning research. It is common for researchers to underestimate the type and possible degrees of possible harm in their own research, and so, independent ethical review remains important. There are seven ethical principles which, on face value, look relatively straightforward but as soon as researchers, research ethicists and REC members seek to apply these principles to research in the real world then some of that clarity is lost and fascinating debates begin. These principles do, however, provide a very useful framework for researchers when planning and conducting their research and for REC members when reviewing applications for research ethics approval. If nothing else, all involved in the discussion will be using the same language. For REC members, adopting a principled approach to ethical review is much more useful than the current most common approach, which is primarily concerned with avoiding risk and which often feels adversarial. A principled approach places greater focus on allowing those who might participate in research to decide what research they should be allowed to participate in. Research ethics in the conduct of the real-world research is extremely complex and has got no less complex since RECs were introduced. Some might argue that RECs might have had their time but others would argue that RECs still have an important role to play as an integral part of the research process. History has taught us that researchers are not always the best judges of the risk in their own research or most balanced when considering the ethical principles underpinning their own research. It is the continued involvement of RECs which helps to ensure some balance when considering the ethics of a research study involving human participants. One of the main reasons that researchers might not always act in an ethically balanced manner is the pressure placed on them to win research grants and to publish their work to progress their careers. For example, in the UK we are building towards the next Research Excellence Framework (REF) during which all universities and academic disciplines have the quality of their research independently judged. The outcome of this review will have significant financial implications for many academic departments and individual academics' careers. Whilst this pressurised climate exists, it is important that someone continues to take an independent view of the ethics of planned research. The history of research ethics has demonstrated that researchers have too often proven themselves not to be the best judges of whether their own research is ethical or not. Of greater concern is the possibility that researchers might be aware of the possible risks but still be willing to proceed with the research because of external factors. It is possible, however, that greater consideration needs to be given to how RECs function. For example, as noted above, it could be argued that there needs to be a shift in thinking about ethical review from one that is primarily risk-averse to one that bases ethical opinions on a principled approach. There should also be greater collaboration and discussion between researchers, research ethicists and RECs that create a climate in which researchers do not talk about “getting through” the ethical review process but where there is greater appreciation of how ethical review processes has added value to the planning of research, even improving that research. But for this to happen, the review process needs to be less adversarial and adopting a principled approach to the ethical review would help facilitate this. Finally, the users of health care should have a greater say in what is ethical and what is not. For example, at NHS RECs there are often applications for research that will involve children and young people as participants. Decisions about whether the research is ethical are then made by a group of middle-aged adults who might be highly qualified and knowledgeable but often would not be able to remember what it was like to be young. So is there a danger that the REC might be making decisions with which children and young people disagree? Why not involve them in some way in making decisions or at least in helping to set the direction for the ethical review of research in which children and young people might be involved? It would be very odd if this editorial were to conclude by suggesting that RECs have had their time but it is possible to argue that much more could be done to make ethical review more relevant to the real-world research in the 21st century. We live in an age where research is getting ever more complex in seeking to meet the increasingly challenging health needs of society. In that real world of research, the ethical challenges that researchers and members of RECs face have also become more complex. What should not be forgotten is that researchers, research ethicists and REC members ultimately have the same objectives: to plan and conduct high-quality research that meets the needs of society and doing it within an ethical framework that is acceptable to society. This editorial is based on a plenary lecture, of the same title, delivered at Sigma's 30th International Nursing Research Congress in Calgary (Canada) in July 2019.

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