By Len Doyal and Jeffrey S Tobias

Belief in the right of individuals to good healthcare, a fundamental precept of the National Health Service in the United Kingdom, goes hand in hand with a moral commitment to support medical research. Without it, how can we claim to have minimised the ill-effects of disease? Since all of us are potential or actual patients at some point during our lives, a public commitment to well designed clinical studies offering reliable information about new treatment methods, must surely be in the common interest. Yet it is also true that in their zeal to make progress, some medical researchers have behaved unethically, sometimes exposing patients to unacceptable risks of further ill health: the polar opposite of what good medicine seeks to promote. As a result of concern about such unethical practice, medical research has become highly regulated over the past three decades.

One component of this regulation is the general duty of researchers to obtain the consent of patients or healthy volunteers before they participate in medical experiments. This emphasis on choice is based on the moral and legal importance of individuals exercising control over what happens to their bodies, especially when they may be subject to the risk of physical or mental harm. Choice to participate in medical research, it is argued, cannot be rationally exercised without information about what is proposed and why, together with the main side-effects and hazards that might occur as a result. Since the capacity to exercise such choice – to act with autonomy is commonly regarded as the most important attribute which sets humans apart from other animals, not to respect this capacity could be seen as an affront to human dignity.

This book is about the principle of informed consent in medical research. It was most notably articulated by the Nuremberg Code in the aftermath of Nazi medical atrocities and has since been adopted both in the Helsinki Declaration of the World Medical Association and by a wide range of other prominent national and international organisations involved in the professional regulation of medical research. The consensus of professional opinion about the general importance of informed consent in research has been fuelled by a number of widely criticised medical experiments over the past 50 years where irrespective of any other harm that may have befallen participants, informed consent was not obtained. As a result, in North America and the United Kingdom, for example, great emphasis is now placed by research ethics committees on ensuring that researchers will routinely obtain informed consent. Yet despite this consensus about the importance, in principle, of respecting the right of participants in medical research to informed consent, there is much less agreement about how to interpret this rule in practice.

On the one hand, some argue that if the principle is interpreted rigidly then it becomes inconsistent with other moral duties. For example, if patients have a strict right to information about potentially distressing aspects of participating in research, does this not then conflict with the clinical duty of researchers not to distress them with information which may be unwanted and might cause considerable harm? Equally, if it is accepted that we all have a right to optimal healthcare, and thus to the benefits of the participation of past volunteers in medical research, do we not have a corresponding duty to participate in such research for the public good and for future generations – whatever our preferences might be to the contrary? Others argue in return that the right to exercise autonomous choice over participation in research trumps any of our other rights and duties, even when these are also accepted as morally important. For example, patients may be more upset by having potentially distressing information withheld about their participation in research than they would be by the information itself. Equally, while it may be accepted – or at least argued – that we do all have a duty to participate in medical research in the public interest, it does not follow that we should be manipulated through lack of information to do so.

Because of such differences of opinion, the BMJ asked us in 1997 to write position papers which would explore both sides of the argument. At that point, our focus was to be the question of whether or not the BMJ should publish the results of research which had been done without the informed consent of participants. These papers, along with other accompanying articles and editorial comment, generated the largest "mail bag" of letters in the history of the BMJ. As a result of this enormous interest, a successful national conference was held in 1998 to debate the issues. In the heady aftermath of this gathering, we decided to create a book which would take the discussion and debate further still, as well as providing a practical guide to researchers about their current obligations concerning informed consent. The book is divided into five parts.

Part 1 explores the historical evolution of the doctrine of informed consent in medical research. The development of international and national regulation concerning consent is outlined, along with its relationship to a variety of examples of unethical research. The impact of the infamous Nazi experiments is described, including an interesting and surprising description of some of the contemporary controversy surrounding the Nuremberg trial.

This general background is followed by the exciting re-publication for the first time of two of the most important works on the ethics of medical research and the principle of informed consent. These often referred to, but seldom seen contributions, are Henry Beecher's famous article in the 1966 New England Journal of Medicine which is reprinted in full and Maurice Pappworth's equally devastating contribution of the following year, Human Guinea Pigs, from which we have chosen representative selections. Both works exhaustively documented examples of un-ethical research in Britain and the United States during the 1950s and 1960s and influenced current national and international patterns of regulating research. Interestingly, the dramatic impact of Beecher's work on the development of North American regulation was only matched by the relatively deaf ears on which Pappworth's efforts fell in Britain. Both contributions are introduced by fascinating historical analyses of the background to these different national responses. Finally, to bring readers up to date, we have included a detailed exposition of more recent and questionable research practice pertaining to informed consent. This chapter outlines research which has been consistently criticised in the United States, Australia, New Zealand, the United Kingdom and elsewhere.

Part 2 includes the publications within the BMJ that generated such an enormous correspondence. First, there are two studies that took place without informed consent and which the BMJ decided to publish anyway. These concern an assessment of a family care worker for patients in the aftermath of a stroke and a study in South Africa concerning rates of HIV admission to surgical intensive care. The reasons why the researchers believed informed consent to be inappropriate are outlined by them, with some preliminary critical reactions of others.

Then our two papers are reproduced, debating whether or not the BMJ should ever publish such research. While fully respecting each other as fellow professionals, we strongly disagree in our arguments and conclusions about this matter. Our contributions are followed by the complete publication of the extraordinary (and for us gratifying) breadth of letters published by the BMJ, representing a huge diversity of perspectives on the moral, legal and professional importance of informed consent in medical research. Finally, a range of other types of responses to the debate also published by the BMJ – editorials, short articles and other forms of comment – are also included. In toto, this is a unique collection of material, highly useful for undergraduate and post-graduate teaching.

The many contributions to Part 2 raise important issues about the appropriate professional boundaries of the principle of informed consent within medical research. However, because of their brevity, most contributions unavoidably lack the detail which justice to these issues demands. Consequently, for Part 3 of the book, we commissioned well-known experts to explore how different countries approach the problem of informed consent in regulating medical research and how this regulation impacts upon the practice of medical research in a variety of clinical disciplines.

Three interesting problems emerge from these contributions:

1. While the general approach to regulating research through North America and Europe continues to support the general appropriateness of informed consent, this does not amount to a blanket endorsement or mandate. Most regulations recognise the acceptability of exceptions to the rule, with respect to other circumstances, where it is believed that there is no risk to patients who participate without their knowledge or where patients are unable to consent and the risk–benefit ratio of doing so is very much in their favour.

2. Several contributors raise practical problems about obtaining consent, even where it is accepted that it should generally be attempted. For example, these often concern difficulties in communicating complex information to patients who may be under enormous stress because of their illness or who have other personal problems about understanding such information.

3. Some contributors note that to overly emphasise the individual right to consent (or not) to participate in research can lead to an underemphasis on the moral responsibility of healthy volunteers and patients to do so.

In Part 4 other experts analyse these three – and other – problems in more detail. For example, the chapters argue in sequence that:

• Respect for the right of patients to give their informed consent to medical research should be understood in the context of broader, internationally recognised human rights. Any compromises which are reached with respect to the specific issue of informed consent should always be understood against the background of the potential abuses of human rights to which they could lead
• A rigid emphasis on informed consent can itself lead to violations of human rights. If patients have a right to be given certain information before they participate in medical research then does it not follow that they also have a right to refuse unwanted and potentially distressing information? Why should they not simply be able to trust their doctor/ researcher to act in their best interests
• Conventional analyses of informed consent in medical research risk dangerously overemphasising the hazards of participation. In fact, much ordinary clinical care is administered without the same attention to evidence and control over clinical administration that is usually found in the conduct of medical research. Without understanding this, patients cannot give proper informed consent to conventional treatment, much less understand why it might be always in their best interests to choose to participate in research
• Placing too much moral emphasis on informed consent detracts from the responsibility of citizens to contribute to the public good through not becoming "free riders" in their use of medical advances. This will result inevitably from refusing to participate in medical research. While not concluding that participation in medical research should be compulsory, these authors do point in the direction of how this might be argued.
  

Finally, it makes little sense to emphasise the moral and legal importance of informed consent without paying equal attention to the practical problems associated with obtaining it. Thus the final chapters reason that:

• There should be more consumer participation in the planning and execution of medical research. Here it is maintained that just as patients can have personal difficulties in understanding information, the same applies to clinical researchers with respect to their communication skills and their understanding of the moral importance of an acceptable level of disclosure of information. For this reason, informed consent in medical research should not just be understood as an ethical issue – it also raises problems about education and professional training
• There is extensive evidence that some healthcare researchers have poor communication skills as regards obtaining informed consent and that these can – and should – be improved
• There is a variety of ways in which the moral importance of informed consent and the practical importance of related communication skills can and should be taught within undergraduate and postgraduate education.

Throughout the development of this book, our goal has been to help researchers understand the moral, legal and professional demands concerning the provision of informed consent by participants in medical research. We have also attempted a fair and incisive analysis to help explain why the principle of informed consent is now taken so seriously, along with the obligation to obtain such consent. We have been consistently gratified by the extremely high quality of the chapters and by the enthusiasm and commitment of the contributors. We thank Janet Bennett, Lesley Doyal, Jayshree Kara, Christine Sinclair, and especially appreciate the advice and support that we received from Mary Banks, Christina Karaviotis and Alex Stibbe at BMJ Books.