A significant minority (cancer research indicates between one tenth and one quarter) of dying people experience refractory symptoms (such as agitated delirium) or extreme distress which is unresponsive to conventional therapies [1, 2]. In such circumstances, sedation may be used to decrease or remove consciousness. Internationally, prevalence studies to ascertain the percentage of patients receiving sedation for refractory symptoms at the end of life report variation in use of between 15% to 60% [3–5]. The wide variation in reported prevalence is likely to be due in part to differences in the care setting, patient populations, methods and the definitions applied. These definitions include: 'palliative sedation', 'terminal sedation', 'continuous deep sedation until death', 'proportionate sedation' and 'palliative sedation to unconsciousness' .
One group of studies exists that have enabled comparisons to be made; these focus on quantifying types of medical end of life decisions, using questionnaires to ask physicians to describe the decision-making and care for recent deaths they attended [7–9]. One of these studies, looking at representative samples of death certificates in six countries in Europe (excluding the UK), employed a narrow definition of 'continuous and deep sedation until death' to compare physicians' reports, and showed a relatively narrow band of variation in prevalence of between 2.5% to 8.5% of deaths . A survey in the UK employing the same definition found that 16.5% of the 2,923 respondents reported use of continuous deep sedation until death, although study limitations may have led to over estimation of prevalence .
An important focus of debate surrounding the practice concerns the relationship between continuous sedation until death for refractory symptoms or distress and any adverse consequences which may result from its use (known as 'double effect' issues) . These include the risk of paradoxical agitation, the loss of ability of the patient to interact and the hastening of an expected death [10–12]. While a systematic review of sedative use  and comparative studies [4, 14] have shown no relationship to exist between the use of sedation for refractory symptoms or distress and timing of death, in the Netherlands and Belgium there is evidence to suggest that continuous sedation until death may sometimes be used by clinicians both as an alternative for euthanasia and to hasten an expected death [15, 16]. More broadly, the ethical dimensions of the therapy are increasingly being debated [17–19].
Ethical concerns surrounding the practice have resulted in the publication of a number of guidelines or frameworks for clinical practice [10, 20, 21]. These recommend that the use of continuous sedation until death for refractory symptoms or extreme distress should occur only when the patient's disease is irreversible and advanced, that benzodiazepines should be the drug of first choice, that decisions to use artificial hydration should be considered separately and offered to sedated patients only when the benefits outweigh harm, and that physicians with little expertise in sedation seek advice from palliative care specialists before initiating continuous sedation until death.
There have been calls for research to examine clinical practice in a qualitative manner to complement the large scale survey studies described above and provide explanatory data about the intentions, practices and understandings associated with continuous sedation until death and its perceived contribution to the management of refractory symptoms and distress . There is, with a few exceptions, little research exploring the understandings, intentions and beliefs of physicians and nurses regarding the use of continuous sedation until death or the perceptions and experiences of bereaved informal care-givers.
Those studies which do exist of health care staff suggest that clinicians, whether physicians or nurses, struggle with the meaning and significance of sedation use in end of life care , are concerned about its possible link to practices which may end life prematurely , or have objections to the practice on the grounds of religious belief or moral conviction  or because of ideas about appropriateness of the practice for certain 'types' of suffering [26, 27]. There is evidence that physicians and nurses have different experiences of the decision-making process relating to continuous sedation until death  and of international differences in clinicians' understandings and perceptions . One small scale qualitative interview study of clinicians and researchers in end-of-life care in England, Belgium and the Netherlands  found that beliefs and attitudes regarding the practice were affected by the socio-legal context of end-of-life care practice within each country and that judgements about refractoriness were regarded as likely to be affected by resource availability.
Studies of bereaved informal care-givers and members of the general public [31, 32] indicate that it is preferable to provide information in advance about the need to sedate, its contribution to the care of the patient and its consequences. One study in Japan shows that one quarter of families who witnessed the use of sedation for refractory symptoms experienced significant distress .
This protocol relates to the UNBIASED study (UK Netherlands Belgium International Sedation Study), which comprises three linked studies with separate funding sources in the UK, Belgium and the Netherlands designed to explore these issues. The UNBIASED study is part of the European Association for Palliative Care Research Network . The study design has been scientifically peer reviewed as part of the grant application process by the Economic and Social Research Council (UK); Fund for Scientific Research (Belgium), the Netherlands Organisation for Scientific Research and the Netherlands Organisation for Health Research and Development.
Aims of the study
To explore decision-making surrounding the application of continuous sedation until death in contemporary clinical practice.
To understand the experiences of clinical staff and decedents' informal care-givers of the use of continuous sedation until death and their perceptions of its contribution to the dying process.
For cancer patients at home, in hospitals and in hospice settings:
1. In accounts of clinical practice, what do physicians and nurses mean by sedation in end of life care?
2. What are the clinical characteristics of the application of continuous sedation until death according to physicians and nurses?
3. How do bereaved informal care-givers, physicians and nurses describe decedents' care at the end of life and the contribution made by continuous sedation until death?
4. Who are, according to physicians, nurses and bereaved informal care-givers, the key people involved in the decision-making with regard to the use of continuous sedation until death, and what role do they play?
5. What accounts do physicians and nurses give about communication and consent in relation to the use of continuous sedation until death?
6. What reasons are reported for the use of continuous sedation until death by physicians, nurses, and bereaved informal care-givers, and what reasons for the use of continuous sedation until death are described in clinical records and in clinical guidelines and protocols?
7. What moral and legal issues emerge from the accounts of physicians, nurses and bereaved informal care-givers about decisions taken regarding continuous sedation until death?
8. What aspects of context, attitudes and experience facilitate or constrain decision-making according to the accounts of physicians, nurses and bereaved informal care-givers?
9. What are the differences between Belgium, the Netherland and the United Kingdom with respect to the findings of research questions 1 to 8?