- Pragmatic definition
- General considerations
- Insufficient knowledge
- Burden on the participants
- Risk versus benefit
- Capacity to consent
- Confidentiality and anonymity
For pragmatic reasons it is reasonable to define limited life expectancy as life expectancy of one year or less for a person with a terminal illness (who cannot be treated with the aim of a cure). Treatment in this period therefore has a life-prolonging and/or palliative purpose. The final phase before death occurs may be described as the terminal phase, or it may be said that the patient is dying. Many people prefer the latter term as it is clearer and therefore more precise. This phase is commonly deemed to represent the final weeks of life.
For the great majority of patients, the final years of life will be characterised by an increase in symptoms and gradual reduction in function. For some groups of patients this occurs gradually; for other groups the changes are most pronounced in the final months of life, while in yet other groups death may occur relatively abruptly and is not preceded by a notable decline in function. There is also significant individual variation. Most patients are elderly and share similar traits with the general geriatric patient population (ill, frail and often with reduced cognitive capacity). For younger cancer patients, the course of illness may manifest itself quite differently than in an elderly cancer patient.
We must assume that most patients in Norway who have a limited life expectancy have been informed that the disease is no longer curable, but we have no empirical knowledge of this. Nor can we presume that the prognosis of limited life expectancy has been communicated – in fact, this is often not the case. Nor is it certain that information on the diagnosis and prognosis has been communicated in precise terms, or has been understood. Uncertainty regarding what patients actually know about their illness, possibilities for treatment, and life expectancy may therefore represent a challenge when preparing factsheets for patients and oral information about studies. Patients will often veer between unrealistic optimism about a long life, and a more pessimistic/realistic awareness that death is approaching.
The ethics of research for this group is in principle no different from the ethics applying to research on other groups, in the sense that this must follow general principles as stipulated, for example, in the Helsinki Declaration. However, it is a matter of debate whether research on persons with limited life expectancy presents unique ethical challenges. Some ethical challenges have been highlighted which are not necessarily unique, but which are accentuated by the fact that life expectancy is limited and the patients are usually very ill. These will be dealt with in this article, and comprise the following: insufficient knowledge; burden on the participants; risk versus benefit; capacity to consent; confidentiality and anonymity; challenges of design and implementation.
The lack of good documentation on the treatment of disease, symptoms and patients in the final year of life represents an overall research ethics challenge. This applies both to research on traditional medical treatment and research into the nursing and care of patients, as well as safeguarding next of kin and making provision for the care situation. Many small-scale studies using inadequate methodology have been conducted on selected groups. This exposes the patients to the burden of participating in the research without this generating any knowledge that is of relevance beyond the group studied. In addition, the absence of clinical studies of sufficient quality is a barrier to the preparation of clinical guidelines to ensure evidence-based treatment for many patients. In the worst case, this absence of good clinical studies combined with single published studies of poor quality may result in the unnecessary use of undocumented treatment.
It is commonly believed that research on patients with limited life expectancy may involve an unnecessary additional burden because patients are already under a severe strain in the form of reduced function and an increased symptom burden. Those who evaluate research, such as the research ethics committees and clinical therapists, tend to use their own perceptions of what patients can or wish to participate in as a means to reject research without any empirical evidence for their viewpoint or without asking the patients about their wishes/wants. Experience shows that the research ethics committees emphasise sparing research participants from any possible mental burden, while the clinicians in question underline the patients' physical limitations. Patients themselves with the capacity to consent are usually in a position to consider whether participation entails too great a burden. Preventing the opportunity to make a decision on participation in studies to protect the individual is termed "gate-keeping", and may involve undermining the patients' autonomy. This is contrary to the positive attitude of many patients and their next of kin towards participation in research for altruistic reasons, through a sense of being meaningful or useful, even though life expectancy is limited and the results cannot benefit them personally.
In any case the burden of participation must be considered specifically for each study, and the patients' right to withdraw or discontinue without consequences must be safeguarded. It is essential that each study is based on clearly considered and formulated research questions that can contribute to improving clinical practice directly or indirectly through increased knowledge about the condition and/or patient group. If many patients discontinue, the basic data may be skewed and the value of the study is thereby reduced. The burden of participation is often difficult to calculate, and non-empirical perception may then replace specific arguments. It is easy to calculate the burden by answering a questionnaire because the number of questions is a concrete expression of this. Interview studies represent a different form of burden due to closeness to the interviewer. This may involve a stronger sense of obligation, and entail greater difficulty in discontinuing and less opportunity to distance oneself from distressing questions.
It can often be difficult to weigh up risk and benefit, as there is little documentation on the effects of an intervention in this population, and therefore also on possible risks. The illness may also involve a risk of negative events that are less of a factor in healthier populations. The significant individual variations within the relevant population may also serve to complicate assessment of risk.
In general, therefore, there is reason to regard this patient group as being vulnerable to unforeseen negative effects due to advanced disease, often advanced age and gradually deteriorating health. The latter may be an important consideration with regard to interventions that extend over a period, since patients change physiologically and psychologically as the disease progresses.
Due to the general characteristics of the population, a certain proportion will experience cognitive failure, and as the disease progresses many will develop a temporary or permanent form of this. In the terminal stage and the final days before death, more than half will exhibit cognitive failure. This affects their capacity to give true informed consent.
Cognitive failure with the resulting incapacity to consent gives rise to several challenges: how to assess cognitive function and hence capacity to consent, how the sample might be skewed because of attrition due to acquired cognitive failure, and how to deal with patients lacking the capacity to consent. An explicit formulation of inclusion/exclusion in relation to cognitive function may be called for. Stipulating capacity to consent as an absolute requirement impedes research on large groups and will prevent these groups from receiving evidence-based treatment. By the same token, those without the capacity to consent constitute a vulnerable group who require special protection and therefore special assessment of risk/benefit.
In quantitative studies, data collection will often be relatively anonymous, for example in the form of questionnaires. In the case of interviews, it is frequently difficult to ensure anonymity between researcher and patient. Interview-based studies are also often small, which may enable recognition of the patients in the reports. It has also been found that patients may mistake an interviewer for a therapist, and clarification of roles in interview studies may therefore constitute a challenge. (See Confidentiality and Data protection.)
Methodological challenges for design and implementation
Interview studies may be personal or intrusive, and thereby represent an unnecessary emotional burden. Clinically controlled studies can be undermined by attrition resulting from death or worsening of the illness, especially if the intervention extends beyond a certain period. A crossover design is oftenimpossible due to limited life expectancy. Recruitment of a sufficient number of patients to answer the research questions is therefore a challenge which in the worst case can invalidate studies. Because of the absence of documented treatment, placebo may be a relevant control arm. "Best Supportive Care" is used as a control arm, but its content is often unspecified. Both these types of control arm may not only entail withholding the active treatment from the control group, but also that the overall service offered to them is inferior to that for the active arm in a period when the need for assistance is significant and increasing as death approaches.
This article has been translated from Norwegian by Jane Thompson, Akasie språktjenester AS.