Advance directives in dementia research: The opinions and arguments of clinical researchers − an empirical study

Abstract

In order to discover an effective treatment for dementia it is necessary to include dementia patients in clinical research trials. Dementia patients face an increased risk to lose the capacity to consent to research participation, and research possibilities with incompetent participants are legally strictly limited. One solution is for patients to consent to research through an advance research directive (ARD) whilst still competent. In order to explore whether such a directive would be useful and valuable in practice we conducted a qualitative study (13 interviews). We explored the opinions and arguments of researchers in the field of dementia, aiming to map the possibilities and constraints of ARDs. It was argued that a positive ARD could be valuable to discuss research participation with proxies, and patients with a negative ARD will be excluded from research trials. However, it is argued that an ARD cannot replace the informed consent procedure, and in practice proxy dissent will overrule written consent. The practical use of these directives is thus limited, as most researchers will not comply with positive directives.

Introduction

With the increase of the ageing population, it is expected that the number of patients with dementia will also increase in the future (Alzheimer Europe, 2009; Corrada et al., 2010). In order to discover an effective treatment for dementia it is necessary to include dementia patients in clinical research trials. However, while it is of great importance that these patients are involved in research, it is also important that their participation is based upon appropriate consent regimes. In medical ethics, informed consent is often described as the way to respect the patient’s autonomy and to prevent abuse (Beauchamp and Childress, 2009; Manson and O’Neill, 2007). Informed consent is valid if the participant is competent to take this decision autonomously. Patients with dementia face an increased risk of losing the capacities to consent to research participation (Berghmans, 1998; Rosenstein and Miller, 2008), and research with incapacitated adults is restricted by most legal guidelines ¹ (Convention of Oviedo, 1997; ICH GCP, 1996; WMA Declaration of Helsinki, 2008).

The group of patients with dementia was, at an earlier stage of their life, able to give their consent to participation in research. Therefore we wondered whether it would be an option to obtain their consent in the phase when they are still competent. If potential research subjects draw up an advance research directive (ARD) this would allow dementia patients to control decisions about research participation after they have lost the capacities to provide informed consent. In an ARD they could describe the circumstances under which they would be willing to participate in research, and to which research goals they would be willing to contribute. The importance of previously expressed wishes is recognized in two European guidelines. According to the additional protocol of the Convention of Oviedo (1997), previously expressed wishes or objections have to be respected, and the European Union Clinical Trials Directive 2001/20/EC (2001) states that the specific protective rules for clinical trials with incompetent adults do not apply if consent is given in advance. ARDs have been discussed as a possible solution (Berghmans, 1998; Dewing, 2008; Muthappan et al., 2005; Pierce, 2010). However, it is not only important to investigate ARDs from a legal and ethical perspective, but it is necessary to understand how ARDs contribute to the practical problems of doing research with incompetent elderly.

Only limited empirical studies are available on the actual use of advance directives in the context of research. Most available data focus on the use of advance directives in the care setting, as advance directives were introduced historically to influence future care decisions (Bond and Lowton, 2011; De Boer et al., 2012; Steward et al., 2011; Van Oorschot and Simon, 2006). Even though both physicians and proxies usually have positive attitudes towards advance care directives, they are seldom complied with and appear to only marginally influence the decision-making process (Bond and Lowton, 2011; De Boer et al., 2012). The patient’s perspective is eventually not the most important factor in medical decision-making in the case of incompetent patients, but the medical judgment of the physician and the opinion of the proxies are decisive. Some empirical studies have shown that elderly people are willing to allow leeway to their proxies, as a way of deliberated authorization, to overrule their earlier choices once they are incompetent (Karlawish et al., 2002, 2008; Stocking et al, 2006; Wendler et al., 2002). The research context, however, differs from care settings. Some studies have described the positive attitudes of elderly people towards including incapacitated elderly in research trials (Karlawish et al., 2002, 2009; Seymour et al., 2004; Wendler et al., 2002). Consent procedures with dementia patients in daily research practice and the expected practical problems of ARDs deserve to be explored. Until we better understand how researchers look upon the use of ARDs, we cannot be sure that these directives can compensate for the lack of subject consent.

In the present work, we investigated how researchers doing clinical research into dementia look upon the introduction of ARDs, what arguments they use to support their attitudes and in particular whether they are willing to comply with such directives. The attitudes and opinions of the researchers are of interest in themselves. However, we are particularly interested in the reasons for their opinions, to identify which ethical arguments are important to them and how these are interpreted. In summary, we focus on the ethical aspects of researchers’ judgments and the practical implications of the introduction of advance directives in dementia research.

Methodology

Participants

Thirteen researchers known for doing research into dementia were interviewed. The participants were neurologists, gerontologists, nursing home physicians, psychiatrists and a psychologist. The first interview was a small group interview of 2 hours’ duration with three participants, in order to explore the main themes in the debate and to investigate how much of the arguments and opinions were shared. The group interview was facilitated by one of the authors (SV) with the other (KJ) present for note-taking and input; particular care was taken to include every participant in the discussion. All ten other interviews were conducted individually (KJ). All interviews were conducted in Dutch and the topic of the study was briefly introduced before the start of the interview. The interviewees were asked to share their experiences in the field of dementia research and to give their opinion freely. Under Dutch law, ethical review is not required for this type of research.

Interviews

The main topics of the interviews were the current research practice, focusing specifically on the informed consent requirement and proxy decision-making, and on the interviewee’s attitude toward the introduction of advance directives in the research context. The interviews were semi-structured, to maintain the focus on the narrations while allowing space for topics relevant to the various research questions (Wengraf, 2001). All interviews were tape-recorded and transcribed verbatim. During the interview, field notes were made and were reflected on with the recorded interview immediately afterwards. Major ideas, concepts, or issues raised by participants were documented.

Analysis

A list of ethical themes and practical implications of ARDs raised in the first group interview was discussed between the authors before conducting the other interviews. The interview process was iterative; any new themes that emerged in an interview were incorporated into the schedule for the subsequent interview(s). The interviews were carried out until consistent themes started to emerge and saturation was achieved; the interviews were stopped when no new themes emerged and there was repetition of previously identified themes. A thematic analysis was undertaken using a contestant comparative method: data were systematically reviewed for supportive/conflicting evidence for emergent themes and coded, and themes and subthemes were generated from the data set. A sample of three interviews was discussed between the authors to ensure agreement about the codes. Quotations have been translated from Dutch by KJ.

Results

In this section we describe our empirical data. First we will focus on the current research practice and discuss the importance of informed consent, and the use and difficulties of proxy consent, which gives us insight into dementia patients as a research population and problems in research practice, after which we will describe the attitudes and opinions of researchers towards ARDs in this group.

Process of informed consent

The interviewed researchers agreed that informed consent is valuable and important, not merely as a moral and legal requirement for research, but also for its practical benefits − a well-considered decision to participate in research results in better compliance in treatment studies and with less drop-out, they argued. Informed consent is, however, already problematic in the early phases of dementia. Patients tend to turn their heads to their carers when asked to make decisions; one interviewee called this the ‘head-turning-syndrome’. Dementia patients typically lean on their carers for taking decisions, including in the research setting: ‘[…] due to his disease, the patient will not take the lead and will not take a strong position. He leans just really on the partner. He will at first look at the partner and if the partner says no, the patient will follow him.’

Even though all underlined the importance of informed consent, hardly any researcher tests whether the participant still understands his participation in research after the onset of the study. Some mentioned they explain the specific procedure or measurement, but the researchers do not verify whether the patient still understands the scope of the research and is still willing to contribute to the research goal. Most interviewees assumed that patients who no longer agree to the research goals, or who simply do not want to participate anymore, drop out of the study or object to measurements: ‘We ask assent for the specific procedure, but not for the whole goal of the research anymore. […] mostly, people do not show up anymore, or appointments are cancelled. The dropout is substantial.’

Necessity and difficulties of proxy consent

It was argued that carers have several roles in the research process. Usually double consent is asked (both informed consent and additional consent of a carer), to ensure continuous (proxy) consent during research if the patient becomes incompetent. The assistance and consent of carers is also necessary for practical reasons such as planning and logistics to the hospital, since these patients are unable to find their own way or to keep their own appointments. It was mentioned that carers also have an important role in motivating participants, who owing to the nature of their disease often lack self-motivation.

Most interviewees argued that proxy consent is more complicated than informed consent. Several reasons were given. Proxy consent involves not only the physician and the patient, but also the proxy as a third person. While some researchers considered incompetent patients able to assent to research participation, others questioned the researchers’ integrity in consent procedures with incompetent participants. It was mentioned that the patient’s decisions are easily influenced by both carers and researchers; raising questions of integrity. ‘The autonomy of the patients decreases rapidly. Making it hard for the researcher to do it [inclusion] integer, because he also wants to include patients in his trial.’ Also, concerns about the patients’ best interests were raised in the context of delegated consent. It was argued to be doubtful whether proxies always take care of the patients’ interests, because some allow for too much and others for too little research with the patient: ‘You suppose the proxy does what is best for the patient.’ Most interviewees agreed that it is important to take decisions that could possibly benefit the patient, but that these were also in the spirit of what the patient would have wanted: ‘Well, I believe that not everyone takes it into careful consideration. What you hope for is a well-considered weighing whether it benefits or harms the patient.’

Advance directives

Several critical remarks were made about the value of ARDs. Some of these remarks are also applicable to the use of advance directives in the care setting. Most mentioned that an advance directive is only practically useful if the researcher can understand and interpret the conditions described. Another general remark about advance directives was that preferences are unstable and the preferences of incompetent dementia patients could have changed over time. The researchers argued that it is uncertain whether the advance directive still represents what the patient wants, once he is incompetent. Some argued that a written directive is nothing but a snapshot of preferences of when the participant was competent, but is not necessarily what the patient still holds valuable: ‘During the disease process the brain and the patient change, they are not the same anymore. For me it is unsure whether the patient still has the same preferences.’

The value of advance research directives

Most argued that ARDs are useful, because they capture the intentions of competent patients and can help proxies in their decision-making: ‘It [ARDs] could help us if we want to conduct studies with incompetent participants. It is a relevant source of information. But preferably there is a person who can weight the participants’ interests.’ Most agreed that a negative directive (not willing to participate in any research) would be easy to follow and would be respected by researchers. A positive advance directive (willingness to participate) could help the physician to bring up the topic of research participation to proxies. There are, however, practical constraints for respecting positive directives. Some argued that a generic consent would not allow for much research in practice, because consent requires the patient to weight his interests against a specific trial, and consent is only valid and valuable when the patient is well informed at the onset of the study. Most of the interviewees agreed that consent is too complex to be given in advance: ‘It [informed consent] is a dynamic process. It is impossible to write it down on paper.’

An advance directive is considered useful in the dialogue with proxies, but most agreed that a written directive cannot replace informed consent: ‘It is an indication, it helps. It helps the person who has to make the decisions and that could be interesting. But the status [of an ARD] is debatable.’

Objection and preferences

The complexity of delegated decision-making goes beyond consent procedures, and becomes problematic when patients included in a research trial object to procedures necessary for the research. All but one agreed that a patient who objects should be dismissed from the research trial, regardless of whether the objection is caused by a lack of understanding or because of the experience of discomfort: ‘If someone has written in a directive − when I become demented I am willing to participate in research − and the person objects to the research procedures, we will always stop. I do not see the surplus value [of an ARD].’ The majority agreed upon the necessity to be watchful for objections of the patient and be careful to monitor the amount of discomfort once the incompetent patient is included in research: ‘Irrespective of what someone said or whether one wrote a bunch of books about it 20 years ago, you cannot say: You chose this. For research it is not possible. For example an epidural, if you see the needle coming and you think, no I do not want this, you must be able to object.’ Suffering or objection was argued to overrule the advance directive. The possibility of changing preferences makes advance directives different from wills. Dementia patients still have preferences and show objections, because they can experience pain and discomfort, while dead people obviously cannot.

Willingness to follow advance research directives

Most interviewed researchers agreed that advance directives are a relevant source of information, but are not a substitute for informed consent. None of them was willing to follow a positive ARD without additional consent: ‘If some says when he is competent: If I get this disease and become incompetent, I find it important to contribute and you may put me in a trial. I find it preferable that a proxy gets saying to weight it in terms of risks and burden. I mean, you cannot just do anything if someone has consented, someone still has to weight it here and now.’ Proxy consent is considered absolutely necessary; proxies need to be informed about the actual research in the actual situation to take care of the patients’ interests: ‘I do not think many researchers will overrule the family, because of a piece of paper you have. It is thus much more complicated.’

Discussion

This current study adds to the literature in several ways. First, we have focused on the use of advance directives in the research context, in which pitfalls and difficulties differ from those in the care setting. This study builds on other findings (Karlawish et al., 2007, 2009; Wendler et al., 2002) that found that elderly people are willing to allow leeway to their proxies to overrule their decisions. Finally, this study adds to literature by describing the use of ARDs according to researchers and describes the practical value such directives might have. There are limitations to this study: this is a qualitative study with Dutch researchers, and researchers from different geographical locations or with different policies may provide different viewpoints. Also, in order to have a broader view of arguments and opinions about the use of advance research directives, both proxies and patient opinions about the use of ARDs should be researched.

To sum up, we have found that clinical researchers doing research in dementia value the informed consent prerequisite, proxy consent is highly valued and ARDs cannot substitute for informed consent. Some concerns regarding advance directives also are valid concerns regarding the use of advance directives in other areas. Because of the difficulties interpreting these directives and uncertainties whether the written preferences are still applicable to the incompetent patient, who often noticeably changes due to the disease, researchers do not value ARDs very highly. The main concern of researchers with ARDs is that dementia patients change their mind about participation after they become incompetent. The epistemological difficulty that we cannot know what an incompetent person with dementia truly wants, is a topic that is also recognized in the philosophical debate. It is, however, a concern that is also relevant to the current research practice. Consent for research is not repeated or tested after the commencement of the study (Butterworth, 2005; Dewing, 2008; Warner and Nomani, 2008), while participants suffering from dementia could also change their mind and face an increased risk of becoming incompetent after inclusion in the study.

Proxies play a role in taking care of the patients’ interests when patients become incompetent and their opinion is highly valued by the clinical researchers. Proxy consent is, according to the clinical researchers, complicated, because it is a delegated consent and it is doubtful whether proxies can take the best decision for an incompetent patient. However, proxy objections overrule a positive advance research directive in practice, meaning that research cannot be done without proxy consent. The third-person perspective of proxy consent is conceptually different from a first-person perspective of informed consent. We find it therefore questionable whether proxy consent is also morally the best solution to consent issues with incompetent elderly, but the interviewees seemed to accept proxy consent as a pragmatic solution.

The concerns mentioned about researchers’ integrity, the influence of carers on participation decisions and the patients’ dependence on both carers and researchers reflect the vulnerability of this population. Several researchers stressed the need to be sensitive to patient objection, but we find it questionable whether objecting should be the only vote patients have in the research process. We argue there is also a need for careful procedures to ensure valid consent. Informed consent aims both at the self-rule of participants and at protecting participants from abuse. An advance directive is an instrument that allows for self-rule after losing competence, and captures precedent autonomy (Berghmans, 1998); however it does not protect research participants against harm and does not make up for their vulnerability. The interviewees stressed the vulnerability of this population, and seem to be more concerned about protection and objections against research than with concepts such as authorization and autonomous choice. This focus on protection is sometimes referred to as ‘gate-keeping’ (Atkinson, 2007). The clinical researchers did not value the advance directive as a compensation for the lack of a patient’s autonomous consent. Negative advance directives will be respected, but a positive directive is considered valuable merely as a discussion paper of intentions, while the authorization power stays with the proxies. The control that such directives offer patients is thus limited.

We recognize the concerns about the vulnerability of this population, but from a moral point of view we argue there should be more attention for the (precedent) autonomy of these patients. We feel it is a lost opportunity that these patients have only little to say in future research decisions. Many other decisions can be made for the future self, and we think that, especially for research-decisions, autonomous decision-making is an important cornerstone.

Conclusions

This study shows that researchers in the field of dementia understand advance directives to be a source of information to make research participation a topic of discussion with proxies. Furthermore, researchers would respect negative ARDs. Positive ARDs are not seen as a substitute for informed consent, but are recognized to have practical value to provide ground for taking decisions according to what the patient would have wanted. ARDs are argued to capture the intentions and attitudes of the patient towards research at the moment the patient was still competent. Most researchers agreed that consent should always be tested at the actual moment of inclusion in research − at the moment the research procedure starts. If either the patient or the proxy does not agree (any more) with the advance directive, the patient should not be included in research. Proxy consent is valued more highly than an advance directive, because it can be given for specific research in the knowledge of specific information. Advance directives are, according to the clinical researchers, not stand-alone solutions to the consent problems with incompetent demented elderly.