Ethical analysis of vulnerabilities in cluster randomized trials involving people living with dementia in long-term care homes

Abstract

Cluster randomized trials (CRT) of non-pharmacological interventions are an important means of improving the quality of care and quality of life of people living with dementia (PLWD) in long-term care (LTC) homes. PLWD in LTC homes are, however, vulnerable in manifold ways. Therefore, researchers require guidance to ensure that the rights and welfare of PLWD are protected in the course of this valuable research. In this article, we introduce a framework for identifying vulnerabilities in randomized trials and apply it to three CRTs involving PLWD in LTC homes. CRTs may render PLWD in LTC homes vulnerable to three autonomy wrongs: inadequately informed consent, inadequately voluntary consent, and invasions of privacy; two welfare wrongs: risks of therapeutic procedure exceed potential benefits, and excessive risk of non-therapeutic procedures; and one justice wrong: unjust impact of research activities on care. We then discuss appropriate, feasible additional protections that can be implemented to mitigate vulnerability while preserving the scientific validity of the CRT. Corresponding additional protections that can be feasibly implemented include capacity assessments, substitute decision-makers, assent, insulation from LTC home employees during the consent process, patient advocates, utilizing LTC home employees for data collection, stakeholder engagement, additional supervision during study procedures, using caregivers to complete questionnaires by proxy, and gatekeeper permission. Reassuringly, many of these additional protections promote, rather than imperil, the scientific validity of these trials.

INTRODUCTION

Dementia is a debilitating disease characterized by progressive deterioration of cognitive and functional abilities.¹ In the later stages of dementia, many people living with dementia (PLWD) move into long-term care (LTC) homes to receive needed assistance with activities of daily living such as medication management, feeding, dressing, and toileting.² Care in LTC homes is often provided by busy, underpaid staff with limited specialized training in dementia management.³ Thus, the quality of care and quality of life for PLWD in this setting can be suboptimal.^4–6

Recognizing the shortcomings in extant care, cluster randomized trials (CRT) evaluating non-pharmacological interventions that aim to improve the quality of life and care received by PLWD in LTC homes have been identified as a research priority.⁴ In CRTs, intact social groups (e.g., entire LTC homes), rather than discrete individuals, are randomized to each intervention arm.⁷ CRTs are advantageous because they can evaluate a range of interventions that target participants at multiple levels in the setting wherein the interventions will be used. These levels may include (1) entire clusters—for example, an investigator might change and evaluate physical layouts of LTC homes,⁸ (2) healthcare professionals— an investigator might implement and assess training programs to help staff manage agitation in LTC homes,⁹ or (3) individual cluster members—an investigator might vaccinate all residents in a LTC home with one influenza vaccine and then compare outcomes of different vaccines across LTC homes.¹⁰ Cluster randomization allows these types of interventions to be evaluated without contamination; in some cases, it may also enhance compliance to the intervention. Developing and evaluating such interventions could greatly improve the evidence-base for care provided to PLWD in LTC homes.

However, CRTs, and especially CRTs involving PLWD in LTC homes, are ethically complex. International guidance documents and national research ethics regulations identify both PLWD and LTC home residents as potentially vulnerable.¹¹ Due to the presence of cognitive and physical impairments and the strictures of institutionalization, these individuals may be dependent on others and have limited ability to self-determine. While it is widely accepted that vulnerable participants are entitled to additional research protections, it may be difficult for researchers to understand in how this population’s vulnerabilities manifest in CRTs and how to devise corresponding protections while also maintaining the scientific validity of the trial.

The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials is the first internationally recognized guidance document on the ethical design and conduct of CRTs.¹² It provides 15 recommendations across seven domains of ethical issues, including “protecting vulnerable participants” (Table 1). The Ottawa Statement provides several examples of vulnerabilities that may arise in CRTs and proposes potential corresponding additional protections. It fails, however, to provide researchers with a framework to think through the range of vulnerabilities that may arise in their trials. Without such a framework, some vulnerabilities will likely be missed. Further, the Ottawa Statement does not provide specific guidance for CRTs in PLWD or LTC home residents. With the increasing popularity of CRTs to improve the quality of life and care received by PLWD in LTC homes, specific guidance for this setting is required.

Table 1.

Recommendations for Protecting Vulnerable Participants from the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials

ETHICAL ISSUE	RECOMMENDATIONS
Justifying the cluster randomized design	1	Researchers should provide a clear rationale for the use of the cluster randomized design and adopt the statistical methods appropriate for this design.
Research ethics committee review	2	Researchers must submit a CRT involving human research participants for approval by a research ethics committee before commencing.
Identifying research participants	3	Researchers should clearly identify the research participants in CRTs. A research participant can be identified as an individual whose interests may be affected as a result of study interventions or data collection procedures, that is, an individual (1) who is the intended recipient of an experimental (or control) intervention; or (2) who is the direct target of an experimental (or control) manipulation of his/her environment; or (3) with whom an investigator interacts for the purpose of collecting data about that individual; or (4) about whom an investigator obtains identifiable private information for the purpose of collecting data about that individual. Unless one or more of these criteria is met, an individual is not a research participant.
Obtaining informed consent	4	Researchers must obtain informed consent from human research participants in a CRT, unless a waiver of consent is granted by a research ethics committee under specific circumstances.
	5	When participants’ informed consent is required, but recruitment of participants is not possible before randomization of clusters, researchers must seek participants’ consent for trial enrollment as soon as possible after cluster randomization—that is, as soon as the potential participant has been identified, but before the participant has undergone any study interventions or data collection procedures.
	6	A REC may approve a waiver or alteration of consent requirements when (1) the research is not feasible without a waiver or alteration of consent, and (2) the study interventions and data collection procedures pose no more than minimal risk.
	7	Researchers must obtain informed consent from professionals or other service providers who are research participants unless conditions for a waiver or alteration of consent are met.
Gatekeepers	8	Gatekeepers should not provide proxy consent on behalf of individuals in their cluster.
	9	When a CRT may substantially affect cluster or organizational interests, and a gatekeeper possesses the legitimate authority to make decisions on the cluster or organization’s behalf, the researcher should obtain the gatekeeper’s permission to enroll the cluster or organization in the trial. Such permission does not replace the need for the informed consent of research participants.
	10	When CRT interventions may substantially affect cluster interests, researchers should seek to protect cluster interests through cluster consultation to inform study design, conduct, and reporting. Where relevant, gatekeepers can often facilitate such a consultation.
Assessing benefits and harms	11	The researcher must ensure that the study intervention is adequately justified. The benefits and harms of the study intervention must be consistent with competent practice in the field of study relevant to the CRT.
	12	Researchers must adequately justify the choice of the control condition. When the control arm is usual practice or no treatment, individuals in the control arm must not be deprived of effective care or programs to which they would have access, were there no trial.
	13	Researchers must ensure that data collection procedures are adequately justified. The risks of data collection procedures must (1) be minimized consistent with sound design and (2) stand in reasonable relation to the knowledge to be gained.
Protecting vulnerable participants	14	Clusters may contain vulnerable participants. In these circumstances, researchers and RECs must consider whether participants additional protections are needed.
	15	When individual informed consent is required and there are individuals who may be less able to choose participation freely because of their position in a cluster or organizational hierarchy, RECs should pay special attention to recruitment, privacy, and consent procedures for those participants.

In this article, we aim to address this gap in the literature, thereby helping researchers and research ethics committees conduct this socially valuable research while safeguarding participants’ rights and welfare. First, we briefly introduce a framework to identify vulnerabilities in randomized trials, including but not limited to CRTs. Next, we apply the framework to three CRTs involving PLWD in LTC homes (Table 2), noting vulnerabilities as well as corresponding additional protections that researchers did and might implement without imperiling scientific validity.

Table 2.

Three example CRTs involving PLWD in LTC homes

Example 1: Managing Agitation and Raising Quality of Life (MARQUE) Trial18 Aim: Evaluate the effectiveness of the MARQUE intervention: training to teach healthcare professionals in LTC homes strategies to manage agitation. Design: Parallel arm CRT involving 20 LTC homes in England. Intervention: Developed with involvement from healthcare professionals, patients, and community representatives. LTC home staff were trained about the etiology and management of agitation and were given feedback on performance. Data collection: Cohen-Mansfield Agitation Inventory and the Neuropsychiatric Inventory at baseline and at 8 months post-training. Proxy-rated quality of life of each PLWD by interviewing a healthcare professional or a family caregiver. Results: No reduction in agitation or improvement in quality of life. Consent procedures: Researchers obtained informed consent for participation from healthcare professionals. Researchers assessed the decision-making capacity of PLWD using the Mental Capacity Act 2005 criteria and obtained informed consent for participation from PLWD with capacity. For PLWD who lacked capacity, researchers obtained surrogate consent for trial participation from a family caregiver or professional consultee. Gatekeeper permission to enrol each LTC home was obtained from the LTC home manager.

Example 2: Elastic Trial19 Aim: Evaluate the effectiveness of the Wheelchair-using Senior Elastic Band (WSEB) intervention: group exercise sessions designed for wheelchair-using PLWD in LTC homes. Design: Parallel arm CRT involving 8 LTC homes in Southern Taiwan. Intervention: WSEB group exercise sessions involving aerobic and resistance training were led by instructors who regularly volunteered in each LTC home and took place thrice weekly for 6 months. Additional instructors were present during exercise sessions to monitor PLWD for physical discomfort. Data collection: Researchers performed physical assessments, measuring activities of daily living, flexibility, joint range of motion, cardiopulmonary function, and muscle strength and endurance. Results: Significant improvement in functional fitness and performance of activities of daily living. Consent procedures: Researchers obtained assent for participation from PLWD and surrogate consent for participation from their family caregivers. Researchers did not report conducting capacity assessments.

Example 3: Bath trial20 Aim: Evaluate the effectiveness of the Bathing Without a Battle (BWAB) intervention: training to teach healthcare professionals in LTC homes noncoercive, individualised, person-centered bathing techniques to make bathing PLWD safe and comfortable. Design: Stepped wedge CRT involving 6 LTC homes in New York State, USA. Intervention: Healthcare professionals were taught to (1) effectively communicate with PLWD, (2) understand behavioural symptoms as an expression of unmet needs, (3) respect the preferences of PLWD, and (4) ensure the physical environment is safe. Data collection: Researchers directly observed each bath and documented physical and verbal aggressive behaviour exhibited by PLWD. Use of antipsychotic medication on bath days was collected from medical records. Results: Significant reduction in agitation during baths and anti-psychotic use on bath days. Consent procedures: LTC home administrators sought informed consent for participation from healthcare professionals. LTC home administrators sought informed consent for participation from either PLWD or their family caregiver. Researchers reported conducting capacity assessments but did not state how capacity was assessed.

VULNERABILITY FRAMEWORK

Vulnerability may be defined as “an identifiably increased likelihood of incurring additional or greater wrongs”.^13,14 To identify vulnerabilities, we must first understand the ways in which a researcher can wrong a participant.

One way to understand a wrong is a failure to discharge a duty. The Belmont Report established the ethical principles of respect for persons, beneficence, and justice.¹⁵ Respectively, these principles ground researchers’ duties to (1) respect the privacy of participants and seek informed consent either from participants or, if they lack capacity, seek informed consent from a surrogate decision-maker and assent from participants; (2) promote the welfare of participants by minimizing risks and ensuring that the risks and potential benefits stand in reasonable relation to each other, and (3) ensure that the burdens and benefits of research are fairly distributed.^15,16 Failing to discharge a duty derived from these principles wrongs participants.

Thus, we propose the following classification of wrongs: autonomy wrongs (e.g., obtaining inadequate consent), welfare wrongs (e.g., exposing participants to undue risk of harm), and justice wrongs (e.g., unjustified exclusion from a trial). Vulnerability can, therefore, fruitfully be thought of as an increased likelihood of incurring autonomy, welfare, or justice wrongs.

APPLICATION OF VULNERABILITY FRAMEWORK

To illustrate the application of the vulnerability framework, we applied our framework to 24 CRTs involving PLWD in LTC homes. These CRTs were identified using a previously published systematic review of 62 pragmatic trials involving PLWD generally (i.e., not only in LTC homes).¹⁷ From the 24 CRTs involving PLWD in LTC homes, we selected three representative trials—the MARQUE trial,¹⁸ the Elastic trial,¹⁹ and the Bath trial²⁰—which capture the full range of vulnerabilities and are summarized in Table 2. In this section, we apply the vulnerability framework to the MARQUE, Elastic, and Bath trials and then use the results to identify protections that correspond to participants’ vulnerabilities. Table 3 offers a summary.

Table 3.

Summary of vulnerabilities and additional protections illustrated in the example studies.

Principle	Wrong	Example	Additional protection
Respect for persons	Inadequate understanding in informed consent	Informed consent is sought from PLWD who lack decision-making capacity	Formal capacity assessments Surrogate consent from substitute decision-makers (e.g., family caregivers or government-affiliated agents) Participant assent
	Inadequate voluntariness in informed consent	PLWD feel as though they must participate in research when approached by LTC staff	Employ researchers with no affiliation to the LTC home to seek informed consent Patient advocates to ensure that prospective research participants understand that participation is voluntary
	Invasion of privacy	Direct observation of PLWD by research personnel during baths	Utilize well-trained LTC home staff as research partners for data collection Stakeholder engagement (e.g., LTC home staff, management, residents, and family caregivers)
Beneficence	Risks of therapeutic procedures are high compared to potential benefits	Physically frail individual in a trial of a group exercise intervention	Additional supervision during exercise sessions
	Risks of non-therapeutic procedures are not minimized consistent with sound scientific design	Distress while filling out questionnaire for data collection	Researcher supervision during data collection Family caregivers or familiar LTC home staff to complete questionnaire by proxy
Justice	Unjust impact on care	Non-participant exposure to research procedures	Gatekeeper permission from LTC home administrators

We note that some of these vulnerabilities discussed herein are not specific to PLWD in LTC homes because they result from the presence of dementia rather than from residence in an institution. Other vulnerabilities may be present for all LTC homes residents, whether they have dementia or not. Nevertheless, our goal here is to highlight the multiple, intersecting vulnerabilities of PLWD in LTC homes.

Vulnerability to autonomy wrongs

PLWD in LTC homes are vulnerable to at least three autonomy wrongs: inadequate comprehension in the informed consent process, inadequate voluntariness in the informed consent process, and invasions of privacy. We consider each in turn.

Inadequate comprehension

Vulnerability.

The principle of respect for persons requires that participants, to degree they are able, have an opportunity to choose what happens to them. This is realized through the process of informed consent. Consent is generally understood to require provision of information, comprehension of that information, and a voluntary choice. It is widely recognized that, as dementia progresses, it may render PLWD vulnerable to inadequately informed consent because they can no longer comprehend information provided to them or otherwise make their choice known.

Protections.

When researchers have reason to believe that a prospective participant lacks decision-making capacity, they typically have a duty to conduct a capacity assessment.¹³ Capacity assessments are an important additional protection in trials involving PLWD because, despite their diagnosis, many PLWD retain capacity to consent to trial participation.^21,22 Of the three representative trials, only the MARQUE trial incorporated formal capacity assessments (Mental Capacity Act 2005 criteria).

A variety of capacity assessment tools are available. They vary in the domains of capacity assessed, administration time (ranging from 5–45 minutes), and format (e.g., questionnaire or interview).^23,24 Decision-making capacity is context and decision dependent and consists of four related domains: (1) understanding relevant information, (2) appreciating the situation and its consequences, (3) manipulating information rationally, and (4) communicating a choice.²⁵ Systematic reviews have identified the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) as the best available capacity assessment tool for clinical research.^23,24 It is a semi-structured interview that evaluates all four domains of capacity as they apply to research, has the most empirical evidence to support its validity, and has been validated for use with older adults.²³ However, the MacCAT-CR requires special training and takes 15–30 minutes to administer.^23,24 The time and resources required to implement the MacCAT-CR may (1) contribute to selection bias and decrease the generalizability of the results by dissuading a subset of PLWD from participating in the trial and (2) deter researchers from conducting large trials in this setting. To avoid this tension, a brief standardized screening questionnaire that focuses on the prospective participants’ understanding of the consent form can be used in lieu of the formal. Palmer and colleagues found that asking three questions: (1) “What is the purpose of the study?” (2) “What are the risks?” and (3) “What are the benefits?” is a sensitive means of identifying PLWD who lack capacity on the MacCAT-CR.²⁶

There may be circumstances in which capacity assessment is not needed. First, some CRTs in LTC homes include only PLWD who have lost the capacity to provide informed consent. For example, the Educational Video to Improve Nursing home Care in End-stage dementia (EVINCE) trial evaluated a decision support intervention that aimed to help substitute decision-makers create advance directives for PLWD whose dementia had progressed such that they could not recognise their family members or speak more than five words.²⁷ In this case, blanket use of surrogate consent without a capacity assessment was appropriate because PLWD at this stage of disease progression can be reasonably assumed to lack decision-making capacity.

Second, many CRTs in PLWD in LTC homes are conducted under a waiver of informed consent for research. To qualify for such a waiver, trials must meet regulatory criteria intended to protect participants even in the absence of consent. For example, in the United States, these criteria include both that the study must be minimal risk, and that the waiver must not adversely affect the rights and welfare of the subjects.²⁸ Notably, satisfaction of these regulatory criteria should be understood to reflect the needs of PLWD in LTC homes.²⁹

There may also be trials in which a less rigorous capacity assessment is sufficient. If a trial is designed such that the research procedures are similar to routine medical practice, researchers may permissibly omit capacity assessments and seek informed consent from whomever makes medical decisions for the PLWD. For example, the High-Dose Influenza Vaccine in Nursing Homes trial evaluated two different licensed influenza vaccine and exclusively collected data from electronic medical records.¹⁰ Deciding whether to participate in this trial is very similar to deciding whether to receive the influenza vaccine in usual care. Because decision-making capacity is dependent on the kind of decision at hand, it would be appropriate to omit the formal capacity assessment and rely on patient records of clinical decision-making capacity to determine whether consent to participate in the trial should be sought from the PLWD or her substitute decision-maker.

Generally, only once the prospective participant is determined to lack decision-making capacity should consent be obtained from a surrogate. There is often a family member or friend who is familiar with the prior expressed preferences of the PLWD. These individuals are well-situated to act as substitute decision makers. However, some PLWD lack family members or friends who are familiar with their wishes. For these prospective participations, a government-affiliated, legally appointed substitute decision-maker (e.g., Australia’s Guardianship Tribunal) may be appropriate.⁸ Surrogate consent was obtained from family members or friends in all three exemplar trials; in the MARQUE trial, if no family member or friend was available, surrogate consent was obtained from a healthcare professional familiar with the participant. Ideally, surrogate consent is obtained in combination with the prospective participant’s assent. Assent serves many of the functions of informed consent, but is sought from patients who lack full decision-making capacity.^30,31 Participant assent was reported only in the Elastic trial.

Inadequate voluntariness

Vulnerability.

As noted above, consent requires voluntariness. Prospective participants in LTC homes may be vulnerable to inadequately voluntary consent because they live in an institutional setting and are dependent on LTC home staff.³² This dependency may erode self-determination by (1) reducing the freedom to decide when and how to complete activities of daily living, (2) accustoming residents to comply with the decisions of authorities, and (3) creating “fear that necessary services or attention will be withheld if [participation] in research is denied”.³³

Protections.

The role of the person seeking informed consent is a key consideration to mitigate this vulnerability. Researchers may adopt various approaches. In the Bath trial, LTC home administrators sought consent for trial participation, whereas in the MARQUE trial and the Elastic trial, researchers sought consent for trial participation. Agrawal argues that the latter is more protective: “The task in overcoming institutional threats is to devise a consent process that will sufficiently insulate the patient from the hierarchical system”.³⁴ He proposes that an independent party, who is not affiliated with the institution (in this case, the LTC home), should ask prospective participants for consent for trial participation.³⁶ Having an independent party may help distinguish research activities from care activities in the LTC home, thereby mitigating the perception that refusal to participate will negatively affect care. In addition to addressing voluntariness, this ethical protection may promote scientific validity, as the independent researcher may be less familiar with the characteristics of prospective participants, thus protecting against selective recruitment or other subjective bias in the recruitment process.³⁵ This is especially important when participant recruitment occurs after clusters have already been randomized, as is often the case in CRTs.³⁵

In some cases, further insulation may be required. An independent patient advocate who is neither a researcher nor a LTC home staff member could be appointed to supervise the informed consent process and to ensure the PLWD understands research participation is voluntary. Patient advocates may be required in studies of interventions that target the behavior of healthcare professionals in the LTC home, such as the MARQUE trial and the Bath trial; knowing that healthcare professionals are participating in a trial may cause residents to feel added pressure to consent to participation. Patient advocates may also be required in studies that pose more than minimal risk to participants, as the consequences of providing involuntary consent could be more severe given the heightened risks and burdens.

Invasions of privacy

Vulnerability.

Independent of research, residents in LTC homes have limited privacy because a substantial portion of the daily activities for which residents require assistance take place in residents’ bedrooms and bathrooms—conventionally private spaces. Conducting research in participants’ homes may render them vulnerable to invasions of privacy. For instance, in the Bath trial, researchers collected data by directly observing participants while they were being bathed by staff members. Kelman argues that “[i]nvasions of privacy occur to the extent that participants are unable to determine what information about themselves they will disclose and how that information will be disseminated”.³⁶

Protections.

There is broad agreement that the norms that govern privacy vary according to the setting and social context.^36–38 Stakeholder engagement may help researchers gain insight into the privacy norms in LTC homes, so that trials can be designed in ways that reduce the risk of privacy wrongs. Further, stakeholder engagement is widely viewed as an effective means of increasing external validity by ensuring that the trial design is compatible with the study intervention’s setting of intended use.^39,40 Relevant stakeholders include residents, family members, patient care attendants, nurses, physicians, LTC home administrators, LTC ombudsman (representatives of LTC residents and their families who report complaints), and community advocacy groups.²⁹

The particularities of the intervention and of the data collection methods may heighten vulnerability concerns. For example, being observed in the bath raises concerns about encroachment on personal space and deprivation of control over self-presentation. One way to mitigate this vulnerability is to limit the presence of researchers in LTC homes. Instead of having a researcher collect data by direct observation, LTC home staff could be trained to observe resident behaviour while they provide care to residents. For example, in the Bath trial, researchers could have trained LTC home staff to quantify agitated behaviour while they bathed PLWD. Alternatively, research staff could be trained to perform a targeted aspect of care and simultaneously collect data while performing the task. For instance, in a trial of a multicomponent intervention to address incontinence, research staff toileted LTC home residents and simultaneously checked garments for incontinence.⁴¹ When staff are engaged in data collection, there may be other practical considerations to address, such as training and research protections. If neither option is feasible, the degree of the invasion of privacy wrong could be decreased by having a researcher assess resident behaviour from a remove, such as by listening to the interaction without seeing the resident. Stakeholders may help identify—and find ways to remediate—privacy concerns.

Vulnerability to welfare wrongs

As dementia progresses, PLWD are more likely to develop behavioural and psychological symptoms, such as agitation and aggression.⁴² PLWD also often have co-morbid physical illnesses, such as strokes, chronic obstructive pulmonary disease, and osteoporosis that put them at increased risk of falls and physical injury that could, in turn, increase their dependency on caregivers for activities of daily living.⁴³ Study procedures that intersect with these factors may render PLWD in LTC homes vulnerable to welfare wrongs.

Risks of therapeutic procedure exceed potential benefits

Vulnerability.

If the risks of a therapeutic intervention outweigh the potential benefits, participants incur a welfare wrong.⁴⁴ In trials involving PLWD, study interventions that pose risk of physical or psychological harm may render PLWD with corresponding symptoms and co-morbidities vulnerable to this welfare wrong.

Protections.

Additional supervision during trials of physical activity interventions, akin to what was implemented in the Elastic trial, is an appropriate additional protection to mitigate the risks of the intervention and thereby ensure that the risks of study participation stand in reasonable relation to the potential benefits. Additional supervision may be provided by LTC home staff or volunteers. Standardized protocols to assess for expressions of pain, fatigue, or aberrant vital signs can be implemented in trials of physical activity interventions. When such supervision is provided, it may increase the generalizability of trial results by making it possible for residents who would otherwise be unable to participate due to physical limitations or fear of harm to be eligible for the trial.

In trials of behavioural interventions, such as the Bath trial and the MARQUE trial, PLWD with behavioural symptoms may be vulnerable to psychological harm or distress. Procedures to monitor for severe agitation and aggression, and protocols to terminate the intervention if indicated, are well-suited to mitigating this vulnerability. If a PLWD does not tolerate the intervention, they should be excluded. Gatekeepers, such as LTC home administrators who know the residents well, may be able to help researchers identify potential participants who are unlikely to tolerate study procedures. Procedures should also be delivered in dementia-friendly ways—for instance, allowing a PLWD’s caregiver to be present, if their presence is comforting. Additionally, it is often advisable to establish a Data Safety Monitoring Board or other independent oversight mechanism, such as a designated Safety Officer, to monitor the safety of participants.

Excessive risks of non-therapeutic procedures

Vulnerability.

If the risks of a non-therapeutic procedure are not minimized consistent with sound scientific design, participants incur a welfare wrong.⁴⁴ Data collection procedures that pose risks that intersect with the symptoms of dementia and co-morbidities may render PLWD vulnerable to this welfare wrong.

Protections.

Patient interviews and questionnaires, akin to those used in the MARQUE trial, may render PLWD with behavioural symptoms vulnerable because complex cognitive tasks can precipitate agitation in PLWD.⁴⁵ In the MARQUE trial, researchers addressed this vulnerability by involving family members or familiar LTC home staff to fill out questionnaires on behalf of PLWD prone to agitation. This additional protection is appropriate because it mitigates the risk of data collection procedures. Despite some evidence to suggest that family members tend to underestimate the quality of life of PLWD relative to what the PLWD self-reports,⁴⁶ this additional protection is a scientifically appropriate means of collecting data about PLWD outcomes because family members are often most familiar with their health. Further, it allows researchers to investigate clinically relevant, patient-centered outcomes (e.g., quality of life) that might otherwise be inaccessible in PLWD who cannot self-report.

Vulnerability to justice wrongs

If researchers do not fairly distribute the burdens and benefits of research, they inflict justice wrongs on participants. The example trials demonstrate that CRTs in LTC homes may render residents vulnerable to unjust exposure to the burdens of research.

Unjust exposure to burdens of research

Vulnerability.

People who are institutionalized should not be enrolled in research simply because it is convenient to do so. Additionally, LTC home residents who are not participants may be vulnerable to unconsented exposure to the burdens of research—especially in LTC homes that have shared bedrooms and living spaces. Typically, when a prospective participant is ineligible for a trial, or is eligible and declines participation, her care is not impacted by the trial. However, in some CRTs in LTC homes, including those in which the study intervention involves training healthcare professionals, the intervention may spillover to and affect residents who are deemed ineligible or decline participation—for example, by changing how they are cared for.

Protections.

Several parties associated with LTC homes may act as gatekeepers, including LTC home administrators, medical directors, social workers, and Resident and Family Council representatives. These gatekeepers are well-situated to ensure residents are participating because there is valuable knowledge to be gained that is relevant to them. Additionally, gatekeepers can provide additional protection for non-participants within LTC homes. Outside of the research context, these gatekeepers have authority over the organisational interests of LTC homes, including ensuring the proper functioning of the LTC home, and promoting the safety and privacy of LTC home workers and residents.⁴⁷ In the research context, these gatekeepers may legitimately use this authority to ensure that research activities do not compromise the care provided to all LTC home residents, including those who are not enrolled in the trial. In the MARQUE trial, researchers obtained gatekeeper permission for cluster participation from senior administrators in LTC homes.

CONCLUSION

CRTs promise to improve the quality of care and quality of life for PLWD in LTC homes. Yet, determining how to safeguard these vulnerable participants’ rights and welfare in CRTs is especially challenging. Using the proposed framework, researchers and research ethics committees can identify and address vulnerabilities to autonomy, welfare, and justice wrongs arising in these trials. Reassuringly, these additional protections are consistent with and can even promote, rather than imperil, scientific validity. This article will inform a forthcoming extension of the Ottawa Statement that aims to address ethical challenges in CRTs in LTC homes.

Impact Statement:

We certify that this work is novel. It provides researchers and research ethics committees with a novel approach to identifying vulnerabilities in cluster randomized trials involving people living with dementia, including those in long-term care homes, and provides feasible strategies to mitigate vulnerability while preserving—and, in some cases, promoting—scientific validity.

KEY POINTS.

• Conducting cluster randomized trials in long-term care homes may render people living with dementia vulnerable to autonomy wrongs, welfare wrongs, and justice wrongs.

• It is feasible to implement additional protections to mitigate vulnerability while preserving, and even promoting, a trial’s scientific validity.

Why does it matter?

Cluster randomized trials of non-pharmacological interventions that aim to improve quality of life and quality of care for people living with dementia in long-term care homes are becoming increasingly common. A systematic approach to identify and mitigate vulnerabilities that arise in these trials will help researchers safeguard the rights and welfare of people living with dementia while conducting this socially valuable research.