A realist review of advance care planning for people with multiple sclerosis and their families.

BACKGROUND: Advance care planning (ACP) is reported to improve the quality of outcomes of care among those with life-limiting conditions. However, uptake is low among people living with multiple sclerosis (MS) and little is known about why or how people with MS engage in this process of decision-making. AIMS: To develop and refine an initial theory on engagement in ACP for people with MS and to identify ways to improve its uptake for those who desire it.
METHODS: Realist review following published protocol and reporting following Realist and Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) guidelines. A multi-disciplinary team searched MEDLINE, PsychInfo, CINAHL, Scopus, Web of Science, Embase, Google Scholar in addition to other sources from inception to August 2019. Quantitative or qualitative studies, case reports, and opinion or discussion articles related to ACP and/or end of life discussions in the context of MS were included, as well as one article on physical disability and one on motor neuron disease, that contributed important contextual information. Researchers independently screened abstracts and extracted data from full-text articles. Using abductive and retroductive analysis, each article was examined for evidence to support or refute 'context, mechanism, and outcome' (CMO) hypotheses, using the Integrated Behaviour Model to guide theory development. Quality was assessed according to methodological rigour and relevance of evidence. Those studies providing rich descriptions were synthesised using a realist matrix to identify commonalities across CMO configurations.
RESULTS: Of the 4,034 articles identified, 33 articles were included in the synthesis that supported six CMO hypotheses that identified contexts and mechanisms underpinning engagement in ACP for people with MS and included: acceptance of their situation, prior experiences, confidence, empowerment, fear (of being a burden, of death and of dying) and the desire for autonomy. Acceptance of self as a person with a life-limiting illness was imperative as it enabled people with MS to see ACP as pertinent to them. We identified the context of MS-its long, uncertain disease trajectory with periods of stability punctuated by crisis-inhibited triggering of mechanisms. Similarly, the absence of skills and confidence in advanced communication skills among health professionals prevented possibilities for ACP discussions taking place.
CONCLUSION: Although mechanisms are inhibited by the context of MS, health professionals can facilitate greater uptake of ACP among those people with MS who want it by developing their skills in communication, building trusting relationships, sharing accurate prognostic information and sensitively discussing death and dying.

Introduction

People with multiple sclerosis (MS) face an uncertain future. While some have little disability others can have profound physical and psychological limitations [1]. Approximately 40–70% of people with MS develop cognitive impairment throughout their illness experience, some severe [1-6]. Consequently, people with MS may have reduced decision-making ability, impairing their everyday functioning [7] that may limit their ability to plan for future circumstances.

Advance care planning (ACP) has been defined as a “process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences regarding future care” [8] and evolved from the advance directive movement for individuals to maintain control and plan their future care in the event of physical or mental incapacity [9]. Whilst advance directives consist of written directions, often within narrow and clearly marked boundaries (such as a Do Not Attempt Resuscitation [DNAR] order), ACP is broader in scope, linked to benefits for patients, health providers, and health systems [10]. The scope of ACP is appealing as it embodies a person and family-centred, holistic approach to facilitate decision-making. Importantly, ACP is not a one-time exercise but is a heterogeneous process of multiple discussions involving different actors across many care settings.

There is a growing interest among people with MS who want to talk about their future with health professionals [1, 11]. However, despite expressed concerns about end of life discussions and choices [12], few people with MS engage in these important conversations [13-15]. Findings from a 2016 study indicated that amongst neurology patients, people with MS are the least likely to be referred to palliative care services and the most likely to die in hospital [13]. Reasons for this are complex; for example, van Vliet et al. suggest that the nature of the relationship between people with MS and neurologists may be important, as well as the association between palliative care and end of life, which speaks to the uncertainty inherent in MS. This clinical uncertainty is due to the unpredictable trajectory of MS, which includes periods of stability punctuated by crisis, and makes it challenging to identify people with MS who are approaching a point where mental capacity is compromised and/or where life may be limited [16-20]. Moreover, health professionals often fail to initiate these discussions, possibly due to their reluctance to discuss disease progression and death and their difficulty managing their own emotions during difficult conversations [21, 22]. Whereas ACP is well-researched in other patient groups [23-25], it has not been widely examined in relation to people with MS.

Additionally, while Lin et al. [26] developed a conceptual model of ACP in cancer patients, no theoretical understanding of the contexts or circumstances in which ACP is relevant to people with MS is yet available. Two questions warrant answers when examining ACP for people with MS: (i) “in what circumstances, with whom, how, and why do people with MS (and their families) engage in ACP?” and (ii) “what works for whom, how, and why, during ACP discussions?” This realist synthesis therefore aims to: identify core mechanisms generating engagement in and completion of ACP by people with MS (and their families); identify contextual factors that trigger (or inhibit) core mechanisms, and contribute to the theoretical understanding of the process of ACP in people with MS.

Methods

The United Kingdom Medical Research Council’s (MRC) guidance on development and evaluation of complex interventions [27] and the Methods of Researching End-of-life Care (MORECare) statement [28] stress that new health care-related interventions are likely to be most effective when they are underpinned by a conceptual framework and a theoretical understanding of the key processes involved in delivering interventions and the contexts in which they are required to operate. This realist review specifically addresses the requirement for theory and conceptual framework development and was developed in April 2019 and published in PROSPERO (registration number: CRD42019142294 https://tinyurl.com/ttdt963). We used a process adapted from the RAMESES publication standards [29] and adhered to Pawson’s realist methodology [30]. The review drew upon the Integrated Behaviour Model (IBM) to guide theory development. Realist reviews are a theory-driven systematic approach that are particularly suited to helping understand causation; they aim to investigate what works (or fails to work) for whom, in what circumstances, and how, by identifying processes (mechanisms) that lead to desired outcomes in particular contexts [30, 31]. Furthermore, they examine how mechanisms or ‘underlying causal forces or powers’ are triggered in particular contexts and lead to outcomes [29]. This specifically relies on using ‘context-mechanism-output’ configurations (CMOs); these represent testable hypotheses that explain the ways in which the context is able to trigger mechanisms and lead to a variety of outcomes [31] (Table 1 for glossary of terms).

Table 1

Glossary of realist terms used in the review.

Term	Explanation
Context	Pre-existing structures, settings, environments, circumstances or conditions that shape whether certain behavioural and emotional responses (for example mechanisms) are subsequently triggered.
Context-mechanism-outcome configurations (CMOs)	Describe the causal relationships between contexts, mechanisms and outcomes, that is, how certain outcomes are realised through mechanisms that are triggered in certain circumstances and contexts.
Mechanisms	The behaviour or emotional response that is triggered in certain contexts. The mechanism is context-specific and is usually hidden.
Outcomes	The final impact of mechanisms that are triggered in certain contexts.

Adapted from Mitchell et al. [71] and Papoutsi et al. [92].

The phases involved in conducting this realist review involved: (i) determining the scope of the review; (ii) formulating or articulating the key theory (iii) searching for key studies; (iv) selecting the studies and appraising their relevance; (v) extracting, analysing and then synthesising the data.

Scope of the review

We clarified the scope of the review by engaging with key informants (clinical experts in neurology, palliative care and rehabilitation from different professional groups including nursing, medicine, physiotherapy and occupational therapy) and members of our study Patient and Public Involvement (PPI) group (people living with MS and their families). This process is recommended for realist syntheses as it can help to shape the direction of the review by articulating themes and ideas relevant to ACP in MS [29, 32, 33]. During informal interviews, we asked key informants to identify salient contextual factors that encourage or discourage ACP discussions that included, but were not limited to, age of onset, symptoms, and salient concepts such as uncertainty or transitions. Interviews were not recorded, however, notes were taken during these meetings which helped to form the basis of our initial search strategy. PPI members identified the desire to discuss ACP with their health care provider but felt discouraged due to lack of information about their disease trajectory as well as time pressures at medical appointments. Health care providers identified uncertainty in the disease trajectory, an unwillingness to discuss death and dying with MS patients, and a presumption that patients did not want to discuss ACP or that ACP was not important to MS patients. Both the health care providers and PPI informants expressed confusion about how to initiate ACP discussions.

Based on the information received from key informants, we then conducted a scoping exercise to identify strategies that promote successful ACP in people with MS and other illness contexts that may share similar characteristics. We discovered a small body of literature on ACP within MS and. From these sources of evidence we gained a broad understanding of ACP to focus the review and develop key theories to underpin our main literature search.

Articulation of key theories

A distinguishing feature of a realist review is the recognition of theoretical drivers for the intervention (ACP), which are scrutinized using evidence from the review. These drivers are the expectations and justifications for why an intervention might work. We developed our initial programme theory through ‘creative thinking sessions’ involving the key informant consultations, the scoping exercise results, and the use of substantive theory (the Integrated Behaviour Model (IBM), based on Azjen’s Theory of Planned Behaviour [34, 35]). This substantive theory helped us to understand how people with MS and health professionals make decisions about ACP by explaining that behaviour changes are linked to underlying beliefs about the behaviour itself, associated outcomes, and an individual’s ability to perform the behaviour. Motivation represents a key driver for behaviour change and is comprised of three elements: attitudes, perceived norms, and personal agency [36] which are influenced by context. We used the ‘context-mechanism-outcome’ (CMO) heuristic to explore various configurations that led to the development six CMO hypotheses that reflected our initial programme theory (refer to Table 2).

Table 2

‘Context-mechanism-outcome’ hypotheses.

	Context	Mechanism	Outcome
1.	If people with MS experience losses	then they will accept that MS is life-limiting and will come to see themselves as a person with a life-limiting illness	and they will be more likely to engage in ACP
2.	If people with MS have a trusting and empathic relationship with their healthcare provider	then they will feel empowered
3.	If people with MS feel they are a burden to family members	then they will look for ways to reduce their family member’s future decisional conflict,
4.	If people with MS want to establish control over their future,	then they will come to understand ACP as a tool for autonomy
5.	If health care professionals have the communication skills to engage in open, frank, and timely discussions	then this would inspire the confidence to discuss death and dying	which would facilitate ACP engagement and completion.
6.	If people with MS have witnessed ‘bad deaths’, then they will fear dying	and will perceive ACP as a way to prevent a ‘bad death’	thus, will be more likely to engage in ACP.

Search methods

Literature searches were conducted from inception to 12 August 2019, in MEDLINE, PsychInfo, CINAHL, Scopus, Web of Science, and Embase databases, using terms presented in Table 3. In keeping with realist methodology, our literature search process was multi-pronged and iterative [29, 33].

Table 3

Search strategy for MEDLINE, PsychInfo, CINAHL, Scopus, Web of Science, and Embase.

Term 1	Term 2
Advance care planning	Multiple sclerosis
Advance* care plan*	MS
Advance directives	Neuro-degenerative diseases
Advance* directive*	Disability
Living will
Decision making
Goal setting
Future
Decision support techniques
Treatment planning
End of life conversation*
End of life decision making
End of life planning
Palliative care
Palliative care conversation*
Attitude to death
Future

Additional search strategies included citation tracking on MEDLINE to identify related papers and the citations within identified papers for relevance and additional reference chaining. We also searched grey literature on the following United Kingdom websites: Multiple Sclerosis (MS) Trust, Multiple Sclerosis (MS) Society, National Health Service (NHS), Google and OpenGrey.

Screening methods and inclusion criteria

Articles were screened for eligibility by two researchers (LC and GE) and selected based on predetermined eligibility criteria (Table 4) for their relevance to theory building and our research question [29, 37]. We revisited our criteria throughout the review process and amended them based on iterative literature searches and preliminary data extraction.

Table 4

Inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
1. Source focused on advance care planning (including end of life conversations, end of life decision making, palliative care conversations)	1. Source focused on completion of advance directives or DNAR orders or on shared decision-making models
	2. Source focused on the following patient groups:
2. Source focused on the following patient groups:
	• cancer patients
	• living with chronic non-neurological illness
• Patients living with multiple sclerosis
	• patients living with intellectual/learning disability
• Patients living with a significant physical disability
	3. Source not written in English or French
3. Source types
• All study designs and other forms of academic and grey literature, including literature reviews, editorials, and guidelines related to advance care planning
4. Source is written in English or French
During the screening we applied the following criteria: “Does this data source provide any evidence, discussion, or conceptual/theoretical perspectives that will enable us to test and refine our understanding of engagement in advance care planning for People with MS”?

Data extraction

To promote consistency, we (LC, GE and JK) developed a bespoke data extraction form and extracted information related to the six CMO hypotheses and information about contexts, mechanisms and outputs to promote consistency in the data extracted. Two researchers (LC and GE) then independently extracted data from all selected papers.

Appraisal of included literature

We supported Pawson and Tilley’s (1997) decision to reject the ‘hierarchy of evidence’ [38] approach to quality appraisal and adopted a system to ensure rigour according to the following principles: (i) faithfulness or correspondence with the programme theories; (ii) trustworthiness or fidelity: the evidence reported was reliable; and; (iii) relevance or application of data to the research aims. The relevance of each document was scrutinized in detail in terms of its ability to contribute to our CMO’s, as well as its credibility or the extent to which its data supported its findings and their clinical utility and applicability [29, 38]. Additionally, for the qualitative studies we used established appraisal techniques [39], an approach used in other realist reviews [40], that enabled us to examine to what extent studies presented ‘thick’ or ‘thin’ accounts of the intervention’s components and their respective contexts and mechanisms.

Data analysis and synthesis

The data analysis and synthesis processes were flexible, iterative, and creative. To maintain transparency, LC, GE and JK kept notes from a series of meetings during which they discussed each article and its contribution to the CMOs. Moving between theory and data we used retroduction to explore, compare, and explain observable patterns in the data, seeking their essential conditions, while looking for and exploring non-observable data not captured by our initial programme theories (CMOs). We used abductive reasoning for the non-observable data to create associations and to recontextualise the data, creating new plausible conclusions [29, 41]. For both processes, researchers (LC, GE, and JK) discussed potential explanations, new findings, and strategies to refine and revise our CMOs. We used flipcharts to outline each CMO and its supporting data, while evaluating its relevance to our findings. Relevant key informants were apprised of our preliminary findings and provided feedback. We then mapped our findings to a schematic of the IBM to synthesise our theoretical understanding of ACP. We retained the notes, flip charts, and schematic as an audit trail of decisions made. The final synthesis is an interpretive yet robust collation of the supporting evidence we located for each of our CMOs. To promote transparency, the data are presented in the findings section as direct quotations from the supporting literature [31].

Results

Study selection

Our searches yielded 4,034 articles. After removing duplicates, two researchers (LC and GE) scanned titles and/or abstracts for relevance, excluding 3,897 articles. They independently read full texts and excluded a further 64 articles resulting in 42 articles. Based on reviewer’s comments, GE and LC scrutinised the included literature and excluded a further nine articles on neurological diseases other than MS, which did not add new data to our CMOs. This resulted in 33 final articles for inclusion in the review. The data screening processes is depicted in Fig 1.

Fig 1

Modified PRISMA flow chart of literature search.

Study characteristics

Of the 33 articles, 17 focused on MS exclusively [20, 42–57] seven on MS in combination with chronic neurologic or non-neurologic illness [17, 58–63]; one on MND [64] seven on neurological illness (non-specified) [18, 19, 65–69], and one on disability [70]. Nineteen were qualitative or quantitative studies [20, 42–44, 46, 47, 49, 50, 54–56, 59, 61–64, 67, 68, 70]; one was a mixed methods study [19]; and 13 were case studies, literature reviews or discussion/opinion articles [17, 18, 45, 48, 51–53, 57, 58, 60, 65, 66, 69] of which seven were opinion or expert panel-based articles [17, 18, 48, 51, 53, 58, 66] three were case-studies [45, 57, 65] and three were literature reviews (narrative/systematic) [52, 60, 69] [refer to S1 File for study characteristics].

The source articles reflect an international scope; two had an international authorship [51, 60], seven from USA [43, 44, 46, 48, 66, 68, 70], seven from UK [17, 18, 52, 56–58, 65] seven from Canada [20, 49, 50, 55, 59, 62, 67], four from Germany [16, 47, 54, 63], two from the Netherlands [61, 69], one from Australia [64], Italy [53], Peru [19] and Turkey [45].

Substantially supported CMO hypotheses

CMO 1: Cumulative losses lead to acceptance of MS as a progressive condition and the creation of a new self-identity where ACP is relevant

For many people with MS this was identified as an important mechanism in both the pre-engagement and engagement phases associated with ACP. By experiencing clinically significant and person-centred losses, including physical functions, roles, paid employment and, in some cases losing touch with friends, people with MS underwent a transition. This markedly disrupted their biography and concept of self to increasingly include MS as more part of their identity. Consequently, they began to see their futures as progressively uncertain and ACP as more relevant to them. This new awareness led to an increased willingness to engage in ACP. This CMO was supported by ten studies; [20, 46–49, 53, 56, 62, 64, 67]. Lowden et al. [20] explored the process of “coming to a redefined self” (p.e17) in nine participants with relapsing-remitting MS. They discovered coming to accept themselves as a person with MS involved “one’s sense of self-being called into question” (p.e21) associated with multiple losses, particularly previous roles. This redefinition of self was integral to decision-making since participants were not prepared to consider making treatment decisions until this transition occurred [20].

Similarly, Paterson et al. [62] observed that decisions about the future were emotionally charged and “implied submitting to the progression of the disease rather than accommodating a temporary setback” (p. 67), a view shared by Lustig et al. [46] that adjustment to loss was vital in people with MS. Murray et al. [64] go further to suggest “ACP was easier for patients and caregivers who accepted encroaching death” (p.473) but was also present at other stages of the disease, albeit to a lesser extent.

Acceptance as the mechanism that underpins optimal timing for ACP discussions can be challenging due, in part, to MS’s uncertain trajectory and people with MS often being overwhelmed by the complexities of treatment initiation, balancing treatment side-effects and the need to learn and re-learn how to live with a progressive disease. Despite this, two articles recommended initiating discussions about ACP as early as possible, even at the point of diagnosis [60, 65], citing as justification future impaired communication or cognitive abilities. However, the most common recommendation to initiate discussions was after people with MS experienced key triggers indicating clinically significant disease progression [20, 49, 53, 57, 58]. Lowden suggests the rationale for this is that: “Participants felt ill-equipped to make treatment decisions early in the disease trajectory (p.e19). Those participants who had not yet reached the point of considering MS as part of their identity were therefore unwilling to receive information, education or decision support (p. e22)” [20]. Similarly, Leclerc-Loiselle and Legault described timing in the context of loss and acceptance: “Professionals all considered the adaptation period of people with MS to their new functional reality following an MS crisis was a pivotal moment to introduce a palliative approach. The moment right after an MS exacerbation was a turning point because there has usually been a reflexive process as a result of grieving the loss of previous functional abilities” [49] (p.267). This reflexive process of acceptance represents the mechanism that underpins potential optimal timing of ACP engagement in discussions in people with MS. Though none of the included studies discussed a definitive time frame, they did suggest that acceptance is a gradual process [20, 62].

CMO 2: Trusting and empathic relationships enable empowerment

Building trust centred on active and reflective listening and validating patient’s concerns and fears are foundational to engagement in ACP. Evidence from 10 studies substantiated this CMO hypothesis [20, 42, 44, 49, 50, 52, 55, 59, 63, 70]. A relationship grounded on trust and empathy was essential when engaging in ACP discussions. This provided a safe space empowering people with MS to share fears and hopes for the future. For example, Thorne et al. [55] noted “although actual communication practices were important, the orientation of the health care providers to the person with MS was even more fundamental” (p.11). This orientation “was centred on respect and trust and involved validation of the patient’s experience” [p.17]. Some people with MS may approach the health professional-patient relationship with suspicion, based on the inherent complexity and length of the MS diagnostic process, during which they may have spent years feeling undermined and unheard by their health provider [50, 71].

Driedger et al. go further, emphasising the importance of trust and empathy in the relationship between people with MS and their neurologist, remarking “the crucial aspect … was not solely what was being said, but also how one was saying it” (p.10) [50]. Additionally, “empathy, respect, and a willingness to acknowledge the perspectives of people with MS” [50] were critical to ACP’s success. Likewise, Col et al. [44] reported that “physicians can encourage or obstruct patient involvement. Patients are more active when interacting with physicians who engage in partnership building and supportive talk that legitimises the patient’s perspective and creates expectations and opportunities for the patient to discuss their needs and concerns” (p.266). Buecken et al. [42] noted that “physician empathy plays a key role” (p.323) in meeting end of life care-related discussions and is paramount in delivering high-quality care. Furthermore, the study observed trust in a patients’ health professional was imperative in initiating shared decision when considering current and future treatment decisions. Mitchell [70] remarked: “a trusting relationship with healthcare providers was a prerequisite to ACP discussions” (p.130).

CMO 3: Fear of being a burden to family motivates engagement in ACP

Six studies supported this CMO [20, 43, 65, 66, 69, 70]. The presence of family was important to both the people with MS and the health professional(s). People with MS relied on and welcomed the support and caregiving provided by family, but occasionally their need for caregiving only increased negative thoughts of being a burden [43, 64, 70]. Some people with MS considered ACP a way to alleviate feeling like a burden. Murray et al. observed, “many participants indicated that documented wishes would reduce the decisional burden and help caregivers avoid regret” (p. 475) [64]. Similarly, participants in Mitchell’s study reported that future planning “constituted a personal responsibility to their family members” (p.128) and “expressed concerns about financial and emotional burdens their families may experience” (p.131) [70]. Caregivers in Murray’s (2016) (p.475) [64] study also described ACP as a “catalyst for communication” to realise open family discussions and ease tension in family negotiations.

For health professionals, family were viewed as invaluable resources whose intimate knowledge of dependants had potential to help initiate timely ACP discussions. Similarly, Seeber stated “involving families in the discussion appears to improve acceptance of decisions for both patient and caregiver” (p.596) [69].

CMO 4: ACP as a tool for enabling control and autonomy in decision-making

Ten studies supported this CMO hypothesis [17, 18, 48, 56, 57, 61, 65, 67, 70, 72], which is the basis underpinning the original development of concept of ACP. Kalb explained: “people living with MS struggle to maintain a feeling of control in the face of an unpredictable disease course and uncertain future. Effective planning and problem-solving […] help people feel prepared—more in control—regardless of what the future holds” (p.532) [48]. Clarke et al. also acknowledged “some participants used advance planning as a way of extending the zone of personal autonomy and involvement in decision-making beyond the stage when their ability to make decisions or communicate their wishes would be lost” (p.6) [56]. Mitchell reported participants felt engaging in ACP “constituted a responsibility to themselves […] and represented asserting agency over [their] care” (p.129) [70]. Family members in Murray et al.’s study similarly reported that ACP “gave (them) control of life” (p.474) [64]

CMO 5: Skilled communication inspires confidence and facilitates ACP discussion

Confidence and communication skills were important mechanisms to facilitate ACP completion, reported in 16 source articles [18, 19, 42, 44, 45, 50, 51, 55, 58, 59, 60, 64, 67–70]. Strong evidence supported an inverse relationship between poor communication skills and the absence of ACP discussions. A participant with MS in Thorne et al.’s study stated: “communication with health care providers can shape the entire course of an illness” (p.10) [55]. Similarly, Driedger and colleagues reported, “how things are said are as important as what is being said” (p.10) [50]. Health professional distance and paternalism were perceived as barriers to engaging in clinical decision-making processes [59]. These attitudes, enacted through behaviours such as using simplistic explanations or deliberately obfuscating with highly technical scientific jargon, were perceived as being counterproductive. As Driedger et al. discovered, “a core problem was that neurologists just generally lack a capacity for good communication and compassionate care” (p.10) [50] possibly a result of health professionals lacking clarity on the situation themselves. Thorne et al. identified withholding information was highly frustrating for people with MS: “I just get the feeling that it’s a very paternalistic sort of attitude […] ‘We don’t need to tell her that” (person with MS) (p.12) [55].

Beneficial communication included strategies that included legitimising and confirming the person with MS’s experience, considering MS in the context of that person’s life, and assisting them to find the language to describe their illness situation [55]. Col et al. observed that “physicians can encourage or obstruct patient involvement [in future care planning]” (p.266) [44]. Additionally, Oliver et al. observed: “families do appreciate honesty and awareness of deterioration” (p.36) [60].

However, we identified only limited agreement on which health professional was best placed to have ACP discussions with people with MS. Seeber [69] stated that the neurologist is “best-poised’ due to their detailed knowledge of neurologic diseases and possible complications” (p.595). Surprisingly, our findings indicate that knowledge was less valued than the ability to establish and maintain what people with MS considered to be a trusting relationship. Our recommendation is therefore that the person best positioned to have discussions with people with MS would be the one with whom they believe to have the strongest and most trusting relationship, a situation that is open to change.

CMO 6: Previous experiences of witnessing death facilitates or hinders engagement in ACP

Seven studies corroborated this CMO [20, 43, 47, 49, 56, 65, 71]. ACP was reported to mitigate the fear of experiencing a distressing or ‘bad’ death [43, 65] and may be a motivating factor for some people with MS. For example, in Chen and Habermann’s study, participants shared views that having witnessed a ‘bad death’ or having experienced a life-threatening illness in a relative acted as a “close call” (p.4) that triggered their own fear of dying and the need to address it through engaging in ACP. Former health professionals were more likely to have witnessed bad deaths, resulting in the acknowledgement that ACP may represent a way to address their concerns [20, 43]. Lowden et al. stated, “previous experiences with illness and treatment influenced participants’ decision making” (p.19) [20].

In addition to these core mechanisms, we identified two related components: the fear of discussing death and dying and the concept of hope in MS. The fear of discussing death and dying was present in four articles [20, 47, 65, 70] and may be considered to be wide-spread in post-modern Western culture [65, 73]. Related to this, the reviewed literature identified that health professionals were reluctant to initiate ACP discussions because they feared discussions would lead to the loss of hope in the person with MS [19, 20, 49, 64]. Correspondingly, some people with MS were reluctant to engage in ACP because they held out expectations of a cure for their MS [56]. As Clarke et al. observed: “Decisions about future care were deferred to a later date, sometimes in the apparent hope that eventualities that they could plan for may never arise” (p.7) [56].

Discussion

We present the first realist review to develop and refine an initial theory to explain engagement in and completion of ACP in people with MS and to guide clinical practice by uncovering in what ways ACP works. Specifically, by testing our six CMOs, we identified mechanisms underpinning the behavioural changes that drive engagement in, and completion of, ACP. They included: acceptance, experience, confidence, empowerment, fear (of being a burden; of death and dying) and the desire for autonomy. In the USA, Levi et al. [74] explored motivations that led people to engage in ACP. The authors explained that motivation to engage in ACP was contingent on four distinct domains: concern for self; concern for others; expectations about the impact of ACP and anecdotes, stories, and experiences. Their findings share similarities with this review; a number of the CMOs we developed and tested could be similarly categorised. For example, ‘concern for others’ aligns closely with our CMO about burden on family; ‘concern for self’ parallels the desire for autonomy and the fear of suffering a ‘bad death’. The influence of prior experiences on ACP motivation echoes Levi et al.’s category of ‘anecdotes, stories, and experiences’, a finding similarly identified by Shaw et al. [75] in a study of ACP in long-term care facilities. They observed “both residents and family members indicated that prior experience with […] the advance care planning process had helped in influencing current perspectives and readiness. As a result, both groups described having engaged and feeling ready to engage in the process” (p.745). However, neither Levi et al. [74] nor Shaw et al. [75] addressed the mechanisms underlying the motivations for engagement in ACP: they identified what the motivations were but did not identify why these mechanisms work or how to trigger them.

We discovered acceptance of self as a person with a life-limiting illness is the core mechanism underpinning engagement in ACP for people with MS. Acceptance facilitates people with MS to see the relevance of ACP and is a driver for subsequent behaviour change, which is the willingness to engage in ACP discussions. According to the IBM, relevance aligns with attitudes, which are a key facet of behaviour change [76]. Attitudes refer to the individual’s perception of the behaviour; in this case, acceptance of self as a person with progressive illness changes their perception of ACP from irrelevant to relevant. Relevance is critical for ACP. Although Solari et al. [14] recently reported that as many as 89% of people with severe MS want to discuss ACP, preliminary findings from a study on ACP in MS indicate that while participants were generally positive about ACP, it was no more relevant to them than to anybody, regardless of their MS diagnosis. Concerning their MS specifically, participants were reluctant to engage in ACP because of the uncertainty of their disease trajectory [15]. The differences in interest in ACP may be due to levels of disease severity, as evidence suggests the notion of ACP often becomes relevant to people with MS when disease severity increases [43, 56].

Questions still remain about how and when to make ACP relevant to those living with, and in some instances dying from the complications associated with MS. Careful and sensitive encouragement of people with MS to accept their situation will help, but we as identified, an important challenge encountered with the uptake of ACP is the actual context in which it is enacted. We initially presumed that two related contextual elements—the fear of discussing death and dying and hoping for cure—would influence consideration of ACP. However, we underestimated their importance. Indeed, both elements created contexts that were largely inhospitable to ACP and represent fundamental issues with its uptake. The mechanisms we uncovered, while important, may not sufficiently overcome these issues, but may function instead as ‘trust mechanisms’ [32]. Trust mechanisms work to influence contexts rather than influencing outcomes directly; in this case, mechanisms enable contexts to be more hospitable to notion of ACP. Trust mechanisms alter the shape of traditional CMO configurations, changing from C + M = O to C + M → C → O.

For clinical practice, work must be aimed at reshaping the context, rather than focusing strictly on outcomes associated with behaviour change or ‘completed’ ACPs. Each mechanism we identified can be leveraged to change the landscape for people with MS, to facilitate acceptance of ACP if that is their preference. For example, relationship building may open a trusting platform on which more accurate and realistic prognostic information can be shared with people with MS; this is essential to help them make sense of their illness and reframe their self-image. Recent European Academy of Neurology (EAN) guidelines for palliative care in MS include early discussion of disease progression and future planning with people with severe MS [14]. Realistic hope is also important; our findings indicate health professionals do not discuss ACP for fear of distressing people with MS. However, false hope may undermine trust, whereas honesty, empathy, and truthfulness are valued by people with MS [50].

Additional to building trusting relationships, advanced communication skills are important for health professionals, many of whom are notably uncomfortable discussing death and dying [19, 67, 68], exacerbating an already difficult conversation. Communication skills training linked to patient-centred outcomes are recommended [77]. This must be accompanied by active listening [44, 55] and the use of accessible language [50]. Andreassen et al. [78] utilised discourse analysis to explore ACP discussions, using the concept of doctor and patient voices. They discovered that health professionals used a variety of ‘voices’: the ‘doctor voice’ was used to ask specific questions; the ‘educator voice’ to share information and help patients understand their illness and treatment, and the ‘fellow human voice’ to convey empathy. Simply by showing empathy through comments for example “I understand” or “that must be really tough”, health professionals shared a ‘fellow human voice’ encouraging patients to discuss ACP.

Additionally, in an attempt to develop a measurement tool for ACP, several author groups mentioned “prerequisites” [79, 80]. These prerequisites, such as personality factors, cognitive style, coping style, role preferences, risk knowledge, numeracy, risk attribution and tolerance, should also be recognized by healthcare professionals as they are part of the patient’s personal context and might influence the communication pathways to be engaged in this communication relationship.

Overall, this realist synthesis uses a theory-testing method to explore, below the surface, what helps or hinders ACP from taking place and to understand how contextual barriers and facilitators operate. This knowledge is critical to design evidence-informed interventions that have the greatest potential to influence underlying mechanisms that drive behaviour change in different contexts and lead to positive person and family-centred outcomes and experiences.

Strengths and limitations

A strength of this approach is both its explanatory and theoretical nature through which to understand the complex mechanisms underlying pre-engagement and engagement of ACP in people with MS. We also actively incorporated key informants’ and PPI views alongside published literature to refine the review focus to areas considered most pertinent to clinical practice and lived experiences of MS. Moreover, this style of synthesis shifts the focus from specific interventions and services to broader underlying mechanisms or principles. Additionally, our evidence included a diverse range of clinical conditions relevant to people living with MS. Thirteen of the studies were qualitative, a strength being that this permitted salient contexts, mechanisms and outcomes to be understood in detail, particularly where ‘thick’ accounts were evident. Whilst we were able to draw on a relatively wide international literature, we are aware that ACP is still a predominantly Western construct [81, 82]. Cultural homogeneity is therefore a limitation of this review. Caution must therefore be exercised when considering the findings of this review for countries where ACP has yet to be implemented.

Institutional factors are undeniably part of the context of ACP, as health care is embedded in discourses of efficiency [83], and the overriding dominance of ‘cure-over-care’ [84] in which palliative care, including ACP, can often be disregarded. Our findings do not extend across multiple levels (micro, meso, macro), but are focused principally on the individual. Since we set out to study pre-engagement and engagement phases of ACP, rather than its implementation, we believe focus on the individual is justifiable, although we recognise a multi-level exploration and analysis could provide complementary evidence [81].

Conclusions and recommendations

We have identified important mechanisms that help to explain how and why ACP works in people with MS. Additionally, based on our findings we suggest strategies to assist health professionals help people with MS to engage in a process where they are able to reframe, perhaps multiple times, their self-image, so that ACP becomes more relevant to them. This research is important, as it is evident that ACP is more than merely an administrative or intellectual task for health professionals to engage in with their patients. Instead, it is a deeply human encounter in which a person reflects on their illness, situation, on-going rehabilitation and management, and impending death and must negotiate a route through at times threatening possibilities.

Consequently, health professionals have a responsibility to train in communications skills [77] and specifically in engaging in difficult conversations [85]. Evidence suggests that people with MS prefer an active role in decision-making [86, 87], therefore health professionals must work towards empowerment through partnerships. Moreover, they must appreciate that offering patients accurate and honest information about the patient’s prognosis is unlikely to destroy their hope and may paradoxically encourage realistic future planning. Importantly, this can only be fostered if authentic relationships are built with patients and their families; creating environments in which respect, trust, and empathy thrive is fundamental to shape a context that supports engagement in ACP discussions.

Future research must now take place that that informs not only the evaluation of effectiveness of ACP among people living with MS and their families, but also actively engages in the CMOs examined in this review to better understand how this complex intervention can successfully and acceptably be enacted. The ‘gold-standard’ randomised controlled trial design alone does not adequately address the ‘context-specific drivers’ behind implementation outcomes and their relationship to the underlying theory. We therefore suggest researchers consider using a realist approach alongside more conventional designs akin to a ‘hybrid trial’ design that includes multiple methods. Realist evaluation is increasingly applied in the examination of complex healthcare interventions, for example ACP, since it seeks to provide a more in-depth understanding of what works, for whom and in what circumstances [38, 88]. Hybrid trials not only focus on assessing clinical effectiveness, but explore the manner in which an intervention is implemented [89, 90], and it has been argued should also consider context [91].

Disclaimer: The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, NIHR, the Department of Health or the MS Society.

Study/Literature characteristics.

(DOCX)

Click here for additional data file.

5 Jun 2020

PONE-D-20-09582

A realist review of advance care planning

for people with multiple sclerosis and their families

PLOS ONE

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Methods

The scope of the review section needs re-considering – if you have engaged with stakeholders evidence is needed of how and why and what the results are. You also mention a rapid literature review which is a type of review in itself – please reconsider this and what information is placed here.

Please reference your searching process so it can be checked

An audit trail is needed to show how you have progressed from data to the final synthesis. It needs to illustrate all stages – of Particular importance is integration because you have mixed methods data? Also you talk about theory being considered Pg7 how did it contribute to analysis?

Please check and identify what is the quality appraisal used for?

Results

Should the results be split by condition types? as mentioned on the end of page 10 and start of 11?

You have 26 experimental studies – but the results look like themes with no experimental data? You have four reviews not sure if it is clear how this evidence is integrated into the results?

As a style a lot of it is about presented quotes – can a justification for your style of presentation and analysis of results be made up front

I don’t see where critical appraisal findings are presented or why they are used?

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Reviewer #1: The authors present a realist review on ACP in people with MS (pwMS). The paper is well written and presents a comprehensive review of the relevant literature for MS as well as other neurological diseases and physical disability. The fact that these conditions are quite heterogeneous and pwMS are hardly comparable with e.g. people with PD, HD, ALS or even dementia or COPD limits the meaningfulness of the analyses. Even though MS might be considered a “life limiting” disease, it surely is not for all people with MS as a considerable number will not experience a limited life expectancy and most will have at least decades with the disease and die at retirement age. I can see that the authors are unable to rerun the whole analysis focussing only on the few study with pwMS, but they should give very clear justification for choosing this broad view and clearly state this as a limitation.

Apart from this major limitations, there are some further aspects that should be addressed within a possible revision.

(1) In the introduction, it is stated that few pwMS engage in discussions about their future, which needs to be proven. The cited references from other neurological diseases are not particularly helpful. The recent paper by Köpke et al. (Eur J Neurol. 2019;26(1):41-50) at least gives some indication that they do. Also the work by Solari and Giovannetti and others on progression to SPMS and palliative care needs could be interesting here. Finally the soon to be published EAN-guideline on palliative care in MS could provide some more specific and important background information. Also the background on information provision and on health care professionals’ abilities to provide information would profit from MS-specific literature e.g. from the groups of Heesen and/or Solari. Finally, as cancer more and more becomes a chronic condition, it should be made clearer why this would be expected to clearly differ from MS. Especially as in the discussion (p.21) the authors refer to people with cancer when it comes to “trust”.

(2) Under “study characteristics” it seems that the first citation should be [15] and not [13]. Also, I cannot see that there are 26 “experimental” studies. At least, I would expect a definition of “experimental” here.

(3) The results section is surely a strength of the paper and the description of the CMOs is mostly transparent and clear. At the end of CMO 5, it is stated that the person that will have ACP discussions with the pwMS should be a trustworthy person, but knowledge and skills seem less or even not important. This does not seem to fit the concept of ACP.

(4) In the second paragraph of the discussion, the authors refer to pwMS’ “subsequent behaviour change” and I am unsure what this refers to. In the same paragraph the final aspects claiming that only few people see the relevance of ACP can surely not be made with a paper more than 10 years old, considering the dynamic development concerning ACP. I like the CMO formula on p.21, but think that figure 2 should be deleted as it does not contain any further information.

(5) As stated above, under “Strengths and limitations”, the fact that “a diverse range of clinical conditions” are included should be stated as limitation as it can surely be doubted that these are “relevant to people living with MS”.

(6) In the conclusion section, I agree that pwMS should be accurately and honestly informed and there is good evidence that this does not lead to harms although frequently feared by health care professionals. Here again the work by Heesen and/or Solari seems relevant including the recently updated Cochrane review on “Information provision…”. In this context, I wonder why the concepts of “shared decision making” and “evidence-based patient information” are not addressed. Also, the point that RCTs are principally not suitable is not convincing, considering the rich discussion on the evaluation of complex intervention e.g. within the MRC framework(s) cited in the introduction.

(7) Finally, I wonder why existing ACP frameworks and interventions such as “Respecting Choices” are not discussed for pwMS.

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Reviewer #1: No

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26 Aug 2020

EDITOR – RESPONSE TO EDITOR

1. The scope of the review section needs re-considering – if you have engaged with stakeholders evidence is needed of how and why and what the results are.

Based on realist evaluation standards (Wong et al., 2016), we met with key informants (or stakeholders) to shape and re-shape CMOs, ensure their relevancy and identify similarities with other conditions that might be used to broaden our understanding of the research question, and to clarify that our preliminary findings were appropriate to both clinical experts and people living with MS. On page 7 of the revised manuscript we have provided evidence of why and how we engaged with key informants of the revised manuscript and listed the results from the informal interviews.

2. You also mention a rapid literature review which is a type of review in itself – Please reconsider this and what information is placed here.

This is an excellent point; thank you. We have changed the terminology from ‘rapid literature review’ to ‘scoping exercise’ to reflect more closely the type of search we completed at the outset of this review process (please refer to page 8 of the revised manuscript)

3. Please reference your searching process so it can be checked.

Our search process is explained in more detail on page 9 of the revised manuscript and we have included an example Medline search strategy as Appendix A, S1. It is important to note however, that unlike a typical literature search for a systematic review, literature searches for realist syntheses are multi-pronged and iterative, conducted in response to emerging data (Booth et al., 2019; Wong et al., 2016). There is not one definitive search, but a series of searches undertaken throughout the data collection and preliminary analysis processes.

4. An audit trail is needed to show how you have progressed from data to the final synthesis. It needs to illustrate all stages – of particular importance is integration because you have mixed methods data?

With respect to an audit trail, we have updated the manuscript on page 11 of the revised manuscript (in the data analysis and synthesis section) to include a description of our process.

5. Also you talk about theory being considered pg 7 how did it contribute to analysis?

The theory being considered (the Integrated Behaviour Model [IBM]) was used to aid in the development of our context-mechanism-output configurations (CMOs). Realist syntheses are driven by theory, which then helps to clarify or uncover mechanisms that are not context-bound and are, therefore, transferable between settings or contexts (Wong et al., 2016). The IBM contributed obliquely to the analysis through its use in the development of our CMOs. This is presented on page 8 of the revised manuscript.

6. Please check and identify what is the quality appraisal used for?

As stated in the Appraisal of Included Literature section (page 10 of the revised manuscript), we supported Pawson and Tilley’s (1997) realist tenet to reject the concept of ‘hierarchical evidence’ and instead to rely on an appraisal of the relevance of each article’s findings to our research question and to our developing theory (Wong et al., 2016).

7. Should the results be split by condition types? As mentioned on the end of page 10 and start of 11?

After further consideration and reviewer comments, we have eliminated nine articles on conditions other than MS, as the reviewer suggested these may be too heterogeneous or potentially too diffuse to contribute meaningfully to our analysis. We have now narrowed down the sample of papers to include those principally focused on MS. Therefore, our results are now focused more clearly on MS alone. We did, however, retain one article on motor neurone disease (Murray et al., 2016) and one on physical disability (Mitchell, 2017) (please refer to our rationale below in our reply to the first comment from Reviewer 1).

8. You have 26 experimental studies – but the results look like themes with no experimental data? You have four reviews not sure if it is clear how this evidence is integrated into the results.

We have changed the terminology (please refer to page 12 of the revised manuscript and in the supporting documents) with which we refer to our included articles, as “experimental” was indeed confusing and did not accurately describe the literature. We hope that the types of included articles are now more clearly defined with the following terms: “qualitative, quantitative, case, or mixed-methods study”, “discussion/opinion” article, and “literature review”.

Our “themes” are in fact CMOs: realist reviews do not report experimental data as such; instead, in a realist synthesis pre-defined CMOs are evaluated for their relevance to the data. CMOs differ from “themes” presented in qualitative literature, and are instead a tool based on an “If/then” statement in the following configuration: “If [context], then [mechanism], leading to or resulting in [outcome]” (Wong et al., 2016).

9. As a style a lot of it is about presented quotes – Can a justification for your style of presentation and analysis of results be made up front?

The presented quotes (in the results section) are data; for transparency, we chose to present them as examples of direct CMO-supporting data from the literature. This is an accepted practice in realist syntheses (Wong et al., 2016; Flynn et al., 2018). In the revised manuscript, we have addressed this on pages 10-11 in the data analysis and synthesis section.

10. I don’t see where critical appraisal findings are presented or why they are used?

In realist methodology, quality appraisal is based on relevance—rather than on the ‘hierarchy of evidence’ associated with more traditional systematic reviews (Pawson & Tilley, 1997; Wong et al., 2016). As stated in the quality appraisal section (now changed to the ‘Appraisal of Included Literature’ section; page 10 of the revised manuscript), we followed Pawson and Tilley’s (1997) advice and included articles if they contributed meaningfully to our CMOs.

11. In your data availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. Plos defines a study’s minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All Plos journals require that the minimal data set be made fully available. for more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability

The minimal data set used to reach the conclusion is provided as a table included in the ‘Appendix A & B, Supplementary File 1’.

REVIEWER #1 - RESPONSE TO REVIEWER #1

1. The authors present a realist review on ACP in people with MS (PwMS). The paper is well written and presents a comprehensive review of the relevant literature for MS as well as other neurological diseases and physical disability. The fact that these conditions are quite heterogenous and PwMS are hardly comparable with e.g. people with PD, HD, ALS or even dementia or COPD limits the meaningfulness of the analyses. Even though MS might be considered a “life limiting” disease, it surely is not for all people with MS as a considerable number will not experience a limited life expectancy and most will have at least decades with the disease and die at retirement age. I can see that the authors are unable to rerun the whole analysis focussing only on the few study with PwMS, but they should give very clear justification for choosing this broad view and clearly state this as a limitation.

Thank you; this is a very fair comment. We chose a realist review because it is a methodology that aims to establish causality between an outcome and events by uncovering the underlying mechanism leading from the events/context to the outcome (Wong et al., 2016). We chose this method because our ultimate aim is to develop an intervention designed to trigger this mechanism; our purpose in this synthesis was to uncover the mechanism(s).

After first focusing our search on MS, we wanted to deepen our exploration of our research question by focusing on those characteristics of MS that could contribute to the situation and constituted the “core” of our context. We were curious to know (a) what these were in people with MS, and (b) if they were unique to people with MS. To do this, we summarised our first results and consulted with our key informants who identified “uncertainty in the disease trajectory”, “uncertainty regarding future autonomy” and “uncertainty regarding acute relapses and their potential to recover” as important characteristics involved in engaging in ACP discussions for people with MS, in addition to “fear of discussing death and dying” with people with MS or “not knowing how to initiate a discussion about ACP”. Then, in collaboration with key informants, we identified that many neurological conditions and COPD share these characteristics with MS and decided to include these conditions, but only when considering the afore-mentioned characteristics. We also included physical disability, which shared many similar characteristics with and for many is a component of living with MS.

This process helped to broaden our understanding of the mechanisms that can occur in MS by relying on similarities with other conditions and is also a tenet of realist methodology (Wong et al., 2016).

However, following your comments, we re-read all included articles on other conditions and reassessed their usefulness to our review. After careful consideration, we made the decision to exclude this literature (9 source articles) from our final CMO analysis, with two exceptions. We decided to retain the study conducted by Murray et al., 2016 (motor neurone disease) because it is relevant to three CMOs and, importantly because it explores in-depth the concept of acceptance, which is salient to the context of MS. We also retained the study conducted by Mitchell et al. 2017 because many people with MS also live with physical disability.

Apart from this major limitation, there are some further aspects that should be addressed within a possible revision.

2. In the introduction, it is stated that few pwms engage in discussions about their future, which needs to be proven. The cited references from other neurological diseases are not particularly helpful. The recent paper by Kopke et al. (eur j neurol. 2019; 26(1):41-50) at least gives some indication that they do. Also the work by Solari and Giovannetti and others on progression to spms and palliative care needs could be interesting here. Finally the soon to be published EAN-guideline on palliative care in MS could provide some more specific and important background information. Also the background on information provision and on health care professionals’ abilities to provide information would profit from MS-specific literature e.g. from the groups of Heesen and/or Solari. Finally, as cancer more and more becomes a chronic condition, it should be made clearer why this would be expected to clearly differ from MS. especially as in the discussion (p. 21) the authors refer to people with cancer when it comes to “trust”

We have revised the manuscript (on pages 4-5 of the revised manuscript) by removing the references from other neurological diseases and by incorporating more recent evidence to support our discussion about PwMS’ views on discussing ACP, including the Kopke et al. (2019) paper, a 2016 study on palliative care in neurology (including MS), and preliminary findings from an in-progress study funded by the UK Multiple Sclerosis Society.

After careful consideration we have eliminated the reference to cancer patients on page 21 of the first iteration of the manuscript to focus more explicitly on patients with MS.

3. Under “study characteristics” it seems that the first citation should be [15] and not [13]. Also, I cannot see that there are 26 “experimental” studies. At least, I would expect a definition of “experimental” here.

We adjusted this section after excluding the non-MS literature and have revised the citation numbers accordingly.

We have changed our terminology throughout the entire revised manuscript to reflect a more accurate description of the included literature; “experimental” was indeed a confusing term. We hope that the types of included articles are now more clearly defined with the following terms: “qualitative, quantitative, case, or mixed-methods study”, “Discussion/opinion” article, and “literature review”.

4. The results section is surely a strength of the paper and the description of the CMOs is mostly transparent and clear. At the end of CMO5, it is stated that the person that will have ACP discussions with the PwMS should be a trustworthy person, but knowledge and skills seem less or even not important. This does not seem to fit the concept of ACP.

Thank for this comment. We agree. This does not seem to fit the concept of ACP and we too were surprised by what we found in the data. Our results suggest that people with MS would be more likely to engage in ACP discussions with someone trusted than with someone considered as knowledgeable. In the revised manuscript, we have altered the text on page 18 of the revised manuscript to reflect this.

5. In the second paragraph of the discussion, the authors refer to PwMS’ “subsequent behaviour change” and I am unsure what this refers to.

We have defined the ‘subsequent behaviour change’ as “willingness to engage in ACP discussions” in the revised manuscript on page 21 to clarify this; thank you very much for bringing this to our attention.

6. As stated above, under “strengths and limitations”, the fact that “a diverse range of clinical conditions” are included should be stated as a limitation as it can surely be doubted that these are “relevant to people living with MS”.

Agreed; we have excluded the articles (with two exceptions) that did not pertain exclusively to MS.

7. In the conclusion section, I agree that PwMS should be accurately and honestly informed and there is good evidence that this does not lead to harms although frequently feared by health care professionals. Here again the work by Heesen and/or Solari seems relevant including the recently updated Cochrane review on “information provision …”.

We have revised the manuscript on page 25 to include the work from Heesen et al. and Solari et al. on the importance of active decision-making and partnerships for PwMS

We have also revised the manuscript on page 23 to include work from Heesen et al and Sudore et al. on patient “prerequisites” that may contribute to the communication context. Thank you for bringing our attention to this important work

8. In this context, I wonder why the concepts of “shared decision making” and “evidence-based patient information” are not addressed.

Again, you bring up an interesting point, and one that we explored rigorously throughout our review process. We did not include the shared-decision making literature for two main reasons. First, our research question was based on decision making in the context of advanced care planning. The process of completing an advance care plan requires that the patient have the ability to face the future and make decisions based on the wishes of a future unknown self. Contrary to this, shared decision making usually focuses on treatment decisions, which are immediate rather than future decisions. In addition, shared decision making differs contextually from ACP, as it does not intervene at the same point in the disease trajectory. Often patients making treatment decisions are newly diagnosed, whereas ACP discussions tend to involve patients who have been living with MS for years, if not decades. Making treatment decisions for immediate care is a significantly different experience than planning for future care and, possibly, impending death. Although at many points we considered including shared decision-making literature, we decided that for these reasons, it detracted contextually too far from our research question to add salient evidence to our CMOs.

9. Also the point that RCTs are principally not suitable is not convincing, considering the rich discussion on the evaluation of complex intervention e.g. within the MRC framework(s) cited in the introduction.

In the conclusion (on pages 25-26 of the revised manuscript) we state that RCTs do not adequately address the context-specific drivers. We do not mean to imply that RCTs are not suitable, but that complementary methodologies exist for exploring complex interventions, such as ACP. We have revised the paragraph (pages 26 of the revised manuscript) to clarify this point.

10. Finally, I wonder why existing ACP frameworks and other interventions such as “Respecting Choices” are not discussed for PwMS.

Although the “Respecting Choices” intervention may have applicability for PwMS, for the purposes of this review whilst we broadly explored grey literature, we confined the evidence to support our CMOs to the MS and neurology literature. In this way we hoped to discover contextual factors and uncover mechanisms unique to this patient population.

References

Booth, A., Briscoe, S., & Wright, J.M. (2019). The ‘realist search’: A systematic scoping review of

current practice and reporting. Research Synthesis Methods. https://doi.org/10.1002/jrsm.1386.

Flynn, R., Newton, A.S., Rotter, T., Hartfield, D., Walton, S., Fiander, M., & Scott, S.D. (2018).

The sustainability of Lean in pediatric healthcare: a realist review. Systematic Reviews,

7, 137.

Pawson, R., & Tilley, N. (1997). An introduction to scientific realist evaluation. In E. Chelimsky &

W.R. Shadish. (Eds.). Evaluation for the 21st Century: A Handbook. (p. 405-418).

Sage Publications Inc. https://doi.org/10.4135/9781483348896.n29

Wong, G., Westhorp, G., Manzano, A., Greenhalgh, J., Jagosh, J., & Greenhalgh, T. (2016).

RAMESES II reporting standards for realist evaluations. BMC Medicine, 14, 96.

Submitted filename: Letter_response to reviewers 06.08.2020.docx

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1 Oct 2020

PONE-D-20-09582R1

A realist review of advance care planning for people with multiple sclerosis and their families

PLOS ONE

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(1) Although papers on other neurological diseases were excluded after the reviewers’ comments, there are still some instances that refer to these diseases (e.g. at the end of the “Scope of the review” section or the “Inclusion criteria” listed in table 3).

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1 Oct 2020

Reviewer comment - Although papers on other neurological diseases were excluded after the reviewers’ comments, there are still some instances that refer to these diseases (e.g. at the end of the “Scope of the review” section or the “Inclusion criteria” listed in table 3).

Our response - We have been through the paper thoroughly and removed mention of other neurological diseases. All these instances are now evident in the track changed manuscript.

Reviewer comment - The flow chart (figure 1) contains some errors: On the left side, the third box from above should read “Records after duplicates removed (n=4003)”, instead of “before”. In addition, the arrows pointing down on the right side should be removed (apart from the top one)

Our response - We have now corrected Figure 1 (flow chart) and also removed the arrows as suggested.

5 Oct 2020

A realist review of advance care planning for people with multiple sclerosis and their families

PONE-D-20-09582R2

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7 Oct 2020

PONE-D-20-09582R2

A realist review of advance care planning for people with multiple sclerosis and their families

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