https://orcid.org/0000-0001-9930-7579
Figures
Abstract
Background
Advance care planning (ACP) practice in people with progressive multiple sclerosis (PwPMS) remains limited. ConCure-SM project aims to assess the effectiveness of a structured ACP intervention (clinician’s training programme and use of a booklet during ACP conversations) using a multi-phased design.
Methods
Single-arm pilot/feasibility trial involving PwPMS, their significant others (SOs), and clinicians from six Italian centers. Primary study outcome was completion of an advance care plan document (ACP-Doc). Other outcomes included safety, feasibility of enrollment and assessment, and (analyzed using mixed-methods approach) Hospital Anxiety and Depression Scale (HADS), quality of communication, quality of life (MSQOL-29), and caregiver burden. Participants were interviewed to identify factors influencing the ACP implementation process.
Results
Seventy-five PwPMS were eligible out of 164 screened; 56/75 (75%) refused participation and 19 were included. Of these, 11 (58% vs 30% hypothesized) completed the ACP-Doc. A total of 25 adverse events (increase in anxiety) occurred, three possibly related to the intervention, and we found a worsening of HADS-Anxiety score (p = 0.02) and MSQOL-29 mental health composite score (p = 0.04) during follow-up. PwPMS/SO interviews revealed four themes: significance of the ACP process (on the individual, on relation with clinicians), its impact (on emotions, on family relations), preparedness as key, and challenges (practicability, SO commitment). Barriers and facilitators for ACP were identified in two clinician focus groups.
Citation: Solari A, De Panfilis L, Zagarella RM, Ghirotto L, Farinotti M, Gajofatto A, et al. (2025) Advance care planning in multiple sclerosis (ConCure-SM): A multicenter single-arm pilot and feasibility study. PLoS One 20(10): e0331220. https://doi.org/10.1371/journal.pone.0331220
Editor: Nayanatara Arun Kumar, Kasturba Medical College Mangalore, INDIA
Received: February 1, 2025; Accepted: August 11, 2025; Published: October 7, 2025
Copyright: © 2025 Solari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data underlying the findings of this study are available in the Zenodo repository at https://doi.org/10.5281/zenodo.17144481, and in the Supporting information files.
Funding: The study was supported by FISM - Fondazione Italiana Sclerosi Multipla – cod. 2020/R-Multi/024 and financed or co-financed with the ‘5 per mille’ public funding to AS. The funding source had no role in study design, data collection, data analysis, data interpretation or report writing. We also thank the Italian Ministry of Health (RRC). There was no additional external funding received for this study.
Competing interests: AL reports grants from Novartis, during the conduct of the study; personal fees from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi/Genzyme, Teva and FISM. FP received personal compensation for serving on advisory board and/or speaking activities by Almirall, Bayer, Biogen, Bristol Meyers & Squibb, Merck, Novartis Roche, Sanofi and TEVA; he further received research grants by Biogen Italy, Biogen Global, Merck, University of Catania, FISM and Reload Onlus Patients Association. AS received personal compensation for serving on advisory board and speaking activities by Almirall and Merck. All the other authors have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Introduction
Multiple sclerosis (MS) is the most common cause of progressive neurological disability in young adults [1]. Around 15% of MS sufferers have a primary progressive course at diagnosis, and a further 35% develop secondary progressive disease after 15 years [2]. People with progressive form (PwPMS) may live for many years experiencing a wide range of symptoms, impairments (including cognitive impairment) and comorbidities [3,4] and may benefit from advance care planning (ACP).
ACP is a process that “enables individuals who have decisional capacity to identify their values, to reflect upon the meanings and consequences of serious illness scenarios, to define goals and preferences for future medical treatment and care, and to discuss these with family and healthcare professionals” [5]. Consistently with the shared decision-making model [6], ACP involves both the patient and their clinician. Together, they make informed decisions about the patient’s (future) care. If the patient wishes, their significant other (SO) can also be involved. ACP differs from general medical decision-making in that it is based on an anticipated health deterioration, and includes a focus on the person’s wishes and preferences for the time when they may lose decisional capacity. The planning process helps the patient to identify their own personal values and goals, understand their health status, and the available treatment/care options. Finally, ACP encourages discussion around end of life (EOL) care – a subject that is generally not considered part of health care planning, and one that can be avoided by both patients and clinicians. The ACP process may result in the patient choosing to produce an advance care plan document (ACP-Doc) and to appoint a trustee (or else).
ConCure-SM is a project aimed to set up and evaluate the efficacy of a structured ACP intervention for PwPMS consisting of a training programme for MS clinicians and a booklet to be used during the ACP conversations. The theoretical basis of the project is the shared decision-making model [6], and its methodological basis is the Medical Research Council framework for developing and evaluating complex interventions [7]. In a previous project phase, we co-developed the ConCure-SM booklet [8] and translated-adapted two self-reported outcome measures (PROMs) not available in Italian [9]. In this pilot phase we assessed the feasibility, acceptability, and preliminary effectiveness of the intervention hypothesizing that it would support completion of an ACP-Doc, increase congruence in treatment preferences between PwPMS and their carers, and the quality of communication. The objectives of the pilot phase are reported in the Box 1.
Materials and methods
Study design and setting
Between March 8, 2022 and March 6, 2023, we conducted a multicenter single-arm explanatory sequential mixed methods pilot and feasibility trial. The study protocol was approved by the ethics committees of the coordinating center, Fondazione IRCCS Istituto Neurologico Carlo Besta (internal ref. 83/2021), and all the six enrolling centers: Verona (55917), Moncrivello (15210), Reggio Emilia (80829), Bologna (90076), Rome (921), Catania (47839). The enrolling centers are located in northern (four centers), central and southern Italy (one center each). Two centers are rehabilitation hospitals (one of which a research hospital), three are MS centers (two university hospitals, one research hospital) and one is a rehabilitation and MS center from a research hospital. The study followed the CONSORT guidance (S1 File) [10,11], and was carried out in accordance with the Good Clinical Practice principles and the Declaration of Helsinki recommendations. All participants (PwPMS, SOs, neurologists, and other clinicians) gave written informed consent.
Intervention
The goal of the intervention was to prime clinicians to discuss goals of care and ACP with PwPMS. It consisted of a clinician training programme and use of the ConCure-SM booklet [8]. The Italian Law 219/217 (Article 5) prescribes that ACP involves the patient, their referring physician, and (when applicable) the trustee. To promote ACP knowledge within the MS team, we also trained non-physician healthcare professionals. Trainers were researchers, clinicians and bioethicists experienced in leading courses and workshops on patient-clinician communication and ACP.
The training programme consisted of three components: 1) A residential, Continuing Medical Education accredited course of one-and-half days (12 hours) duration. It included: one 2.5-hour theoretical session on the clinical, ethical and statutory principles of shared decision-making and ACP; two 4-hour empirical sessions (one on each day) on conducting ACP conversations in various clinical scenarios using the ConCure-SM booklet through guided role play exercises; two 45-minute self-evaluation sessions (at the beginning and at the end of the programme). 2) Four booster sessions (teleconference) followed the residential training, each lasting 90–120 minutes. Trainees shared their experiences and discussed difficult cases, guided by two trainers. 3) One-to-one videoconference or telephone calls with trainers for issues emerging during ACP conversations.
The ConCure-SM booklet [8] consists of an introduction, a ‘guidance’, and the ACP-Doc, which the PwPMS and their referring physician must complete electronically or manually.
Assessments and participants
There was a baseline assessment, a first ACP conversation taking place within one month from baseline, and a follow-up assessment within one week of the first ACP conversation (T1) and six months thereafter (T2). The baseline and follow-up assessments were performed via a web-based trial platform [9] that contained the case report form (eCRF) and the PROMs. The physician recorded on the platform subsequent ACP conversations that occurred during follow-up.
Eligibility and screening.
Adult PwPMS were included if they were able to communicate in Italian, had one or more of seven conditions that would make ACP relevant (S1 Box), and gave written consent [9]. PwPMS were excluded if they had severe cognitive compromise (MMSE < 19), impairments preventing communication, psychosis or other serious psychiatric conditions, or if they had already completed an ACP-Doc. The PwPMS could involve their SO (family member, relative, or friend, who is next of kin or is key decision-maker as designated by the PwPMS).
Before baseline assessment, PwPMS and SOs gave signed informed consent. Then they completed the baseline questionnaires/instruments by accessing the trial platform or via a telephone call with one trained interviewer.
Each center collected information on the number of PwPMS and SOs approached, screened, and eligible prior to enrollment, with reasons for non-enrolment.
The ACP conversation.
The first ACP conversation was scheduled at the center, was intended to be one hour long, and was audio-recorded. It involved the PwPMS, the ACP-trained neurologist, and, when applicable, the SO. In addition, another ACP-trained clinician participated, if the PwPMS agreed. Subsequent conversations were documented/noted in the eCRF.
Outcome measures.
A range of measures were collected to capture the full process of ACP and whether the ConCure-SM intervention had any effect on completion of an ACP-Doc (primary outcome measure), quality of patient-clinician communication, and caregiver burden. In addition, as a study-related increase in emotional burden could not be excluded, serious adverse events (SAE: admission to psychiatric ward, suicide attempt, death) were monitored by an independent Data and Safety Monitoring Committee.
We used the published Italian version of the following inventories: Control Preference Scale (CPS) [12,13]; Hospital Anxiety and Depression Scale (HADS) [14,15]; Observing Patient Involvement in Decision Making (OPTION) [16,17]; 29-item Multiple Sclerosis Quality of Life (MSQOL-29) [18]; Zarit Burden Interview (ZBI) [19,20]. The 4-item ACP-Engagement and the Quality Of Communication (QOC) inventories were translated/culturally adapted from source language [21–23].
We assessed the quality of the first ACP conversation (which was unobtrusively audio-recorded and transcribed verbatim) considering three perspectives: an independent observer, the PwPMS, and the physician (manuscript in preparation).
Nested qualitative study.
We conducted one-on-one semi-structured interviews with PwPMS and SOs, and two focus groups of clinicians involved in intervention delivery. Interviews and focus groups were held via videoconference to ease participation of PwPMS with high disability and SOs with caregiving commitments, as well as clinicians. PwPMS and/or SOs who had difficulty in using personal computer or other devices, were interviewed on the telephone. All participants were informed of the aim and procedure of the interview/focus group, and provided written consent. Further details are reported in the (published [9]) protocol (S2 File), in S3 (Interview/ focus group guides) and S4 Files (COREQ checklist) [24].
Data analysis
Study power.
There are no data available on the occurrence of ACP in MS: by hypothesizing a proportion in the PwPMS population of 10%, a sample size of 35 subjects achieves a power of 90%, assuming a type I error of 5%, to detect a proportion of ACP-Doc of 30%. By hypothesizing a proportion in the PwPMS population of 8%, a sample size of 35 subjects achieves a power of 95%, assuming a type I error of 5%, to detect a proportion of ACP-Doc of 30%. Considering drop-outs and withdrawals, we aimed to recruit at least 40 PwPMS.
Statistics.
Categorical variables were compared using the chi-squared or Fisher’s exact test. Within-group comparisons were carried out using the Wilcoxon signed-rank test.
Our primary end-point was the proportion of PwPMS completing an ACP-Doc during the six-month period. Change in the secondary outcome measures were calculated using generalized estimating equations. Data were analyzed according to the intention-to-treat principle, using multiple imputation of missing values. A p-value < 0.05 was considered statistically significant. No correction for multiple comparisons was applied. All analyses were performed using STATA 16 (College Station, Texas 77845 USA).
Qualitative data.
Interviews and focus groups were audio-recorded and transcribed verbatim. Five researchers (MP, RMZ, SV, LDP, and LG) analyzed interviews and focus groups using thematic analysis [25], with interpretation guided by the Normalization Process Theory (NPT) [26].
Qualitative analysis.
The data material was analyzed line-by-line using inductive coding to identify factors influencing the process of ACP. After that, the factors were mapped to the constructs of the NPT and their specific domains as a conceptual framework that explains implementation processes [27]. NPT identifies four essential determinants of ‘normalizing’ complex interventions into clinical practice: coherence (the extent to which an intervention is understood as being meaningful, achievable and valuable); cognitive participation (the engagement of clinicians necessary to deliver the intervention); collective action (the work that brings the intervention into use); and reflexive monitoring (the ongoing process of adjusting the intervention to keep it in place) [26]. Before the focus groups, clinicians completed the Normalisation MeAsure Development (NoMAD) questionnaire [28]. The NoMAD consists of 23 items assessing the four NPT domains from the perspective of professionals directly involved in the work of implementing complex healthcare interventions.
Results
Enrolment and participants’ characteristics at baseline
164 PwPMS were screened, and 89 were excluded. Of 75 eligible patients, 19 (25%) accepted to participate and were analyzed (Fig 1).
ACP, advance care planning; PROM, patient-reported outcome; RRMS, relapsing remitting multiple sclerosis; SO, significant other; ZBI, Zarit Burden Interview. Boxes with dotted line identify missing PROMs.
Details of the screened PwPMS across centers are reported in S1 Table. Characteristics of enrolled PwPMS at baseline, SOs, ACP-trained neurologists, and centers are reported in Table 1. Participants’ characteristics by center are reported in S2 Table. CPS data were not available due to a technical problem.
The ACP conversations and primary outcome
Twenty-four ACP conversations occurred during follow-up: 19 first ACP conversations, and 5 second conversations. Median time from baseline to first conversation was 20 days, from the first to the second conversation 27 days. The main features of the conversations are reported in Table 2.
Overall, 11/19 (58%) PwPMS completed the ACP-Doc over the six-month period: seven during the first and four during the second ACP conversation.
Mean QOC subscale scores (0–100) were 92.4 (SD 9.6) for ‘general communication’ and 90.1 (SD 10.2) for ‘communication about EOL care’. Mean QOC-SO scores were 95.2 (SD 6.4) for ‘general communication’ and 94.3 (SD 7.0) for ‘communication about EOL care’. Finally, mean QOC-Doc score was 69.5 (SD 16.0) (Table 2).
Adverse events and attrition
There was one SAE (hospitalization for pneumonia and pre-coma), unrelated to the intervention. There were 25 adverse events (Table 3) in 13 PwPMS; 3/25 (increase in anxiety) were deemed to be possibly related to the intervention.
HADS-Anxiety score increased significantly over time (p = 0.02), while this was not the case for HADS-Depression score (p = 0.46) (Table 3; S1 and S2 Figs).
One patient refused conversation audio-recording and did not complete PROMs. One patient did not complete PROMs at 6-month follow-up. Two SOs did not complete ZBI at baseline. Two SOs did not complete ZBI at 6-month follow-up (Fig 1).
Other outcome measures
There were no differences for 4-item ACP Engagement survey scores over time (p = 0.47) (Table 3; S3 Fig), and for MSQOL-29 physical health composite scores (p = 0.32), whereas there was a significant worsening for MSQOL-29 mental health composite scores over time (p = 0.04) (Table 3; S4 Fig). There were no differences for ZBI scores over time (p = 0.44) (Table 3; S5 Fig). These findings should be interpreted with caution (see Discussion, ‘Study limitations’ section) due to small sample size and multiplicity problem.
Per-protocol analysis findings matched those of the main analysis for all outcomes (S3 Table).
Qualitative findings and process evaluation
Five PwPMS and four SOs were interviewed (interviewees’ characteristics are not given to prevent their identification); two were dyads. Interview guides are reported in S3 File. Representative quotations are shown in Table 4.
All PwPMS and SOs recognized the existential significance of the ACP process. The ACP conversation strengthened the partnership with the caring clinicians, and participants felt supported by them during enrollment and discussions, appreciating clinicians’ clarity and competence. However, engaging in ACP came with emotional costs. Eight out of nine interviewees experienced the discussion of EOL topics as demanding despite appreciating its value. One SO (and trustee) felt embarrassed, likening his role to a “squire” protecting his loved one from strong emotions. Another SO (and trustee) worried about his future “emotional resilience” and described his role as “heavy”. Generally, ACP discussion and family relationships influenced each other. Specifically, in some instances, ACP facilitated broader family conversations about EOL decisions, and in other instances, discussion within the family impacted PwPMS choices. Finally, most of the PwPMS felt supported by involving the family in the ACP discussion, and SOs felt relieved by beginning such discussion. Preparedness (of PwPMS and SOs) reduced anxiety during discussions, while lack of preparedness increased difficulty and led to negative emotions. Preparedness (of PwPMS and SOs) reduced anxiety during discussions, while lack of preparedness increased difficulty and led to negative emotions. In one case, misunderstanding about PwPMS preparedness negatively impacted the experience of both the PwPMS and her SO. Two main challenges emerged: one was the uncertainty of actually implementing one’s choices, and the other was the difficulty of SOs in fully understanding the commitment required by their role as a trustee.
We held two focus groups with 14 clinicians from the six participating centers (clinicians’ characteristics are not given to prevent their identification). Focus group guide is reported in S3 File. Fig 2 summarizes the facilitators and barriers identified using NPT constructs. Coherence was facilitated by clear study objectives and well-defined roles within the ACP process. Barriers included neurologists feeling pressured by PwPMS or SOs to skip thorough discussions, and a tendency to start ACP discussion in the late phase of the disease trajectory.
Cognitive participation was facilitated by promoting ACP through study posters; moreover, clinicians considered the availability of psychological support to assess PwPMS readiness to ACP a resource. Barriers included the fact that ACP practice is rare, the unpreparedness of PwPMS in discussing disease worsening and EOL issues, and the difficulty in sharing the training insights within the team. Clinicians suggested more comprehensive team training to enhance ACP’s legitimacy and effectiveness.
Collective action benefited from collaboration among professionals with diverse competences. Clinicians emphasized the need for thorough ACP training and the primacy of the relationship over use of the booklet. To minimize barriers, particularly time and space availability, clinicians proposed reorganizing activities, embedding ACP in MS care pathways, and establishing a network of ACP-trained professionals.
Reflexive monitoring showed that clinicians described their participation in the trial as a positive, enriching experience, which changed their perspective towards ACP, increased their relational capabilities, and their openness in dealing with goals of care discussions. However, clinicians had difficulty in actively promoting ACP in their work context due to the atypia of the topic (individual appraisal). The booklet was helpful despite some limitations (redundancy and hastily presentation of EOL choices). Another barrier was the clinician’s difficulty in distinguishing between advance directives/living wills (completed by any adult person with decisional capacity) and ACP. Finally, a trial-specific barrier was the impractical trial platform (Box 1).
Participants made suggestions to improve the intervention, mainly by letting the neurologist organize the time of ACP discussion, using the booklet flexibly (as a tool to be completed or a starting point for reflection), making ACP traceable; including other professionals (e.g., palliative care professionals) in the multidisciplinary team; identifying trigger points to propose ACP (e.g., transition to a progressive MS phase, unplanned hospitalizations); have dedicated space and time for ACP conversation; maintaining ACP training within the MS team and integrating it with case-based discussion.
The NoMAD subscale scores ranged between 79.6 (collective action) and 91.1 (coherence) out of a maximum value of 100 (S4 Table).
Box 1. Findings of each pre-specified objective [9] of the study. ACP-Doc, advance care plan document; MSQOL-29, 29 item Multiple Sclerosis Quality of Life; PwPMS, person with progressive multiple sclerosis; SO, significant other; ZBI, Zarit Burden Interview.
Discussion
This study examined the feasibility of an intervention to improve implementation of ACP for PwPMS using a mixed-methods approach. Study findings suggest that the training programme and use of the booklet helped the clinicians in guiding PwPMS reflection on their personal values and preferences, treatment options and their consequences, and devise an ACP-Doc. Trial procedures and outcome measure collection are also feasible except for a difficult-to-use trial platform by PwPMS and SOs, including poor visibility of the CPS score validation button (Box 1). The main study challenge was that, even if we extended the recruitment period from six to 12 months, and placed study posters in the waiting rooms, the planned sample of 40 PwPMS was not reached due to two-thirds of eligible PwPMS refusing participation (Box 1). This high PwPMS refusals point to the need for a broader cultural change towards EOL issues and discussion (reconfiguration). For this reason, we decided that moving to the next project phase is premature, and a new intervention component targeting PwPMS and SOs is required. This is in line with the suggestion of a multiple-component ACP intervention targeting clinicians and patients simultaneously [29], measuring first, the level of readiness for ACP of patients and carers [30].
Given that this was a small pilot/feasibility study, the sample size was not powered to detect changes in the proposed outcome measures of the definitive (cluster) randomized controlled trial (RCT). However, it is worth mentioning the increase in PwPMS anxiety symptoms after the first ACP conversation and at six-month follow-up. As from a systematic review on ACP interventions [31], only two RCTs assessed patient anxiety symptoms, both in advanced cancer sufferers: Bernacki et al. found significant reduction in the proportion of patients with moderate-to-severe anxiety approximately 12 weeks post-intervention [32]; Clayton et al. did not find any between-group difference in mean State Anxiety Inventory score change three weeks post-intervention [33]. We believe that the existential issues covered during the ACP discussion may lead to an increase of anxiety, and this response should not be necessarily considered as the expression of a psychopathological disorder. Nevertheless, it is important that this symptom is properly identified and managed by the caring physician. A deeper understanding of the main determinants of this psychological reaction deserves further investigation.
Two main barriers for ACP discussions in MS were identified in a literature review: the long and uncertain MS trajectory, and lack of ACP communication skills and confidence of clinicians [34]. The MS trajectory challenges the inclusion of long-term outcomes (chiefly concordance between preferred and received EOL care and treatments [35]) in the typical timeframe of a clinical trial. For this reason and in coherence with the ACP principles, we agreed not to narrow the inclusion criteria only to PwPMS in the late disease stage. Nevertheless, one enrolled PwPMS had a SAE (Table 3) and on that occasion the intensive care clinicians applied his ACP-Doc. Concerning clinicians’ skills, a recent online survey revealed that only 18% of Italian residents in neurology had received training in ACP and only 13% had participated in the ACP process, half within their residency programme [36]. Consistent with this survey, none of the clinicians who participated in the present study had previous experience of ACP. We explored the QOC scores of one neurologist who participated in 5/19 ACP discussions, and found an increase in QOC-Doc scores over time, with values ranging between 25 (first conversation) and 80 (fourth and fifth conversation) out of a maximum value of 100 (Spearman’s rho 0.97, p = 0.005). Moreover, structured observation of the audio-recorded ACP conversations (manuscript under review) revealed that in the first conversation the neurologist was quite anchored to the booklet, while subsequently she used the tool in a less mechanistic way.
Study limitations
Although valuable for assessing the feasibility and potential of a larger study, pilot and feasibility studies are typically underpowered. Additionally, we did not reach the target number of participants and used (as from the study protocol) advanced statistical methods (i.e., mixed-method analysis and generalized estimating equations). Finally, we assessed several secondary outcome measures, without adjusting for multiplicity testing. Therefore, the results of the quantitative analysis should be interpreted with caution.
Conclusions
The ConCure-SM intervention is feasible and acceptable to PwPMS, their SOs, and clinicians. Our findings suggest that the training programme and use of the booklet have the potential to support PwPMS reflection on their personal values and preferences, clarification of treatment options and their consequences, and devise of an ACP-Doc. However, before moving on to the evaluation phase it is necessary to enrich the intervention with a component that improves the ACP preparedness of both PwPMS and their SOs. In addition, flexibility in intervention delivery across different contexts (outpatient versus inpatient services) should be pursued, yet preserving the integrity of its core components.
Supporting information
S1 File. CONSORT 2010 extension to randomized pilot and feasibility trials checklist.
https://doi.org/10.1371/journal.pone.0331220.s001
(PDF)
S1 Box. Conditions that would make advance care planning (ACP) relevant.
https://doi.org/10.1371/journal.pone.0331220.s005
(PDF)
S1 Table. Characteristics of subjects at screening across centers.
https://doi.org/10.1371/journal.pone.0331220.s006
(PDF)
S2 Table. Participant’s characteristics at baseline across centers.
https://doi.org/10.1371/journal.pone.0331220.s007
(PDF)
S3 Table. Per protocol analysis of the secondary outcome measures.
https://doi.org/10.1371/journal.pone.0331220.s008
(PDF)
S4 Table. NoMAD frequencies of agreement and total scores of 13 clinicians (7 neurologists, 6 other professionals) from the six participating centers.
https://doi.org/10.1371/journal.pone.0331220.s009
(PDF)
S1 Fig. Scatter plots of Hospital Anxiety and Depression Scale (HADS)-Anxiety scores at baseline, after the first advance care planning (ACP) conversation (T1), and at 6-month follow-up (T2) (per-protocol data).
Codes of people with progressive multiple sclerosis who completed the ACP-Document are reported in bold.
https://doi.org/10.1371/journal.pone.0331220.s010
(PDF)
S2 Fig. Scatter plots of Hospital Anxiety and Depression Scale (HADS)-Depression scores at baseline, after the first advance care planning (ACP) conversation (T1), and at 6-month follow-up (T2) (per-protocol data).
Codes of people with progressive multiple sclerosis who completed the ACP-Document are reported in bold.
https://doi.org/10.1371/journal.pone.0331220.s011
(PDF)
S3 Fig. Scatter plots of 4-item ACP Engagement survey scores at baseline, after the first advance care planning (ACP) conversation (T1), and at 6-month follow-up (T2) (per-protocol data).
Codes of people with progressive multiple sclerosis who completed the ACP-Document are reported in bold.
https://doi.org/10.1371/journal.pone.0331220.s012
(PDF)
S4 Fig. Box plots of MSQOL-29 Physical Health Composite (A) and MSQOL-29 Mental Health Composite scores (B) at baseline and at 6-month follow up (T2).
The boxes represent the interquartile range, horizontal lines inside boxes represent medians and tails represent the 5th–25th and 75th–95th percentile range. Dots are outliers. MSQOL-29, 29-item Multiple Sclerosis Quality of Life; MHC, mental health composite; PHC, physical health composite.
https://doi.org/10.1371/journal.pone.0331220.s013
(PDF)
S5 Fig. Box plots of ZBI scores at baseline, after the first advance care planning conversation (T1), and at 6-month follow up (T2).
The boxes represent the interquartile range, horizontal lines inside boxes represent medians and tails represent the 5th–25th and 75th–95th percentile range. Dots are outliers. ZBI, Zarit Burden Interview.
https://doi.org/10.1371/journal.pone.0331220.s014
(PDF)
Acknowledgments
We thank all of the PwPMS and SOs who participated in the study.
ConCure-SM project investigators
ConCure-SM Steering Committee: LDP, SV, Michela Bruzzone, Italian Multiple Sclerosis Society, Genoa, Italy; AG, MGG, PK, AL, SM, FP, EP, CS, AGi, AS.
Data Safety and Monitoring Committee: David Oliver, The Tizard Centre, University of Kent, Canterbury, UK (Chair); Kevin Brazil, School of Nursing and Midwifery, Queen’s University of Belfast, Belfast, Northern Ireland, UK; Bobbie Farsides, Brighton & Sussex Medical School, Falmer, Brighton, United Kingdom; Luciano Orsi, The Italian Society of Palliative Care (SICP), Milan, Italy; Carlo Peruselli, SICP, Milan, Italy.
Data Management and Analysis Committee: AGi, MF.
Qualitative Analysis Panel: LDP, SV, MP, LG, KM, RMZ.
HP Training Panel: LDP, SV, Marta Cascioli, Hospice La Torre sul Colle, Spoleto, Italy; KM, EP, MR, AS.
Linguistic Validation Panel: MF, PK, SV, AGi, AS.
Enrolling Centers and Investigators: Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona; Unit of Neurology, Borgo Roma Hospital, Azienda Ospedaliera Universitaria Integrata Verona, Verona: AG, Angelica Filosa, Riccardo Orlandi. Department of Rehabilitation M. L. Novarese Hospital, Moncrivello, Vercelli: CS, Erica Grange. Multiple Sclerosis Center, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia: SM, Francesca Sireci. UOSI Riabilitazione Sclerosi Multipla, IRCCS Istituto delle Scienze Neurologiche di Bologna; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna: AL, Federica Pinardi, Loredana Sabbatini, Cinzia Scandellari, Elisa Ferriani. Fondazione IRCCS Santa Lucia, Rome: MGG, Giorgia Presicce, Luigi Iasevoli. University Hospital Policlinico Vittorio Emanuele, Catania: FP, Clara Grazia Chisari, Simona Toscano.
References
- 1. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020;26(14):1816–21. pmid:33174475
- 2. Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, et al. Multiple sclerosis. Nat Rev Dis Primers. 2018;4(1):43. pmid:30410033
- 3. Harding K, Zhu F, Alotaibi M, Duggan T, Tremlett H, Kingwell E. Multiple cause of death analysis in multiple sclerosis: A population-based study. Neurology. 2020;94(8):e820–9. pmid:31932517
- 4. Lunde HMB, Assmus J, Myhr K-M, Bø L, Grytten N. Survival and cause of death in multiple sclerosis: a 60-year longitudinal population study. J Neurol Neurosurg Psychiatry. 2017;88(8):621–5. pmid:28365589
- 5. Rietjens JAC, Sudore RL, Connolly M, van Delden JJ, Drickamer MA, Droger M, et al. Definition and recommendations for advance care planning: an international consensus supported by the European Association for Palliative Care. Lancet Oncol. 2017;18(9):e543–51. pmid:28884703
- 6.
Coulter A, Collins A. Making shared decision-making a reality. London, United Kingdom: King’s Fund; 2011 [cited 15 December 2024. ]. Available from: http://assets.kingsfund.org.uk/f/256914/x/73b4098901/making_shared_decisions_making_reality_july_2011.pdf
- 7. Skivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, et al. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. BMJ. 2021;374:n2061. pmid:34593508
- 8. Giordano A, De Panfilis L, Veronese S, Bruzzone M, Cascioli M, Farinotti M, et al. User appraisal of a booklet for advance care planning in multiple sclerosis: a multicenter, qualitative Italian study. Neurol Sci. 2024;45(3):1145–54. pmid:37816932
- 9. De Panfilis L, Veronese S, Bruzzone M, Cascioli M, Gajofatto A, Grasso MG, et al. Study protocol on advance care planning in multiple sclerosis (ConCure-SM): intervention construction and multicentre feasibility trial. BMJ Open. 2021;11(8):e052012. pmid:34389580
- 10. Grant S, Mayo-Wilson E, Montgomery P, Macdonald G, Michie S, Hopewell S, et al. CONSORT-SPI 2018 Explanation and Elaboration: guidance for reporting social and psychological intervention trials. Trials. 2018;19(1):406. pmid:30060763
- 11. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. pmid:27777223
- 12. Degner LF, Sloan JA, Venkatesh P. The Control Preferences Scale. Can J Nurs Res. 1997;29:21–43.
- 13. Solari A, Giordano A, Kasper J, Drulovic J, van Nunen A, Vahter L, et al.; AutoMS project. Role Preferences of People with Multiple Sclerosis: Image-Revised, Computerized Self-Administered Version of the Control Preference Scale. PLoS One. 2013;8(6):e66127. pmid:23823627
- 14. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70. pmid:6880820
- 15. Costantini M, Musso M, Viterbori P, Bonci F, Del Mastro L, Garrone O, et al. Detecting psychological distress in cancer patients: validity of the Italian version of the Hospital Anxiety and Depression Scale. Support Care Cancer. 1999;7(3):121–7. pmid:10335929
- 16. Elwyn G, Hutchings H, Edwards A, Rapport F, Wensing M, Cheung W, et al. The OPTION scale: measuring the extent that clinicians involve patients in decision‐making tasks. Health Expect. 2005;8(1):34–42.
- 17. Goss C, Fontanesi S, Mazzi MA, Del Piccolo L, Rimondini M. The assessment of patient involvement across consultation. The Italian version of the OPTION scale. Epidemiol Psichiatr Soc. 2007;16(4):339–49. pmid:18333430
- 18. Rosato R, Testa S, Bertolotto A, Scavelli F, Giovannetti AM, Confalonieri P, et al. eMSQOL-29: Prospective validation of the abbreviated, electronic version of MSQOL-54. Mult Scler. 2019;25(6):856–66. pmid:29761738
- 19. Hébert R, Bravo G, Préville M. Reliability, Validity and Reference Values of the Zarit Burden Interview for Assessing Informal Caregivers of Community-Dwelling Older Persons with Dementia. Can J Aging. 2000;19(4):494–507.
- 20. Chattat R, Cortesi V, Izzicupo F, Del Re ML, Sgarbi C, Fabbo A, et al. The Italian version of the Zarit Burden interview: a validation study. Int Psychogeriatr. 2011;23(5):797–805. pmid:21205379
- 21. Engelberg R, Downey L, Curtis JR. Psychometric characteristics of a quality of communication questionnaire assessing communication about end-of-life care. J Palliat Med. 2006;9(5):1086–98. pmid:17040146
- 22. Sudore RL, Heyland DK, Barnes DE, Howard M, Fassbender K, Robinson CA, et al. Measuring Advance Care Planning: Optimizing the Advance Care Planning Engagement Survey. J Pain Symptom Manage. 2017;53(4):669–81.e8.
- 23. De Panfilis L, Veronese S, Perin M, Cascioli M, Farinotti M, Kruger P, et al. Italian cross-cultural adaptation of the Quality of Communication questionnaire and the 4-item advance care planning engagement questionnaire. PLoS One. 2023;18(3):e0282960. pmid:36952509
- 24. Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007;19(6):349–57. pmid:17872937
- 25. Braun V, Clarke V. Using thematic analysis in psychology. Qualitat Res Psychol. 2006;3(2):77–101.
- 26. May CR, Cummings A, Girling M, Bracher M, Mair FS, May CM, et al. Using Normalization Process Theory in feasibility studies and process evaluations of complex healthcare interventions: a systematic review. Implement Sci. 2018;13(1):80. pmid:29879986
- 27. Moore GF, Audrey S, Barker M, Bond L, Bonell C, Hardeman W, et al. Process evaluation of complex interventions: Medical Research Council guidance. BMJ. 2015;350(mar19 6):h1258.
- 28. Finch TL, Girling M, May CR, Mair FS, Murray E, Treweek S, et al. Improving the normalization of complex interventions: part 2 - validation of the NoMAD instrument for assessing implementation work based on normalization process theory (NPT). BMC Med Res Methodol. 2018;18(1):135. pmid:30442094
- 29. Schichtel M, Wee B, Perera R, Onakpoya I, Albury C, Barber S. Clinician-targeted interventions to improve advance care planning in heart failure: a systematic review and meta-analysis. Heart. 2019;105(17):1316–24. pmid:31118199
- 30. Rezaei MA, Zahiri A, Kianian T, Hashemi E, Askari A, Golmohammadi M, et al. Factors related to patients’ readiness for advance care planning: a systematic review. BMC Public Health. 2025;25(1):78. pmid:39773395
- 31. Ryan RE, Connolly M, Bradford NK, Henderson S, Herbert A, Schonfeld L, et al. Interventions for interpersonal communication about end of life care between health practitioners and affected people. Cochrane Database Syst Rev. 2022;7(7):CD013116. pmid:35802350
- 32. Bernacki R, Paladino J, Neville BA, Hutchings M, Kavanagh J, Geerse OP, et al. Effect of the Serious Illness Care Program in Outpatient Oncology: A Cluster Randomized Clinical Trial. JAMA Intern Med. 2019;179(6):751–9. pmid:30870563
- 33. Clayton JM, Butow PN, Tattersall MHN, Devine RJ, Simpson JM, Aggarwal G, et al. Randomized Controlled Trial of a Prompt List to Help Advanced Cancer Patients and Their Caregivers to Ask Questions About Prognosis and End-of-Life Care. J Clin Oncol. 2007;25(6):715–23.
- 34. Cottrell L, Economos G, Evans C, Silber E, Burman R, Nicholas R, et al. A realist review of advance care planning for people with multiple sclerosis and their families. PLoS One. 2020;15(10):e0240815. pmid:33064749
- 35. Higginson IJ, Evans CJ, Grande G, Preston N, Morgan M, McCrone P, et al. Evaluating complex interventions in end of life care: the MORECare statement on good practice generated by a synthesis of transparent expert consultations and systematic reviews. BMC Med. 2013;11:111. pmid:23618406
- 36. Bombaci A, Di Lorenzo F, Pucci E, Solari A, Veronese S. Education needs in palliative care and advance care planning of Italian residents in neurology: An online survey. Eur J Neurol. 2024:e16376.