Immediate versus delayed short-term integrated palliative care for advanced long-term neurological conditions: the OPTCARE Neuro RCT

Article history

The research reported in this issue of the journal was funded by the HS&DR programme or one of its preceding programmes as project number 12/130/47. The contractual start date was in April 2014. The final report began editorial review in February 2019 and was accepted for publication in September 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HS&DR editors and production house have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

Irene J Higginson was a member of the Health Technology Assessment Efficient Study Board (2015–16) and the Health Technology Assessment End of Life Care and Add-on Studies Board (2015–16). Wei Gao was member of the Health Technology Assessment End of Life Care and Add-on Studies Board (2015–16) and the Health Services and Delivery Research Commissioning Board (2009–15).

Disclaimer

This report contains transcripts of interviews conducted in the course of the research and contains language that may offend some readers.

Copyright statement

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Hepgul et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

2020 Queen’s Printer and Controller of HMSO

Long-term neurological conditions

Long-term neurological conditions (LTNCs) are a diverse set of conditions resulting from injury or disease of the nervous system that affect individuals for the rest of their lives. This includes long-term progressive conditions, such as idiopathic Parkinson’s disease (IPD), motor neurone disease (MND), multiple sclerosis (MS), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Affecting > 200,000 individuals in the UK, these progressive conditions lead to substantial deterioration in quality of life and result in the patient needing lifelong support from health and social care services. 1 Many patients have inadequate symptom control and inadequate psychological and social support, and there is a high burden for family caregivers. 2–5 There are also significant financial burdens to the individual, their families and the NHS, with increasing costs associated with disease progression. 6–8 Despite the progressive nature of these conditions, the scope for improving services to enhance quality of life of affected individuals through the provision of palliative care may be substantial.

Current treatment and service provision

In 2005, the Department of Health and Social Care published the National Service Framework, which set 11 quality requirements to transform the way health and social care services support people with LTNCs and their caregivers. 9 It highlighted the need for integrated care and joined-up services, and made recommendations for the provision of specialist neurology, rehabilitation and palliative care services to support people throughout and to the end of their lives.

However, a National Audit Office report concluded that implementation of the framework has been poor and that although access to neurology services improved, other important indicators of the quality of care for people with neurological conditions worsened. 10 The report highlighted that information and advice to patients and caregivers is inadequate, and ongoing care is fragmented and poorly co-ordinated. Indeed, in the UK and in many other health systems, there is often division among general practitioners, staff working in the community and hospital-based specialists. 11,12 It is increasingly recognised that a hard separation of these functions does not meet the needs of those with long-term conditions; therefore, much of the burden of illness often falls on the community and on lay caregivers. 2,5,13,14 This results in greater negative effects for both patient and caregiver well-being, as well as increased financial burden. 8,15 Attempts have been made to better co-ordinate care through integrative processes, such as joint budgets, governance, information systems, flows of data or case management. 16,17 These may be brought together more formally through different kinds of vertical integration, in which agencies involved at different stages of the care pathway form part of a single organisation or function, as well as horizontal integration of community-based services in examples such as health and social care teams for the frail elderly. 18 Another issue is that multimorbidity is the norm for people with LTNCs. Equally, their spouses or family caregivers may have health conditions that affect their ability to care, and the burden of caring may affect the health of caregivers. 2,13 Palliative care is person rather than disease focused and may have the potential to address these unmet needs.

Palliative care for long-term neurological conditions

Palliative care focuses on improving quality of life through a multidisciplinary approach and has been recognised as a valuable component of care for patients with chronic, life-limiting illnesses. 19–21 The place for palliative care in rapidly fatal neurological conditions is increasingly recognised; however, the evidence is scarce. 22 Indeed, a recent consensus review concluded that there is limited evidence to support any recommendations for the provision of palliative care for progressive neurological disease and that further research is urgently needed. 23 There are three Phase II trials of palliative care for patients with neurological conditions. 24–26 The results of our own Phase II trial of short-term integrated palliative care (SIPC) among 52 patients severely affected by MS found an improvement in pain and a significant reduction in informal caregiver burden at a lower cost and with no harmful effect, compared with standard care. 24 Similarly, in 78 MS patients and their caregivers, a 6-month home-based palliative care service was found to reduce symptom burden compared with usual care. 26 Furthermore, a new 4-month home-based specialist palliative care service for 50 patients with advanced neurodegenerative disorders (MND, MS, IPD, MSA and PSP) found a significant improvement in quality of life and physical symptoms (pain, breathlessness, sleep disturbance and bowel symptoms) across the conditions, although no effect was seen on caregiver burden. 25 We have also previously reported findings from a longitudinal observational study of IPD, MSA and PSP patients demonstrating the profound and complex mix of non-motor and motor symptoms in late stages of disease. 27 Symptoms were highly prevalent in all three conditions and were often unresolved, with half of patients deteriorating over 1 year. Furthermore, palliative problems were predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention. 27 However, to the best of our knowledge, there are currently no Phase III trials.

Conceptual framework

People severely affected by LTNCs have many problems and concerns similar to those affected by advanced cancer, including symptoms, psychological needs, and family and caregiver concern. 28 Specialist multiprofessional palliative care teams (MPCTs) successfully improve these problems for cancer patients and are now available widely across the globe. 29,30 The Cochrane handbook outlines31 that, if there is empirical evidence that similar or identical interventions have an impact on other populations, these are quite likely to be effective. Thus, as a starting point, it is reasonable to hypothesise that input from specialist palliative care will help people with LTNCs. Our modelling work demonstrated that people severely affected by MS, Parkinson’s disease-related disorders and MND had many similar symptoms to those affected by advanced cancer,32 with additional problems of loss of care co-ordination. 33–35 These needs are within the remit of specialist palliative care, which offers a holistic approach attending to symptoms, psychological needs and better co-ordination of care. 36 People severely affected by LTNCs often have a longer trajectory of illness than those with advanced cancer and so our modelling found that staff, patient and caregiver groups favoured the idea of specialist palliative care input for a short term, working in a way that was well integrated with existing neurology and rehabilitation services.

Short-term integrated palliative care is modelled on our work to date, following the Medical Research Council guidance for the development and evaluation of complex interventions. 37 This included literature reviews38 and qualitative studies33,34 to determine need and to develop the theoretical underpinning of the service, appraisal of trial methods,32,39 service modelling and a successful Phase II trial randomising 52 patients. 24,29,40

Short-term integrated palliative care is a complex intervention41 in that it:

• contains several components (assessment, symptom management, future care planning, follow-up visits)

• aims to change behaviours by those staff delivering the intervention, those providing usual care to this patient group, and, to some extent, patients and families

• targets patients, families and staff in primary, hospital and voluntary care, thus including different groups and organisational levels

• has several complex outcomes, including change in symptom management and hospital admissions

• is tailored to individual patient need and circumstances by those delivering SIPC

• operates in a context in which there may be some variability between patient groups and settings in the usual care provided to patients with LTNCs; usual care is offered to patients in the intervention and control arms of the trial.

Short-term integrated palliative care could be developed with only small adaptions to existing health-care services. It is much more likely to be possible than other proposed alternatives, such as developing long-term palliative care models. The latter would be difficult to achieve without considerably expanding the number of palliative care specialists, beds and services. In contrast, SIPC builds on and integrates with existing services across the UK and seeks to empower patients, improve symptom control and integrate with existing services, improving their expertise. If found to be effective, the new SIPC service has the potential to be beneficial for a wider range of conditions and in more diverse care settings for patients and their families. This could result in better symptom control and improved quality of life for patients, as well as improved co-ordination of care, more efficient and appropriate use of services, and a reduction in the number of unnecessary emergency admissions at the end of life. This is also in line with other NHS initiatives seeking to move palliative care and discussions about preferences and priorities further upstream and encouraging patients to think about care preferences earlier in their disease trajectory. 42 Understanding whether or not SIPC is clinically effective and cost-effective, and its potential mechanism of action, will help to develop studies in these initiatives. Equally, if the SIPC is not cost-effective in more conditions and in wider settings, the findings will prompt development of customised improvement and modifications in specific LTNCs. 8,43–45

Importance of economic analysis

Health-care costs in the last year of life are high (18–30% of health-care spending), with resource use increasing in the last months of life. 43–45 Despite this, it is known that this expenditure offers poor value, as symptoms often remain uncontrolled. 46 In long-term conditions, including neurological conditions, costs rise with increased disability and as the disease advances. 8 These costs can be unpredictable and can affect caregivers and patients, as well as health and social services. 8 Hospitalisation is a main cost driver of health care and a major public health problem. Indeed, NHS England reports that £750M is spent on urgent and emergency care for patients with neurological conditions, including admissions to hospital, with nearly 4% growth in emergency admissions year on year. 47 Compared with age-matched controls, people with LTNCs, such as MS and Parkinson’s disease, are experiencing higher rates of hospitalisation. 48–50

However, maintaining patients in the community can also be costly to health and social care services. It can also place an increased burden on families and carers. Therefore, it is imperative to evaluate proposed service models in patients with advanced disease to see whether or not they affect health and social care costs. SIPC seeks to alleviate symptoms, prevent symptom escalation, improve care, and help patients and caregivers plan the future care they need, all of which may potentially avoid inappropriate hospitalisation. A full understanding of the cost-effectiveness of SIPC for the NHS is central to decision-making. Despite this need, health economic evaluations of interventions in advanced illness remain rare, especially cost-effectiveness studies. Most studies consider only costs, randomised trials are rare and many studies fail to account for confounding. 51,52

Evaluating a new service model for LTNCs, as well as addressing the concerns for people severely affected by these diseases, develops a potential model of service provision for other long-term diseases in advanced stages. With the ageing population, the predicted rise in the annual number of deaths, the increasing prevalence of long-term conditions and the likely increase in need for palliative care,53,54 it is both highly relevant and timely to robustly test new service models to improve care for this group. This project answers this need and tests an intervention that could be implemented by the current workforce and services.

Research group

This project was led by the Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation at King’s College London, with the following collaborating institutions: The University of Nottingham; Nottingham University Hospitals NHS Trust; Cardiff and Vale University Health Board; University of Sussex; Brighton and Sussex Medical School; The Walton Centre NHS Foundation Trust; Sussex Community NHS Foundation Trust; Ashford and St. Peter’s Hospitals NHS Foundation Trust; Sheffield Teaching Hospitals NHS Foundation Trust and King’s College Hospital NHS Foundation Trust.

Aim

The OPTCARE Neuro trial aimed to determine the clinical effectiveness and cost-effectiveness of SIPC services in improving symptoms, improving selected patient- and caregiver-reported outcomes and reducing hospital utilisation for people severely affected by LTNCs.

Primary objective

To determine the clinical effectiveness and cost-effectiveness of SIPC for people severely affected by LTNCs compared with standard care, according to the primary outcome of reduction in key symptoms at 12 weeks.

Secondary objectives

• To map current practice and document the services available (and common care pathways) for patients with LTNCs and their caregivers and families in the areas of the study, to better understand variations in normal practice experienced by the control group.

• To test the feasibility of offering SIPC and the trial methods across five centres, for people severely affected by LTNCs, and to modify the intervention and trial methods accordingly.

• To determine the clinical effectiveness and cost-effectiveness of SIPC for people severely affected by LTNCs compared with standard care in the secondary outcomes: palliative care needs and other symptoms, patient psychological well-being and quality of life, caregiver burden/positivity and quality of life, improvement in patients’ and caregivers’ satisfaction and communication.

• To determine the effects of SIPC for people severely affected by LTNCs on hospital admissions, length of hospital stay, emergency attendance and other service use over the trial period.

• To determine the cost-effectiveness of SIPC for people severely affected by LTNCs.

• To understand how the change process may work and to identify components of the SIPC that are most valued by patients, their families and caregivers, and other health-care professionals.

• To determine how the effects change over time, whether or not earlier referral to palliative care affects the subsequent response to palliative care and when assessment or re-referral might be beneficial.

Study design

This is a mixed-methods study comprising a Phase III, randomised controlled, multicentre, fast-track trial, including assessment of cost-effectiveness and an embedded qualitative component. It is a multicentre evaluation of a complex intervention, following the Medical Research Council guidance for the development and evaluation of complex interventions. 37 This study incorporates:

1. a set-up and feasibility phase to refine recruitment and methods

2. mapping usual care for patients with LTNCs across the different centres (by prior work collecting information about the services, and during the study recording services received at baseline and in the standard care group) to understand the context and baseline variations in practice and resources

3. a randomised controlled trial of SIPC offered from a MPCT, compared with best usual care in terms of outcomes and cost-effectiveness

4. an embedded qualitative component, to explore the ways in which the SIPC affects patients and caregivers, how the change process may work, how SIPC may be improved and to interpret quantitative results

5. a survey of health professionals to understand the impact of SIPC on local practice

6. economic modelling to estimate the NHS and societal resources required for and longer-term impacts of SIPC.

Mapping methods

Parts of the text have been reproduced from van Vliet et al. 55 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

The mapping exercise was conducted in eight centres with neurology and palliative care services in the UK. The centres were purposively selected to include our main recruitment centres and other larger centres. The eight centres included different geographical areas and represented both rural and urban areas. Data were provided by the respective neurology and specialist palliative care teams. Questions focused on catchment and population served, service provision and staffing, and integration and relationships. Data were transferred into tables to facilitate comparison between centres.

Survey methods

Parts of the text have been reproduced from Hepgul et al. 56 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Research teams from six trial centres (London, Nottingham, Liverpool, Cardiff, Brighton and Ashford) identified local neurology and palliative care professionals who were then approached via e-mail by the central trial team. Professionals were informed that, by completing the survey, they provided informed consent for use of their anonymised data. The surveys consisted of multiple-choice or open-comment questions, 13 questions for neurology or 10 questions for palliative care, with responses collected using online forms. The survey was launched in July 2015 and closed in April 2016. Data were transferred into tables to facilitate comparison of professional groups and data were explored descriptively.

Randomised trial methods

This was a randomised controlled, multicentre, fast-track, single-blinded trial of SIPC, provided in addition to existing services, compared with standard care. It was conducted and reported in accordance with Consolidated Standards of Reporting Trials (CONSORT)57 and Methods of Researching End of Life Care (MORECare) statements. 58 The economic components were conducted and reported in accordance with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. 59

Statistical methods

Health economic methods

An economic component was included to assess the cost-effectiveness of SIPC compared with standard care. Cost-effectiveness was assessed by linking data on formal cost differences and outcome measurements differences.

Qualitative methods

Embedded within the trial was a qualitative component conducted concurrently,83 to explore which aspects of SIPC were most valued or had most impact on patients’ and caregivers’ experiences of care, how the change process of SIPC may be working and how the intervention is delivered in practice. The intention was to form a theoretical model of SIPC to inform implementation requirements and processes, and intended outcomes. The embedded qualitative study involved patients, caregivers and health-care staff.

Patient and public involvement

Patient and public involvement has been an integral part of all our research processes. An independent PPI group was set up specifically for OPTCARE Neuro, comprising both patients and caregivers with lived experience of MS, IPD, MSA and MND. The group advised on the application for ethics approval and the development of all participant materials, as well as the delivery of the trial and the interpretation of the findings. We engaged with our PPI members on multiple levels but predominantly through 3-monthly face-to-face meetings at which we benefited from the expert views of our members to help us prioritise the research questions and ensure that the study was undertaken in a way that was meaningful and relevant to both patients and caregivers. A member of our PPI group was a co-applicant on the funding application and an active member of the Study Steering Committee. We had PPI representation in the Data Monitoring and Ethics Committee, which had oversight and responsibility for the conduct of the trial. We actively involved our PPI members in the interpretation of data, particularly the qualitative components of the study. This provided the study team with valuable insight to understand the data and their relevance for addressing the needs of this patient population.

Engagement

Engagement took place throughout the study. First, charities and patient societies supported and publicised the trial in order to improve recruitment and dissemination. Specifically, the PSP Association, the MS Society and Parkinson’s UK, which all featured details of the trial on their research web pages. The trial was also featured in an issue of the Multiple Sclerosis Trust’s Way Ahead magazine for MS health professionals, and in the PSP Association’s PSP Matters magazine, with two trial participants contributing to the article. In May 2016, the study team hosted a 2-day workshop and conference on palliative care in neurology. The first of these days was a closed meeting for OPTCARE Neuro teams, with representation from principal investigators, research nurses, clinicians and PPI members from all trial centres. A representative from each site gave a brief overview of local progress, and our PPI group also presented on their involvement. It was extremely productive to have all the teams together to exchange ideas and learn from each other. The second day was a conference that focused on clinical components of palliative care for patients with LTNCs, and some interim data from the mapping exercise and survey for professionals were presented. The conference had > 100 registrations and was attended by a mixture of clinicians, researchers, students, PPI members and representatives from charitable organisations and patient societies. The great turnout for the conference and the interest from the audience members highlighted the importance of the OPTCARE Neuro work. Last, throughout the course of the study, we have circulated 6-monthly newsletters to our study contacts, which included palliative care and neurology clinicians, academics, researchers and charities.

Ethics approval and research governance

The trial was conducted in compliance with the principles of the Declaration of Helsinki (2013)86 and the principles of Good Clinical Practice and in accordance with all applicable regulatory requirements, including, but not limited to, the Research Governance Framework and the Mental Capacity Act 2005. 62 The protocol and related documents were submitted for review and approved by the London South East Research Ethics Committee (14/LO/1765).

Mapping results

Parts of the text have been reproduced from van Vliet et al. 55 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Centres varied in size of catchment areas (39–5840 square miles) and population served (142,000–3,500,000). Neurology and specialist palliative care were often not co-terminous. Service provision for neurology and specialist palliative care also varied; for example, neurology services varied in the number and type of clinics provided, and palliative care services varied in the settings in which they worked. The integration between neurology and palliative care teams varied between centres, but more clearly between diseases. For MS, the integration was limited, with most centres having no formal links. Only two centres broke this trend; one held an 8-weekly multidisciplinary team (MDT) meeting, in which both MS and palliative care teams participated, and the other held a 3-monthly complex problem clinic with palliative care attendance. For MND, a different picture emerged of stronger integration. Most centres either held joint clinics or had a palliative care presence at MDT meetings. At one site, all MND patients were invited to clinics at the local hospice; whereas at another, all patients received a palliative care assessment. Good informal links were reported in one site where the MND and palliative care nurses shared an office, but there were with no joint visits. The least integrated site had no joint clinics and referrals were based on needs. Last, in Parkinson’s disease-related disorders the integration was very mixed. Approximately half of the centres had no joint clinics or formal relationships. Others had 2- to 3-monthly clinics or MDT meetings, with one site having a palliative care presence at weekly clinics. There was a difference between the subsets of diseases, with greater integration for MSA and PSP. The number of neurology patients per annum receiving specialist palliative care reflected these differences in integration (a range of 9–88 patients with MND, a range of 3–5 patients with Parkinson’s disease-related disorders and a range of 0–5 patients with MS).

Survey results

Parts of the text have been reproduced from Hepgul et al. 56 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

The survey received responses from 33 neurology and 26 palliative care professionals (20% response rate). Two-thirds of respondents in both groups had > 10 years of experience in their respective fields. Current levels of collaboration between the two specialties were reported to be ‘good/excellent’ by 36% of neurology professionals and by 58% of palliative care professionals. However, nearly half (45%) of neurology compared with only 12% of palliative care professionals rated current levels of collaboration ‘poor/none’. When asked if there were any particular disease areas for which links were better, both groups reported stronger links for MND. In addition, both professional groups felt that the new SIPC service being trialled would influence future collaborations for the better (65–70% in both groups). Participants were also asked what they thought would be the main barriers for the new SIPC service. The most common barriers identified by neurologists were resources, clinician awareness of services offered, continuing collaborations, and communication between teams beyond the trial and geographical limitations. Similarly, palliative care professionals also identified resources and clinician awareness of services offered (and importantly the appropriateness of referrals they may receive) as barriers. However, the key barrier they identified was that there may be a possible need for longer-term care beyond that offered by the SIPC service. They also drew attention to patients’ perceptions of palliative care as a potential barrier.

Randomised trial results

Participant flow

Recruitment began in three centres in April 2015. Two centres opened in July 2015 and November 2015, with an additional two centres opening in February 2016 and September 2016. The total recruitment period was 31 months, ending in November 2017, with all follow-up visits completed in May 2018. One centre, Sheffield, was opened but failed to sustain recruitment and therefore was closed. Other centres’ recruited numbers were broadly reflective of their catchment areas and local populations. Monthly recruitment rates over the course of the recruitment period are presented in Appendix 1. The trial recruited 350 patients living with a LTNC, plus 229 caregivers, with 176 patients in the immediate SIPC intervention arm and 174 in the standard care waiting list control arm. Table 1 details the screening and enrolment by each site and Figure 1 outlines the participant flow up to the primary end point of 12 weeks post randomisation.

TABLE 1 - Screening and enrolment by recruiting centre

Screening and enrolment	Site							Total
	London	Liverpool	Nottingham	Cardiff	Brighton	Ashford	Sheffield
Site opened	April 2015	April 2015	April 2015	July 2015	November 2015	February 2016	September 2016
Referred	158	69	100	67	71	64	6	535
Not in catchment area	8	1	1	1	5	0	0	16
Already receiving palliative care	11	2	0	1	1	6	0	21
Lacks capacity and no caregiver	1	0	0	1	0	1	0	3
Not meeting diagnostic criteria	2	0	0	0	0	1	0	3
Declined	25	16	19	22	15	12	3	112
Other	11	2	4	6	0	7	0	30
Enrolled patients (caregivers)	100 (79)	48 (37)	76 (32)	36 (23)	50 (31)	37 (26)	3 (1)	350 (229)

FIGURE 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram showing the flow of participants. Reproduced with permission from Gao et al. 87 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

Reproduced with permission from Gao et al. 87. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. The figure includes minor additions and formatting changes to the original figure.

Health economics

Cost-effectiveness analysis

Incremental cost-effectiveness ratios were calculated for those for whom both cost data and the outcome measures were available. ICERs were calculated as the ratio of differences in health and social care cost and outcomes (rescaled IPOS Neuro-S8 and EQ-5D index score). Using health and social care cost, in other words, when taking an NHS perspective, the change in cost in the SIPC group between baseline and 12 weeks was –£1076, compared with –£514 in the standard care group, leading to a –£562 between-group difference. For the rescaled IPOS Neuro-S8, the change scores were 0.75 and 0.38, respectively, resulting in a between-group difference of 0.37. For the EQ-5D index score (QALY), as presented above, the respective change scores were –0.01 and –0.03, with a resulting between-group difference of 0.02.

As shown in Table 14, the ICER for IPOS Neuro-S8 was –£1519. As the IPOS Neuro-S8 was rescaled, higher scores correspond to lower symptom burden. The ICER suggests that an improvement of 1 unit in IPOS Neuro-S8 is associated with an on average per patient decrease in health and social care costs of –£1519 compared with standard care. The ICER for EQ-5D index score was –£23,545. With higher scores indicating better quality of life, an improvement of 1 unit (QALY) was less costly in the SIPC group than in the standard care group by £23,545.

TABLE 14 - Incremental cost-effectiveness ratio of health and social care cost and EQ-5D and IPOS Neuro-S8

	Changes in outcomes and cost between baseline and follow-up at 12 weeks						ICER (£)
	Δ EQ-5D index score		Δ Rescaled IPOS Neuro-S8		Δ Cost (£)		EQ-5D index score	IPOS Neuro-S8
	SIPC	Standard care	SIPC	Standard care	SIPC	Standard care
Imputed data (n = 350)	–0.01	–0.03	0.75	0.38	–1076	–514	–23,545	–1519

The ICER for health and social care cost and EQ-5D index score was well below our pre-determined threshold of £20,000. Sensitivity analyses conducted in line with the main effectiveness analyses produced consistent results.

Bootstrapping was used to obtain 1000 replications of the ICERs. As presented in Figure 2, when bootstrapped differences in EQ-5D index score and health and social care costs were plotted on cost-effectiveness planes, 74% of replications were found in the fourth quadrant and with rescaled IPOS Neuro-S8 as the outcome measure, 84% of replications were in the fourth quadrant (which represents better outcomes and lower costs in the intervention group than in the standard care group).

FIGURE 2.

Cost-effectiveness planes of outcome measures (a) EQ-5D index score (QALY); and (b) rescaled IPOS Neuro-S8, and health and social care cost.

Qualitative findings

Theme 1: adapting to losses and building resilience

Patients and caregivers described living with a LTNC as ‘always troublesome’. Adapting to losses and building resilience were key strategies to adjust to increasing disability and declining function. Psychosocial interventions were valued to support resilience and adaptation, and counter feelings of loneliness and isolation, often combined with little understanding of their progressive condition. The theme is formed by two subcategories: (1) care beyond medicines, exploring psychosocial interventions; and (2) asked about everything, focusing on planning future care.

Asked about everything

Difficult conversations about ‘emotional things’ to adapt to a progressive condition and end of life required trust and rapport. The short-term nature of the intervention confined the time to build this. Sensitive topics were introduced by palliative care practitioners asking about thoughts on the future, but patients and caregivers seemed uncertain about engaging in such conversations. Planning future care for the end of life was marked by uncertainty in ‘not knowing what’s going to take hold’ when living with a LTNC, and fear of increasing disability and loss of capacity. Engagement ranged from ‘not at all’ to ‘I’ve been writing stuff down for years’, as demonstrated in Figure 3.

FIGURE 3.

Engagement with planning future care for the end of life. DNACPR, do not attempt cardiopulmonary resuscitation.

For both patients and caregivers, these conversations were difficult, and when broached by palliative care team members there was a tendency to ‘skirt-around’ talking about the future. Although individuals could see the practical benefits of planning care for the future, fear and uncertainty seemed to inhibit pursuit of such conversations. It was an area that required time for building trust and pacing to the individual:

. . . and I dread the thought of that [what happened to my mother with dementia] happening to me. Being spoken to like a small boy, I, that would just finish me off. I mean I, my mother had her own house. She had dementia, they spoke to her like a little girl, and I thought ‘you’ll not do that to me, speak to me like a child’ because I’m the one that owns this house, I pay the bills and just because I’m not well, whatever which shape or form, I won’t have that. I could be quite a difficult patient I feel as I get older . . . I haven’t got a family so I care for myself and when I can’t do, then maybe I’ll have to think again. But at the moment I don’t want to [think about wishes for care and treatment in the future].

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Planning care seemed to focus on the present of managing each day, or confined to practical issues of setting up a power of attorney or making a funeral plan. Advance care planning discussions appeared to be the beginning of a conversation: checking in about what the person thought and offering contact with the palliative care team to discuss in the future:

Yeah I think you have to, everybody with any kind of medical condition you have to talk about things like that [wishes for care and treatment in the future].

Yeah that wasn’t, we hadn’t really thought about things like that before.

Yeah that was beneficial, to think about it . . .

Open our minds a bit I suppose.

. . . of what might happen in the future.

Theme 2: attending to function, deficits and maintaining stability

It was important for patients and caregivers for SIPC to attend to physical needs. This required services to encompass the duality of supporting function to maintain independence, however small, and optimal management of deficits of unstable symptoms amenable to changes to reduce distress. Behind this duality was a background of maintaining stability, requiring daily adaptation and resilience by patients and caregivers to manage a progressive condition with ongoing multiple losses across domains of health. These areas formed two subcategories: (1) little things make a big difference, and (2) maintaining stability.

Theme 3: enabling caregivers to care

Acknowledging and valuing the work and care given by caregivers meant a lot, with appreciation of someone to talk to and to be reassured of doing a good job. When not acknowledged, this was a source of frustration for caregivers, who wanted to be asked ‘How are you?’, and when they were asked this they were surprised, as there was a tendency for care and attention to focus on the patient. Caregivers expressed feelings of having had to ‘fight for everything’ and to become experts in the person’s care. The ability to call the palliative care team for advice, particularly out of hours, as well as opportunities to talk through care and treatment, were important to empower decision-making:

Errm you’ve either got to be a strong-minded person or just plod along and put up with it which I have. I’ve had a lot of stress, fighting the system for everything. As far as she [the palliative care nurse] was concerned, she was here mostly for [my husband] and not for the person who’s here 24 hours a day, or not 24 hours a day but lives here as his wife and carer. Errm she didn’t say to me ‘Is there anything you think that could be done to help you with caring for your husband?’.

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Caregivers indicated a tendency not to ask for help, putting their loved ones before themselves and not allowing themselves to be vulnerable or ‘selfish’ in putting their own needs first. Not acknowledging need for help was complex, linked to fear that asking may trigger thinking that they are unable to cope, ‘Better to keep coping rather than risk downward spiral of thinking I can’t manage’. Without support there was a risk of caregivers eventually breaking psychologically and physically from the strain and worry, particularly when not recognising the limits of their resources and the importance of caring for themselves. This type of ongoing work required trust and rapport for the caregiver, to gradually understand the increasing demands placed on them and how to best manage these. Supporting caregivers who had complex concerns required the continuity of care provided by neurology services, particularly community-based nurse specialists. Working with the palliative care team provided the ‘final prompt or prod’ to enable change:

Well not so much someone to talk to but [Parkinson Clinical Nurse Specialist, NN1], she’s been absolutely brilliant and errm her sort of enthusiasm, I mean she’s been talking to me about giving up work for a long time and kept on saying stop being so stubborn, you know, why can’t you just listen or why can’t you just you know give up and look after [your wife] full time, have quality of life, and I, it came to the stage where it was really difficult in that it was now, it has to happen now and you just sort of errm put it aside, put it aside until we moved, errm where it just suddenly hit me, you know just near the kitchen I thought ‘no I can’t carry on’. I phoned my boss, I said ‘look I’m having a bit of a breakdown here’ . . . he [my boss] said ‘well we’ve actually been waiting, wondering how long you’re going to last for, we’ve been waiting for your breakdown’. I thought ‘thanks’ you know [laughs] but that was done, they were brilliant you know up until I finally left.

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Change process and delivery in practice

The overarching themes provided understanding on the outcomes that are important for patients and caregivers, and linkages with key components of models of care to delivery. Important outcomes from SIPC centred on three main areas:

1. Psychosocial well-being of adapting and having the resilience required to live with, and accommodate, multiple ongoing losses leading eventually to end of life.

2. Physical well-being of supporting function to promote independence, optimal management of physical symptoms, with emphasis on person-centred care, pharmacological and non-pharmacological interventions, and accessible services responsive to points of deterioration to minimise a domino effect of decline.

3. Empowering caregivers to care through recognition and valuing of work, shared decision-making and accessible services for advice and support, including practical support.

Complexity was an over-riding feature across the narrative data, surrounding all aspects of care: management of progressive disease; symptoms that appeared refractory, with little response to pharmacological interventions; maintaining independence with increasing disability; adapting to a multitude of losses leading eventually to end of life, with huge uncertainty as to when; and empowering caregivers to continue caring over many years, with increasing demands and losses. Linkage with the outcomes important for patients and caregivers, their experiences of receiving SIPC and the processes of delivery described by practitioners’ informed understanding of the overarching components of a service delivery model for integrated palliative and neurological care. These components include:

• Comprehensive assessment, encompassing health domains and the priorities for both patients and their caregivers.

• Person-centred, holistic care, focusing on the person and not the disease alone.

• MDT working, to provide the expertise for attending to function and deficits of symptoms and concerns across health domains.

• Integrated working between health-care services, to ensure continuity of care between palliative care and neurological services, and with community and primary care services.

• Integrated working fostered through reciprocal learning and training between specialties, in order to enhance the provision of palliative care approaches in neurological services and, conversely, expertise in management of advanced neurological disease in palliative care, with joint case review of individuals with complex symptoms and concerns.

Intervention fidelity

Of the 176 patients allocated to receive the SIPC, 173 patients received the intervention. Three patients did not receive the intervention, as two patients withdrew from the trial and one patient could not be contacted by the respective palliative care team following referral. Of the 173 patients who received the intervention, all had an initial face-to-face visit for a comprehensive palliative care assessment. Following this, 152 patients had a second key worker contact (100 via face-to-face meeting and 52 via telephone), and 153 patients had a third key worker contact (91 via face-to-face meeting and 37 via telephone; for 48 patients the type of contact was not recorded). The intervention manual described the core elements to be covered when assessing patients as part of the SIPC, as well as the minimum standards for capturing and reporting delivery of the SIPC intervention. The completion rates of key pro forma documents and core intervention elements are presented in Table 16.

Key findings

To the best of our knowledge, this is the largest palliative care trial in people with LTNCs. 87 We found that none of the evaluated primary or secondary outcomes were significantly different between those in the SIPC group and those in the standard care group. However, safety outcomes, including deaths, survival and hospitalisations, were similar between the two groups, as were rates of withdrawals. The health economics data showed that care costs fell in both groups between baseline and 12 weeks, with no statistically significant differences between groups. However, ICERs for EQ-5D index score and (rescaled to match direction of EQ-5D) IPOS Neuro-S8 were –£23,545 and –£1519, respectively, considerably better than our threshold for cost-effectiveness. The bootstrapped point estimates in the cost-effectiveness analysis favoured SIPC, indicating a larger reduction in symptoms on IPOS Neuro-S8 or improvement in EQ-5D along with lower cost. Patients receiving SIPC did show a statistically significant improvement on the primary outcome of eight key physical symptoms (IPOS Neuro-S8) and the secondary outcome of 24 physical symptoms (IPOS Neuro-S24) from baseline to 12 weeks after randomisation. A similar improvement was not seen in the control group. Other than the level of care satisfaction (as measured by FAMCARE-P16), which became worse in the standard care group, there were no statistically significant changes in other patient or caregiver outcomes, for example quality of life, anxiety and distress, caregiver burden and positivity, over 12 weeks, in either group. The qualitative data illustrated the complexity of living with LTNCs for both patients and caregivers, and the value that participants placed on the holistic and timely assessment received through SIPC, with attention and assistance given to psychological, social and physiological concerns. Many symptoms were seen as intractable. The qualitative, mapping and survey data all demonstrate the need and opportunities for increased collaboration and integration between neurology and palliative care services, and the challenges resulting from variation across centres and diseases.

Comparison with literature

Trials evaluating the effectiveness of palliative care for LTNCs are rare, and the existing evidence comes from a small number of feasibility/pilot studies. In comparison, our trial is large and both multicentre and multicondition. The overall pattern of results we see is similar to that of the previous Phase II trial of an early palliative care intervention in people with advanced MS. 24 However, in that trial, at 12 weeks, there was a significant difference in the change score of pain, as well as a significant improvement on caregiver burden, in the early palliative care group compared with the usual care group. In contrast, we have not investigated symptoms individually and we did not observe any improvement on caregiver burden. The latter may not be surprising, as a recent systematic review and meta-analysis highlighted that findings on caregiver burden in palliative care interventions are conflicting. 88 Our qualitative findings iterate this, illuminating understanding on the complexity of caregivers’ sense of legitimacy to receive support and the priority they placed on this. In another Phase II trial26 with 78 MS patients and their caregivers, a 6-month home-based palliative care service was found to significantly reduce symptom burden as compared with usual care (p = 0.047), with a stronger effect at 6 months (effect size = 0.32) than at 3 months (effect size = 0.2). 26 The authors also observed no difference in other outcomes, such as quality of life or caregiver burden. A 4-month home-based specialist palliative care service for 50 patients with advanced neurodegenerative disorders (MND, MS, IPD, MSA and PSP) found a significant improvement in quality of life and physical symptoms (pain, breathlessness, sleep disturbance and bowel symptoms) across the conditions, but, again, no effect was seen for caregiver burden. 25 In contrast with our trial, that trial did not include patients without capacity. Of note, none of the abovementioned trials reported data on intervention fidelity, which is a key factor when evaluating complex interventions. Indeed, implementation fidelity in randomised controlled trials of palliative care for complex interventions is under-recognised and under-reported. 89 In contrast to our trial and the reported trials in neurological condition, studies testing the effectiveness of palliative care interventions for advanced cancer have shown benefit to multidimensional quality-of-life outcomes and survival, but less so for physical symptoms. 36,90,91 Although the prognosis and trajectories of LTNCs are vastly different from cancer and even vary for each type of LTNC. In a trial92 evaluating palliative care for heart failure patients, an improvement on anxiety and depression outcomes, as measured by the HADS, was also reported.

Interpretation

In this trial, we did not detect a difference between trial arms in the primary outcome, although we note that, compared with baseline, the scores on the primary outcome improved in both arms, significantly in the SIPC group and not significantly in the control group. The secondary outcome, IPOS Neuro-S24, followed this pattern, and the significant reduction in patient satisfaction seen in the standard care group further supports the trial findings in favour of SIPC. Compared with baseline, health and social care costs, including inpatient care, community care, outpatient care and home care, were reduced in both arms at 12 weeks. Although there was no significant difference between groups, this reduction in costs was larger in the SIPC group. The ICER suggests that, compared with SIPC, the control arm has a 1 point deterioration in utility at an additional cost of around £1000 per patient. The ICERs for SIPC are well within the usual thresholds for decision-making in the NHS and recommended by the National Institute for Health and Care Excellence (e.g. £20,000 or £50,000, as often used in end-of-life care therapies), making SIPC acceptable as a cost-effective intervention. No harms were identified and, in general, patients and clinicians welcomed the intervention. In addition, crucially, there were no increased costs to informal carers and, if anything, their costs may have been slightly lower in the intervention group.

To base the decision of effectiveness on the statistical significance is a long-recognised misuse of the p-value. The American Statistical Association released a policy statement in 2016 specifically targeting this issue. 93 A comment paper published in Nature earlier this year updated this concern regarding pervasive categorisation on the basis of the p-values. 94 However, through the mapping, survey and qualitative components, we also observed variations in integrated working and delivery of care, and more work is needed to understand the best ways to provide palliative care to this group and how to improve standard care, which varies considerably.

There may be several possible explanations for the non-significant results. The first relates to the outcome measures. The primary outcome measure of eight key symptoms (IPOS Neuro-S8) was selected based on the five symptoms that were most responsive to a palliative care intervention in our Phase II trial and symptom profile data from a longitudinal observational study of late-stage Parkinsonism syndromes. 27,40 In a preliminary psychometric evaluation, the measure exhibited promising psychometric properties. 68 In this trial, some items of the IPOS Neuro-S8, as well as the IPOS Neuro-S24, showed strong floor effects at baseline, indicating that some further refinement of the outcome measures, particularly for a more heterogeneous trial setting like the present one, may be necessary. In our data, the IPOS Neuro-S8, which measured participants’ psychological and spiritual well-being, information needs and practical issues, rather than their symptoms, appears to detect more changes.

The other key question is the match between the patient needs and the interventions offered by the services. Palliative care was first developed mainly for patients with cancer, although it should be noted that early studies of need and problems identified concerns for people with many different diseases, including neurological conditions. 95–97 It may be that palliative care has not sufficiently adapted and developed symptom and other treatments as yet for patients with complex LTNCs. Much research and therapeutic developments in palliative care have focused on cancer pain and other cancer symptoms, rather than on the most prevalent symptoms in this population. These include chronic pain and spasms found in neurological conditions, fatigue, weakness, difficulty sleeping, breathlessness and problems with mobility. 69 These are continuing serious concerns for these patients and their families, and should be the topic of future research. Such research could benefit care widely, and the therapies discovered could be applied by those with neurology and rehabilitation backgrounds. Furthermore, the models of palliative care operation also derived from cancer, and many staff working in palliative care have a cancer training and not a neurological training. Therefore, the models and approaches offered by the services may not have been optimal. It may also be that better targeting of the population likely to benefit from integrated palliative care is needed. Better working and integration between palliative care and neurology is needed to further improve the models of care for people seriously affected by neurological conditions. Such an approach needs to rise beyond specialist-defined boundaries and focus on the best ways of meeting the needs of patients and those important to them.

Additionally, as we used a trial design randomising at the individual level, there may have been some contamination, whereby participants in the standard care group received some components of the SIPC intervention. Indeed, this appears to have been the case, because our economic data found that some people in the standard care arm reported receiving palliative care by 12 weeks, when according to our design they should not have. Referrals to the palliative care teams for the intervention were carefully monitored to avoid contamination, but it seems that this did not fully work. Participation in the trial itself may function as an intervention on some level. This contamination may have occurred through the research contacts, when participants were visited in their homes by friendly, caring researchers (often research nurses), who gave them the time to air their concerns and feel listened to. Indeed, our qualitative findings demonstrate that this was a valued aspect of the holistic assessment received as part of the intervention and may have been mistaken for palliative care in the standard care arm. As such, receiving this to some level through the research contacts probably had benefits for those in the standard care group. In both groups, we saw a reduction in the burden of symptoms, though to a lesser degree in the standard care group; therefore, although the mean change score in the SIPC group for the primary outcome was statistically different from zero, this potential contamination may have further reduced the effect size.

Finally, the SIPC may not have had enough time for the intervention teams to build sufficient rapport with patients and caregivers to address some of the more complex issues, such as advance care planning, supporting caregivers and optimal management of refractory symptoms. Some of the needs identified could be addressed only by referring or signposting to other services (e.g. social services for review of benefits). Therefore, SIPC often had to rely on the actions of other services that it referred to or that were catalysed by SIPC. The time scale of 12 weeks may not have been sufficient to ensure that SIPC could directly act on, or follow up on, its recommendations. It may also be that for some of the longer-term, more intractable, difficulties that it took longer than 12 weeks to see an effect, especially of referrals to other services. We were able to collect longer-term follow-up data, and these will be analysed in future research. Ideally, population-based routine data could be used to augment this analysis. Nevertheless, the few other trials assessing palliative care interventions in this population had similar findings despite varying lengths of intervention (up to 6 months). 24–26

Strengths and limitations

There are several strengths to this study. To the best of our knowledge, this is the largest palliative care trial in a non-cancer population and also the first to include more than one common LTNC. We included patients with cognitive decline who lacked capacity, which is common in neurological conditions, and recruited their caregivers as the proxy to provide data to inform the imputation process. We recruited a large number (n = 229) of caregivers of patients with advanced LTNCs and collected a range of caregiving outcomes, including quality of life, caregiver burden and positivity. The randomisation process appears to be successful. The only imbalanced variable at baseline was ethnicity, with slightly more non-white patients in the standard care group, for which we have adjusted in-group comparisons. Our data quality was high, with much lower attrition and fewer missing data than would be expected in a palliative care trial of this scale. When planning the study, we set the attrition rate at 17%, three times of that in our Phase II MS trial, to accommodate heterogeneities across centres and conditions. The missing data for the primary outcome due to withdrawal or for unknown reasons were 4% at 12 weeks. Although it is impossible to blind the participants and the persons delivering the interventions, research nurses collecting the data were blinded, and the chief investigators and analysis team were kept blinded until the planned analyses were completed. The embedded qualitative component enables us to have a better understanding about the process, the active ingredients and the mechanism of intervention.

We acknowledge that there are some limitations of this study. The sample largely comprised patients with MS and IPD, who tend to have a longer disease course. This is also reflected in the embedded qualitative study, which included mainly patients living with MS. It is possible that the baseline symptom profiles and therefore the subsequent impact and experience of SIPC are different for patients with LTNCs, with a more rapid decline. As mentioned above, the outcome measures used may not have been sensitive enough and did demonstrate some floor effects at baseline for some symptoms. The cost data were based on patient- (or carer-) reported use of services, which relies on their memory of the services received. They may have under- or over-reported some services, and/or may have made some miscategorisations, such as mistaking types of community care or palliative care. It is often difficult for patients to correctly categorise the types of nurses or others visiting them in the community; however, the mistaken categories in community home visiting services would have had little influence on the overall costs. The main driver of costs was hospital admissions, which are less susceptible to miscategorisation as non-admission.

Although every effort was made to standardise the intervention, and our fidelity data show that this was, on the whole, well managed, there were some differences across centres, namely some intervention teams were hospice based and others were hospital based, which led to differences in the make-up of their MDTs, as well as the services and therapies they were able to offer. In addition, the clinical services at baseline and the integration between palliative care and neurology varied across our centres and across diseases. Some patients in the standard care arm reported that they were receiving palliative care at baseline and, although this did not change during the study, this is because either they mistook the research interviews for palliative care or there was contamination, which would have reduced the chances of finding a difference between groups.

Implications

Conclusions

To the best of our knowledge, this is the largest palliative care trial in people with a variety of LTNCs. Although no significant between-group differences were seen, we have demonstrated that SIPC provides improvements in patient-reported physical symptoms, at a lower cost and without any harmful effects when compared with standard care. However, further work is needed to refine SIPC and the provision of holistic, palliative care approaches for this patient group, with a particular focus on better integration of existing services and specialties, as well as the appropriate timing and criteria for the referral of LTNC patients to specialist palliative care.

OPTCARE Neuro investigators

Professor Irene J Higginson (co-chief investigator), Dr Wei Gao (co-chief investigator, trial statistician), Professor Ammar Al-Chalabi, Dr Cynthia Benz, Dr Rachel Burman, Dr Anthony Byrne, Professor K Ray Chaudhuri, Dr Vincent Crosby, Dr Catherine Evans, Professor Matthew Hotopf, Dr Diana Jackson, Professor P Nigel Leigh, Professor Paul McCrone, Dr Fliss Murtagh, Professor Andrew Pickles, Dr Eli Silber, Dr Andrew Wilcock and Professor Carolyn A Young.

Data Monitoring and Ethics Committee

We thank the external members of the Data Monitoring and Ethics Committee, Professor Mike Bennett (chairperson), Professor Gunn Grande, Dr David Oliver, Professor Raymond Voltz and Professor Stephen Walters, for their advice and support.

Study Steering Committee

We thank the external members of the Study Steering Committee, Professor Marie Fallon (chairperson), Dr Cynthia Benz, Professor Mogens Groenvold, Professor William Hollingworth, Dr Denise Howel, Professor Huw Morris, Mr Foster Murphy, Dr Diane Playford, Professor Julia Riley and Professor Jane Seymour, for their advice and support.

Patient and public involvement

Our thanks go to the OPTCARE Neuro PPI members, Dr Cynthia Benz, Mr David Charlton, Mr Colin Fellows, Ms Helen Findlay and Mrs Savita Jain, for their guidance and contributions throughout the study.

Researchers

The team thank all the researchers involved in recruitment, data collection and input: Dr Sarah Awan, Virginia Bray, Evelyne Burssens, Gillian Carey, Rebecca Cloudsdale, Joanna Davies, Mim Evans, Dr Caroline Facey, Lynne Harry, Asmah Hussain, Kate Jones, Paramjote Kaler, Loretta Kerr, Julie Lynch, Cathann Manderson, Jenifer Newton, Caty Pannell, Louise Pate, Maria Preece, Helen Santander, Sarah Schofield, Chifundo Stubbs, Caroline Sunderland, Patricia Thomas, Richard Turner and Dr Liesbeth van Vliet.

Administrative support

Our thanks go to those who provided administrative support: Deborah Tonkin, Zaynah Sheikh, Daniel Gulliford, India Tunnard and Anna Johnston.

Palliative care teams

We offer our appreciation to the palliative care teams and their members who delivered the intervention and provided care for our participants: Marsha Dawkins, Dr Sabrina Bajwah, Connie Jackson, Nottingham University Hospital palliative care team, Martlets Hospice, Queenscourt Hospice, City Hospice, Marie Curie Hospice for Cardiff and the Vale, Ashford and St. Peter’s Hospital palliative care team, Dr Ellie Smith and St. Luke’s Hospice Sheffield.

King’s College London Clinical Trials Unit

The UK Clinical Research Collaboration-registered King’s College London CTU at King’s Health Partners provided the trial database and randomisation systems. We thank the entire King’s College London CTU team, in particular Caroline Murphy, Joanna Kelly and Beverley White-Alao.

Finally, we are extremely grateful to all the participants who supported this study and gave their time so generously.

Contributions of authors

Dr Nilay Hepgul (https://orcid.org/0000-0002-5980-1457) (Research Associate and Trial Manager, King’s College London) managed the study and contributed to data collection, site monitoring, data cleaning, data analysis, interpretation of the data and leading the writing of the report.

Dr Rebecca Wilson (https://orcid.org/0000-0003-4709-7260) (Research Associate, King’s College London) contributed to data cleaning, data analysis, interpretation of the data and leading the writing of the report, especially relating to the analysis of effectiveness.

Dr Deokhee Yi (https://orcid.org/0000-0003-4894-1689) (Health Economist, King’s College London) contributed to data cleaning, data analysis, interpretation of the data and leading the writing of the report, especially relating to health economic components.

Dr Catherine Evans (https://orcid.org/0000-0003-0034-7402) (Senior Clinical Lecturer in Palliative Care, King’s College London; Honorary Nurse Consultant, Sussex Community NHS Foundation Trust) contributed to study design, qualitative data analysis, interpretation of the data and leading the writing of the report, especially relating to qualitative components.

Dr Sabrina Bajwah (https://orcid.org/0000-0001-5338-8107) (Consultant and Honorary Senior Lecturer in Palliative Care, King’s College London) was the site principal investigator and contributed to intervention design, intervention delivery, interpretation of the data and leading the writing of the report, especially relating to intervention fidelity.

Dr Vincent Crosby (Consultant in Palliative Care, Nottingham University Hospitals NHS Foundation Trust) was the site principal investigator and contributed to study design, intervention design, intervention delivery, interpretation of the data and writing of the report, especially relating to intervention fidelity.

Dr Andrew Wilcock (https://orcid.org/0000-0002-3214-1188) (Consultant in Palliative Care, Nottingham University Hospitals NHS Trust) contributed to study design, interpretation of the data and writing of the report.

Dr Fiona Lindsay (https://orcid.org/0000-0003-4223-959X) (Consultant in Palliative Care, Martlets Hospice) was the site principal investigator and contributed to study design, intervention delivery, interpretation of the data and writing of the report.

Dr Anthony Byrne (https://orcid.org/0000-0002-1413-1496) (Consultant in Palliative Care and Clinical Director, Marie Curie Research Centre, Cardiff University) was the site principal investigator and contributed to study design, intervention delivery, interpretation of the data and writing of the report.

Professor Carolyn Young (https://orcid.org/0000-0003-1745-7720) (Consultant Neurologist, The Walton Centre NHS Foundation Trust) was the site principal investigator and contributed to study design, recruitment, interpretation of the data and writing of the report.

Dr Karen Groves (Consultant in Palliative Care, Queenscourt Hospice) contributed to intervention delivery, interpretation of the data and writing of the report.

Dr Clare Smith (https://orcid.org/0000-0002-7754-9769) (Consultant in Palliative Care, Ashford and St Peter’s NHS Foundation Trust) was the site principal investigator and contributed to intervention delivery, interpretation of the data and writing of the report.

Dr Rachel Burman (https://orcid.org/0000-0002-9276-7174) (Consultant in Palliative Care, King’s College Hospital) contributed to study design, interpretation of the data and writing of the report.

Professor K Ray Chaudhuri (https://orcid.org/0000-0003-2815-0505) (Consultant Neurologist, King’s College Hospital) contributed to study design, recruitment, interpretation of the data and writing of the report.

Dr Eli Silber (https://orcid.org/0000-0002-3972-0780) (Consultant Neurologist, King’s College Hospital) contributed to study design, recruitment, interpretation of the data and writing of the report.

Professor Irene J Higginson (https://orcid.org/0000-0002-3687-1313) (Professor of Palliative Care and Policy, King’s College London) was co-chief investigator and led the conception and design of the study, organisation of the conduct of the study, development of study protocol, interpretation of the data and leading the writing of the report, as co-senior author.

Dr Wei Gao (https://orcid.org/0000-0001-8298-3415) (Reader in Statistics and Epidemiology, King’s College London) was co-chief investigator and trial statistician, and led the conception and design of the study, organisation of the conduct of the study, development of the study protocol, statistical analysis plan, data analysis, interpretation of the data and leading the writing of the report, as co-senior author.

All authors approved the final version.

Publications

Gao W, Crosby V, Wilcock A, Burman R, Silber E, Hepgul N, et al. Psychometric properties of a generic, patient-centred palliative care outcome measure of symptom burden for people with progressive long term neurological conditions. PLOS ONE 2016;11:e0165379.

van Vliet LM, Gao W, DiFrancesco D, Crosby V, Wilcock A, Byrne A, et al. How integrated are neurology and palliative care services? Results of a multi-centre mapping exercise. BMC Neurol 2016;16:63.

Ang K, Hepgul N, Gao W, Higginson IJ. Strategies used in improving and assessing the level of reporting of implementation fidelity in randomised controlled trials of palliative care complex interventions: a systematic review. Palliat Med 2018;32:500–16.

Hepgul N, Gao W, Evans CJ, Jackson D, van Vliet LM, Byrne A, et al. Integrating palliative care into neurology services: what do the professionals say? BMJ Support Palliat Care 2018;8:41–4.

Wilson R, Hepgul N, Saha RA, Higginson IJ, Gao W. Symptom dimensions in people affected by long-term neurological conditions: a factor analysis of a patient-centred palliative care outcome symptom scale. Sci Rep 2019;9:4972.

Gao W, Wilson R, Hepgul N, Yi D, Evans C, Bajwah S, et al. Effect of short-term integrated palliative care on patient-reported outcomes among patients with advanced long-term neurological conditions: a randomized clinical trial. JAMA Netw Open 2020;3:e2015061.

Data-sharing statement

All data requests should be submitted to the corresponding author for consideration. Access to available anonymised data may be granted following review.

Patient data

This work uses data provided by patients and collected by the NHS as part of their care and support. Using patient data is vital to improve health and care for everyone. There is huge potential to make better use of information from people’s patient records, to understand more about disease, develop new treatments, monitor safety, and plan NHS services. Patient data should be kept safe and secure, to protect everyone’s privacy, and it’s important that there are safeguards to make sure that it is stored and used responsibly. Everyone should be able to find out about how patient data are used. #datasaveslives You can find out more about the background to this citation here: https://understandingpatientdata.org.uk/data-citation.

Disclaimers

This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HS&DR programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HS&DR programme or the Department of Health and Social Care.