Is Short-Term Palliative Care Cost-Effective in Multiple Sclerosis? A Randomized Phase II Trial

Article Outline

• Abstract
• Introduction
• Methods
  • Design Overview, Setting, and Participants
  • Randomization and Interventions
  • Data Collection, Outcomes, and Follow-Up
  • Costs
  • Statistical Analysis
• Results
  • Outcomes
  • Service Use and Cost-Effectiveness
• Discussion
  • Characteristics of Patients and Caregivers Included in the Study
  • Did the PCT Work as Expected?
  • How Much Did the PCT Appear to Save in Terms of Costs?
  • How Could Our Results Be Flawed?
  • How Do Our Results Compare with Others?
• Conclusions
• Acknowledgments
• References
• Copyright

Abstract 

Context

Palliative care is being advocated for noncancer patients but needs evidence of effectiveness and cost-effectiveness.

Objective

We evaluated the cost-effectiveness of a new palliative care service for people with multiple sclerosis (MS).

Methods

We used a randomized fast-track Phase II controlled trial. Patients in South East London who were severely affected by MS were referred by clinicians to the trial. After baseline interview, patients were randomly allocated to either a multiprofessional palliative care team (PCT) immediately (fast track) or the control care group who continued best usual care for three months and then were offered the PCT. Data were collected at baseline, 6, 12, 18, and 26 weeks on use of services, patient symptoms, other outcomes, and caregiver burden.

Results

Fifty-two patients were randomized: 25 fast track and 21 control patients completed the trial. There was a high level of disability, and mean Expanded Disability Status Scale score was 7.7 (median 8, standard deviation 1.0). At 12 weeks, caregiver burden was 4.47 points lower (95% confidence interval [CI]: 1.05–7.89) in the fast track compared to the control group. Mean service costs, including inpatient care and informal care, over the 0–12-week follow-up were £1,789 lower for the fast-track group (bootstrapped 95% CI: −£5,224 to £1,902). There was a trend toward lower community costs in the fast-track group and no differences in costs to informal caregivers.

Conclusions

The trial suggests that short-term palliative care for people severely affected by MS and their caregivers will be cost-effective and warrants further study. The fast-track trial design could be used to assess this.

Key Words: Palliative, palliative care, cost-effective, multiple sclerosis, hospice, end-of-life care, caregiver

Back to Article Outline

Introduction 

Health care costs in the last year of life are high, between 12% and 25% of health care spending.¹ In chronic disease, costs rise with the increasing disability as disease advances.², ³, ⁴, ⁵ Despite these high costs, many patients have inadequate symptom relief, coordination, and psychological and social support, with a high burden for the informal caregivers.⁶, ⁷ Palliative care offers a means to improve this situation. Although there is evidence to support the effectiveness of hospices⁸ and palliative care teams (PCTs),⁹, ¹⁰, ¹¹ this is mainly confined to studies in cancer, close to the end of life, and rarely considers the effects on informal carers.¹⁰, ¹² Palliative care has been proposed for conditions other than cancer, and earlier in the disease trajectory, but as yet few evaluations or health economic assessments have been undertaken.⁸, ¹¹, ¹³, ¹⁴

Over 2.5 million people worldwide are affected by multiple sclerosis (MS); it is the most common cause of neurological disability in young adults in Western countries.¹⁵ Although most follow a relapsing-remitting course initially, about 15% present with a primary progressive course, and half with relapsing-remitting disease develop secondary progression.¹⁵ Although early disease-modifying therapies in relapsing-remitting MS show promise, they are of little benefit in progressive disease.¹⁵ Much of the burden of illness falls on the community and on lay caregivers.⁷, ¹⁶ The more advanced stages are accompanied by profound physical and psychological symptoms, in some instances worse than among people affected by cancer.¹⁷, ¹⁸, ¹⁹

Studying palliative care in MS addresses an important gap in service provision and provides a potential model for palliative care in other neurological and noncancer diseases with a similar trajectory, such as organ failure. We, therefore, conducted a trial to determine if there was sufficient evidence of cost-effectiveness of a new palliative care service for people with MS to warrant further development.

Back to Article Outline

Methods 

Design Overview, Setting, and Participants 

Patients were randomized to receive a PCT immediately (fast track) or after a 12-week wait (usual best practice, control).¹⁸, ²⁰

Subjects were 69 people with MS, 52 of whom took part in the trial (Fig. 1). Inclusion criteria were patients in South East London, living with MS and deemed (by clinicians) to have one or more of unresolved symptoms, psychosocial concerns, end-of-life issues, progressive illness, or complex needs (i.e., palliative care needs). Referrals were screened by a consultant in palliative medicine who was independent from delivering the service (P. M. E./I. J. H). Educational seminars informed local health and social care professionals about the PCT. Exclusion criteria included if the referring staff or the screening deemed patients had very urgent needs or were deteriorating rapidly when immediate referral to the service was offered. Caregivers were identified through patients. Reasons for drop out, no interview, and refusal were recorded whenever possible. The King's College Hospital Research Ethics Committee gave full ethical (Institutional Review Board) approval for the study, and all participating patients gave written consent.

• 
  • View Large Image
  • Download to PowerPoint

• Fig. 1 

  CONSORT diagram showing the flow of patients through the study. N (N)=patients remaining in study (interviews actually completed at this stage). A small number of interviews were missed because the patient was unavailable (away/in hospital) and one error in scheduling.

Randomization and Interventions 

After consent and baseline interview, the researcher e-mailed relevant data to independent statisticians who conducted the randomization using the minimization method²¹ to give an equal balance of gender, age, date of diagnosis, and according to whether patients could or could not communicate. Patients were randomized to receive either the PCT immediately (fast track) or usual best practice alone (control) for 12 weeks, after which they were offered the service. The statistician informed researchers who then informed patients of their allocation. If patients were randomized to the fast track, their information was passed to the PCT, which contacted them within 48 hours. If patients were in the control arm, the researcher held their data until after the third research interview at 12 weeks.

In addition to continuing to receive usual services (see below), patients in the fast-track group received care from a PCT.¹⁸, ²⁰ This comprised one part-time consultant in palliative medicine, one part-time clinical nurse specialist, one administrator, and one psychosocial worker, and was based in a large teaching hospital. Patients were visited in their own homes or sometimes outpatient clinics, nursing homes, or hospital. The PCT undertook assessments, suggested ways to improve physical, emotional, social, and other problems, provided specialist welfare benefits advice and bereavement support, and liaised with and acted as a catalyst for local services, both primary and specialist teams. After initial assessment, treatment was recommended.¹⁸, ²⁰ Care was provided in a similar way to palliative care consultation services described elsewhere,⁹, ¹¹ although the PCT worked in both hospital and the community, and so could visit patients wherever they were. Patients had one to three contacts (visits and/or phone calls) from the PCT, although a small number (around 12%) were referred for longer-term “community” palliative care.²⁰ For patients randomized to the control group, community and hospital services (including neurologists, MS nurses, rehabilitation, neurological, and social services) were offered as usual.

Data Collection, Outcomes, and Follow-Up 

We conducted face-to-face interviews with patients and gave self-complete questionnaires to caregivers. At baseline, we collected demographic and clinical data, and the patient's functional status (both self-report, using the United Kingdom Neurological Disability Scale [UNDS]²² and interviewer-assessed using the Expanded Disability Status Scale [EDSS],²³ administered by a consultant neurologist [E. S.]). We collected outcome and cost data at baseline (before randomization) and at 6, 12, 18 (only control group—after they received PCT), and 24 weeks.

Our standardized questionnaires included the Palliative Care Outcome Scale (POS-8),²⁴, ²⁵ comprising eight questions on anxiety, patient and carer concerns, and practical needs, each rated 0–4; a single-item POS pain score (rated 0 [best] to 4 [worst]); and caregivers' burden (using the 12-item version of the Zarit Carer Burden Inventory [ZBI]).²⁶ Higher scores represent greater problems on all the scales. We were unable to blind the interviewers or participants from group allocation.

Costs 

Costs were assessed using a broad perspective—including costs to health, social, and voluntary services, and informal caregivers. Data regarding the use of health and social services in the previous three months were collected at each interview using a standard schedule.²⁷ Service costs were calculated by combining service use data with nationally applicable unit costs. These took into account salaries, overheads, and training, and the ratio of direct patient contact time to noncontact time.²⁸ Informal care costs were estimated by assuming that in the absence of a carer, the help would need to be provided by a home care worker, and the unit costs of the latter were, therefore, used as a “shadow price.”

Statistical Analysis 

We planned an intention-to-treat analysis, irrespective of whether patients were assessed as having palliative care needs or the nature of contact with the PCT. We tested the differences between the two arms (expressed as differences between follow-up and baseline interviews) using one-way analysis of variance (ANOVA), checking statistical assumptions and adjusting for baseline scores. Our primary point of analysis was at 12 weeks (before the control group received the PCT). We separately explored missing data²⁰ and tested imputations (last value carried forward, next value carried backward, and mean value) in a sensitivity analysis. We also explored whether changes seen in the outcome data in the fast-track group following receipt of the PCT were reflected in the control group after 12 weeks, when they also received the PCT.

Cost data are usually skewed; therefore, we used a bootstrapped regression model to produce confidence intervals (CIs) around the cost differences between the two groups. Comparisons were made of total service costs, and also costs that excluded inpatient care and informal care. Cost-effectiveness was analyzed by combining data on cost differences between the groups with data on outcome differences (POS-8 and ZBI at 12 weeks). Uncertainty around the cost-effectiveness estimates was explored by generating 1,000 resamples using bootstrapping and computing cost, and outcome differences for each. These were then plotted on cost-effectiveness planes. These are valuable for a Phase II study because they indicate whether the PCT would have better outcomes at higher costs, better outcomes at lower costs, worse outcomes at higher costs, or worse outcomes but at lower costs. For all of these analyses, we assessed cost-effectiveness only when both cost and outcome data were present.

We estimated that a sample of more than 25 patients in each arm would enable us to detect differences of >2 on the POS-8 at P<0.05, power 80% (with a standard deviation [SD] of 2.25) at 12 weeks. Because of the Phase II nature of the trial, we also estimated effect sizes and sample size estimates for future studies for those outcomes appearing close to significance.

Back to Article Outline

Results 

The 52 patients who were randomized to fast-track or control groups had a high level of disability (EDSS mean 7.7). There were no differences between the two groups in characteristics (Table 1, Table 2). Twenty-five of 26 fast track and 21 of 26 control patients completed the trial²⁰ (CONSORT diagram, Fig. 1). Main reasons for loss to follow-up were death or illness. There was one death in the fast-track group and three in the control group. Two hundred seventeen of 225 possible questionnaires were completed.²⁰ Caregiver data were missing when patients did not have caregivers.

Table 1. Characteristics of Patients and Caregivers in the Two Randomized Groups

	Fast Track (n=26)	Control (n=26)
Characteristic	n	n
Demographic characteristics
Women	17	19
Age, mean (median, SD)	53 (53, 10.5)	53 (52, 10.4)
Ethnic group
White (UK, Irish, European)	23	24
Other	3	2
Type of MS
Primary progressive MS	13	10
Secondary progressive MS	12	14
Other (includes Relapsing/Remitting MS (2) and Devic's Disease (1))	1	2
Education: continued after minimum school-leaving age	11	14
Informal caregiver
No informal caregiver	6	3
Partner/spouse	14	15
Offspring (daughter/son)	4	3
Sibling (sister/brother)	1	2
Parent(s)	1	3
Type of caregiver contact
Lives alone	5	4
Lives with caregiver	20	21
Other caregiver contact	1	1
Functional status, mean (median, SD)—high scores indicate greater severity
UNDS function score (total range 0–60 [worst])	28 (28, 8.9)	30 (29, 9.2)
EDSS function score (total range 0–10 [worst])	7.7 (8, 1)	7.9 (8, 1)

Note: There were no significant differences between groups at baseline in any of these characteristics.

Table 2. Mean (SD) Outcome Scores at Baseline and Mean (95% CI) Differences in Score from Baseline Over Time

Measure and Group	Baseline n, Mean (SD)	Six-Week Mean Difference from Baselinea (95% CI)	Twelve-Week Mean Difference from Baselineb (95% CI)
Palliative Outcome Scale-8 (range=0–32)
Fast track	24, 13.7 (3.7)	−0.68 (−2.22 to 0.86)	−0.42 (−2.50 to 1.67)
Control	21, 13.4 (3.7)	−0.55 (−2.42 to 1.33)	−0.95 (−2.87 to 0.97)
POS pain (range=0–4)
Fast track	26, 1.69 (1.35)	−0.23 (−0.66 to 0.20)	−0.46 (−0.98 to 0.05)c
Control	25, 1.28 (1.24)	0.09 (−0.36 to 0.54)	0.30 (−0.16 to 0.76)
ZBI-12 (range=0–48)
Fast track	13, 20.5 (10.7)	1.10 (−3.43 to 5.63)	−2.88 (−5.99 to 0.24)d
Control	19, 22.6 (6.2)	−1.13 (−3.41 to 1.14)	1.58 (−0.51 to 3.67)

Note: High scores indicate greater burden/symptoms, a negative change in score implies a reduction (i.e., an improvement).

Outcomes 

There was no significant difference over time in POS-8, but at Week 12, caregiver burden ZBI scores had reduced in the fast-track group and increased slightly in the control group. The difference in change in burden was 4.47, 95% CI 1.05 to 7.89 (the effect size was 1.3 and the total sample size required to detect this is 20). There was a trend toward a reduction in pain in the fast-track group and an increase in the control group (with an effect size of 0.6 and a total sample size required to detect this is 56). The results were similar in nonimputed and imputed data, for all the imputation methods. When we followed up the patients and caregivers from 12 to 24 weeks, we found there was a tendency for caregiver burden to reduce in the control group, after beginning to receive the intervention. In the control group, the ZBI-12 fell (i.e., improved) by 1.40 (95% CI −3.54 to 0.74) between Week 12 and Week 18, and by 1.58 (95% CI −3.21 to 0.07) between Week 12 and Week 24. Pain followed a similar pattern, reducing from a mean of 1.5 at 12 weeks, to 1.3 at 18 weeks and 1.1 at 24 weeks in the control group following care from the PCT. Caregiver burden and pain remained largely unchanged in the fast-track group between Week 12 and Week 24.

Service Use and Cost-Effectiveness 

At baseline in both groups, over two-thirds were in contact with either district or practice nurses and half of each group were in contact with MS nurse specialists (Table 3). By the 12-week follow-up, 39% of the fast-track group reported having received palliative care nursing, with a mean of almost three contacts. Almost one-quarter reported seeing a specialist at home, most of whom were likely to be palliative care consultants. The control care patients were more likely to be in contact with general practitioners, to receive help from family/friends and to be admitted to or seen in hospital. Receipt of MS nurses was similar in the two groups. The total costs, with inpatient and informal care costs included, over the 0–12-week follow-up were £1,789 lower for the fast-track group (bootstrapped 95% CI −£5,224 to £1,902). Excluding inpatient care and informal care, mean service costs were £1,195 lower for the fast-track group (bootstrapped 95% CI −£2,916 to £178, Table 4).

Table 3. Service Use in the Previous Three Months Prior to Baseline Assessment and Twelve-Week Interviews—Self-Report of Patients

n = number of patients who reported receiving that service.

Table 4. Mean (SD) Service Costs in the Three Months Prior to Baseline Assessment and Twelve-Week Follow-Up Interviews

Costs are in 2005 £s.

The point estimates in the cost-effectiveness planes suggest that it was cost saving, with equivalent outcomes on the POS-8 and improved outcomes for the ZBI. The cost-effectiveness plane in Fig. 2A (POS-8 data) shows 33.8% replications were in the lower right quadrant, indicating that the fast-track group has better outcomes and lower costs than the control group, and 54.9% were in the quadrant indicating worse outcomes but lower costs. By contrast, when basing the cost-effectiveness results on the caregiver burden (ZBI) (Fig. 2B), 47.3% replications were in the quadrant showing lower costs and better outcomes and 48.0% in the quadrant showing higher costs and better outcomes.

• 
  • View Large Image
  • Download to PowerPoint

• Fig. 2 

  Cost-effectiveness analysis at 0–12 weeks for PCT compared with control for (A) POS-8 and (B) ZBI. Dots to the right of the axis indicate improved outcomes; dots below the horizontal axis show lower costs. Therefore, dots in the lower right quadrant show both improved outcomes and lower costs, and those in the upper left quadrant show worse outcomes and higher costs.

Back to Article Outline

Discussion 

For those who experience MS in advanced stages, it often can be a devastating condition. Acute care for patients with chronic or progressive neurological conditions in general wards can often be inappropriate and insensitive to the needs of patients and their caregivers.⁷ Palliative care may offer an alternative approach. The results of this Phase II trial suggest that, on average, three contacts with a PCT may reduce, for people affected by MS, caregiver burden, costs to the health service, and possibly patient pain, but not patient anxiety and information needs as assessed by POS-8. The cost-effectiveness planes suggest that the effects of the PCT are most often in the quadrants with both better outcomes and lower costs.

Characteristics of Patients and Caregivers Included in the Study 

Our group was a highly disabled group of patients with a mean EDSS score of about 8, which means “essentially restricted to bed or chair or perambulated in wheelchair.”²² Most had primary or secondary progressive MS, suggesting that normally, over time, they would deteriorate. They had initial POS-8 scores of 13–14, which suggest moderate levels of palliative care need and pain scores of 1–2, suggesting moderate pain. However, caregiver burden was high. Interpretation of the Zarit Scale suggests that a score of greater than 6.5 on the 12-item scale (12 on the full 22-item scale) is abnormal.²⁹ These caregivers had mean scores on the ZBI-12 of over 20 at baseline, considerably higher than found among caregivers supporting people with moderate dementia (mean score of 13)³⁰ and cancer (mean 12).³¹ The improvement in caregiver burden of 4.5 points on the ZBI-12 compares extremely favorably with other interventions, for example, with a nonrandomized study of rivastigmine for Alzheimer's disease,³⁰ where improvement was only 1.7 points on the 22-item ZBI (which equates to <1 on the 12-item ZBI scale) and is of similar magnitude to training caregivers of stroke patients.³²

Did the PCT Work as Expected? 

In the fast-track group at 12 weeks, two-thirds of patients reported having seen either a palliative care nurse or a specialist at home, which was most likely to be the palliative care consultant. The number of visits was small and agreed with the planned strategy of intervention by the PCT, which aimed to complement existing services rather than replacing them, with most patients receiving around three visits. Much of the work was in patients' homes, with some specialist contact in hospital being reported. Interestingly, contrary to initial concerns, input from MS nurses was not lower in the fast-track group—in fact there was a nonsignificant trend for it to be higher. It may be that some patients mistook the PCT nurses for MS nurses, although equally the reverse also may have been possible.

How Much Did the PCT Appear to Save in Terms of Costs? 

The PCT potentially offered a saving of £1,195 in community costs per patient over three months and a total cost saving per patient of £1,789 (including inpatient and informal caregiver savings). These savings appeared to be mainly due to a lower use of primary and acute hospital services. The informal care costs were little affected by the PCT—if anything, there was a slight reduction. The implications of these findings could be considerable—around 85,000 people of the 57 million UK population have MS, of whom about 11% (9,350)¹⁵, ³³ are severely affected, with an EDSS of 8 or more (note this cut-off may underestimate the number of people who would benefit). Even if the palliative care service produced only three months of cost savings, rolling it out across the UK could result in total cost savings of almost £17 million per year. If the savings were extended over a longer period, for example, six months, cost savings would be double this. Our data support the trial by Brumley et al.,¹⁴ which found that in-home palliative care for people with chronic obstructive pulmonary disease (COPD), cancer, and heart failure produced cost savings. However, they did not measure the effects on informal care, and our intervention was of a shorter duration earlier in care, and, in contrast to their findings, did not shorten survival. Indeed, survival was slightly but nonsignificantly better in our palliative care group, a finding that, although small, warrants attention in future studies.

How Could Our Results Be Flawed? 

Our study was a Phase II rather than Phase III trial and, therefore, aimed to determine whether the service offered sufficient benefit to warrant further trial, but lacked power because of the small sample. Our groups were similar at baseline, showing our randomization using the minimization method worked well and differences between the groups were not due to selection or recruitment biases. The trial did suggest that there are improvements for caregiver burden and patient pain—which should be key outcomes in a Phase III trial. It is possible that the PCT affects other outcomes that either we did not measure or the study was not powered to detect, but this does not alter our conclusion that the PCT may have an effect. The effect sizes of 1.3 (caregiver burden) and 0.6 (patient pain) suggest that such a trial would be feasible with final sample sizes of over 60, which, allowing for some loss to follow-up and some missing data, especially when patients did not have informal caregivers, would mean that at least 80–100 patients would need to be recruited.

The randomization of patients appeared successful and we were able to recruit our target numbers using this fast-track trial design.²⁰ Randomized trials are the gold standard for reducing bias. Although analytical techniques, such as propensity scoring,⁹ attempt to control for selection biases, they can only control for known and recorded biases. Our data are more robust, making the differences unlikely to be due to patient preferences or selection.

There is a possibility of measurement bias, as neither our patients nor our interviewers were blinded. However, it is difficult to envisage any way patients could be blinded—as they would know whether they were receiving the intervention. Brumley et al.¹⁴ in their trial of in-home palliative care, blinded interviewers, but they collected data by telephone and did not ask about services received. In a randomized trial of a breathlessness service, we attempted to blind interviewers, but found that patients can report service activity in a way that made it clear which group they were in. We attempted to reduce measurement biases by ensuring that interviewers were completely separate from the PCT, were supportive of the need to find out whether the service was effective, and by using a range of interviewers, some of whom were not aware in advance to which group patients were allocated.

Our results are strengthened further by conducting the intention-to-treat analysis. However, it was clear to the clinical team that (1) a few patients were assessed as not having many palliative care needs and (2) our data show that a few patients received very little contact with the PCT. Further exploration of the data may help to identify those patients who appeared to benefit most, helping to refine the referral criteria. We used patient reports of service use to determine costs. Patient reports may not exactly reflect billing data—although it is questionable which is the most valid. We observed that on some occasions patients confused some services (e.g., distinguishing between the palliative care and the MS nurse), but they appeared to be very clear about the total number of services visiting. A further validation might be in the future to collect service use data from caregivers and/or hospitals. We were able to collect data on lay caregiver costs, which was the largest contributor to care costs and was largely unaffected by the PCT. It could be argued that we should have used different assumptions for lay caregiver costs—for example, minimum wage or no cost at all. However, as the PCT did not affect the lay caregiver costs very much, this would not have altered our results. The PCT appeared to reduce both hospital and community service costs.

Because of our trial design, we were only able to measure differences during the 12 weeks before the control group received the PCT. It may be that the cost savings and outcome benefits extended beyond this time, and we were unable to measure this. It could be argued that ideally a traditional randomized trial, without offering the control group the PCT, should have been conducted. However, we achieved much better recruitment than most palliative care trials using this fast-track design, and maintained the good will of patients, caregivers, and staff. It is questionable whether a traditional randomized trial would have achieved this.

How Do Our Results Compare with Others? 

In a climate where randomized trials of palliative care services are rare and often suffer from problems of failure to recruit, attrition, and other biases,¹⁸, ³⁴ our Phase II trial, following careful service modeling (Phase I),¹⁸ was successful in achieving the intended numbers in the time expected. We believe that this fast-track trial method is important for palliative care trials in the future. The cost savings of our PCT were similar to, but slightly smaller than, those of two retrospective comparisons of cost savings offered by PCTs, one using comparisons of contemporary patients in the United States⁹ and the other using historical data¹³ in Spain. Our differences may be because of our shorter follow-up period of three months for the cost data, the different population (patients with MS), the different countries (United States, Spain, United Kingdom), or that the nonrandomized studies overestimated cost savings because of biases that could not be accounted for. We also took a broader approach to costs, measuring community costs, informal caregiver costs, and inpatient costs – which were the main focus of the other studies. Our study provides sufficient evidence to continue to a Phase III trial for palliative care in MS and suggests that palliative care may be useful in other noncancer conditions. A negative finding at this stage would have been important, as it would have suggested palliative care for people with noncancer conditions should be rethought.

Back to Article Outline

Conclusions 

Overall, this Phase II randomized trial suggests that a short-term PCT for people severely affected by MS is likely to be cost-effective, reducing inpatient and community costs, caregiver burden, and possibly patient pain. As the first trial in such conditions, it suggests that further trials are now needed to test palliative care in people with MS and other noncancer and chronic neurological conditions. Further analysis of the effects of the PCT on symptoms other than pain also is needed. It appears that the intervention can be of effect after relatively short duration; however, ideally longer follow-up would be desirable. The fast-track design could be useful in future trials in noncancer populations.

Back to Article Outline

Acknowledgments 

The authors thank the MS Society (UK) whose funding made this project possible. Most importantly, they thank the patients and families for sharing their thoughts, experiences, and concerns with them and for taking part in the study. The authors thank the clinical staff involved in recruitment and in the service and those staff involved in interviewing, including Bella Vivat, Tariq Saleem, Troy Cartwright, Gay Foxwell, Barbara Gomes, Farida Malik, and Michael Walton, and the Project Advisory Committee (Keith Andrews, Fiona Barnes, Cynthia Benz, Colin Campbell, Sharon Haffenden, Martin Hunt, Robin Luff, David Oliver, Michael Ritchie, Sally Plumb, and Carolin Seitz) who oversaw the development of methods and trial conduct. The authors also specially thank Dr. Massimo Costantini who originally suggested using the delayed intervention randomized controlled trial and Dr. Gao Wei for assistance in the analysis.

Back to Article Outline

References 

1. Emanuel EJ, Emanuel LL. The economics of dying. The illusion of cost savings at the end of life. N Engl J Med. 1994;330(8):540–544
   • View In Article
   • MEDLINE
   • CrossRef
2. McCrone P, Allcock LM, Burn DJ. Predicting the cost of Parkinson's disease. Mov Disord. 2007;22(6):271–274
   • View In Article
3. The Canadian Burden of Illness Study Group. Burden of illness of multiple sclerosis: part I: cost of illness. Can J Neurol Sci. 1998;25(1):23–30
   • View In Article
   • MEDLINE
4. Grima DT, Torrance GW, Francis G, et al. Cost and health related quality of life consequences of multiple sclerosis. Mult Scler. 2000;6(2):91–98
   • View In Article
   • MEDLINE
   • CrossRef
5. Kobelt G, Berg J, Lindgren P, Fredrikson S, Jonsson B. Costs and quality of life of patients with multiple sclerosis in Europe. J Neurol Neurosurg Psychiatry. 2006;77(8):918–926
   • View In Article
   • CrossRef
6. Kristjanson LJ, Aoun SM, Oldham L. Palliative care and support for people with neurodegenerative conditions and their carers. Int J Palliat Nurs. 2006;12(8):368–377
   • View In Article
   • MEDLINE
7. Wollin JA, Yates PM, Kristjanson LJ. Supportive and palliative care needs identified by multiple sclerosis patients and their families. Int J Palliat Nurs. 2006;12(1):20–26
   • View In Article
   • MEDLINE
8. Taylor DH, Ostermann J, Van Houtven CH, Tulsky JA, Steinhauser K. What length of hospice use maximizes reduction in medical expenditures near death in the US Medicare program?. Soc Sci Med. 2007;65(7):1466–1478
   • View In Article
   • CrossRef
9. Morrison RS, Penrod JD, Cassel JB, et al. Cost savings associated with US hospital palliative care consultation programs. Arch Intern Med. 2008;168(16):1783–1790
   • View In Article
   • CrossRef
10. Lorenz KA, Lynn J, Dy SM, et al. Evidence for improving palliative care at the end of life: a systematic review. Ann Intern Med. 2008;148(2):147–159
    • View In Article
11. Higginson IJ, Finlay IG, Goodwin DM, et al. Is there evidence that palliative care teams alter end-of-life experiences of patients and their caregivers?. J Pain Symptom Manage. 2003;25(2):150–168
    • View In Article
12. Harding R, Higginson IJ. What is the best way to help caregivers in cancer and palliative care? A systematic literature review of interventions and their effectiveness. Palliat Med. 2003;17(1):63–74
    • View In Article
    • MEDLINE
    • CrossRef
13. Gomez-Batiste X, Tuca A, Corrales E, et al. Resource consumption and costs of palliative care services in Spain: a multicenter prospective study. J Pain Symptom Manage. 2006;31(6):522–532
    • View In Article
14. Brumley R, Enguidanos S, Jamison P, et al. Increased satisfaction with care and lower costs: results of a randomized trial of in-home palliative care. J Am Geriatr Soc. 2007;55(7):993–1000
    • View In Article
15. Murray TJ. Diagnosis and treatment of multiple sclerosis. BMJ. 2006;332(7540):525–527
    • View In Article
    • CrossRef
16. MacLurg K, Reilly P, Hawkins S, et al. A primary care-based needs assessment of people with multiple sclerosis. Br J Gen Pract. 2005;55(514):378–383
    • View In Article
    • MEDLINE
17. Edmonds P, Vivat B, Burman R, Silber E, Higginson IJ. Loss and change: experiences of people severely affected by multiple sclerosis. Palliat Med. 2007;21(2):101–107
    • View In Article
    • MEDLINE
    • CrossRef
18. Higginson IJ, Vivat B, Silber E, et al. Study protocol: delayed intervention randomised controlled trial within the Medical Research Council (MRC) Framework to assess the effectiveness of a new palliative care service. BMC Palliat Care. 2006;5:7
    • View In Article
19. Higginson IJ, Hart S, Silber E, Burman R, Edmonds P. Symptom prevalence and severity in people severely affected by multiple sclerosis. J Palliat Care. 2006;22(3):158–165
    • View In Article
    • MEDLINE
20. Higginson IJ, Hart S, Burman R, et al. Randomised controlled trial of a new palliative care service: compliance, recruitment and completeness of follow-up. BMC Palliat Care. 2008;7:7
    • View In Article
21. Roberts C, Torgerson D. Randomisation methods in controlled trials. BMJ. 1998;317(7168):1301
    • View In Article
    • MEDLINE
    • CrossRef
22. Rossier P, Wade DT. The Guy's Neurological Disability Scale in patients with multiple sclerosis: a clinical evaluation of its reliability and validity. Clin Rehabil. 2002;16(1):75–95
    • View In Article
    • MEDLINE
    • CrossRef
23. Rossier P, Wade DT. Validity and reliability comparison of 4 mobility measures in patients presenting with neurologic impairment. Arch Phys Med Rehabil. 2001;82(1):9–13
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (56 KB)
    • CrossRef
24. Hearn J, Higginson IJ. Development and validation of a core outcome measure for palliative care: the palliative care outcome scale. Qual Health Care. 1999;8:219–227
    • View In Article
    • MEDLINE
25. Higginson IJ, Donaldson N. Relationship between three palliative care outcome scales. Health Qual Life Outcomes. 2004;2:68–75
    • View In Article
    • MEDLINE
    • CrossRef
26. Bedard M, Molloy DW, Squire L, et al. The Zarit Burden Interview: a new short version and screening version. Gerontologist. 2001;41(5):652–657
    • View In Article
    • MEDLINE
    • CrossRef
27. Douglas HR, Normand CE, Higginson IJ, Goodwin DM, Myers K. Palliative day care: what does it cost to run a centre and does attendance affect use of other services?. Palliat Med. 2003;17(7):628–637
    • View In Article
    • MEDLINE
    • CrossRef
28. Curtis L, Netten A. Unit costs of health and social care. Canterbury: Personal Social Services Research Unit, University of Kent; 2005;
    • View In Article
29. Ory MG, Williams TF, Emr M, et al. Families, informal supports, and Alzheimer's disease. Current research and future agendas. Res Aging. 1985;7(4):623–644
    • View In Article
    • MEDLINE
    • CrossRef
30. Mets T, Vandewoude M, Jacquy J, et al. Patient and caregiver outcomes after 6 +/- 1.5-months of rivastigmine therapy for mild-to-moderate Alzheimer's disease: the Belgian FExT study. Curr Med Res Opin. 2007;23(10):2485–2501
    • View In Article
    • CrossRef
31. Harding R, Higginson IJ, Donaldson N. The relationship between patient characteristics and carer psychological status in home palliative cancer care. Support Care Cancer. 2003;11:638–643
    • View In Article
    • MEDLINE
    • CrossRef
32. Patel A, Knapp M, Evans A, Perez I, Kalra L. Training care givers of stroke patients: economic evaluation. BMJ. 2004;328(7448):1102
    • View In Article
    • CrossRef
33. Weinshenker BG, Rice GP, Noseworthy JH, et al. The natural history of multiple sclerosis: a geographically based study. 3. Multivariate analysis of predictive factors and models of outcome. Brain. 1991;114(Pt 2):1045–1056
    • View In Article
34. Jordhoy MS, Fayers P, Saltnes T, et al. A palliative-care intervention and death at home: a cluster randomised trial. Lancet. 2000;356(9233):888–893
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (90 KB)
    • CrossRef