816 Journal of Pain and Symptom Management Vol. 38 No.

6 December 2009

Original Article

Is Short-Term Palliative Care Cost-Effective

in Multiple Sclerosis? A Randomized
Phase II Trial
Irene J. Higginson, BMedSci, BMBS, PhD, FFPM, FRCP, Paul McCrone, BSc Hons,
MSc, PhD, Sam R. Hart, BA, Rachel Burman, MA, FRCP, Eli Silber, MD,
FCP(Neuro)SA, and Polly M. Edmonds, MBBS, MRCP, FRCP
Department of Palliative Care, Policy and Rehabilitation (I.J.H., S.R.H., R.B., P.M.E.), Institute of
Psychiatry (P.M.), King’s College London; Department of Palliative Care (I.J.H., R.B., P.M.E.) and
Department of Neurology (E.S.), King’s College Hospital, London, United Kingdom

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]: 1.05e7.89) in the fast track compared to the control group. Mean service
costs, including inpatient care and informal care, over the 0e12-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. J Pain
Symptom Manage 2009;38:816e826. Ó 2009 U.S. Cancer Pain Relief Committee.
Published by Elsevier Inc. All rights reserved.

This study was funded by the Multiple Sclerosis So- Palliative Care, Policy and Rehabilitation, King’s
ciety of Great Britain and Northern Ireland. College London School of Medicine, Weston Educa-
tion Centre, Cutcombe Road, London SE5 9RJ,
Clinical Trial Registration: www.ClinicalTrials.gov,
United Kingdom. E-mail: irene.higginson@kcl.ac.uk
Identifier: NCT00364936.
Accepted for publication: July 13, 2009.
Address correspondence to: Irene J. Higginson, BMed
Sci, BMBS, PhD, FFPM, FRCP, Department of

Ó 2009 U.S. Cancer Pain Relief Committee 0885-3924/09/$esee front matter

Published by Elsevier Inc. All rights reserved. doi:10.1016/j.jpainsymman.2009.07.002
Vol. 38 No. 6 December 2009 Is Short-Term Palliative Care Cost-Effective?
Key Words
Palliative, palliative care, cost-effective, multiple sclerosis, hospice, end-of-life care, caregiver
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.2e5
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 ef-
fectiveness of hospices8 and palliative care
teams (PCTs),9e11 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 evalua-
tions or health economic assessments have
been undertaken.8,11,13,14
Over 2.5 million people worldwide are af-
fected 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 ini-
tially, about 15% present with a primary
progressive course, and half with relapsing-
remitting disease develop secondary progres-
sion.15 Although early disease-modifying thera-
pies in relapsing-remitting MS show promise,
they are of little benefit in progressive disease.15
Much of the burden of illness falls on the com-
munity and on lay caregivers.7,16 The more ad-
vanced stages are accompanied by profound
physical and psychological symptoms, in some
instances worse than among people affected
by cancer.17e19
Studying palliative care in MS addresses an
important gap in service provision and pro-
vides a potential model for palliative care
in other neurological and noncancer diseases
with a similar trajectory, such as organ fail-
ure. We, therefore, conducted a trial to de-
termine if there was sufficient evidence of
cost-effectiveness of a new palliative care ser-
vice for people with MS to warrant further
development.
817
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, psychoso-
cial 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). Ed-
ucational seminars informed local health and
social care professionals about the PCT. Exclu-
sion criteria included if the referring staff or
the screening deemed patients had very urgent
needs or were deteriorating rapidly when imme-
diate referral to the service was offered. Care-
givers 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.
Randomization and Interventions
After consent and baseline interview, the
researcher e-mailed relevant data to indepen-
dent statisticians who conducted the randomi-
zation 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 im-
mediately (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 pa-
tients of their allocation. If patients were ran-
domized to the fast track, their information
was passed to the PCT, which contacted them
within 48 hours. If patients were in the control
818 Higginson et al. Vol. 38 No. 6 December 2009

Patients Baseline Interview

Indicates point of
69 52 clinical intervention
Randomized
Fast track Control

Excluded / Refused
17 26 26
Withdrawn
5 - urgent need
5 - refused consent 2
3 - communication F – I2 C– I2 (1 Protocol violation
difficulties too severe 1 Pt w/MS died)
1 - lived outside area
26(25) 24(23)
1 - did not have MS
1 - cognitive problems
F – I3 C – I3
too severe
1 - administrative error 26 24 Withdrawn
2
Withdrawn
C– I4 (2 Pt w/MS died)
1
22(21)
(1 Pt w/MS died) Withdrawn
1
F –final C –final
(1 Pt w/MS became
25 21 severely ill)

Fig. 1. CONSORT diagram showing the flow of patients through the study. N (N ) ¼ 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.

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 com-
prised one part-time consultant in palliative
medicine, one part-time clinical nurse special-
ist, one administrator, and one psychosocial
worker, and was based in a large teaching hos-
pital. Patients were visited in their own homes
or sometimes outpatient clinics, nursing
homes, or hospital. The PCT undertook assess-
ments, suggested ways to improve physical,
emotional, social, and other problems, pro-
vided specialist welfare benefits advice and be-
reavement 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 con-
sultation services described elsewhere,9,11 al-
though 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, re-
habilitation, 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 demo-
graphic 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 groupdafter 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 0e4; 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.
Vol. 38 No. 6 December 2009 Is Short-Term Palliative Care Cost-Effective?
Costs
Costs were assessed using a broad perspec-
tivedincluding 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 ap-
plicable unit costs. These took into account sal-
aries, overheads, and training, and the ratio of
direct patient contact time to noncontact
time.28 Informal care costs were estimated by as-
suming 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, ir-
respective of whether patients were assessed as
having palliative care needs or the nature of
contact with the PCT. We tested the differ-
ences between the two arms (expressed as dif-
ferences 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 sepa-
rately explored missing data20 and tested im-
putations (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 pro-
duce confidence intervals (CIs) around the
cost differences between the two groups. Com-
parisons were made of total service costs, and
also costs that excluded inpatient care and infor-
mal 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 out-
come differences for each. These were then
819
plotted on cost-effectiveness planes. These are
valuable for a Phase II study because they indi-
cate whether the PCT would have better out-
comes at higher costs, better outcomes at lower
costs, worse outcomes at higher costs, or worse
outcomes but at lower costs. For all of these anal-
yses, 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.
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 charac-
teristics (Tables 1 and 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 ill-
ness. There was one death in the fast-track
group and three in the control group. Two
hundred seventeen of 225 possible question-
naires were completed.20 Caregiver data were
missing when patients did not have caregivers.
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 dif-
ference 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 sam-
ple size required to detect this is 56). The results
were similar in nonimputed and imputed data,
for all the imputation methods. When we fol-
lowed 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 interven-
tion. In the control group, the ZBI-12 fell (i.e.,
improved) by 1.40 (95% CI 3.54 to 0.74)
820 Higginson et al. Vol. 38 No. 6 December 2009

Table 1
Characteristics of Patients and Caregivers in the Two Randomized Groups
Fast Track (n ¼ 26) Control (n ¼ 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)dhigh scores indicate greater severity
UNDS function score (total range 0e60 [worst]) 28 (28, 8.9) 30 (29, 9.2)
EDSS function score (total range 0e10 [worst]) 7.7 (8, 1) 7.9 (8, 1)
Note: There were no significant differences between groups at baseline in any of these characteristics.

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, reduc-
ing 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 re-
ported having received palliative care nursing,
with a mean of almost three contacts. Almost
one-quarter reported seeing a specialist at

Table 2
Mean (SD) Outcome Scores at Baseline and Mean (95% CI) Differences in Score from Baseline Over Time
Six-Week Mean Difference Twelve-Week Mean Difference
Measure and Group Baseline n, Mean (SD) from Baselinea (95% CI) from Baselineb (95% CI)

Palliative Outcome Scale-8 (range ¼ 0e32)

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 ¼ 0e4)
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 ¼ 0e48)
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).
a
Score at six weeks minus total score at baseline.
b
Score at 12 weeks minus total score at baseline.
c
ANOVA, F ¼ 5.15, P ¼ 0.028. Adjusting for baseline score, difference between scores ¼ 0.56 (95% CI: 0.75 to 1.19).
d
ANOVA, F ¼ 7.96, P ¼ 0.011. Adjusting for baseline score, difference between scores ¼ 4.47 (95% CI: 1.05 to 7.89).
Vol. 38 No. 6 December 2009 Is Short-Term Palliative Care Cost-Effective? 821

Table 3
Service Use in the Previous Three Months Prior to Baseline Assessment and Twelve-Week
InterviewsdSelf-Report of Patients
Baseline Twelve-Week Follow-up

Fast Track Control Fast Track Control

Mean (SD) Mean (SD) Mean (SD) Mean (SD)

Service n (%) Contacts n (%) Contacts n (%) Contacts n (%) Contacts

District/practice nurse 18 (72) 29.6 (56.8) 18 (69) 10.3 (8.6) 20 (87) 12.3 (19.7) 13 (62) 31.9 (50.7)
MS nurse 14 (54) 1.6 (1.6) 13 (50) 1.6 (1.2) 11 (48) 1.8 (1.8) 7 (33) 1.1 (0.2)
Palliative care nurse 1 (4) 4.0 (e) 0 (0) d 9 (39) 3.0 (1.5) 0 (0) d
Other nurse 5 (19) 3.3 (2.3) 5 (19) 4.2 (2.5) 7 (30) 40.0 (63.8) 7 (33) 95.0 (79.6)
General practice 17 (65) 4.1 (0.6) 12 (46) 3.7 (0.9) 8 (35) 3.8 (0.5) 11 (52) 3.4 (1.2)
Specialist (home) 0 (0) d 2 (8) 2.5 (2.1) 5 (22) 5.2 (4.5) 0 (0) d
Specialist (hospital) 12 (48) 1.0 (0.0) 13 (50) 1.2 (0.8) 8 (35) 1.0 (0.0) 16 (76) 1.3 (0.7)
Specialist (ward) 4 (15) 1.8 (1.5) 8 (31) 1.0 (0.0) 5 (22) 1.0 (0.0) 7 (33) 9.6 (12.1)
Specialist (other) 7 (27) 13.9 (34.0) 2 (8) 1.0 (0.0) 4 (17) 1.1 (0.3) 5 (24) 1.0 (0.0)
Occupational therapist/ 17 (65) 15.1 (21.6) 17 (65) 15.2 (20.9) 16 (70) 10.6 (9.9) 14 (67) 22.5 (47.7)
physiotherapist
Dietician/chiropodist/ 12 (48) 2.5 (2.0) 13 (50) 3.9 (3.5) 12 (52) 3.5 (2.5) 13 (62) 2.6 (1.3)
dentist
Speech therapist 6 (23) 4.0 (0.6) 2 (8) 2.5 (2.1) 5 (22) 2.1 (2.5) 1 (5) 13.0 (-)
Social services 7 (27) 6.6 (8.6) 14 (54) 4.3 (2.2) 10 (43) 6.4 (7.7) 8 (38) 4.1 (2.4)
Informal caregiver 15 (58) 146.5 (55.3) 17 (65) 151.4 (60.1) 15 (65) 152.5 (53.7) 16 (76) 151.1 (57.7)
Day center 3 (12) 32.0 (25.0) 7 (27) 18.7 (15.2) 5 (22) 20.2 (21.0) 5 (24) 20.4 (15.9)
Inpatient care 4 (15) 21.8 (18.0) 6 (23) 16.2 (26.0) 4 (17) 19.0 (21.6) 6 (29) 30.7 (32.1)
Respite care 4 (15) 38.3 (37.7) 4 (15) 7.3 (5.3) 2 (9) 9.5 (0.7) 5 (24) 10.0 (5.9)
n ¼ number of patients who reported receiving that service.

home, most of whom were likely to be pallia-
tive 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 hospi-
tal. Receipt of MS nurses was similar in the two
groups. The total costs, with inpatient and
informal care costs included, over the 0e12-
week follow-up were £1,789 lower for the fast-
track group (bootstrapped 95% CI £5,224
to £1,902). Excluding inpatient care and infor-
mal care, mean service costs were £1,195 lower
for the fast-track group (bootstrapped 95% CI
£2,916 to £178, Table 4).

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

Service Fast Track Control Fast Track Control

District/practice nurse 489 (1,140) 163 (197) 224 (420) 398 (922)
MS nurse 37 (62) 35 (50) 33 (62) 13 (22)
Palliative care nurse 7 (33) 0 (0) 46 (72) 0 (0)
Other nurse 28 (71) 32 (82) 451 (1,573) 922 (2,078)
General practice 128 (114) 76 (103) 48 (87) 68 (96)
Specialist (home) 0 (0) 18 (74) 93 (258) 0 (0)
Specialist (hospital) 45 (47) 57 (79) 29 (44) 78 (76)
Specialist (ward) 25 (77) 29 (44) 18 (37) 260 (707)
Specialist (other) 347 (1,656) 7 (25) 16 (39) 19 (39)
Occupational therapist/ 314 (492) 299 (438) 290 (425) 389 (897)
physiotherapist
Dietician/chiropodist/dentist 26 (41) 44 (73) 41 (65) 33 (29)
Speech therapist 32 (65) 8 (35) 16 (58) 25 (122)
Social services 38 (71) 90 (117) 69 (152) 46 (89)
Informal caregiver 2,197 (2,199) 2,574 (2,283) 2,288 (2,254) 2,620 (2,247)
Day center 100 (340) 136 (305) 110 (321) 115 (290)
Inpatient care 1,037 (3,143) 1,157 (4,205) 906 (3,173) 2,377 (6,265)
Respite care 312 (1,017) 59 (172) 39 (137) 110 (255)
Costs are in 2005 £s.
5162 4784 4717 7473

1978
9879 11857
822 Higginson et al. Vol. 38 No. 6 December 2009

A Cost-effectiveness plane using POS-8 as outcome measure

10000

8000

6000

4000

2000

Difference in POS 0
-15 -10 -5 0 5 10 15

-2000

-4000

-6000

-8000

-10000
Difference in costs

B
Cost-effectiveness plane using ZBI-12 as outcome measure.
8000

6000

4000

2000

Difference in ZBI 0
-20 -15 -10 -5 0 5 10 15 20

-2000

-4000

-6000

-8000
Difference in costs

Fig. 2. Cost-effectiveness analysis at 0e12 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 quad-
rant show worse outcomes and higher costs.
Vol. 38 No. 6 December 2009 Is Short-Term Palliative Care Cost-Effective?
The point estimates in the cost-effectiveness
planes suggest that it was cost saving, with
equivalent outcomes on the POS-8 and im-
proved 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 bur-
den (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.
Discussion
For those who experience MS in advanced
stages, it often can be a devastating condition.
Acute care for patients with chronic or progres-
sive 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 ap-
proach. 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 infor-
mation 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, sug-
gesting that normally, over time, they would
deteriorate. They had initial POS-8 scores of
13e14, which suggest moderate levels of palli-
ative care need and pain scores of 1e2, sug-
gesting 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
823
mean scores on the ZBI-12 of over 20 at base-
line, 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 inter-
vention by the PCT, which aimed to comple-
ment 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 ini-
tial concerns, input from MS nurses was not
lower in the fast-track groupdin 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 care-
giver savings). These savings appeared to be
mainly due to a lower use of primary and acute
hospital services. The informal care costs were lit-
tle affected by the PCTdif anything, there was
a slight reduction. The implications of these
findings could be considerabledaround
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 pallia-
tive care service produced only three months of
cost savings, rolling it out across the UK could
824 Higginson et al.
result in total cost savings of almost £17 million
per year. If the savings were extended over a lon-
ger 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 obstruc-
tive 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 dura-
tion earlier in care, and, in contrast to their find-
ings, did not shorten survival. Indeed, survival
was slightly but nonsignificantly better in our pal-
liative 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 be-
cause of the small sample. Our groups were sim-
ilar 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 paindwhich
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 fol-
low-up and some missing data, especially when
patients did not have informal caregivers, would
mean that at least 80e100 patients would need
to be recruited.
The randomization of patients appeared
successful and we were able to recruit our tar-
get numbers using this fast-track trial design.20
Randomized trials are the gold standard for re-
ducing 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
Vol. 38 No. 6 December 2009
blinded. However, it is difficult to envisage any
way patients could be blindeddas they would
know whether they were receiving the inter-
vention. 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 random-
ized trial of a breathlessness service, we at-
tempted 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 ef-
fective, 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 con-
ducting the intention-to-treat analysis. How-
ever, 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 con-
tact with the PCT. Further exploration of the
data may help to identify those patients who ap-
peared to benefit most, helping to refine the re-
ferral criteria. We used patient reports of service
use to determine costs. Patient reports may not
exactly reflect billing datadalthough it is ques-
tionable 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 ap-
peared 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 costsdfor exam-
ple, 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 be-
fore the control group received the PCT. It may
be that the cost savings and outcome benefits
extended beyond this time, and we were unable
Vol. 38 No. 6 December 2009 Is Short-Term Palliative Care Cost-Effective?
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 us-
ing 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 palli-
ative 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 suc-
cessful in achieving the intended numbers in
the time expected. We believe that this fast-track
trial method is important for palliative care tri-
als 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 con-
temporary patients in the United States9 and
the other using historical data13 in Spain. Our
differences may be because of our shorter fol-
low-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 non-
randomized 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 e 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 non-
cancer conditions should be rethought.
Conclusions
Overall, this Phase II randomized trial sug-
gests that a short-term PCT for people severely
affected by MS is likely to be cost-effective,
reducing inpatient and community costs, care-
giver burden, and possibly patient pain. As the
first trial in such conditions, it suggests that
825
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.
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, experi-
ences, and concerns with them and for taking
part in the study. The authors thank the clini-
cal staff involved in recruitment and in the ser-
vice and those staff involved in interviewing,
including Bella Vivat, Tariq Saleem, Troy Cart-
wright, 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 Caro-
lin Seitz) who oversaw the development of
methods and trial conduct. The authors also
specially thank Dr. Massimo Costantini who
originally suggested using the delayed inter-
vention randomized controlled trial and
Dr. Gao Wei for assistance in the analysis.
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