Total costs and predictors of costs in patients

with systemic lupus erythematosus

N. Sutcliffe, A. E. Clarke
1
, R. Taylor
2
, C. Frost
2
and D. A. Isenberg
Centre for RheumatologyuBloomsbury Rheumatology Unit, Department of
Medicine, University College London, UK,
1
Divisions of Clinical
ImmunologyuAllergy and Clinical Epidemiology, Montreal General Hospital,
McGill University, Montreal, Quebec, Canada and
2
Medical Statistics Unit,
London School of Hygiene and Tropical Medicine, London University,
London, UK
Abstract
Objective. To determine the annual direct, indirect and total costs and predictors of costs in
patients with systemic lupus erythematosus (SLE).
Methods. One hundred and ve patients with SLE completed questionnaires on health-care
utilization and employment history. Predictors of costs were determined by multiple regression
analyses using direct, indirect and total costs as outcome variables. Demographics, health status,
disease activity, end-organ damage, social support and satisfaction with care were used as
predictor variables.
Results. The mean annual total cost per patient was 7913. Direct costs were a third and
indirect costs two-thirds of the total cost. Higher education level, greater disease activity and
lower physical functioning were associated with higher direct, indirect and total costs. Higher
direct costs were also associated with greater damage and younger age.
Conclusion. SLE has a considerable impact on the health-care system and society.
Improvement in disease activity and physical health and prevention of end-organ damage
may reduce costs in SLE.
KEY WORDS: SLE, Direct costs, Indirect costs, Total costs, Predictors of costs.
In the current political atmosphere of limited health-
care budgets, it is increasingly important to determine
the economic consequences of disease. The economic
impact of rheumatic conditions is immense and is likely
to increase with the ageing of the population w1x. It has
been shown that health-care costs and wages lost as
a result of rheumatic disease equal 2.5% of the gross
national product in the USA w2x. Thus it is not surprising
that there has been increasing interest in the cost of
caring for patients with these diseases. There have been
a number of studies evaluating the costs of rheumatic
diseases, particularly rheumatoid arthritis (RA) w3, 4x.
However, very few studies have examined the nancial
consequences of systemic lupus erythematosus (SLE)
w5, 6x.
The present paper reports part of a trinational study
which looked at the health status, health services utiliza-
tion and the direct, indirect and total costs for patients
with SLE in the UK, the USA and Canada w711x.
The trinational study showed that annual resource
utilization did not vary signicantly between the three
countries. However, differences were observed within
each resource category. Canadians saw more specialists
than the British, the British more generalists. Canadians
and Americans were more frequent users of the emer-
gency room, Americans of laboratoryuimaging proce-
dures. Canadians had greater hospital utilization than
Americans. However, the trinational studydidnot express
health costs using British prices and did not investigate
predictors of costs.
SLEcan serve as a model for studying the management
of many chronic rheumatic diseases. It is a prototypical
autoimmune condition that primarily affects women,
involves multiple systems and is treated with poten-
tially toxic therapies, mainly by specialists. Therefore
the methods used and the conclusions derived from this
study can be applied to other SLE populations and,
to a certain extent, to populations affected by other
multisystem autoimmune diseases w12x.
Cost analysis is an important step in performing
an economic evaluation. Although cost studies do not
answer the question of whether the costs are worth
paying for, they are still valuable for their ability to
determine the magnitude of a problem and to identify
areas for further investigation w13x.
Correspondence to: N. Sutcliffe, Centre for Rheumatology,
Bloomsbury Rheumatology Unit, Arthur Stanley House, 4th Floor,
4050 Tottenham Street, London W1P 9PG, UK.
Submitted 31 January 2000; revised version accepted 24 July 2000.
Rheumatology 2001;40:3747
2001 British Society for Rheumatology 37
The cost of illness is often expressed through three
components: direct costs, indirect costs and intangible
costs. Direct costs refer to all the resources consumed
in delivering care to the patient and can be categorized
into direct health-care costs and direct non-health-care
costs w14x. Direct health-care costs include the costs for
in-patient, out-patient and emergency care, while direct
non-health-care costs include, for example, transport
to receive health care and the time caregivers spend in
delivering or aiding the patient in receiving health care.
Indirect costs result from loss of productivity due to
disease. These may include values for paid or unpaid
labour. Intangible costs are attributable to pain and
psychological suffering. These are the most difcult to
express in monetary terms and are often conveyed as
clinical effects or quality-of-life scores w5, 15x.
The indirect costs of illness result from output loss
because of cessation or reduction of productivity due
to morbidity and mortality. Output loss may arise from
diminished activity in both the labour market and the
non-labour market or household, and can represent
a signicant portion of the overall cost of illness. For
diseases affecting predominantly women, much of the
output loss will result from a reduction in non-labour
market activities, such as housekeeping and childcare.
The method of valuing these non-labour activities
is therefore critical if the cost estimates of women's
diseases are to be comprehensive w10x.
In this study we assessed costs from a societal per-
spective, which incorporates all costs regardless of who
incurs them. We studied only a single centre in the UK.
The costs examined also included those attributable to
comorbidity. Since SLE can cause a broad spectrum of
health problems, we considered it to be impossible for
either the patient or the caring physician to ascertain if
problems were SLE-related. The aim of our study was to
investigate all costs incurred by these patients. We also
identied the predictors of costs. Once the contributors
and determinants of costs have been identied, it may be
possible to assess whether investment in these areas can
reduce costs and improve patient outcomes.
Methods
One hundred and seven consecutive out-patients with
SLE attending a specialized SLE clinic were enrolled
in a trinational study of health services utilization and
outcomes in SLE. Costs incurred by these patients
had already been estimated using Canadian prices for
services w7x. We estimated the costs to patients of the
University College London Hospitals (UCLH) using
local prices. All patients were assessed between June and
September 1995. Information about sociodemographics,
disease activity, as assessed by the revised Systemic
Lupus Activity Measure (SLAM-R), and end-organ
damage, as assessed by the Systemic Lupus Inter-
national Collaborating ClinicsuAmerican College of
Rheumatology Damage Index (SLICCuACR DI), were
obtained during an out-patient clinic visit. Disease
duration was calculated from the time the patient
rst fullled four of the revised American College of
Rheumatology (ACR) criteria for the classication of
SLE w16x. Patients were also asked to ll in self-report
questionnaires about health status using the Medical
Outcomes Study Short Form 36 (SF-36), social support
using the Interpersonal Support Evaluation List (ISEL),
their satisfaction with medical care using the Patient
Satisfaction Questionnaire (PSQ) and an economic ques-
tionnaire. The economic questionnaire was repeated
after 6 months.
Measures
The SLAM was developed by Liang et al. w18x in Boston
on the basis of a consensus of members of the Lupus
Council of the American College of Rheumatology.
It includes 32 items, divided into 11 organ systems, and
assigns a degree of severity on a scale of 13, with 1 being
mild and 3 most severe. The total possible score is
86 w17x. Its validity and reliability have been shown
previously w18, 19x. We used the revised SLAM
(SLAM-R) in this study, which differs very little from
the original SLAM w18x.
The SLICCuACR DI is a measure of cumulative end-
organ damage in SLE. Its validity and reliability have
been shown previously w2022x. Damage is described as
non-reversible change, not related to active inamma-
tion, occurring since the onset of lupus, ascertained by
clinical assessment and present for at least 6 months
unless stated otherwise. It is dened for 12 organs or
systems: ocular (range 02), neuropsychiatric (06),
renal (03), pulmonary (05), cardiovascular (06),
peripheral vascular (05), gastrointestinal (06), mus-
culoskeletal (07), skin (02), gonadal (01), endocrine
(01) and malignancy (02). The maximum possible
total score is 46.
The SF-36 is a short-form, 36-item health question-
naire that measures eight multi-item dimensions:
physical function; role limitations due to physical
problems; role limitations due to emotional problems;
social function; mental health; general health perception;
vitality; and pain. Thirty-ve of the items contribute
to these scales. There is a further unscaled single item
asking respondents about health change over the
past year. For each dimension, item scores are coded,
summed and transformed onto a scale from 0 (worst
possible health) to 100 (best possible health state) w23x.
Physical (PCS) and mental component summary (MCS)
scores, generated by collapsing the eight subscales, were
also calculated w24x. The UK version of the question-
naire was used in this study w25x. Its internal consis-
tency, validity and reliability have been demonstrated
w23, 25, 26x.
The ISEL scale was developed to assess social support
w27x. It includes scales measuring four social support
functions: belonging (availability of people one can
do things with); appraisal (availability of someone
to talk to); tangible (availability of material aid); and
self-esteem (availability of a positive comparison when
comparing oneself with others). Each ISEL subscale
consists of 10 items with four possible responses (03)
38 N. Sutcliffe et al.
with a total subscale score range from 0 (least support)
to 30 (most support). The total ISEL score is the sum of
the four component scores (0120).
The Medical Outcomes Study PSQ was originally
developed by Ware et al. w28x. We used version IV in this
study. This questionnaire enquires about global level
of satisfaction, considering all health-care providers
and settings, without specifying a particular provider or
hospitalization. It comprises seven dimensions: general
satisfaction; technical competence (i.e. diagnosis and
management); interpersonal satisfaction (e.g. courtesy
and respect); communication satisfaction; time spent
with doctor; and access to care. The nancial dimension
was omitted because it poses questions of limited appl-
icability in the British system of health-care funding.
Each scale is scored 0100. Higher scores indicate more
satisfaction with care. A summary score has not been
developed.
The economic questionnaire asked about health service
utilization and diminished (work force and non-work
force) productivity over the preceding 6 months and was
repeated 6 months after study entry to develop annual
cost estimates. It enquired about the utilization of all
health services without asking the respondent to make
attribution to SLE or other conditions. Given that SLE
can cause such a broad spectrum of health problems, it
was believed that it would be impossible for either the
patient or the treating physician to ascertain if problems
were SLE-related. It is a modied version of the
economic portion of the Stanford Health Assessment
Questionnaire (HAQ) w29x. This questionnaire has
previously been used and validated for both SLE
and other rheumatic diseases w5, 12, 30x. Health services
utilization included the number of out-patient visits to
doctors and other health-care professionals; out-patient
imaging, laboratory and other diagnostic procedures;
prescription and non-prescription medications; renal
dialysis; assistive devices (e.g. walking stick); visits to
the accident and emergency department and mode of
transport; use of day-case surgery; and stays in hospitals
or nursing homes. Patients were also asked about their
employment history over the preceding 6 months. They
indicated their employment status, annual income, days
of activity limitation with respect to labour-force and
household activities, and their need for domestic help.
Assessment of costs
Direct costs were recorded initially as units of service
and then given a sterling value per unit of a service,
expressed in 19961997 UK pounds. For each patient,
the unit price of a service was multiplied by the number
of units of each service and the products were summed.
To determine the annual costs, the 6-monthly costs were
summed. The prices were assigned to each unit of service
as follows.
Visits to health-care professionals
The prices for out-patient visits to hospital doctors were
calculated by subtracting the diagnostic procedure
costs from the total out-patient costs for each speciality
at UCLH and dividing this result by the number of
out-patient attendances. This provided the cost per
attendance for each hospital specialist. The cost of
general practitioner (GP) visits was based on a report
of the Department of Health and Ofce of Population
Censuses and Surveys w31x. For visits to psychiatrists,
psychologists and district nurses (health professionals
not employed directly by our hospital trust), the
costs per attendance were obtained from the local com-
munity health services trust (personal communication).
The cost of a visit to a physiotherapist was obtained
from our hospital's physiotherapy department (personal
communication). For a social worker visit, the cost per
visit was obtained from the local city council (personal
communication). All the cost calculations mentioned
above were comprehensive and included the overhead
allowances.
The prices for diagnostic investigations and renal
dialysis were either obtained from the relevant hospital
department (personal communication with clinical ser-
vices directory and business management) or based on
our hospital's imaging charges for 199697. These prices
included the cost of technicians and reporting physi-
cians as well as overhead allowances. Prescription and
non-prescription medication prices were calculated as
the product of the price per milligram, total daily dose
and therapy duration. The price per milligram for each
medication was based on the drug tariff w32x. It was
assumed that most of our patients had their medications
supplied by community pharmacists every 3 months
(community pharmacists are reimbursed according to
the drug tariff ). A xed price per medication, reecting
professional fees and overhead allowances, was added to
the cost of drugs.
The cost of attendance at the accident and emergency
department was obtained from the management
accounts department at UCLH and the cost of transport
by ambulance was obtained from London Ambulance
Service NHS Trust (personal communication). The costs
of assistive devices were obtained from the surgical
appliances and surgical supplies departments at the
UCLH (personal communication).
The prices for day-case surgery and hospital stays
were assigned according to the UCLH NHS Trust
GP fundholders tariff (199697) for patients who had
specic procedures or operations. For patients who
had medical treatment only, the average cost of a stay
at UCLH (according to the number of days) was
used. These prices were comprehensive and included the
running costs, expenditure on doctors and nurses and
diagnostic tests.
Indirect costs refer to impaired productivity due to
illness and work time lost, either in market work or
unpaid work at home, and represent productivity losses
to the economy for the length of impairment w10x.
We identied two groups of patients: (i) labour-force
participants, i.e. those working either full-time or part-
time; and (ii) those not in the labour force, i.e. those who
were retired, disabled, unemployed or homemakers, and
others.
39 Total costs and predictors of costs in SLE
For labour-force participants, we used the `human
capital' method to calculate indirect costs, applying
employment income to value lost time. Specically,
indirect costs were determined as follows. Patients
indicated their annual personal income in ranges
(i.e. -5000, 500010 000, 10 00015 000, 15 000
20 000, 20 00025 000 and )25 000). The midpoint
of each range was taken as the income; for the minimum
and maximum ranges actual values were taken. Hourly
and daily incomes were derived from these values. The
patients' hourly income was multiplied by the number
of extra hours per week they stated they would be
working if they did not have SLE. This result was then
multiplied by 26 (number of weeks that would be
worked in a 6-month period). The number of self-
reported days of lost work was also multiplied by the
daily income. These two products were summed.
For non-labour-force participants, we calculated the
implicit income losses. These patients were divided into
two categories. For those who indicated they would
be working if they did not have SLE, we used the
opportunity cost method, which is based on the idea
that the economic value of non-market work is equal to
its best alternative economic use, i.e. the amount the
person could have earned in market work. The income
loss was therefore calculated by multiplying the number
of hours per week they would be working by the hourly
income of a sex- and occupation-matched person w33x.
The result was then multiplied by 26 (number of
weeks that would be worked in a 6-month period). For
the remaining non-labour-force participants, we used
the replacement cost approach, which imputes market
values to perform equivalent duties at home, i.e. income
loss was calculated by multiplying the number of
self-reported days the individual was unable to attend
to activities of daily living by the daily income of
a sex-matched domestic worker w33x.
The cost of employing a paid helper was also added
to the indirect cost for the patients who worked. To
determine the annual indirect cost, costs for the rst
and second 6-month periods were added. All cost data
were expressed in 199697 UK pounds. The total cost
was the sum of the direct and indirect costs.
Statistical analysis
Multiple regression analyses were used to determine the
predictors of direct, indirect and total costs. Predictive
models were tted for direct, indirect and total costs
separately. In regression models for cost data, it is
desirable to analyse untransformed costs so that the
models predict actual costs in pounds. Because of the
skewed nature of cost data, it is recommended w34x
that non-parametric bootstrap methods w35x be used to
calculate condence intervals for regression coefcients.
Because no automated bootstrap methods are available
to select important variables for inclusion in regression
models, standard parametric analyses were used to
identify a number of candidate regression models, and
condence intervals for each of these candidate models
were calculated using bootstrap methods. The can-
didate models were obtained by tting models with
every combination of the predictor variables and using
Mallows' Cp criteria w36x to determine how many
variables were required in the model and the best-tting
model with this number of predictors. The next
four best-tting models of this dimension and the four
best-tting models of dimension one greater than
this best-tting model were also identied. Bias-adjusted
bootstrap condence intervals were constructed from
1000 replicate samples for each of the parameters in
each of these models. The candidate model selected as
the nal best-tting model was that in which all of
the bootstrap 95% condence intervals excluded a null
effect. The all-subsets regression analysis was carried out
in MINITAB. The bootstrap condence intervals were
computed using STATA version 5. All other analyses
were carried out in SAS.
Results
Of the 107 patients initially enrolled at our centre, two
were lost to follow-up. The remaining 105 patients were
included in the analyses. Ninety-four per cent were
female. Seventy-ve per cent were Caucasian. Fifty-eight
per cent were married. Mean age was 39.9"11.8 yr
(median 38.5 yr, range 18.875.3 yr). Mean disease dura-
tion was 10.5"6.6 yr (median 10.8 yr, range 133.5 yr).
Mean duration of education was 13"2.7 yr (median
12 yr, range 620 yr). The disease characteristics of the
patients are shown in Table 1.
The number of visits to health-care professionals over
1 yr varied between 1 and 131, with a median of 12
visits (mean 17.4"17.8). Ninety per cent or more of
the patients visited a rheumatologist in each 6-month
period. More than 70% of patients visited their GP.
Only a small number of patients visited allied health
professionals. Details of visits to other medical special-
ists in the rst and second 6-month periods are shown in
Table 2A and B. The number of diagnostic procedures
per year varied between 0 and 66, with a median of 12
(mean 14.7"11.5). Although a majority of patients had
blood tests (90 and 74% in the two 6-month periods
respectively) and urine tests (77 and 68%), the more
expensive tests were used for relatively small numbers of
patients (-20% of patients had at least one of these
expensive investigations in each 6-month period).
Ninety-ve per cent of patients were on medications.
The most commonly used medications, in order of
frequency of use, were oral prednisolone, hydroxy-
chloroquine, paracetamol, azathioprine and aspirin.
Only two patients in the rst 6 months and one patient
in the second 6 months had peritoneal dialysis. About
a third of patients used aids. Twenty-two per cent of
patients had emergency room visits over 1 yr. Fourteen
patients made 19 visits during the rst 6-month period
and 15 visits during the second 6-month period. Forty-
three per cent of patients had day-case surgery or
in-patient treatment. Six patients underwent six out-
patient surgeries in the rst 6-month period and ve
40 N. Sutcliffe et al.
patients underwent ve out-patient surgeries in the
second 6-month period. Twenty-eight patients had
40 hospital stays in the rst 6-month period, and 18
patients had 30 hospital stays in the second 6-month
period. The average length of stay for hospitalized
patients was 8 and 9 days in the two 6-month periods
respectively. None of the patients used a nursing home.
Employment characteristics of patients at study entry
and at 6 months are shown in Table 3A. Almost half of
the patients did not work. Of the patients who worked,
TABLE 2A. Mean number of visits and cost of health professionals (rst 6 months)
No. of patients with
at least one visit
Mean no. of visits Cost per visit
Six-monthly cost
per patient
n (%) in 6 months () ()
Rheumatologist 102 97 3.02 61 184
Physician 5 5 0.12 48 6
GP 80 77 2.86 15.5 44
Nephrologist 19 18 0.60 52 32
Dermatologist 13 13 0.32 62 20
Ophthalmologist 23 21 0.31 73 23
Miscellaneous
a
36 35 0.82 58.4 48
Surgical specialist
b
5 5 0.09 28.5 2
Physiotherapist 9 9 0.94 20 19
Social worker 3 3 0.11 15.6 2
District nurse 5 5 0.07 26 2
a
Miscellaneous medical specialist (cardiologist, chest physician, etc.). Cost per visit refers to the weighted average cost.
b
Miscellaneous surgical specialist (orthopaedic surgeon etc.). Cost per visit refers to the weighted average cost.
TABLE 2B. Mean number of visits and cost of health professionals (second 6 months)
No. of patients with
at least one visit
Mean no. of visits Cost per visit
Six-monthly cost
per patient
n (%) in 6 months () ()
Rheumatologist 94 90 2.15 61 131
Physician 6 6 0.12 48 6
GP 77 73 2.53 15.5 39
Nephrologist 14 13 0.4 52 21
Dermatologist 8 8 0.14 62 9
Ophthalmologist 21 20 0.29 73 21
Miscellaneous
a
30 29 0.74 52.8 39
Surgical specialist
b
6 6 0.78 57.5 45
Physiotherapist 6 6 0.66 20 13
Social worker 3 3 0.2 15.6 3
District nurse 7 7 0.19 26 5
a
Miscellaneous medical specialist (cardiologist, chest physician, etc.). Cost per visit refers to the weighted average cost.
b
Miscellaneous surgical specialist (orthopaedic surgeon etc.). Cost per visit refers to the weighted average cost.
TABLE 1. Disease characteristics of patients
Mean (S.D.) Median Range
SLAM (081; higher sgreater activity) 6.3 (3.9) 5 022
SLICC (046; higher sgreater damage) 1.1 (1.3) 1 05
ISEL (0120; higher smore support) 89.7 (19.9) 94 32119
SF-36 (higher sbetter health)
PCS 36.4 (12.5) 33.9 13.266.8
MCS 42.9 (12.8) 44.6 10.365.5
PSQ (higher smore satisfaction)
General satisfaction 62.6 (16.8) 62.5 16.7100
Technical quality 63.8 (14.7) 63.9 25100
Interpersonal satisfaction 72.3 (15.7) 75 25100
Communication satisfaction 67.5 (17.6) 70 20100
Time spent with doctor 61.8 (22.9) 75 12.5100
Access to care 65 (14.3) 66.7 20.897.9
41 Total costs and predictors of costs in SLE
about a third (18.1% of all patients at study entry) to
a quarter (13.5% at 6 months) worked part-time. Of the
patients who were disabled, the majority indicated that
they were disabled because of SLE. Similarly, of the
patients who were retired, the majority indicated that
they were retired because of their SLE. Overall, 22%
of the patients were either disabled or retired because of
their SLE. A signicant portion of working patients
missed some days of work (Table 3B). The number
of work days lost was variable (5 and 2% of working
patients declared work loss of more than 1 month
at 0 and 6 months respectively). A similar proportion
of unemployed patients declared disability days (days
they were unable to carry out their usual activities).
Again, the number of disability days was very variable
(23 and 16% of unemployed patients declared more
than 1 month of disability days at 0 and 6 months
respectively).
Components of costs are shown in Table 4. Direct
costs were a third of the total cost. Indirect costs were
twice the direct costs. Nineteen patients incurred no
indirect costs. Four patients had extremely high indirect
costs over 1 yr ()20 000). Six patients had very high
annual direct costs ()10 000). The biggest components
of direct costs were the costs of in-patient care and day-
case surgery. These were followed by the cost of visits to
health-care professionals; visits to the rheumatologists
accounted for between 48% (at study entry) and 39%
(at 6 months) of this component (Table 2A and B). The
costs of medications, including dialysis and diagnostic
procedures, were also important contributors to direct
costs. The costs of aids and emergency room visits were
small.
The results of multiple regression analyses for annual
direct, indirect and total costs are shown in Tables 5, 6
and 7 respectively. The tables show unadjusted and
adjusted regression coefcients for each of the potential
predictors of costs. These coefcients represent the costs
associated with changes in each of these factors. The
parametric analysis of direct costs suggested that disease
activity and end-organ damage were positively asso-
ciated with direct costs and that age and technical
competence were negatively associated with direct costs.
Calculation of the more reliable bootstrap 95% con-
dence intervals for the model with these four factors
and for other models identied as having similarly good
ts conrmed that the associations between direct costs
and disease activity, end-organ damage and age were
TABLE 3A. Employment characteristics of patients at study entry and
at 6 months
No. of patients (%) in different categories
At study entry At 6 months
(n s105) (n s104)
a
Employed 57 (54.3) 54 (52)
Disabled 16 (15.2) 15 (14.4)
Disabled due to SLE 15 (14.3) 13 (12.5)
Retired 11 (10.5) 14 (13.4)
Retired due to SLE 8 (7.6) 10 (9.6)
Homemaker 10 (9.5) 9 (8.7)
Other 11 (10.5) 12 (11.5)
a
One patient did not declare employment status at 6 months.
TABLE 3B. Employment characteristics of patients with SLE at study entry and at 6 months
At study entry At 6 months
Patients reporting lost work days
a
63.1% 55.5%
Patients reporting disabled days
b
58.3% 60%
Mean"S.D. Median (range) Mean"S.D. Median (range)
No. of lost work days
a
10.5"20.4 4 (0120) 8.2"21 3 (0150)
No. of disabled days
b
32.8"50.9 8 (0180) 28.3"47.7 9 (0180)
a
Of the patients who worked.
b
Of the patients who did not work.
TABLE 4. Annual costs for patients with SLE (1996 UK pounds)
Mean cost (S.D.) Percentage Median Range
Visits to health professionals 714 (687) 27
a
534 154796
Diagnostic procedures 388 (309) 15
a
296 01448
Medications and dialysis 451 (1883) 17
a
157 015291
Aids 20 (44) 0.7
a
0 0225
Emergency room visits 37 (85) 1
a
0 0484
In-patient careuday-case surgery 1003 (1949) 38
a
0 011915
Total direct cost 2613 (3163) 33
b
1392 2015724
Total indirect cost 5299 (6981) 67
b
2187 043423
Total cost (directqindirect) 7913 (8668) 4677 2048160
a
Of total direct costs.
b
Of total costs.
42 N. Sutcliffe et al.
statistically signicant. However, bootstrap 95% con-
dence intervals for the effect of technical quality on
direct costs included zero in all of these models. In
addition, bootstrap 95% condence intervals for the
effects of education level and physical component
summary scores (narrowly) excluded zero when these
terms were included in the model with disease activity,
end-organ damage and age. This provides some evidence
(P-0.05) that higher education level and lower physical
component summary scores are associated with higher
costs.
Similar analysis of the indirect and total costs showed
that higher education level, greater disease activity and
lower physical component scores were statistically
signicantly associated with higher indirect and total
costs. No other predictor variables were signicantly
related after adjusting for the effects of these three
variables.
Discussion
Our study is the rst prospective cost-identication
study in SLE in the UK. We identied both direct
and indirect costs, thus determining the burden of this
disease on the health-care system and society. Although
we assessed costs from a societal perspective, we were
not able to evaluate all components of the direct costs.
However, we included non-physician health-care pro-
viders, such as psychologists and social workers, as well
as some transport costs, which are often omitted in
studies of the cost of illness.
TABLE 5. Direct costs () associated with changes in potential predictors of costs
Change in cost () (95% condence interval)
Variable Unadjusted Adjusted
Age (1 yr increase) 47.7 (90.9 to 15.3)* 38.9 (75.8 to 11.1)*
Sex (male s1) 501.2 (2465.7 to 5344.9)
Ethnic origin (non-Caucasians1) 827.4 (808.8 to 2914.8)
Marital status (unmarried s1) 339.8 (872.9 to 1641.2)
Education level (1 yr increase) 260.9 (68.4 to 550.9)* 204.6 (61.7 to 403.5)*
Disease duration (1 yr increase) 2.2 (83.6 to 82.5)
SLAM (1 point increase) 356.2 (199.9 to 595.7)* 239.4 (115.4 to 364.6)*
SLICC (1 point increase) 1146.8 (583.6 to 1720.1)* 875.7 (411.7 to 1503.4)*
ISEL (1 point increase) 5.6 (32.8 to 23.3)
PCS (1 point increase) 92.5 (144.9 to 50.2)* 38.0 (81.0 to 2.1)*
MCS (1 point increase) 20.5 (24.8 to 71.6)
General satisfaction (1 point increase) 40.1 (84.2 to 3.8)*
Technical (1 point increase) 46.0 (107.7 to 1.4)*
Interpersonal (1 point increase) 19.6 (84.5 to 23.1)
Communication (1 point increase) 30.4 (85.3 to 18.5)
Time spent with doctor (1 point increase) 37.9 (66.7 to 9.1)
Access to care (1 point increase) 25.3 (69.4 to 11.2)
*P-0.05.
TABLE 6. Indirect costs () associated with changes in potential predictors of costs
Change in cost () (95% condence interval)
Variable Unadjusted Adjusted
Age (1 yr increase) 20.6 (128.9 to 102.9)
Sex (male s1) 1933.2 (6039.1 to 7593.6)
Ethnic origin (non-Caucasians1) 1.5 (279.5 to 3148.9)
Marital status (unmarried s1) 508.5 (2007.6 to 3891.3)
Education level (1 yr increase) 428.1 (8.0 to 997.0)* 407.5 (14.9 to 875.4)*
Disease duration (1 yr increase) 20.0 (156.5 to 226.5)
SLAM (1 point increase) 577.0 (230.0 to 939.4)* 317.4 (14.2 to 669.1)*
SLICC (1 point increase) 560.0 (393.0 to 1432.8)
ISEL (1 point increase) 9.8 (63.4 to 41.5)
PCS (1 point increase) 223.6 (360.8 to 137.1)* 188.5 (313.6 to 93.1)*
MCS (1 point increase) 25.3 (124.6 to 73.2)
General satisfaction (1 point increase) 48.7 (156.7 to 27.1)
Technical (1 point increase) 58.5 (206.4 to 38.0)
Interpersonal (1 point increase) 37.7 (130.6 to 35.6)
Communication (1 point increase) 13.0 (72.8 to 60.1)
Time spent with doctor (1 point increase) 55.4 (135.1 to 10.0)
Access to care (1 point increase) 3.3 (84.5 to 70.8)
*P-0.05.
43 Total costs and predictors of costs in SLE
The assignment of hospital costs was mainly based on
our hospital's previously determined charges for other
providers and GP fundholders. For this reason they
reect the direct costs for a patient treated at UCLH.
In other parts of the country, hospital costs may be
lower because of lower running costs and cheaper land.
Many other economic evaluations conducted for other
diseases in the UK used local cost data, sometimes in
conjunction with national data w3739x. We would not
be able to conduct such a detailed cost analysis based
entirely on national cost data because of a lack of such
detailed data.
We determined the mean annual total cost of caring
for patients with SLE as 7913 per patient. The direct
cost constituted a third of the total cost (2613). The
costs of in-patient careuday-case surgery and visits to
health-care professionals contributed almost two-thirds
of the direct cost. Although a relatively small number of
patients had in-patient care, this high cost was due to the
high prices of hospital care. Patients made many visits
to health-care professionals, especially their rheumato-
logists and GPs. The cost of medications, including
dialysis and diagnostic procedures, contributed almost a
third of the direct costs. We may have underestimated
the cost of medications since we only included the drugs
SLE patients most commonly used. Further analysis,
as was done in the trinational study, indicates that other
drugs may contribute to almost half of the overall cost
of medications w7x.
The indirect cost was two-thirds of the total cost. The
mean annual indirect cost was 5299 per patient. Almost
half of the patients did not work. Most disability
and retirement was due to SLE. Signicant numbers of
patients either lost work days or had disability days. Our
indirect cost analysis was comprehensive and valued
patients who did not work (patients who were unem-
ployed but claimed they would be employed if they did
not have SLE, and others who did not work, such as
homemakers and retirees). This is particularly important
for a condition like SLE, since the majority of patients
are young women of reproductive age who may not be
in the labour force. By considering the days they were
unable to perform their household chores because of
illness, we partially eliminated the potential bias against
this group. However, by using the replacement cost
method to value the lost time of those non-labour-force
participants who would not be working if they were not
ill, we may have understated their indirect costs. Since
the wage information used in the replacement cost
method is based on the wages of low-paid workers, this
method might underestimate the indirect cost in patients
with SLE. This is because our SLE patients tend to have
an educational attainment near the average, which is
higher than that of low-wage workers. Educational
attainment is known to be related to the value of
time w40, 41x. Therefore, replacement costs probably
underestimate the true value of the average SLE patient.
Although we attempted to be as comprehensive as
possible in estimating both direct and indirect costs, we
did not assess intangible costs. An alternative approach,
used in costbenet studies estimating the social cost
of disease, the willingness-to-pay approach, values not
just the impact on productivity but also improved health
per se. There are certain challenges in this method, and
it was not used in this study.
We think the conclusions of our study can be gener-
alized. Although this study was performed at a spe-
cialized SLE centre, the patients represented a spectrum
from mild to severe cases, and there is no reason to
suspect that our practice pattern should be different
from that of others in the UK who treat patients with
this condition. Furthermore, as was shown in the tri-
national study, the characteristics of our patients were
similar to those of other SLE populations w7x.
TABLE 7. Total costs () associated with changes in potential predictors of costs
Change in cost () (95% condence interval)
Variable Unadjusted Adjusted
Age (1 yr increase) 69.8 (210.8 to 62.8)
Sex (male s1) 1432.0 (8495.8 to 122)
Ethnic origin (non-Caucasians1) 828.9 (3605.5 to 4534.6)
Marital status (unmarrieds1) 848.3 (2155.0 to 4948.4)
Education level (1 yr increase) 689.0 (121.4 to 1487.6)* 584.1 (36.4 to 1158.0)*
Disease duration (1 yr increase) 17.8 (204.3 to 275.4)
SLAM (1 point increase) 933.2 (476.3 to 1343.5)* 557.0 (157.9 to 973.9)*
SLICC (1 point increase) 1706.7 (629.4 to 2961.8)*
ISEL (1 point increase) 29.1 (107.3 to 37.9)
PCS (1 point increase) 316.0 (468.5 to 204.3)* 232.2 (398.0 to 99.1)*
MCS (1 point increase) 4.7 (121.0 to 107.8)
General satisfaction (1 point increase) 88.7 (196.1 to 1.4)
Technical (1 point increase) 104.5 (234.9 to 32.1)
Interpersonal (1 point increase) 57.2 (158.7 to 38.4)
Communication (1 point increase) 43.4 (134.8 to 47.6)
Time spent with doctor (1 point increase) 93.4 (176.7 to 11.7)*
Access to care (1 point increase) 24.0 (70.3 to 122.9)
*P-0.05.
44 N. Sutcliffe et al.
There have been no previous studies examining
the cost of care for patients with SLE in the UK.
Comparison of our ndings with those of other
cost-of-illness studies of SLE in other countries or
other diseases in the UK would be of limited value
because of the differences in the categories of cost, the
methods used, the pattern of health services utilization
and the health-care systems. In Canada, Clarke et al. w5x
studied the total medical costs for patients with SLE
using similar methods to assess health services utiliza-
tion and lost productivity, although their assignment of
prices was somewhat different, reecting the Canadian
health-care system. They determined the mean total
annual cost as $13 094 in 1990 Canadian dollars. Indirect
costs constituted 54% of this, in comparison with 67% in
our study. The total cost of in-patient care and day-case
surgery was the biggest contributor to direct costs, as in
our study (38%). This was followed by visits to health
professionals in our study but diagnostic procedures in
their study. In their study, predictors of higher direct
costs were higher values of creatinine and a poorer level
of physical functioning. Predictors of higher indirect
costs were a poorer SLE well-being score, a combination
of education and employment status (higher levels), and
a weaker level of social support. Their study did not
include standard measures of disease activity and
damage. In the same cohort they also used regression
trees to characterize patients with SLE who were
expected to experience the highest direct and indirect
costs and greatest diminished productivity. They found
that patients with poor physical or poor psychological
functioning incurred the highest direct costs, those with
the poorest psychological functioning incurred the high-
est indirect costs, and those with the most intense pain
experienced the greatest impairment in productivity w6x.
In the USA, Finn et al. w42x determined the direct
annual medical cost for SLE patients in 198892. They
found that in-patient costs were the major compon-
ent of total costs. Blacks, females, hypertensives and
patients with higher activity or damage scores had higher
costs w42x.
Health-care costs vary between countries. Gironimi
et al. w12x showed that direct health-care costs for
patients with SLE in the USA were almost twice those
in Canada as a result of the higher price of health
services in the USA and the more severe disease
mix w12x. Although Canada has a national health-care
system similar to the UK, the pattern of health services
utilization is somewhat different and the applicability
of Canadian studies to the UK is limited w7x.
We also determined the predictors of cost. Patients
with higher levels of education incurred higher costs.
An increase of 1 yr in education was associated with
increases of 205, 408 and 584 in direct, indirect and
total costs respectively. This effect of education level
on direct costs may be due to higher levels of com-
pliance with treatment, higher attendance rates for
clinic appointments and investigations, and perhaps the
more demanding nature of the more highly educated.
The effect on indirect costs is likely to be due to the
higher earning capacity of this group, and thus any
time lost from work would be more highly valued.
Higher disease activity was also associated with higher
costs. An increase of 1 score point in disease activity
was associated with increases of 239, 317 and 557 in
direct, indirect and total costs respectively. This is not
surprising, since it is expected that patients with more
active disease will make more use of the health services
and will also take more time off work. Clarke et al. w5x
also showed the effects of SLE activity (as represented
by renal and physical functioning) on direct costs and
the effects of global well-being on indirect costs. In our
study, damage also had an impact on costs, although
only on direct costs. An increase of 1 score point in total
damage was associated with an increase of 876 in direct
cost. It is to be expected that patients with more damage
use more health services.
It is also interesting that patients with better physical
functioning incurred lower direct, indirect and total
costs. The effect of physical functioning appears to
be less than the effects of education level, disease
activity and damage (an increase of 1 point in physical
component summary scores was associated with reduc-
tions of 38, 189 and 232 in direct, indirect and total
costs respectively). However, it is likely that a 1-unit
change in physical functioning is not as clinically
important as a 1-unit change in disease activity or
damage. The association of physical functioning with
direct costs was also shown in the studies by Clarke et al.
w5, 6x. Patients with better physical health may use
health services less and lose less time from work. Unlike
the studies of Clarke et al. mentioned above, our study
showed that psychological functioning and social
support did not inuence costs. Age also had an effect
on direct costs in our study, older patients incurring
lower costs (an increase of 1 yr in age was associated
with a reduction of 39 in the direct cost). This may
have been due to the reduction in disease activity as
patients age, especially after the menopause.
Our study had a different and more appropriate
approach to statistical analysis compared with the
studies of SLE costs mentioned above. Our approach
did not require normative assumptions and was there-
fore more appropriate for this sort of data. We used
non-logged models, which are easier to interpret than
log models. Log models are also a problem in studies
which have large numbers of zero cost values (about
20% for indirect costs in this study).
There have been a number of costs-of-illness (COI)
studies for other rheumatic diseases in Europe, particu-
larly RA. McIntosh w3x studied the cost of RA in
England. The total economic effect of RA was estimated
to be 1.256 billion in 1992, of which 52% was a result
of production loss caused by RA disability. Direct costs
amounted to 604.5 million, with hospitalization by
far the largest expenditure, accounting for almost 30%
of the direct cost. Nurse visits and home help visits
combined made up 24% of the direct cost, with drugs,
including toxicity management, accounting for 15%
of the total. Van Jaarsveld et al. w4x studied the direct
45 Total costs and predictors of costs in SLE
cost of RA during the rst 6 yr of disease in The
Netherlands. The annual direct cost of RA averaged
3680 per patient. A high total direct cost in the rst
6 yr of disease was related to severe functional disability
and lower age.
COI studies have been criticized because of limitations
in their comparability. Apart from the usual problems
of measurement errors and biases, such as recall bias,
the comparability of indirect cost of illness estimates
may be compromised as a result of the different methods
used w13x.
McIntosh w3x also pointed out the limitations of COI
studies. However, as she indicated, the COI framework,
if used correctly and imaginatively, can be a valuable
tool in cost-effectiveness analysis. By documenting the
disaggregated costs of illness, as we have done in this
paper, COI estimates can help policy-makers examine
resource utilization, cost patterns, the effects of different
treatment packages, the effects of changing patterns of
service utilization and the results of health service cost-
cutting procedures. These patterns can be monitored
within the COI framework and provide invaluable
information on shifting resource utilization and the
effects on costs.
In summary, we have shown that SLE has consider-
able impact on the patient, the health-care system and
society in general. Improvements in treatment to reduce
disease activity and prevent damage, as well as improve-
ments in physical health, are likely to reduce the costs
incurred by these patients.
Acknowledgements
We gratefully acknowledge Jean Heath and Dimitria
Panaritis for their technical assistance, Peter Large for his
help in the assessment of costs at UCLH, Panos Kanavos
at the London School of Economics for his advice and
Bruce Bovill at the SAS Institute, Maidenhead, UK, for
his support and advice.
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47 Total costs and predictors of costs in SLE