Clinical Nutrition xxx (2012) 1e7

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Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Cost-effectiveness of nutritional intervention on healing of pressure ulcers

Akinori Hisashige a, *, Takehiko Ohura b
a
The Institute of Healthcare Technology Assessment, 2-24-10, Shomachi, Tokushima 770-0044, Japan
b
Pressure Ulcers and Wound Healing Research Center, 7F, H&B Plaza Bld. 1-1, South 3, West 2, Chuo-ku, Sapporo 060-0063, Japan

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: Pressure ulcers not only affect quality of life among the elderly, but also bring a large
Received 19 October 2011 economic burden. There is limited evidence available for the effectiveness of nutritional interventions for
Accepted 20 April 2012 treatment of pressure ulcers. In Japan, recently, a 60-patient randomized controlled trial of nutritional
intervention on pressure ulcers demonstrated improvement in healing of pressure ulcers, compared with
Keywords: conventional management. To evaluate value for money of nutritional intervention on healing of pres-
Pressure ulcers
sure ulcers, cost-effective analysis was carried out using these trial results.
Nutritional intervention
Methods: The analysis was carried out from a societal perspective. As effectiveness measures, pressure
Healing
Cost-effectiveness
ulcer days (PUDs) and quality-adjusted life years (QALYs) were estimated. Prevalence of pressure ulcers
Quality-adjusted life years was estimated by the KaplaneMeier method. Utility score for pressure ulcers is derived from a cross-
sectional survey among health professionals related to pressure ulcers. Costs (e.g., nutritional
interventions and management of pressure ulcers) were estimated from trial data during observation
and follow-up. Stochastic and qualitative sensitivity analyses were performed to examine the robustness
of results.
Results: For observation (12 weeks) and follow-up (12-week observation plus 4-week follow-up),
nutritional intervention reduced PUDs by 9.6 and 16.2 per person, and gained 0.226
102 QALYs
and 0.382
102 QALYs per person, respectively. In addition, costs were reduced by $542 and $881 per
person, respectively. This means nutritional intervention is dominant (cost savings and greater effec-
tiveness). The sensitivity analyses showed the robustness of these results.
Conclusion: Economic evaluation of nutritional intervention on healing pressure ulcers from a small
randomized controlled trial showed that this intervention is cost saving with health improvement.
Further studies are required to determine whether this is a cost-effective intervention for
widespread use.
Ó 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

1. Introduction
Pressure ulcers are a serious and costly problem within the
hospital and aged care setting. The burden of having pressure ulcers
is high, in clinical, emotional and economic terms. Prevalence rates
of pressure ulcers in the UK, the US and Canada are reported to
range from 4.7 to 32.1% in hospitals, 4.4e33% in community care
and 4.6e20.7% in nursing homes.1 In Japan, their prevalence rates
are recently estimated to be from 2.2 to 3.3% in general hospitals,
2.5% in long-term care facilities, and 8.3% in home-visiting nursing
care, respectively.2 Prevalence rates vary in each country and
between countries, since they are influenced by multiple factors,
including definition, method of calculation and time. Therefore, it is
difficult to directly compare them.
* Corresponding author. Tel./fax: þ81 88 631 3313.
E-mail address: akih@k3.dion.ne.jp (A. Hisashige).
Pressure ulcers can reduce overall quality of life due to pain,
treatments, and increased length of institutional stay, and may also
contribute to premature mortality in some patients.3 The economic
burden of pressure ulcers is substantial. The annual costs for
treatment of pressure ulcers are estimated to be £750 million in the
UK, US$3 billion in the US, and A$285 million in Australia.4,5 These
costs are likely to be an underestimate, since they do not take into
account additional costs for community-based nursing and long-
term care, and loss of productivity for the patient and family.
With aging populations and structural changes in disease
patterns, the prevalence and burden of pressure ulcers are
continuously increasing. Therefore, any intervention that may help
to prevent or treat pressure ulcers is important to reduce costs of
pressure ulcer care and improve health and quality of life for
affected individuals. Although limited evidence-based research is
available,6e9 general consensus and guidelines indicate that
nutrition is an important aspect of a comprehensive care plan for

0261-5614/$ e see front matter Ó 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
doi:10.1016/j.clnu.2012.04.013

Please cite this article in press as: Hisashige A, Ohura T, Cost-effectiveness of nutritional intervention on healing of pressure ulcers, Clinical
Nutrition (2012), doi:10.1016/j.clnu.2012.04.013
2 A. Hisashige, T. Ohura / Clinical Nutrition xxx (2012) 1e7
prevention and treatment of pressure ulcers and it is essential to
address nutrition in every individual with pressure ulcers.3,10,11
Recently, the first randomized controlled trial in Japan, which
was also the first in Asia, has been conducted to evaluate the effi-
cacy and safety of nutritional intervention on healing of pressure
ulcers, and showed that nutritional intervention could directly
enhance the healing process in pressure ulcers.12 Since there has
not been any economic evaluation of nutritional intervention for
pressure ulcers, based on a randomized controlled trial, we con-
ducted a study to confirm the cost-effectiveness of this interven-
tion. This study would provide basic information on the
cost-effectiveness of nutritional intervention on healing of pres-
sure ulcers not only in Japan, but also in other countries.
2. Methods
2.1. Analytical overview
Economic analysis was conducted based on the nutritional
intervention trial on healing of pressure ulcers.12 In economic
analysis, 4-week follow-up was added to 12-week trial observation
to capture continuous benefits over the intervention period.
Therefore, the two evaluation periods, i.e., the observation
(12-week) and the follow-up (12-week observation plus 4-week
follow-up), were set. Subjects were 60 tube-fed, bed-ridden
patients with stage IIIeIV pressure ulcers classified by the NPUAP
staging system13 in the sacral, coccygeal, trochanteric or calcaneal
region. They were hospitalized in long-term care facilities. They
were randomly assigned to either nutritional intervention (N ¼ 30)
or conventional care (N ¼ 30). The inclusion criteria were albumin
(Alb) 2.5e3.5 g/dL, OhuraeHotta (OH) scale14 8.5 or lower, and
Braden scale15 9e17. The albumin range stipulated in the inclusion
criteria represents the mean values in patients hospitalized in long-
term care facilities. The OH scale, which is the Japanese patient
intrinsic risk measurement, consists of the following four assess-
ment items: deterioration of self sustainability, morbid bony
prominence, edema, and joint contracture.
While the control group received the same nutrition manage-
ment as that prior to participating in this trial, the intervention
group was given a goal energy in the range calculated by Basal
Energy Expenditure
active factor (1.1)
stress factor (1.3e1.5).
RacolÒ was administered as a feeding formula to both groups.
RacolÒ has been used for nutritional support in postoperative
patients or extensively burned patients, especially for tube feeding
in patients who for long periods of time either consume insufficient
amounts of oral meals or are unable to do so at all. Racol contains
1.0 kcal/mL and it is characterized by its rich amount of protein and
high ratio of omega-3 fatty acids compared to similar nutritional
supplements. The formula contains protein 4.38 g, fat 2.23 g, and
carbohydrate 15.62 g, all per 100 mL of product. The ratio of omega-
3 to omega-6 essential fatty acids is 1:3 in this formula, which also
includes Cu 125 mg and Zn 0.64 mg. Mean (SD) daily calories
administered during the intervention period were 1,092.1 (161.8)
kcal in the control group and 1,383.7 (165.6) kcal in the interven-
tion group. The mean (SD) daily amount of protein administered
during the intervention period was 46.4 (7.7) g in the control group,
and 58.6 (5.8) g in the intervention group. During 4-week follow-up
after intervention, both groups received the same level of
calories as before the trial. Mean (SD) daily calories during this
period were 1,142  238 kcal/day in the intervention group and
1,094  188 kcal/day in the control group, respectively.
In this trial, the management of pressure ulcers as regards
nursing, care and treatment was consistently standardized among
both groups.12 Also, the patients were treated according to the
guidelines for local treatment of pressure ulcers in Japan.2
Please cite this article in press as: Hisashige A, Ohura T, Cost-effectiveness of nutritional intervention on healing of pressure ulcers, Clinical
Nutrition (2012), doi:10.1016/j.clnu.2012.04.013
Changes over time in the condition of pressure ulcers were
evaluated according to DESIGN (Japanese evaluation tool of pres-
sure ulcers: depth, exudates, size, inflammation/infection, granu-
lation tissue, necrotic tissue and undermining).16 The Braden scale
and the OH scale were also used for observation. The healing and its
process for pressure ulcers were determined by the investigators
based on the NPUAP classification and DESIGN tool for evaluation.
The total score of DESIGN for healing of pressure ulcers is zero. The
number of subjects for a full analysis set, in the intervention and
control groups, was 29 and 21, respectively.
As a type of economic analysis,17 a cost-effective analysis was
performed. Incremental costs and effectiveness of nutritional
intervention to conventional management were evaluated.
According to the effectiveness measure used (i.e., pressure ulcer
days (PUDs) reduced and quality-adjusted life-years (QALYs)
gained), incremental cost-effectiveness ratios (ICERs) were
calculated.
The societal perspective was adopted as a perspective of
economic analysis to evaluate value for money of the nutritional
intervention.17 As to cost items, direct medical care costs (e.g., costs
of tests, nutrition, drugs, health care personnel, and so on) were
examined. Indirect costs (e.g., time costs or production loss among
patients and their families) were not examined, since both groups
of patients were hospitalized due to debilitating diseases (e.g.,
stroke) during and after the intervention, and indirect costs were
the same for both groups. Therefore, the societal perspective in this
study is very similar to a perspective of health care providers. As
a time horizon for evaluation, two levels of time periods, 1)
observational period (i.e., 12 weeks), 2) follow-up period (i.e., 12-
week observation plus 4-week follow-up ¼ 16 weeks in total)
were considered. As the base case analysis, follow-up period (16
weeks) was used, since this period covered relatively long-term
consequences of intervention on health and costs.
2.2. Effectiveness
The results of the nutritional intervention trial12 were used as
evidence of effectiveness in the economic analysis. The clinical
results have been presented in detail elsewhere.12 As is shown in
Table 1, between the intervention group and the control group, no
statistical differences were observed in age, sex, and conditions for
pressure ulcers and nutrition. The main underlying diseases for
pressure ulcers and their proportion among the subjects were
cerebrovascular diseases (50%), senile dementia (30%), and Par-
kinson’s disease (6%). The main co-morbidities and their prevalence
rates were hypertension (16%), sequel after stroke (16%), diabetes
mellitus (16%), senile dementia (8%), and Parkinson’s disease (6%).
There was no statistical difference in the proportions and
Table 1
Characteristics of subjects and interventional outcomes.
Item Nutritional Control Test, p value
intervention (N ¼ 29)
(N ¼ 21)
Sex (male) 28.6% 34.5% c2, p ¼ 0.658
Age 81.4 (8.1) 80.6 (8.9) t, p ¼ 0.746
BMI 18.6 (4.0) 17.1 (2.6) Welch, p ¼ 0.147
OH scale 7.0 (4.5e8.5) 7.0 (3.0e8.5) Wilcoxon, p ¼ 0.747
Braden scale 11.0 (9.0e11.0) 11.0 (9.0e11.0) Wilcoxon, p ¼ 0.572
Albumin (g/dL) 3.01 (0.24) 2.92 (0.27) t, p ¼ 0.224
Duration of 248 (206) 207 (180) t, p ¼ 0.462
PU days
Intervention outcomes (12 weeks)
Wound size (cm2) 0.7 (0e155.3) 11.6 (0e144.0) Wilcoxon, p ¼ 0.019
Numerical value: mean (SD), Italic numerical value: median (range), PU: pressure
ulcer, OH scale: OhuraeHotta scale.
 A. Hisashige, T. Ohura / Clinical Nutrition xxx (2012) 1e7
prevalence rates of these diseases between the intervention and
the control groups.
Using patients’ data, the prevalence rate of pressure ulcers was
estimated by the KaplaneMeier method, up to 16 weeks from the
start of the trial (Fig. 1). The mean number of PUDs in each group
was estimated as the area under the prevalence curve.18 In addition,
QALYs were estimated from the prevalence curve for pressure
ulcers by weighting each PUD by a utility value (i.e., preference-
based quality of life which evaluates the value of health states in
a single score) for pressure ulcers. This value was derived from
a cross-sectional survey among the Hokkaido district members
(N ¼ 227) of the Japanese Society of Pressure Ulcers. The utility
value (e.g., death ¼ 0, perfect health ¼ 1.0, as anchor points) was
evaluated by a group interview method, using a time trade-off
approach.17 The mean values of utility for the health states of
bed-ridden and bed-ridden with pressure ulcers were 0.39 and
0.30, respectively. The utility value for pressure ulcers was obtained
as the difference of these values. Thus, the mean value (SD) for
pressure ulcers was 0.086 (0.012).
2.3. Cost
Costs incurred for resources used during trial and subsequent
follow-up were estimated from trial data. Resource utilization
during trial and follow-up was derived from individual patient
data. As items for direct costs, nutrition, wages for health profes-
sionals, drugs, tests, dressing materials, pressure redistribution
mattresses and consumables are examined. Quantities for these
items used were recorded by a diary record method. Acquisition
prices for these items were used as unit costs, except for the
following items. For drug costs, the National Health Insurance
reimbursement list and drug price were used.20 Cost per day for
pressure redistribution mattresses was calculated by the equivalent
annual cost method,17 with a discount rate of 5%. Wages per hour
for health professionals were estimated by the basic survey on
wage structure in Japan.21
Mean costs and their standard deviation per patient were
calculated by summing up the costs listed above. Since
Fig. 1. Prevalence curve for pressure ulcers.
Please cite this article in press as: Hisashige A, Ohura T, Cost-effectiveness of nutritional intervention on healing of pressure ulcers, Clinical
Nutrition (2012), doi:10.1016/j.clnu.2012.04.013
3
observations on several patients are censored in a clinical trial,
subsequent costs are unknown. To correct for censoring, the cost
history method proposed by Lin et al18,19 was applied. This method
makes use of the survival function combined with the set of costs
incurred during defined intervals. All costs were converted from
Japanese yen to US dollars based on OECD purchasing power parity
in 2010 ($1 ¼ U111).22 Discounting for the time value of money was
not applied to either costs or effectiveness, since intervention and
follow-up were done within a short period.
2.4. Sensitivity analysis
The results of economic evaluation can be sensitive to the value
taken by key parameters. Sensitivity analysis is used to evaluate
their uncertainty by showing how they respond to parameter
changes. The uncertainty of the results was explored by stochastic
and qualitative sensitivity analyses of important factors.17,23,24 The
impact of uncertainty on the estimated ICER due to the stochastic
nature of sampled data was analyzed by applying a bootstrap re-
sampling technique (i.e., 3,000 times) to both costs and effective-
ness. Its results were shown as a contour curve according to
distribution density. Also, cost-effectiveness acceptability curve
(CEAC) analysis23,24 was performed. A number of qualitative one-
way sensitivity analyses were conducted to explore the impact of
alternative parametric assumptions on the results. These included
alternative assumptions concerning time horizon, key cost
parameters and utility value. All statistical analyses were per-
formed using SPSS 16.0J and TreeAge software.
2.5. Ethical considerations
The study was based on a clinical trial and a follow-up study
approved by the institutional review board review at each of the
study sites and was performed in accordance with the principles of
the Declaration of Helsinki. Informed consent was obtained from all
the patients or their legal guardians. The clinical trial was registered
in the University Hospital Medical Information Network Clinical
Trials Registry.
3. Results
3.1. Effectiveness
The mean PUDs and QALYs in each group are shown in Table 2A.
For 12-week observation and 16-week follow-up, the mean PUDs
for nutritional intervention were 69.0 and 84.6 per person,
respectively. Those for control were 78.6 and 100.8 per person,
respectively. The mean QALYs for nutritional intervention
were 1.63
102 and 2.00
102 QALYs per person, respec-
tively. Those for control were 1.86
102 and 2.38
102 QALYs
per person, respectively.
Nutritional intervention reduced PUDs by 9.6 and 16.2 (P < 0.05)
and gained 0.226
102 and 0.382
102 QALYs per person,
respectively (P < 0.05).
3.2. Cost
The mean costs per patient in each group for the 16-week
observation are shown in Table 3. The mean total cost per person
was $3,718 in the nutritional intervention group and $4,603 in the
control group. The cost of wages for nurses was the major
component in both groups. Although nutritional intervention
added $78 per patient to the ingredient cost of control, this was
offset by the reduction of costs in wages of nurses and physicians.
As is shown in Table 2, for 12-week observation and 16-week
4 A. Hisashige, T. Ohura / Clinical Nutrition xxx (2012) 1e7

Table 2 A number of qualitative sensitivity analyses are shown in

Cost-effectiveness of nutritional intervention. Table 2A and B. As to time horizon (Table 2A), for 12-week obser-
A. Incremental effectiveness and costs of nutritional intervention per person vation and 16-week follow-up, cost-effectiveness ratios were all
Period Nutritional intervention Control Incremental effectiveness
negative, indicating more benefits and less costs (i.e., dominance).
and costs (95% CI) The results of one-way sensitivity analyses are shown in
Effectiveness Table 2B. Variations in utility value, QALYs, total costs and other
PUDs main cost components, including the quantity of nutritional inter-
Observation 69.0 78.6 9.6 (4.9 w 14.2) vention, did not influence the dominance of nutritional
(12 weeks)
intervention.
Follow-up 84.6 100.8 16.2 (8.7 w 23.7)
(16 weeks)
QALYs (
102) 4. Discussion
Observation 1.63 1.86 0.226 (0.116e0.335)
(12 weeks) Although systematic reviews suggested the effectiveness of
Follow-up 2.00 2.38 0.382 (0.205e0.559)
nutritional interventions on prevention and treatment of pressure
(16 weeks)
ulcers,6e9 there has been little evidence on economic evaluation of
Costs nutritional interventions. Only one economic evaluation of nutri-
$
Observation 3,081 3,624 542 (823 w 261)
tional intervention is available.25 This study has speculated that
(12 weeks) a specific sip feed, which is rich in protein, arginine, antioxidants,
Follow-up 3,718 4,603 881 (1,285 w 478) selenium and zinc, could reduce costs, if extra nursing care was
(16 weeks) reduced by one day.25 However, there was no evidence to support
Incremental cost-effectiveness that this nutritional intervention improved pressure ulcers and
Cost ($) per PUD decreased Cost ($) per QALY gained reduced nursing care and costs.
Observation 9 (93 w 93) 32,532 Our study is the first attempt to evaluate the cost-effectiveness
(12 weeks) (3,145,337 w 3,003,122)
Follow-up 11 (816 w 559) 38,726
of nutritional intervention based on a randomized controlled trial.
(16 weeks) (2,926,499 w 3,096,049) In other interventions besides nutritional intervention, there are
several economic evaluations for pressure ulcers,26e28 but they
B. One-way sensitivity analysis of cost-effectiveness ratio
were based on before-after studies, which is very weak in study
Factor Cost-effectiveness ratio design. From the societal perspective, this cost-effectiveness anal-
($ per QALY gained)
ysis of nutritional intervention on healing of pressure ulcers saved
Base case analysis (follow-up period) 38,726
costs and improved health outcomes, compared with conventional
Observation period (12 weeks) 32,532
Utility (95% CI) 47,297 w 30,155 nutrition management (Table 2). This result can be ranked near the
Difference in QALYs (95% CI) 72,114 w 26,470 top of a league table of cost-effectiveness in health care, since less
Difference in total costs (95% CI) 56,420 w 21,032 than 20% of published cost-effectiveness studies showed cost
Difference in wages (95% CI) 53,038 w 24,592 savings with health improvement.29
Nurse wages (95% CI) 44,889 w 33,403
Difference in Racol quantity during observation 41,766 w 35,713
In this study, nutritional intervention improved the healing of
period (95% CI) pressure ulcers. This led to reduced costs for managing pressure
Difference in dressing quantity (95% CI) 39,360 w 38,091 ulcers (mainly those for health professionals such as nurses and
Difference in drug costs (95% CI) 39,998 w 37,324 physicians) (Table 3). Then, this reduction compensated for the cost
Price of pressure redistribution mattress (range) 38,921 w 38,482
of nutritional intervention. To estimate the uncertainty of these
PUD: pressure ulcer day, CI: confidence interval, QALYs: quality-adjusted life-years. results due to sampling bias, probabilistic sensitivity analyses17,23,24
were performed (Table 2A, Fig. 2). The cost-effectiveness contour
curve showed that ICER mostly located in the quadrant of both cost
follow-up, nutritional intervention reduced costs per person by
savings and greater effectiveness on the cost-effectiveness plane.
$542 and $881 compared with control, respectively (P < 0.05).
The cost-effectiveness acceptability curve gives additional infor-
mation. Even if a decision maker was unwilling to invest anything
3.3. Incremental cost-effectiveness ratio to achieve additional QALY, the likelihood of nutritional interven-
tion being acceptable as cost-effective was 67% (Fig. 2B). These
Nutritional intervention showed dominance (cost savings and results show that the dominant cost-effectiveness of nutritional
greater effectiveness). As is shown in Table 2A, ICER for 12-week intervention is robust in taking several main factors into consid-
observation and 16-week follow-up was estimated to eration (Table 2B).
be $32,532 and $38,726 per QALY gained, respectively, using the Therefore nutritional intervention is a highly efficient approach
bootstrap method. ICER per PUD decreased was $9 and $11, for managing pressure ulcers, and can be considered as a cost-
respectively. effective intervention to be accepted for wide use in Japan. Nutri-
tional intervention offers value for money among health care
3.4. Sensitivity analysis providers and long-term care facilities, since cost savings and
health improvement can be achieved without budgetary increase.
The results of a probabilistic sensitivity analysis are shown in There are several points for discussion in the analysis that
Fig. 2. Figure 2A shows ICER (cost per QALY gained) contour curve, should be commented on, and health professionals and policy
where higher density of distribution for scatter plots of cost- makers should treat the results with caution. First, the analysis was
effectiveness ratio, based on 3,000 samples, is shown as a darker based on a small RCT.12 Since it would be vulnerable to biases,
area. More than 45% of the points were placed in the quadrant of extensive sensitivity analyses were performed to examine this
both cost saving and greater effectiveness. The cost-effectiveness uncertainty. However, large-scale RCTs are crucial to resolving this
acceptability cure is presented in Fig. 2B. Even if additional QALY issue, since systematic reviews of nutritional interventions on
was valued as 0, the likelihood of nutritional intervention being pressure ulcers indicated that large RCTs with high quality are
cost-effective was 67%. required to confirm current clinical evidence.6e9

Please cite this article in press as: Hisashige A, Ohura T, Cost-effectiveness of nutritional intervention on healing of pressure ulcers, Clinical
Nutrition (2012), doi:10.1016/j.clnu.2012.04.013
 A. Hisashige, T. Ohura / Clinical Nutrition xxx (2012) 1e7 5

Table 3
Mean costs per patient (follow-up period, 16 weeks).

Item Nutritional intervention Control

Unit cost ($/unit)
Quantity (No. of units) Cost ($) Quantity (No. of units) Cost ($)
Nutritional management
Observation (w12 weeks)
Racol ($0.82/100 ml) 943 773.4 848 695.2
After observation (13 weeksw)
Racol ($0.82/100 ml) 80 65.8 53 43.6
High density liquid foods ($1.14/100 ml) (range: $0.99e1.70) 43 49.4 108 123.5
Others ($1.18/100 ml) (range: $0.98e1.28) 14 16.7 24 28.2
Management of pressure ulcers
Wage per hour
Physician ($48.6/hr) 5.7 277.2 8.0 387.0
Nurse ($20.6/hr) 82.0 1,686.7 113.5 2,335.2
Assistant nurse ($12.8/hr) 33.2 424.5 34.9 446.3
Others ($17.7/hr) 6.9 121.7 5.6 98.4
Drugs
Sucrose, povidone-iodine ($0.10/g) (range: $0.01e0.39) 307.0 29.5 571.2 54.8
Iodine ($0.72/g) 23.2 16.6 40.1 28.7
Sulfadiazine silver cream ($0.13/g) 230.2 28.8 468.8 58.7
Normal saline ($0.42/100 ml) (range: $0.22e0.83) 18.9 8.0 23.3 9.9
Bucladesine sodium ointment ($0.48/g) 8.5 4.1 16.2 7.8
Tretinoin tocoferil ointment ($0.47/g) 14.1 5.3 10.4 3.6
Buromeline ointment ($0.22/g) 23.7 5.3 40.6 9.1
Other drugs e 0.9 e 0.9
Dressing materials ($0.81/100 cm2) (range: $0.08e12.86) 122.8 99.6 169.9 137.8
Consumables
Absorbent gauze ($0.05/piece) (range: $0.001e0.13) 194.8 9.0 295.3 14.1
Paper diaper ($0.31/piece) (range: $0.12e1.39) 60.5 18.9 102.8 32.2
Medical glove ($0.02/piece) (range: $0.01e0.03) 608.9 11.9 653.2 12.7
Towel cleaning ($0.12/piece) (range: $0.09e0.13) 41.6 4.8 45.5 5.2
Other consumables e 2.4 e 1.7
Pressure redistribution mattress ($0.68/day) (range: $0.32e0.97) 81.8 57.6 96.8 68.2
Total cost per patient (95%CI) 3,718 (3,006e4,340) 4,602 (4,117e5,008)

Numerical values in unit cost: mean.

Cost of pressure redistribution mattress is calculated based on the equivalent annual cost.
The significance of italic values is only to differentiate the value of quantity from that of costs.

Second, the time horizon for analysis is an important issue in
sufficiently capturing relevant costs and health outcomes of
nutritional intervention. In this study, since the observation period
of the trial (i.e., 12 weeks) was limited, we extended observation to
16-week follow-up. Cost savings increased according to this
extension. In taking the prevalence curve into consideration (Fig. 1),
the effect of nutritional intervention seems to continue for a long
period. The time horizon in this study would underestimate the
value of nutritional intervention.
Third, the perspective of this analysis is that of a society.
Although a societal perspective examines a broader range of costs
compared with that of health care payers, there are some conflicts
between these perspectives. In Japan, fixed and bundling payments
have been introduced to the management of pressure ulcers. Basic
admission covers all care related to hospitalization, including
pressure ulcers, and there is no specific fee for management of
pressure ulcers, except for specific cases. As to specific cases,
additional fees for management of pressure ulcers ($1.8 per
hospitalization, for patients with risk factor or pressure ulcer) and
care of patients with high risk of pressure ulcers ($45.0 per
hospitalization, for patients with difficulties for prevention and
management), as well as for treatment of severe pressure ulcers
($8.1e$45.0 per day according to severity, which is two times
higher than that for mild pressure ulcers) have been set up. These
“management and care” consist of risk and/or clinical assessment of
pressure ulcers, making plans for counter measures, and their
implementations and evaluation. This payment system transfers
financial risks to health care providers with some incentives for
efficient management of pressure ulcers. However, there is no
costing information corresponding to resource use for
hospitalization, and the basic admission fee seems not to cover
actual resource use for pressure ulcers, which was estimated as
$29e$44 per day in this study. While this situation will hamper
diffusion of nutritional intervention, the payment system should be
changed to reflect evidence-base management of pressure ulcers.
In fact, there is a big controversy between payers and providers
around the appropriateness of the fee.
Fourth, PUDs as an intermediate outcome and QALYs as a final
outcome were used as economic outcome measures for the
analysis. There are a very limited number of studies on quality of
life for pressure ulcers, and moreover they used a general profile
approach, which can not be used in economic evaluation.30,31 Both
intermediate and final measures are usually used in economic
evaluation,17 but not in these studies on pressure ulcers. In
particular, QALYs are valuable for decision making in health care,
and utility is its essential component. In this study, health care
professionals for pressure ulcers were used to evaluate utility as
surrogate respondents for patients with pressure ulcers. It seems
difficult to interview the patients themselves, since they are often
bed-ridden elderly with debilitating diseases such as stroke, and
disturbance in recognition and speech. Also, it is reported that
there are generally small differences in utility values among
groups including patients, general population, and health
professionals.32
Fifth, nutritional support for pressure ulcers has been
proposed in various guidelines,2e4 but there is no optimal
support or intervention proposed yet. Although the nutritional
intervention in this study showed effectiveness and cost-
effectiveness on healing of pressure ulcers, head-to-head evalu-
ations comparing other or new emerging interventions will need

Please cite this article in press as: Hisashige A, Ohura T, Cost-effectiveness of nutritional intervention on healing of pressure ulcers, Clinical
Nutrition (2012), doi:10.1016/j.clnu.2012.04.013
6 A. Hisashige, T. Ohura / Clinical Nutrition xxx (2012) 1e7
Fig. 2. Stochastic sensitivity analyses. A: Incremental cost-effectiveness contour curve
in 2A shows the relative concentration of points in the scatter plot for cost-
effectiveness ratios, with a range of shades. B: An oblique line in 2A shows that
cost-effectiveness ratio is $5
104 per QALY.
to be carried out in the future. Our study provides basic infor-
mation in comparing cost-effectiveness of nutritional interven-
tion on pressure ulcers.
Sixth, although the results of this study (i.e., cost saving and
health improvement) are very desirable in both clinical and health
policy, they must be cautiously examined in transferring to other
countries. In transferring evaluation data, several key factors (e.g.,
characteristics of patients, clinical practice patterns, relative costs
and the health care system) should be considered. On the other
hand, there is fair evidence for effectiveness of nutritional inter-
vention on healing pressure ulcers internationally, and this study
showed promising evidence for its cost-effectiveness. In taking this
study into consideration, economic evaluation based on good RCTs
Please cite this article in press as: Hisashige A, Ohura T, Cost-effectiveness of nutritional intervention on healing of pressure ulcers, Clinical
Nutrition (2012), doi:10.1016/j.clnu.2012.04.013
would be internationally and urgently needed for clinical and
health policy making.
In conclusion, economic evaluation of nutritional intervention
on healing pressure ulcers showed that this intervention is cost
saving with health improvement. Therefore nutritional interven-
tion is a highly efficient approach for managing pressure ulcers in
Japan, and can be considered as a latent cost-effective intervention
to be accepted for wide use.
Statement of authorship
Authorship contributions are as follows:
AH: study concept and design, acquisition, analysis and inter-
pretation of economic data, and preparation of manuscript.
TO: acquisition of subjects and/or clinical data, analysis and
interpretation of clinical data.
Both authors read and approved the final manuscript.
Conflict of interest
None declared.
Acknowledgments
This study was partly supported by the Institute of Healthcare
Technology Assessment, Tokushima, Japan. The institute had no
role in any aspect of this study.
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