Modern Economy, 2013, 4, 9-13 Published Online October 2013 (
Economic Evaluation of Continuous Subcutaneous Insulin
Infusion for Children with Diabetes—Part II*
Elina Petkova1, Valentina Petkova1, Maia Konstantinova2, Guenka Petrova1
1Department of Social Pharmacy, Faculty of Pharmacy, Medical University, Sofia, Bulgaria
2Endocrinology Clinic, University Pediatric Hospital, Medical University, Sofia, Bulgaria
Received September 4, 2013; revised September 28, 2013; accepted October 7, 2013
Copyright © 2013 Elina Petkova et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The aim of this study is to assess long-term metabolic outcomes in children with diabetes mellitus and to compare the
efficacy, feasibility and metabolic control expenses for treatment with continuous subcutaneous insulin infusion (CSII),
compared to human insulin treatment. The study sample included 34 children aged 3 to 18 years with type 1 diabetes,
17 with continuous subcutaneous insulin infusion (CSII) therapy and 17 with standard treatment with human insulin.
The study observed for the following variables: duration of the disease, diabetic control, HbA1c deviation scores; height
and weight deviation and price of the treatment. Methods applied include meta-analyses in the published medical lit-
erature, pharmacoeconomic analysis and statistical analysis. From the 34 children with diabetes type 1 observed retro-
spectively during the period 1999-2012, 17 were on CSII (mean age 10 years, mean duration of the disease—7 years,
average usage of CSII—3 years). The test stripes cost 533 Euro/year (1100 stripes per year) and their average cost ac-
cording to the duration of the disease is 3779.45 Euro since diagnosis. The blood glucose monitoring system costs 20
Euro and for the duration of the disease—4.96 Euro per patient per year. The average improvement of HbA(1c) after the
CSII introduction is 1.85, while after the applicatio n of human insulin—0.28. Th e treatment with CSII leads to signifi-
cant improvement in glycemic control compared to the treatment with human insulin. The reduced HbA(1c) shows
good diabetes management, from one point of view, and good quality of life—from another.
Keywords: Diabetes; CSII; Metabolic Control
1. Introduction
The exponential rise in th e prevalence of diabetes can be
associated with an increase in the long-term complica-
tions that associate with this disease. Type-1-diabetes
(T1DM) patients treated with unmodified regular human
insulin (RHI) rarely achieve their glycemic target and
often suffer from postprandial hyperglycemic incidents,
together with an increased risk of hypoglycemia in the
post-absorptive period [1]. The pattern of diabetic com-
plications is changing. Western Europe advanced reti-
nal disease and end-stage renal failure are diminishing,
while coronary heart disease has become a leading com-
plication. Recent meta-analyses in the literature have
been found to improve g lycemic control with continuous
subcutaneous insulin infusion (CSII) compared with
multiple daily injections (MDI) of insulin for patients
with diabetes mellitus. For example, in Australia, CSII is
predominantly used in type-1-diabetes mellitus patient
populations [2]. Continuous subcutaneous insulin infu sion
(CSII) is considered an option for type-1 diabetic patien ts
unsatisfactorily controlled with multiple daily injections
(MDI). Short-acting analogs are superior to regular hu-
man insulin in CSII. There is evidence supporting the
advantages of short-acting analog-based CSII over MDI
in type-1 diabetes. The reduction of glycated hemoglobin
(hba1c) level with CSII was evident in trials enrolling
patients with mean age greater than 10 years [3]. The
main goals for managing children with type-1-diabetes
mellitus include achieving normal blood sugar levels,
minimizing hypoglycemic incidents, optimizing quality
of life, and preventing or delaying long-term comp-
lications. Continuous subcutaneous insulin infusion (CS II )
is a treatment option that can assist in achieving all of
these goals in all ages of children [4]. European Union
countries reimburse insulin therapy for individuals with
health insurance, but for CSII reimbursement, a variety
of approaches exist [5-7]. The objective of this study is to
assess the cost of using CSII of insulin to treat children
*Competing Interests: the authors declare that they have no competing
opyright © 2013 SciRes. ME
with type-1 diabetes in Bulgaria and to compare it with
the changes in BMI and HbA(1c). The study was per-
formed from the perspective of the Bulgarian NHIF and
patients. The main study question discussed is “will the
use of CSII be cost-effective for the Bulgarian health
care system?”
2. Methods
2.1. Literature Review
PubMed was searched using keywords CSII, type-1 dia-
betes, pediatric population and all articles analyzing the
safety, efficacy, and cost-effectiveness of CSII usage and
human insulin treatment in the pediatric population were
selected. In total, 4 studies were selected and their objec-
tives, methodologies, results and conclusions were com-
pared [2,8 -10].
2.2. Type of the CSII Usage Study
In order to perform the main aim of the study a combined
retrospective and prospective analysis of children patient
records after the introduction of CSII was performed
based on the patients’ records and observation. The main
setting is Endocrinology Clinic of University pediatric
hospital of the Medical University, Sofia. The study was
reviewed and approved by the Ethics committee of the
Science medical council of the Medical University in
2.3. Patient Screening
A total of 34 children with type-1-diabetes were ob-
served divided into two groups: with an active group
using CSII and a control group using human insulin
therapy. Thirty children in the country use CSII, and of
these, 17 were included in the survey, after their parents
signed informed-consent forms. The active group in-
cluded all children who began using the CSII pumps
during the period 2007-2011 when the data collection
began. Also since 2010, all children were transferred to
real time insulin pumps; therefore at the moment of ob-
servation, they all used the same type of pump from the
same manufacturer. The control group was formed after
reviewing patient records and random selection accord-
ing to age, duration of diabetes, entrance BMI and HbA 1c
level. Their parents also signed informed-consent forms.
2.4. Data Collection
The duration of the observation was from 01.02.2012 to
31.08.2012 (7 months). During this period, the diabetes
maintenance phase after CSII in trod uc tion was measured.
Data for the selected children was collected on their
demographics, age, gender, weight, duration of disease,
therapeutic schema (CSII or analogue insulin treatment
with a pen device) and HbA1c before the inclusion in the
pump program, and at the end of the observation.
2.5. Cost-Effectiveness Analysis
For both groups of children, the health care resources
used by them were recorded, namely insulin, pumps (1
for 4 years), consumables for pumps (6 - 10 sets and 6 -
10 reservoirs), strips (n = 1100 per patient per year),
glucometers (1 for 5 years including sensor prices), GP
and endocrinology visits, and hospitalization due to dia-
betes. Sensors were used from 7 to 10 days. Yearly costs
of CSII, blood glucose monitoring systems, insulin ther-
apy, and strips were calculated by multiplying the num-
ber of resource s used by their prices. Prices of pumps and
blood glucose monitoring systems were collected from
the manufacturers’ websites. To calculate the yearly
pump costs, the prices were divided by 4, which is rec-
ommended by the manufacturers as the period of use for
initial users [11]. All other costs were taken from the
Bulgarian NHIF tariff [12]. Costs are presented in Bul-
garian leva (BGN). At the time, the exchange rate was 1
Euro: 1.95 BGN. The primary outcome observed was the
change in HbA(1c) before the pump introduction and at
the end of the study. The secondary outcome observed
was the BMI change during the same period. In this pilot
study we did not include the hypoglycemia episodes due
to lack of data for all children. Children were introduced
to pumps in different time periods, and in order to calcu-
late the corresponding decrease in the HbA1c level, the
total decrease during the period was divided into the du-
ration of the period when the particular child was using
the pump. Finally the average decrease for both groups
was calculated.
2.6. Sensitivity Analysis
To test the robustness of the results, a one-way sen-
sitivity analysis was performed by consecutively varying
the changes in the HbA1c within the standard deviation
interval for both groups of patients with 0.05.
2.7. Statistical Processing
Descriptive statistics were applied to the patient’s charac-
te r i s tic and ou tcomes. A T-test analysis was also perfor med
to test the statistical significance in the outcome changes.
3. Results
Subcutaneous insulin infusion (CSII) systems are not a
standard treatment for the Bulg arian children. So th ey are
of a limited usage and are not includ ed in the Positive list
for reimbursement.
3.1. Analysis of Published Studies
There are 4 studies in the literature that discuss the effi-
Copyright © 2013 SciRes. ME
cacy, safety and/or cost-effectiveness of CSII usage in
the pediatric population—Table 1. The number of ob-
served patients varied from 19 to 95. All of these studies
measured the decrease in HbA1C, and some, in addition ,
focused on patients’ demographic characteristics, glucose
level, hypoglycemia, and quality of life. All of the stud-
ies conclude that CSII is safe and effective, leading to
greater decreases in HbA1c levels, allowing for im-
proved quality of life, decreased hypoglycemic events
and improved child and parent adherence as shown in
Table 1.
The published studies define the HbA1c level as the
widely accepted measure of diabetes control in pediatric
practice. Positive therapeutic results after CSII introduc-
tion that might lead to better long-term outcomes are ob-
3.2. Results of the Study
The University pediatric clinic has been introducing CSII
on the request of the parents, with only 30 children hav-
ing applied so far. From 1999 to 2011, 17 children with
diabetes type-1 were observed (mean age 113.82 months
in the active group and 112.41 in the control group). The
duration of diabetes was a little lower in the control
group—Table 2. The average improvement of HbA (1c)
in the active group after the CSII introduction is 1.85,
while after the application of human insulin—0.28 (Table
From the 34 children with diabetes type 1 observed
retrospectively during the period 1999-2012 17 were on
CSII (mean age 10 years, mean duration of the disease—
7 years, average usage of CSII—3 years). The test stripes
costs 533 Euro/year (1100 stripes per year) and their av-
erage cost according to the duration of the disease is
3779.45 Euro since diagnosis. The blood glucose moni-
toring system costs 20 Euro and for the duration of the
disease—4.96 Euro per patient per year. The CSII price
is 3896 Euro and compared to the duration of usage it
costs 1290 euro pe r patient per year. Adding and the cost
of insulin and pumps consumables the total yearly cost
per patient in the active group treated with CSII is
2735.79 Euro. The total yearly cost weighed with the
duration of the disease for the passive group treated with
human insulin is 930.39 Euro (Table 3).
Based on these calculations the cost-effectiveness ra-
tion for the active group is 1563.31 Euro and for the
group on human insulin is 3322.82 Euro. Thus the in-
vestment in the therapy of children diabetes with con-
tinuous infusion of insulin with pumps is cost-effective
in comparison with the therapy with human insulin be-
cause it costs less for unit of HbA1c level improvement.
The one way sensitive analysis shows that the CSII
therapy remains cost-effective within the established thera-
peutic interval.
4. Discussion
Continuous subcutaneous insulin infusion (CSII) systems
are of a limited usage because they are not reimbursed by
the Health Insurance Fund in Bulgaria. No official crite-
ria for CSII usage in child populations have been estab-
lished and only parents with sufficiently high income are
able to afford such a therapeutic approach. In this sense,
evaluation of the cost-effectiveness of CSII usage is in-
fluenced by a number of factors, such as health insurance
policy, parents’ preferences, income and therapeutic
standards. This study shows that the usage of CSII with
child populations is an efficient therapy and confirms
similar findings reported in the literature on improve-
ments in terms of better metabolic control, reduced rates
of complications and better quality of life [2,13].
The study also shows that the children using CSII
manage to maintain stable and target HbA1c levels,
which are preconditions for better diabetes management
(UKPDS, DCCT). The studies of the CSII usage in child
populations are very limited for comparing long-term
results in detail, but bearing in mind the evidence for the
adult population, it can be predicted that strict and reli-
able disease control for children will support their long-
term survival.
One limitation of this study is the small pati ent sample
due to the limited number of child ren on CSII in Bulg aria,
but it includes more than 57% of all the CSII users in the
country, which ensures reliable results for the whole
group. The number of the patients is twice as high as
Wilsons’ study [8]. We did not calculate the cost-effec-
tiveness of CSII pumps related to the second observed
outco me—BM I, bec ause an incre ase in child ren’s weight
as a result of their normal developmental growth was
observed in the both groups.
The results from the study can be an evidence for the
Bulgarian NHIF to include CSII within the reimburse-
ment system. Strict criteria for appropriate selection of
children must be developed, as well as cost controls in
order to make the final decision. The reimbursement
practice in some countries provides such evidence, as in
Serbia, where insurance authorities are paying for con-
sumables and patients’ families are paying for pumps. In
countries with high GDP, CSII is included within the
scope of the reimbursement system [7].
5. Conclusion
The treatment with CSII leads to significant improve-
ment in glycemic control compared to the treatment with
human insulin. The reduced HbA(1c) shows good diabe-
tes management, fr om one point of view, and good qual-
ity of lifefrom another.
6. Acknowledgements
We wish to thank to the staff of University paediatric
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Table 1. Summary of the main findings from the published studies.
Authors Objective Methodology Results Conclusions
Plotnick et al.,
To evaluate the safety
and effectiveness of
insulin pump therapy in
children and adolescents
with type-1 diabetes.
All patients who started
insulin pump therapy between
1 January 1990 and 31
December 2000 w ere
included in this study.
HbA1c was measured at
each visit by cation-exchange
high-performance liquid
There was a small but significant
decrease in HbA1c at 3 - 6 months
after starting with pump (7.7 vs.
7.5%; P < 0.03). HbA1c levels then
gradually increased and remained
elevated after 1 year of follow-up.
There were fewer hypoglycem i c
events after pump start (12 vs. 17,
rate ratio 0.46, 95 % CI 0.21 - 1.01).
Insulin pump use was safe and
effective. After adjusting for age
and duration of diabetes, HbA1c
was in fact lower after pump
placement. Both monitoring
frequency and parental
involvement were significantly
associated with lower
HbA1c levels.
Bode et. al,
To compare multiple
daily injections (MDI),
and CSII and to assess
the effects on quality
of life.
Comparative analysis
The effectiveness of CSII
and improvements in pump
technology have fueled a dramatic
increase in the use of this therapy.
Insulin pump or continuous
subcutaneous insulin infusion
(CSII) therapy provides a treatment
option that can dramatically aid in
achieving all of these goals.
Wilson et al,
To compare cont inuous
subcutaneous insulin
infusion (CSII), and
continuing multiple
daily injections (MDIs),
in respect to their safety
in young children,
glycemic c o nt rol,
hypoglycemia and
quality of life.
A randomized 1-year
feasibility trial comparing
CSII with continu ing MDIs
in preschool children with
a history of type-1 diabetes for
at least 6 months’ duration.
Overall metabolic control, diabetes
quality of life, and the incidence of
hypoglycemia were similar in t he
two groups. No subject had diabetic
ketoacidosis, while one subject in
each group had an episode of severe
hypoglycemia. No CSII subject
discontinued usi ng the pump
during or after the study.
CSII can be a safe and effective
method to delive r insulin in
young children.
Cohen et al.,
To project long-term
costs and outcomes of
CSII compared with
MDI in adult and
adolescent T1DM.
The study modeled analysis
utilizing a lifetime horizon
in adult and adolescent
specialty-care type-1-diabetes
patient populations from
Treatment with CSII is associated
with an improvement in life
expectancy of 0.393 years for
adults compared with MDI and
0.537 years for adolescents. The
corresponding gains in QALYs
were 0.467 QALYs and 0.560
QALYs for adults and adolescents,
respectively. This produced
incremental cost effectiveness
ratios (ICERs ) of $A88220 and $A
77851 per life-year gained for C S II
compared with MDI for adult and
adolescent T1DM.
The analysis suggests that CSII
is associated with ICERs in the
range of $A53022 - 259646 per
QALY gained with most ICERs
representing a significant savings
in Australia under the majority
of scenarios explored.
Table 2. Patient demographic.
Gender Age months HbA(1c) 1 HbA(1c) 2 Months with diabetes
Pumps 1.41 ± 0.5 11 3.82 ± 49.0 8.79 ± 0.88 6.94 ± 0.65 66.65 ± 41.07
HI 1.47 ± 0.1 10 8.65 ± 10.2 10.68 ± 0.2 10.40 ± 0.3 22.76 ± 2.92
Table 3. Yearly cost of therapy in both groups.
Insulin cost Pump cost Pen cost Consum. Stripes Monitoring
Pumps 37.83 ± 12.0 0 1290.0 - 870.00 533.00 4.96
Human Insulin 17.43 ± 1.68 150 225.00 533.00 4.96
clinic for their contribution to this project; and for their
valuable techn ical support and for their help in collecting
the data.
[1] A. Mosca, A. Lapolla and P. Gillery, “Glycemic Control
in the Clinical Management of Diabetic Patients,” Clini-
cal Chemistry and Laboratory Medicine, Vol. 51, No. 4,
2013, pp. 753-766.
[2] N. Cohen, M. E. Minshall, L. Sharon-Nash, K. Zakrzewska,
W. J. Valentine and A. J. Palmer, “Continuous Subcu-
taneous Insulin Infusion versus Multiple Daily Injections
of Insulin: Economic Comparison in Adult and Ado-
lescent Type 1 Diabetes Mellitus in Australia,” Pharma-
coeconomics. Vol. 25, No. 10, 2007, pp. 881-897.
[3] M. Monami, C. Lamanna, N. Ma rchionni and E. M an n u c c i,
“Continuous Subcutaneous Insulin Infusion versus Mul-
tiple Dailyinsulin Injections in Type 1 Diabetes: A Meta-
Analysis,” Acta Diabetologica, Vol. 47, No. 1, 2010, pp.
[4] W. Tamborlane, K. Swan, K. Sikes, A. Steffen and S.
Weinzime r, “The Renaissa nce of Insulin Pump Treatment
in Childhood Type 1 Diabetes,” Reviews in Endocrine &
Metabolic Disorders, Vol. 7, No. 3, 2006, pp. 205-213.
[5] G. Soltesz, C. C. Patterson and G. Dalquist, “EUR ODIA B
Study Group Worldwide Childhood Type 1 Diabetes In-
cidence—What Can We Learn from Epidemiology?” Pe-
diatric Diabetes, Vol. 8, Suppl. 6, 2007, pp. 6-14.
[6] F. Carle, R. Gesuita, G. Bruno, G. V. Coppa, A. Falorni,
R. Lorini, et al., “Diabetes Incidence in 0- to 14-Year
Age-Group in Italy,” Diabetes Care, Vol . 27, No. 1 2, 2004,
pp. 2790-2796.
[7] G Stipancic, L. La Grasta Sabolic, M. Sepec, A. Radica,
V. Skrabic, S. Severinski and M. Tiljak, “Regional Dif-
ferences in Incidence and Clinical Presentation of Type 1
Diabetes in Children Aged under 15 Years in Croatia,”
Croatian Medical Journal, Vol. 53, No. 2, 2012, pp. 141-
[8] L. Plotnik, et al., “Safety and Effectiveness of Insulin
Pump Therapy in Children and Adolescents with Type 1
Diabetes,” Diabetes Care, Vol. 26, No. 4, 2003, pp. 1142-
[9] B. W. Bode, H. T. Sabbah, T. M. Gross, L. P. Fredrickson
and P. C. Davidson, “Diabetes Management in the New
Millennium Using Insulin Pump Therapy,” Diabetes/
Metabolism Research and Reviews, Vol. 18, No. S1, 2002,
pp. S14-S20.
[10] D. Wilson, et al., “A Two-Center Randomized Controlled
Feasibili ty Tr ial of I nsuli n Pump T hera py in Young Children
with Diabetes,” Diabetes Care, Vol. 28, No. 1, 2005, pp.
[13] O. Cohen, A. Korner, R. Chlup, C. S. Zoupas, A. K.
Ragozin, K. Wudi, et al., “Improved Glycemic Control
through Continuous Glucosesensor-Augmented Insulin
Pump Therapy: Prospective Results from a Community
and Academic Practice Patient Registry,” Journal of Dia-
betes Science and Technology, Vol. 3, No. 4, 2009, pp.
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