Economic Evaluation of Continuous Subcutaneous Insulin Infusion for Children with Diabetes—Part II

doi:10.4236/me.2013.410A002

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Modern Economy, 2013, 4, 9-13

http://dx.doi.org/10.4236/me.2013.410A002 Published Online October 2013 (http://www.scirp.org/journal/me)

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

Email: guenka.pet[email protected]

Received September 4, 2013; revised September 28, 2013; accepted October 7, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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

interests.

E. PETKOVA ET AL.

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

Sofia.

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-

E. PETKOVA ET AL. 11

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-

served.

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

2).

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 life—from another.

6. Acknowledgements

We wish to thank to the staff of University paediatric

E. PETKOVA ET AL.

Table 1. Summary of the main findings from the published studies.

Authors Objective Methodology Results Conclusions

Plotnick et al.,

2003

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

chromatography.

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,

2002

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,

2005

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.,

2007

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

Australia.

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.

REFERENCES

[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.

http://dx.doi.org/10.1515/cclm-2012-0594

[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-

E. PETKOVA ET AL. 13

lescent Type 1 Diabetes Mellitus in Australia,” Pharma-

coeconomics. Vol. 25, No. 10, 2007, pp. 881-897.

http://dx.doi.org/10.2165/00019053-200725100-00006

[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.

77-81. http://dx.doi.org/10.1007/s00592-009-0132-5

[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.

http://dx.doi.org/10.1007/s11154-006-9018-9

[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.

http://dx.doi.org/10.1111/j.1399-5448.2007.00280.x

[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.

http://dx.doi.org/10.2337/diacare.27.12.2790

[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-

148. http://dx.doi.org/10.3325/cmj.2012.53.141

[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-

1146. http://dx.doi.org/10.2337/diacare.26.4.1142

[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. http://dx.doi.org/10.1002/dmrr.205

[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.

15-19. http://dx.doi.org/10.2337/diacare.28.1.15

[11] http://www.medtronic-diabetes.bg/

[12] http://www.nhif.bg

[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.

804-811.