Vol 10, Special Issue 1, 2018

ISSN - 0975-7058
Research Article
COST-EFFECTIVENESS ANALYSIS OF CEFTRIAXONE GENERIC AND PATENT IN CHILDREN
WITH TYPHOID

SANTI PURNA SARI1*, ICUT DIKI ADESTIA PUTRI1, BINAR NURSANTI2

1
Faculty of Pharmacy, Clinical Pharmacy Laboratory, Universitas Indonesia, Depok, 16424, Indonesia, 2Department of Financial, Karya
Bhakti Pratiwi Hospital, Bogor, 16880, Indonesia. Email: santisari@farmasi.ui.ac.id
Received: 29 June 2018, Revised: 27 September 2018, Accepted: 25 October 2018

ABSTRACT

Objective: This study aimed to measure and compare the effectivity and cost of the two types of ceftriaxone to determine the more cost-effective
treatment.

Methods: In a cross-sectional analytical study, prescription and administrative financial data were retrospectively collected using the total sampling
method. Data of 63 patients, comprising 43 and 20 patients treated with generic and patent ceftriaxone, respectively, were analyzed. The effectiveness
of the treatment was measured in terms of the length of hospital stay of the patients. The total cost of the treatment was the total median of the costs
of drugs, laboratory examinations, medical device usage, physician service, and hospitalization.

Results: The effectiveness of both generic and patent ceftriaxone was 4 days of hospital stay. Cost-effectiveness ratio of generic ceftriaxone was Rp
575,937.25/day and that of patent ceftriaxone was Rp 888,601.75/day.

Conclusion: Generic ceftriaxone was more cost-effective than patent ceftriaxone.

Keywords: Cost-effectiveness analysis, Pharmacoeconomic, Typhoid fever, Ceftriaxone, Karya Bhakti Pratiwi Hospital.

© 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.
org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ijap.2018.v10s1.16

INTRODUCTION those undergoing treatment with antibiotics other than ceftriaxone,

and those with a change of treatment class or antibiotic type during the
Typhoid fever is a communicable disease accounting for 22 million inpatient period.
cases annually and is the cause of mortality in 216,000–600,000 people
worldwide. Typhoid fever is an endemic disease in Indonesia [1]. Data were analyzed using Microsoft Excel and IBM Statistical Package
The aim of prescribing antibiotics is to cease the bacterial growth for the Social Sciences 20.0., Armonk, NY: IBM Corp. with a confidence
and shorten the duration of signs and symptoms of the disease. interval of 95% and an α=0.05. The calculation of effectivity and
The selection of antibiotics is based on sensitivity pattern in each medication cost included the effectivity proportion of medications
hospital [2]. In Karya Bhakti Pratiwi Hospital, generic and branded including the length of hospital stay and total medication cost in rupiah
antibiotics have been used as the first-line treatment for pediatric in each group of generic and patent ceftriaxone.
patients with typhoid fever since 2012. Based on the CPOB manuals,
generic and branded medicines should have equal effectivity. However, Total medication cost was obtained from the total cost of direct
the effectivity of generic and branded medicines remains different, medical components including drugs, medical device use, laboratory
as reported in a previous study [3]. This probability of a significant examinations, and service in each group of generic and patent ceftriaxone.
cost difference as well as effectivity difference between generic and
branded medicines encouraged us to perform a pharmacoeconomic After obtaining total medication cost, CEA was performed, which
analysis of these medicines using cost-effectiveness analysis (CEA). In comprised cost-effectiveness ratio (CER), cost-effectiveness incremental
this study, CEA was used to measure and compare the effectiveness and ratio (CEIR), and sensitivity analysis. CER was obtained by comparing
cost between these two types of treatments to identify the more cost- total medication cost on medication effectiveness (only in patients free
effective treatment. of nausea and vomiting).

METHODS CER=
Totalof medicationcost
Effectiveness(cliniclaoutcomes)
In this cross-sectional analytical study, secondary of prescription and
cost administrative data of patients were retrospectively obtained [4].
The study was conducted at the inpatient installation of Karya Bhakti CEIR was obtained by comparing total incremental medication cost
with incremental effectiveness between the two ceftriaxone groups.
Pratiwi Hospital, Bogor, from February to April 2017. The study
The value obtained considered CEIR score, which represented the
included all children with typhoid fever who were administered generic
additional cost in changing from one alternative drug to another.
or patent ceftriaxone in 2016 and who met the inclusion criteria. Data
were obtained using the total sampling method. Variables measured
Drugcost A-Drugcost B
included medication effectivity, total medication cost, age, and sex. CEIR=
Drugeffect A-Drugeffect B
Inclusion criteria were children with typhoid fever aged 1–19 years
who were treated with generic or patent ceftriaxone. Exclusion criteria Two types of one-way sensitivity analyses were used in this study: Using
were patients with unclear, incomplete, or untracked medical records, simulated increase and decrease in total medication cost and using

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Int J App Pharm, Vol 10, Special Issue 1, 2018

maximum and minimum simulations from total medication cost. Both Laboratory examinations were performed in the diagnostic stage,
sensitivity analyses were performed with a fixed effectiveness value. therapy progress observation, and final results of the treatment.
Laboratory examinations for pediatric patients with typhoid fever
RESULTS usually include the Widal test, immunochromatography test,
and polymerase chain reaction test (3.1 [EN] Please expand the
Based on prescription data in 2016, 167 pediatric patients used generic abbreviation). Median laboratory examination cost during the use of
or patent ceftriaxone as treatment for typhoid fever in 2016. After ceftriaxone was calculated and compared between the generic and
adjusting the inclusion and exclusion criteria, the study included 63 patent ceftriaxone groups. Based on the sample data obtained from
children. Patients’ characteristics are summarized in Table 1. Information System and Management of Hospital, median laboratory
costs for the two groups were Rp 308,000 and Rp 365,000, respectively.
CEA Based on non-parametric Mann–Whitney U-test, the p-value obtained
Treatment effectiveness in this study was measured in terms of the was 0.963 (p>0.05), indicating that laboratory examination cost was
length of hospital stay of patients. The results of effectiveness analysis not significantly different between the two groups.
parameter were presented as the median length of stay of the generic
and patent ceftriaxone groups. Based on the analysis, the median Median medical device use cost during the use of ceftriaxone was
length of hospital stay was 4 days. Mann–Whitney U-test revealed no calculated and compared between the generic and patent ceftriaxone
significant difference between generic and patent ceftriaxone treatment groups. Medical devices included needle, syringe, infusion equipment,
effectiveness in terms of the length of hospital stay (p=0.548). NaCl 0.9% solution, alcohol swab, bandage, mask, and gloves. Based
on cost data stated on Information System of Hospital in each patient,
The results of cost analysis using the total cost of direct medical median medical device use cost in the generic and patent ceftriaxone
components for the two groups are presented in Table 2. groups was Rp 87,351 and Rp 133,529, respectively. Based on
nonparametric Mann–Whitney U-test, the p-value obtained was 0.040
Drug cost was defined as the cost of ceftriaxone used during the (p<0.05), indicating that medical device use cost was significantly
hospitalization period. The median drug cost of generic and patent different between the two groups.
ceftriaxone was Rp 97,000 and Rp 1,070,880, respectively. Based on
non-parametric Mann–Whitney U-test, the p-value obtained was 0.000. Service cost included physician service cost during patients’ stay in the
Drug costs of generic and patent ceftriaxone were significantly different hospital. Median service cost in generic and patent ceftriaxone groups
(p<0.05). was Rp 130,000 and Rp 260,000, respectively. Based on non-parametric

Table 1: Patient characteristics

Patient characteristics Total Generic ceftriaxone Patient ceftriaxone

n=63 (%) n=43 (%) n=20 (%)
Age
Toddlers (0–5 years) 35 (55.55) 22 (51.16) 13 (65)
Children (>5–11 years) 25 (39.69) 18 (41.87) 7 (35)
Adolescents (>11–19 years) 3 (4.76) 3 (6.97) 0 (0)
Total 63 (100) 43 (100) 20 (100)
Sex
Male 28 (44.45) 18 (41.86) 10 (50)
Female 35 (55.55) 25 (58.14) 10 (50)
Total 63 (100) 43 (100) 20 (100)
Payment source
Self‑found 24 (38.1) 13 (30.23) 11 (55)
BPJS (National Health Insurance) 24 (38.1) 22 (51.16) 2 (20)
Private Health Insurance 15 (23.8) 8 (18.61) 7 (35)
Total 63 (100) 43 (100) 20 (100)
Treatment class
Class I 13 (20.63) 11 (25.58) 2 (10)
Class II 12 (19.04) 10 (23.25) 2 (10)
Class III 23 (36.50) 15 (34.88) 8 (40)
First Class 3 (4.76) 1 (2.32) 2 (10)
VIP Class 11 (17.49) 5 (11.65) 6 (30)
VVIP Class 1 (1.58) 1 (2.32) 0 (0)
Total 63 (100) 43 (100) 20 (100)
Length of hospital stay
Median (days) 4 4 4
Range 3–7 3–7 3–7

Table 2: Comparison of medical cost between generic and patent ceftriaxone groups

Cost Type Generic Patent p‑value

ceftriaxone (Rp) ceftriaxone (Rp)
Median drug cost 97,000 1,070,880 0.000*
Median laboratory cost 308,000 365,000 0.953
Median medical device use cost 87,351 133,529 0.040*
Median service cost 130,000 260,000 0.153
Median hospitalization cost 1,555,000 1,695,000 0.170
Median total medication cost 2,303,749 3,554,407 0.000*
*significant difference

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Mann–Whitney U-test, the p-value obtained was 0.153 (p>0.05), medication groups. However, total medication cost in the generic
indicating that service cost was not significantly different between the ceftriaxone group was lower than that in the patent group; hence,
two groups. generic ceftriaxone was in a dominant position in the effectiveness
and cost table (Table 5). Meanwhile, the patent ceftriaxone group was
Median hospitalization cost in the generic and patent ceftriaxone in the dominant position. A clear position between the medication
groups was Rp 1,555,000 and Rp 1,695,000, respectively. Based on groups showed that generic ceftriaxone was more cost-effective than
non-parametric Mann–Whitney U-test, the p-value obtained was 0.170 patent ceftriaxone; hence, calculation of the CEIR was not necessary.
(p>0.05), indicating that hospitalization was not significantly different Subsequently, a sensitivity analysis was performed to measure
between the two groups. uncertainty from various data used as well as resulting from the
pharmacoeconomic analysis.
Median total medication cost for patent ceftriaxone (Rp 3,554,407)
was higher than that for generic ceftriaxone (Rp 2,303,749). Based Sensitivity analysis
on non-parametric Mann–Whitney U-test, the p-value obtained was Sensitivity analysis was performed by simulating 25% or 50% increase
0.000 (p<0.05), indicating that total medication cost was significantly and decrease in median total medication cost. The results of the
different between the two groups. Median total medication cost for sensitivity analysis are shown in Table 6.
each medication was used further in CEA, which consisted of CER, CEIR,
and sensitivity analysis. The results of the sensitivity analysis showed that even though median
total medication cost from generic ceftriaxone was decreased by 25%
CER and 50% or increasing by 25% and 50%, CER of the generic ceftriaxone
Mean CER was calculated by comparing median total medication group remained lower than that of the baseline CER of the patent
cost with medication effectiveness in generic and patent ceftriaxone ceftriaxone group (Rp 888,601.8). Meanwhile, a significant difference
groups. Based on normality test, total cost data distribution was not in the CER of the patent ceftriaxone was observed only at 50% decrease
normal; hence, median total medication cost used in the calculation was median total medication cost, at which point the CER of the patent
considered total medication cost. Medication effectiveness was defined ceftriaxone group (Rp 444,300.88) became lower than the baseline CER
as median length of hospital stay. The CER of each medication group is of the generic ceftriaxone group (Rp 575,937.3).
shown in Table 3.
DISCUSSION
CER of the generic ceftriaxone group was lower (Rp 575,937.25/
day) than that of the patent ceftriaxone group (Rp 888,601.75/day). Of the 63 patients in this study, 43 and 20 patients were administered
Moreover, CER was calculated according to the treatment class of generic or patent ceftriaxone of a brand, respectively. The analysis
patients. CER of each medication group based on their treatment class was performed by comparing total medicinal cost and treatment
is shown in Table 4. effectiveness of the generic and patent ceftriaxone groups.

The length of hospital stay in the generic and patent ceftriaxone Among the patients who met the inclusion criteria, the number of
groups was similar, showing effectiveness equality between the two patients using generic ceftriaxone (71.67%) was more than that of
patients using patent ceftriaxone (28.33%). This might be explained
by the fact that a majority of patients were covered under BPJS
Table 3: CER
health insurance (National Health Insurance), and the use of generic
ceftriaxone was recommended according to BPJS terms and conditions
Ceftriaxone Total medication Length of CER (Rp/day)
in 2014 stated in National Formularies based on Keputusan Menkes RI
type Cost (Rp) hospital stay
No.328/Menkes/SK/2013 [5].
Generic Rp 2,303,749 4 575,937.25
Patent Rp 3,554,407 4 888,601.75 Based on the payment source type, 24 patients paid total medication
CER: Cost‑effectiveness ratio cost independently (38.09%); 24 patients paid total medication cost

Table 4: CER according to treatment class

Ceftriaxone type Treatment class Total medication cost (Rp) Length of stay CER
(Rp/day)
Generic Class I 2,979,218 4 744,804.5
Class II 1,604,913 4 401,228.25
Class III 1,690,996 4 422,749
First Class 3,422,989 4 855,747.25
VIP Class 4,234,205 4 1,058,551.25
VVIP Class 4,703,229 4 1,175,807.25
Patent Class I 4,607,705 4 1,151,926.25
Class II 3,697,294 4.5 821,620.89
Class III 3,040,111 4 760,027.75
First Class 4,690,747 4 1,172,686.75
VIP Class 5,901,886.5 4 1,475,471.63
CER: Cost‑effectiveness ratio

Table 5: Effectiveness and cost of generic and patent ceftriaxone use for pediatric patients with typhoid fever

Effectiveness and cost Lower cost Same cost Higher cost

Lower effectiveness (Need CEIR calculation) Patent to generic ceftriaxone in Class II+(Domined)
Same effectiveness Overall generic to patent ceftriaxone+(Dominant) Overall patent to generic ceftriaxone+(Domine)
Higher effectiveness Generic to patent ceftriaxone in Class II+(Dominant) (Need CEIR calculation)
CEIR: Cost‑effectiveness incremental ratio

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Table 6: One‑way sensitivity analysis with simulation of increase and decrease in median total medication cost

Strategy Median total medication Length of hospital CER

cost (Rp) stay (days) (Rp/day)
Generic ceftriaxone
% decrease in median total medication cost 2,303,749 4 575,937.3
25% decrease in median total medication cost 1,727,812 4 431,952.9
50% decrease in median total medication cost 1,151,875 4 287,968.6
25% increase in median of total medication cost 2,879,686 4 719,921,6
50% increase in median total medication cost 3,455,624 4 863,905.9
Patent ceftriaxone
Decrease of 0% from the median of total medication cost 3,554,407 4 888,601.8
Decrease of 25% from the median of total medication cost 2,665,805 4 666,451.31
Decrease of 50% from the median of total medication cost 1,777,204 4 444,300.88
Increase of 25% from the median of total medication cost 4,443,009 4 1,110,752.19
Increase of 50% from the median of total medication cost 5,331,611 4 1,332,902.63
CER: Cost‑effectiveness ratio

using BPJS (38.09%), with 3 using BPJS COB, 20 using BPJS non-PBI, of uncertainty was identified, scored, and interpreted with sensitivity
and one patient using BPJS PBI, and 15 patients (23.81%) paid total analysis. On the basis of the results of sensitivity analysis, it can be
medicinal cost using other insurance. Patients with BPJS PBI had the concluded that before and after cost simulations, CER of the generic
right to avail treatment Class III. Meanwhile, patients with BPJS non- ceftriaxone group was lower than that of the patent ceftriaxone group,
BPI and BPJS CPB had the right to avail treatment Class I, II, or III except when median total medicinal cost of patent ceftriaxone was
depending on the premise paid. Patients with BPJS non-PBI and COB decreased by 50%. This study is suggested to be taken as evaluation
could propose to change for a better treatment class by paying the consideration for the regulator so that generic ceftriaxone can be
cost difference outside the BPJS premise. Based on hospital policy, taken as it is more cost-effective than branded ceftriaxone. However,
patients hospitalized with insurance were referred to treatment further study is needed and if it possible, to consider other effectivity
Classes I, II, first class, VIP, and VVIP. However, room selection parameters such as number of anti-salmonella immunoglobulin M
was based on patients’ need and desire. This caused the variable counted, number of decreased fever temperature, and the count of
distribution of treatment classes in pediatric patients with typhoid leukocytes. It is also suggested to consider including indirect cost and
fever in this study. intangible cost in further study.

Karya Bhakti Pratiwi Hospital provides five types of treatment classes CONCLUSION
for inpatients: Class I, Class II, Class III, first class, VIP class, and
VVIP class. Based on the treatment class type, of the 43 patients with The medication effectiveness of generic ceftriaxone was equal to
typhoid fever who were administered generic ceftriaxone, 11 were that of patent ceftriaxone, as evident by the equal median length of
in Class I (25.58%), 10 were in Class II (23.25%), 15 were in Class III hospital stay (4 days) for both drug types. Statistically, there was no
(34.88%), 1 was in first class (2.32%), 5 were in VIP class (11.65%), significant difference in medication effectiveness between generic and
and 1 was in VVIP class (2.32%). Meanwhile, of the 20 patients with patent ceftriaxone in terms of the length of hospital stay (p=0.548).
typhoid fever who were administered patent ceftriaxone, two were in Median total medication cost of patent ceftriaxone was higher (Rp
Class I (10.00%), two were in Class II (10%), eight were in Class III 3,554,407) than that of generic ceftriaxone (Rp 2,303,749), and there
(40.00%), three were in first class (15.00%), and four were in VIP class was a statistically significant difference in medication effectiveness
(20.00%). Treatment cost for each class was different, which affected between generic and patent ceftriaxone in terms of median total
total medication cost. medication cost (p=0.000). Based on CEA, generic ceftriaxone (CER:
Rp 575,937.25/day) was more cost-effective than patent ceftriaxone
The length of hospital stay was defined as the total number of days from (CER: Rp 888,601.75/day).
the day patients was hospitalized until discharge from the hospital.
Median length of hospital stay in patients who were administered CONFLICTS OF INTEREST
generic or patent ceftriaxone was 4 days, ranging from 3 to 7 days. The authors declare that they have no conflicts of interest.

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