Markov Modeled Cost - effectiveness analysis of ICS/Formoterol versus Fluticasone/Salmeterol in the Outpatients treatment of Bronchial Asthma at Binh Thanh District Hospital

1. NGUYỄN DUY ANH
Bachelor of Pharmacy (2016 – 2021)
University of Medicine and Pharmacy Ho Chi Minh City
Clinical Pharmacist (2021 – Present)
Binh Thanh District Hospital
THE 12th HO CHI MINH CITY HOSPITAL
15th - 17th September, 2023 | Quy Nhon - Binh Dinh
PHARMACY CONFERENCE

3. CONTENTS
INTRODUCTION
Current Situation: Healthcare System, Economic Burden of Asthma, Why Health Technology Assessment?
METHODOLOGY
RESULT
S
Study design, Measuring Effectiveness, Measuring Cost, Markov Modeling, ICER
Final Model, Incremental Cost-effectiveness Ratio, One-Way Sensitivity Analysis-Tornado Diagram, PSA
CONCLUSIONS
Primarily Results, Perspectives

4. INTRODUCTION Current Situation & Asthma – Economic Burden of Disease
[
DEATHS
per year
+
250.000
cases
worldwide
~339M cases
~4M cases
WORLD Vietnam
“asthma affects about 4 millions people in Vietnam,
with an estimated 14.8% (children from 13-14
years old), and caused approximated 4,000
deaths annual”
Universal health coverage (UHC) means
everyone – all individuals and communities
– having access to quality, needed services
that are affordable.
Allocation decisions can’t be avoided:
Limited resources vs. unlimited
“WANTs”
Chronic disease burden to income was
approximately 80% (2019)
Increasing non-communicable diseases and
growing aging population

5. Why Health Technology Assessment?
Burden of diseases
Cost-effectiveness analysis
Budget impact analysis
Multi-criteria decision analysis
“IF YOU CAN NOT MEASURE IT, YOU CAN NOT IMPROVE IT”
Lord Kelvin
Value-based Medicine Hospital-based HTA
GINA 2019 – a fundamental change in asthma management
no longer recommends treatment of asthma in adolescents and adults with SABA alone, to reduce risk of serious
exacerbations, patients should receive either symptom-driven (in mild asthma) or daily inhaled corticosteroid (ICS)-containing
treatment
Vietnamese Ministry of Health 2022
ICS/Formoterol is the preferred therapy in maintenance and reliever in patients with mild asthma
INTRODUCTION

6. OBJECTIVES
Cost-effectiveness analysis
of ICS/Formoterol vs. Salmeterol/Fluticasone Therapy in the
Maintenance Treatment of Bronchial Asthma in Outpatients
at Binh Thanh District Hospital
by Markov modeling

7. METHODOLOGY
Pharmacy Department – Binh Thanh District Hospital (BTD Hospital)
132 Le Van Duyet, Ward 1, Binh Thanh District, Ho Chi Minh City
Study Start Date: 1st March, 2022
Study Completion Date: 30th September, 2022
Eligibility Criteria: Patients with a diagnosis of asthma treated as outpatients at BTD Hospital
Inclusion Criteria:
Provision of informed consent prior to any study specific procedures. For patients under-age, signed
informed consent from both the patient and the patient's parent/legal guardian is required
Male or Female, ≥ 12 years of age
Are being treated with study therapy for at least 3 consecutive months
Exclusion Criteria:
Current or previous smoker with a smoking history of ≥ 10 pack years
Pregnancy, breast-feeding or planned pregnancy during the study
Study Design

8. METHODOLOGY
EFFECTIVENESS
TREATMENT
COSTS
ICER
DIRECT
COST
QALY WILLINGNESS
TO PAY
Study Design
Sample Size Formula
(Yamane’s formula)
Scale of patients with mild-moderate asthma managed
an average of 120 patients per group. Therefore,
choose P (each group) = 120 and e = 0.05. Sample
each group is n ~ 92 patients.
n =
P
1 + P × e2
n: the sample size
P: the population size
e: the acceptable sampling error
Sample
ICS/Formoterol
(IFO)
Salmeterol/
Fluticasone (SF)
Cost (IFO)
Effect (IFO)
Cost (SF)
Effect (SF)

9. METHODOLOGY Measuring Effectiveness
identify and describe
states of health
choose a method of
determining utility
select the object to
determine the utility
perfect health
illness,
complications
death
determine QALY
for full lifetime
direct method
indirect method
utility (U)
number years of life
1.0
0.8
0.6
0.4
0.2
0.0
1
1 QALY
steps to determine the QALY of a state of health
(*)
(*) Đánh giá Công nghệ Y tế (HTA) Hướng dẫn thực hành trong ngành Dược, Prof. PhD. Hoang Thy Nhac Vu
About
QALYs
QALY is a method of valuing
the cost-effectiveness of
medicines by considering both
the patient’s lifespan and
quality of life. By definition,
one QALY means one year of
living a perfect health, both
physically and mentally. QALY
is used to measure health
technology by considering
whether the medicine or
technology assessed is more
cost-effective when compared
with other one

10. METHODOLOGY Measuring Effectiveness
treatment A treatment B
Time (Life Years)
1
0
0.3
0.6
0.9
2 3 4 5 6
current
treatment
2.1
QALYs
+0.6 QALYs
+2.2 QALYs
Utility
If a person lives for 3 years with a disease and
the current treatment (treatment A) for that
disease with a utility score of 0.7, that person
will have 2.1 QALYs.
If that person receives a new treatment
(treatment B) whereby his/her utility score
increases to 0.9, that person will now have 2.7
QALYs during the initial 3 years, the benefit of
the new treatment will add 0.6 QALYs as this is
the increase over the current treatment.
If the new treatment (treatment B) in addition
prolongs the patient’s life by 3 years,
however at decreasing utility value (year 4 and 5
at 0.8, year 6 at 0.6) the new treatment will
provide an additional 2.2 QALYs.

11. METHODOLOGY Measuring Effectiveness
Steps to Measure Quality of Life (QoL)
(1) Respondents answered questionnaire EQ-5D-5L
(2) Record the answers, determine the corresponding health
status of the surveyed people
(3) Use an althorithm to translate health status domain
measurement into utilites weights
Health status measures – psychology
emphasis on rating specific domains of health
mapped to specific health states
“Health utility is a number that describes
the health state or outcome of a patient,
ranging from zero (representing death) to
one (representing full health)”

12. METHODOLOGY Measuring Cost
Perspective
Health system Payer
Patient Societal
Social Healthcare Insurance
Societal
drug visits to the physicians laboratory tests/imaging hospitalisation/others
All expenses are converted
to the value of 2021 by
Consumer Price Index (CPI)
Fautrel B, Boonen A, de Wit M, et al
Cost assessment of health interventions and diseases
RMD Open 2020

13. METHODOLOGY Markov Model & ICER
INPUTS
Target Population
MARKOV MODEL
Transition Probabilities
matrix of transition
probabilities between
Markov states
package of therapies
OUTPUTS
Number of people distributed in
Markov states at cycle N
Cost, QALY of the entire study sample
and per person after N Markov cycles
Cost of treatment per
person
Utility (QALY)
C
A B
current therapy
△COS
T
△
EFFECTIVENESS
ICER
less effective
and more costly
more effective
and less costly
definitely a wasted buy
v
definitely a best buy
WTP threshold

14. Sample Characteristics
RESULT
S
Probability
density
Age
ICS/Formoterol
Probability
density
Age
Salmeterol/Fluticasone
24.5% 75.5% 27.8% 72.2%
n = 98 n = 97
62.5 64.0

15. Final Model
RESULT
S
Model structure
TRANSITION PROBABILITIES MARKOV MODEL (Weekly Transiton)
pSC
>>
pNC
pNC
>>
pSC
pSoC
<>
pSE
pNC >> pSE
pSE >> pNC
pSC >> pSoC
pSoC >> pSC
The model simulates the
outcomes of a hypothetical
cohort through progression
across time cycles. During
each cycle patients either
transition to a different
health state or remain in
their current state
Time horizon: 50 years
Cycle: Weekly
Annual discount rate: 3%
Price MJ, Briggs AH. Pharmacoeconomics 2002

16. RESULT
S
Final Model
Input parameters – Data sources (Transition Probabilities)

17. RESULT
S
Final Model
DRUG ACQUISITION COSTS (VND)
THERAPY INHALER COST PER INHALER COST PER INHALATION
IFO
ICS/Formoterol (160/4,5mcg) (120 dose) 486.948 4.057,9
ICS/Formoterol (160/4,5mcg) (60 dose) 286.440 4.774,0
SF Salmeterol/Fluticasone (25/250mcg) (120 dose) 278.090 2.317,4
Input parameters – Data sources (Costs and Utilities)
TOTAL EXACERBATION COSTS (VND) (*)
IFO SF
1.464.704,67 3.389.490,14
HEALTH STATE UTILITY VALUES
IFO SF
Severe exacerbation 0.6020 0.4956
Non-exacerbation 0.9557 0.9388
(*) Emergency department visit, Hospitalisation, Medicines, Laboratory tests, Imaging, Other services

18. Incremental Cost-effectiveness Ratio
RESULT
S
ICS/Formoterol (IFO) Salmeterol/Fluticasone (SF) Difference (95% CI)
COSTs (VND)
Drug costs 134,153,611.78 87,663,494.20
Severe exacerbation costs 11,690,810.00 27,053,832.41
Total 145,844,421.78 114,717,326.61 31,127,095.17
(-23,345,321.38 – 85,599,511.72)
QALYs
Severe exacerbation 0.0924 0.0760
Non-exacerbation 24.8315 24.3924
Total 24.9239 24.4684 0.4555
(-0.3417 – 1.2526)
ICER (Incremental Cost-Effectiveness Ratio) 68,336,103.55
Willingness to pay threshold (WTPT) = 3 GDP2021 ~ 260,000,000 VND
Model Outcomes

19. Incremental Cost-effectiveness Ratio
RESULT
S
CERIFO = COSTIFO/QALYIFO = 5,851,559 VND/QALY
CERSF = COSTSF/QALYSF = 4,688,386 VND/QALY
Treatment with IFO has a cost per 1 QALY that is
1.25 times higher than the SF regimen.

20. Monte Carlo Simulation & Probability Sensitivity Analysis
RESULT
S
Input parameters Distribution
Transition probabilities Beta (⍺; β)
Costs Gamma (⍺; β)
Effects Beta (⍺; β)
Beta
(⍺; β)
Mean:
Standard deviation:
Gamma
(⍺; β)
Mean:
Standard deviation:

21. RESULT
S
Monte Carlo Simulation & Probability Sensitivity Analysis
A
B
C D
9,760/10,000 cases of the IFO therapy had a higher QALY value than the SF therapy, and 8,713/10,000 cases (87.13%)
of the cost-effective IFO therapy when compared to WTP threshold
WTP = 3GDP ~ 260M VND (2021)

22. 20 40 60 80 100 120 1,000,000 VND/QALY
Discount annual rate - Costs & Outcomes (0-5%)
Discount annual rate - Costs (0-5%)
Discount annual rate - Outcomes (0-5%)
Non-exacerbation Costs (-/+20%)
Severe exacerbation Costs (-/+20%)
Utility value non-exacerbation (-/+20%)
Utility value severe exacerbation (-/+20%)
Time horizon (5-10 years)
EV: 68,336,103 ICER with high value
ICER with low value
RESULT
S
One-Way Sensitivity Analysis - Tornado Diagram
The cost of hospitalization related to an asthma exacerbation was the most influential factor in
the ICER value. When the cost of the exacerbation ranged from -20% to 20%, the variation of ICER
value decreased by 36,590,561.61 VND/QALY and 23,099.433.26 VND/QALY respectively.

23. CONCLUSIONS
Primarily results
ICER value after Markov simulation with the period of 50 years reaching 68,336,103.55 VND/QALY which is
lower when compared with the willingness to pay threshold according to the recommendation reported by
WHO (3 x GDP in Vietnam)
PSA with 10.000 Monte Carlo simulation loops, the IFO regimen achieved over 80% cost-effective
From a healthcare payer perspective, IFO therapy can be considered as a cost-effective option
Perspectives
Improving the value in health care is a major policy challenge
Cost-effectiveness analysis plays a key role in assessing and promoting value in health care
There is a need for coordination between experts and it is necessary to carry out epidemiological studies to
have the most relevant data for the Vietnamese population in the health economic assessment.

24. Thank you for
your attention!
THE 12th HO CHI MINH CITY HOSPITAL
15th - 17th September, 2023 | Quy Nhon - Binh Dinh
Binh Thanh District Hospital
▪ Thanh-Thuy Truong Thi (FDS)
▪ Truong-An Nguyen (PGJ)
University of Medicine and Pharmacy HCMC
▪ Hai-Yen Nguyen Thi (PhD. Assoc. Prof.)
▪ Gia-Han Tran (BPharm.)
NGUYEN DUY ANH (BPharm.)
nguyenduyanhpharm@gmail.com
PHARMACY CONFERENCE
MARKOV MODELED COST-EFFECTIVENESS ANALYSIS
ICS/FORTEROL VS. SALMETEROL/FLUTICASONE