2017 Ekokes Sesi 5 6 7 JAT Economic Valuation
Economic Evaluation Health Economics
Dr. Jarir At Thobari, MSc, DPharm, PhD
Faculty of Medicine, UGM
1. Dept. Pharmacology and Therapy Div.
Pharmacoepidemiology & Pharmacoeconomy
2. Clinical Epidemiology & Biostatistics Unit
1
Increasing demand of healthcare
2
Budget & resources constraint
3
Financing HIV in developing countries
4
Increasing choices of technology
5
HTA for decision making
• Increase expenditure on drug therapy
• Resources limited (scarcity of budget)
♦ Solution?
– Efficient use of resources within the health care setting
(e.g. switch to cheaper generic drugs1,2)
– Making choices priority
6
Clinical
effectiveness
Medical &
biological
knowledge
Social
aspects
HTA
Costs and
financing
Organisational aspects
Epidemiology
Ethical
consequences
Based on Habbema et al., 1989
What is health technology assessment
(HTA)?
HTA is a multidisciplinary field of policy analysis. It studies the medical, social,
ethical, and economic implications of development, diffusion, and use of
health technology.
Any intervention that may be used to promote health, to prevent, diagnose or
treat disease or for rehabilitation or long-term care. This includes the
pharmaceuticals, devices, procedures and organizational systems used in
health care.
Source: INAHTA/glossary http://www.inahta.net/
Using HTA to inform priority setting
• Applied HTA can be considered as a process for
considering scientific evidence, economic evidence and
social values, to inform decisions as to whether to fund a
treatment / service
– Includes cost-effectiveness analysis (CEA); not just clinical
effectiveness
– Drawing comparisons: Compared to the status quo, what do we
gain out of the new treatment, and at what extra cost?
– Not a merely technical exercise: The process and social values
are equally important
•
NOTE: HTA is one component to support overall quality improvement…
Definition of areas
10
HTA system
11
Economic evaluation (PE)
INPUT
PHARMACEUTICAL
PRODUCT OR SERVICE
Cost Analysis
(a partial economic evalution)
OUPUT
Clinical or Outcome Study
(not an economic study)
Pharmacoeconomic Analysis
Economic Evaluations
Cost A
Intervention A
Consequences A
Cost B
Intervention B
Consequences B
Difference
in costs?
Difference in
consequences?
Relationship?
Cost Effectiveness
new drug/device is cost-effective!
•
•
•
•
•
•
•
•
•
•
•
Reduce the cost
More benefit
Which one more effective and lower costs
Optimal balance costs and effect
Good effect for lowest cost
Highest benefit and lowest cost and safe
Willingness to pay for optimal balance
Cheaper and better!
More expensive and better
Cheaper and lower benefit
Cheaper and same benefit
More Expensive
Negative
Consequences
Positive
Consequences
Less Expensive
Components of economic evaluation (Torrance, 1986)
Resources
consumed
(costs)
Health
improvement
(consequences)
Health care
programme
Direct
costs
Health
effects
Economic
benefits
Value of
health
improvement
per se
Indirect
costs
(prod. Loss)
morbidity
Economic
benefits
direct
Ad hoc
numeric
scales
mortality
Indirect
benefits
(prod. gains)
Willingness
to pay
Intangible
cost
Intangible
benefits
1st ed 1987
Utilities
(Qaly’s)
Costs from what perspective?
Health care costs
- Direct medical costs
Procedures
Treatment
Care
Healthcare payments
- Indirect medical costs
As above but due to a longer
life (expectancy)
Health care
perspective
Societal
perspective
Non-health care costs
- Direct non-medical costs
Informal care
Non-healthcare payments
Travel and time
- Indirect non-medical costs
Productivity costs
Other societal sectors
Intangibles
Happiness
Well-being
Decision makers’
perspective
19
Hospitalized Tarif (in IDR million)
for Non-bacterial Infection based on JKN tariff 2014
Hospital Class
Mild
Hospitalization
- Hospital Class A
o Class 3
o Class 2
o Class 1
- Hospital Class B
o Class 3
o Class 2
o Class 1
- Hospital Class C
o Class 3
o Class 2
o Class 1
- Hospital Class D
o Class 3
o Class 2
o Class 1
Severity Level
Moderate Severe
3408
4090
4771
4244
5093
5942
4530
5435
6341
1948
2338
2727
3081
3697
4314
3522
4226
4930
1557
1868
2980
1989
2387
2784
2123
2547
2972
1299
1559
1818
1676
2011
2347
2075
2490
2905
Types of Pharmacoeconomic Studies
Methodology
Cost
Measurement Unit
Outcome
Measurement Unit
Cost-Minimization Analysis (CMA)
Dollars or Monetary Units
Assumed to be equivalent in
comparable groups
Cost-Effectiveness Analysis (CEA)
Dollars or Monetary Units
Natural units (life years gained, mm
Hg blood pressure, mMol/L blood
glucose)
Cost-Utility Analysis (CUA)
Dollars or Monetary Units
Quality-adjusted life year (QALY) or
other utilities
Cost-Benefit Analysis (CBA)
Dollars or Monetary Units
Dollars or monetary units
Rascati, 2009
Other Types of economic evaluation
• Cost Consequences Analysis (CCA)
– List of costs and various outcomes presented but
no comparisons made
• Cost of illness
– Estimate of total economic burden (prevention,
treatment, losses in productivity) of particular
condition (illness) or disease on society
22
Different effects
•
•
•
Effects
Natural effects
Utilities
Monetary terms
different economic evaluations
Economic Evaluation
- Cost Effectiveness Analysis (CEA)
- Cost Utility Analysis (CUA)
- Cost Benefit Analysis (CBA)
Broad comparison
Level of analysis
Narrow comparison
Cost-Minimization Analysis (CMA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Dollars or Monetary Units
Assumed to be equivalent in
comparable groups
24
Cost-Minimization Analysis (CMA)
Cost-Minimization Analysis (CMA)
– PE analysis where outcomes of two or more
interventions are assumed to be equivalent
• Thus, only costs of intervention are compared
– Objective: choose the least costly alternative
25
Cost-Minimization Analysis (CMA)
Example Problem: Administration of prostaglandin E2 gel intracervically to expectant
mothers on the day before labor was to be induced.
•
•
Outpatient Group: administer medication monitor 2 hours send home overnight
admit next day induce labor
Inpatient Group: administer medication monitor 2 hours send to maternity unit
for the night induce labor
Type of Cost
Costs for Outpatients
(n = 40)
Mean (SD)
Costs for Inpatients
(n = 36)
Mean (SD)
Statistical Difference
Labor cost
$575 ($366)
$902 (482)
Yes (p = 0.002)
Delivery cost
$471 ($247)
$453 ($236)
No (p = 0.754)
Pharmacy cost
$150 ($102)
$175 ($139)
No (p = 0.084)
Hospital Costs
$3835 ($2172)
$5049 ($2060)
Yes (p = 0.015)
Would you recommend the outpatient program?
Farmer KC, Schwartz III WJ, Rayburn WF, Turnbull G. A cost-minimization analysis of intracervical prostaglandin for cervical
ripening in an outpatient versus inpatient setting. Clin Ther. 1996;18(4):747-756.; as reported in Rascati, 2009
Cost-Minimization Analysis (CMA)
Common Applications
– Common CMA application:
• Cost comparison of two generic medications rated as
equivalent by Drug Regulatory
• Cost comparison of same drug therapy in different
settings
– Not appropriate for comparing different classes of
medications
27
Cost-Minimization Analysis (CMA)
Advantages and Disadvantages
– Advantage: simplest analysis to conduct
– Disadvantage: cannot be used when outcomes of
each intervention are different
28
Stroke. 2000;31:1032-1037
29
Stroke. 2000;31:1032-1037
30
Stroke. 2000;31:1032-1037
31
Cost-Effectiveness Analysis (CEA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Exercise
Dollars or Monetary Units
Natural units
(life years gained, mm Hg
blood pressure, mmol/L
blood glucose)
32
Cost-Effectiveness Analysis (CEA)
Cost-Effectiveness Analysis
– PE analysis where outcomes are measured in natural
or clinical units
– CEA is most common type of PE analysis
Two methods of reporting cost-effectiveness:
• Average Cost-Effectiveness Ratio (CER) =
Cost of Intervention
Effectiveness of Intervention
• Incremental Cost-Effectiveness Ratio (ICER) =
Cost of Intervention B – Cost of Intervention A
Effectiveness of Intervention B – Effectiveness of Intervention A
Cost-Effectiveness Analysis (CEA)
• Effectiveness of oral antidiabetic (OAD)
– OAD- A (new drug)
: 25/100 patients
– OAD- B (standard drug) : 19/100 patients
• Clinical outcome:
– number of patients with ≥ 1% decrease in ‘HBA1c’
over one year
34
Cost-Effectiveness Analysis (CEA)
Medicine cost
Lab cost
Adverse event
Physician
Total
Medicine cost
Lab cost
Adverse event
Physician
Total
Cost/unit
No. of
units
(USD)*
Medicine A
40
12
20
1
50
2
25
2
25
20
50
25
Medicine B
12
2
3
3
No. of
patients
Total cost
(USD)
100
100
100
100
48,000
2,000
10,000
5,000
65,000
100
100
100
100
30,000
4,000
15,000
7,500
56,500
*USD = U.S. dollar
Cost-Effectiveness Analysis (CEA)
• Comparison between OAD - A and B for 100 patients for 1
year
Medicine A
Medicine B
• Net costs USD*
65,000
56,500
• Effectiveness
No. patients with ≥ 1%
decrease in glycosylated
hemoglobin
25
19
• Incremental Cost Effectiveness Ratio =
(65,000-56,500)/(25-19) = USD1,416.67 per extra patient
with ≥ 1% decrease in glycosylated hemoglobin
36
Average and incremental ratios
CB
ICER = CB-CA
EB-EA
Treatment B
CB-CA
EB - EA
CA Treatment A
O
EA
EB
Effect (Utility, Benefit)
ICER: Incremental Cost-Effectiveness Ratio
Average vs. ICER
Programme
Breast screening
Costs
Effects
C/E
ΔC/ΔE
A
110
20
5.50
-
B
120
29
4.14
1.11
C
150
50
3.00
1.43
D
190
60
3.17
4.00
E
240
70
3.42
5.00
Average ratios have no role in decision making
Cost-Effectiveness Analysis (CEA)
Common Applications
– Common CEA application: medications with the
same type of primary outcomes, and most often
for treatment of the same types of health
condition
– CEA is only performed when the outcome of one
intervention is both better than another AND the
cost is greater.
39
Cost-Effectiveness Analysis (CEA)
Advantages and Disadvantages
– Advantages:
• Health units are common outcomes routinely measured in clinical
trials – familiar to clinicians
• Outcomes are easier to quantify than CUA or CBA
– Disadvantages:
• Interventions with different types of outcomes cannot be
compared
• Can’t combine more than one important outcome
• Difficult to collapse both the effectiveness and the side effects into
one unit of measurement
• CEA estimates extra cost associated with each additional unit of
outcome, but who is to say that added cost is worth added
outcomes? Requires judgment call.
40
The Cost Effective Plane of ICER
+
Differenc
rence in cost
IV
I
> Costs
>> Effective
>> Costs
-
+
Effective
= 0
• Laupacis et al (1992)
– < Can$20,000 Go ; > Can$100,000 No Go
– Inbetween → professional judgment required
• Owens (1998)
– < US$50,000 Go ; > US$50,000 No Go
• NICE: ₤ 30,000 ₤ 50,000
• Netherlands: € 20,000 € 50,000
• Belgium: € 50,000
Maximum acceptable
• Willingness to pay
• WHO Commission on Macroeconomics and Health
– cost-effective:
• interventions had a positive net benefit at a
willingness-to-pay of three times the per capita GDP
– highly cost-effective:
– interventions had a positive net benefit at a
willingness-to-pay of one times the per capita GDP
44
45
Cost-Utility Analysis (CUA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Question
Dollars or Monetary Units
Quality-adjusted life year
(QALY) or other utilities
48
Cost-Utility Analysis (CUA)
Cost-Utility Analysis (CUA)
– A PE analysis which measures outcomes based on years of life that are adjusted by
“utility” weights (patient preferences); range [0, 1]
– Most common utility is the Quality-Adjusted Life Year (QALY)
• 1.0 QALY = 1 year of life in perfect health
• 0.0 QALY = death
• 0.0 < QALY < 1.0: a year when health is diminished by disease or treatment
Quality Adjusted Life Years (QALYs) weight the life years remaining by the utility
weight (QALY)
• Ex: 4 years of life post cancer treatment at 0.6 utility wt = 2.4 QALYs
– Average vs. Incremental Cost per QALY: (similar to CEA):
• Average Cost per QALY =
Incremental Cost per QALY =
–
Cost of Intervention
Cost of Intervention B – Cost of Intervention A
–
QALYs of Intervention
QALYs of Intervention B – QALYs of Intervention A
49
Cost-Utility
Analysis
(CUA)
Health
Related Quality
of Life
(HRQoL)
HRQoL - Health state value or utility
1
4 * 0.9 = 3.6
5 * 1.0 = 5.0
3 * 0.7 = 2.1
2 * 0.8 = 1.6
2 * 0.2 = 0.4
4 * 0.2 = 0.8
Total QALY:
6.3
7.4
Quality
of Life
0
4
7
9
Life expectancy 9 years
11
11 years
Cost-Utility Analysis (CUA)
Example
Human papillomavirus (HPV) vaccine +screening vs. screening only.
Total Lifetime Costs
Quality-Adjusted Life
Expectancy
A. Current Screening Program
Only
(“PAP test”)
B. HPV Vaccine at 90% Efficacy
+ Screening
$1111
$1400
25.9815 QALYs
25.9934 QALYs
Average
$1111 / 25.9815 QALYs
Cost-Utility
Ratio
Would
you recommend
the new =HPV
vaccine
program?
$42.76
per
QALY
(Cost / QALYs)
$1400 / 25.9934 QALYs
= $53.86 per QALY
Incremental
($1400 - $1111) / (25.9934 – 25.9815)
Cost-Utility Ratio
= $289 / 0.0119
(Δ
Costs
/
Δ
QALYs)
Would you recommend the new HPV vaccine
program?
= $24,286
per additional QALY
Adapted from Goldie SJ, Kohli M, Grima D, Weinstein MC, Wright TC, Bosch FX, et al. Projected Clinical Benefits and Cost-effectiveness of a
Human Papillomavirus 16/18 Vaccine. J Natl Cancer Inst. 2004;96(8):604-615; as reported in Arnold, 2010
Cost-Utility Analysis (CUA)
Example 2
Dabigatran 150 mg twice daily vs. warfarin for stroke prophylaxis in 70-yearold patients with atrial fibrillation.
Total Costs
A. Warfarin
B. Dabigatran
$23,000
$43,700
Quality-Adjusted Life
8.40 QALYs
8.65 QALYs
Expectancy
Average
$23,000 / 8.4 QALYs
$43,700 / 8.65 QALYs
Cost-Utility Ratio
= $2738 per QALY
= $5052 per QALY
(Cost / QALYs)
Incremental
($43,700 - $23,000) / (8.65 – 8.40)
Would
youRatio
recommend dabigatran over warfarin?
Cost-Utility
= $20,700 / 0.25
(Δ Costs / Δ QALYs)
= $82,800 per additional QALY
Would you recommend dabigatran over warfarin?
Adapted from Shah S, Gage B. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011;123(22):2562-70.
Cost-Utility Analysis (CUA)
Common Applications
• CUA is useful when utility adjustments are
needed, such as when:
– Length of life (quantity) and quality of life are
different
– Length of life (quantity) is unaffected and quality of
life is different
– Outcomes are very different
• CUA is not warranted when:
– Number of life years saved (quantity) is different but
quality of each year of life is very similar
53
Cost-Utility Analysis (CUA)
Advantages and Disadvantages
– Advantages:
• Can incorporate both morbidity and mortality
• Can compare multiple programs with either similar or
unrelated outcomes (anticoagulation and diabetes clinics)
• Can use a threshold or cutoff cost per QALY (such as
$50,000) and decide somewhat objectively if an intervention
is cost effective
– Main disadvantages:
• No consensus on calculating utility weights
• Utility weights are “rough estimates”
• Many clinicians are not familiar with QALYs
54
Cost-Utility Analysis (CUA)
Question:
• Do negative QALYs make sense?
55
Cost-Utility Analysis (CUA)
Question:
• Do negative QALYs make sense?
Answer:
• Some researchers point out that there are disease
states worse than death – such as living in
uncontrollable, excruciating pain, or living in a coma –
so negative QALYs may be needed to depict these
values. Whether or not negative QALYs make sense is
debatable.
56
QALY League Table
Intervention
$ / QALY
GM-CSF in elderly with leukemia
235,958
EPO in dialysis patients
139,623
Lung transplantation
100,957
End stage renal disease management
53,513
Heart transplantation
46,775
Didronel in osteoporosis
32,047
PTA with Stent
17,889
Breast cancer screening
5,147
Viagra
5,097
Treatment of congenital anorectal malformations
2,778
GM-CSF : Granulocyte-macrophage colony-stimulating,
11/6/2017
PTA: Percutaneous transluminal angioplasty
57
Health Related Quality of Life (HRQoL)
• Functioning
– Social: get along with family and
friends
– Physical: perform daily activities
– Emotional: stability and self-control
– Intellectual: decision-making ability
• Perceptions
– Life satisfaction: sense of wellbeing
– Health Status: compared to others
Quality of life is multi factorial. Being in a
wheelchair does not preclude a satisfying life
(Levine and Croog)
59
Health Related Quality of Life (HRQoL)
Perfect health
Influenza (2 weeks)
Diabetes (without serious complications)
Mild angina pectoris
Major outcomes of Chlamydia
Serious asthma
AIDS
Death
1.00
0.99
0.93
0.92
0.89
0.64
0.44
0.00
Specific Instruments
•
•
•
•
•
•
Arthritis Impact Measurement Scales (AIMS)
Asthma Quality of Life Questionnaire (AQLQ)
Diabetes Quality of Life (DQOL)
Kidney Disease Quality of Life (KDQOL)
Quality of Life Epilepsy (QOLIE)
Medical Outcomes Study HIV Health Survey (MOS-HIV)
Yogyakarta, October 2012
Methods to assess preferences
Direct method
– Individuals asked to choose (declare preferences)
between their current health state and alternative
health status scenarios
– Individuals make these choices based on their own
comprehensive health state (or the composite
described to them).
Direct measures of HealthHealthState Preferences
• May be necessary if effects of intervention are
complex:
– Multiple domains
– Effects not captured in disease-specific instrument
• Not the “community value” specified by Gold et al
• Methods:
– Visual Analog Scales
– Standard Gamble
– Time Trade Off
Value a health state
• You are in a wheelchair
• No pain or discomfort
• No psychosocial problems
Visual Analogue Scale (VAS)
Best
imaginable
health state
100
90
80
• It is easy to use and achieve high
response rate
• It is a choice-less assessment
70
60
50
40
Please draw a line at the point on
the scale that summarises your
current health status
Your own health state
today
Master Program of
Yogyakarta, March 2009
Basic Medical Sciences
30
20
Worst
imaginable
health state
10
0
Standard Gamble
taking gamble on a
new treatment for
which the outcome is
uncertain
Healthy (p)
Dead (1-p)
living in health state
i with certainty
State i
Standard Gamble
Measures the preferences of individuals under risky situations
95%
Complete health
Alternative 2:
uncertain outcome
5%
Death
100%
Alternative 1:
certain outcome
Limited health
Standard Gamble (SG)
• Wheelchair
• Life expectancy is not important here
• How much are risk on death are you prepared
to take for a cure?
– Max. risk is 20%
– 100% life on wheels = (100%-20%) life on feet
– V(Wheels) = 80% or .8
Time Trade Off
Healthy 1.0
State i
hi
Dead
0.0
x
t
time
Time Trade off
How much
reduction in
total life
willing to give
up in order to
live in perfect
health
Time Trade-Off (TTO)
• Wheelchair
– With a life expectancy: 50 years
• How many years would you trade-off for a cure?
– Max. trade-off is 10 years
• QALY(wheel) = QALY(healthy)
– Y * V(wheel) = Y * V(healthy)
– 50 V(wheel) = 40 * 1
• V(wheel) = .8
Indirect measures of HealthHealthState Preferences
•
•
•
•
Short Form-6D
EuroQol (EQ-5D)
Health Utility Index (HUI)
Quality of Well-Being Scale (QWB)
Euro Qol 5D
• Mobility
1. No problems walking
2. Some problem walking about
3. Confined to bed
• Self-care
1. No problems with self-care
2. Some problems washing or dressing self
3. Unable to wash or dress self
• Pain/discomfort
1. No pain or discomfort
2. Moderate pain or discomfort
3. Extreme pain or discomfort
• Anxiety/depression
1. Not anxious or depressed
2. Moderately anxious or depressed
3. Extremely anxious or depressed
• Usual activities
1. No problems with performing usual
activities (e.g. work, study, housework,
family or leisure activities)
2. Some problems with performing usual
activities
3. Unable to perform usual activities
EQ-5D space: 35
= 243 health states
Scoring patient 11223
Full health
=
Constant
Mobility (level 1)
Self-care (level 1)
Usual activities (level 2)
Pain/discomfort (level 2)
Anxiety/depression (level 3)
N3
Estimated value for 11223
1.000
- 0.081
-0
-0
- 0.036
- 0.123
- 0.236
- 0.269
0.255
QALY vs. DALY
Healthy 1.0
DALYs
0.8
QALYs
Dead
0.0
20
50
70
Life expectancy (years)
Cost-Benefit Analysis (CBA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Exercise
Dollars or Monetary Units
Dollars or Monetary Units
78
Cost-Benefit Analysis (CBA)
Cost-Benefit Analysis (CBA)
– A PE analysis in which both costs and benefits are valued
in monetary units
– The results of a CBA can be presented in several formats:
1. Net Benefit = Total Benefits – Total Costs
Cost beneficial if Net Benefit > 0
2. Benefit-to-Cost Ratio = Total Benefits / Total Costs
Cost beneficial if Benefit-to-Cost > 1
3. Internal Rate of Return (IRR) = The rate of return that equates the
present value of benefits to the present value of costs
4. Break-Even Point = The time required to recoup the investment
79
Cost-Benefit Analysis (CBA)
Example problem: Implementation of a pharmacy barcode system to reduce medication dispensing errors.
5-year time horizon
Pharmacy Bar-Code System
Total (Incremental) Costs
$2.24 million
Total (Incremental) Benefits
$5.73 million
Net-Benefit =
Total Benefits – Total Costs
$5.73 million - $2.24 million = $3.40 million
Benefit to Cost Ratio =
Total Benefits / Total Costs
$5.73 million / $2.24 million = 2.56
Internal Rate of Return
104% annualized return on investment
Was the bar-code system a good financial decision?
Break-Even Point
Within the first year of operation
Adapted from Saverio M, et al. Cost-Benefit Analysis of a Hospital Pharmacy Bar Code Solution. Arch Intern Med. Apr 23, 2007;167(8):788-94.
Cost-Benefit Analysis (CBA)
Common Applications
• CBA is most useful when
– Analyzing a single intervention to determine whether its
total benefits exceed the costs, or
– Comparing alternative interventions to see which one
achieves the greatest benefit.
81
Cost-Benefit Analysis (CBA)
Advantages and Disadvantages
– Major advantages:
• Can determine if benefits exceed costs of
program
• Can compare multiple programs with
either similar or unrelated outcomes
– Disadvantage:
• Difficult to place a monetary value on
health outcomes
82
Other Methodology Issue
•
•
•
•
•
Time Horizon
Discounting
Sensitivity Analysis
Modelling
Transferability
83
THANK YOU
85
Dr. Jarir At Thobari, MSc, DPharm, PhD
Faculty of Medicine, UGM
1. Dept. Pharmacology and Therapy Div.
Pharmacoepidemiology & Pharmacoeconomy
2. Clinical Epidemiology & Biostatistics Unit
1
Increasing demand of healthcare
2
Budget & resources constraint
3
Financing HIV in developing countries
4
Increasing choices of technology
5
HTA for decision making
• Increase expenditure on drug therapy
• Resources limited (scarcity of budget)
♦ Solution?
– Efficient use of resources within the health care setting
(e.g. switch to cheaper generic drugs1,2)
– Making choices priority
6
Clinical
effectiveness
Medical &
biological
knowledge
Social
aspects
HTA
Costs and
financing
Organisational aspects
Epidemiology
Ethical
consequences
Based on Habbema et al., 1989
What is health technology assessment
(HTA)?
HTA is a multidisciplinary field of policy analysis. It studies the medical, social,
ethical, and economic implications of development, diffusion, and use of
health technology.
Any intervention that may be used to promote health, to prevent, diagnose or
treat disease or for rehabilitation or long-term care. This includes the
pharmaceuticals, devices, procedures and organizational systems used in
health care.
Source: INAHTA/glossary http://www.inahta.net/
Using HTA to inform priority setting
• Applied HTA can be considered as a process for
considering scientific evidence, economic evidence and
social values, to inform decisions as to whether to fund a
treatment / service
– Includes cost-effectiveness analysis (CEA); not just clinical
effectiveness
– Drawing comparisons: Compared to the status quo, what do we
gain out of the new treatment, and at what extra cost?
– Not a merely technical exercise: The process and social values
are equally important
•
NOTE: HTA is one component to support overall quality improvement…
Definition of areas
10
HTA system
11
Economic evaluation (PE)
INPUT
PHARMACEUTICAL
PRODUCT OR SERVICE
Cost Analysis
(a partial economic evalution)
OUPUT
Clinical or Outcome Study
(not an economic study)
Pharmacoeconomic Analysis
Economic Evaluations
Cost A
Intervention A
Consequences A
Cost B
Intervention B
Consequences B
Difference
in costs?
Difference in
consequences?
Relationship?
Cost Effectiveness
new drug/device is cost-effective!
•
•
•
•
•
•
•
•
•
•
•
Reduce the cost
More benefit
Which one more effective and lower costs
Optimal balance costs and effect
Good effect for lowest cost
Highest benefit and lowest cost and safe
Willingness to pay for optimal balance
Cheaper and better!
More expensive and better
Cheaper and lower benefit
Cheaper and same benefit
More Expensive
Negative
Consequences
Positive
Consequences
Less Expensive
Components of economic evaluation (Torrance, 1986)
Resources
consumed
(costs)
Health
improvement
(consequences)
Health care
programme
Direct
costs
Health
effects
Economic
benefits
Value of
health
improvement
per se
Indirect
costs
(prod. Loss)
morbidity
Economic
benefits
direct
Ad hoc
numeric
scales
mortality
Indirect
benefits
(prod. gains)
Willingness
to pay
Intangible
cost
Intangible
benefits
1st ed 1987
Utilities
(Qaly’s)
Costs from what perspective?
Health care costs
- Direct medical costs
Procedures
Treatment
Care
Healthcare payments
- Indirect medical costs
As above but due to a longer
life (expectancy)
Health care
perspective
Societal
perspective
Non-health care costs
- Direct non-medical costs
Informal care
Non-healthcare payments
Travel and time
- Indirect non-medical costs
Productivity costs
Other societal sectors
Intangibles
Happiness
Well-being
Decision makers’
perspective
19
Hospitalized Tarif (in IDR million)
for Non-bacterial Infection based on JKN tariff 2014
Hospital Class
Mild
Hospitalization
- Hospital Class A
o Class 3
o Class 2
o Class 1
- Hospital Class B
o Class 3
o Class 2
o Class 1
- Hospital Class C
o Class 3
o Class 2
o Class 1
- Hospital Class D
o Class 3
o Class 2
o Class 1
Severity Level
Moderate Severe
3408
4090
4771
4244
5093
5942
4530
5435
6341
1948
2338
2727
3081
3697
4314
3522
4226
4930
1557
1868
2980
1989
2387
2784
2123
2547
2972
1299
1559
1818
1676
2011
2347
2075
2490
2905
Types of Pharmacoeconomic Studies
Methodology
Cost
Measurement Unit
Outcome
Measurement Unit
Cost-Minimization Analysis (CMA)
Dollars or Monetary Units
Assumed to be equivalent in
comparable groups
Cost-Effectiveness Analysis (CEA)
Dollars or Monetary Units
Natural units (life years gained, mm
Hg blood pressure, mMol/L blood
glucose)
Cost-Utility Analysis (CUA)
Dollars or Monetary Units
Quality-adjusted life year (QALY) or
other utilities
Cost-Benefit Analysis (CBA)
Dollars or Monetary Units
Dollars or monetary units
Rascati, 2009
Other Types of economic evaluation
• Cost Consequences Analysis (CCA)
– List of costs and various outcomes presented but
no comparisons made
• Cost of illness
– Estimate of total economic burden (prevention,
treatment, losses in productivity) of particular
condition (illness) or disease on society
22
Different effects
•
•
•
Effects
Natural effects
Utilities
Monetary terms
different economic evaluations
Economic Evaluation
- Cost Effectiveness Analysis (CEA)
- Cost Utility Analysis (CUA)
- Cost Benefit Analysis (CBA)
Broad comparison
Level of analysis
Narrow comparison
Cost-Minimization Analysis (CMA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Dollars or Monetary Units
Assumed to be equivalent in
comparable groups
24
Cost-Minimization Analysis (CMA)
Cost-Minimization Analysis (CMA)
– PE analysis where outcomes of two or more
interventions are assumed to be equivalent
• Thus, only costs of intervention are compared
– Objective: choose the least costly alternative
25
Cost-Minimization Analysis (CMA)
Example Problem: Administration of prostaglandin E2 gel intracervically to expectant
mothers on the day before labor was to be induced.
•
•
Outpatient Group: administer medication monitor 2 hours send home overnight
admit next day induce labor
Inpatient Group: administer medication monitor 2 hours send to maternity unit
for the night induce labor
Type of Cost
Costs for Outpatients
(n = 40)
Mean (SD)
Costs for Inpatients
(n = 36)
Mean (SD)
Statistical Difference
Labor cost
$575 ($366)
$902 (482)
Yes (p = 0.002)
Delivery cost
$471 ($247)
$453 ($236)
No (p = 0.754)
Pharmacy cost
$150 ($102)
$175 ($139)
No (p = 0.084)
Hospital Costs
$3835 ($2172)
$5049 ($2060)
Yes (p = 0.015)
Would you recommend the outpatient program?
Farmer KC, Schwartz III WJ, Rayburn WF, Turnbull G. A cost-minimization analysis of intracervical prostaglandin for cervical
ripening in an outpatient versus inpatient setting. Clin Ther. 1996;18(4):747-756.; as reported in Rascati, 2009
Cost-Minimization Analysis (CMA)
Common Applications
– Common CMA application:
• Cost comparison of two generic medications rated as
equivalent by Drug Regulatory
• Cost comparison of same drug therapy in different
settings
– Not appropriate for comparing different classes of
medications
27
Cost-Minimization Analysis (CMA)
Advantages and Disadvantages
– Advantage: simplest analysis to conduct
– Disadvantage: cannot be used when outcomes of
each intervention are different
28
Stroke. 2000;31:1032-1037
29
Stroke. 2000;31:1032-1037
30
Stroke. 2000;31:1032-1037
31
Cost-Effectiveness Analysis (CEA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Exercise
Dollars or Monetary Units
Natural units
(life years gained, mm Hg
blood pressure, mmol/L
blood glucose)
32
Cost-Effectiveness Analysis (CEA)
Cost-Effectiveness Analysis
– PE analysis where outcomes are measured in natural
or clinical units
– CEA is most common type of PE analysis
Two methods of reporting cost-effectiveness:
• Average Cost-Effectiveness Ratio (CER) =
Cost of Intervention
Effectiveness of Intervention
• Incremental Cost-Effectiveness Ratio (ICER) =
Cost of Intervention B – Cost of Intervention A
Effectiveness of Intervention B – Effectiveness of Intervention A
Cost-Effectiveness Analysis (CEA)
• Effectiveness of oral antidiabetic (OAD)
– OAD- A (new drug)
: 25/100 patients
– OAD- B (standard drug) : 19/100 patients
• Clinical outcome:
– number of patients with ≥ 1% decrease in ‘HBA1c’
over one year
34
Cost-Effectiveness Analysis (CEA)
Medicine cost
Lab cost
Adverse event
Physician
Total
Medicine cost
Lab cost
Adverse event
Physician
Total
Cost/unit
No. of
units
(USD)*
Medicine A
40
12
20
1
50
2
25
2
25
20
50
25
Medicine B
12
2
3
3
No. of
patients
Total cost
(USD)
100
100
100
100
48,000
2,000
10,000
5,000
65,000
100
100
100
100
30,000
4,000
15,000
7,500
56,500
*USD = U.S. dollar
Cost-Effectiveness Analysis (CEA)
• Comparison between OAD - A and B for 100 patients for 1
year
Medicine A
Medicine B
• Net costs USD*
65,000
56,500
• Effectiveness
No. patients with ≥ 1%
decrease in glycosylated
hemoglobin
25
19
• Incremental Cost Effectiveness Ratio =
(65,000-56,500)/(25-19) = USD1,416.67 per extra patient
with ≥ 1% decrease in glycosylated hemoglobin
36
Average and incremental ratios
CB
ICER = CB-CA
EB-EA
Treatment B
CB-CA
EB - EA
CA Treatment A
O
EA
EB
Effect (Utility, Benefit)
ICER: Incremental Cost-Effectiveness Ratio
Average vs. ICER
Programme
Breast screening
Costs
Effects
C/E
ΔC/ΔE
A
110
20
5.50
-
B
120
29
4.14
1.11
C
150
50
3.00
1.43
D
190
60
3.17
4.00
E
240
70
3.42
5.00
Average ratios have no role in decision making
Cost-Effectiveness Analysis (CEA)
Common Applications
– Common CEA application: medications with the
same type of primary outcomes, and most often
for treatment of the same types of health
condition
– CEA is only performed when the outcome of one
intervention is both better than another AND the
cost is greater.
39
Cost-Effectiveness Analysis (CEA)
Advantages and Disadvantages
– Advantages:
• Health units are common outcomes routinely measured in clinical
trials – familiar to clinicians
• Outcomes are easier to quantify than CUA or CBA
– Disadvantages:
• Interventions with different types of outcomes cannot be
compared
• Can’t combine more than one important outcome
• Difficult to collapse both the effectiveness and the side effects into
one unit of measurement
• CEA estimates extra cost associated with each additional unit of
outcome, but who is to say that added cost is worth added
outcomes? Requires judgment call.
40
The Cost Effective Plane of ICER
+
Differenc
rence in cost
IV
I
> Costs
>> Effective
>> Costs
-
+
Effective
= 0
• Laupacis et al (1992)
– < Can$20,000 Go ; > Can$100,000 No Go
– Inbetween → professional judgment required
• Owens (1998)
– < US$50,000 Go ; > US$50,000 No Go
• NICE: ₤ 30,000 ₤ 50,000
• Netherlands: € 20,000 € 50,000
• Belgium: € 50,000
Maximum acceptable
• Willingness to pay
• WHO Commission on Macroeconomics and Health
– cost-effective:
• interventions had a positive net benefit at a
willingness-to-pay of three times the per capita GDP
– highly cost-effective:
– interventions had a positive net benefit at a
willingness-to-pay of one times the per capita GDP
44
45
Cost-Utility Analysis (CUA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Question
Dollars or Monetary Units
Quality-adjusted life year
(QALY) or other utilities
48
Cost-Utility Analysis (CUA)
Cost-Utility Analysis (CUA)
– A PE analysis which measures outcomes based on years of life that are adjusted by
“utility” weights (patient preferences); range [0, 1]
– Most common utility is the Quality-Adjusted Life Year (QALY)
• 1.0 QALY = 1 year of life in perfect health
• 0.0 QALY = death
• 0.0 < QALY < 1.0: a year when health is diminished by disease or treatment
Quality Adjusted Life Years (QALYs) weight the life years remaining by the utility
weight (QALY)
• Ex: 4 years of life post cancer treatment at 0.6 utility wt = 2.4 QALYs
– Average vs. Incremental Cost per QALY: (similar to CEA):
• Average Cost per QALY =
Incremental Cost per QALY =
–
Cost of Intervention
Cost of Intervention B – Cost of Intervention A
–
QALYs of Intervention
QALYs of Intervention B – QALYs of Intervention A
49
Cost-Utility
Analysis
(CUA)
Health
Related Quality
of Life
(HRQoL)
HRQoL - Health state value or utility
1
4 * 0.9 = 3.6
5 * 1.0 = 5.0
3 * 0.7 = 2.1
2 * 0.8 = 1.6
2 * 0.2 = 0.4
4 * 0.2 = 0.8
Total QALY:
6.3
7.4
Quality
of Life
0
4
7
9
Life expectancy 9 years
11
11 years
Cost-Utility Analysis (CUA)
Example
Human papillomavirus (HPV) vaccine +screening vs. screening only.
Total Lifetime Costs
Quality-Adjusted Life
Expectancy
A. Current Screening Program
Only
(“PAP test”)
B. HPV Vaccine at 90% Efficacy
+ Screening
$1111
$1400
25.9815 QALYs
25.9934 QALYs
Average
$1111 / 25.9815 QALYs
Cost-Utility
Ratio
Would
you recommend
the new =HPV
vaccine
program?
$42.76
per
QALY
(Cost / QALYs)
$1400 / 25.9934 QALYs
= $53.86 per QALY
Incremental
($1400 - $1111) / (25.9934 – 25.9815)
Cost-Utility Ratio
= $289 / 0.0119
(Δ
Costs
/
Δ
QALYs)
Would you recommend the new HPV vaccine
program?
= $24,286
per additional QALY
Adapted from Goldie SJ, Kohli M, Grima D, Weinstein MC, Wright TC, Bosch FX, et al. Projected Clinical Benefits and Cost-effectiveness of a
Human Papillomavirus 16/18 Vaccine. J Natl Cancer Inst. 2004;96(8):604-615; as reported in Arnold, 2010
Cost-Utility Analysis (CUA)
Example 2
Dabigatran 150 mg twice daily vs. warfarin for stroke prophylaxis in 70-yearold patients with atrial fibrillation.
Total Costs
A. Warfarin
B. Dabigatran
$23,000
$43,700
Quality-Adjusted Life
8.40 QALYs
8.65 QALYs
Expectancy
Average
$23,000 / 8.4 QALYs
$43,700 / 8.65 QALYs
Cost-Utility Ratio
= $2738 per QALY
= $5052 per QALY
(Cost / QALYs)
Incremental
($43,700 - $23,000) / (8.65 – 8.40)
Would
youRatio
recommend dabigatran over warfarin?
Cost-Utility
= $20,700 / 0.25
(Δ Costs / Δ QALYs)
= $82,800 per additional QALY
Would you recommend dabigatran over warfarin?
Adapted from Shah S, Gage B. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011;123(22):2562-70.
Cost-Utility Analysis (CUA)
Common Applications
• CUA is useful when utility adjustments are
needed, such as when:
– Length of life (quantity) and quality of life are
different
– Length of life (quantity) is unaffected and quality of
life is different
– Outcomes are very different
• CUA is not warranted when:
– Number of life years saved (quantity) is different but
quality of each year of life is very similar
53
Cost-Utility Analysis (CUA)
Advantages and Disadvantages
– Advantages:
• Can incorporate both morbidity and mortality
• Can compare multiple programs with either similar or
unrelated outcomes (anticoagulation and diabetes clinics)
• Can use a threshold or cutoff cost per QALY (such as
$50,000) and decide somewhat objectively if an intervention
is cost effective
– Main disadvantages:
• No consensus on calculating utility weights
• Utility weights are “rough estimates”
• Many clinicians are not familiar with QALYs
54
Cost-Utility Analysis (CUA)
Question:
• Do negative QALYs make sense?
55
Cost-Utility Analysis (CUA)
Question:
• Do negative QALYs make sense?
Answer:
• Some researchers point out that there are disease
states worse than death – such as living in
uncontrollable, excruciating pain, or living in a coma –
so negative QALYs may be needed to depict these
values. Whether or not negative QALYs make sense is
debatable.
56
QALY League Table
Intervention
$ / QALY
GM-CSF in elderly with leukemia
235,958
EPO in dialysis patients
139,623
Lung transplantation
100,957
End stage renal disease management
53,513
Heart transplantation
46,775
Didronel in osteoporosis
32,047
PTA with Stent
17,889
Breast cancer screening
5,147
Viagra
5,097
Treatment of congenital anorectal malformations
2,778
GM-CSF : Granulocyte-macrophage colony-stimulating,
11/6/2017
PTA: Percutaneous transluminal angioplasty
57
Health Related Quality of Life (HRQoL)
• Functioning
– Social: get along with family and
friends
– Physical: perform daily activities
– Emotional: stability and self-control
– Intellectual: decision-making ability
• Perceptions
– Life satisfaction: sense of wellbeing
– Health Status: compared to others
Quality of life is multi factorial. Being in a
wheelchair does not preclude a satisfying life
(Levine and Croog)
59
Health Related Quality of Life (HRQoL)
Perfect health
Influenza (2 weeks)
Diabetes (without serious complications)
Mild angina pectoris
Major outcomes of Chlamydia
Serious asthma
AIDS
Death
1.00
0.99
0.93
0.92
0.89
0.64
0.44
0.00
Specific Instruments
•
•
•
•
•
•
Arthritis Impact Measurement Scales (AIMS)
Asthma Quality of Life Questionnaire (AQLQ)
Diabetes Quality of Life (DQOL)
Kidney Disease Quality of Life (KDQOL)
Quality of Life Epilepsy (QOLIE)
Medical Outcomes Study HIV Health Survey (MOS-HIV)
Yogyakarta, October 2012
Methods to assess preferences
Direct method
– Individuals asked to choose (declare preferences)
between their current health state and alternative
health status scenarios
– Individuals make these choices based on their own
comprehensive health state (or the composite
described to them).
Direct measures of HealthHealthState Preferences
• May be necessary if effects of intervention are
complex:
– Multiple domains
– Effects not captured in disease-specific instrument
• Not the “community value” specified by Gold et al
• Methods:
– Visual Analog Scales
– Standard Gamble
– Time Trade Off
Value a health state
• You are in a wheelchair
• No pain or discomfort
• No psychosocial problems
Visual Analogue Scale (VAS)
Best
imaginable
health state
100
90
80
• It is easy to use and achieve high
response rate
• It is a choice-less assessment
70
60
50
40
Please draw a line at the point on
the scale that summarises your
current health status
Your own health state
today
Master Program of
Yogyakarta, March 2009
Basic Medical Sciences
30
20
Worst
imaginable
health state
10
0
Standard Gamble
taking gamble on a
new treatment for
which the outcome is
uncertain
Healthy (p)
Dead (1-p)
living in health state
i with certainty
State i
Standard Gamble
Measures the preferences of individuals under risky situations
95%
Complete health
Alternative 2:
uncertain outcome
5%
Death
100%
Alternative 1:
certain outcome
Limited health
Standard Gamble (SG)
• Wheelchair
• Life expectancy is not important here
• How much are risk on death are you prepared
to take for a cure?
– Max. risk is 20%
– 100% life on wheels = (100%-20%) life on feet
– V(Wheels) = 80% or .8
Time Trade Off
Healthy 1.0
State i
hi
Dead
0.0
x
t
time
Time Trade off
How much
reduction in
total life
willing to give
up in order to
live in perfect
health
Time Trade-Off (TTO)
• Wheelchair
– With a life expectancy: 50 years
• How many years would you trade-off for a cure?
– Max. trade-off is 10 years
• QALY(wheel) = QALY(healthy)
– Y * V(wheel) = Y * V(healthy)
– 50 V(wheel) = 40 * 1
• V(wheel) = .8
Indirect measures of HealthHealthState Preferences
•
•
•
•
Short Form-6D
EuroQol (EQ-5D)
Health Utility Index (HUI)
Quality of Well-Being Scale (QWB)
Euro Qol 5D
• Mobility
1. No problems walking
2. Some problem walking about
3. Confined to bed
• Self-care
1. No problems with self-care
2. Some problems washing or dressing self
3. Unable to wash or dress self
• Pain/discomfort
1. No pain or discomfort
2. Moderate pain or discomfort
3. Extreme pain or discomfort
• Anxiety/depression
1. Not anxious or depressed
2. Moderately anxious or depressed
3. Extremely anxious or depressed
• Usual activities
1. No problems with performing usual
activities (e.g. work, study, housework,
family or leisure activities)
2. Some problems with performing usual
activities
3. Unable to perform usual activities
EQ-5D space: 35
= 243 health states
Scoring patient 11223
Full health
=
Constant
Mobility (level 1)
Self-care (level 1)
Usual activities (level 2)
Pain/discomfort (level 2)
Anxiety/depression (level 3)
N3
Estimated value for 11223
1.000
- 0.081
-0
-0
- 0.036
- 0.123
- 0.236
- 0.269
0.255
QALY vs. DALY
Healthy 1.0
DALYs
0.8
QALYs
Dead
0.0
20
50
70
Life expectancy (years)
Cost-Benefit Analysis (CBA)
Definition
Sample Problem
Common
Applications
Advantages and
Disadvantages
Exercise
Dollars or Monetary Units
Dollars or Monetary Units
78
Cost-Benefit Analysis (CBA)
Cost-Benefit Analysis (CBA)
– A PE analysis in which both costs and benefits are valued
in monetary units
– The results of a CBA can be presented in several formats:
1. Net Benefit = Total Benefits – Total Costs
Cost beneficial if Net Benefit > 0
2. Benefit-to-Cost Ratio = Total Benefits / Total Costs
Cost beneficial if Benefit-to-Cost > 1
3. Internal Rate of Return (IRR) = The rate of return that equates the
present value of benefits to the present value of costs
4. Break-Even Point = The time required to recoup the investment
79
Cost-Benefit Analysis (CBA)
Example problem: Implementation of a pharmacy barcode system to reduce medication dispensing errors.
5-year time horizon
Pharmacy Bar-Code System
Total (Incremental) Costs
$2.24 million
Total (Incremental) Benefits
$5.73 million
Net-Benefit =
Total Benefits – Total Costs
$5.73 million - $2.24 million = $3.40 million
Benefit to Cost Ratio =
Total Benefits / Total Costs
$5.73 million / $2.24 million = 2.56
Internal Rate of Return
104% annualized return on investment
Was the bar-code system a good financial decision?
Break-Even Point
Within the first year of operation
Adapted from Saverio M, et al. Cost-Benefit Analysis of a Hospital Pharmacy Bar Code Solution. Arch Intern Med. Apr 23, 2007;167(8):788-94.
Cost-Benefit Analysis (CBA)
Common Applications
• CBA is most useful when
– Analyzing a single intervention to determine whether its
total benefits exceed the costs, or
– Comparing alternative interventions to see which one
achieves the greatest benefit.
81
Cost-Benefit Analysis (CBA)
Advantages and Disadvantages
– Major advantages:
• Can determine if benefits exceed costs of
program
• Can compare multiple programs with
either similar or unrelated outcomes
– Disadvantage:
• Difficult to place a monetary value on
health outcomes
82
Other Methodology Issue
•
•
•
•
•
Time Horizon
Discounting
Sensitivity Analysis
Modelling
Transferability
83
THANK YOU
85