Introduction to Economic evaluation & its application · Defining the scope of the study ......
Transcript of Introduction to Economic evaluation & its application · Defining the scope of the study ......
HTA workshop:
Introduction to Economic evaluation &
its application
ดร.ภญ.ศิตาพร ยังคง คณะเภสัชศาสตร์ มหาวิทยาลัยมหิดล
3 พฤษภาคม 2560
Outline
What is economic evaluation?
Understanding economic evaluation studies and its
application
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A 2007 survey amongst decision makers on Issues to Consider for New Health Technology Adoption
Source: Chaikledkaew et al. Value Health 2009;12(Suppl 3):S31-S35.
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Safety
Efficacy/Effectiveness
Quality of life
Cost-effectiveness
Disease severity
Equity/Equality
Public demand
Budget impact
Price
Other available choices
Political issue
Least important Slightly important ImportantVery important Most important
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Application of PE/EE in Policy Decision Making in Thailand
Source: Chaikledkaew et al. Value Health 2009;12(Suppl 3):S31-S35.
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
National drug formulary
Hospital drug formulary
Clinical practice guidelines
Comunication toprescribers
other resource allocation
Most useful Very useful Useful Slightly useful Least useful
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Value for money (efficiency)
“... the comparative analysis of alternative courses of action in terms of both their costs and consequences.”
Drummond, Stoddart & Torrance, 1987
New treatment
Current treatment
Costs value of extra
resources used (loss to other
patients)
Consequences
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Economic evaluation
Outcome Analysis
Full Economic evaluation
Source: Drummond et al, 2005 6
Methods Cost Outcomes Results
Cost-minimization analysis (CMA)
-
(assume to be equal)
Cost per case
Cost-benefit analysis (CBA)
Net benefit
Benefit-to-cost ratio
Return on investment (ROI)
Cost-effectiveness analysis (CEA)
health outcome in natural unit
Life year gained
ICER (cost per LYG)
Cost-utility analysis (CUA)
Outcome in a common unit e.g. QALY
ICER (cost per QALY)
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Pharmacoeconomics methods
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The components of economic evaluation
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1. Defining the scope of the study – perspective, target population
2. Selection of comparator(s)
3. Defining the type of economic evaluation
4. Measurement of costs
5. Measurement of outcomes: Effectiveness/Efficacy, Utility, Benefits
6. Modeling techniques
7. Handling time in the economic evaluation studies
8. Handling uncertainty and sensitivity analysis
9. Presentation of data and results
1. Defining the scope of the study
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o Background
o Perspective
o Target population
o The description of the intervention or program of interest
2. Selection of Comparator(s)
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o Should be clearly specified in the context of the analysis.
o If the aim of study is to replace the most commonly used intervention with the intervention of interest, the comparator should be the most widely used one.
o If the aim of study is to replace the standard therapy, the comparator should be the most effective alternative.
o In some circumstances where do-nothing is current practice or standard of care, no treatment can be a viable alternative.
3. Defining the type of economic evaluation
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o CMA and CBA are not recommended in the Thai guideline.
o CUA is recommended when data and resources are available or when possible since it provided more complete picture of the compared alternatives.
o However, CEA is more appropriate in case only intermediate outcomes of the compared alternatives are available.
4. Measurement of costs (1)
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o Economic or opportunity cost
o Cost components to be included are depended on study perspective
Patient Provider Purchaser or payer Employer or other sponsor Government Societal
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Cost Valuation by perspective Category Subcategory Patient Provider 3rd -party
payer Health system
Public/ government
Societal
Direct medical
Treatment/ health care: Study setting
charge cost Reimburse Copay premium
- cost cost
Other health facilities charge - -/+ reimburse
charge charge charge
Direct non medical
Personal facilities charge - - - - charge
Travel charge - - - - charge Food charge - - - - charge House charge - - - - charge Time loss income loss - - - - Productivity cost Informal care income loss - - - - Productivity cost Personal care charge - - - - charge Indirect Morbidity cost income loss - - - - Productivity cost
Mortality cost income loss - - - Productivity cost
Other sectors
Welfare travel/food/ fee/material
- -/+ reimburse - cost cost
Education travel/food/ fee/material
- -/+ reimburse - cost cost
4. Measurement of costs (2)
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o The source of cost data used: Rank 1: Prospective data collection or analysis of reliable
administrative data for specific study Rank 2: Recently published results of prospective data collection or
recent analysis of reliable administrative data – same jurisdiction Rank 3: Unsourced data from previous economic evaluation – same
jurisdiction Rank 4: Recently published results of prospective data collection or
recent analysis of reliable administrative data – different jurisdiction Rank 5: Unsourced data from previous economic evaluation –
different jurisdiction Rank 6: Expert opinion
4. Measurement of costs (3)
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o Estimating the value of resources Direct measurement
• Gross or top-down approach • Micro-costing or bottom-up approach
Valuing productivity costs • Human capital approach • Friction cost method • Non-market items • Willingness to pay (WTP)
5. Measurement of outcomes
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Outcomes: The outputs or any end results of a particular treatment and/or intervention
Clinical • blood pressure • HBA1c • Cure rate for infectious disease • Number of recurrence • Number of fracture • Mortality
Economic • Cost (baht)
Humanistic • Health Related Quality of Life • Patient Satisfaction
5. Measurement of outcomes Efficacy/Effectiveness (1)
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o Clinical efficacy VS Clinical effectiveness
o The use of surrogate indicators should be avoided
o The inclusion of the grey literature such as research reports, master dissertations or Ph.D. theses is also considered to be very important in the Thai context
5. Measurement of outcomes Efficacy/Effectiveness (2)
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1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias.
1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias.
1- Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias.
2++ High-quality systematic reviews of case control or cohort studies. High-quality case control or cohort studies with a very low risk of confounding, bias, or chance and a high probability that the relationship is causal.
2+ Well-conducted case control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal.
2- Case control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal.
3 Non-analytic studies: for example, case reports, case series. 4 Expert opinion.
(Killoran A, Kelly MP. Evidence-based public health : effectiveness and efficiency. Oxford : Oxford University Press, 2010)
Levels of clinical evidence
5. Measurement of outcomes: Utility (1)
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Effects of intervention Quality • Pain reduction • Less side effect • Ability to perform self care • etc.
Quantity • Life years gained
5. Measurement of outcomes: Utility (2)
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Quality-adjusted life years
Short life – Full health
Long life – Reduced health
5. Measurement of outcomes: Utility (3)
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*Utility can be ranged from 0 (worst health state) to 1 (best health state/healthy)
Patient 1: • Utility = 0.9 • Number of years = 10 • QALYs = 0.9 x 10 = 9
Patient 2: • Utility = 0.5 • Number of years = 10 • QALYs = 0.5 x 10 = 5
QALYs = number of years lived x utility*
Quality weight that represents HRQOL
5. Measurement of outcomes: Utility (4)
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Valuation techniques o Single (comprehensive) measurement
Visual Analogue Scale
Standard Gamble
Time Trade-Off
o Multi-attribute utility measurement
e.g. EuroQol(EQ-5D), Health Utility Index (HUI), Quality of Well-being (QWB), Short Form 6D (SF-6D)
Visual Analogue Scale (VAS)
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100
0
80
60
40
20
U = X / D = X/100
X D
Death
Perfect health
Standard Gamble
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Alternative b
Alternative a
Chronic health state A (t years)
Perfect health (t years)
Death
(p)
(1-p)
Utility (of chronic health state A) = p
Time Trade Off
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healthy
Dead
state i
Choice 2
Choice 1
x t TIME
uti
lity
Ui = x/t
EQ-5D-5L
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5. Measurement of outcomes: Benefits (1)
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Valuing the benefits
- Direct Benefits
The amount of saving ($) from “expenditures for prevention, detection, treatment, rehabilitation, training, drug, medical supplies, professional services”
Cost Savings - Benefits realized by eliminating a planned expenditure or expenses
Cost Avoidance - Benefits realized by avoiding a relatively certain future expenditure, although the projected expenditure has not been budgeted or obligated.
5. Measurement of outcomes: Benefits (2)
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Valuing the benefits (cont.)
- Indirect Benefits Potential increased earning or productivity gains ($) they would not have been possible without the particular healthcare program The human capital approach - Intangible Benefits Psychological benefits of health such as satisfaction with life or health ($)
The stated preferences of willingness to pay (or contingent valuation)
5. Measurement of outcomes: Benefits (3)
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The human capital approach Most frequently applied Quantification of lost earnings or output due to morbidity
or premature mortality - If the patients could avoid being admitted into hospitals after providing pharmacy intervention, they were able to work - It is assumed that they would have the same employment experience as the general population - 2 days X 500 baht = 1,000 baht
5. Measurement of outcomes: Benefits (4)
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Willingness To Pay (WTP) The amount measured in
monetary terms, that an individual would be willing to sacrifice to obtain the benefits from the program
Estimated directly via questionnaires asking individuals how much they are willing to pay to reduce their risk of death or illness
Ask how much they would pay to receive pharmacy intervention?
Example
6. Modeling techniques (1)
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o Why do the study need modeling??
Consideration of all relevant comparators
Appropriate time horizon
Handling uncertainty used in the evaluation
o Type of models commonly used in economic evaluation
1. Decision analysis -- decision trees
2. State-transitional models -- Markov models
6. Modeling techniques (2)
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• Identify the available options when faced with a decision
• Predict the outcomes of each option
• Select the decision that will yield the best pay-off
Decision tree
Choice A Choice B
Decision Tree
Outcomes of
Choice A
Outcomes of
Choice B
Choice nodes
Terminal nodes
Example of decision tree
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6. Modeling techniques (3)
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Markov model
Source: Inadomi JM. Eur J Gastroenterol Hepatol. 2004, 16:535–542
Absorbing state
Transient state
Temporary state
Example
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All DM patients will enter Markov models
7. Handling Time in the EE studies
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o Time horizon should be long enough to capture the full costs and effects of the intervention.
o If a time horizon > 1 year, the opportunity costs of investments and their health consequences should be taken into account through discounting.
PV = FVn / (1+r)n
PV = present value FV = future value r = discount rate n = year from start of program
8. Handling Uncertainty & Sensitivity Analysis (1)
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o Methodological uncertainty - Methodological disagreement among analysts e.g. rate of discounting, method for costing
o Parameter uncertainty - The uncertainty in parameter inputs to a study that includes sampling variation
o Modeling uncertainty - The uncertainty due to the model ‘structure’ relating to the function form of the model
o Generalizability/Transferability - Using economic evaluation results conducted in one setting in other settings
8. Handling Uncertainty & Sensitivity Analysis (2)
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o A mathematical and analytical technique designed to improve the quality and usefulness of analyses. Because many of estimates used in economic evaluation are uncertain, we need to test the sensitivity of the results.
Deterministic sensitivity analysis
Probabilistic sensitivity analysis
8. Handling Uncertainty & Sensitivity Analysis (3)
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o A mathematical and analytical technique designed to improve the quality and usefulness of analyses. Because many of estimates used in economic evaluation are uncertain, we need to test the sensitivity of the results.
- Deterministic sensitivity analysis
Tornado diagram
Threshold sensitivity analysis
- Probabilistic sensitivity analysis
Cost-Effectiveness Acceptability Curve
One-way sensitivity analysis: Tornado diagram
(Leerahavarong P, 2009) 40
One-way sensitivity analysis: Threshold SA
41 (Spiegel et al., 2003)
Probabilistic sensitivity analysis
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If a third party payer was willing to pay $50,000 per QALY gained for COX-2 therapy, only 0% of the patents in this simulation would fall within the budget.
Cost-effectiveness plane
Probabilistic sensitivity analysis
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Probabilistic sensitivity analysis
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Cost-effectiveness acceptability curve Cost-effectiveness acceptability curve
-
0.100
0.200
0.300
0.400
0.500
0.600
0.700
0.800
0.900
1.000
0 100,000 200,000 300,000 400,000 500,000 600,000
Value of ceiling ratio
Pro
babili
ty t
hat
LC
is b
ein
g c
ost-
eff
ective
(Teerawattananon Y., 2005)
9. Presentation of Data and Results (1)
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Clearly state all key elements Parameter and model assumptions Transitional probabilistic used in the model Source of costs and outcomes data Breakdown of costs and effects Base-cases estimates and probabilistic distribution ICER and Cost-effectiveness acceptability curve Discussion
• Limitations of the study • Comparing results to relevant results from other studies • Potential impact on healthcare expenditure • Equity alongside policy recommendations
9. Presentation of Data and Results (2)
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Incremental cost-effectiveness ratio (ICER) Compares a specific (new) intervention to a stated alternative (std) intervention
Costnew – Costold / Benefitnew - Benefitold
Incremental resources required by the
intervention
Incremental health effects gained by using
the intervention
Cost-effectiveness threshold
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UK: Less than £30,000 per QALY gained
USA: Less than $50,000 per QALY gained
Countries in the World: Less than 3 x GDP per capita per DALY averted
Thailand ICER < 160,000 THB per QALY gained (about 1.2 GNI per
capita in 2013)
Source: (1) Devlin, N. and Parkin, D. Health Economics, 2004; 13: 437-452; (2) Towse, A., Devlin, N., Pritchard, C (eds) (2002) Cost effectiveness thresholds: economic and ethical issues. London: Office for Health Economics/King's Fund; (3) National List of Essential Medicines. Appropriate Threshold in Thailand. Meeting of National List of Essential Medicines 9/2007, December 20, 2007; Chaiyanardnarentorn meeting room. Thai Food and Drug Administration; (4) Thavorncharoensap et al, 2013.
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9. Presentation of Data and Results: Example
(Leelahavarong P et al., 2010)
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9. Presentation of Data and Results: Example
(Leelahavarong P et al., 2010)
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9. Presentation of Data and Results: Example
(Leelahavarong P et al., 2010)
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9. Presentation of Data and Results: Example
(Leelahavarong P et al., 2010)
HTA workshop:
Application of HTA or EE results
Application of HTA results in Thailand
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UHC health benefit package
Drug reimbursement list
Drug price negotiation
The Thai UC benefit package development
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Health interventions
Universal Coverage Benefit package
National List of Essential Medicines (NLEM) Development Process
The Thai UC health
benefit package
development
Secretariat (IHPP & HITAP)
Working group on health topic selection
Subcommittee on development of health
benefit package & services system of the
National Health Security Office (NHSO)
NHSO board
7 groups of stakeholders
Submitted topics
Preliminary assessment of each submitted topic
Prioritized topics
Recommendations
HTA researchers (IHPP & HITAP)
HTA results/ Preliminary recommendations
Topic nomination
Topic
prioritization
for assessment
Technology assessment
Appraisal
Decision making
• No. of people affected
• Disease/health problem
severity
• Effectiveness of
technologies
• Variation in practice
• Financial impact to the
households
• Equity/ethical
implications (affecting
the poor & rare diseases)
• Cost-effectiveness
• Budget impact
Subcommittee on health financing NHSO board 55
56 NLEM development process
Coverage decision platforms
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Non-pharmaceutical products Pharmaceutical products
Subcommittee on development of
health benefit package & services
system of NHSO
National Health Security Office (NHSO) board
Working group on health topic selection
Working group on health topic nomination
Recommendations
HTA results
Submitted topics
National List of Essential Medicines (NLEM) Committee
NLEM Sub-committee
Recommendations
Working group on price negotiation
Working group on economic evaluation
21 working groups based on specialty
EE results
Submitted medicines
Medicines Indications Baht/QALY Decision Year
Peg-interferon alpha 2b chronic hepatitis C subtype 2, 3 cost-saving Yes 2011
Peg-interferon alpha 2a chronic hepatitis C subtype 2, 3 cost-saving Yes 2011
lamivudine or tenofovir chronic hepatitis B cost-saving Yes 2011
bevacizumab Age-related macular degeneration, diabetic macular edema
cost-saving Yes 2012
intravenous immunoglobulin Dermatomyositis cost-saving Yes 2013
intravenous immunoglobulin chronic inflammatory demyelinating polyneuropathy (CIDP)
57,000 Yes 2013
intravenous immunoglobulin idiopathic thrombocytopenic purpura (ITP) 87,000 Yes 2013
oxaliplatin (FOLFOX) advance colorectal cancer 126,000 Yes* 2012
sidenafil pulmonary arterial hypertension 168,000 Yes 2013
Galantamine, donepezil or rivastigmine
mild-to-moderate Alzheimer's disease 157,000-240,000 No 2010
alendronate, risedronate, raloxifene
osteoporosis 300,000-800,000 No 2008
rituximab + CHOP regimen diffused large B-cell lymphoma 600,000 No 2013
bosentan or iloprost pulmonary arterial hypertension after failing sidenafil 1,023,000-4,462,000
No 2013
sunitinib metastasis renal cell carcinoma 2,400,000 No 2013
rituximab rheumatoid arthritis 1,100,000 No 2013
gefitinib or erlotinib Second-line treatment for non-small cell lung cancer 1,500,000-2,000,000
No 2013
ustekinumab chronic plaque psoriasis 3,500,000 No 2013
imiglucerase Gaucher disease type 1 6,300,000 Yes* 2012 58
Example: Cost-effectiveness on the national drug reimbursement list development Thailand: ICER threshold around 160,000 THB per QALY gained (1.2 GNI per capita) (2013)
Appraisal results and decision making
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Imiglucerase for Gaucher Type I
PD-first policy for ESRD
Sourch: Youngkong S et al. Multi-criteria decision analysis for including health interventions in the universal health coverage benefit package in Thailand. Value in Health 2012; 15(6): 961-970.
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Examples of using economic evaluation info. in coverage decision
0
3 , 0 0 0
6 , 0 0 0
9 , 0 0 0
1 2 , 0 0 0
1 5 , 0 0 0
1 8 , 0 0 0
Vaccination at the
age of 15 years
Vaccination at the
age of 20 years
Vaccination at the
age of 25 years
Vaccination at the
age of 30 years
HPV price threshold at 1X GDPHPV price threshold at 3X GDP
48%
55%61%
26%
86%
74%
37%
97%
The analysis of pricing threshold of the HPV vaccine against the WTP threshold
0
2,000
4,000
6,000
8,000
10,000
original price negotiated price
Threshold analysis for price of oxaliplatin
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Examples of using economic evaluation info. in price negotiations
Medicine Original price
(THB) Reduced price
(THB) Potential saving (THB per year)
Tenofovir 43 12 375 million
Pegylate interferon alpha-2a (180 mcg) 9,241 3,150 600 million
Oxaliplatin (injection 50 mg/25 ml) 8,000 2,500 152 million
Threshold price that makes oxaliplatin cost-effective in the Thai health care setting
Source: Teerawattananon et al, Z. Evid. Fortbild. Qual. Gesundh. wesen (ZEFQ) (2014) 108, 397—404
Universal Health Coverage Benefit package development
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Challenges
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Excessive demand for EE with limited supply
Inadequate infrastructures e.g. lack of local data related
to technology used especially clinical data
Lack of knowledge and understanding related to EE
amongst decision makers