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Decision Analysis in Transfusion Medicine
With Specific Reference to Pathogen Inactivation
James P. AuBuchon, MD
President & Chief Executive Officer
Puget Sound Blood Center
Professor of Medicine and of Laboratory Medicine
University of Washington
Seattle, Washington
Definition: Decision Analysis
A mathematical method of projecting the effects of a
clinical decision.
The model often allows projection of the (health)
outcomes of a choice and the resource consumption
required in its delivery and consequences.
Goals of Decision Analysis: I
Better
Better Health
Health
Treatment A
?
Side
Side Effect
Effect
Better
Better Health
Health
Treatment B
Side
Side Effect
Effect
Predict relative effect of alternative treatments
Goals of Decision Analysis: II
11
11
One
One Dollar
Dollar
11
11
One
One Dollar
Dollar
Determine relative benefit for resources expended
Health Improvement
Population
Health
Resources Utilized
Forms of Economic Evaluation
Cost minimization analysis
Assumption: Similar outcomes
Cost-benefit analysis
Compilation of all costs and benefits
Difficulty: Comparison
Cost-effectiveness analysis
Cost-Effectiveness Analysis
Cost-effectiveness analysis: a methodology for evaluating the
outcomes and costs of interventions designed to improve health.
A cost-effectiveness analysis evaluates a given health intervention
through the use of a cost-effectiveness ratio.
In this ratio, all health effects of the intervention (relative to a
stated alternative) are captured in the denominator and changes in
resource use (relative to the alternative) are captured in the
numerator and valued in monetary terms.
Cost-Effectiveness Ratio
Marginal cost-effectiveness
= Difference in Resources
Difference in Outcome
=
CostsAA - CostsBB
Life expectancyAA*QualityAA - Life expectancyBB*QualityBB
Modeling the Decision
p2A
Intervention A
p1A
1-p2A
Outcome A-1 Probability = p1A * p2A
Outcome A-2
Outcome A-3
S = 1.00
1-p1A
Population
Population
p2B
p1B
Intervention B
1-p2B
Outcome A-4
Outcome B-1 Probability = p1B * p2B
Outcome B-2
Outcome B-3
1-p1B
Outcome B-4
S = 1.00
Assigning Values to Outcomes
Outcome:
Life expectancy (LE)
Life Expectancy Calculations
Gompertz Function
Exponential Function
Probability
Probability
of
of
Survival
Survival
Years
Years After
After Starting
Starting Treatment
Treatment
Life Expectancy Calculations
The Declining Exponential Approximation of Life Expectancy
(DEALE)
-mt
Stt = S00e-mt
m = average annual mortality rate = (-1/t) * ln(Stt/S00)
mTOTAL
= mGENDER&AGE-SPECIFIC
+ mDISEASE1
+ mDISEASE2
+ ...
TOTAL
GENDER&AGE-SPECIFIC
DISEASE1
DISEASE2
LE = 1/mTOTAL
TOTAL
Assumptions:
Assumptions:
Age
Age has
has no
no effect
effect on
on disease-specific
disease-specific mortality
mortality
Presence
Presence of
of second
second disease
disease has
has no
no effect
effect on
on mortality
mortality from
from first
first
Disease
Disease not
not common
common (i.e.,
(i.e., not
not reflected
reflected in
in population
population statistics)
statistics)
Estimating Outcomes with Multiple States
The Markov Process
Multiple
Multiple states
states of
of disease
disease defined.
defined.
Probability
Probability of
of transition
transition from
from one
one to
to another
another (or
(or no
no transition)
transition)
defined
defined per
per cycle.
cycle.
Transition
Transition probability
probability unaffected
unaffected by
by previous
previous history.
history.
Cycles
Cycles repeated
repeated for
for defined
defined period
period or
or until
until all
all patients
patients are
are dead.
dead.
p:1-4
p:1-4
p:1-3
p:1-3
p:1-2
p:1-2
p:2-4
p:2-4
Status 2
Status 1
p:2-1
p:2-1
p:3-1
p:3-1
p:3-4
p:3-4
p:2-3
p:2-3
Status 3
p:3-2
p:3-2
Status 4
(Death)
Next Step: Assigning Values to Outcomes
Outcome:
Life expectancy (LE)
- and –
Quality of Life (QoL)
Quantitating Quality and Quantity of Life
100%
100%
Health-related
quality of life
100%
DEATH
Maximum:
x years
100% quality
Reduced area under curve
= reduced quality-adjusted life years
Quantitating Quality and Quantity of Life
Health-related
quality of life
D = QALY
WITH INTERVENTION
WITHOUT INTERVENTION
Longevity Improvement
Health Outcome Quantitation: QALYs
Quality Adjustment
QALY = Quality-Adjusted Life Year
Good
Good health:
health: 100%
100%
22 years,
years, good
good health:
health:
2.0
2.0 QALYs
QALYs
Fatigue:
Fatigue: 80%
80%
22 years,
years, fatigue:
fatigue:
1.6
1.6 QALYs
QALYs
Severe
Severe illness:
illness: 10%
10%
22 years,
years, severe
severe illness:
illness: 0.2
0.2 QALYs
QALYs
Quantitating Costs
Healthcare resources consumed by
or because of the intervention
Micro-costing analysis
Labor+ supply + equipment expense for each step
Fixed (capital) costs change: Will they change?
Cost – NOT charge
Dealing with Uncertainty
Sensitivity Analysis
Vary applied value of a variable across possible range
Marginal
Cost-effectiveness
ratio
Frequency
Monte Carlo Analysis
Define distribution of possible values for variable(s)
Randomly assign variable(s) for individual calculations
Output: Range of possible outcomes
Cost-effectiveness
Cost of Intervention
ratio
Cost-Effectiveness Comparisons
Medical
Medical Practice
Practice
Cost
Cost per
per Year
Year of
of Life
Life Saved
Saved
RhIG
RhIG prophylaxis
prophylaxis for
for HDN
HDN
Pneumococcal
Pneumococcal vaccine
vaccine for
for elderly
elderly
Annual
Annual mammography
mammography << 50
50 year
year old
old
$2,000
$2,000
$11,400
$11,400
$68,000
$68,000
CABG
CABG (left
(left main
main disease
disease with
with angina)
angina)
CABG
CABG (one
(one vessel
vessel disease
disease with
with angina)
angina)
$6,000
$6,000
$46,000
$46,000
Propranolol
Propranolol for
for hypertension
hypertension
Captopril
Captopril for
for hypertension
hypertension
$12,000
$12,000
$79,000
$79,000
Kidney
Kidney transplantation
transplantation
Hemodialysis
Hemodialysis for
for ESRD
ESRD
Heart
Heart transplantation
transplantation
$18,000
$18,000
$48,000
$48,000
$30,000
$30,000
Most commonly accepted interventions: < $50,000/QALY
Decision Analysis: Overview
Strong Points
Comparison of alternative treatments
Objectivity
Limitations
Valuation of intangibles
Current vs. future value
Application to a particular patient
Assumptions of the model
Decision Analysis: Commentary
Resource Management
Society must decide.
We must participate.
Decision analysis is an incomplete decision assistance
tool as it cannot capture all relevant elements.
Decision Analysis: Commentary
$$
The Physician as
Patient Advocate
The Physician as Rationer
Alternatives in Transfusion:
Cost-Effectiveness Considerations
Marginal cost-effectiveness
= Difference in Resources
Difference in Outcome
=
Costs AA - Costs BB
Life expectancyAA*QualityAA - Life expectancyBB*QualityBB
Small differences
Large
Poor cost-effectiveness
Cost-Effectiveness Comparisons
Cost-effectiveness
Cost-effectiveness
($/YLE)
($/YLE)
8,000,000
8,000,000
6,000,000
6,000,000
Transfusion
Transfusion Safety
Safety Interventions
Interventions
4,000,000
4,000,000
2,000,000
2,000,000
600,000
600,000
400,000
400,000
200,000
200,000
Commonly
Commonly Accepted
Accepted Medical
Medical Practices
Practices
RhIg/HDN HTN
Annual Cardiac CABG
Prophy- Therapy Mammo- Translaxis
gram plantation
AntiHIV
PADCABG
HCV
Lookback
p24 Ag
Testing
ALT
Testing
SD FP
SD NAT
Cost-effectiveness of PI: Platelets
DISTRIBUTION OF PATIENTS
Setting:
Groningen,
The Netherlands
DISTRIBUTION OF TRANSFUSIONS
Postma MJ et al. Transf Med 2005;15:379-87.
Cost-effectiveness of PI: Platelets
(1/3200)
MCER = $720,000/YLE
Range (based on bacterial threat): ± 14%
Postma MJ et al. Transf Med 2005;15:379-87.
Cost-effectiveness of PI vs. Bacterial Culturing
90% SENSITIVITY
Little impact
on model
Cost-Effectiveness Ratios
Culturing vs. nothing
PI vs. nothing
$91,000/QALY
$500,000/QALY
“No individual
should
be exposed
to an activity
Culturing
+ PI vs.
culturing
$3,500,000/QALY
imposing a risk of death greater than one in a
million (10-6) per year.”
Dutch Government, 1989
COST-BENEFIT
ANALYSES
Janssen MP et al. Transfusion 2006;46:956-65.
Cost-Effectiveness Analysis of Pathogen Inactivation
Risks assessed
HIV
HBV
HCV
HTLV-I/II
Syphilis
Bacteria
Chikungunya virus
T. cruzi
CMV
GvHD
Febrile reactions
Immunomodulation
Not emerging agents
Protocol
Additive, not replacement
Setting
Canada
- Available ID data
- Available cost data
- Active hemovigilance
- Interest
Immunosuppressed: 25%
Post-transfusion mortality: +50%
Custer B et al. Transfusion 2010;50:2461-73.
Cost-Effectiveness Analysis of Pathogen Inactivation
Whole-blood Pathogen Inactivation
$1,300,000/QALY
Platelet/Plasma Pathogen Inactivation
$1,400,000/QALY
Custer B et al. Transfusion 2010;50:2461-73.
Cost-Effectiveness Analysis of Pathogen Inactivation
Whole-blood Pathogen Inactivation
Base case: 1/47,000 (0.0002)
Custer B et al. Transfusion 2010;50:2461-73.
Cost-Effectiveness Analysis of Pathogen Inactivation
Where Are the Risks?
Number of Transmissions
Agent causing chronic disease
Agent causing acute disease
PRT: None
Plt
FP
Plt+FP
PRT: None
Plt
FP
Plt+FP
Kleinman S et al. Transfusion 2010;50:2592-606.
Cost-Effectiveness Analysis of Pathogen Inactivation
Number of Transmissions
Where Are the Risks?
With PI, healthcare costs subsequent to a
“catastrophic” agent’s emergence would
decrease by 20%. [Assumptions: Canada]
Wait for RBC PI?
Plasma
40%
60%
Platelets
Red Cells
Kleinman S et al. Transfusion 2010;50:2592-606.
Cost-Effectiveness Analysis of Pathogen Inactivation
PI: Substantial cost, small effect with current risks
(except perhaps bacterial contamination)
 Poor marginal cost-effectiveness
Pathogen Inactivation of
Blood Components
√ Reduction in pathogen transmission
√ Reduction in current testing
√ Avoidance of new testing
√ Avoidance of GvHD
± Reduction in TRALI risk
√ Safety
? Poor cost-effectiveness
The question – for society: How to allocate healthcare resources?
How safe should the blood supply be?