Decision Analysis: Utilities and QALYs

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Decision Analysis Utilities and QALYs

• Miriam Kuppermann, PhD, MPH
• Professor of Obstetrics, Gynecology and
  Epidemiology
• January 15, 2009

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Todays Lecture

• Utilities and utility measurement
• Calculating quality-adjusted life years
• Back to the aneurysm example To Clip Or
  Not To Clip?
• Using utility measurement and cost-utility
  analysis to change clinical guidelines

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ReviewLast Lecture

• Formulated an explicit question
• to clip or not to clip (incidental aneurysm
  )
• Made a decision tree
• Conducted an expected value calculation to
  determine which course of action would likely
  yield the highest life expectancy

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To Clip or not to Clip?

• Has an impact on life expectancy
• Also may affect health-related quality of life
• Clipping can cause mild/moderate disability
• Not clipping can cause anxiety associated with
  being at risk of aneurysm rupture

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How do we incorporate quality-of-life effects
into DA?

• Measure and apply utilities
• Use utilities to quality-adjust life expectancy
  for decision and cost-effectiveness analysis

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PreviewWhere We Are Going with this Analysis?

• Recall Ms. Brooks and her incidental aneurysm --
  to clip or not to clip?
• We want to
• Determine her utilities
• Use them to generate QALYs
• Evaluate incremental QALYs and cost (CEA/CUA)
• Compare incremental cost effectiveness ratios
  (ICER) to other currently accepted medical
  interventions

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What is a Utility?

• Quantitative measure of the strength of an
  individuals preference for a particular health
  state or outcome.
• Utilities can be obtained for
• Disease states (diabetes, depression)
• Treatment effects (cure, symptom management)
• Side effects (impotence, dry mouth)
• Process (undergoing surgery, prenatal
  diagnostic procedure)

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Utilities are the currency we use to assign
values to outcomes

• Scaled from 0 to 1
• 1 perfect or ideal health or health in the
  absence of the condition being studied
• 0 dead

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How do we measure utilities?

• Visual Analog Scale
• Standard Gamble
• Time Trade-off
• -----
• Conjoint analysis

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BKA vs. AKA Example

• Patient in the hospital has infection of the leg
  
• Two options
• 1) BKA with medical management
• BKA 1 mortality risk
• Medical management 20 chance of infection
  worsening
• 2) AKA above the knee amputation
• 10 mortality risk
• Lets draw a decision tree

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For which outcomes do we need to measure
utilities?

• Death?
• Risk of worsening?
• Living with part of a leg (below the knee)
  missing?
• Living with a bigger part of a leg (above the
  knee) missing?
• Others?

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Visual Analog Scaling
Full health intact leg
100
98
99
65
BKA
55
AKA
2
1
Dead
0
Outcomes rated on a 0-to-100 feeling
thermometer.
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Standard Gamble

• What chance of immediate death would you be
  willing to incur to avoid living with the outcome
  being assessed?
• Method relies on respondents choosing between
• 1) a certain outcome (BKA)
• 2) a gamble between an ideal outcome (intact
  leg) and the worst outcome (dead)

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Standard Gamble Question

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Standard Gamble Exercise
Which do you prefer?
Choice A
Choice B
Spend the rest of your life with BKA
p chance of immediate death 1-p chance of
spending the rest of your life with an intact leg
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Time Tradeoff

• How many years of your life would you be willing
  to give up to spend your remaining life without
  the condition/health state being assessed?
• Method relies on respondents choosing between
• 1) Full life expectancy with the
  condition/outcome being assessed (BKA)
• 2) A reduced life expectancy with the ideal
  outcome (intact leg)

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Time Tradeoff Preference Elicitation
Which do you prefer?
Choice A
Choice B
Spend the remaining 40 years of your life with BKA
Live 40 more years of life with an intact leg
(give up 0 years of life)
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Time Tradeoff Preference Elicitation
Which do you prefer?
Choice A
Choice B
Spend the remaining 40 years of your life with BKA
Live 30 more years of life with an intact leg
(give up 10 years of life)
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Pros and Cons - VAS

• Advantage Easy to understand
• Disadvantages Doesnt require the respondent to
  think about what theyd be willing to give up,
  doesnt explore risk preference, values spread
  over the range, doesnt require much engagement

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Pros and Cons SG

• Advantages Requires assessor to give something
  up, incorporates risk attitude
• Disadvantages Choices may be difficult to make,
  most confusion-prone method, lack of engagement
  or willingness to participate in exercise values
  tend to cluster near 1

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Pros and Cons TTO

• Advantages While still asking assessor to give
  something up, easier choices to consider. Values
  not so clustered near 1, while still more
  meaningful than VAS scores.
• Disadvantages Fails to incorporate risk, lack
  of clarity of when time traded occurs, isnt
  something that one can choose to give up. (One
  can take on a risk of death, but not pay with
  life years.)

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Other sources of/ways to measure utilities

• Catalogs (Beaver Dam Study)
• Multi-attribute health status classification
  systems (HUI)
• EuroQol/EQ-5D
• SF-6

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Utilities in decision analysis

• Utilities can be to adjust life expectancy in DA
  where outcomes include morbidity/quality-of-life
  effects.
• Quality Adjusted Life-Years (QALYs)

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QALYs

• QALYs are generally considered the standard unit
  of comparison for outcomes
• QALYs time (years) x quality (utility)
• e.g. 40 years life expectancy after AKA, utility
  (AKA) 0.875
• 40 x 0.875 35 QALYs

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Back to aneurysm
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Calculating expected value
.55
0
.55
0
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Calculating expected value, cont
.9825
.9921
.55
1.0
.55
.977
Diff -0.0151
0
.865 vs .977
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Now we want to add utilities for intermediate
outcomes
Normal survival (top) 1.0
Worry about possibility of aneurysm rupture 0.95
Stroke (clipping complication or aneurysm rupture) (0.76.25)/20.5
Immediate death (bottom) 0.0
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Including utility for stroke0.5
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Adding utility for worry .95
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A Real World Example
Prenatal Testing for Chromosomal Disorders
Using utilities and cost-effectiveness analysis
in an evidence-based approach to challenging
guidelines and effecting change.
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Prenatal Tests for Chromosomal Disorders

• Diagnostic Tests (invasive)
• Amniocentesis
• Chorionic villus sampling (CVS)
• Screening Tests (non-invasive)
• Maternal age
• 1st trimester nuchal translucency
• 1st trimester combined screening
• 2nd trimester expanded maternal serum AFP (triple
  or quad marker)
• 1st and 2nd trimester sequential, contingent, or
  integrated screening

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Guidelines For Prenatal Testing Have Historically
been Dichotomized by Maternal Age

• Women gt 35
• Diagnostic testing offered
• Screening as an option
• (No testing)

• Women lt 35
• Screening offered/encouraged
• Diagnostic testing offered only if positive
  results
• (No testing)

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Rationale for Guidelines

• Need to limit access to invasive testing
• Inherent risk of procedure
• Limited availability of providers, laboratories
• Age 35 selected as the threshold
• Threshold set where risks equal
• Cost/benefit considerations

Kuppermann, Nease, Goldberg, Washington. Who
should be offered prenatal diagnosis? The
35-year-old question. Am J Public Health 1999
89160-3
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Threshold set where risks are equal, but are
these equal outcomes?
Risk of Miscarriage Risk of Down Syndrome
Implicit assumption women value these two
outcomes equally
Procedure-related miscarriage
Down-syndrome affected infant
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How do Women Feel about Prenatal Testing Outcomes?

• Do women value procedure-related miscarriage and
  Down-syndrome-affected birth equally?
• How much value to women place on receiving
  prenatal testing information?
• Do women who are 35 or older or receive positive
  screening results necessarily want to undergo
  prenatal diagnosis?
• How do women view having an abortion after
  receiving news of an abnormal karyotype?
• How do women view the prospect of raising a child
  with Down syndrome?

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Simplified Decision Tree for Prenatal Testing
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Generating Evidence on how Women Value Prenatal
Testing Outcomes

• 1082 socioeconomically and age-diverse women
• English-, Spanish- or Chinese-speaking
• Interviewed lt20 weeks pregnant
• Measured TTO utilities for 11 testing outcomes
• Administered demographic/attitudinal questions
• Collected data on subsequent testing behavior

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Time Tradeoff Preference Elicitation
Which do you prefer?
Choice A
Choice B
40 years of life remaining with DS- affected
child
40 years of life remaining with unaffected child
(give up 0 years of life)
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Time Tradeoff Preference Elicitation
Which do you prefer?
Choice A
Choice B
40 years of life remaining with DS-affected child
30 years of life remaining with unaffected child
(give up 10 years of life)
Both are the same
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Calculation of Time Tradeoff Scores
reduced life expectancy with unaffected child
(30 years) UTTO _______________________________
___________ full life expectancy with
DS-affected child (40 years)

0.75
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On average, women do not equally weight the
outcomes of procedure-related miscarriage and
Down syndrome-affected birth
 
Median value for procedure-related
miscarriage 0.86
Median value for Down-syndrome affected infant
0.73
Plt0.001 by Wilcox sign rank test
Kuppermann, Nease, Learman, Gates, Blumberg,
Washington. Procedure-related miscarriages and
Down syndrome-affected births implications for
prenatal testing based on womens preferences.
Obstet Gynecol 2000 96511-6.
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Utility Difference Score

• One way to look at the relative value women
  assign to procedure-related miscarriage and
  DS-affected birth
• Utility misc Utility score DS
• Higher score greater preference for
  miscarriage over DS

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Preferences Vary Substantially
200
175
150
125
Number
100
75
50
25
0
-1
-.75
-.5
-.25
0
.25
.5
.75
1
Value misc - Value DS
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First Evidence-Based Conclusion

• Guidelines do not adequately reflect the
  distribution of pregnant womens preferences, and
  they should be changed to allow for these
  variations in preferences.

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Rationale for Guidelines

• Need to limit access to invasive testing
• Inherent risk of procedure
• Limited availability of providers, laboratories
• Age 35 selected as the threshold
• Threshold set where risks equal
• Cost/benefit considerations

Kuppermann, Nease, Goldberg, Washington. Who
should be offered prenatal diagnosis? The
35-year-old question. Am J Public Health 1999
89160-3
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Second Challenge to Guideline

• Old paradigm COST BENEFIT
• Benefits (in terms) of program should exceed
  costs.
• Costs of offering testing should be offset by
  savings accrued by averting the birth of
  Down-syndrome-affected infants
• New paradigm COST EFFECTIVENESS
• No value assigned to outcomes.
• Cost of offering testing should be worth the
  gain in quantity and quality of life.

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Cost Effectiveness of Prenatal Diagnosis
QALYs Lifetime cost Cost-utility ratio
Age 20
Amniocentesis 2416 54,080 14,200
No testing 2408 52,940
Age 35
Amniocentesis 2039 61,490 12,600
No testing 2030 60,360
Age 44
Amniocentesis 1708 59,020 11,300
No testing 1698 57,890
Harris, Washington, Nease, Kuppermann. Cost
utility of prenatal diagnosis and the risk-based
threshold. Lancet 2004 363276-82.
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Second Evidence-Based Conclusion

• Offering invasive testing to women of all ages
  and risk levels can be cost effective.

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Recommendation 1

• Guidelines should be changed to enable all women
  to make informed choices about which prenatal
  tests, if any, to undergo.

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Guidelines Have Been Changed!

• ACOG Practice Bulletin Number 77, Jan 2007
  Screening for Fetal Chromosomal Abnormalities
• Should invasive diagnostic testing for aneuploidy
  be available to all women?
• All women, regardless of age, should have the
  option of invasive testing . . . Studies that
  have evaluated womens preferences have shown
  that women weigh these potential outcomes
  miscarriage, birth of an affected infant
  differently . . . Thus, maternal age of 35 years
  alone should no longer be used as a cutoff to
  determine who is offered screening versus who is
  offered invasive testing.

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Guidelines Have Been Changed!

• ACOG Practice Bulletin Number 88, Dec 2007
  Invasive Prenatal Testing for Aneuploidy
• Who should have the option of prenatal diagnosis
  for fetal chromosomal abnormalities?
• Invasive diagnostic testing for aneuploidy
  should be available to all women, regardless of
  maternal age . . . The differences between
  screening and diagnostic testing should be
  discussed with all women. . . . Studies that
  have evaluated womens preferences have shown
  that women weigh the potential outcomes of
  testing decisions differently. The decision to
  perform invasive testing should take into account
  these preferences. . .