Decision Analysis: Decision Analysis: Utilities and QALYsUtilities and QALYs

Miriam Kuppermann, PhD, MPHMiriam Kuppermann, PhD, MPH

ProfessorProfessor

Departments of Obstetrics, Departments of Obstetrics, Gynecology & Reproductive Gynecology & Reproductive Sciences and Epidemiology & Sciences and Epidemiology & BiostatisticsBiostatistics

January 17, 2008January 17, 2008

Today’s LectureToday’s Lecture

Utilities and utility measurementUtilities and utility measurement

Calculating Quality-Adjusted Life YearsCalculating Quality-Adjusted Life Years

Back to the aneurysm example: To Clip Or Not To Back to the aneurysm example: To Clip Or Not To Clip? Clip?

Using utility measurement and cost-utility analysis Using utility measurement and cost-utility analysis to change clinical guidelinesto change clinical guidelines

Review—Last LectureReview—Last Lecture

• Formulated an explicit questionFormulated an explicit question

““To clip or not to clip” (aneurysm )To clip or not to clip” (aneurysm )• Made a decision treeMade a decision tree• Conducted an expected value calculation to Conducted an expected value calculation to

determine which course of action would determine which course of action would likely yield the highest life expectancylikely yield the highest life expectancy

To Clip or not to Clip?To Clip or not to Clip? Can have an impact on life Can have an impact on life

expectancyexpectancy Also may affect health-related Also may affect health-related

quality of life:quality of life:Clipping can cause Clipping can cause

mild/moderate mild/moderate disabilitydisabilityNot clipping can cause anxiety Not clipping can cause anxiety

associated with being at risk of associated with being at risk of aneurysm ruptureaneurysm rupture

Incorporating Quality-of-Life Effects Incorporating Quality-of-Life Effects into DAinto DA

Measure and apply Measure and apply utilitiesutilities Use utilities to quality-adjust life expectancy Use utilities to quality-adjust life expectancy

for decision and cost-effectiveness analysis for decision and cost-effectiveness analysis

Preview—Where We Are Preview—Where We Are Going with this Analysis?Going with this Analysis?

Recall Ms. Brooks and her incidental aneurysm -- to Recall Ms. Brooks and her incidental aneurysm -- to clip or not to clip?clip or not to clip?

We want to: We want to: • Determine her utilities Determine her utilities • Use them to generate QALY’s Use them to generate QALY’s ______• Evaluate incremental QALY’s and cost (CEA/CUA)Evaluate incremental QALY’s and cost (CEA/CUA)• Compare incremental cost effectiveness ratios Compare incremental cost effectiveness ratios

(ICER) to other currently accepted medical (ICER) to other currently accepted medical interventionsinterventions

What is a Utility?What is a Utility?Quantitative measure of the strength of an Quantitative measure of the strength of an individual’s preference for a particular individual’s preference for a particular health state or outcome.health state or outcome.

Utilities can be obtained for:Utilities can be obtained for:Disease states (diabetes, depression)Disease states (diabetes, depression)Treatment effects (cure, symptom Treatment effects (cure, symptom management)management)Side effects (impotence, dry mouth)Side effects (impotence, dry mouth)______Process (undergoing surgery, prenatal Process (undergoing surgery, prenatal diagnostic procedure) diagnostic procedure)

Utilities are the Currency we Utilities are the Currency we use to Assign a Value use to Assign a Value

OutcomesOutcomes

Scaled from 0 to 1Scaled from 0 to 1

1 = perfect or ideal health or health in 1 = perfect or ideal health or health in the absence of the condition being the absence of the condition being studiedstudied

0 = dead0 = dead

How do we Measure How do we Measure Utilities?Utilities?

• Visual Analog ScaleVisual Analog Scale• Standard GambleStandard Gamble• Time Trade-offTime Trade-off

----------

Conjoint analysisConjoint analysis

BKA vs. AKA ExampleBKA vs. AKA ExamplePatient in the hospital has infection of the leg Patient in the hospital has infection of the leg • Two options: BKA v. medical managementTwo options: BKA v. medical management• BKA –1% mortality riskBKA –1% mortality risk• Medical management – 20% chance of infection Medical management – 20% chance of infection worsening:worsening:

AKA – above the knee amputation (10% AKA – above the knee amputation (10% mortality risk) mortality risk)

Let’s draw a decision tree Let’s draw a decision tree

For Which Outcomes do we need For Which Outcomes do we need to Measure Utilities?to Measure Utilities?

Death?Death? Risk of worsening?Risk of worsening? Living with part of a leg (below the Living with part of a leg (below the

knee) missing?knee) missing? Living with a bigger part of a leg Living with a bigger part of a leg

(above the knee) missing?(above the knee) missing? Others?Others?

Visual Analog ScalingVisual Analog Scaling

100 98

2

0

99

65

55

1

Full health: intact leg

Dead

Outcome being evaluated: BKA

Asks respondents to rate the outcome on a 0 to 100 “feeling Asks respondents to rate the outcome on a 0 to 100 “feeling thermometer.”thermometer.”

Standard GambleStandard Gamble

Asks respondents what chance of Asks respondents what chance of immediate death they would be wiling to immediate death they would be wiling to incur to avoid living with the outcome incur to avoid living with the outcome being assessed. being assessed.

Method relies on respondents choosing Method relies on respondents choosing between:between:

1) a certain outcome (BKA)1) a certain outcome (BKA)

2) a gamble between an ideal outcome 2) a gamble between an ideal outcome (intact leg) and the worst outcome (dead)(intact leg) and the worst outcome (dead)

Standard Gamble QuestionStandard Gamble Question

Choose BKA?

Yes

No

BKA (intermediate outcome)

Perfect health

Death

Live?

p %

(100-p) %

Standard Gamble Exercisexercise

Spend the rest of your life with BKA

[p]]% chance of immediate deathimmediate death

1-[p]% chance of 1-[p]% chance of spending the rest of your spending the rest of your

life with an intact leglife with an intact leg

Which do you prefer?

Choice A Choice B

Time TradeoffTime Tradeoff

Asks respondents how many years of their Asks respondents how many years of their own life they would be willing to give up to own life they would be willing to give up to spend that life expectancy the without the spend that life expectancy the without the condition/health state being assessed. condition/health state being assessed.

Method relies on respondents choosing Method relies on respondents choosing between:between:

1) Full life expectancy with the 1) Full life expectancy with the condition/outcome being assessed (BKA)condition/outcome being assessed (BKA)

2) A reduced life expectancy with the the 2) A reduced life expectancy with the the ideal outcome (intact leg)ideal outcome (intact leg)

Time Tradeoff Preference Elicitation

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)

Which do you prefer?

Choice A Choice B

Time Tradeoff Preference Elicitation

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)

Which do you prefer?

Choice A Choice B

Pros and Cons - VASPros and Cons - VAS

Advantages: Advantages: Easy to understand, visual Easy to understand, visual

Disadvantages: Disadvantages: Doesn’t require the Doesn’t require the respondent to think about what they’d be respondent to think about what they’d be willing to give up, doesn’t explore risk willing to give up, doesn’t explore risk preference, values spread over the range, preference, values spread over the range, doesn’t require much engagement doesn’t require much engagement

Pros and Cons – SGPros and Cons – SG

Advantages: Advantages: Requires assessor to give Requires assessor to give something up, incorporates risk attitudesomething up, incorporates risk attitude

Disadvantages: Disadvantages: Choices may be difficult to Choices may be difficult to make, most confusion-prone method, lack make, most confusion-prone method, lack of engagement or willingness to participate of engagement or willingness to participate in exercise; values tend to cluster near 1.in exercise; values tend to cluster near 1.

Pros and Cons – TTOPros and Cons – TTO

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

Utility Measurement – Utility Measurement – Additional InformationAdditional Information

• Multi-Attribute Health Status Classification Multi-Attribute Health Status Classification SystemSystem

• Developed by Health Utilities, Inc.Developed by Health Utilities, Inc.

•Available at: Available at: http://www.healthutilities.com/overview.htmhttp://www.healthutilities.com/overview.htm

Utilities in Decision Utilities in Decision AnalysisAnalysis

• Utilities can be to adjust life expectancy in Utilities can be to adjust life expectancy in DA where outcomes include DA where outcomes include morbidity/quality-of-life effects.morbidity/quality-of-life effects.

• Quality Adjusted Life-Years (QALYs)Quality Adjusted Life-Years (QALYs)

QALYsQALYs• QALYs are generally considered the standard QALYs are generally considered the standard unit of comparison for outcomes unit of comparison for outcomes

• QALYs = time (years) x quality (utility)QALYs = time (years) x quality (utility)

• e.g. 40 years life expectancy after AKA, utility e.g. 40 years life expectancy after AKA, utility (AKA) = 0.875(AKA) = 0.875

= 40 x 0.875 = 35 QALYs= 40 x 0.875 = 35 QALYs

QALYsQALYsAneurysm ExampleAneurysm Example

• We said life expectancy is reduced by 2/3, We said life expectancy is reduced by 2/3, so instead of 35, it is = 35 * .333 = 11.67so instead of 35, it is = 35 * .333 = 11.67

• Here, we have assigned a utility of .5 to Here, we have assigned a utility of .5 to surgery-induced disability, so QALYs = surgery-induced disability, so QALYs =

years * utils = 11.67 * .5 = 5.8years * utils = 11.67 * .5 = 5.8

QALYsNo aneurysm rupture0.9825

No surgery34.86 Die

Aneurysm rupture 0.450.0175 Survive

0.55

No aneurysm ruptureDifference 1

_ QALYs -2.85 Survive surgery0.902 Die

Aneurysm rupture 0.45Clipping 0 Survive

32.01 0.55Key Inputs Surgery-induced disabilityRupture risk/yr 0.0005 0.075Expected life span 35RR rupture w/ surgery 0 Surgical deathSurgical mortality 0.023 0.023Surg morb (disability) 0.075

0.0

Ms. Brooks

17.5

35.0Normal survival

Disability, shorter survival

5.8

Immediate death

Normal survival 35.0

Normal survival

Normal survival

Early death

Early death

35.0

17.5

35.0

QALYsQALYs

Department of Obstetrics, Gynecology, & Reproductive Sciences

Using utilities and cost-effectiveness analysis in an evidence-based approach to challenging guidelines and effecting change.

A “Real World” Example

Prenatal Testing for Chromosomal Disorders

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

Guidelines For Prenatal Testing Have Historically been

Dichotomized by Maternal Age

Women > 35 Diagnostic testing

offered Screening as an

option (No testing)

Women < 35 Screening

offered/encouraged Diagnostic testing

offered only if “positive” results

(No testing)

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; 89:160-3

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-syndromeaffected infant

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?

Simplified Decision Tree for Prenatal Testing

Generating Evidence on how Women Value

Prenatal Testing Outcomes 1082 socioeconomically and age-diverse women English-, Spanish- or Chinese-speaking Interviewed <20 weeks pregnant Measured TTO utilities for 11 testing outcomes Administered demographic/attitudinal questions Collected data on subsequent testing behavior

Time Tradeoff Preference Elicitation

Choice A Choice B

Which do you prefer?

40 years of life remaining with DS-

affected child

40 years of life remaining with unaffected child (give up 0 years of life)

Time Tradeoff Preference Elicitation

40 years of life remaining with DS-

affected child

30 years of life remaining with unaffected child

(give up 10 years of life)

Which do you prefer?

Choice A Choice B

Both are the same

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

 

Median value for procedure-related

miscarriage= 0.86

Median value for Down-syndromeaffected infant

= 0.73

On average, women do not equally weight the outcomes of procedure-related

miscarriage and Down syndrome-affected birth

P<0.001 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 women’s preferences. Obstet Gynecol 2000; 96:511-6.

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

0

25

50

75

100

125

150

175

200

Num

ber

-1 -.75-.5 -.25 0 .25 .5 .75 1

Preferences Vary Substantially

Value misc - Value DS

First Evidence-Based Conclusion

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

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; 89:160-3

Second Challenge to GuidelineSecond Challenge to Guideline

Old paradigm: COST BENEFITBenefits (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 EFFECTIVENESSNo $$ value assigned to outcomes. Cost of offering testing should be “worth” the gain in quantity and quality of life.

Cost Effectiveness of Prenatal Diagnosis QALYs Lifetime cost Cost-utility ratio

Age 20

Amniocentesis 24·16 $54,080 $14,200

No testing 24·08 $52,940

Age 35

Amniocentesis 20·39 $61,490 $12,600

No testing 20·30 $60,360

Age 44

Amniocentesis 17·08 $59,020 $11,300

No testing 16·98 $57,890

Harris, Washington, Nease, Kuppermann. Cost utility of prenatal diagnosis and the risk-based threshold. Lancet 2004; 363:276-82.

Second Evidence-Based Conclusion

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

Recommendation #1

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

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 women’s 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.”

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 women’s 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. . .”