Outcomes in Decision Outcomes in Decision Analysis: Utilities, Analysis: Utilities,

QALYs & DALYs, and QALYs & DALYs, and DiscountingDiscounting

DCEA24 January 2013

James G. Kahn

OverviewOverview

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

Clinical OutcomesClinical Outcomes Utilities and utility measurementUtilities and utility measurement

Direct Direct IndirectIndirect

QALYs (& DALYs)QALYs (& DALYs) DiscountingDiscounting

Review—Last LectureReview—Last Lecture

• Formulated an explicit questionFormulated an explicit question

““to clip or not to clip” (incidental to clip or not to clip” (incidental aneurysm)aneurysm)

• Made a simple decision treeMade a simple 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 ClipTo Clip or Not To Clip

.865 vs .977

M s. B rooks

N o trea tm ent

S urgery

Surgery:yes or no?

AneurysmRupture?

Nop=0.9825 Norm al surviva l=1

Yesp=0.0175

Early Death=0

SurgicalDeath?

Nop=0.977

Yesp=0.023 Early Death=0

Death?

Nop=.55

Yesp=.45

Norm al surviva l=1

AneurysmRupture?

Nop=1.0 Norm al surviva l=1

Yesp=0

Early Death=0

Death?

Nop=.55

Yesp=.45

Norm al surviva l=1

=1.0

=.55

=.55

=.9921

=.977

Diff = -0.0151 =0

To Clip or not to Clip?To Clip or not to Clip? Has an impact on life expectancyHas an impact on life expectancy

Also actual clinical outcomes:Also actual clinical outcomes: Surgical deathSurgical death Aneurysm ruptureAneurysm rupture Death from aneurysm ruptureDeath from aneurysm rupture Neurologic InjuryNeurologic Injury

MajorMajor MinorMinor

Fear of aneurysm ruptureFear of aneurysm rupture

Quantifying Health OutcomesQuantifying Health Outcomes• Mortality • Life Years

number of expected years of life • Significant Morbidity

Paralysis, loss of sight• Quality Adjusted Life Years

Life years adjusted for value of health state• Disability Adjusted Life Years

Disease burden – lost years + disability• Financial Valuation of Outcomes

Costs to patient, payer, or society Willingness to pay to avoid outcomes

Health Outcomes – MortalityHealth Outcomes – Mortality• MortalityMortality

Death from disease/accident/procedureDeath from disease/accident/procedure

e.g. If Ms. Brooks undergoes surgery, one of the e.g. If Ms. Brooks undergoes surgery, one of the possible outcomes is mortalitypossible outcomes is mortality

• Life Years Life Years Calculate an expected value of life years using a Calculate an expected value of life years using a

probabilistically weighted average of expected life probabilistically weighted average of expected life

e.g. If Ms. Brooks does not undergo surgery, her life e.g. If Ms. Brooks does not undergo surgery, her life expectancy is less than if she did not have expectancy is less than if she did not have aneurysm, these outcomes are measured in aneurysm, these outcomes are measured in expected life yearsexpected life years

Health Outcomes – MorbidityHealth Outcomes – Morbidity

• MorbidityMorbiditySome health state that is less than perfectSome health state that is less than perfecte.g. disability from stroke, chronic paine.g. disability from stroke, chronic pain

• Comparison of morbiditiesComparison of morbidities Difficult – apples and oranges problem Difficult – apples and oranges problem e.g. which is worse:e.g. which is worse:Blind v. DeafBlind v. DeafDeaf v. ParaplegiaDeaf v. ParaplegiaParaplegia v. BlindParaplegia v. Blind

To Clip or not to Clip?To Clip or not to Clip? Clinical outcomes for clinician readersClinical outcomes for clinician readers

Outcomes may affect health-related Outcomes may affect health-related quality of life: quality of life: how do we compare?how do we compare?

Neurologic injury can cause Neurologic injury can cause mild/moderate disabilitymild/moderate disability

Not clipping can cause anxiety associated Not clipping can cause anxiety associated with being at risk of aneurysm rupturewith being at risk of aneurysm rupture

Outcomes may occur at different timesOutcomes may occur at different times

How do we incorporate quality-of-life How do we incorporate quality-of-life effects into decision analysis?effects into decision analysis?

Measure/estimate and apply Measure/estimate and apply health state health state utilitiesutilities

Use utilities to quality-adjust life expectancy Use utilities to quality-adjust life expectancy for decision and cost-effectiveness analysisfor 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 QALYs Use them to generate QALYs • Evaluate incremental QALYs and cost (CEA/CUA)Evaluate incremental QALYs 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?UtilityUtility - Quantitative measure of the strength of - Quantitative measure of the strength of an individual’s preference for a particular an 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 statesDisease states (diabetes, depression) (diabetes, depression)* * Treatment effectsTreatment effects (cure, symptom (cure, symptom management)management)* * Side effectsSide effects (impotence, dry mouth) (impotence, dry mouth)* * ProcessProcess (undergoing surgery, prenatal (undergoing surgery, prenatal diagnostic procedure) diagnostic procedure)

UtilitiesUtilities

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 = death

How are utilities measured?How are utilities measured?

• Direct Direct – compare with 0 / 1 anchors– compare with 0 / 1 anchors - Visual Analog Scale- Visual Analog Scale - Standard Gamble- Standard Gamble - Time Trade-off- Time Trade-off• IndirectIndirect Assess standard health domains (e.g., Assess standard health domains (e.g.,

physical functioning, pain, and cognition) physical functioning, pain, and cognition) and calculate 0-1 utility with an equation. and calculate 0-1 utility with an equation.

Direct utility Direct utility measurementmeasurement

BKA vs. AKA ExampleBKA vs. AKA ExamplePatient in hospital has infection of the leg Patient in hospital has infection of the leg

Two options: Two options:

1) 1) BKA – below knee amputationBKA – below knee amputation

BKA –1% mortality riskBKA –1% mortality risk

2)2) Medical management Medical management – 20% chance of – 20% chance of infection worsening and needing AKA (above infection worsening and needing AKA (above the knee amputation), 10% mortality riskthe knee amputation), 10% mortality risk

For which outcomes do we need For which outcomes do we need to measure utilities?to measure utilities?

Living without part of a leg (below the Living without part of a leg (below the knee)knee)

Living without a bigger part of a leg Living without a bigger part of a leg (above the knee)(above the knee)

PainPain WorryWorry OtherOther

Visual Analog ScaleVisual Analog Scale

100 98

2

0

99

65

55

1

Full health: intact leg

Dead

BKA

Outcomes rated on a 0-to-100 “feeling thermometer.”Outcomes rated on a 0-to-100 “feeling thermometer.”

AKA

Standard GambleStandard Gamble

What chance of immediate death would you What chance of immediate death would you be willing to incur to avoid living with the be willing to incur to avoid living with the outcome being assessed?outcome 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) %

Death

Perfect Health

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

Standard GambleStandard Gamble

• Standard gamble measurement involves questioning patients to determine the p at which the two outcomes are equivalent

• Using expected utilities, the value of p implies the utility

Utility (BKA) x Prob (BKA) = Utility(cure) x (1-p) + Utility(death) x (p)

Thus, if utility of cure = 1 and of death = 0, the utility of BKA = 1-p.

Time TradeoffTime Tradeoff

How many years of your life would you be How many years of your life would you be willing to give up to spend your remaining willing to give up to spend your remaining life without the condition/health state being life without the condition/health state being assessed? assessed?

Method relies on respondents Method relies on respondents choosing between:choosing 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 2) A reduced life expectancy with 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

Utility Measurement – Time Utility Measurement – Time Trade-offTrade-off

Find years of life at which patient is indifferent between Choice A (with health problem) & Choice B (shorter life).

We assume that: Time A * Utility A = Time B * Utility B

And thus Utility A = [Time B * Utility B] / Time A

If willing to give up 4 years to avoid BKA: Utility of BKA = [(40-4) * 1] / 40 = 36/40 = 0.9

Pros and Cons - VASPros and Cons - VAS

Advantage: Advantage: Easy to understandEasy to understand

Disadvantages: Disadvantages:

Doesn’t require the respondent to: Doesn’t require the respondent to:

- Think about what they’d be willing to give up- Think about what they’d be willing to give up

- Explore risk preference- Explore risk preference

Values spread over the rangeValues spread over the range

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 make Choices may be difficult to make

Most confusion-prone methodMost confusion-prone method

Lack of engagement or willingness to participate Lack of engagement or willingness to participate in exercisein exercise

Utility values tend to cluster near 1Utility values tend to cluster near 1

Pros and Cons – TTOPros and Cons – TTOAdvantages: Still asking assessor to give something up Easier choices than SG. Values not so clustered near 1

Disadvantages: Fails to incorporate riskLack of clarity of when time traded occurs Isn’t something that one can choose to give up. (One can take on a risk of death, but not “pay with life years.”)

Indirect measures of utilityIndirect measures of utility First assess features of health using

standard domains (attributes) respondents complete a questionnaire

Then calculate utility (0 - 1) with equation score using a “multi-attribute scoring

function” derived from community preferences for health states defined by these attributes

http://www.healthutilities.com/hui3.htm

Source: Arnold 2009 BMJ

Utilities in decision Utilities in decision analysisanalysis

• Utilities are used to add Utilities are used to add morbiditymorbidity effects effects to life expectancy.to life expectancy.

• Quality Adjusted Life-Years (QALYs)Quality Adjusted Life-Years (QALYs) (we’ll return to DALYs later) (we’ll return to DALYs later)

QALYsQALYs• QALYs are usually considered the standard unit QALYs are usually considered the standard unit of comparison for outcomes for CEAs in OECDof comparison for outcomes for CEAs in OECD

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

• e.g. 40 years life expectancy after AKA, e.g. 40 years life expectancy after AKA, • utility (AKA) = 0.9utility (AKA) = 0.9 = 40 x 0.9 = 36 QALYs (undiscounted)= 40 x 0.9 = 36 QALYs (undiscounted)

•Mortality lowers LY, morbidity lowers QAMortality lowers LY, morbidity lowers QA

Back to aneurysmBack to aneurysm

M s. B rooks

No treatm ent

Surgery

Surgery:yes or no?

AneurysmR upture?

N op=0.9825 N orm al survival=1

Yesp=0.0175

Early Death=0

SurgicalDeath?

N op=0.977

Yesp=0.023 Early Death=0

Death?

N op=.55

Yesp=.45

N orm al survival=1

AneurysmR upture?

N op=1.0 N orm al survival=1

Yesp=0

Early Death=0

Death?

N op=.55

Yesp=.45

N orm al survival=1

Now we want to add utilities Now we want to add utilities for intermediate outcomesfor intermediate outcomes

Normal survivalNormal survival 1.01.0

Worry about possibility of Worry about possibility of aneurysm ruptureaneurysm rupture

0.950.95

Stroke utility (clipping compli-Stroke utility (clipping compli-cation or aneurysm rupture)cation or aneurysm rupture)

(0.76+.25)/2=0.5 (0.76+.25)/2=0.5

Survival adjmt due to strokeSurvival adjmt due to stroke 0.330.33

Immediate deathImmediate death 0.00.0

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

Including utility for early death Including utility for early death and disability due to strokeand disability due to stroke

Adding utility for worry =.95Adding utility for worry =.95(in No surgery arm)(in No surgery arm)

QALYsNo aneurysm rupture0.9825

No surgery34.78 Die

Aneurysm rupture 0.45

0.0175 Survive0.55

No aneurysm ruptureDifference 1

Δ QALYs -2.77 Survive surgery0.902 Die

Aneurysm rupture 0.45

Clipping 0 Survive32.01 0.55

Key Inputs Surgery-induced disabilityRupture risk/yr 0.0005 0.075

Expected life span 35RR rupture w/ surgery 0 Surgical deathSurgical mortality 0.023 0.023

Surg morb (disability) 0.075

Normal survival,worry

34.91

Normal survival

Normal survival

Early death,worry

Early death

35.0

17.5

35.0

0.0

Ms. Brooks

17.46

34.91Normal survival,

worry

Disability, shorter survival

5.8

Immediate death

Outcomes - DiscountingOutcomes - Discounting• Aneurysm ExampleAneurysm Example• We said since life expectancy is reduced by We said since life expectancy is reduced by 2/3, so instead of 35, it is = 35 * .333 = 11.672/3, so instead of 35, it is = 35 * .333 = 11.67

• However, However, are all years considered equalare all years considered equal??• Consider: Consider: Favorite MealFavorite Meal

Extreme PainExtreme Pain

Lifetime IncomeLifetime Income

Outcomes - DiscountingOutcomes - Discounting• Generally, present value more than futureGenerally, present value more than future• One way to value the different times is One way to value the different times is discounting discounting • Essentially this year is worth D more than Essentially this year is worth D more than next yearnext year• D (annual discount rate) usually set at 3%D (annual discount rate) usually set at 3%• To compare values of all future times, a To compare values of all future times, a calculation, net present value, is often usedcalculation, net present value, is often used• NPV = 1 / (1 + D)NPV = 1 / (1 + D)t t Where t is number of years Where t is number of years in the futurein the future

Outcomes - DiscountingOutcomes - Discounting• Aneurysm ExampleAneurysm Example• If utility is 0.6 and life expectancy is If utility is 0.6 and life expectancy is 3 years3 years• NPV would be: NPV would be: Utility / (1 + D) Utility / (1 + D)tt or or

NPV = 0.6 / 1 + 0.6 / (1.03)NPV = 0.6 / 1 + 0.6 / (1.03)11 + 0.6 / + 0.6 / (1.03)(1.03)22

• However, since events in year 1 occur However, since events in year 1 occur on average half way through, we can on average half way through, we can use 0.5 for year 1:use 0.5 for year 1:

NPV = 0.6 / (1.03)NPV = 0.6 / (1.03)0.50.5 + 0.6 / (1.03) + 0.6 / (1.03)1.51.5 + + 0.6 / (1.03)0.6 / (1.03)2.52.5

Outcomes - DiscountingOutcomes - DiscountingQALYs

discNo aneurysm rupture0.9825

No surgery21.37 Die

Aneurysm rupture 0.450.0175 Survive

0.55

No aneurysm ruptureDifference 1

Δ QALYs -1.63 Survive surg.0.902 Die

Aneurysm rupture 0.45Clipping 0 Survive

19.74 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

Normal survival,worry

21.4

Normal survival

Normal survival

Early death,worry

Early death

21.5

Ms. Brooks

13.3

21.4Normal survival,

worry

0.0

Disability, shorter survival

13.4

21.5

4.8

Immediate death

QALYs vs. DALYsQALYs vs. DALYs “Quality Adjusted Life Years” (QALYs)

came first; still used for CEAs in OECD measure of health. An illness which shortens life by 2 years and lowers

“health status utility” by 20% for 5 years decreases QALYs by -2 - 0.2 * 5 = -3

Interventions are designed to increase QALYs

“Disability Adjust Life Years” (DALYs) most common health metric in global health. measure of disease burden – i.e., the negative of QALYs. An illness which shortens life by 2 years and raises

“disability” by 20% for 5 years increases DALYs by 2 + 0.2 * 5 = 3

Interventions are supposed to avert DALYs.

Geographic setting

Measures Components Goal is to:

Quality-Adjusted Life Years (QALYs)

U.S., Europe, and other OECD

countries

Health status

“LY” is gain in life years due to intervention.

“QA” is gain in health status utility* due to better health.

Gain

Disability-Adjusted Life Years (DALYs)

Global, and developing

world

Disease burden

“LY” is life years lost due to premature death.

“DA” is disability* due to morbidity.

Avert

* In practice, methods to estimate disability weight and health status utility often overlap, relying on similar elicitation of expert or patient or population opinion.

Excel workbook

Exponential DiscountingExponential Discounting

Exponential discounting first described in 1937* Mathematically easy to manipulate

Assumed discounting in “simple regular fashion”

Does not differentiate difference between: Today vs. tomorrow Ten years vs. ten years plus one day

*Samuelson PA. A Note on Measurement of Utility. Rev Econ Stud 1937;4:155-61

Overall ReviewOverall Review• Outcomes - ClinicalOutcomes - Clinical

Mortality - timingMortality - timing

Morbidity – severity, duration, timingMorbidity – severity, duration, timing

• Measuring UtilitiesMeasuring UtilitiesDirect – TTO most oftenDirect – TTO most often

Indirect – may underestimate utilityIndirect – may underestimate utility

• QALYs - health, DALYs – disease burdenQALYs - health, DALYs – disease burden• Discounting Discounting

NPV = NPV = Utility / (1 + D) Utility / (1 + D)t t