1. Decision Analysis: Utilities and QALYs Miriam Kuppermann, PhD, MPH Professor Departments of Obstetrics, Gynecology & Reproductive Sciences and Epidemiology & Biostatistics January 17, 2008

2. Today’s 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

3. Review—Last Lecture Formulated an explicit question Formulated an explicit question “To clip or not to clip” (aneurysm ) “To clip or not to clip” (aneurysm ) Made a decision tree Made a decision tree Conducted an expected value calculation to determine which course of action would likely yield the highest life expectancy Conducted an expected value calculation to determine which course of action would likely yield the highest life expectancy

4. To Clip or not to Clip? Can have an impact on life expectancy Can have an impact on life expectancy Also may affect health-related quality of life: 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

5. Incorporating Quality-of-Life Effects into DA Measure and apply utilities Measure and apply utilities Use utilities to quality-adjust life expectancy for decision and cost-effectiveness analysis Use utilities to quality-adjust life expectancy for decision and cost-effectiveness analysis

6. Preview—Where 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 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 (ICER) to other currently accepted medical interventions Compare incremental cost effectiveness ratios (ICER) to other currently accepted medical interventions

7. What is a Utility? Quantitative measure of the strength of an individual’s 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)

8. Utilities are the Currency we use to Assign a Value Outcomes Scaled from 0 to 1 1 = perfect or ideal health or health in the absence of the condition being studied 0 = dead

9. How do we Measure Utilities? Visual Analog Scale Visual Analog Scale Standard Gamble Standard Gamble Time Trade-off Time Trade-off----- Conjoint analysis

10. BKA vs. AKA Example Patient in the hospital has infection of the leg Two options: BKA v. medical management Two options: BKA v. medical management BKA –1% mortality risk BKA –1% mortality risk Medical management – 20% chance of infection worsening: Medical management – 20% chance of infection worsening: AKA – above the knee amputation (10% mortality risk) AKA – above the knee amputation (10% mortality risk) Let’s draw a decision tree

11. For Which Outcomes do we need to Measure Utilities? Death? Death? Risk of worsening? Risk of worsening? Living with part of a leg (below the knee) missing? Living with part of a leg (below the knee) missing? Living with a bigger part of a leg (above the knee) missing? Living with a bigger part of a leg (above the knee) missing? Others? Others?

12. Visual 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 thermometer.”

13. Standard Gamble Asks respondents what chance of immediate death they would be wiling to incur to avoid living with the outcome being assessed. Method relies on respondents choosing between: 1) a certain outcome (BKA) 1) a certain outcome (BKA) 2) a gamble between an ideal outcome (intact leg) and the worst outcome (dead) 2) a gamble between an ideal outcome (intact leg) and the worst outcome (dead)

14. Standard Gamble Question

15. xercise Standard Gamble Exercise Spend the rest of your life with BKA ] immediate death [p]% chance of immediate death 1-[p]% chance of spending the rest of your life with an intact leg Which do you prefer? Choice AChoice B

16. Time Tradeoff Asks respondents how many years of their own life they would be willing to give up to spend that life expectancy the without the condition/health state being assessed. Method relies on respondents choosing between: 1) Full life expectancy with the condition/outcome being assessed (BKA) 1) Full life expectancy with the condition/outcome being assessed (BKA) 2) A reduced life expectancy with the the ideal outcome (intact leg) 2) A reduced life expectancy with the the ideal outcome (intact leg)

17. 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 AChoice B

18. 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 AChoice B

19. Pros and Cons - VAS Advantages: Easy to understand, visual Disadvantages: Doesn’t require the respondent to think about what they’d be willing to give up, doesn’t explore risk preference, values spread over the range, doesn’t require much engagement

20. 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.

21. 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, isn’t something that one can choose to give up. (One can take on a risk of death, but not “pay with life years.”)

22. Utility Measurement – Additional Information Multi-Attribute Health Status Classification System Multi-Attribute Health Status Classification System Developed by Health Utilities, Inc. Developed by Health Utilities, Inc. Available at: http://www.healthutilities.com/overview.htm Available at: http://www.healthutilities.com/overview.htm

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

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

25. QALYs Aneurysm Example We said life expectancy is reduced by 2/3, so instead of 35, it is = 35 *.333 = 11.67 We said life expectancy is reduced by 2/3, so instead of 35, it is = 35 *.333 = 11.67 Here, we have assigned a utility of.5 to surgery-induced disability, so QALYs = Here, we have assigned a utility of.5 to surgery-induced disability, so QALYs = years * utils = 11.67 *.5 = 5.8 years * utils = 11.67 *.5 = 5.8

26. QALYs

27. 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

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

29. 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)

30. 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

31. 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

32. 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?

33. Simplified Decision Tree for Prenatal Testing

34. 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

35. Time Tradeoff Preference Elicitation Choice AChoice 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)

36. 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

37. Calculation of Time Tradeoff Scores reduced life expectancy with unaffected child (30 years) U TTO = __________________________________________ full life expectancy with DS-affected child (40 years) = 0.75

38. Median value for procedure-related miscarriage = 0.86 Median value for Down-syndrome affected 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.

39. 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

40. 0 25 50 75 100 125 150 175 200 Number -.75-.5-.25 0.25.5.751 Preferences Vary Substantially Value misc - Value DS

41. 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.

42. 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

43. 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.

44. Cost Effectiveness of Prenatal Diagnosis QALYs Lifetime cost Cost-utility ratio Age 20 Amniocentesis24·16$54,080$14,200 No testing24·08$52,940 Age 35 Amniocentesis20·39$61,490$12,600 No testing20·30$60,360 Age 44 Amniocentesis17·08$59,020$11,300 No testing16·98$57,890 Harris, Washington, Nease, Kuppermann. Cost utility of prenatal diagnosis and the risk-based threshold. Lancet 2004; 363:276-82.

45. Second Evidence-Based Conclusion Offering invasive testing to women of all ages and risk levels can be cost effective.

46. Recommendation #1 Guidelines should be changed to enable all women to make informed choices about which prenatal tests, if any, to undergo.

47. 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.”

48. 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...”