A Review and Meta- Analysis of Utility Values for Lung Cancer Julie Migrin ASPH Environmental Health Fellow at the U.S. EPA

Outline Background: QALYs and lung cancer Illustrate the problem Suggest potential explanations Methods Results and conclusions Next steps

QALYs and utilities Quality adjusted life year, QALY, is a measure of health- related quality of life  Incorporates measures of both quantity (years) and quality of life (utility) Utility value (preference score, preference weight)  Ranges from 0 to 1  Indicator of global, health related quality of life  No one way to elicit Uses: Regulatory cost effectiveness analysis, medical decision making ·Assume a policy extends the baseline health profile (white) · The gain in QALYs is shown in gray

Lung Cancer 200,000 new U.S. cases each year (CDC data) Cost: $9.6 billion per year in U.S. (CDC data) Environmental/Occupational Causes  Radon  Pesticides  Asbestos  Polycyclic aromatic hydrocarbons (PAHs)  Vinyl Chloride (monomer of PVC)  Arsenic  Chromium What’s Lurking in Your Countertop? July 24, 2008

Small Cell Lung Cancer Lung Cancer Types Non Small Cell Lung Cancer

Which utility should you use??? There are numerous published utility estimates for lung cancer, spanning a very broad range of values In this study:  Metastatic/Advanced lung cancer Range:  Nonmetastatic/Early stage lung cancer Range:  Mixed or unspecified severity lung cancer Range: Results of this variation?

Possible explanations for utility variation Upper and lower bound labels Possibilities:  Death----- perfect health  Absence of disease normal health  Worst imaginable well  Or…. No given bound labels Death Worst imaginable Absence of disease???Normal health??? Well Perfect health

Possible explanations for utility variation Elicitation techniques Examples:  Standard gamble  Time trade-off  Rating Scale  Generic index/ Multi- attribute utility index(Health Utilities Index, EQ-5D)  Judgment AttributeLevelDescription SENSATION1Able to see, hear, and speak normally for age. 2Requires equipment to see or hear or speak. 3Sees, hears, or speaks with limitations even with equipment. 4Blind, deaf, or mute. Multi-Attribute Health Status Classification System: Health Utilities Index Mark 2 (HUI2)

Possible explanations for utility variation Respondent Examples:  Patients  Physicians or researchers  Family members  Members of the public

Findings from the Literature Bound Labels Perfect health < Absence of disease (Fryback and Lawrence, 1997) (King et al., 2003) Normal health < Perfect health Excellent health < Perfect health (Tengs and Lin, 2003) Elicitation Technique Rating Scale < Time tradeoff < Standard Gamble (Read et al., 1984) (Stiggelbout et al., 1996) (Stiggelbout et al., 1994) Standard Gamble < Rating Scale < Time tradeoff (Hornberger et al., 1992) Respondent Nonpatients < Patients (Gabriel et al., 1999) (Boyd et al., 1990) Polsky et al., 2001) (Sackett and Torrance, 1978) (Tengs and Lin, 2002)

Study Objectives Objective 1: Provide pooled estimates which reflect the available lung cancer utility literature Objective 2: Determine which methodological factors significantly influence the value of utility for lung cancer

Methods Data Collection  Searched PubMed, National Health Service Economic Evaluation Database, and Cost Effectiveness Analysis Registry from the Center for the Evaluation of Value and Risk in Health  Search terms: “lung cancer” + one of the following: “quality of life”, “utility”, “preference score”, “cost- effectiveness”, “cost-utility”, “QALY”  Inclusion criteria: Written in English ≥1 unique utility Noted elicitation technique Noted respondent

Methods 23 articles (2 to 45 utilities each) 223 unique utility values Reviewed for 1. Mean or median utility value 2. Measure of variance 3. Number of respondents 4. Type of respondent 5. Elicitation technique 6. Bounds on utility scale 7. Lung cancer type 8. Lung cancer severity

Methods Statistical modeling  Meta-regression Using study characteristics (at the group or individual level) as explanatory variables Summary measure of effect (utility) as dependent variable  Hierarchical Linear Model (aka Mixed, Multilevel, Random Effects Models) Nested data structure Violation of assumption of independence Allows addition of group level variables

Methods HLM (i=1,...n j individual in j=1,…J groups)  First Level Equation Y ij =b 0j + b 1j X ij + … + ε ij ε ij ~ N (0,σ 2 )  Second level equation b 0j = γ 00 + γ 01 C j + U 0j U 0j ~ N (0,τ 00 ) b 1j = γ 10 (constant slope across groups)  Full model Y ij = (γ 00 + γ 01 C j + U 0j ) + (γ 10 )X ij + ε ij Y ij = γ 00 + γ 01 C j + γ 10 X ij + U 0j + ε ij Group effect Individual Effect Random intercept Individual Level error Individual level model in each group Group specific intercept Group specific slope

Methods Level one/observation level variables  Type of respondent  Elicitation technique  Lung cancer severity Level two/study level variables  Lower bound of utility scale  Upper bound of utility scale  Lung cancer type Dummy variables  Categorical predictor variables  Example: two dummies used to represent the three categories of respondent (patient, expert, public)  Full reference case: metastatic, non-small-cell lung cancer (NSCLC), patient, standard gamble method, with scale ranging from death to perfect health Observation weights  Number of respondents / variance of utility value

Results. Study Characteristics VariableNumber of utilities (n=223) Percentage of utilities Cancer stage Metastatic Nonmetastatic Mixed/Not specified Lung cancer type NSCLC SCLC114.9 Mixed/Not specified Lower bound Death Worst imaginable 20.9 Not stated VariableNumber of utilities (n=223) Percentage of utilities Upper bound Perfect health Well / Full health Normal health Not stated Respondent Patient Expert Public103.6 Elicitation technique Standard Gamble Judgment Direct rating HALex62.7 AQOL EQ-5D Time trade-off125.4

Results Variable Coefficient estimate Standard errorP value Intercept <.0001 Cancer stage Metastatic 0 Nonmetastatic <.0001 Mixed/Not specified <.0001 Lung cancer type NSCLC 0 SCLC Mixed/Not specified Lower bound Death 0 Worst imaginable Not stated Variable Coefficient estimate Standard errorP value Upper bound Perfect health0 Well / Full health Normal health Not stated Respondent Patient0 Expert Public Elicitation technique Standard gamble0 Judgment Direct rating HALex AQOL EQ-5D Time trade-off

Results Variable Coefficient estimate Standard errorP value Intercept <.0001 Cancer stage Metastatic 0 Nonmetastatic <.0001 Mixed/Not specified <.0001 Lung cancer type NSCLC 0 SCLC Mixed/Not specified Lower bound Death 0 Worst imaginable Not stated Pooled estimates (all other variables set to reference values*) Metastatic: Nonmetastatic: Mixed/ Not specified: *Reference: NSCLC, death- perfect health, patient as respondent, standard gamble method

Results Variable Coefficient estimate Standard errorP value Intercept <.0001 Cancer stage Metastatic 0 Nonmetastatic <.0001 Mixed/Not specified <.0001 Lung cancer type NSCLC 0 SCLC Mixed/Not specified Lower bound Death 0 Worst imaginable Not stated Lung Cancer Type Small-cell lung cancer: Utility is estimated to be lower than for non-small-cell lung cancer Mixed/Not specified: Utility is estimated to be lower than for non-small-cell lung cancer

Results Variable Coefficient estimate Standard errorP value Upper bound Perfect health0 Well / Full health Normal health Not stated Respondent Patient0 Expert Public Elicitation technique Standard gamble0 Judgment Direct rating HALex AQOL EQ-5D Time trade-off Upper Bound Well/full health: Utility is estimated to be higher than for those values with perfect health as the upper bound label Respondent Expert: Utility is estimated to be higher than for those values with patients as respondents Public: Utility is estimated to be lower than for those values with patients as respondents

Results Variable Coefficient estimate Standard errorP value Upper bound Perfect health0 Well / Full health Normal health Not stated Respondent Patient0 Expert Public Elicitation technique Standard gamble0 Judgment Direct rating HALex AQOL EQ-5D Time trade-off Elicitation technique HALex: Utility is estimated to be higher than for those values elicited with the standard gamble method AQOL: Utility is estimated to be lower than for those values elicited with the standard gamble method Time trade-off: Utility is estimated to be lower than for those values elicited with the standard gamble method

Results

Limitations  Lack of gray literature  Model predicts values outside standard range of 0-1  No demographic information included  Using weights

Conclusions Objective 1: Provide pooled estimates which reflect the available lung cancer utility literature Metastatic lung cancer: Nonmetastatic lung cancer: Mixed/Not specified lung cancer: 0.772

Conclusions Objective 2: Determine which methodological factors significantly influence the value of utility for lung cancer Significant predictors: Lung cancer stage, lung cancer subtype, respondent Near significant: Elicitation method Not significant: Upper and lower bound labels

Next steps… Larger meta-analysis looking at 12 common cancers Do different kinds of cancers impact quality of life more of less severely? With a larger sample, which methodological factors significantly impact the value of utility? Which demographic factors significantly impact the value of utility?

Thank you!!! Chris Dockins Will Wheeler Colleen Reid

References Fryback, D.G. and W.F. Lawrence, Jr., Dollars may not buy as many QALYs as we think: a problem with defining quality-of-life adjustments. Medical Decision Making, (3): p King, J.T., et al., "Perfect health" versus "disease free": the impact of anchor point choice on the measurement of preferences and the calculation of disease-specific disutilities. Medical Decision Making, (3): p Tengs, T.O. and T.H. Lin, A meta-analysis of quality-of-life estimates for stroke. Pharmacoeconomics, (3): p Read, J.L., et al., Preferences for health outcomes. Comparison of assessment methods. Medical Decision Making, (3): p Stiggelbout, A.M., et al., The 'utility' of the visual analog scale in medical decision making and technology assessment. Is it an alternative to the time trade-off? International Journal of Technology Assessment in Health Care, (2): p Stiggelbout, A.M., et al., Utility assessment in cancer patients: adjustment of time tradeoff scores for the utility of life years and comparison with standard gamble scores. Medical Decision Making, (1): p Hornberger, J.C., D.A. Redelmeier, and J. Petersen, Variability among methods to assess patients' well-being and consequent effect on a cost-effectiveness analysis. Journal of Clinical Epidemiology, (5): p Gabriel, S.E., T.S. Kneeland, and L.J. Melton, Health-related quality of life in economic evaluations for osteoporosis: whose values should we use? Medical Decision Making, : p Boyd, N.F., et al., Whose utilities for decision analysis? Medical Decision Making, (1): p Polsky, D., et al., A comparison of scoring weights for the EuroQol derived from patients and the general public. Health Economics, (1): p Sackett, D.L. and G.W. Torrance, The utility of different health states as perceived by the general public. Journal of Chronic Disease, : p Tengs, T.O. and T.H. Lin, A meta-analysis of utility estimates for HIV/AIDS. Medical Decision Making, : p