INTERGRATION OF QUALITY OF LIFE AND SURVIVAL FOR COMPARATIVE HEALTH RISK/OUTCOME ASSESSMENT

1. INTERGRATION OF QUALITY OF LIFE AND SURVIVAL FOR COMPARATIVE HEALTH RISK/OUTCOME ASSESSMENT Jung-Der Wang, M.D., Sc. D. National Taiwan University College of Public Health National Taiwan University Hospital

2. OUTLINES • Estimating health expectancy in Taiwan • Revisiting the integration of survival and quality of life (QOL), and concept of QALY (quality-adjusted life year) as a common unit for risk/outcome evaluation and cost-effectiveness, especially quantifying health benefits of prevention of a disease by QALY • Extending to psychometric measurement for QOL and clinical decision making • Integrating with medical cost of the NHI

3. Problems in direct comparison between EU and Taiwan for HLY: Taiwan: (National Health Survey) surveyed age: 12-85; self-administered questionnaire ; SF-36 and WHOQOL-BREF (age 12-65) EU countries: Are you restricted in daily activities as a result of longstanding illness, condition or handicap? All the time (severe); now and then (moderate); seldom or no (no disability)

4. SF-36 physical function • The following items are about activities you might do during a typical day. Does your health now limit you in these activities? If so, how much? • (Vigorous activities, such as running, etc.) b. Moderate activities, such as moving a table, etc. c to j. Lifting or carrying groceries; climbing several flights of stairs; climbing one flight of stairs, bending or stooping; walking > one block; bathing or dressing yourself. Yes, limited a lot;Yes, limited a little; No, not limited at all

5. SF-36 physical function Yes, limited a lot;Yes, limited a little; No, not limited at all (male)

6. SF-36 physical function Yes, limited a lot;Yes, limited a little; No, not limited at all (female)

7. SF-36 physical function Yes, limited a lot;Yes, limited a little;No, not limited at all

8. SF-36 physical function (male) Yes, limited a lot;Yes, limited a little;No, not limited at all

9. SF-36 physical function (female) Yes, limited a lot;Yes, limited a little;No, not limited at all

10. Redefining health care (2006):by Michael Porter and Elizabeth Teisberg • Value is the health outcomes per dollar spent in providing services. Outcomes are multidimensional, and include not only survival but quality of life, extent of recovery or disability, errors, complications, recovery time, recurrences, and other aspects of the patient’s health experience.

11. Evidence based medicine: • There is no room for spending money on ineffective diagnosis and treatment for any medical condition. • Preventive medicine must also be evidence-based • Quantification of health benefit of preventing the occurrence of a specific disease (How much loss of health benefit for a specific disease ?)

12. No. articles in PubMed database with two specific key words

13. A common question raised: • Is there a common unit to measure both the survival and utility or psychometry of quality of life? • Live vs. Dead ---- counting the no. of lives saved • More delicate measures: --Length of survival S(t) or S(ti|xi) --Quality of life Qol(ti|xi) • Can we measure S(ti|xi) or Qol(ti|xi)? • Can we develop a method to combine both? • (Can we quantify the cost paid by the NHI? )

16. Estimated survival function, mean QOL and quality adjusted survival curve; The area under the QAS curve is the expected quality adjusted survival time (Hwang JS, et al Statistics in Medicine 1996;15:93-102)

17. Health-Adjusted life expectancy (HALE) kdifferenthealth states hkwith weight Wk at time t Quality-Adjusted life expectancy (QALE) Qol(t): quality of life function at time t

18. Can be calculated by the mean of quality of life at time t (in terms of utility) wk: weight of health state k hk: utiluty value of health state k

19. male

20. female

21. Notation of a typical life table with added columns of QOL (quality of life) and QAST (quality adjusted survival time)

22. A more general model: • xi:determinant(s) of S(survival) and U(utility) functions e.g. head injury, stroke,….., etc. • Quality adjusted survival Qol(t| xi): quality of life function (Wang JD. Basic principles and practical applications in epidemiological research. 2002)

23. Cost of illness approach: • Human capital left over for determinant xi WA(t| xi): work ability function • Direct medical cost of determinant xiCost(t| xi): medical cost function

24. Gain of health benefits from successful prevention of a disease xi Let x0 denotes age- and gender- matched referents simulated from the general population or vital statistics __

25. ILLUSTRATIVE EXAMPLES: • How much utility of health (in QALY) does it cost for a case of end stage renal disease or liver cancer? • --- Survival curve • --- Quality of life estimation --- General population of Taiwan in 1995 as the reference population assuming QOL=1

26. Utility measured by standard gamble (SG)

27. Shaded area =233.6 QALM loss due to liver cancer

28. Pit dug for washing underground soil and water

29. RISK: LIKELIHOOD OF EVENT (Incidence rate or probability) X CONSEQUENCE OF EVENT (loss of utility due to the event) (need to establish a cohort to estimate)

30. Cancer risks based on RME (reasonable maximal exposure) and cancer slopes Vinyl chloride QALM 8.4 x 10-6 (X233.6 .002 Tetrachloroethylene QALM) = 1.9 x 10-4 .044 Trichloroethylene 1.4 x 10-4 .032 IF there are 1000 people at risk, then the above numbers must be multiplied with 1,000

31. Example 2:helmet law for motor cycle riders

32. Utility gained from the enforcement of helmet law • Number of cases of head injury prevented by wearing a helmet --- full face vs. half- face covered • Number of QALY lost per case of head injury --- case registry of head injury in Taipei city followed for 7 years (Tsauo JY, et al. Accident Analysis & Prevention 1999;31:253-63)

33. The survival function of the head injury cases and the reference population in the 80 months after onset

34. The health-related quality of life of the head injury cases and the reference population in the 80 months after onset

35. The quality-adjusted survival time of the head injury cases and the reference population in the 80 months after onset

36. EXTENSION TO HEALTH PROFILE (PSYCHOMETRIC SCORE) • Consequence of the event can be replaced by QOL measured by psychometrics • Hwang JS, Wang JD. Quality of Life Research 2004; 13:1-10

37. Psychometric mean score • The sum of scores of those who are still alive plus those who die • The following simple equation establishes the relationship between population mean QoL score function and survival function, where Qs(t) is the average QOL of surviving subjects at time t

38. Estimations • The estimate of expected psychometric score-adjusted survival (PAS) for an index population, is obtained by firstly estimatingand at chosen time points ’s

39. Survival-weighted Health Profile in Long-term Survivors of Acute Myelogenous Leukemia (AML) Chiun Hsu1, Jung-Der Wang1, Jing-Shiang Hwang2, and Jih-Luh Tang 1 • National Taiwan University Hospital1 • Academia Sinica2 • Taipei, Taiwan • (Quality of Life Research 2003 ;12:503-517)

40. Comparison of life time psychometric Scores for BMT and chemotherapy (WHOQOL generic instrument)

41. Comparison of life time psychometric scores for BMT and chemotherapy (WHOQOL generic measurement)

42. HOW MUCH DOES IT COST FOR A UNIT OF SCORE-TIME? • Through questioning 157 patients with disability caused by occupational injury under contingent valuation method or stated preference, we found that people are willing to pay US$ 65.1-69.6 for a pain-killer pill that can remove pain for 24 hours. Ho JJ, et al. et al. (monetary value of score time) Accident Analysis & Prevention 2005;37:537-48 • The WTP money for removing a longer duration of pain is even bigger

44. Lifetime cost (NT$) for hemodialysis

45. Conclusion: for outcome/risk assessment in health and medicine • The QALY or life year gained or loss plus the psychometric score time can be estimated for comparative assessment of health risks/outcomes in national health resources allocation and clinical decision makings (and for cost-effectiveness analysis). • Measurements of QOL had better be improved to an interval scale.

46. Life-time utility (Economist) 經濟學家：終生預期效用 survival function人命(存活函數)utility function --HRQL(健康相關生活品質) --working ability, wages, medical costs 工作能力、薪資、醫療費用 • Quality-adjusted life expectancy or healthy life expectancy (生活品質調整後預期壽命)

48. Hwang JS, Tsauo JY, Wang JD. (theory of QAS) Stat Med 1996;15:93-102 Hwang JS, Wang JD. (QAS extrapolation to lifetime) Stat Med 1999;18:1627-40 Tsauo JY, et al. (Utility of enforcement of helmet law) Accident Anal Prev 1999;31:253-63 Yao KP, et al. (WHOQOL-BREF Taiwan version) J Formos Med Assoc 2002;101:342-51 Lee LJH, et al. (Risk assessment for water pollution) J Toxicol Environ Health 2002;65:219-35 Hwang JS, Wang JD (extended to psychometry) Quality Life Res 2004; 13:1-10 Hsu J, et al. (bone marrow transplantation for leukemia) Qual Life Res 2003 ;12:503-517 Chuang HY, et al. (occupational health policy for lead) J Toxicol Environ Health 2005; 68:1485-96. Ho JJ, et al. (monetary value of score time) Accident Anal Prev 2005;37:537-48. Ho JJ, et al. (survival of occupational disability) Scand J Work Environ Health 2006; 32(2):91-98. Ho WL, et al. (survival and cost of thalassemia) Bone Marrow Transplant 2006; 37(6):569-574. Ho JJ, et al. Estimation of reduced life expectancy. Accident Anal Prev 2006; 38:961-968. Fang CT et al. (Life expectancy of patients with HIV/AIDS). Quarterly J Med 2007; 100:97-105. Fang CT et al. (Cost-effectiveness for HAART policy) J Formos Med Assoc 2007; 106(8):631–640 Chu PC et al. (Lifetime financial burden to the National Health Insurance for 17 different cancer in Taiwan) J Formos Med Assoc 2008; 107:54-63 Chu PC et al. (Life expectancy and loss of life expectancy for major cancer in Taiwan) Value in Health 2008; 7:1102-1109 Chang CY et al (Quality of life in obese patients) Obesity Surg 2008; DOI 10.1007/s11695-008-9513-z

49. THANK YOU FOR YOUR ATTENTION

50. Extrapolation of survival under high censored rate: Semi-parametric modeling (Hwang & Wang 1999, Fang et al. 2007) Total Hazard Background Hazard H (t | patient) = H (t | reference) + constant excess hazard C1 age- and gender-matched logit W(t) = ln [exp (C0 – C1 × t)/(1 – exp (C0 – C1 × t))] = C0 – C1 × t – ln [1 – exp (C0 – C1 × t)] Because C1 > 0, the residual item ln [1 – exp (C0 – C1 × t)] will converge to 0 when t. As a result, when t, logit W(t) will approximate to C0 – C1 × t , which is a straight line with a slope of – C1.