Comparative health risk/impact assessment for occupational and

environmental health: Integration of survival and quality of life

Jung-Der Wang, M.D., Sc. D.

National Taiwan University College of Public Health

National Taiwan University Hospital

OUTLINES• Introducing the needs and concepts of

survival, quality of life (QOL), and quality-adjusted survival as outcome indicators with QALY (quality-adjusted life year) and/or life year as a common unit for risk/impact and cost-effectiveness assessment

• Quantification of contribution from preventive services and examples

• Integration with medical cost from the NHI

Determinants of RISK: (BS8800)

LIKELIHOOD OF EVENT

(Incidence rate or probability)

X

CONSEQUENCE OF EVENT

(loss of utility due to the event)

(survival integrated with quality of life)

Environmental and Occupational Health Risk Assessment

• For sustainable development, we always want to reduce health risk or replace toxic substances by a less toxic compound. But how do you compare nephrotoxicity with hepatotoxicity?

• Different health events cannot be directly compared, unless quantified with the same unit in health

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? )

Summary Measures of Population Health WHO 2002

Concepts, Ethics, Measurementand Applications

Edited by Christopher J.L. Murray, Joshua A. Salomon, Colin D. Mathers and Alan D. Lopez

http://www.who.int/publications/smph/en/

Comparative Quantification of Health Risks- WHO2004

Global and Regional Burden of Disease Attributable to Selected Major Risk Factors

Edited by Majid Ezzati, Alan D. Lopez, Anthony Rodgers and Christopher J.L. Murray

http://www.who.int/publications/cra/en/

Treatments for Existing Conditions (NEJM2008;358:661-3)

• Cognitive-behavioral family intervention for patients with Alzheimer’s disease Cost-saving

• Cochlear implants in profoundly deaf children Cost-saving

• Combination antiretroviral therapy for HIV-infected patients $29,000/QALY

• Liver transplantation in patients with primary sclerosing cholangitis $41,000/QALY

• Implantation of cardioverter defibrillators in appropriate populations, compared with medical management alone $52,000/QALY

Preventive Measures (NEJM2008;358:661-3)

• Haemophilus influenzae type b vaccination of toddlers Cost-saving

• One-time colonoscopy screening for colorectal cancer in men 60-64yr of age Cost-saving

• Newborn screening for medium-chain acyl-coenzyme A dehydrogenase deficiency

$160/QALY

• High-intensity smoking-relapse prevention program, as compared with a low-intensity program $190/QALY

• Intensive tobacco use prevention program for 7th and 8th graders $23,000/QALY

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)

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

. . . . . . . . .

. . . . . . . . .

. . . . . . . .

. . . . . . . . .

1 0

ConditionalProportionSurviving

CumulativeProportionSurvivingInterval

NumberLost toFollow-up

NumberWithdrawn Alive

NumberDying

NumberEnteringInterval

NumberExposedTo Risk

ConditionalProportion Dying

QOL ti( ) QAST

21 tt l1 w1 d1 n'1 n1 1q̂ 1p̂ 00.1)(ˆ 1 ts qol t( )1 QS1

32 tt l 2 w2 d 2 n'2 n2 2q̂ 2p̂ )(ˆ 2ts qol t( )2 QS 2

1 ii tt li wi di n i' ni iq̂ ip̂ )(ˆ its qol ti( ) QSi

ss tt 1 ls 1 ws 1 ds 1 n s' 1 ns 1 1ˆ sq 1ˆ sp )(ˆ 1sts qol ts( ) 1 QSs 1

st ls ws ds n s' ns )(ˆ sts qol ts( ) QSs

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)

)dt|()]|([ ii xtSxtUE

)dt|()]|([ ii xtSxtQolE

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

2000 as the reference population assuming QOL=1

quality of life

quality-adjusted survival

survival curve

17.5 QALY

Pit dug for washing underground soil and water

*MCLG: Maximum Contaminant Level Goal†MCL: Maximum Contaminant Level

EPA’s Drinking water standard

(µg/L) VOCs

Solubility in water

mg/L at 25℃

MCLG* MCL†

Concentration range µg/L

1,1-Dichloroethane 6000 NA NA ND-227.9

1,1-Dichloroethene 2500 7 7 ND-1240.4

cis 1,2-Dichloroethene

3500 70 70 ND-1376.0

Tetrachloroethene 150 0 5 ND-5228.3

1,1,1-Trichloroethane

1495 200 200 ND-1504.4

Trichloroethene 1100 0 5 ND-5479.7

Determinants of RISK: (BS8800)

LIKELIHOOD OF EVENT

(Incidence rate or probability)

X

CONSEQUENCE OF EVENT

(loss of utility due to the event)

(survival integrated with quality of life)

Cancer risks based on RME (reasonable maximal

exposure) and cancer slopes

Vinyl chloride 8.4 x 10-6

Tetrachloroethylene 1.9 x 10-4

Trichloroethylene 1.4 x 10-4

Measure Quality-adjusted survival up to 18 years

QALE by Huang’s extrapolation method

QALE loss due to a case of liver cancer

Liver cancer

GeneralPopulation

Mean (SE)

2.5 (0.10) QALY 3.1 (0.12)QALY

20.6 (0.03)QALY

17.5 (0.13) QALY

Chemical cancer risk Population at risk in the downstream community

Excess number of liver cancer

Utility loss due to liver cancer in the community

Vinyl chloride Trichloro-ethylene

Tetrachloro-ethylene

8.4×10-6 1.4×10-4 1.9×10-4 5,000 1.7 29.8 QALY

Cancer site Cohort size

Mean age at Dx (SD)

Life expectancy

Years of life loss

Lifetime cost (3% discount)

Pancreas 7,931 65.6 (12.7) 2.81 (0.17) 12.87 263

Lung 58,773 66.6 (11.7) 3.09 (0.07) 11.79 342

Liver 68,585 60.4 (13.5) 3.45 (0.08) 15.61 238

Esophagus 9,710 63.0 (12.1) 3.54 (0.20) 13.25330

Gallbladder & bile duct

5,097 66.5 (12.0) 4.98 (0.20) 10.36446

Stomach 35,477 64.9 (13.6) 7.51 (0.14) 8.80 609

Prostate 14,288 73.1 (8.0) 8.17 (0.13) 1.72 527

Oral cavity 26,681 53.8 (12.9) 9.58 (0.61) 14.00910

Cancer site Cohort size

Mean age at Dx (SD)

Life expectancy

Years of life loss

Lifetime cost (3% discount)

Colon & rectum

60,789 63.8 (13.7) 10.86 (0.11) 6.36 692

Kidney & urinary tract

11,671 62.7 (15.1) 10.97 (0.85) 6.74 528

Bladder 15,092 66.7 (12.6) 10.99 (0.20) 3.83 519

Leukemia 9,224 41.8 (25.5) 11.61 (0.94) 19.34 2,404

Nasopharynx 15,231 49.6 (13.4) 12.59 (0.74) 14.79 632

Skin 14,005 63.3 (16.9) 16.16 (0.22) 1.59 354

Ovary 6,436 49.3 (17.0) 17.71 (0.80) 11.91 1,277

Cervix uteri 29,636 54.7 (13.8) 19.77 (0.30) 6.18 808

Breast 36,668 50.5 (12.5) 20.01 (0.80) 9.35 1,081

Examples helmet law for motor cycle riders

Comparison of QALY loss from head injuries occurred

in motorcyclists with and without wearing a helmet

(Lee HY et al. Am J Public Health 2009 accepted)

Comparison of QALY loss from head injuries occurred

in motorcyclists with and without wearing a helmet

(Lee HY et al. Am J Public Health 2009 accepted)

Head Injury Registry in Taiwan Head Injury Registry in Taiwan

3328 hospitalized patients with motorcycle-related head injuries 22 major hospitals 2001~2007

3328 hospitalized patients with motorcycle-related head injuries 22 major hospitals 2001~2007

dtxtSxtQolE )|()]|([QALE

Follow-up limit 50-year extrapolation

0

1QOL

Survival

QALE

0~1 utility score

EuroQol-5D questionnaire EuroQol-5D questionnaire

Mobility

Usual activities

Self-care

Pain/discomfort

Anxiety/depression

Telephone interviewed: 190 cases Telephone interviewed: 190 cases

Good outcome Bad outcome

good outcome:35.3 QALYs

bad outcome:7.6 QALYs

goodoutcomebadoutcome

goodoutcomebadoutcome

Helmeted ridersQALE: 31.7 QALYs

Loss: 5.8 QALYs

Non-helmeted ridersQALE: 25.9 QALYsLoss: 10.7 QALYS

Proportion to weight

88% 35.3

12%7.6

66%x35.3

34%x7.6

In addition to reduced incidence rate,

Simple use of a helmet could save 5 QALYs in a motorcycle-related head injury

In addition to reduced incidence rate,

Simple use of a helmet could save 5 QALYs in a motorcycle-related head injury

Health risk assessment for occupational lead exposure

policy• 649 female lead workers• Exposure assessment: blood lead• Hazard identification: lead can impair IQ of

offspring of lead workers• Dose response: < 30 ug/dl reversible

> 30 ug/dl irreversible

. Risk characterization: estimation of QALY loss due to different policy

Chuang HY, et al. J Toxicol Environ Health 2005 ;68:1485-96

No. of different blood lead levels and estimated N of offspring

age stratum

ASFR <10 offspring 10-19 offspring 20-29 offspring 30-39 offspring

<20 0.017 4 0.07 12 0.20 19 0.32 18 0.31

20-24 0.092 14 1.29 17 1.56 33 3.04 34 3.13

25-29 0.149 6 0.89 21 3.13 27 4.02 38 5.66

30-34 0.068 3 0.20 23 1.56 39 2.65 36 2.45

35-39 0.016 6 0.10 17 0.27 30 0.48 38 0.61

40-44 0.002 2 0.00 6 0.01 21 0.04 21 0.04

>45 0 1 0.00 6 0.00 11 0.00 19 0.00

total   36 2.55 102 6.75 180 10.56 204 12.19

Table 1 Numbers of prospective offspring from female lead workers in 1991. (ASFR - age specific fertility rate)

No. of different blood lead levels and estimated N of offspring

age stratum

ASFR 40-49 offspring 50-59 offspring >60 offspring total offspring

<20 0.017 9 0.15 5 0.09 3 0.05 70 1.19

20-24 0.092 7 0.64 3 0.28 0 0.00 108 9.94

25-29 0.149 20 2.98 5 0.75 0 0.00 117 17.43

30-34 0.068 14 0.95 5 0.34 5 0.34 125 8.50

35-39 0.016 10 0.16 1 0.02 2 0.03 104 1.66

40-44 0.002 6 0.01 6 0.01 3 0.01 65 0.13

>45 0 11 0.00 9 0.00 3 0.00 60 0.00

total   77 4.90 34 1.47 16 0.43 649 38.85

Table 1 (Continued)

No. of worker with blood lead >10 ug/dl

No. of offspring with blood lead >10 ug/dl

Potential utility loss

(QALY)

Distribution of blood lead in 1991:

10-29 (ug/dl) 282 17.3 51.6

30-59 (ug/dl) 331 19.0 164.4

Total 216.0

Policy 1: Improve industrial hygiene

reduce 5 ug/dl in blood lead 567 33.1 169.5

reduce 10 ug/dl in blood lead 511 29.6 126.8

reduce 15 ug/dl in blood lead 425 24.1 92.3

Policy 2: Raise employment age

up 5 years 613 29.8 174.6

up 10 years 613 18.2 107.4

Sensitivity analysis (different ASFRs):

1991 613 36.3 216.0

5-year average 613 36.9 219.6

Table 3 Estimated utility loss in QALY from 2 different occupational health policies

Cost of illness approach:

• Human capital left over for determinant xi

WA(t| xi): work ability function

• Direct medical cost of determinant xi

Cost(t| xi): medical cost function

)dt|()]|([ ii xtSxtWE A

)dt|()]|([ ii xtSxtCostE

Monthly cost (NT$) for hemodialysis

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

0 5 10 15 20 25 30 35 40 45 50Duration of Hemodialysis(month)

Cost(NTD)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Survival Rate

mean_costmedian_costSurvival Rate

Lifetime cost (NT$) for hemodialysisAnnual cost

Discount rate

Lifetime cost

mean median mean median

Out patient clinic

476,553 606,800 0% 3,870,084 4,927,820

2% 3,303,139 4,205,923

4% 2,890,398 3,680,375

Hospitalization 43,133 24,600 0% 350,279 199,776

2% 298,965 170,510

4% 261,608 149,204Total 422,863 578,100 0% 3,434,073 4,694,748

2% 2,931,001 4,006,994

4% 2,564,760 3,506,303

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

Conclusion: for risk/impact assessment in health and medicine

• The QALY or life year gained or loss can be estimated for comparative risk/impact assessment of occupational and environmental health

• Lifetime medical cost and human capital cost saved by prevention can also be quantified and compared with all other health care services

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

Lee HY, et al. How many quality-adjusted life years can a helmet save for a motorcyclist when head injury occurs? Am J Public Health 2009 (accepted)

THANK YOU FOR YOUR ATTENTION

• 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 )

)dt|()]|([ xitSxitUE

)dt|()]|([ xitSxitQolE