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1 DOH94-DC-1048 凃

2 1 Abstract Hib (CP) 19 Hib PP 20 Hib AI 21 I (ID) Hib Hib Hib I

3 HRQL 34 QALY Hib (CP) 39 Hib PP 41 Hib AI 42 I (ID) Hib Hib 48 Hib II

4 ICD_9 Hib ICD_9 HRQL 8993 Hib / ICD_ Hib 5 Hib Hib Decision Tree Model III

5 b Hib 5 Hib 6-12 Hib Hib 1.9 Hib Hib Hib Hib 0-5 Hib Hib Hib Hib 1

6 Hib 92 3 Hib Quality-adjusted life-years(qalys) Incremental cost effectiveness CSF 57 Hib CSF Hib HIB Hib QALY 99% QALY HIB b 2

7 Abstract According to the statistics of World Health Organization, there were about 3 million cases of Hemophilus influenza type b (Hib), causing 400,000 to 700,000 deaths each year globally. In prevaccination era, there were 20,000 children less than 5 years old infected with Hib each year in the United States. The incidence of Hib among children 6-12 months old was 180 per 100,000 population in the US. In Taiwan, there have been 109 invasive Hib cases reported during 1996 to Serious complications of Hib included hydrocephalus, encephalitis, mental retardation, hearing defect, motor function deficit and death. The incidence of Hib among children less than 5 years old was 1.9 per 100,000 population, far less than that in the western countries. Due to the low incidence, Hib vaccination has never been included into national immunization program in Taiwan. However, given the severe consequences of Hib and its unknown incidence in Taiwan, the necessity of Hib vaccination in Taiwan needs to be further evaluated. The purposes of this study were to describe the epidemiology of Hib among children less than 5 years old in Taiwan and conduct the cost-effectiveness analysis of Hib vaccination program. 3

8 In order to estimate the incidence of Hib, the following steps were taken: 1. Chart review; 2. estimating the number of cases whose bacteria had been cultured; 3. estimating the range of positive results; 4. calculating total number of hospital visits of Hib cases; 5. estimating total number of Hib cases; and 6. calculating the Hib incidence. In cost-effectiveness analysis, the cost was estimated by vaccinating 3 doses of Hib vaccine to the 2003 birth cohort during 0 to 5 years old. The effectiveness was expressed by quality-adjusted life-years (QALYs) and compared with the cost of vaccination. The sensitivity analysis was done by assuming 80%, 90%, and 99% vaccine efficacy. The results showed that if the proportion of CSF test was low (57%), the estimated number of Hib cases were 110.7, 54.0, and 31.8 during 2001 to 2003, if the proportion of CSF test was high (77%), the number of Hib cases were 81.9, 40.0, and The annual incidence of Hib meningitis ranged between 4.68 per 100,000 in 2001 and 1.49 per 100,000 in If 75% of Hib related diseases manifested as meningitis, there would have been 31.3 to Hib cases among children less than 5 years old per year, the estimated annual incidence would have been 1.98 to 8.44 per 100,000 population. 4

9 The cost-effectiveness of Hib vaccination program increased as the vaccine efficacy increased, however, the cost was too high. If the vaccine efficacy was 99%, the cost of each unit increase in QALY reached nearly 790,000 NT dollars, far more than the average GNP of 450,000 NT dollars in Taiwan. Therefore, the Hib vaccination program was not recommended to be included in the national vaccination program in Taiwan. Keywords: hemophilus influenza type b, Vaccine, Meningitis, Incidence, Cost-effectiveness analyis. 5

10 Hib Hib Hib Hib Hib [1] Hib Hib 3-5[2] Hib Hib Hib Hib 2 Hib Hib Hib Hib 6

11 Hib Hib [3,4] Hib [3-6] Hib [7-9] Hib Hib Hib 3~4 Hib Hib Hib Hib 峯 [10] Hib HIV H [11] Hib 20~50 Hib Hib 10~20 [12] Hib 7

12 Hib Hib 1986~ Hib Hib 44 Hib 1 Hib 5 77 CSF Hib CSF 6 CSF 2 Hib Hib Hib 8

13 9

14 Hib / < %3981.3%3175.6%1568.2%787.5% %612.5%24.9%313.6%112.5% > %36.2%819.5%418.2% 00% 89 Hib Hib Hib CSF Hib Hib Hib (population-based) CSF 10

15 1~2 Hib [13] Hib Hib Shepond et al. [14] Hib QALY(quality-adjusted life year) 78 1 Hib Hib

16 5.60 Levine et al.1998 Hib 1 [13] WHO Hib [13] (herd immunity) Hib Hib Hib ($1582 ) DALY ( $35 ) (best buy) [15] Hib Hib Hib Hib Hib Hib Hib Hib Hib 12

17 Hib 13

18 0-5 Hib Hib Hib Hib Hib Hib 92 3 Hib Hib Quality-adjusted life-years(qalys) incremental CE incrementa l CE = Cost,intervention 1- Cost,intervention 2 Effectiveness,intervention 1- Effectiveness,intervention 2 Cost EffectivenessQALY 3 14

19 (Discount rate) Cost Discount cost = Cost t (1+ r) Costintervention r3 tyears lost 15

20 : 0-5 Hib Hib Hib Hib HIB <10 28(60.9%) 39(81.3%) 31(75.6%) 15(68.2%) (13.0%) 6(12.5%) 2(4.9%) 3(13.6%) >60 12(26.1%) 3(6.2%) 8(19.5%) 4(18.2%) Hib (Meningitis) (Epiglottitis) (Bacteremia) (Pneumonia) (Cellulitis) (Arthtitis) 16

21 CSF Hib Hib Hib Hib Hib ICD ~ ~ ICD9 ICD_ Meningitis due to Coxsackie virus ( ) 17

22 047.1 Meningitis due to ECHO virus ( ) Other specified viral meningitis ( ) Unspecified viral meningitis( ) Hemophilus meningitis( ) Pneumococcal meningitis( ) Streptococcal meningitis( ) Staphylococcal meningitis( ) Meningitis in other bacterial diseases classified elsewhere( ) Meningitis due to other specified bacteria ( ) Anaerobic meningitis(2001)( ) Meningitis due to Gram-negative bacteria, not elsewhere classified(2001)( NEC) Meningitis due to other specified bacteria(2001) ( ) Meningitis due to unspecified bacterium ( ) Cryptococcal meningitis( ) Meningitis in other fungal diseases ( ) 18

23 321.2 Meningitis due to viruses not elsewhere classified ( ) Meningitis due to trypanosomiasis ( ) Meningitis in sarcoidosis( ) Meningitis due to other nonbacterial organisms classified elsewhere( ) Nonpyogenic meningitis( ) Eosinophilic meningitis( ) Chronic meningitis( ) Meningitis, unspecified( ) (ICD9) CSF (CP) (CP)[0-5 CSF A]/[ 0-5 N] 19

24 Hib PP A Hib Hib Hib- Hib (O+) proxy 1 0 ICD ICD9 ICD9 CSF 20

25 CSF Hib CSF Hib Hib (PP)={[ Hib ]+[ Hib ]}/{0-5 CSF } Hib AI

26 (ICD-9-CM) ICD-9-CM 047.0~ ~ ICD-9-CM 0,Hib 0-5 AI I Hib AI Hib PP (CP) I 22

27 I=(AI*PP)/(CP) ID ID ID=(I / 0-5 )*100,000 Hib Hib Hib Hib Decision Tree Model ( ) 1 1-efficacy100%

28 /3 510 B 60%

29 Hib 0-5 Hib Hib

30 26

31 92 3 Hib Hib Hib ,076 a. 1. b 1,200 1,

32 Hib DTP ,076 b. = Hib DTP 10 c. =( ) 28

33 12 d. =( ) /12 /22 /2 1. : e. =( ) 1. Hib 29

34 Hib 39 C 2% 3. ( /12 /22 ) ICD_9 30

35 HIB ICD_9 (Meningitis) (Hemiplegia) (Epilepsy) (Deafness and Hearing Lost) (Mental Retardation) (Epiglottotos) (Bateremia) (pneumonia) (Cellulitis) (Septic Arthritis) ICD_ v v18.4 v79.9 v ICD9 ICD9 Hib Hib 31

36 a. b. c. d. e % % % % % % % % % % % Hib 3 32

37 4 a. b. c. a. 50 b. 18 c. 50 Hib indirect a b c d e f

38 HRQL Health utility index quality-adjusted life years(qalys) HRQL HRQL HRQL HRQL Efficacy 0.8 Efficacy 0.9 Efficacy

39 Efficacy 0.8 Efficacy 0.9 Efficacy QALY Quality-adjusted life-years(qalys) HRQL QALY lost QALY lost 1 discounted QALY lost. decision tree model incremental cost effectiveness [ QALY QALY] /[ 35

40 ] incrementa l CE = Cost,intervention 1- Cost,intervention 2 Effectiveness,intervention 1- Effectiveness,intervention 2 Cost EffectivenessQALY 3 (Discount rate) Cost Discount cost = Cost t (1+ r) Costintervention r3 tyears lost 36

41 0-5 Hib Hib 10 Hib 8993 Hib /10 Age All ages All ages All ages Hib

42 ICD9 N 1 CSF% CSF % 6 Virus % 7 % 8 % total ICD_

43 4. 5. CSF 6.CSF ~ ~ ICD 047.0, ICD ICD ICD / / /237 ICD9 ICD (CP) 77.2 CSF

44 CSF (ICD ) CSF CSF CSF CSF ICD

45 CSF CSF 77.2 CSF 5777 Hib PP Hib 95 Hib 95 CSF CSF CSF /24,

46 0.239 Hib PP {[ HIB ]+[ Hib ]}/{0-5 CSF } [ ]/[183]= 1.22% CSF Hib 1.22 Hib AI ,173 2,5231, ICD_ ICD9 N % n % n % , ,

47 , , total 5, , , Hib I (1)(3) (AI) Hib PP (CP) 90 CP 57 I=[AI*PP]/CP=(5173*1.22%)/57%=

48 90 (AI=5173) 91 (AI=2523) 92 (AI=1486) CP=57% CP=77% CSF CSF age year , , , , , ,039 1,749, , , , , , ,703 1,674, , , , , , ,540 1,577,

49 Hib ,076 a. =( )*3*227,076=126,452,947.5 b. = = 20/2 3227,0766,812,280 c. =( ) = ,07616,349,472 d. =( ) /12 /22 /2 =452,259/12/22/2 3227, ,506,617.5 e. =( ) 45

50 =476*3*2%*227,076 6,485,290.6 f. ( /12 /22 ) = 452,259/12/22 3 *2%*227,076 23,340,264.7 Hib 126,452, ,812,280 16,349, ,506, ,485, ,340, ,946, N

51 Efficacy 0.8 (0.8) 597,333,102 (0.97) (0.001) 968,258,565 (0.2) (0.999) 149,183,942 (0.05) 0 (0.03) (0.001) 32,737,713 (0.95) (0.999) 0 (0.8) 215,532,563 (0.35) (0.001) 83,655,515 (0.2) (0.999) 53,829,258 (0.05) 0 (0.65) (0.001) 801,683,829 (0.95) (0.999) 0 Efficacy 0.9 1,714,775,609 32,737, ,017, ,683,829 1,747,513,322 1,154,701,165 47

52 (0.9) 671,999,740 (0.97) (0.1) (0.001) 127,677,868 (0.999) 7,459,197 (0.05) 0 (0.03) (0.001) 32,727,585 (0.95) (0.999) 0 (0.9) 242,474,133 (0.35) (0.1) (0.001) 57,608,057 (0.999) 26,914,629 (0.05) 0 (0.65) (0.001) 801,683,829 (0.95) (0.999) 0 Efficacy 0.99 (0.99) 739,199,714 (0.97) (0.001) 13,199,925 (0.01) (0.999) 7,459,197 (0.05) 0 (0.03) (0.001) 32,727,585 (0.95) (0.999) 0 (0.99) 266,721,546 (0.35) (0.001) 5,760,806 (0.01) (0.999) 2,691,463 (0.05) 0 (0.65) (0.001) 801,683,829 (0.95) (0.999) 0 807,136,805 32,727, ,864, ,996, ,683,829 1,128,680, ,858, ,586, ,173, ,683,829 1,076,857,644 Hib 80 Hib HRQL

53 QALY 3 discount QALY lost , , QALY Efficacy 80% number of death years lost total years lost HRQL QALY Discount QALY Efficacy 90% Efficacy 99% Hib

54 QALY 6 3 incremental cost effectiveness QALY 20 5 HIB QALY incremental cost effectiveness QALY QALY 78 7 Efficacy Program Total cost 1 Total Incremental Incremental Incremental effective- cost Effective- CE ness 1 ness 80% Vaccination No Vaccination ( ) ( ) 90% Vaccination

55 No Vaccination % Vaccination No Vaccination

56 Hib 5 B B 20,000 Hib 12, B Hib Hib CSF CSF CSF /10 52

57 5.57/ Hib Hib 75 Hib Hib CSF 5 Hib Hib [1,7,17-22] 5 Hib Hib /100, N/A N/A 53 Hib

58 N/A b Hib Hib CSF Hib (22) 82 54

59 b Hib QALY 99% QALY (BEST BUY) Hib CE >125 19, ,

60 Hib Hib 56

61 catch up plan catch up plan Hib Hib Hib catch up plan catch up plan catch up plan

62 catch up plan hib catch up plan Hib Hib 1,200 1,500 30,31 58

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