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1 David B. Rein, PhD a, Katherine A. Hiks, MS a, Kathleen E. Wirth, BA a, Kaafee Billah, PhD b, Lyn Finelli, DrPH b, Anthony E. Fiore, MD, MPH b, Thomas J. Hoerger, PhD a, Beth P. Bell, MD, MPH b and Gregory L. Armstrong, MD b a RTI International, Atlanta, Georgia; b Centers for Disease Control and Prevention, National Center for Infetious Diseases, Division of Viral Hepatitis, Atlanta, Georgia ( ) (1999 ) (ost-effetiveness); (hepatitis A); (vaination); Markov (publi poliy); 1 (eonomis); 2003 (ACIP) FLF = fulminant liver failure HAV = hepatitis A virus ACIP = Advisory Committee on Immunization Praties QALY = quality-adjusted life year NNDSS = National Notifiable Disease Surveillane System CDC = Centers for Disease Control and Prevention (quality-adjusted life year) Address orrespondene to David 1 B. Rein, PhD, RTI Inter-national, Flowers Rd, Suite 119, Atlanta, GA (Advisory Committee on Immunization Praties) PEDIATRICS

2 [12] ( ) ACIP d [1, 2] (year of life) [3] (FLF) (QALY) [13] (HAV) ACIP ( ) [4] Markov ( [5, 6] (ACIP) ACIP [7] ACIP ACIP [8] ACIP ACIP ACIP ( 33 1) [9, 10] FLF [11] ACIP REIN et al

3 ( ) 1 y 18 y ( ) [14] ( 1) (life years) QALY (age-speifi) 3% / y [14] [4] 5 15 y 1 ( ) [4] 1994 [9] 1990 [15] 1.4% 1990 (NNDSS) [14] PEDIATRICS

4 1 (Base-Case Value) [41] (2003 ) [41] (2003 ) [41] (2003 ) a Samandari [9] (2004 ) Samandari [9] (2004 ) Samandari [9] (2004 ) / % 1.4 Samandari [9] (2004 ) CDC [26] (2004 ) CDC [26] (2004 ) b Fiore [11] (2005 ) 0.25 Fiore [11] (2005 ) 0.01 Fiore [11] (2005 ) / miu ml Van Herk [30] (2000 ) Van Herk [30] (2000 ) / % 0 4 y 20 Van Herk [30] (2000 ) 5 95 y 5 / miu ml Delem [42] (1993 ) y Armstrong [4] (2002 ) 5 14 y Armstrong [4] (2002 ) y Armstrong [4] (2002 ) Shiodt [17] ( y CDC [14] (2001 ) 5 14 y CDC [14] (2001 ) y CDC [14] (2001 ) y CDC [14] (2001 ) y CDC [14] (2001 ) 0.23 Armstrong [4] (2002 ) 0 4 y 0.05 CDC [14] (2001 ) 5 14 y 0.17 CDC [14] (2001 ) y 0.23 CDC [14] (2001 ) 642 REIN et al

5 40 59 y 0.19 CDC [14] (2001 ) y 0.2 CDC [14] (2001 ) / CDC [27] (2004 ) CDC [27] (2004 ) d 1 6 CDC [14] (2001 ) [21] 274 Berge [2] (2000 ) 821 Berge [2] (2000 ) Dalton [19] (1996 ) Berge [2] (2000 ) Berge [2] (2000 ) ( 1 ) Hauboldt [20] (1999 ) ( ) Berge [2] (2000 ) 667 CDC 0.41 Jaobs [24] (2002 ) 0.83 Mittmann [25] (2001 ) /d 34.4 Berge [2] (2000 ) /d 67.8 Berge [2] (2000 ) /d 3 ( a b 2 d 1 1 (National Hospital Disharge Survey) FLF FLF [2, 19, 20] 1 / 3 [21] 50% [16] FLF NNDSS [2, 22] FLF FLF FLF QALY [17] (United Network for Organ Sharing) [18] NNDSS QALY PEDIATRICS

6 2 (time tradeoff) 1 y ACIP [2] QALY 1 2 a 3 b QALY QALY [26] QALY QALY QALY QALY QALY ( ) FLF QALY / QALY / d a 1 2 ACIP 6 b ACIP d [24,25] b [27] [11] 2003 (Vaines for Children program) [28] 59% (CDC) / 200 [29] 1 / 100 [23] [30, 31] REIN et al

7 3 1 2 ) 20 miu / ml [31] 1 2 y ACIP 1 2 a 3 b 1 37% 1 10 y 20% y 30% y 13% 41 y 2 20 y 10% y 90% 41 y / n QALY d / n / ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) QALY ( ) d QALY d a 1 2 ACIP 6 b 3 33 d QALY 11 ACIP % 1 1y 100% 2 1y 5y 20% [30] 5% (P. Van Damme MD PhD 2005 [9] % 3 0.8% HAV QALY QALY QALY 2005 PEDIATRICS

8 (17 50 ) ( 25%) (0% 5%) QALY ( ) HAV (0 2x) (0 2x) 2005 (0 2x) (0 2x) QALY / 2 1 QALY (4.9%) HAV (disounted life years) QALY ( 3) FLF ( 2) QALY [10] REIN et al

9 QALY 13.2 QALY 4.5 ( ) ( ) 1 2 QALY 4 QALY QALY QALY QALY QALY / 1 000s QALY PEDIATRICS

10 ( 2) ( QALY 4.2 ) [33] 17 ( 1 HIV ) 1 QALY ( QALY 3.4 ) [34] [35] % QALY QALY [36, 37] QALY 7.1 HAV ( ) QALY (ACIP 6.2 ) ( QALY 13.8 ) [38] [39] [40] ( QALY 13.2 ) [37] QALY 82% 5 15% % % % ( 3) % 3 99% ( QALY 2.8 ) (HIV) HAV ( QALY 3.6 ) [32] 648 REIN et al

11 ) ACIP 5y ACIP [14] ( ) 1 O Connor JB, et al. Hepatology 1999;30: Berge JJ, et al. Hepatology 2000;31: Craig AS, et al. N Engl J Med 2004;350: Armstrong GL, et al. Pediatris 2002;109: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 2005;54: Food and Drug Administration. Havrix produt approval information. Available at: havgsk101705l. htm. Aessed November 3, Advisory Committee on Immunization Praties. MMWR Reomm [35] Rep 1996;45: Advisory Committee on Immunization Praties. MMWR Reomm Rep 1999;48: y 9 Samandari T, et al. Vaine 2004;22: [40] 10 Wasley A, et al. JAMA 2005;294: Fiore A, et al. MMWR Morb Mortal Wkly Rep 2005;54: Reuters Health Information. CDC ommittee reommends routine hepatitis A vaination for hildren. Available at: 14 Centers for Disease Control and Prevention. MMWR Morb Mor- QALY om/viewartile/ Aessed November 3, 2005 [26] NY: Oxford University Press; 1996 tal Wkly Rep 2001;48: Bownds L, et al. J Community Health 2003;28: Gold MR, et al, eds. Cost-Effetiveness in Health and Mediine. 16 National Center for Health Statistis. National Hospital Disharge Survey Publi use data file and doumentation. Hyattsville, MD: National Center for Health Statistis. Available at ftp://ftp.d.gov/pub/health_statistis/nchs/datasets/nhds. ACIP [10] Aessed November 8, 2006 ( 17 Shiodt FV, et al. Am J Gastroenterol 2003;98: United Network for Organ Sharing. Liver Kaplan-Meier patient survival rates for transplants performed Primary diagnosis hepatitis A. Available at: Aessed PEDIATRICS

12 November 10, Dalton CB, et al. Arh Intern Med 1996;156: Hauboldt RH. Cost Impliations of Human Organ and Tissue Transplantations, an Update: Seattle, WA: Milliman, Robertson; Amerian College of Physiians. Preventive strategies for influenza: is influenza prophylaxis ost-effetive? Available at: www. aponline.org/flu/ost_effetiveness_evidene.htm. Aessed Deember 1, Current Population Survey BoLS. Table 2. Median usual weekly earnings of full-time wage and salary workers by age, rae, Hispani or Latino ethniity, and gender, fourth quarter 2003 averages, not seasonally adjusted. Available at: Aessed November 8, Meltzer MI, et al. Vaine 2001;19: Jaobs RJ, et al. Pharmaoeonomis 2002;20: Mittmann N, et al. Dis Manage Health Outomes 2001;9: Centers for Disease Control and Prevention National Immunization Survey. Hyattsville, MD: National Center for Health Statistis; Centers for Disease Control and Prevention. Vaines for Children Program: vaine prie list. Available at: vf/d_va_prie_list.htm. Aessed November 10, Innis BL, et al. JAMA 1994;271: Van Damme P, et al. Lanet 2003;362: Van Herk K, et al. J Med Virol 2000;60: Paltiel AD, et al. N Engl J Med 2005;352: Sanders GD, et al. N Engl J Med 2005;352: Hoerger TJ, et al. Ann Intern Med 2004;140: Jaobs RJ, et al. Pediatr Infet Dis J 2003;22: Shepard CW, et al. Pediatris 2005;115: Lee GM, et al. Pediatris 2005;115: Lieu TA, et al. JAMA 1994;271: Margolis HS, et al. JAMA 1995;274: Armstrong GL, et al. Pediatris 2007;119(1). Available at: www. pediatris.org/gi/ontent/full/119/1/e22 40 Lee GM, et al. Health Qual Life Outomes 2005;3:17 41 National Vital Statistis Reports. Nat Vital Stat Rep 2003;52:10 42 Delem A, et al. Vaine 1993;11: Centers for Disease Control and Prevention. Vaines for Children Program: maximum regional harges for vaine administration by state. Available at: htm#feetable. Aessed August 6, 2004 PEDIATRICS 2007;119(1):e12 e REIN et al