GUE ST E DIT OR I A L

PharmacoEronornics.5 (2) : 85-87; 1994 1170-769(W94.0002-OO85/$01 . .m'O C> Ad;< I n~mationallimited. All righlli ..,served.

Cost Effectiveness of Hepatitis B Immunisation Strategies

ALan L Hillman, 1,2 Ion Blasco,2 Bernard S. Bloom 2,3 and 1. Sanford Schwartz 1.2

Division of General Internal Medicine, School of Medicine, The University of Pennsylvania, Philadelphia. USA

2 Cenler for Health Policy, Leonard Davis ln51itute for Health Economics. The University of Pennsylvania, Philadelphia, USA

3 School of Dema] Medicine, The University of Pennsylvania. Philadelphia, Pennsylvania

AllilOUgh a safe and effective vaccine to prevenl infection with hepatitis B virus (HBV) was intro­duced as early as 1981, HB V today remains the world's most common blood-borne virus, chroni­cally infecting morc than 200 million people world­wide in growing numbers. In the US, for example, the incidence of HBV has increased by 37% in the last 10 years. with approximately 300 000 ad­ditional Americans becoming infected with the vi­rus annually. Serological evidence indicates that 4.8% of the US population has been infected with HBV at some point, reflecting the challenges that stand between the scientific development of a pow­erful preventative measure and its implementation to achieve desired individual and social benefits. Hepatitis B is responsible for substantial morbidity and monality including a spectrum of acute dis­ease, as well as chronic outcomes such as chronic persistent hepatitis, chronic active hepatitis, hepato­cellular carcinoma and cirrhosis.

1. Alternative Vaccination Strategies

The strategy of screening and vaccinating un­protected high-risk populations has been advo­cated since 1982 (Mulley et al . 1982). Recently,

however, the increasing prevalence of HBV and the advent of recombinant. genetically-engineered vaccines have made broader vaccination strategies increasingly attractive, according to several eco­nomic analyses. Although these studies agree that broader vaccination programmes are appropriate and cost effective, there is some disagreement about which specific populations should be tar­geted by an ideal vaccination programme and how the programmes should be implemented.

Universal vaccination programmes have been advocated as cost effecti ve in countries with high and moderate HBV endemicity, suggesting that those countries should begin universally vaccinat­ing their citizens at binh. Examples include Tai­wan. Saudi Arabia, Greece and Spain. In more de­veloped countries like the US where endemicity is lower, more complex vaccination strategies which ide.ntify and immunise high risk individuals also have been considered (Margolis et al. 1990). How­ever, compliance by individuals. physicians and governments with such strategies is low. In addi­tion, many of the patients who contract HBV within the US each year do not belong to a high risk group. Thus, there is substantial additional benefit to be gained from effective implementation of uni-

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versal immunisation programmes. One recent study concluded that HBV vaccination was cost effecti ve not only a mong high risk healthcare workers ex­posed to HBY at least 1 2 times per year, but among lower fi sk healthcare personnel as well (Mauskopf et al. 199 1).

Two recent si mulation models (Bloom et aL 199 1: Krahn & Detsky 1993) evaluated the eco­nomic impl ications of broader vaccination poli ­cies. Both were decision analytic models that con­sidered efficacy. compliance, cost. acute and chronic outcomes, and other factors in various populations. Both concluded that morc widespread vaccinalion programmes are cost effective a nd warranted . One study found that uni versal vacci nation of all citi­zens is cost effecti ve in both the US and Canada, wi th an incremental societal cost of roughly $US30 000 per discounted year of life saved and a third­party incremental cost of roughly $US50 000 per discounted year of life saved ( 1990 US dollars) [Krahn & Detsky 19931. The other concluded that vaccination of neonates born to maternal carriers of HBY, followed by uni versal vaccinat ion of ad­olescents (with a booster vaccin ation given every 10 years thereafter), was the most cost-effective way to prevj!nt hepatitis B (B loom et at. 199 1). This study a lso supported the economic effi ciency of universal vaccination of neonates, and showed that the cost effecti veness o f immun is ing the ge neral adu lt US popu lation was simi lar to that of many common ly used medical interventions (Bloometal . 199 1).

Both of the studies agree that broader vaccina ­tion programmes are appropriate and cost effecti ve compared with not vaccinating, with disagreement confined only to the mostcosl-effecti ve way to im­plement universal vacc ination.

2. Making Sense Out of It All

When and where should hepatitis B vaccination be given? Minor differences in the conclusions of the 2 recent analyses result from the different as­sumptions built into each model. rather than from different philosophies. Most importantly. the stud­ies used different assumptions about the duration

Pharmaco£Conomics 5 (2) 1994

of protection conferred by a full series of 3 vacci­nations. Of course, the longer the period Ihat the vaccine is assumed 10 confer protection, the more cost effect ive its use, and the more :lItracti ve early vaccination becomes. When 5-year protection is assumed, vaccination is cost effective on ly fo r high ri sk individuals such as healthcare workers. Other sens itiv ity ana lyses assume lifetime protection, IO-year protection or a fo rmula of decreasi ng pro­tection with each passing year. Although antibody liues decrease over time after vaccination, epide­miological studies to date have not indicated that such decreases result in reduced protection against HBY in fec tion. However, these studies are only 7 years in durat ion and, therefore, lifelong immunity is far from proven. Antibody ti tre curves remai n compatible with a more limited period of protec­tion (e.g. 10 years) fro m a complete primary im­munisation series.

Compliance is another important variable. Ne­onates are most likely to comply with vaccination, since they are easily accessihle for at least the first of the 3 requi red doses. However, vacc ination rates for preschool children in the US average only about 34% (Goldstein et al. 1993). Combining HBY vac­cination with diphtheria-pertussis-tetanus vacc ina­tion programmes, which are already required by law in some cou ntries, including the US, could facili tate compli ance and access. Alternati vely, however, a vaccine with a limited period of effec­ti veness might be wasted on neonates born to un­infected mothers, suggesting that a uni versal vac­cination programme for adolescents (the highest ri sk grou p by age because of the start of sexual activ ity) might be preferred. In contrast [Q early chi ldhood immunisation, school-mandated vac­cination with diptheria-pertussis-tetanus (OPT), measles-mumps-rubella (MMR) and polio vac­cines have been extremely s uccessful in the US, with over 95% of children immuni sed by age 5. Mandating HB V vaccination (or entrance into sec­ondary school, or establi shing school-based vacci­nation programmes, could help to improve compli­ance among adolescents.

Hepnlilis Imrnuni~lion

3. Conclusions

HBV remains a challenging bUI surmountable problem. N ow that an effec tive vaccine is avail­able, effective delivery strategies must be deve l­oped a nd implemented. If immunity is s hown to be permanent, uni versal immun isation of infants is appropriate. If immunity turns out to be transient, then a 'screen and vacc inate' strategy in neonates is more efficient than a . vaccinate all' strategy, be­cau se nearly all hepatiti s B di sease in the first de­cade of li fe results from vertical transmi ssion at birth. This strategy could be followed by manda­tory vaccination of adolescents, wi th booste r shots gi ven thereafter at interval s consistent with emerg­ing research about the duration of protection con­ferred by the vaccine. In the US, for example, vac­cination could be performed upon entrance into middle o r junior high school, just as children en­te ring elementa ry sc hoo l must show proof of vaccination against polio, meas les and other con­tagious childhood diseases. Unti l the issue of the du ration of immunity is resolved, booster shots should be conside red every 10 years, at least in hi gh risk populations.

Broad educational campaigns should be aimed at both physicians and the public, to help overcome the failure of the US medical community to recog­ni se the risk presented b y HB V and the va lue o f the vacci ne. Physicians' persona l health promo­ti on/di sease preve nti on be havio ur is correlated with the care provided to pati ents (Lewis et a1. 199 1), s uggestin g that inc reasing HBV vaccina­tion of physicians may be a particularly e ffect ive strategy.

The HBY vaccine is a safe, readily available, cost-effec tive intervention that demands increased

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attention and emphasis. Formulated vacci nation strategies need to be implemented and enfo rced. We must use all available means to achieve sub­stantia l improvements in the public health in a cost-effective fash ion. Just like the batt le against smallpox, the battle agai nst HB V can be won, pro­vided that rationa l vaccination strategies are de­signed and pursued aggressively.

References

Bloom BS. Hil1m~n AL. Fendric ~ AM. Schwanz JS. A reappraisal of hepatitis B viru~ vaccination strategies using cost·effectivcncss analysis. Annab of Inte rnal Medicine 118 (4): 298·)06, 1993

Gotdstein KP. Kvil. fl. Daum RS. et al. Accuracy of immunisation histuries prov ided by aduhs accompanying preschool chitdren to a pediauic emergency depanment. Journal Orthe Amcrican Med· ical Association 270 (18): 2 1 9().2 1 9~ . 1993

Hadler Sc. Francis DR. Maynard JE.llIompson SE. Judson FN. et al. Long· ternl imiliunogcnicity and. efficacy of hepatitis B vaccine in h omosuuaJ men. New England Journal of Medicine 31.5: 209· 2 14.1986

Krahn M. Det>;ky AS. Should Canada lind the US un iversally vacci· nate infant>; against hepatitis B1 Medical Dec ision Making 13 ( I ): 4-20.1993

Lewis CEo Clancy C. Schwanz JS. The counseling pnoclices of in ­ternists. Annals of lmemal Medicine 114: 54·S8. 1991

Lo KJ. Lee SD. Tsai YT. Wu TC, Chan CY. el al. Long·lerm immu­nogenicity and eFrlCacy of hepatilis B 'xcine in infantS born to HBeAg-positive HBsAg-<:arrier mochers . He~lology 8: 1647· 1650,1988

Margolis HS. SchaI"LGC. Kane MA. Development of ra:ommenoia­tion for control of hepatitis B virus inf",lions: the role of coo analysis. Vaccine 8 (Supp1.): S81·S8S. 1990

Po.huskopf JA. Bradley CJ. FR'nch MT. Benefilo(:ost analys is of Hepatitis b vaccine programs for occup.:Itionally t~poscd worio;.ers. Journal ofOcrupational Medicine 33 (6): 69 1.698. 1991

Mulley AG. Si lverstein MD. Diensla, JL. tndications for the use of hepatitis B vaccine. based Of! cosI·effectiveneS' analysis. New En. gland Journal of Medicine 307: 644·6.52. 1982

Wainwrighl RB. McMahon RJ . Rulkow LK, Parkinson AJ, Harpsler AP. et al. Protection provided by hepatitis B vaccine in a Yupik Eskimo populatinn. Jou rnal of the American Medical Assoc iation 261 : 2362·2366. 1989

Corrcspondcm.:e and repri nts: Dr A/Ill' L Hillman. uonard Davis

Insutute of Hta lth Economics. 3641 Locust Wal~ . Philude lphia.

PA 1 91~·62 t 8. USA.