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Cost effectiveness of hepatitis B vaccination at HIV counseling and testing sites |
Kim S Y, Billah K, Lieu T A, Weinstein M C |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The study examined four strategies for vaccinating against hepatitis B virus (HBV) in potentially high-risk adults attending freestanding human immunodeficiency virus (HIV) counselling and testing sites (CTSs) or sexually transmitted disease (STD) clinics. The strategies were:
routine vaccination without screening for prior immunity or infection (routine vaccination);
screening for antibody to hepatitis B core antigen (anti-HBc), an HBV marker of current or past infection, with an initial dose given during the first visit and with follow-up doses based on screening results (screening with initial dose);
screening and vaccination based on screening results (screening and vaccination); and
no intervention.
In terms of vaccine administration, adult doses of 10 microg per dose for RECOMBIVAX-HB or 20 microg per dose for ENERGIX-B were administered according to the current standard three-dose regimen (0, 1 and 6 months, 0, 2 and 4 months, or 0, 1 and 4 months).
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population The study population comprised a hypothetical cohort of high-risk adults aged 20 to 49 years who were attending CTSs and STD clinics for HIV testing.
Setting The setting was CTSs and STD clinics. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data were derived from studies published between 1974 and 2005. Data on resource use and costs came from studies published between 1995 and 2003. The price year was 2000.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of published studies.
Modelling A decision model was constructed to simulate the clinical and economic consequences of the four alternative strategies under examination. The target populations in each setting were subdivided into 39 sub-groups stratified by gender, age, race/ethnicity and risk level. The model was developed as a decision tree embedded with Markov nodes.
In the first phase of the decision tree, which was assumed to last 6 months, individuals were offered screening and/or vaccination. Depending on their acceptance of the vaccine, dose completion, and previous vaccination and/or infection history, they could achieve immunity, remain infected, or remain susceptible to HBV infection.
In the second phase, individuals entered a corresponding Markov model of the natural history of HBV infection and progressed through various health states. These health states included acute infection, chronic hepatitis, compensated cirrhosis, decompensated cirrhosis, inactive chronic infection, liver cancer and liver transplantation.
The model was run over a time horizon of 45 to 75 years (depending on the average age of each sub-group). A detailed description of the decision model and a graphical representation of the Markov model were provided in the study.
Outcomes assessed in the review The outcomes estimated from the literature were:
the profile of clients attending the freestanding CTSs or STD clinics (gender, race/ethnicity, age structure and risk profile),
data on the natural history of HBV infection,
the accuracy of screening,
vaccination behaviour, and
health-related quality of life weights.
Study designs and other criteria for inclusion in the review It was not stated whether a systematic review of the literature was undertaken to identify the primary studies. Clinical data came from multiple sources, including the National Health and Nutrition Examination Survey III, the 2000 HIV Counseling and Testing System database, and the Centers for Disease Control and Prevention. Utility weights were obtained from the Medical Expenditure Survey Panel. Details of the other studies were not provided.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included The clinical evidence came from approximately 25 primary studies.
Methods of combining primary studies The primary studies were not combined as each study provided a discrete series of estimates.
Investigation of differences between primary studies Results of the review At baseline, the percentage of high-risk individuals was 15.2% in freestanding CTSs and 8.2% in STD clinics. The percentages of men were 55% (CTSs) and 55.6% (STD clinics), respectively.
In freestanding CTSs the majority of patients were white and non-Hispanic (55.4%), while in STD clinics most individuals were black and non-Hispanic (49.9%).
In both settings, most patients were aged between 20 and 29 years (36.4% in freestanding CTSs and 43.5% in STD clinics).
HBV prevalence, prior hepatitis B vaccination rate and HBV incidence were age-, gender- and race-dependent, and were reported for the 39 sub-groups of patients.
In terms of the natural history of HBV infection:
the likelihood of symptomatic infection was 30% (range: 20 to 40),
the rate of hospitalisation after symptomatic infection was 17% (range: 12 to 25),
the rate of fulminant cases among hospitalisation was 4%,
the rate of liver transplantation among fulminant cases was 39% (range: 13 to 58),
the rate of successful transplantation was 87%,
the rate of death among fulminant cases was 70% (range: 63 to 93), and
the likelihood of developing chronic hepatitis was 6% (range: 3 to 10).
Transition probabilities in cases of chronic hepatitis, invasive carrier, and decompensated compensated cirrhosis, liver cancer and transplantation, were also reported.
The sensitivity of screening was 0.98 (range: 0.8 to 1) and the specificity was 0.95 (range: 0.8 to 1).
The vaccine protection rate was 90% for a complete series, 75% for two doses, and 30% for one dose. Protective immunity continued life long and no booster doses were necessary.
The acceptance rate for vaccination was 67% for freestanding CTSs and 74% for STD clinics.
For dose completion, the assumed first and second return rates were 44% and 38%, respectively, for freestanding CTSs and 53% and 57% for STD clinics. The third return rate was 30% for both settings.
The health-related quality of life weights were as follows:
susceptible/immune, 1.00;
inactive carrier, 0.99 (range: 0.95 to 1);
chronic hepatitis, 0.94 (range: 0.85 to 1);
compensated cirrhosis, 0.82 (range: 0.46 to 1);
decompensated cirrhosis, 0.54 (range: 0.19 to 1);
liver cancer, 0.49 (range: 0.15 to 0.95);
liver transplantation, 0.86 (range: 0.66 to 1).
Measure of benefits used in the economic analysis The summary benefit measures used were the life-years (LYs) and quality-adjusted life-years (QALYs). Utility weights required for the calculation of QALYs were derived from the literature. The EQ-5D questionnaire was used to estimate quality of life weights for all the health states of the Markov model. Cases of HBV infection prevented were also reported. A discount rate of 3% was applied to future health benefits.
Direct costs The analysis of the costs was performed from a societal perspective. It included not only the direct costs such as those associated with vaccination (vaccine, supplies, administration and overhead costs) and avoided future HBV-related medical treatment, but also non-medical costs such as travel expenses. The direct costs associated with HBV treatment covered acute hepatitis, chronic hepatitis, inactive cancer, cirrhosis, hepatocellular carcinoma and liver transplantation. However, the costs of antiviral therapy and liver transplantation were excluded from the base-case analysis. The unit costs were reported only for a few items, as most costs were presented as macro-categories. Few details of resource use were presented. The estimation of the costs and quantities of resources used was based on published studies and data from the Centers for Disease Control and Prevention. All costs were adjusted to 2000 values (which represented the price year) using the medical care component of the Consumer Price Index. Discounting was relevant, as the costs were incurred during a long time, and an annual rate of 3% was used.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were included in the analysis, which was appropriate given the societal perspective. These comprised the cost of time spent for travel, waiting and receiving treatment. However, productivity costs due to future HBV-related diseases were not included. The unit costs and resource quantities appear to have been derived from a published study, although no information on the calculation of indirect costs was provided. As in the analysis of the direct costs, the price year was 2000 and an annual discount rate of 3% was applied.
Sensitivity analysis Univariate sensitivity analyses were carried out to assess the robustness of the cost-effectiveness ratios to variations in several model inputs. Such inputs included HBV prevalence, immunity rates due to previous vaccination, acceptance rate of vaccination and screening, return rates, sensitivity and specificity of anti-HBc test, sensitivity and specificity of self-reporting of prior vaccination, anti-HBc test cost, vaccine administration cost, clients' time and travel costs for return visits, and HBV-related disease treatment costs. Alternative ranges of values appear to have been based on published evidence. A sub-group analysis was also performed in which the 39 sub-groups of clients stratified by gender, age, race/ethnicity and risk level were considered.
Estimated benefits used in the economic analysis All results refer to a cohort of 100,000 individuals.
In the setting of freestanding CTSs, the expected QALYs and LYs saved in comparison with no intervention were, respectively, 155 and 155 with routine vaccination, 61 and 60 with screening and vaccination, and 152 and 152 with screening with initial dose.
In the setting of STD clinics, the expected QALYs and LYs saved in comparison with no intervention were, respectively, 214 and 214 with routine vaccination, 107 and 108 with screening and vaccination, and 209 and 209 with screening with initial dose.
The cases of HBV infection prevented with respect to no intervention were 452 for routine vaccination, 176 for screening and vaccination, and 442 for screening with initial dose in freestanding CTSs. The corresponding values in STD clinics were 628 for routine vaccination, 316 for screening and vaccination, and 613 for screening with initial dose.
Cost results All results refer to a cohort of 100,000 individuals.
In the setting of freestanding CTSs, the additional costs (in millions) in comparison with no intervention were $0.68 with routine vaccination, $0.85 with screening and vaccination, and $1.22 with screening with initial dose.
In the setting of STD clinics, the additional costs (in millions) in comparison with no intervention were $0.74 with routine vaccination, $0.96 with screening and vaccination, and $1.32 with screening with initial dose.
Synthesis of costs and benefits Incremental cost-effectiveness ratios and cost-utility ratios were calculated in order to combine the costs and benefits of the alternative strategies.
In the two settings, the incremental analysis revealed that both screening and vaccination and screening with initial dose were dominated (they were more costly and less effective) by routine vaccination. Compared with no intervention, routine vaccination had an incremental cost per QALY gained and an incremental cost per LY saved of $4,400 in the setting of freestanding CTSs, and an incremental cost per QALY gained and an incremental cost per LY saved of $3,500 in the setting of STD clinics.
At a national level (260,000 and 340,000 clients aged 20 to 49 years attending freestanding CTSs and STD clinics annually, respectively), the routine vaccination strategy prevented 3,310 cases of new HBV infection (undiscounted) and would save 1,130 QALYs and 1,130 LYs at an additional cost of $4.3 million compared with no intervention.
The sub-group analysis revealed that the ranking of alternatives did not change in any sub-group of clients. However, more favourable results were achieved for patients who were younger, of non-white race, and who had a history of HBV-related risk factors. In no case did the incremental cost per LY or QALY exceed the value of $40,000.
The base-case results were stable to plausible variations in the model inputs, as carried out in the sensitivity analysis. In effect, routine vaccination dominated the alternative strategies in all scenarios. The variables with the greatest impact on the results were the clients' time and travel costs for return visits and the discount rate.
Authors' conclusions The integration of routine hepatitis B vaccination programmes into existing human immunodeficiency virus (HIV) freestanding counselling and testing sites (CTSs) and sexually transmitted disease (STD) clinics represented a cost-effective public health intervention in the USA.
CRD COMMENTARY - Selection of comparators The rationale for the selection of the comparators was clear and the choice of the three screening strategies was appropriate. The doses and frequency of vaccination were provided. A strategy of no intervention was also considered, and might reflect actual patterns of care in several settings. You should decide whether these are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The clinical data used in the decision model were derived from published sources. The authors did not report the details of a systematic review of the literature, thus it was unclear whether the primary studies were identified using a systematic approach or whether they were used selectively. National databases were used for some data but, in general, few details of the primary sources were provided. This presents difficulties in terms of assessing the validity of the primary studies. The authors did not discuss the issue of the heterogeneity of the primary studies and the primary estimates were not combined. The impact of key clinical estimates on the results of the analysis was tested in the sensitivity analysis.
Validity of estimate of measure of benefit The use of LYs and QALYs as the summary benefit measures was appropriate, not only because these measures capture the impact of the interventions on quality of life and survival, which are two relevant dimensions of health for patients at risk of HBV infection, but also because they can be compared with the benefits of other health care interventions. Discounting was performed in accordance with US guidelines. Utility weights were obtained using the EQ-5D, a standard and appropriate questionnaire.
Validity of estimate of costs The authors stated that the analysis was carried out from a societal perspective. However, the indirect costs associated with productivity losses of future HBV-related diseases were not included. These costs might represent an important component of the analysis given that the target population was in the workforce. The authors did not provide a breakdown of the cost items, and most costs were presented as macro-categories. Similarly, few details of the quantities of resources used were presented. This will limit the possibility of replicating the analysis in other settings. Most cost categories were derived from published cost analyses. Statistical analyses of the costs were not performed, but extensive sensitivity analyses were carried out. Therefore, the cost results may be transferable to other settings. The price year was reported, which will help in reflating costs in other time periods.
Other issues The authors did not compare their findings with those from other studies. They also did not address the issue of the generalisability of the study results to other settings. However, the extensive use of sensitivity analysis enhances the external validity of the study. The authors noted that the main limitation of the analysis was the use of data from mixed sources in the model. Several assumptions were made to make some data from different databases comparable. However, the sensitivity analysis showed that none of the clinical data had any substantial effect on the results of the study. The results of the sensitivity analyses were not reported extensively, which would have been useful.
Implications of the study The study results support the implementation of a routine vaccination programme for HBV infection among high-risk adults attending existing CTSs.
Source of funding Supported by the National Immunization Program via the Joint Initiative in Vaccine Economics under a cooperative agreement with the Association of Teachers of Preventive Medicine.
Bibliographic details Kim S Y, Billah K, Lieu T A, Weinstein M C. Cost effectiveness of hepatitis B vaccination at HIV counseling and testing sites. American Journal of Preventive Medicine 2006; 30(6): 498-506 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information
Rich JD, Ching CG, Lally MA, et al. A review of the case for hepatitis B vaccination of high-risk adults. Am J Med 2003;114:316-8.
Mast EE, Williams IT, Alter MJ, Margolis HS. Hepatitis B vaccination of adolescent and adult high-risk groups in the United States. Vaccine 1998;16 Suppl:S27-9.
Beutels P. Economic evaluations of hepatitis B immunization: a global review of recent studies (1994-2000). Health Econ 2001;10:751-74.
Weber B, Michl U, Muhlacher A, et al. Evaluation of the new automated enzymun-test anti-HBc plus for the detection of hepatitis B virus core antibody. Intervirology 1998;41:17-23.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Ambulatory Care Facilities; Cost-Benefit Analysis; Counseling; Female; HIV Infections /diagnosis; Hepatitis B /epidemiology /prevention & Hepatitis B Vaccines; Humans; Male; Middle Aged; Prevalence; Risk Factors; United States /epidemiology; Vaccination /economics; control AccessionNumber 22006001047 Date bibliographic record published 31/01/2007 Date abstract record published 31/01/2007 |
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