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Economic evaluation of a 2-dose hepatitis B vaccination regimen for adolescents |
Levaux H P, Schonfeld W H, Pellissier J M, Cassidy W M, Sheriff S K, Fitzsimon 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 A 2-dose hepatitis B virus (HBV) vaccination regimen (Recombivax HB; 10 microg/1.0 mL given at 0 and 4-6 months) was compared with the current 3-dose vaccination regimen (Recombivax HB; 5 microg/0.5mL given at 0, 1, and 6 months) for adolescents (11-15 years of age).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised adolescents (aged 11-15 years) receiving either the 2-dose or 3-dose HBV vaccination regimen in three settings: public schools, public health clinics, and private sector settings in USA. The study population had no previous HBV infection or vaccination and no personal reasons to refuse vaccination. "This age group was selected because it is the only group for which the 2-dose regimen is indicated and because efficacy data were available".
Setting Three settings were examined: public schools, public health clinics, and private sector settings. The economic analysis was carried out in the USA.
Dates to which data relate Effectiveness and resource data were mainly derived from studies published in 1995 and 2001. Prices were adjusted to 2001 dollars.
Source of effectiveness data Effectiveness data were derived from a review/synthesis of the literature and estimates of effectiveness based on opinions.
Modelling A decision analytic model was used to examine short-term and lifetime scenarios for an adolescent cohort receiving the two different regimens. In the short-term analysis, the vaccination programme costs were compared for the two regimens. In the lifetime analysis, the model also incorporated long-term disease costs for those individuals who contract HBV.
Outcomes assessed in the review The outcomes assessed from the literature and used as model inputs were the percentage of patients seroprotected and the following probabilities related to HBV: asymptomatic and symptomatic HBV, chronic HBV (chronic persistent, chronic active, cirrhosis, primary hepatocellular cancer, and primary hepatocellular cancer given cirrhosis), acute HBV (fulminant or non-fulminant HBV), and hospitalised or non-hospitalised patients within those suffering from non-fulminant HBV.
Study designs and other criteria for inclusion in the review The study designs were not explicitly reported. The two main studies used as sources of data for input into the decision model were Margolis et al (1995) and Cassidy et al (2001). Margolis et al used a decision analytic model to carry out an economic analysis of HBV prevention. Cassidy et al carried out a randomised trial to compare the 2-dose and 3-dose regimens. Data for the proportion of adolescents developing vaccine-induced immunity were taken from recommendations made by the Immunization Practices Advisory Committee.
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 two primary studies used as inputs into the model were those by Margolis et al (1995) and Cassidy et al (2001).
Methods of combining primary studies Primary studies were combined in a narrative fashion to provide inputs into the decision model. The lifetime clinical and economic consequences associated with HBV infection were updated from the Margolis study. Data for the proportion of adolescents developing vaccine-induced immunity were taken from recommendations made by the Immunization Practices Advisory Committee. The degree of seroprotection resulting from partial or complete 2- or 3-dose regimens was obtained from Cassidy et al.
Investigation of differences between primary studies Results of the review The percentage of patients seroprotected were 72.8% after one dose and 99.2% after two doses in the two-dose regimen and 44% after one dose, 89.4% after two doses and 98.3% after three doses in the three-dose regimen.
The probabilities related to HBV were 0.6 for asymptomatic HBV and 0.4 for symptomatic HBV, 0.15 for chronic HBV, 0.25 for chronic persistent HBV, 0.25 for chronic active HBV, 0.25 for cirrhosis, 0.125 for primary hepatocellular cancer, and 0.125 for primary hepatocellular cancer given cirrhosis, 0.85 for acute HBV, 0.007 for fulminant HBV, 0.993 for non-fulminant HBV, 0.12 for hospitalised patients, and 0.88 for non-hospitalised patients within those suffering from non-fulminant HBV.
Methods used to derive estimates of effectiveness Authors' assumptions were used to derive estimates of effectiveness. In addition, unpublished results from a (telephone) questionnaire survey carried out by the authors were used to estimate the compliance rates from each health care setting.
Estimates of effectiveness and key assumptions The authors assumed that an adolescent with vaccine-induced immunity would not develop HBV infection, even if exposed to HBV, whereas an adolescent with no protective response was assumed to have a 5% chance of lifetime HBV infection. The overall compliance rates for the 3-dose regimen and the 2-dose regimen were 85.9% and 88.9% in public schools, 60.2% and 79.7% in public health clinics, and 68% and 79% in the private sector, respectively.
Measure of benefits used in the economic analysis The outcome measures derived from the decision model were the overall probability of any vaccination, of seroprotection, and of preventing infection. Life-years gained and HBV infections prevented were the main benefit measures used in the economic analysis, but their actual number was not reported.
Direct costs Both short- and long-term direct costs were measured. A detailed breakdown of costs was not provided, but the main categories of costs were preparation work of each vaccine dose administration (including vaccine acquisition), administration and disposal of vaccine doses, and follow-up of patients who may have missed a scheduled dose. The resources assessed included advertising and promotion materials used to encourage vaccination, equipment used in programme set-up, vaccine and vaccine-related materials, and staff time required for administrative and clinical duties. For the public sector, Centers for Disease Control and Prevention contract prices were used for vaccine costs and the national average Medicaid reimbursement rates for administration costs. Private sector drug costs represented national average reimbursement rates obtained from samples of health plans. Private sector administration costs reflected the average per dose reimbursement for administration found in a subset of health plans. Other costs of resources consumed by the vaccination programme in each health care setting were estimated either by applying unit costs to each item or by using the total costs indicated on the questionnaires. For the analysis of lifetime costs, discounting was carried out at rate of 5% per annum. Estimation of total costs and quantities was derived using modelling. Costs were adjusted to 2001 dollars using the medical component of the consumer price index. The study reported average and incremental costs.
Statistical analysis of costs Deterministic costs were reported.
Indirect Costs Among the long-term costs of HBV infection, taken from the study by Margolis et al, were indirect costs. Assumptions were made that individuals were employed productively between the ages of 20 and 65 years. Average lifetime earnings during the period of Margolis et al's study were estimated from the US Bureau of Labor Statistics. Costs were discounted at 5% per year. Costs included loss of earnings as a result of illness, as well as work time lost in medical care visits and the consequences of premature mortality measured in terms of lost productivity. Estimation of quantities and costs was derived using modelling. Costs were adjusted to 2001 dollars using the medical component of the consumer price index.
Sensitivity analysis Both one-way and multivariate (using Monte Carlo simulations) sensitivity analyses were conducted to test the robustness of the model to changes in the values of all input variables. Most variables were varied from 50% (lower limit) to 150% (upper limit) of the base-case values. For the assessment of short-term costs in the multivariate analyses, the model was run allowing the compliance for the 3-dose vaccine and the cost of vaccine administration to vary over the chosen ranges. For the lifetime analysis, in addition to these variables, the probability of HBV infection given no protective response and the cost of HBV infection also were allowed to vary in the simulation.
Estimated benefits used in the economic analysis The overall probability of any vaccination with the 3-dose and 2-dose vaccines was 0.968 in public schools, 0.972 in public health clinics, and 0.940 in the private sector.
The probabilities of seroprotection with the 3-dose and 2-dose vaccines were 0.906 and 0.939 in public schools, 0.843 and 0.918 in public health clinics, and 0.833 and 0.893 in the private sector.
The probabilities of preventing infection with the 3-dose and 2-dose vaccines were 0.045 and 0.047 in public schools, 0.042 and 0.046 in public health clinics, and 0.042 and 0.045 in the private sector.
A 5% discount rate was used.
Cost results In the public schools, short-term costs per person were $69.76 for 3-dose and $80.89 for 2-dose.
Respective lifetime costs per person were $90.04 for 3-dose and $93.96 for 2-dose.
In the public health clinics, short-term costs person were $45.75 for 3-dose and $59.87 for 2-dose.
Respective lifetime costs per person were $79.58 for 3-dose and $77.54 for 2-dose.
In the private sector, the short-term costs per person were $92.75 for 3-dose and $110.26 for 2-dose.
Respective lifetime costs were $128.81 for 3-dose and $133.36 for 2-dose.
Lifetime costs were discounted at 5%.
Synthesis of costs and benefits An incremental cost-effectiveness analysis was carried out to combine costs and benefits. In the short-term analysis, the cost per infection prevented in public schools was $1,550 for 3-dose and $1,721 for 2-dose. The incremental cost-effectiveness ratio (ICER) for the 2-dose schedule with respect to the 3-dose schedule was $5,565.
In public health clinics, the cost per infection prevented was $1,089 for 3-dose and $1,302 for 2-dose. The ICER was $3,530.
In the private sector, the cost per infection prevented was $2,208 for 3-dose and $2,450 for 2-dose. The ICER was $5,837.
In terms of lifetime costs (using a 5% discount rate for costs and life years), the cost per infection prevented in public schools was $2,001 for 3-dose and $1,999 for 2-dose. The ICER was $1,960.
In the public health clinics, the cost per infection prevented was $1,895 for 3-dose and $1,686 for 2-dose, with the latter being the dominant strategy.
In the private sector, the cost per infection prevented was $3,067 for 3-dose and $2,964 for 2-dose. The ICER was $1,517.
In public schools, the ICER in terms of cost per year of life gained was $1,246.
In public health clinics, the 2-dose was the dominant strategy in terms of cost per life-year gained.
In the private sector, the ICER was $964 in terms of cost per year of life gained.
Sensitivity analyses identified cost per dose of vaccine and the probability of completing the regimens as the most sensitive model variables for both the short-term and lifetime cost scenarios.
In terms of the per-dose cost of the vaccine, the threshold values (defined as the per-dose cost at which the expected costs for the two regimens were equal) were $21.60 for school-based programmes, $24.90 for public health clinics, and $52.00 for private sector third-party payers. "The use of Monte Carlo simulation of 1,000 iterations supports the robustness of results".
Authors' conclusions The authors concluded that "when the long-term consequences of HBV infection were included, the 2-dose regimen would be cost-effective compared with the 3-dose regimen in all settings and cost saving in public health clinic settings". The estimated cost per life-year saved was lower than those accepted as thresholds in the health care system.
CRD COMMENTARY - Selection of comparators The justification for the selection of the two comparators was clearly reported, with the potentially more cost-effective 2-dose regimen being compared to the current, widely accepted strategy for HBV vaccination among adolescents. You, as a user of this database, should assess whether it represents a widely used intervention in your own setting.
Validity of estimate of measure of effectiveness It is difficult to assess the validity of the effectiveness measure as the authors provided little discussion as to why other primary studies were not included in the review/synthesis. The studies they did include appeared to be highly relevant in terms of providing data for input into the decision model. However, the primary studies and other data sources were few in number. In addition, the authors did not always justify their assumptions regarding estimates of effectiveness measures. However, estimates were comprehensively investigated using sensitivity analyses.
Validity of estimate of measure of benefit The summary benefit measure used in the economic analysis was the number of life-years gained. This appeared appropriate, especially as regards the decision model, although details on the results were not reported.
Validity of estimate of costs Both direct and indirect costs were included in the analysis. In addition, variations in costs were subjected to rigorous sensitivity analyses, although costs were treated deterministically in the base case analysis. Unit costs and quantities of resources used were reported only for a few items. The price year was reported.
Other issues The authors discussed their findings in the context of other relevant studies. The findings relate to a number of different settings, therefore the generalisability of the results should be good, as it was enhanced by the performance of several sensitivity analyses on all model inputs. The authors do not appear to have presented their results selectively.
Implications of the study The implications of the study are that the introduction of a 2-dose vaccination programme could have a significant impact on the clinical and economic outcomes of HBV vaccination in a wide range of settings.
Bibliographic details Levaux H P, Schonfeld W H, Pellissier J M, Cassidy W M, Sheriff S K, Fitzsimon C. Economic evaluation of a 2-dose hepatitis B vaccination regimen for adolescents. Pediatrics 2001; 108(2): 317-325 Other publications of related interest Margolis HS, Coleman PJ, Brown RE, et al. Prevention of hepatitis B virus transmission by immunization: an economic analysis of current recommendations. JAMA 1995;274:1201-1208.
Cassidy WM, Watson B, Ioli VA, Williams K, Bird S, West DJ. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatircs 2001;107:626-631.
Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adolescent Health Services /economics /utilization; Age Factors; Antibody Formation /immunology; Community Health Services /economics /utilization; Cost-Benefit Analysis; Decision Support Techniques; Dose-Response Relationship, Immunologic; Health Behavior; Health Care Costs; Hepatitis B /economics /immunology /prevention & Hepatitis B Vaccines /administration & Humans; Immunization Programs /economics /utilization; Immunization Schedule; Models, Economic; School Health Services /economics /utilization; United States; Vaccination /economics; control; dosage /economics AccessionNumber 22001001541 Date bibliographic record published 31/10/2002 Date abstract record published 31/10/2002 |
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