The cost-effectiveness of vaccination against Lyme disease Shadick N A, Liang M H, Phillips C B, Fossel K, Kuntz K M

Transcription

1 The cost-effectiveness of vaccination against Lyme disease Shadick N A, Liang M H, Phillips C B, Fossel K, Kuntz K M 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 use of vaccination to prevent Lyme disease. Type of intervention Primary prevention. Economic study type Cost-utility analysis. Study population The study population comprised persons living in areas of moderate to high risk of Lyme disease, in the USA. Moderate to high risk was approximately defined as the risk to persons living in areas with yearly attack (by the Ixodes tick) rates of approximately 1% per season. Setting The setting was community care. The study was carried out at the Harvard School of Public Health in Massachusetts, USA. Dates to which data relate The effectiveness data were derived from studies published between 1983 and Resource use data were derived from the model. The cost data were taken from different sources, but were updated to 1998 US dollars. Source of effectiveness data The effectiveness data were derived from a review of published studies. Modelling A decision-analytic model (Markov model) was developed to evaluate the cost-utility of vaccination in comparison with no vaccination. The model simulated a cohort of 10,000 individuals through 10 seasons (years), with each individual facing a 1% chance of contracting Lyme disease each year. Outcomes assessed in the review The model parameters assessed in the review were: vaccination parameters such as efficacy, compliance, risk of adverse effects associated with vaccination, and persistence of the effect; Page: 1 / 6

2 Lyme disease parameters such as the attack rate per season, erythema migrans, disseminated Lyme disease, arthritic sequelae, cardiac sequelae and neurologic sequelae. Several treatment efficacy parameters were also estimated. For the health-related quality of life adjustments see the 'Measure of Benefits used in the Economic Analysis' section. Study designs and other criteria for inclusion in the review A systematic review of the literature was not performed and no inclusion criteria were specified. 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 Twenty-two studies were included in the review. Methods of combining primary studies The specific method used to combine the studies was not reported, although it was stated in the article that the efficacy and compliance rates from two studies were pooled. Investigation of differences between primary studies Results of the review The following were the base-case values for the model parameters. For vaccination with 2 shots, efficacy was 0.63 and compliance was For vaccination with 3 shots, efficacy was 0.87 and compliance was The risk of adverse effects associated with vaccination was 0.06 and persistence of the effect was 3. The attack rate per season from Lyme disease was 0.01, and 0.7 of patients who contracted Lyme disease and who presented with erythema migrans were treated. The probability of dissemination among patients not adequately treated for early Lyme disease was Among this group, the probability of arthritic sequelae was 0.73, cardiac sequelae 0.07 and neurologic sequelae The treatment efficacy was 0.95 for patients with erythema migrans, 0.85 for arthritic sequelae, 0.90 for cardiac sequelae and 0.90 for urologic sequelae. The risks of treatment reactions were 0.04 (minor) and (major) with doxycycline, and 0.06 (minor) and (major) with ceftriaxone. The authors made some significant assumptions. Estimates of effectiveness and key assumptions Page: 2 / 6

3 The authors assumed that the course of Lyme disease was no different between vaccinated and non-vaccinated populations. They also assumed that partially compliant persons were only protected for the first season. Measure of benefits used in the economic analysis Both cases averted and QALYs gained were used as measures of benefit. The health-related quality of life weights were estimated from a random sample of 105 residents from Nantucket Island (MA), an area with one of the highest incidences of Lyme disease, in the USA. A visual analogue scale was used to rate the health states. The rating scores were converted to utilities using a power transformation (details provided). The estimated utilities were multiplied by the expected duration in each health states to estimate the QALYs over a 10-year period. The QALYS were discounted at a rate of 3% per annum. Direct costs The costs and life-years were discounted at an annual rate of 3%. This was relevant as the model simulated 10 seasons (i.e. 10 years). The quantity/cost boundary adopted was that of society. The direct costs were for the management and treatment of Lyme disease, vaccination, and the adverse effects associated with vaccination. The cost estimates for the management and treatment of Lyme disease were derived primarily from a study published in 1992, then updated to 1998 US dollars using the Medicare component of the consumer price index. The other source was the 1998 pharmacy costs at the Brigham and Women's Hospital. The unit costs were reported. The costs were discounted at a rate of 3% per annum. Statistical analysis of costs The costs were treated deterministically. Indirect Costs Morbidity costs were assumed to have been incorporated in the QALY results in the base-case. However, this assumption was relaxed by including the indirect costs in a sensitivity analysis. The indirect costs were taken from a cost of illness study (Maes et al., see Other Publications of Related Interest). The costs were discounted at a rate of 3% per annum. The range of indirect costs used in the sensitivity analysis was not reported. Currency US dollars ($). Sensitivity analysis Sensitivity analyses were performed on all variables to assess the robustness of the results. The clinical probabilities, efficacy, vaccine efficacy and cost estimates were varied over a plausible range, according to estimates from the literature. The utilities and seasonal attack rates were varied over a range that reflected the variation in the patients' responses. The cost of vaccination was varied from $50 to $300 for a 3-shot series as well as an annual booster scenario. One-way and 2-way sensitivity analyses were performed. Estimated benefits used in the economic analysis In the base-case analysis, without discounting, 202 cases of Lyme disease were averted during a 10-year period for every 10,000 persons vaccinated who lived in an endemic area. With discounting the figure became 196. The incremental QALY gain was 18 without discounting and 16 with discounting. The discount rate was 3%. Cost results Page: 3 / 6

4 The cost associated with the vaccination of all residents in the selected endemic area was $1,405,603. This cost became $1,393,637 when discounted at 3%. The cost associated with treating Lyme disease was $1,766,885 for the 'no vaccination' strategy and $1,407,268 for the 'vaccination' strategy. The discounted values (3%) were $1,551,108 (no vaccination) and $1,203,222 (vaccination), respectively. The total cost was $1,766,885 (discounted value $155,108) for the 'no vaccination' strategy and $2,812,871 (discounted value $2,596,859) for the 'vaccination' strategy. Synthesis of costs and benefits Incremental cost-effectiveness ratios (ICERs) were calculated. The strategy of vaccination, compared with no vaccination, for persons living in areas of moderate to high risk of Lyme disease had an incremental cost of $62,300/QALY gained and cost per case averted of $5,300. Given the ranges used, the results were most sensitive to the treatment effectiveness and cost of vaccination for the 3-shot series. If the treatment effectiveness was 80% of the base-case, the ICER of vaccination would be $18,800/QALY. If the treatment was 100% effective, the ICER would be $301,900/QALY. If the vaccination costs were only $50, then the cost-effectiveness ratio of vaccination was $6,900/QALY gained. If the vaccination costs were as high as $300, then the ICER of vaccination was $145,300/QALY gained. The results of all the sensitivity analyses were reported comprehensively and clearly in the paper. Authors' conclusions Vaccination against Lyme disease appears to have only been economically attractive for individuals who have a seasonal probability of Borrelia burgdorferi (Lyme disease) infection of greater than 1%. CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparator (no vaccination) was clear. In terms of other comparators, however, the authors did not consider simple measures such as providing information and support to residents living in highly endemic areas in relation to precautionary measures (e.g. use of tick repellents and protective clothing). You must decide whether it represents a valid comparator in your setting. Validity of estimate of measure of effectiveness The model parameters were obtained from a non-systematic review of the literature. Given the uncertainty in the results, all parameters were tested over plausible ranges in the sensitivity analyses with clear and comprehensive reporting. The authors acknowledged that the persistence of vaccination efficacy has not been demonstrated and that both the duration and protection varies on an individual basis. They also acknowledged that additional information is necessary to determine the true duration of protection. Validity of estimate of measure of benefit Quality of life estimates were specifically derived from residents living in an area of high risk of Lyme disease. Therefore, the validity of the results is likely to be good. The benefits were appropriately discounted at a rate of 3% since they were realised over a time period of longer than 2 years. Validity of estimate of costs Most of the costs were included given the societal perspective of the study. The costs were derived from several sources. Some of the cost estimates were taken from Although the costs were appropriately updated using the Medicare component of the consumer price index, if possible, it would have been better if more recent estimates of the Page: 4 / 6

5 costs had been used. The unit costs and the price year were reported, which helps the reproducibility of the results. The costs were appropriately discounted at a rate of 3% since they were incurred over more than 2 years. The indirect costs, though not included in the base-case, were included in the sensitivity analysis. A good feature of the cost results was that the total costs of the vaccination programme were presented under various scenarios. This enables decision-makers to choose the scenario that is most likely to arise in their locality and to evaluate the likely impact of the programme on their health care budget. Other issues The robustness of the results was appropriately tested using sensitivity analyses. However, decision-makers should be aware that the ICER of vaccination compared with no vaccination varied substantially depending on the rate of endemicity of Lyme disease. The results were also sensitive to assumptions about the persistence of vaccine efficacy, treatment effectiveness associated with Lyme disease and utility weights. In addition, vaccination against Lyme disease does not protect against other tick-borne illness and may actually increase the incidence of other tick-born illnesses, as individuals may be less likely to use precautions. Also, little is known about the duration of protection against Lyme disease that vaccination offers. Additional information is necessary to determine the true duration of protection against Lyme disease through vaccination. The model and its results were thoroughly reported and the authors' conclusions reflected the scope of the analysis. Implications of the study The authors have stated that additional information is needed on the true protection provided by vaccination, as very little is known about this. Guidelines are necessary for the appropriate use of vaccination, both from an individual and societal point of view. This study demonstrated that in areas with a seasonal rate of Lyme disease of greater than 1%, vaccination of individuals compares somewhat favourably with other preventive treatments. Residents living in these areas may be appropriate recipients for vaccination against Lyme disease. Source of funding Supported in part by the National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases), grant numbers AR-43653, AR and AR-36308; and a KO8 Mentored Clinical Scientist Award. Bibliographic details Shadick N A, Liang M H, Phillips C B, Fossel K, Kuntz K M. The cost-effectiveness of vaccination against Lyme disease. Archives of Internal Medicine 2001; 161: PubMedID Other publications of related interest Steere AC, Sikand V, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outersurface lipoprotein A with adjuvant. New England Journal of Medicine 1998;339: Sigal LH, Zahradnik JM, Lawrence DA. A vaccine consisting of recombinant Borrelia burgdorferi outer surface protein A to prevent Lyme disease. New England Journal of Medicine 1998;339: Meltzer M, Dennis DT, Orloski KA. The cost-effectiveness of vaccinating against Lyme disease. Emerging Infectious Diseases 1999;5: Magid D, Schwartz B, Craft J, Schwartz JS. Prevention of Lyme disease after tick bites: a cost-effectiveness analysis. New England Journal of Medicine 1992;327: Nichol G, Dennis DT, Steere AC, et al. Test-treatment strategies for patients suspected of having Lyme disease: a cost- Page: 5 / 6

6 Powered by TCPDF ( effectiveness analysis. Annals of Internal Medicine 1998;128: Indexing Status Subject indexing assigned by NLM MeSH Cost-Benefit Analysis; Costs and Cost Analysis; Decision Support Techniques; Humans; Lyme Disease /economics /prevention & control; Lyme Disease Vaccines /economics; Prognosis; Quality of Life; Quality-Adjusted Life Years; Risk Factors; United States AccessionNumber Date bibliographic record published 29/02/2004 Date abstract record published 29/02/2004 Page: 6 / 6