Vaccination Against Herpes Zoster and Postherpetic Neuralgia
Vaccination Against Herpes Zoster and Postherpetic Neuralgia
Comparing incremental cost with incremental effectiveness for a new HZ vaccination policy versus current therapeutic strategy (no vaccination) from a national health insurance perspective in the 70–79-year-old population produces the following ICERs: €9513 per QALY gained, €2240 per HZ case avoided and €3539 per PHN case avoided. Vaccinating this age group in France makes particular sense since they endure a higher epidemiological burden and increased disease severity. This age-related specific benefit counteracts the expected physiological diminution of vaccine efficacy with age. However, when considering a vaccination implementation strategy/policy, recommending a similar age group that already undergoes influenza vaccination may facilitate greater vaccination uptake, and extending the vaccination program to all persons over 65 years of age would still be very cost effective, with an ICER of €12,304/QALY compared with no vaccination. Sensitivity analyses showed that the pain classification and epidemiology data used, utilities, vaccine price and discount rates considered have the greatest impact on ICERs. Nevertheless, even when using the most unfavorable parameters, the study produced ICERs under the most favorable threshold defined by the WHO (one GDP per capita), which is the one that we chose to retain for this analysis.
This study is the first cost–effectiveness analysis of vaccination to prevent HZ and PHN neuralgia in France. Our cost–effectiveness study identified an ICER well below the two cost–effectiveness thresholds defined by the WHO. Our results match those from several European studies that have found similar cost-effective results despite applying different sets of empirical data. The results of the current model included extensive sensitivity analyses that have explored the effects of numerous data and which are considered good modeling practice.
Another strength of this study is its use of a model that has already been used in economic analyses in other countries. Furthermore, using specific French-based epidemiological and economic data as well as clinical efficacy data from a large-sample-size (38,500), randomized controlled clinical trial combined to increase the veracity of the evidence and provide more definitive country-specific results. In addition to a large amount of evidence from randomized clinical trials to support vaccine efficacy, use of conservative parameters at each decision point, especially related to vaccine efficacy duration and waning of efficacy assumptions, as well as numerous sensitivity analyses, provided more certainty of the overall benefits of HZ vaccination. Conclusions are not only similar to those obtained when using the same model in other countries but also to findings obtained from different model structures in Europe, the USA or Canada. These findings strengthen the good cost–effectiveness profile of HZ vaccination whatever methodology has been used to measure it.
The model was validated both internally and externally, indicating that it is robust. Indeed, it is reasonable to suggest that the model reflects the natural progression of the disease as well as a valid estimation of the clinical benefit of vaccination since it closely predicted the number of HZ cases and nearly the same number of PHN cases as was reported in the pivotal clinical trial.
This study has some limitations that are mainly related to the availability of country-specific data. The absence of French disease-specific utilities was tested in sensitivity analyses by using alternative value sources, and even if results showed a moderate impact on results, ICERs remained within reasonable thresholds. In addition, the study does not model reduction in HZ pain in patients who have HZ despite vaccination, nor does it account specifically for ophthalmic zoster cases, which are more complicated. These factors could result in an underestimation of the potential health benefits and cost savings from HZ vaccination. Although this study does address QALYs from persistent long-lasting PHN pain, it does not account for loss in QoL from other sources related to HZ. Indeed, even in uncomplicated HZ, acute pain, numbness and itching affect QoL greatly, leaving patients with enduring impairments in physical and emotional functioning. PHN extends this painful experience 90 days or more after the initial HZ outbreak, with allodynia and persistent pain described by most patients as moderate to severe (pain scores ≥4 on a 0–10 scale). Affecting all four health domains – physical, psychological, emotional and social – PHN may plague individuals with fatigue, insomnia, depression, anxiety, interference with social roles and leisure activities, and impaired basic and instrumental activities of daily living. Another limitation concerns the cohort-based model used. Although this model is sufficient to estimate the cost–effectiveness of an HZ vaccination strategy, further improvements (multicohort approach) could be considered to more accurately capture all public health benefits and estimate the true budget impact. Model structure would also require adaptation in a context of childhood varicella vaccination (currently not recommended in France). Should a clear statement on this pediatric vaccination impact on HZ incidence be established, its relative impact on HZ vaccination benefits should be evaluated using a specifically developed dynamic model.
Based on epidemiological, clinical and economic evidence, country-specific decisions may vary. Key criteria that led to recommending and/or funding HZ vaccination in some European countries include the high burden and severity of HZ disease in the older population, lack of suitable alternative treatment, significant vaccine efficacy in reducing burden of illness, and the long-term efficacy duration and evidence of cost–effectiveness for the HZ vaccine. In Europe, to date, three countries have issued national recommendations related to HZ vaccination, at ≥50 years (Austria), ≥60 years (Greece) and 70–79 years (UK). In addition, HZ vaccine reimbursement has been approved in Sweden for patients aged ≥50 years.
Discussion
Comparing incremental cost with incremental effectiveness for a new HZ vaccination policy versus current therapeutic strategy (no vaccination) from a national health insurance perspective in the 70–79-year-old population produces the following ICERs: €9513 per QALY gained, €2240 per HZ case avoided and €3539 per PHN case avoided. Vaccinating this age group in France makes particular sense since they endure a higher epidemiological burden and increased disease severity. This age-related specific benefit counteracts the expected physiological diminution of vaccine efficacy with age. However, when considering a vaccination implementation strategy/policy, recommending a similar age group that already undergoes influenza vaccination may facilitate greater vaccination uptake, and extending the vaccination program to all persons over 65 years of age would still be very cost effective, with an ICER of €12,304/QALY compared with no vaccination. Sensitivity analyses showed that the pain classification and epidemiology data used, utilities, vaccine price and discount rates considered have the greatest impact on ICERs. Nevertheless, even when using the most unfavorable parameters, the study produced ICERs under the most favorable threshold defined by the WHO (one GDP per capita), which is the one that we chose to retain for this analysis.
Strengths
This study is the first cost–effectiveness analysis of vaccination to prevent HZ and PHN neuralgia in France. Our cost–effectiveness study identified an ICER well below the two cost–effectiveness thresholds defined by the WHO. Our results match those from several European studies that have found similar cost-effective results despite applying different sets of empirical data. The results of the current model included extensive sensitivity analyses that have explored the effects of numerous data and which are considered good modeling practice.
Another strength of this study is its use of a model that has already been used in economic analyses in other countries. Furthermore, using specific French-based epidemiological and economic data as well as clinical efficacy data from a large-sample-size (38,500), randomized controlled clinical trial combined to increase the veracity of the evidence and provide more definitive country-specific results. In addition to a large amount of evidence from randomized clinical trials to support vaccine efficacy, use of conservative parameters at each decision point, especially related to vaccine efficacy duration and waning of efficacy assumptions, as well as numerous sensitivity analyses, provided more certainty of the overall benefits of HZ vaccination. Conclusions are not only similar to those obtained when using the same model in other countries but also to findings obtained from different model structures in Europe, the USA or Canada. These findings strengthen the good cost–effectiveness profile of HZ vaccination whatever methodology has been used to measure it.
The model was validated both internally and externally, indicating that it is robust. Indeed, it is reasonable to suggest that the model reflects the natural progression of the disease as well as a valid estimation of the clinical benefit of vaccination since it closely predicted the number of HZ cases and nearly the same number of PHN cases as was reported in the pivotal clinical trial.
Limitations
This study has some limitations that are mainly related to the availability of country-specific data. The absence of French disease-specific utilities was tested in sensitivity analyses by using alternative value sources, and even if results showed a moderate impact on results, ICERs remained within reasonable thresholds. In addition, the study does not model reduction in HZ pain in patients who have HZ despite vaccination, nor does it account specifically for ophthalmic zoster cases, which are more complicated. These factors could result in an underestimation of the potential health benefits and cost savings from HZ vaccination. Although this study does address QALYs from persistent long-lasting PHN pain, it does not account for loss in QoL from other sources related to HZ. Indeed, even in uncomplicated HZ, acute pain, numbness and itching affect QoL greatly, leaving patients with enduring impairments in physical and emotional functioning. PHN extends this painful experience 90 days or more after the initial HZ outbreak, with allodynia and persistent pain described by most patients as moderate to severe (pain scores ≥4 on a 0–10 scale). Affecting all four health domains – physical, psychological, emotional and social – PHN may plague individuals with fatigue, insomnia, depression, anxiety, interference with social roles and leisure activities, and impaired basic and instrumental activities of daily living. Another limitation concerns the cohort-based model used. Although this model is sufficient to estimate the cost–effectiveness of an HZ vaccination strategy, further improvements (multicohort approach) could be considered to more accurately capture all public health benefits and estimate the true budget impact. Model structure would also require adaptation in a context of childhood varicella vaccination (currently not recommended in France). Should a clear statement on this pediatric vaccination impact on HZ incidence be established, its relative impact on HZ vaccination benefits should be evaluated using a specifically developed dynamic model.
Based on epidemiological, clinical and economic evidence, country-specific decisions may vary. Key criteria that led to recommending and/or funding HZ vaccination in some European countries include the high burden and severity of HZ disease in the older population, lack of suitable alternative treatment, significant vaccine efficacy in reducing burden of illness, and the long-term efficacy duration and evidence of cost–effectiveness for the HZ vaccine. In Europe, to date, three countries have issued national recommendations related to HZ vaccination, at ≥50 years (Austria), ≥60 years (Greece) and 70–79 years (UK). In addition, HZ vaccine reimbursement has been approved in Sweden for patients aged ≥50 years.
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