Cost-effectiveness of administering 13-valent pneumococcal conjugate vaccine in addition to 23-valent pneumococcal polysaccharide vaccine to adults with immunocompromising conditions

Background

In June, 2012 a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was added to the recommendation for immunocompromised adults who were previously recommended to receive only 23-valent pneumococcal polysaccharide vaccine (PPSV23). PCV13 may be more effective, though it covers fewer disease-causing strains.

Objective

We examined the incremental cost-effectiveness of adding one dose of PCV13 to the pre-2012 recommendation of PPSV23 for adults with 4 immunocompromising conditions who are at increased risk of pneumococcal disease: HIV/AIDS, hematologic cancer, solid organ transplants, and end stage renal disease.

Methods

We used a probabilistic model following a single cohort of 302,397 immunocompromised adults. We used vaccination coverage and disease incidence data specific to each immunocompromising condition. Assumptions about PPSV23 and PCV13 vaccine effectiveness were based on two randomized controlled trials and several observational studies conducted among HIV-infected adults. Because no such studies have been conducted among other immunocompromised populations, we made further assumptions about the relative vaccine effectiveness in those groups. Cost-effectiveness ratios were determined for each condition and for all 4 groups in total.

Results

Our model indicated that adding one dose of PCV13 to adults in the United States with 4 immunocompromising conditions would cost $16 million (in 2009$) but provide off-setting savings of $21 million per cohort from the societal perspective. These savings come largely from decreased medical costs among adults with end stage renal disease. This dose of PCV13 would prevent 57 cases of invasive pneumococcal disease, 619 cases of hospitalized all-cause pneumonia, avert 93 deaths, and save 1360 quality adjusted life years per cohort.

Conclusion

The addition of one dose of PCV13 to the previously recommended PPSV23 doses for adults with selected immunocompromised conditions potentially reduces both disease and costs.     

Cost-effectiveness analyses of monovalent mumps vaccination programs for Japanese children

BackgroundThe most common preventative measure against mumps is vaccination with mumps vaccine. Over 122 countries have implemented mumps vaccine routine immunization programs, mostly via Measles-Mumps-Rubella (MMR) vaccine. In Japan, the unexpectedly high incidence of aseptic meningitis caused by mumps vaccine led to the discontinuation of the MMR national vaccination program in 1993, inadvertently resulting in the re-emergence of mumps. Plans of introducing monovalent mumps vaccine into routine vaccination schedule have become one of the emerging topics in health policy that has warranted the need in evaluating its value for money.MethodsWe conducted cost-effectiveness analyses with Markov model and calculated incremental cost-effectiveness ratios (ICERs) of two different vaccination programs (a single-dose program at one-year-old, a two-dose program with second dose uptakes at five) compared to status quo from both payers’ and societal perspectives. Transition probabilities and utility weights in estimating quality-adjusted life-year (QALY), and disease treatment costs were either estimated or obtained from literature. Costs per vaccination were assumed at ¥6140 (US$58;1US$ = ¥106).ResultsBoth programs reduce disease treatment costs compared to status quo, while the reduction cannot offset vaccination cost. ICER of either program is found to be under ¥5,000,000 (US$47,170)/QALY willingness-to-pay (WTP) threshold from either perspective. Results of probabilistic sensitivity analyses expressed by net monetary benefit indicated that at the WTP threshold, the acceptability is at 92.6% for two-dose vaccination program, 0% for single-dose vaccination program, and 7.4% for current no vaccination program. Two-dose program was optimal among the alternatives. One-way sensitivity analyses revealed that proportion of mumps-related hearing loss among mumps cases and vaccine effectiveness (VE) were key variables in changing the ICERs.ConclusionRoutine vaccination program of single- and two-dose programs were cost-effective from both payers’ and societal perspectives. Between the two, the two-dose vaccination program was observed to be more favorable.     

Cost-effectiveness of 13-valent pneumococcal conjugate vaccine in Switzerland

The 7-valent pneumococcal conjugate vaccine (PCV7) has been shown to be highly cost-effective. The 13-valent pneumococcal conjugate vaccine (PCV13) offers seroprotection against six additional serotypes. A decision-analytic model was constructed to estimate direct medical costs and clinical effectiveness of PCV13 vaccination on invasive pneumococcal disease (IPD), pneumonia, and otitis media relative to PCV7 vaccination. The option with an one-dose catch-up vaccination in children of 15-59 months was also considered. Assuming 83% vaccination coverage and considering indirect effects, 1808 IPD, 5558 pneumonia and 74,136 otitis media cases could be eliminated from the entire population during a 10-year modelling period. The PCV13 vaccination programme would lead to additional costs (+€26.2 Mio), but saved medical costs of -€77.1 Mio due to cases averted and deaths avoided, overcompensate these costs (total cost savings -€50.9 Mio). The national immunisation programmes with PCV13 can be assumed cost saving when compared with the current vaccine PCV7 in Switzerland.     

Cost-effectiveness analysis of the 10- and 13-valent pneumococcal conjugate vaccines in Argentina

Objective

Since the 10-valent pneumococcal conjugate vaccine (PCV-10) and 13-valent pneumococcal conjugate vaccine (PCV-13) were recently licensed for use in Argentina, both vaccines were evaluated to estimate the costs, health benefits and cost-effectiveness of adding a PCV to the routine child immunization schedule.

Methodology

The integrated TRIVAC vaccine cost-effectiveness model from Pan American Health Organization's ProVac Initiative (Version 1.0.65) was used to assess the health outcomes of 20 successive cohorts from birth to 5 years of age. PCV-10 and PCV-13 were each compared to a scenario assuming no PCV vaccination. A 3 + 1 (three doses + booster) schedule and a vaccination price of US$ 20.75 per dose was assumed in the base case for both vaccines.

Results

Introduction of PCV-13 rather than PCV-10 would increase the number of life years gained (LYG) by at least 10%. The number of LYG (and LYG after adjustment for DALY morbidity weights) was 56,882 (64,252) for PCV-10 compared to 65,038 (71,628) for PCV-13. From the health system perspective, the cost per DALY averted was US$ 8973 and US$ 10,948 for PCV-10 and PCV-13 respectively, and US$ 8546 and US$ 10,510 respectively, after incorporating costs saved by households. When PCV13 was compared to PCV10 directly, the additional benefits of PCV-13 was conferred at a cost of US$ 28,147 per DALY averted. Cost-effectiveness was influenced mainly by vaccine price, serotype replacement, pneumonia mortality and discount rate.

Conclusion

Routine vaccination against S. pneumoniae in Argentina would be cost-effective with either PCV-10 or PCV-13. PCV-13, with higher coverage of local serotypes, would prevent more cases of pneumonia, invasive pneumococcal disease, sequelae and deaths with a higher number of LYG and DALYs averted, but PCV-10, due its higher impact in the prevention of AOM, would save more costs to the healthcare system.     

Ten years of experience with the pneumococcal conjugate 7-valent vaccine in children

In children, pneumococcus became the predominant infectious agent, after the routine use of the Hib conjugate vaccine dramatically decreased Haemophilus Influenzae type b prevalence. The incidence of invasive pneumococcal infections (IPI) and of non-invasive infections due to vaccine serotypes (VS) decreased by 80% in Europe along with a 30–40% decrease in the global incidence of IPI in this age group, after the implementation of Prevenar 7^® routine immunization in children below 2 years of age. The decrease of IPI due to VS in other age groups was an indirect benefit. The moderate increase of non-vaccinal serotype IPI incidence did not impede the benefit of the overall program. Serotype 19A was the most frequent and carried resistance to antibiotics. Prevenar 13^®, a second-generation vaccine with six new serotypes, replaced Prevenar 7^® in most countries after 2010, with available evidence of its effectiveness (United Kingdom, US, France).     

Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults

13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014.     

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study

BackgroundPneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010–11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet).MethodsWe compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012–2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose.ResultsThe PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0–88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8–96.1) < 12 months to 85.1% (72.0–92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7–94.7) against fatal PCV13 IPD, 64.5% (43.7–77.6), 83.2% (73.7–89.3) and 85.1% (67.6–93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3–94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4–92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2–96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and ?14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively.ConclusionsPCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.     

The risk of febrile seizures following influenza and 13-valent pneumococcal conjugate vaccines

BackgroundEvidence on the risk of febrile seizures after inactivated influenza vaccine (IIV) and 13-valent pneumococcal conjugate vaccine (PCV13) is mixed. In the FDA-sponsored Sentinel Initiative, we examined risk of febrile seizures after IIV and PCV13 in children 6–23 months of age during the 2013–14 and 2014–15 influenza seasons.MethodsUsing claims data and a self-controlled risk interval design, we compared the febrile seizure rate in a risk interval (0–1 days) versus control interval (14–20 days). In exploratory analyses, we assessed whether the effect of IIV was modified by concomitant PCV13 administration.ResultsAdjusted for age, calendar time and concomitant administration of the other vaccine, the incidence rate ratio (IRR) for risk of febrile seizures following IIV was 1.12 (95% CI 0.80, 1.56) and following PCV13 was 1.80 (95% CI 1.29, 2.52). The attributable risk for febrile seizures following PCV13 ranged from 0.33 to 5.16 per 100,000 doses by week of age.The age and calendar-time adjusted IRR comparing exposed to unexposed time was numerically larger for concomitant IIV and PCV13 (IRR 2.80, 95% CI 1.63, 4.83), as compared to PCV13 without concomitant IIV (IRR 1.54, 95% CI 1.04, 2.28), and the IRR for IIV without concomitant PCV13 suggested no independent effects of IIV (IRR 0.94, 95% CI 0.63, 1.42). Taken together, this suggests a possible interaction between IIV and PCV13, though our study was not sufficiently powered to provide a precise estimate of the interaction.ConclusionsWe found an elevated risk of febrile seizures after PCV13 vaccine but not after IIV. The risk of febrile seizures after PCV13 is low compared to the overall risk in this population of children, and the risk should be interpreted in the context of the importance of preventing pneumococcal infections.     

Cost-effectiveness of varicella vaccine against herpes zoster and post-herpetic neuralgia for elderly in Japan

BackgroundThe extended use of varicella vaccine in adults aged 50 and older against herpes zoster (HZ) was recently approved in Japan, which has raised the need to evaluate its value for money.MethodsWe conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of varicella vaccine immunisation programme for the elderly in Japan. Four strategies with different ages to receive a shot of vaccine were set, namely: (1) 65–84, (2) 70–84, (3) 75–84 and (4) 80–84 years old (y.o.). Incremental cost-effectiveness ratios (ICERs) compared with no programme from societal perspective were calculated. The health statuses following the target cohort are as follows: without any HZ-related disease, acute HZ followed by recovery, post-herpetic neuralgia (PHN) followed by recovery, post HZ/PHN, and general death. The transition probabilities, utility weights to estimate quality-adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Costs of per course of vaccination were assumed at ¥10,000 (US$91). The model with one-year cycle runs until the surviving individual reached 100 y.o.ResultsICERs ranged from ¥2,812,000/US$25,680 to ¥3,644,000/US$33,279 per QALY gained, with 65–84 y.o. strategy having the lowest ICER and 80–84 y.o. strategy the highest. None of the alternatives was strongly dominated by the other, while 80–84 y.o. and 70–84 y.o. strategy were extendedly dominated by 65–84 y.o. strategy. Probabilistic sensitivity analyses showed that the probabilities that ICER is under ¥5,000,000/US$45,662 per QALY gained was at 100% for 65–84 y.o., 70–84 y.o., 75–84 y.o. strategy, respectively, and at 98.4% for 80–84 y.o. strategy.ConclusionWe found that vaccinating individuals aged 65–84, 70–84, 75–84, and 80–84 with varicella vaccine to prevent HZ-associated disease in Japan can be cost-effective from societal perspective, with 65–84 y.o. strategy as the optimal alternative. Results are supported by one-way sensitivity analyses and probabilistic sensitivity analyses.     

Cost-effectiveness of a 3-dose pneumococcal conjugate vaccine program in the province of Quebec,Canada

In the province of Quebec, Canada, the pneumococcal 7-valent conjugate vaccine (PCV-7) was licensed in 2001 and a publicly funded program was implemented in 2004, recommending 3 doses for healthy children. An economic analysis was performed both from a health care and societal perspective. Outcomes possibly prevented by PCV-7 and observed in 2006–2007 were compared to expected frequencies based on rates measured before PCV-7 use. Annual program costs were close to $21 M for the health system and $23 M for society. Approximately 20 000 infections were prevented annually and estimated economic benefits were $5 M for the health system and $23 M for society, using a 3% per annum discounting rate. The incremental cost-effectiveness ratio was $18 000 per QALY gained for the health system and the program was close to the break-even threshold in a societal perspective.     

Revaccination with 23-valent pneumococcal polysaccharide vaccine in the Japanese elderly is well tolerated and elicits immune responses

BackgroundFollowing primary vaccination of adults ⩾65 years of age with 23-valent pneumococcal polysaccharide vaccine (PPSV23), immune responses increase and thereafter appear to decrease over time. With increased life expectancy worldwide, revaccination with PPSV23 may be required for continued protection of the elderly population against pneumococcal disease. The present study evaluated the immunogenicity and safety of revaccination with PPSV23 in the Japanese elderly.MethodsDepending on prior history of PPSV23 vaccination, adults aged ⩾70 years were given a first dose (primary group; N = 81) or second dose (revaccination group; N = 161, at least 5 years after first dose) of PPSV23 intramuscularly. Subjects were matched for gender, age, and number and type of comorbidity across both groups. Blood samples were collected before and 4 weeks postvaccination to measure serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic killing activity (OPA) antibody titers to serotypes included in the vaccine. Injection-site and systemic adverse events (AEs) were collected for 14 days postvaccination.ResultsBaseline serotype-specific IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) were generally higher in subjects with a prior history of PPSV23 vaccination than in PPSV23-naïve subjects. The levels of IgG GMCs and OPA GMTs after revaccination were generally comparable to those observed after primary vaccination. Incidences of systemic AEs were comparable between the 2 groups. Although incidences of injection-site AEs were higher following revaccination than primary vaccination, the difference was not clinically significant as most AEs were mild to moderate in intensity and resolved within 5 days after revaccination without treatment.ConclusionRevaccination with PPSV23 was well tolerated and associated with increases in serotype-specific IgG concentrations and OPA titers in the elderly who received a prior PPSV23 dose at least 5 years before. Revaccination with PPSV23 can be safely implemented in the elderly for continued prevention against pneumococcal disease.Clinical trial registry number: NCT02260882     

Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and Wales

In 2003 the existing 23-valent pneumococcal vaccine (PPV23) programme for high risk groups was extended to include all ≥65 year olds in England and Wales, starting with ≥80 year olds and moving to 75–79 and 65–74 year olds by 2005. We conducted an ecological study to assess the impact of the extended PPV23 programme on serotype-specific incidence of invasive pneumococcal disease (IPD) and a case–control study to assess vaccine effectiveness (VE) using the national IPD surveillance dataset. Between 1998 and 2006 IPD incidence caused by PPV23 serotypes in the targeted age-groups was unchanged. IPD caused by the serotypes covered by the 7-valent conjugate vaccine (PCV7) introduced for children in 2006 declined in ≥65 year olds after 2006 but was offset by an increase in non-PCV7 serotypes. This increase was similar for the additional 16 serotypes covered by PPV23 and the non-PPV23 serotypes. For the VE study, vaccine history was obtained for controls (n = 1270) with non-PPV23 IPD diagnosed between November 2003 and December 2010 and a subset of cases (n = 1272) matched for age and time period. VE declined from 48% (95% confidence interval; 32–60%) within two years of vaccination to 15% (−3% to 30%) after five years. Although differences in VE by age and having risk conditions were not statistically significant the highest estimates were in the youngest age group (65–74 years) and in those without risk conditions with a VE estimate of 65% (23–84%) within 2 years of vaccination for non-risk 65–74 year olds. VE differed by serotype (p = 0.005), from −23% (−85% to 19%) for serotype 3 to 63% (29–81%) for 12F. In conclusion PPV23 was effective, particularly in healthy under 75 year olds, but protection waned after 5 years. There was no discernible impact of PPV23 on IPD incidence or PCV7-induced serotype replacement, consistent with the modest overall effectiveness, the 45% increased coverage over the former risk-based programme and lack of herd immunity from the PPV23 programme. Based on the VE estimates PPV23 was still considered a cost-effective intervention for the low risk elderly.     

Economic evaluation of vaccination programme of 13-valent pneumococcal conjugate vaccine to the birth cohort in Japan

Japan is now preparing to incorporate PCV-7 into the national childhood immunisation programme. Our recently published economic evaluation of using PCV-7 to the birth cohort suggests that the cost to gain one QALY is lower than the WHO's cost-effectiveness criterion for intervention. However, many countries have started to introduce PCV-13 into their national immunisation schedule replacing PCV-7 for preventing pneumococcal diseases among young children. These raise the need to appraise the ‘value for money’ of replacing PCV-7 with PCV-13 vaccination programme in Japan.     

Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study

BackgroundWhile herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population.MethodsFor a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100.ResultsWe enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) −5.8%–51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65–74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4–77.5)] and against NBPP [effectiveness 35.0% (2.3–56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6–98.8) for PPV23-unique serotypes and 81.3% (38.6–94.3) for PPV23 serotypes excluding serotype 3.ConclusionsThis study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.     

Cost-effectiveness of the CRM-based 7-valent pneumococcal conjugated vaccine (PCV7) in Argentina

Due to the region's own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial.     

Cost-effectiveness of conjugate pneumococcal vaccination in Singapore: comparing estimates for 7-valent, 10-valent, and 13-valent vaccines

Introduction

Although multiple studies of cost-effectiveness of pneumococcal conjugate vaccines have been conducted, no such study has examined Singapore's situation nor compared the licensed conjugate vaccines in an Asian population. This paper estimates the costs and public health impacts of pneumococcal conjugate vaccine programs, varying estimates of serotype replacement and herd immunity effects as key parameters in the analysis. Based in part on a 2008 analysis also presented here, Singapore has approved the PCV-7, PHiD-10, and PCV-13 pneumococcal conjugate vaccines as part of its National Childhood Immunisation Programme.

Methods

An economic evaluation was performed using a Markov simulation model populated with Singapore-specific population parameters, vaccine costs, treatment costs, and disease incidence data. The vaccinated infant and child cohort of 226,000 was 6% of the Singapore resident population of 3.8 million. Vaccine efficacy estimates were constructed for PCV-7, PHiD-10, and PCV-13 vaccines based on their serotype coverage in Singapore and compared to ‘no vaccination’. The model estimated impacts over a five-year time horizon with 3% per year discounting of costs and health effects. Costs were presented in 2010 U.S. dollars (USD) and Singapore dollars (SGD). Sensitivity analyses included varying herd immunity, serotype replacement rates, vaccine cost, and efficacy against acute otitis media.

Results

Under base case assumptions for the revised analysis (i.e., herd effects in the unvaccinated population equivalent to 20% of direct effects) PCV-13 prevented 834 cases and 7 deaths due to pneumonia, meningitis, and bacteremia in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population over the 5-year time horizon. Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 (SGD $51,854) per QALY. Without herd effects, however, the ratio was USD $204,535 (SGD $281,743) per QALY. The PCV-7 cost per QALY including herd effects was USD $43,275 (SGD $59,610) and for PHiD-10 the ratios were USD $45,100 (SGD $62,125). The original 2008 analysis, which had higher estimates of pneumonia prevention due to herd immunity and lower estimates of cost per dose, had found a cost-effectiveness ratio of USD $5562 (SGD $7661) per QALY for PCV-7.

Conclusions

When compared to cost-effectiveness thresholds recommended by the World Health Organization (WHO), our 2008 analysis found that vaccination of infants in Singapore with PCV-7 was very cost-effective if herd immunity effects were present. However, knowledge on herd immunity and serotype replacement that emerged subsequent to this analysis changed our expectations about indirect effects. Given these changed inputs, our current estimates of infant vaccination against pneumococcal disease in Singapore find such programs to be moderately cost-effective compared to WHO thresholds. The different findings from the 2008 and 2011 analyses suggest that the dynamic issue of serotype replacement should be monitored post-licensure and, as changes occur, vaccine effectiveness and cost-effectiveness analyses should be re-evaluated.     

上海市金山区农村老年人肺炎疫苗免费接种知识、态度和行为调查

目的评价60岁以上老年人接种23价肺炎球菌多糖疫苗(PPV23)的效果。方法在上海市宝山区17个社区中抽取6个社区的13个村/里委,共抽取2014年4—6月的接种对象950名及未接种对象1 000名。通过队列研究,调查接种PPV23后1年中肺炎、其他呼吸道感染的患病及抗生素使用情况。结果利用倾向评分匹配法将调查对象进行匹配,最终保留接种组和未接种组各875例。随访满1年,两组人群肺炎患病率分别为0.91%和3.43%,差异有统计学意义(χ²=13.020,P＜0.01),接种疫苗对人群患肺炎的保护率为73.47%;两组人群支气管炎患病率分别为2.40%和7.89%,差异有统计学意义(χ²=26.988,P＜0.01),疫苗的保护率为69.71%;慢性支气管炎急性发作的患病率分别为0.11%和1.60%,差异有统计学意义(χ²=11.364,P＜0.01),疫苗的保护率为93.13%;上呼吸道感染患病率分别为18.63%和27.43%,差异有统计学意义(χ²=19.114,P＜0.01)。两组人群抗生素使用率分别为4.46%和10.29%, 差异有统计学意义(χ²=21.767,P＜0.01)。结论老年人接种PPV23后可以降低发生呼吸道感染和患肺炎的风险,并减少抗生素的使用。     

Pharmacoeconomic evaluation of 10- and 13-valent pneumococcal conjugate vaccines

Introduction

There are three different pneumococcal vaccines available for infants, each oriented to a specific set of serotypes. The vaccination of newborns will prevent pneumococcal disease in this vaccinated group via direct effects, and will also affect the non-vaccinated population through indirect or “herd” immunity.

Objective

To develop a model that compares the health and economic consequences between the three vaccines.

Method

We developed a simulation model for an entire population, providing vaccine to children less than 2 years of age. The vaccines varied by serotypes covered and included a 7- (4, 6B, 9V, 14, 18C, 19F and 23F), 10- (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) and 13-valent (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) vaccines. The base case was PCV-7, and clinical and economic outcomes were estimated for the vaccinated persons and for other persons through assumptions about a herd effect. By comparison, clinical and economic outcomes for the population were also estimated for the 10 and 13 serotype vaccines.

Results

In the base case (PCV-7), with the seven serotype vaccine, there were 9.38 cases of hospitalized pneumonia, 0.22 cases of meningitis, 3.69 cases of bacteremia, 60.19 cases of otitis media, and 373 cases of pneumonia, per 100,000 persons in the population, at all ages. With the 10-valent vaccine and a herd effect, invasive pneumonia fell to 8.71 cases, meningitis to 0.21 cases, and bacteremia to 3.39 cases. Otitis media fell to 57 cases and pneumonia to 344 cases. There were further reductions with the 13-valent vaccine, with invasive pneumonia falling to 8.37 cases, bacteremia to 3.33 cases, otitis media to 51.9 cases and all-cause pneumonia to 336.2 cases. Among the vaccines evaluated, PCV-13 was associated with the lowest health services costs and the greatest improved health outcomes.

Conclusions

Increased serotype coverage of the 13-valent vaccine is expected to have a substantial public health and economic impact on infectious disease, when considering direct and indirect effects.     

Long-term population impact of infant 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in adults in Finland

BackgroundLimited data are available on long-term indirect effects of ten-valent pneumococcal conjugate vaccine (PCV10) programmes. We evaluated changes in invasive pneumococcal disease (IPD) incidence, mortality, and serotype distribution in adults up to 9 years after infant PCV10 introduction.MethodsCulture-confirmed IPD cases ≥18 years (n = 5610; 85% were pneumonia) were identified through national, population-based laboratory surveillance; data were linked with population registry to conduct nationwide follow-up study. In a time-series model, we compared serotype-specific IPD incidence and associated 30-day mortality rates before and after PCV10 by using negative binomial regression models.ResultsDuring pre-PCV10 period (7/2004–6/2010), overall IPD incidence in adults ≥18 years increased yearly by 4.8%. After adjusting for trend and seasonality, the observed PCV10 serotype IPD incidence in 7/2018–6/2019 was 90% (12/100,000 person-years) lower than the expected rate without PCV10 program. Non-PCV10 serotype incidence was 40% (4.4/100,000 person-years) higher than expected; serotypes 3, 19A, 22F, and 6C accounted for most of the rate increase. However, incidence of non-PCV10 IPD levelled off by end of follow-up. The observed-expected incidence rate-ratio (IRR) was 0·7 (95 %CI 0·5–0.8) for all IPD and 0·7 (95 %CI 0·3–1·3) for IPD-associated 30-day mortality. Case-fatality proportion decreased from 11·9% to 10.0% (p < 0.01). In persons ≥65 years, the IRR was 0·7 (95 %CI 0·5–0.95).ConclusionsSignificant indirect effects were seen for vaccine-serotype IPD and for overall IPD in all adult age groups. For non-vaccine IPD, the incidence stabilized 5 years after infant PVC10 program introduction, resulting in a steady state in which non-vaccine IPD accounted for nearly 90% of overall IPD. Substantial pneumococcal disease burden remains in older adults.     

Economic evaluation of vaccination programme of 7-valent pneumococcal conjugate vaccine to the birth cohort in Japan

Aiming to introduce 7-valent pneumococcal conjugate vaccine (PVC-7) into routine vaccination schedule, the government of Japan gives a temporary budget to encourage municipalities in launching public vaccination programme which started on November 26, 2010 and ends on March 31, 2012. This study aims to appraise the 'value for money' of PCV-7 vaccination programme from the societal perspective and the budget impact from the perspective of municipalities, which is responsible for providing routine vaccination. We conducted a cost-effectiveness analysis with Markov modelling and calculated incremental cost-effectiveness ratio (ICER) value of launching such programme with two levels of co-payment, ￥1000 (US$13) or ￥0, and two scenarios of the uptake of vaccine (vaccinated-alone or co-vaccinated with other vaccines). We found that when vaccinated-alone, ICERs in QALY were ￥7,441,000 (US$93,013) or ￥9,065,000 (US$113,313), and when co-vaccinated ￥7,441,000 (US$93,013) or ￥5,489,000 (US$68,613), without or with productivity loss, respectively, regardless of co-payment level of the programme. Co-vaccinated programmes had lower ICER than vaccinated-alone programmes due to the savings in productivity loss. By adopting WHO's classification that an intervention is 'cost-effective' if ICER (in QALY) is between 1 and 3 times of GDP as a criterion, PCV-7 vaccination programme in Japan is concluded as "cost-effective" from the perspective of society. The introduction of either no co-payment or ￥1000 (US$13) co-payment vaccination programme appears to be not budget saving for the first 6 years, whereas the level of budget impact are less than ￥11,000,000 (US$137,500) or ￥8,500,000 (US$106,250), respectively, for a municipality with 1000 birth cohort in the 1st year and 2nd to 5th year birth cohort proportional to the birth cohort population of estimated future population.