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1.
Abstract

Objective:

The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13).

Methods:

The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature.

Results:

The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively.

Limitations:

The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper.

Conclusion:

This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV’s potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.  相似文献   

2.
3.
Abstract

Objective:

To update an earlier evaluation estimating the cost-effectiveness of quadrivalent influenza vaccination (QIV) compared with trivalent influenza vaccination (TIV) in the adult population currently recommended for influenza vaccination in the UK (all people aged ≥65 years and people aged 18–64 years with clinical risk conditions).  相似文献   

4.
OPTIMAL DISTRIBUTION OF POWERS IN A FEDERATION: A SIMPLE, UNIFIED FRAMEWORK   总被引:1,自引:0,他引:1  
In a federation with n≥ 2 regions the relative optimality of five regimes – autarky, centralization, unregulated devolution, regulated devolution and direct democracy – is examined. Public policy consists of redistribution and regional public good provision. Regional incomes are uncertain and correlated. Estimates of the usefulness of regional public goods are uncertain and the federal government's estimates are noisier relative to those of regional governments. The optimality of each regime is influenced by four margins – regional insurance, coarseness of federal information, internalization of spillovers and raiding the commons. Regulated devolution is the only regime that is capable of producing the constrained first best level of public goods. Federal insurance under direct democracy can be inadequate relative to that under a utilitarian federal government. An increase in the number of regions allows better risk pooling but also greater opportunities for raiding the commons.  相似文献   

5.

Widespread vaccination acceptance is of critical import to society dealing with the continuing aftermath of the COVID-19 pandemic. The risky behaviours that predict whether individuals vaccinate for seasonal influenza can help policymakers fashion plans to improve vaccination rates and more reliably establish herd immunity. To this end, Canadian Community Health Survey (CCHS) data were employed to determine how an individual’s choice to engage in various risky behaviours relates with the likelihood that the same individual gets the seasonal influenza vaccine. Controls were included for demographic, geographic, and health insurance factors. In addition to controlling for these factors, regressions were further stratified based upon gender, the presence of children in the home, and age. I found that excess sun exposure, poor oral hygiene, smoking, and unhealthy diet choices correlated with reduced vaccination probability—both over the subsequent year and for that individual’s lifetime. These results have important implications for properly targeting individuals for widespread vaccinations.

  相似文献   

6.
Objective: In Japan, the National Immunization Program (NIP) includes PPV23 as the primary vaccination for adults and catch-up cohorts. The Japanese Association for Infectious Diseases recommends revaccination for older adults who received primary vaccination ≥5 years earlier. The cost-effectiveness of adding revaccination and/or continuing catch-up vaccination in the NIP was evaluated from the public payer perspective in Japan.

Methods: The Markov model included five health states: no pneumococcal disease, invasive pneumococcal diseases (IPD), non-bacteremic pneumococcal pneumonia (NBPP), post-meningitis sequelae, and death. Cohorts of adults aged 65–95 were followed until age 100 or death: 2014 cohort (aged 65–95, vaccinated: 2014); 2019 cohort (aged 65: 2019); and 2019 catch-up cohort (aged 70–100: 2019, unvaccinated: 2014). Strategies included: (1) vaccinate 2014 and 2019 cohorts; (2) vaccinate 2014 and 2019 cohorts and revaccinate both; (3) strategy 1 and vaccinate 2019 catch-up cohort; (4) strategy 2 and vaccinate 2019 catch-up cohort; and (5) strategy 4 and revaccinate 2019 catch-up cohort. Parameters were retrieved from global and Japanese sources, costs and QALYs discounted at 2%, and incremental cost-effectiveness ratios (ICERs) estimated.

Results: Strategy 1 had the highest number of IPD and NBPP cases, and strategy 5 the lowest. Strategies 3–5 dominated strategy 1 and strategy 2 was cost-effective compared to strategy 1 (ICER: ¥1,622,153 per QALY gained). At a willingness-to-pay threshold of ¥5 million per QALY gained, strategy 2 was cost-effective and strategies 3–5 were cost-saving compared to strategy 1.

Conclusions: Strategies including revaccination, catch-up, or both were cost-effective or cost-saving in comparison to no revaccination and no catch-up. Results can inform future vaccine policies and programs in Japan.  相似文献   

7.
Aims: The World Health Organization (WHO) recommends the use of Haemophilus influenzae type b (Hib) conjugate vaccines, but China and Thailand have not used Hib vaccination in their national immunization programs. This systematic review aimed to update published economic evaluations of Hib vaccinations and to determine factors that potentially affected their cost-effectiveness.

Methods: Searches were performed from the inception until December 2015 using 13 databases: CAB direct; CEA registry; EconLit; EMBASE; E-library; NHSEED; PAHO; POPLINE; PubMed; Redalyc project; RePEc; SciELO; and WHOLIS. Reference lists of relevant studies and grey literature were also searched. Full economic evaluations of Hib vaccination with results of costs and outcomes were included. The WHO checklist was used to evaluate the quality of the included studies. Data from eligible studies were extracted using a standardized data collection form.

Results: Out of 830 articles, 27 were included. Almost half of the studies (12/27) were conducted in high-income countries. Twelve studies (12/27) investigated the Hib vaccine as an addition to the existing vaccination program. Most studies (17/27) examined a 3-dose schedule of Hib vaccine. Nineteen studies (19/27) reported the model used, where all were decision tree models. Most of the studies (23/27) demonstrated an economic value of Hib vaccination programs, key influential parameters being incidence rates of Hib disease and vaccine price.

Conclusions: Hib vaccination programs are mostly found to be cost-effective across geographic regions and country income levels, and Hib vaccination is recommended for inclusion into all national immunization programs. The findings are expected to support policy-makers for making decisions on allocating limited resources of the Hib vaccination program effectively.  相似文献   


8.
《Journal of medical economics》2013,16(10):1216-1227
Abstract

Objective:

To evaluate the impact of universal vaccination with a pentavalent rotavirus vaccine (RV5) on the healthcare burden and costs associated with rotavirus gastroenteritis (RGE) in Japan.

Methods:

The model included a hypothetical cohort of 1,091,156 children followed for their first 5 years of life. In the absence of universal vaccination, there were 19 deaths, 78,000 hospitalizations, and 678,000 outpatient visits due to RGE. The efficacy of RV5 is based on international clinical trial data, which was similar to the efficacy observed in clinical trials conducted in Japan. The primary outcome measure is the cost per quality-adjusted-life-year (QALY) gained. In the base case, the QALY loss per 1000 RGE episodes included 2.2 for children and 1.8 per parent.

Results:

Universal vaccination is projected to reduce hospitalizations by 92%, outpatient visits by 74%, and work-loss days by 73%. For the base case analysis, the total vaccination cost was ¥26 billion. The estimated reduction in medical costs was ¥16 billion. Of 2500 QALYs gained with the vaccination program, approximately half are directly attributed to the child. In the base case analysis, the incremental cost-effectiveness ratio (ICER) for vaccination vs no vaccination is ¥4 million and ¥2 million per quality-adjusted life year (QALY) gained from the healthcare payer and societal perspectives, respectively. The ICERs are ¥8 million and ¥4 million if parental disutilities are excluded.

Key limitation:

The QALY decrements for children and parents were evaluated using different instruments, and the QALY decrements do not vary based on episode severity. Given the interdependence between children and their parents, excluding parental disutilities may under-estimate the impact of RGE.

Conclusion:

Universal vaccination with RV5 in Japan is projected to have a substantial public health impact and may be cost-effective from both the payer and societal perspectives if parental disutilities are included in the cost-effectiveness ratios.  相似文献   

9.
Abstract

Objective:

A Markov model was used to assess the impact of RV5, a pentavalent (G1, G2, G3, G4, P1A[8]) human bovine (WC3 strain) reassortant rotavirus vaccine, on reducing the healthcare burden and cost associated with rotavirus gastroenteritis (RGE) in Taiwan. Other cost-effectiveness analyses for rotavirus vaccination in industrialized countries have produced varying results depending on the input parameters assumed.

Methods:

Vaccination with RV5 is compared to no vaccination in a hypothetical cohort of Taiwanese children during their first 5 years of life to determine the per dose prices at which vaccination would be cost neutral or provide good value based on established standards from the healthcare (direct medical care costs only) and societal (all RGE-related costs) perspectives. The effects of vaccination on RGE healthcare utilization and days of parental work loss missed are based on results from the Rotavirus Efficacy and Safety Trial.

Results:

Without vaccination there would be 122,526 symptomatic episodes of RGE. Universal vaccination would reduce RGE-related deaths, hospitalizations, emergency department, and outpatient visits by 91.7%, 92.1%, 83.7%, and 73.4%, respectively. The price per dose at which vaccination would be cost-neutral is US$ 21.80 (688 NTD) and US$ 26.20 (827 NTD) from the healthcare and societal perspectives, respectively. At $25 per dose, the cost per QALY gained is US$ 2261 (71,335 NTD) from the healthcare perspective and cost saving from the societal perspective.

Key limitations:

The model only assesses the effect of RV5 on vaccinated children and does not account for herd immunity. However, given that high levels of coverage are anticipated in Taiwan, the effects of herd immunity are likely to be short-term.

Conclusion:

A pentavalent rotavirus vaccination program is likely to substantially reduce the healthcare burden associated with rotavirus gastroenteritis at a cost per QALY ratio within the range defined as cost-effective.  相似文献   

10.
Abstract

Objective:

To determine the cost-effectiveness of vaccination against herpes zoster (HZ) and post-herpetic neuralgia (PHN) in individuals aged 60 years and older in Belgium.

Methods:

A Markov model was developed to compare the cost-effectiveness of vaccination with that of a policy of no vaccination. The model estimated the lifetime incidence and consequences of HZ and PHN using inputs derived from Belgian data, literature sources, and expert opinion. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life-year (QALY) gained.

Results:

Vaccination in individuals aged 60 years and older resulted in ICERs of €6,799 (third party payer perspective), €7,168 (healthcare perspective), and €7,137 (societal perspective). The number needed to vaccinate to prevent one case was 12 for HZ, and 35 or 36 for PHN depending on the definition used. Univariate sensitivity analyses produced ICERs of €4,959–19,052/QALY; duration of vaccine efficacy had the greatest impact on cost-effectiveness. Probabilistic sensitivity analysis showed at least a 94% probability of ICERs remaining below the unofficial €30,000 threshold.

Discussion:

Key strengths of the model are the combination of efficacy data from a pivotal clinical trial with country-specific epidemiological data and complete sensitivity analysis performed. Main limitations are the use of non country-specific PHN proportion and non Belgian disease-specific utilities. Results are comparable with those recently published.

Conclusions:

HZ vaccination in individuals aged 60 years and older would represent a cost-effective strategy in Belgium.  相似文献   

11.
12.
Objective:

Invasive pneumococcal disease (IPD) and pneumococcal pneumonia cause substantial morbidity and mortality worldwide. This retrospective study was conducted to estimate the disease burden from pneumococcal disease in older adults in Taiwan from a health insurer’s perspective.

Methods:

Data for the years 2002–2009 from patients aged ≥50 years with insurance records indicating pneumococcal meningitis, pneumococcal bacteremia, or hospitalized or outpatient pneumonia were obtained from the National Health Insurance Research Database in Taiwan. Admission data for inpatients, visit data for outpatients, and associated costs were extracted from the database to estimate the incidence, case fatality rates, and direct and indirect costs of pneumococcal disease episodes. These data were applied to the estimated population of Taiwan in 2010 to provide an estimated disease burden for a single year from the payer perspective.

Results:

The average incidence per 100,000 person years was 2.4 for IPD, 278.8 for hospitalized pneumococcal pneumonia, and 1376.4 for outpatient pneumococcal pneumonia. The average case fatality rate was 12.3% for IPD and 10.0% for hospitalized pneumonia. Hospitalized pneumonia accounted for over 90% of direct medical costs. The incidence of hospitalized pneumococcal pneumonia per 100,000 person years was 84.4 for adults of 50–64 years, 313.1 for adults of 65–74 years, 820.3 for adults of 75–84 years, and 1650.9 for adults of 85+ year of age. In 2010, it was estimated there were over 113,000 episodes of pneumococcal disease, causing almost 2000 deaths, with direct medical costs of more than NT$3.4 billion annually.

Conclusions:

Pneumococcal disease is a significant cause of mortality and excess healthcare expense among the elderly in Taiwan. Disease burden in older adults increases with advancing age.  相似文献   


13.
Abstract

Objective:

Decision-makers in the US may be interested in the applicability to their populations of cost-effectiveness results generated from clinical trial populations.

Methods:

An economic model estimating the cost-effectiveness of prasugrel plus aspirin relative to clopidogrel plus aspirin for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) was developed from a managed care organization (MCO) perspective. The model estimated 15-month cardiovascular events or bleeding-related outcomes, life expectancy, and costs for patients who received thienopyridine treatment during and after a PCI following a diagnosis of ACS. Post-ACS event rates for patients treated with clopidogrel were from an MCO. The relative risks of these events with prasugrel compared with clopidogrel were from a head-to-head clinical trial.

Results:

The results of the base-case analysis indicated that, in an MCO population, use of prasugrel-based therapy rather than clopidogrel-based therapy at current prices resulted in cost-savings and fewer clinical events over the 15 months after an ACS diagnosis followed by PCI. At possible lower prices for generic clopidogrel-based therapy, the cost-effectiveness ratio for prasugrel-based therapy compared with clopidogrel-based therapy was between $6643 and $13,906 per life-year gained. The results were most sensitive to the relative costs of the two treatments and the cost for hospital stays.

Limitations:

Limitations of the study included lack of follow-up of patients disenrolling from the MCO before the end of the 15-month observation period, the assumption of equal relative risks of events in an MCO as in the clinical trial, and the lack of information on the ratio of cost to charges in the MCO database.

Conclusions:

Use of prasugrel-based therapy compared with clopidogrel-based therapy in ACS patients having a PCI resulted in cost-savings at current prices and favorable cost-effective ratios at likely generic prices for clopidogrel-based therapy because of offsetting savings in the costs of rehospitalization.  相似文献   

14.
Abstract

Objective:

To quantify the differences in hospital length of stay (LOS) and cost between healthy and vulnerable children with cystic fibrosis (CF), insulin-dependent diabetes mellitus (IDDM), cancer, and epilepsy who contract rotavirus (RVGE) or respiratory syncytial virus (RSV).

Methods:

Hospital Episode Statistics (HES) data were collected for England, for children <5 years old, admitted between April 2001 and March 2008, using ICD-10 codes for RVGE and RSV. Cases were identified as having RVGE and/or RSV plus CF, IDDM, cancer, or epilepsy. Healthy controls had RVGE and/or RSV only, additional controls had eczema only. Cost, hospital LOS, and demographics were collected.

Results:

Four hundred and eighty-six (0.5%) cases and 101,784 (99.5%) healthy controls were admitted with RVGE or RSV, with 17,420 eczema controls. RVGE was present in 153 (31.5%) cases and 7532 (7.4%) healthy controls, and RSV in 333 (68.5%) cases and 94,252 (92.6%) healthy controls. Cases were older (1.1 years, SD?=?1.3 years), had greater LOS (9.9 days, SD?=?19.9), and cost more (£3477, SD?=?£7765) than healthy controls (age?=?0.2, SD?=?0.5, p?<?0.001; LOS?=?1.9 days, SD?=?3.1, p?<?0.001; cost?=?£595, SD?=?£727, p?<?0.001). Cost for cases was 6-times greater than healthy controls (p?<?0.001). Controls had a 0.3 day greater LOS (p?<?0.001) with RSV, but a £17 (p?=?0.085) lower mean cost than RVGE.

Conclusion:

RVGE and RSV are more serious diseases in vulnerable children, requiring more intense resource use. The importance of preventing infection in vulnerable children is underlined by hygiene and appropriate isolation and vaccination strategies. When universal vaccination is under consideration, as for rotavirus vaccines, evaluation of a vaccination programme should consider the potentially positive impact on vulnerable children.

Limitations:

Limitations of the study include a dependency on accurate coding, an expectation that patients are identified through laboratory testing, and the possibility of unidentified underlying conditions affecting the burden.  相似文献   

15.
Abstract

Objective: A transmission dynamic model was used to assess the epidemiological and economic impact of a quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine in preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), CIN 1 and genital warts in Hungary.

Methods: The routine vaccination of 12-year-old girls and the routine vaccination of 12-year-old girls plus a temporary catch-up programme for girls and women aged 12–24 years was evaluated.

Results: The model projected that at year 100, both strategies could reduce the incidence of HPV 6/11/16/18-related cervical cancer, CIN 2/3, CIN 1 and genital warts cases among Hungarian women by 90%, 90%, 85% and 93%, respectively. Twenty-five years after the introduction of HPV vaccination in the population, routine vaccination of girls by the age of 12 reduced the cumulative number of cases of cervical cancer, CIN 2/3, CIN 1 and genital warts by 685, 13,473, 3,423 and 163,987, respectively. The incremental cost-effectiveness ratios of the two vaccination strategies were €9,577 and €10,646 per quality-adjusted life-year (QALY) gained over a time horizon of 100 years.

Key limitations: The model did not account for the health and economic impact of other HPV diseases which may result from HPV 16, 18, 6, and 11 infections such as vaginal, vulvar, penile, anal and head-neck cancers, and recurrent respiratory papillomatosis. Epidemiological data from Hungary on these other HPV diseases as well genital warts are needed.

Conclusion: A quadrivalent HPV vaccination programme can reduce the incidence of cervical cancer, CIN and genital warts in Hungary at a cost-per-QALY ratio within the range defined as cost effective.  相似文献   

16.
17.
Abstract

Objective:

This study uses real-world US managed-care claims data to estimate dose escalation rates over the first and second years of therapy among biologic naïve rheumatoid arthritis (RA) patients initiating tumor necrosis factor (TNF) blocker therapy with etanercept, adalimumab, or infliximab.

Methods:

Non-elderly adult (age 18–65 years) RA patients initiating etanercept, adalimumab, or infliximab from July 1, 2005 to April 30, 2009, were identified using the MarketScan Commercial Database. National and regional dose-escalation patterns were evaluated 12 and 24 months after initiation. In the single-instance method, dose escalation was defined as having one average weekly dose 115%, 130%, or 150% greater than the initial average weekly dose. By the two-instances method, dose escalation was defined as having two consecutive claims with an average weekly dose 115% or 130% greater than the initial average weekly dose.

Results:

A total of 2747 patients met the inclusion criteria (mean age 50 years [SD?=?10]; 74% female). More patients initiated etanercept (44%) than adalimumab (37%) or infliximab (20%). Using the single-instance method, dose escalation at 12 months ranges were 0.8–1.5% for etanercept, 10.8–12.5% for adalimumab, and 16.4–42.5% for infliximab; ranges at 24 months were 0.8–2.1% for etanercept, 14.3–17.5% for adalimumab, and 26.4–57.6% for infliximab. The two-instances method showed a similar relationship among the treatment cohorts at both 12 and 24 months, with lower dose-escalation rates for etanercept (0.8%, 0.8%) than adalimumab (8.7%, 13.3%) or infliximab (22.9%, 37.6%) at the 130% threshold (p?<?0.001). Dose-escalation rates for etanercept, adalimumab, and infliximab were consistent across US geographic regions.

Conclusion:

Patients initiating etanercept had lower rates of dose escalation than patients initiating adalimumab or infliximab in the first and second year following therapy initiation, as well as across US geographic regions. These results may not be generalizable to the entire US RA population.  相似文献   

18.
Abstract

Objective:

To explore treatment patterns and resource utilization and cost for subjects with pulmonary arterial hypertension (PAH).

Research design:

Retrospective claims database analysis of 706 patients with PAH enrolled in a large, geographically diverse US managed-care organization.

Results:

In the final sample of PAH patients treated with bosentan (n?=?251) or sildenafil (n?=?455), average age was 57 years, 86% of patients were commercially insured, and 52% of patients were male. Gender distribution varied significantly across subgroups, with a lower proportion of males in the bosentan (30%) subgroup compared with the sildenafil group (64%) (p?<?0.001). Average baseline Charlson comorbidity score was 2.4. Average numbers of fills per month were 0.8 and 0.4 for bosentan and sildenafil patients, respectively (p?<?0.001). Over 80% of patients received only one PAH treatment in the first 90 days following the index date, with 28% of bosentan and 13% of sildenafil patients receiving combination therapy (p?<?0.001). Over one-third of bosentan patients and one-quarter of sildenafil patients experienced a dose increase in the follow-up period (p?=?0.009). Sixteen percent of sildenafil patients experienced a dose decrease in the follow-up period, while a smaller proportion of patients receiving bosentan (4%) experienced a dose decrease (p?<?0.001). On average, number of PAH-related per subject per month (PSPM) inpatient stays and emergency department visits and PSPM length of inpatient stays were statistically similar between the subgroups. PAH-related PSPM healthcare costs were high for both subgroups, with average monthly costs of $5,332 and $3,632 among bosentan and sildenafil patients, respectively (p?=?0.003). Differences in total costs were driven mainly by differences in pharmacy expenditures.

Conclusions:

Of the oral agents approved for treating PAH at the time of this study, sildenafil was most commonly prescribed as index therapy and was also associated with the lowest costs, largely due to significantly lower pharmacy costs. This study is characterized by limitations inherent to claims database analyses, such as the potential for coding errors and lack of information on whether a drug was taken as prescribed. Furthermore, PAH severity (WHO functional class) was not assessed.  相似文献   

19.

The change in China's regional output disparities can be attributed to the variation in market orientation in individual regions, and the change in China's livelihood disparities can be attributed to the weakening of government intervention in the form of regional income redistribution in the reform process. The study suggests that China should accelerate economic growth of backward interior regions by deepening market-oriented reforms on the one hand, and help residents in these regions by strengthening fiscal transfer from richer to poorer regions on the other.  相似文献   

20.
Objective: The objective of this review was to determine, from a systematic assessment of published data, the cost effectiveness of the neuraminidase inhibitor antiviral medication oseltamivir in comparison with usual care (i.e. over-the-counter medication such as analgesics and antipyretics for symptomatic relief) for the treatment of influenza. How the findings of each of the studies considered related to the methods used for each analysis and the assumptions made were specifically reviewed.

Results: The online search found 80 individual articles, 66 of which did not meet the pre-defined screening criteria. The 14 studies remaining reported cost, cost-effectiveness and cost-utility analyses for oseltamivir treatment in various groups: healthy adults and adolescents, children, elderly, and individuals at increased risk.

Conclusion: Despite the range of values assumed for key probabilities such as the diagnostic certainty of influenza among people presenting with influenza-like illness, and how much work time is lost due to illness in healthy adults, base-case analyses consistently showed oseltamivir treatment to be cost effective or even cost saving for the four population groups studied, a conclusion that is in-line with previous reviews on this topic. However, clarity was frequently lacking in the published data in terms of various model assumptions and results, particularly with regards to the exact distributions of the constituting elements of savings and of quality-adjusted life years gained.  相似文献   

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