Precision Reimbursement for Precision Medicine: Using Real-World Evidence to Evolve From Trial-and-Project to Track-and-Pay to Learn-and-Predict.

Basic scientists and drug developers are accelerating innovations toward the goal of precision medicine. Regulators create pathways for timely patient access to precision medicines, including individualized therapies. Healthcare payors acknowledge the need for change but downstream innovation for coverage and reimbursement is only haltingly occurring. Performance uncertainty, high price-tags, payment timing, and actuarial risk issues associated with precision medicines present novel financial challenges for payors. With traditional drug reimbursement frameworks, payment is based on an assumed randomized controlled trial (RCT) projection of real-world effectiveness, a "trial-and-project" strategy; the clinical benefit realized for patients is not usually ascertained ex post by collection of real-world data (RWD). To mitigate financial risks resulting from clinical performance uncertainty, manufacturers and payors devised "track-and-pay" frameworks (i.e., the tracking of a pre-agreed treatment outcome which is linked to financial consequences). Whereas some track-and-pay arrangements have been successful, inherent weaknesses include the potential for misalignment of incentives, the risk of channeling of patients, and a failure to use the RWD generated to enable continuous learning about treatments. "Precision reimbursement" (PR) intends to overcome inherent weaknesses of simple track-and-pay schemes. In combining the collection of RWD with advanced analytics (e.g., artificial intelligence and machine learning) to generate actionable real-world evidence, with prospective alignment of incentives across all stakeholders (including providers and patients), and with pre-agreed use and dissemination of information generated, PR becomes a "learn-and-predict" model of payment for performance. We here describe in detail the concept of PR and lay out the next steps to make it a reality.

Rates and costs of invasive pneumococcal disease and pneumonia in persons with underlying medical conditions.

BACKGROUND: The presence of certain underlying medical conditions is known to increase the risk of pneumococcal disease in persons of all ages and across a wide spectrum of conditions, as demonstrated in two recent evaluations. Corresponding estimates of attributable economic costs have not been well characterized. We thus undertook a retrospective evaluation to estimate rates and costs of pneumococcal disease among children and adults with and without underlying medical conditions in the United States. METHODS: Data were obtained from three independent healthcare claims repositories. The study population included all persons enrolled in participating health plans during 2007-2010, and was stratified into subgroups based on age and risk profile: healthy; at-risk, due to selected comorbid conditions; and high-risk, due to selected immunocompromising conditions. At-risk and high-risk conditions, as well as episodes of invasive pneumococcal disease (IPD) and all-cause pneumonia (PNE), were identified via diagnosis, procedure, and drug codes. Rates and healthcare costs of IPD and PNE (2010US$) among at-risk and high-risk persons were compared with those from age-stratified healthy counterparts using incidence rate ratios (IRR) and cost ratios. RESULTS: Rates of IPD and PNE were consistently higher among at-risk persons (IRR = 4.1 [95 % CI 3.9-4.3] and 4.5 [4.49-4.53]) and high-risk persons (IRR = 10.3 [9.7-11.0] and 8.2 [8.2-8.3]) of all ages versus their healthy counterparts. Rates were notably high for at-risk persons with ≥2 conditions (IRR = 9.0 [8.4-9.7] and 10.3 [10.3-10.4]), as well as those with asthma (IRR = 3.4 [3.0-3.8] and 4.5 [4.47-4.53]) or diabetes (IRR = 4.3 [4.0-4.6] and 4.7 [4.6-4.7]). Healthcare costs totaled $21.7 million per 100,000 at-risk person-years and $58.5 million per 100,000 high-risk person-years, which were 8.7 [8.5-8.8] and 23.4 [22.9-23.8] times higher than corresponding costs for healthy persons. CONCLUSIONS: Rates and costs of IPD and PNE are substantially higher among persons with certain chronic and immunocompromising conditions versus those without any such conditions. Rates and costs for persons with asthma and diabetes were especially increased, and rates and costs for individuals with ≥2 at-risk conditions approached those among persons with high-risk conditions.

Rates of pneumonia among children and adults with chronic medical conditions in Germany.

BACKGROUND: The objective of this study is to evaluate rates of all-cause pneumonia among "at-risk" and "high-risk" children and adults in Germany-in comparison with age-stratified healthy counterparts-during the period following the 2006 recommendation for universal immunization of infants with pneumococcal conjugate vaccine. METHODS: Retrospective cohort design and healthcare claims information for 3.4 M persons in Germany (2009-2012) were employed. Study population was stratified by age and risk profile (healthy, "at-risk" [with chronic medical conditions], and "high-risk" [immunocompromised]). At-risk and high-risk conditions, as well as episodes of all-cause pneumonia, were identified via diagnosis, procedure, and drug codes. RESULTS AND DISCUSSION: Rates of all-cause pneumonia were 1.7 (95 % CI 1.7-1.8) to 2.5 (2.4-2.5) times higher among children and adults with at-risk conditions versus healthy counterparts, and 1.8 (1.8-1.9) to 4.1 (4.0-4.2) times higher among children and adults with high-risk conditions. Rates of all-cause pneumonia among at-risk persons increased in a graded and monotonic fashion with increasing numbers of conditions (i.e., risk stacking). CONCLUSIONS: An increased risk for all-cause pneumonia in German children and adults with a spectrum of medical conditions persists in the era of widespread pneumococcal vaccination, and pneumonia risk in persons with ≥2 at-risk conditions is comparable or higher than those with high-risk conditions.

Despite High Cost, Improved Pneumococcal Vaccine Expected To Return 10-Year Net Savings Of $12 Billion.

In 2010 the US Advisory Committee on Immunization Practices recommended that the seven-valent pneumococcal conjugate vaccine (PCV7) be replaced by the thirteen-valent version (PCV13), which provides protection against six additional serotypes of the bacterium Streptococcus pneumoniae. The higher price of PCV13, compared to PCV7, may be a concern for funding agencies and payers, as has been the case with other new vaccines. This study estimated the budgetary impact on both public and private US insurance payers of the routine use of PCV13 instead of PCV7 from 2010 to 2019. Implementing the PCV13 vaccine is projected to cost public and private payers $3.5 billion and $2.6 billion, respectively, more than PCV7. However, PCV13 is expected to provide net cost savings of $6.1 billion and $4.2 billion, respectively, to those payers during the ten-year period by preventing pneumococcal disease and its associated costs. An additional $1.7 billion in cost savings would be realized for uninsured patients, whose costs ultimately fall on those payers. Despite its higher price, compared to PCV7, this new vaccine is expected to provide payers with substantial net budgetary savings.

Rethinking risk for pneumococcal disease in adults: the role of risk stacking.

Using data from 3 private healthcare claims repositories, we evaluated the incidence of pneumococcal disease among adults with US Advisory Committee on Immunization Practices (ACIP) defined at-risk conditions or rheumatoid arthritis, lupus, Crohn's disease, and neuromuscular disorder/seizures and those with traditional high-risk conditions. We observed that adults with ≥2 concurrent comorbid conditions had pneumococcal disease incidence rates that were as high as or higher than rates observed in those with traditional high-risk conditions.

Risk of pneumococcal disease in children with chronic medical conditions in the era of pneumococcal conjugate vaccine.

BACKGROUND: In the current era of universal immunization of young children with pneumococcal conjugate vaccine, it is unclear whether the high risk ratios for pneumococcal disease previously attributed to specified chronic conditions have persisted. In addition, further analysis of pneumococcal disease risk may clarify whether certain chronic conditions that currently are not specified as significantly increasing the risk of pneumococcal disease should be so considered. METHODS: We conducted a retrospective cohort analysis utilizing healthcare claims data from the period 2007-2010 to compare rates of pneumococcal disease among children <5 and 5-17 years of age with high-risk and at-risk conditions to rates among children without these conditions in the same age group. Risk profiles and manifestations of pneumococcal infection were ascertained from diagnosis, procedure, and drug codes. RESULTS: Among at-risk children, rate ratios for invasive pneumococcal disease (vs children without at-risk/high-risk conditions) were 1.8 (95% confidence interval [CI], 1.4-2.3) in children <5 years of age and 3.3 (95% CI, 2.4-4.4) in children 5-17 years of age. Corresponding rate ratios for high-risk children were 11.2 (95% CI, 7.0-17.9) and 40.1 (95% CI, 28.8-56.0). Rate ratios increased in asthmatic children with increasing disease severity and in all at-risk children by the number of concurrent at-risk conditions. Rate ratios for pneumococcal pneumonia and all-cause pneumonia demonstrated similar patterns. CONCLUSIONS: Children with high-risk and at-risk conditions continue to demonstrate an increased burden of pneumococcal disease. Pneumococcal disease rates are high among asthmatic children with moderate and severe disease and children with multiple at-risk conditions.

Rates of pneumococcal disease in adults with chronic medical conditions.

BACKGROUND: Although it is widely accepted that adults with immunocompromising conditions are at greatly increased risk of pneumococcal infection, the extent of risk among immunocompetent adults with chronic medical conditions is less certain, particularly in the current era of universal vaccination of children with pneumococcal conjugate vaccines. METHODS: We conducted a retrospective cohort study using data from 3 healthcare claims repositories (2006-2010) to compare rates of pneumococcal disease in immunocompetent adults with chronic medical conditions ("at-risk") and immunocompromised adults ("high-risk"), with rates in adults without these conditions ("healthy"). Risk profiles and episodes of pneumococcal disease-all-cause pneumonia, pneumococcal pneumonia, and invasive pneumococcal disease (IPD)-were ascertained from diagnosis, procedure, and drug codes. RESULTS: Rates of all-cause pneumonia among at-risk persons aged 18-49 years, 50-64 years, and ≥65 years were 3.2 (95% confidence interval [CI], 3.1-3.2), 3.1 (95% CI, 3.1-3.1), and 3.0 (95% CI, 3.0-3.0) times the rates in age-matched healthy counterparts, respectively. We identified rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, and neuromuscular or seizure disorders as additional at-risk conditions for pneumococcal disease. Among persons with at-risk conditions, the rate of all-cause pneumonia substantially increased with the accumulation of concurrent at-risk conditions (risk stacking): among persons 18-49 years, rate ratios increased from 2.5 (95% CI, 2.5-2.5) in those with 1 at-risk condition to 6.2 (95% CI, 6.1-6.3) in those with 2 conditions, and to 15.6 (95% CI, 15.3-16.0) in those with ≥3 conditions. Findings for pneumococcal pneumonia and IPD were similar. CONCLUSIONS: Despite widespread use of pneumococcal conjugate vaccines, rates of pneumonia and IPD remain disproportionately high in adults with at-risk conditions, including those with conditions not currently included in the Advisory Committee on Immunization Practices' guidelines for prevention and those with multiple at-risk conditions.

Impact of 13-valent pneumococcal conjugate vaccine (PCV13) in a pandemic similar to the 2009 H1N1 in the United States.

BACKGROUND: High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza ("flu") pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. METHODS: We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009-2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. RESULTS: In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009-2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of $1.0 B compared to PCV7. CONCLUSIONS: In a flu pandemic similar to the 2009-2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs.

Community-acquired pneumonia: symptoms and burden of illness at diagnosis among US adults aged 50 years and older.

PURPOSE: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in older adults, yet few studies have comprehensively measured the burden of CAP symptoms and their impact from the patient perspective. Our Web-survey used the newly developed CAP burden of illness questionnaire (CAP-BIQ) designed to assess the presence of key symptoms, comorbid conditions affected by CAP, psychosocial impacts, productivity, and CAP-associated physician visits in US adults aged 50 years and older. METHODS: The CAP-BIQ was developed from semi-structured one-on-one interviews and finalized after cognitive debriefings with recently diagnosed CAP patients. The CAP-BIQ was then administered to 500 survey participants with a CAP diagnosis within the past 120 days confirmed by chest imaging recruited from a Web-based panel. Analyses of survey results were weighted for national representativeness, and were compared between relevant age, hospitalization status, and pneumonia-risk subgroups. RESULTS: The survey participants' mean age was 62.4 years; 45 % were men; and 39.6 % were hospitalized due to CAP. On average, the surveys were completed 56.9 days after pneumonia diagnosis. Nearly all participants reported tiredness, cough, body aches, weakness, shortness of breath, wheezing, and a weak appetite at the time of diagnosis (99.0, 96.8, 96.9, 94.1, 89.1, 85.8, and 78.5 %, respectively). There was generally greater symptom prevalence at diagnosis in younger, nonhospitalized, or high-risk subgroups when compared to their respective older, hospitalized, or low-risk counterparts. Most participants reported at least one cough-related and weakness-related impact on their daily life and activities from CAP. Over three quarters of the respondents (77.4 %) needed assistance from a friend or family member during their bout with pneumonia and a majority of respondents (83.6 %) were satisfied with the care they received from their doctors across the course of their illness. CONCLUSIONS: This study systematically assessed CAP symptoms and their impacts using the CAP-BIQ, a questionnaire with established content validity. At CAP diagnosis, the range of patient-reported symptoms was broader than previous studies have reported. Additionally, the overwhelming need for caregiver assistance demonstrates the burden this illness places on older adults.

Cost-effectiveness of a 10- versus 13-valent pneumococcal conjugate vaccine in Denmark and Sweden.

BACKGROUND: The introduction of a 7-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) had profound public health effects across the globe. PCV7 vaccination in a national immunization program is generally considered cost-effective and potentially cost-saving. Two new PCVs have been launched, a 10-valent pneumococcal conjugate vaccine (PCV10) and a 13-valent pneumococcal conjugate vaccine (PCV13). OBJECTIVE: This article examines the public health and economic effects of pediatric national immunization programs of PCV10 and PCV13 in Denmark and Sweden. METHODS: A previously published decision-analytic model was used to estimate the impact of PCV10 and PCV13 on reducing cases of invasive pneumococcal disease (IPD), pneumonia (PNE), and acute otitis media (AOM) by using country-specific incidence, serotype coverage, disease sequelae, mortality, vaccine effectiveness, indirect effects, costs, and utilities. Direct effects for PCV13- and PCV10-covered serotypes were assumed similar to PCV7. PCV13 was assumed to confer an indirect effect, similar to PCV7, whereas PCV10 was not. Assumptions were tested in sensitivity analyses. RESULTS: PCV13 is expected to save 280.7 million DKK (Danish kroner) in Denmark and 288.2 million SEK (Swedish kronor) in Sweden in direct costs compared with a vaccination program with PCV10. In both Denmark and Sweden, the results of this study indicate that, compared with PCV10, PCV13 will have a greater impact on disease in life-years gained (LYG), quality-adjusted life-years (QALYs) gained, IPD cases avoided, PNE cases avoided, AOM cases avoided, and in deaths avoided. For Denmark PCV13, it was estimated to result in 10,051 LYG; 9063 QALYs gained; 237 additional IPD cases avoided; 12,094 additional PNE cases avoided; 958 additional cases of AOM avoided; and 882 additional deaths avoided. For Sweden PCV13, it was estimated to result in 4245 LYG; 3953 QALYs gained; 379 additional IPD cases avoided; 8210 additional PNE cases avoided; 1459 additional cases of AOM avoided; and 378 additional deaths avoided. In all sensitivity analyses, PCV13 was less costly and more effective compared with PCV10. CONCLUSIONS: In this analysis, a national immunization program with PCV13 was found to be good value for money and estimated to prevent additional cases of disease among children and nonvaccinated individuals and save additional costs due to treatment of pneumococcal disease, when compared with PCV10 in Denmark and Sweden.

Cost-effectiveness models of pneumococcal conjugate vaccines: variability and impact of modeling assumptions.

Currently, 13-valent pneumococcal conjugate vaccine (PCV); and ten-valent PCV vaccine are marketed. Neither vaccine obtained regulatory approval based on efficacy trials, but instead were approved based on a surrogate end point: immunogenicity data measuring effective antibody levels. Therefore, direct measures of efficacy were unavailable at the time economic analyses were conducted. The authors systematically reviewed cost-effectiveness studies of ten-valent PCV and 13-valent PCV from the literature to analyze the methodologies and compare the assumptions made about vaccine effectiveness. The following three inputs were found the most variant across analyses: efficacy against acute otitis media; inclusion of indirect effects; and cross protection. These assumptions are discussed with regard to the validity of supporting data and implications on decision-making.

Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data.

BACKGROUND: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. METHODS: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. RESULTS: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤ 59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. CONCLUSIONS: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort.

Public health and economic impact of 13-valent pneumococcal conjugate vaccine in US adults aged ≥50 years.

BACKGROUND: A 13-valent pneumococcal conjugate vaccine (PCV13) was recently developed for use in older adults, and may be effective not only against invasive pneumococcal disease (IPD) but also nonbacteremic pneumococcal pneumonia. The potential public health and economic impact of PCV13 in this population is unknown. METHODS: A microsimulation model depicting risk and costs of IPD and all-cause nonbacteremic pneumonia (NBP) in US adults aged ≥50 years (n=96.1 million), as well as expected impact of vaccination, was developed. Effectiveness of PPSV23 was based on published literature, and for all-cause NBP, was zero; effectiveness of PCV13 was based on PCV7 data in children, and for all-cause NBP, was varied across a reasonable range. Lifetime outcomes and costs were projected assuming: (1) use of PCV13 in all subjects at model entry, with and without periodic revaccination; and (2) use of PPSV23 per current ACIP recommendations. RESULTS: Use of PCV13 in all subjects at model entry without revaccination - in lieu of PPSV23 use per recommendations - reduced cases of IPD by 15,000 (95% CI 9000-21,000); cases of NBP by 1.2 million (0.9-1.5); total healthcare costs by $3.5 billion (1.9-5.2); and total societal costs by $7.4 billion (5.3-9.8). Use of PCV13 with revaccination every 5-10 years resulted in fewest cases of disease and lowest total costs. Findings were largely unchanged in sensitivity analyses. CONCLUSIONS: Assuming that the effectiveness of PCV13 in adults is comparable to that observed for PCV7 in children and under reasonable assumptions regarding the underlying risks and costs of IPD and NBP, model projections suggest that routine use of PCV13 - in lieu of PPSV23 - would result in a greater reduction in the overall burden of pneumococcal disease in older US adults.

Economic burden of acute lower respiratory tract infection in South African children.

BACKGROUND: Acute lower respiratory tract infections (ALRTI) are a leading cause of childhood mortality, but there are few data on disease costs in developing countries. OBJECTIVES: This study's purpose was to analyse ALRTI's costs-of-illness and economic burden in urban South African children. METHODS: ALRTI costs-of-illness (expressed in US$ 2010) at a tertiary hospital were measured using a micro-costing approach nested within a clinical trial. Demographic, epidemiological and data on use of health resources were integrated with costs-of-illness to estimate the economic burden of ALRTI in urban South African children aged <5 years. RESULTS: 745 children experiencing 858 ALRTI episodes were studied. 338 (39.4%), 513 (59.8%) and 7 (0.8%) episodes were managed in short-stay, paediatric ward and intensive care settings, respectively. Mean lengths of stay in short-stay, paediatric ward and intensive care (ICU) were 1.4, 8.1 and 14.4 days, respectively. The societal costs-of-illness per ALRTI episode managed in short-stay and paediatric ward settings, respectively, were US$266 (95% CI 245-286) and 1287 (95% CI 1174-1401) in HIV-infected patients, and US$257 (95% CI 247-267) and 1032 (95% CI 931-1133) in HIV-uninfected patients. Family costs were not collected in ICUs. ICU direct medical costs were US$5968 (95% CI 4025-8056) in HIV-uninfected patients and US$7849 in one HIV-infected patient. Under-5 children experienced an estimated 424,220 episodes annually of ALRTI. ALRTI treatment cost the public health system an estimated US$28,975,000 while an additional US$539,000 of costs were borne by families. CONCLUSION: ALRTIs in children <5 years impose a heavy economic burden on families and the South African public health-care system.

Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada.

BACKGROUND: Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 10-valent pneumococcal conjugate vaccine (PCV10) are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi). We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs) in Canada. METHODS: A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars) were presented. RESULTS: In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only) than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination) were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. CONCLUSIONS: Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public health and economic benefits relative to PCV10.

Cost-effectiveness of 13-valent pneumococcal conjugate vaccine: Germany, Greece, and The Netherlands.

BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) had profound public-health impacts and is considered cost-effective and potentially cost saving. Two new PCVs have been launched, a 10-valent vaccine (PCV10) and a 13-valent vaccine (PCV13). We examined public-health and economic impacts of PCV pediatric national immunization programs (NIPs) in Germany, Greece, and the Netherlands. METHODS: A decision-analytic model was developed to estimate the impact of PCV13, PCV7, and 10-valent pneumococcal conjugate vaccine (PCV10) on invasive pneumococcal disease (IPD), pneumonia (PNE), and acute otitis media (AOM). Using epidemiological data, we calculated the cases of IPD, PNE, and AOM, using country-specific incidence, serotype coverage, disease sequelae, mortality, vaccine effectiveness, indirect effects, costs, and utilities. Direct effects for PCV13- and PCV10-covered serotypes were assumed similar to PCV7. PCV13 was assumed to confer an indirect effect, while PCV10 was not. Assumptions were tested in sensitivity analyses. RESULTS: In a NIP, PCV13 was estimated to eliminate 31.7%, 46.4%, and 33.8% of IPD in Germany, Greece, and the Netherlands, respectively. Compared with PCV7 and PCV10, PCV13 was found to be cost-effective or cost saving in all cases when PCV13 indirect effects were included. CONCLUSIONS: Pediatric NIPs with PCV13 in Europe are expected to have dramatic public-health impacts and be cost-effective or cost saving.

[Economic evaluation of an infant immunization program in Mexico, based on 13-valent pneumococcal conjugated vaccines]. / Evaluación económica de un programa de inmunización infantil en México basado en la vacuna neumocócica conjugada 13-valente.

OBJECTIVES: Vaccination is an effective intervention for reduce child morbidity and mortality associated to pneumococcus. The availability of new anti-pneumococcal vaccines makes it necessary to evaluate its potential impact on public health and costs related to their implementation. The aim of this study was to estimate the cost-effectiveness and cost-utility of immunization strategies based on pneumococcal conjugated vaccines (PCV's) currently available in Mexico from a third payer perspective. MATERIAL AND METHODS: A decision tree model was developed to assess both, economic and health impact, of anti-pneumococcal vaccination in children <2 years (lifetime time horizon, discount rate: 5% annual). Comparators were: no-vaccination (reference) and strategies based on 7, 10 and 13-valent PCV's. Effectiveness measures were: child deaths avoided, life-years gained (LYG) and quality adjusted life years (QALY's) gained. Effectiveness, utility, local epidemiology and cost of treating pneumococcal diseases were extracted from published sources. Univariate sensitivity analysis were performed. RESULTS: Immunization dominates no-vaccination: strategy based on 13-valent vaccine prevented 16.205 deaths, gained 331.230 LY's and 332.006 QALY's and saved US$1.307/child vaccinated. Strategies based on 7 and 10-valent PCV's prevented 13.806 and 5.589 deaths, gained 282.193 and 114.251 LY's, 282.969 and 114.972 QALY's and saved US$1.084 and US$731/child vaccinated, respectively. These results were robust to variations in herd immunity and lower immunogenicity of 10-valent vaccine. CONCLUSIONS: In Mexico, immunization strategies based on 7, 10 and 13-valent PCV's would be cost-saving interventions, however, health outcomes and savings of the strategy based on 13-valent vaccine are greater than those estimated for 7 and 10-valent PCV's.