Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine in Argentinean Adults.

INTRODUCTION: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. METHODS: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. RESULTS: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. CONCLUSIONS: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18­64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs­15-valent PCV (PCV15) and 20-valent PCV (PCV20)­are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18­64 years with underlying risk conditions and all adults aged 65­99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

INTRODUCTION: A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. METHODS: A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6 years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. RESULTS: Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6 years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. CONCLUSIONS: Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase.

Background: Estimates of the cost of medically attended lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) in adults, especially beyond the acute phase, is limited. This study was undertaken to estimate the attributable costs of RSV-LRTI among US adults during, and up to 1 year after, the acute phase of illness. Methods: A retrospective observational matched-cohort design and a US healthcare claims repository (2016-2019) were employed. The study population comprised adults aged ≥18 years with RSV-LRTI requiring hospitalization (RSV-H), an emergency department visit (RSV-ED), or physician office/hospital outpatient visit (RSV-PO/HO), as well as matched comparison patients. All-cause healthcare expenditures were tallied during the acute phase of illness (RSV-H: from admission through 30 days postdischarge; ambulatory RSV: during the episode) and long-term phase (end of acute phase to end of following 1-year period). Results: The study population included 4526 matched pairs of RSV-LRTI and comparison patients (RSV-H: n = 970; RSV-ED: n = 590; RSV-PO/HO: n = 2966). Mean acute-phase expenditures were $42 179 for RSV-H (vs $5154 for comparison patients), $4409 for RSV-ED (vs $377), and $922 for RSV-PO/HO (vs $201). By the end of the 1-year follow-up period, mean expenditures-including acute and long-term phases-were $101 532 for RSV-H (vs $36 302), $48 701 for RSV-ED (vs $27 131), and $28 851 for RSV-PO/HO (vs $20 523); overall RSV-LRTI attributable expenditures thus totaled $65 230, $21 570, and $8327, respectively. Conclusions: The cost of RSV-LRTI requiring hospitalization or ambulatory care among US adults is substantial, and the economic impact of RSV-LTRI may extend well beyond the acute phase of illness.

A formula for predicting emphysema extent in combined idiopathic pulmonary fibrosis and emphysema.

BACKGROUND: No single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema. METHODS: The development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema. RESULTS: The formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) - (0.65 x percent predicted forced expiratory volume in 1 second) - (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R2 = 0.25, P < 0.0001; R2 = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105). CONCLUSION: The formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests. TRIAL REGISTRATION: NCT00047645; NCT00075998.

Episodic Cost of Lower Respiratory Tract Illness Due to Respiratory Syncytial Virus Among US Infants During the First Year of Life.

A study using two healthcare claims databases (commercial, Medicaid) was undertaken to estimate episodic cost of lower respiratory tract illness due to respiratory syncytial virus (RSV-LRTI) among infants aged <12 months overall, by age, and by birth gestational age (weeks [wGA]). Among commercial-insured infants, mean costs were $28,812 for hospitalized episodes, $2,575 for emergency department episodes, and $336 for outpatient clinic episodes; costs were highest among infants aged <1 month and infants with wGA ≤32, and were comparable-albeit somewhat lower-among Medicaid-insured infants. Cost of RSV-LRTI during acute phase of illness is high, especially among youngest and premature infants.

Cost-utility of 20-valent pneumococcal conjugate vaccine compared to no vaccination and recommended alternative vaccines among Belgian adults.

BACKGROUND: The Belgian Superior Health Council (SHC) preferentially recommended the 20-valent pneumococcal conjugate vaccine (PCV20) for adults aged ≥65 years, immunocompromised patients, and patients aged ≥50 years suffering from conditions that increase their risk for pneumococcal infections. The objective of this paper is to present the cost-utility of PCV20 compared to no vaccination and the alternative sequence of PCV15 followed by the 23-valent pneumococcal polysaccharide vaccine (PPV23) in this population. RESEARCH DESIGN AND METHODS: The analysis employed a static Markov model capturing lifetime risk of pneumococcal infections, associated disutility, mortality, and costs from different healthcare payer perspectives. RESULTS: Results indicated use of PCV20 among Belgian older and at-risk adults is highly cost-effective compared to no vaccination, with an incremental cost per quality-adjusted life-year (QALY) of €4,164. Compared to the sequential regimen (PCV15+PPV23), PCV20 vaccination is a cost-saving strategy. Subgroup analysis indicated PCV20 vaccination of at-risk adults aged 65-84 years would also be cost-saving from the national healthcare perspective. CONCLUSION: Based on current knowledge, this analysis suggests that access to PCV20 should be proposed in all adults recommended for vaccination by the SHC as PCV20 prevents additional hospitalizations and deaths caused by pneumococcal infection at an affordable cost.

Pneumococcal infections cause a high burden on infected patients and society. Vaccination of patients at risk of severe infection has been recommended for decades, but uptake of pneumococcal vaccines in adults has historically been low in Belgium, where patients have borne the vaccine costs and the recommended vaccination schedule required the sequential administration of two vaccines. A single PCV20 dose is recommended as the preferred vaccine for adults at risk due to age or other factors in Belgium as it is expected to provide lasting protection against more types of disease-causing pneumococcal bacteria as well as being simpler to administer than alternatives requiring multiple injections. Uptake is expected to improve with the recent reimbursement of the new PCV20 vaccine, though reimbursement covers only a portion of the recommended population. This paper presents a detailed analysis of the PCV20 cost-effectiveness in all adults at increased risk of severe pneumococcal disease, including immunocompromised adults younger than 65 years. Our analysis captures and compares the lifetime risk of pneumococcal disease and associated healthcare costs in an unvaccinated cohort, a cohort vaccinated with the alternative recommendation of PCV15 and PPV23 vaccines and a cohort vaccinated with PCV20. This cost-effectiveness analysis indicates that use of PCV20 will help decrease the number of pneumococcal disease cases, hospitalizations, and premature deaths at an affordable healthcare cost: PCV20 is a cost-effective option compared to no vaccination and a cost-saving option compared to the sequential regimen PCV15 followed by PPV23 in the Belgian adult population recommended for pneumococcal vaccination.

Cost-effectiveness of use of 20-valent pneumococcal conjugate vaccine among adults in Germany.

OBJECTIVES: Despite national recommendations for use of pneumococcal vaccines, rates of community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) remain high in Germany. New pneumococcal conjugate vaccines (PCVs) with expanded coverage have the potential to reduce the pneumococcal disease burden among adults. METHODS: Using a Markov model, we evaluated the lifetime outcomes/costs comparing 20-valent PCV (PCV20) with standard of care (SC) vaccinations for prevention of CAP and IPD among adults aged ≥60 years and at-risk adults aged 18-59 years in Germany. PCV20 also was compared with sequential vaccination with 15-valent PCV (PCV15) followed by PPSV23 in a scenario analysis. RESULTS: Over the course of a lifetime (82 years), use of PCV20vs. SC would prevent 54,333 hospitalizations, 26368 outpatient CAP cases, 10946 disease-related deaths yield 74,694 additional life-years (LYs), while lowering total medical costs by 363.2 M €. PCV20 remained cost saving (i.e. dominant) versus SC even in numerous sensitivity analyses, including a sensitivity analysis assuming moderate effectiveness of the SC pneumococcal polysaccharide vaccine against noninvasive pneumococcal CAP. In several scenario analyses and a probabilistic sensitivity analysis, PCV20 was also cost-saving compared toPCV15 PPSV23 vaccination. CONCLUSIONS: One dose of PCV20 among adults aged ≥60 years and adults aged 18-59 years with moderate- and high-risk conditions wouldsubstantially reduce pneumococcal disease, save lives, and be cost saving compared with SC.

Cost-effectiveness of using a 20-valent pneumococcal conjugate vaccine to directly protect adults in England at elevated risk of pneumococcal disease.

OBJECTIVES: Despite the current pneumococcal vaccination program in England for older adults and adults with underlying conditions, disease burden remains high. We evaluated cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to current pneumococcal recommendations for adults in England. METHODS: Lifetime outcomes/costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65-99 years and adults aged 18-64 years with underlying conditions in England were projected using a deterministic cohort model. Vaccination with PCV20 was compared with 23-valent pneumococcal polysaccharide vaccine (PPV23) from the National Health Service perspective. RESULTS: PCV20 was cost saving compared with PPV23 in base case and most sensitivity analyses. In the base case, replacing PPV23 with PCV20 prevented 7,789 and 140,046 cases of IPD and hospitalized CAP, respectively, and 22,199 associated deaths, resulting in incremental gain of 91,375 quality-adjusted life-years (QALYs) and incremental savings of £160M. In probabilistic sensitivity analyses, PCV20 (vs. PPV23) was cost saving in 85% of simulations; incremental cost per QALY was below £30,000 in 99% of simulations. CONCLUSIONS: PCV20 vaccination in adults aged 65-99 years and those aged 18-64 years with underlying comorbidities in England is expected to prevent more hospitalizations, save more lives, and yield lower overall costs than current recommendations for PPV23.

Public health and budgetary impact of 20-valent pneumococcal conjugate vaccine for adults in England.

BACKGROUND: Despite use of 23-valent pneumococcal polysaccharide vaccine (PPV23) in England, disease burden among at-risk adults remains high. We evaluated the public health and budgetary impact of 20-valent pneumococcal conjugate vaccine (PCV20) compared to the current adult pneumococcal vaccination program. METHODS: Five-year outcomes and costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65-99 years and adults aged 18-64 years with underlying conditions in England were projected using a deterministic cohort model. Hypothetical vaccination with PCV20 versus PPV23 was compared from the National Health Service (NHS) perspective. RESULTS: Replacing PPV23 with PCV20 would prevent 785 IPD hospitalizations, 11,751 CAP hospitalizations, and 1,414 deaths over 5 years, and would reduce medical care costs by £48.5 M. With vaccination costs higher by £107.2 M, projected net budgetary impact is £58.7 M. The budgetary impact would be greatest in year 1 (£26.3 M), and would decrease over time (to £1.6 M by year 5). The average budget increase (£11.7 M/year) represents <0.01% of the Department of Health and Social Care total budget and <3% of the vaccine budget. CONCLUSIONS: Use of PCV20 among adults currently eligible for PPV23 in England would substantially reduce the burden of pneumococcal disease, with modest budgetary impact.

Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis.

Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count. Objectives: We used pooled data from pirfenidone and IFNγ-1b trials to explore the association between monocyte count and prognosis in patients with IPF. Methods: This retrospective pooled analysis included patients (active and placebo arms) from the following four phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in FVC% predicted, ≥50 m decline in 6-minute-walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models. Measurements and Main Results: This analysis included 2,067 patients stratified by monocyte count (at baseline: <0.60 × 109 cells/L [n = 1,609], 0.60 to <0.95 × 109 cells/L [n = 408], and ≥0.95 × 109 cells/L [n = 50]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60 to <0.95 × 109 cells/L or ≥0.95 × 109 cells/L versus <0.60 × 109 cells/L experienced IPF progression (P = 0.016 and P = 0.002, respectively), all-cause hospitalization (P = 0.030 and P = 0.003, respectively), and all-cause mortality (P = 0.005 and P < 0.001, respectively) over 1 year. Change in monocyte count from baseline was not associated with any of the outcomes over 1 year and did not appear to be affected by study treatment. Conclusions: In patients with IPF, elevated monocyte count was associated with increased risks of IPF progression, hospitalization, and mortality. Monocyte count may provide a simple and inexpensive prognostic biomarker in IPF.

Bleeding and recurrent VTE with apixaban vs warfarin as outpatient treatment: time-course and subgroup analyses.

In the phase 3 trial Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy, apixaban was noninferior to enoxaparin, overlapped and followed by warfarin, in the treatment of venous thromboembolism (VTE) with significantly less bleeding; in a real-world evaluation, risks for bleeding and recurrent VTE were lower with apixaban vs warfarin plus parenteral anticoagulant (PAC) bridge therapy. The present study extends this research by comparing outcomes over time and within selected subgroups. A retrospective observational cohort design and 4 US private health care claims databases were used. Study population included patients who initiated outpatient treatment with apixaban or warfarin (plus PAC bridge therapy) for VTE. Major bleeding, clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE were compared during the 180-day follow-up period, at selected follow-up time points (days 21, 90, 180), and within subgroups (pulmonary embolism [PE] with or without deep vein thrombosis [DVT], DVT only, provoked VTE, unprovoked VTE) using multivariable shared frailty models. Study population consisted of 20 561 apixaban patients and 35 080 warfarin patients; baseline characteristics were comparable. Overall, at selected follow-up time points, and within the aforementioned subgroups, adjusted risks were lower among apixaban vs warfarin patients: major bleeding, by 27% to 39%, CRNM bleeding, by 17% to 28%, and recurrent VTE, by 25% to 39% (all P ≤ .01). In this real-world study of VTE patients, risks of bleeding and recurrent VTE were lower among apixaban (vs warfarin) patients during the 180-day follow-up period, at selected follow-up time points, and within subgroups defined by index VTE episode.

Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis.

BACKGROUND: Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. Angiotensin modulators are used to treat arterial hypertension, a frequent comorbidity of IPF. This post hoc analysis evaluated associations of antihypertensive treatments with disease-related outcomes in IPF. METHODS: All patients randomized to placebo (n = 624) in the CAPACITY and ASCEND studies were categorized by antihypertensive treatment at baseline. Outcomes of disease progression (first occurrence of ≥ 10% absolute decline in % predicted FVC, ≥ 50-m decline in 6-min walk distance, or death) and all-cause mortality were assessed over 52 weeks. RESULTS: At baseline, 111 and 121 patients were receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), respectively; 392 were receiving neither. In multivariable analyses adjusted for differences in baseline characteristics compared with the non-ACEi/ARB group, ACEi treatment (hazard ratio [HR], 0.6 [95% CI, 0.4-0.9]; P = .026), but not ARB (HR, 0.9 [95% CI, 0.6-1.2]; P = .413), was associated with slower disease progression. Furthermore, the increase in all-cause mortality associated with cardiovascular disease was not observed in the ACEi group (HR, 1.1 [95% CI, 0.5-2.9]; P = .782), which presented a similar percentage of IPF-related mortality as the non-ACEi/ARB group (3.6% vs 3.6%). In contrast, patients in the ARB group had greater risk of all-cause mortality (HR, 2.5 [95% CI, 1.2-5.2]). These observations were validated in a pooled analysis that included patients from the INSPIRE trial. CONCLUSIONS: Prospective clinical trials are needed to evaluate whether angiotensin modulators may be beneficial to clinical outcomes in IPF. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT01366209, NCT00287716, NCT00287729, NCT00075998; URL: www.clinicaltrials.gov).

Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice.

In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64-0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71-0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70-0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.

Cost-effectiveness of PCV13 vaccination in Belgian adults aged 65-84 years at elevated risk of pneumococcal infection.

BACKGROUND: The Belgian Superior Health Council (SHC) recently added a 13-valent pneumococcal conjugate vaccine (PCV13) to its recommendations for adult pneumococcal vaccination. This study addresses the policy question regarding whether a single dose of PCV13 should be reimbursed among Belgian adults aged 65-84 years with chronic comorbidities ("moderate-risk") or immunosuppression ("high-risk"). METHODS: A cohort model was developed to project lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Parameter values were estimated using published literature and available databases, and were reviewed by Belgian experts. PCV13 effectiveness was assumed to be durable during the first 5 years following receipt, and to progressively decline thereafter with 15 years protection. The Belgian National Health Insurance perspective was employed. RESULTS: Use of PCV13 (vs. no vaccine) in moderate/high-risk persons aged 65-84 years (n = 861,467; 58% vaccination coverage) would be expected to prevent 527 cases of IPD, 1,744 cases of pneumococcal CAP and 176 pneumococcal-related deaths, and reduce medical care costs by €20.1 million. Vaccination costs, however, would increase by €36.9 million and thus total overall costs would increase by €16.8 million. Cost per QALY gained was €17,126. In probabilistic sensitivity analyses, use of PCV13 was cost-effective in 97% of 1,000 simulations. CONCLUSIONS: Reimbursement of PCV13 in moderate/high-risk Belgian adults aged 65-84 years would be cost-effective from the Belgian healthcare perspective.

Cost-effectiveness of alternative strategies for use of 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian adults.

OBJECTIVES: The Canadian National Advisory Committee on Immunization (NACI) recommends use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in a sequential schedule (PCV13 → PPV23) among adults aged ≥ 65 years and those aged ≥ 18 years who are immunocompromised. In light of recent PCV13 efficacy data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), and new sero-epidemiology data on community-acquired pneumonia (CAP), we examined the economic implications of funding an expanded adult pneumococcal immunization program in Canada. METHODS: A microsimulation model depicting expected lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and CAP was developed. PPV23 effectiveness was based on published literature, and PCV13 effectiveness was based on CAPiTA; all other model parameters were based on published data or secondary sources. Herd effects from the PCV13 pediatric program were considered. Outcomes and costs were evaluated assuming use of PPV23 alone, and alternatively, use of PCV13 → PPV23 among (1) all adults aged ≥ 65 years (n = 5.4 M) and (2) immunocompromised and high-risk adults aged ≥ 65 years (n = 3.0 M). RESULTS: For population no. 1, PCV13 → PPV23 reduced IPD cases by 1100, CAP cases by 7000, and disease costs by $135.8M; vaccination costs increased by $254.3M, and cost per QALY gained was $35,484. For population no. 2, PCV13 → PPV23 reduced IPD cases by 900, CAP cases by 6000, and disease costs by $120.3M; vaccination costs increased by $149.8M, and cost per QALY gained was $10,728. CONCLUSION: Expanding use of PCV13 → PPV23 by funding PCV13 among Canadian adults aged ≥ 65 would be a cost-effective use of healthcare resources.

Cost-effectiveness of an autoantibody test (EarlyCDT-Lung) as an aid to early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules.

OBJECTIVE: Patients who have incidentally detected pulmonary nodules and an estimated intermediate risk (5-60%) of lung cancer frequently are followed via computed tomography (CT) surveillance to detect nodule growth, despite guidelines for a more aggressive diagnostic strategy. We examined the cost-effectiveness of an autoantibody test (AABT)-Early Cancer Detection Test-Lung (EarlyCDT-LungTM)-as an aid to early diagnosis of lung cancer among such patients. METHODS: We developed a decision-analytic model to evaluate use of the AABT versus CT surveillance alone. In the model, patients with a positive AABT-because they are at substantially enhanced risk of lung cancer-are assumed to go directly to biopsy, resulting in diagnosis of lung cancer in earlier stages than under current guidelines (a beneficial stage shift). Patients with a negative AABT, and those scheduled for CT surveillance alone, are assumed to have periodic CT screenings to detect rapid growth and thus to have their lung cancers diagnosed-on average-at more advanced stages. RESULTS: Among 1,000 patients who have incidentally detected nodules 8-30 mm, have an intermediate-risk of lung cancer, and are evaluated by CT surveillance alone, 95 (9.5%) are assumed to have lung cancer (local, 73.6%; regional, 22.0%; distant, 4.4%). With use of the AABT set at a sensitivity/specificity of 41%/93% (stage shift = 10.8%), although expected costs would be higher by $949,442 ($949 per person), life years would be higher by 53 (0.05 per person), resulting in a cost per life-year gained of $18,029 and a cost per quality-adjusted life year (QALY) gained of $24,330. With use of the AABT set at a sensitivity/specificity of 28%/98% (stage shift = 7.4%), corresponding cost-effectiveness ratios would be $18,454 and $24,833. CONCLUSIONS: Under our base-case assumptions, and reasonable variations thereof, using AABT as an aid in the early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules who are estimated to be at intermediate risk of lung cancer and are scheduled for CT surveillance alone is likely to be a cost-effective use of healthcare resources.

Estimating the cost-effectiveness of a sequential pneumococcal vaccination program for adults in Germany.

INTRODUCTION: In Germany, a 23-valent polysaccharide pneumococcal vaccine (PPSV23) is recommended for elderly (60+) and patients 16+ with chronic diseases not associated with immune suppression. For all other patients at risk, sequential immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) first, followed by PPSV23 is recommended. Repeated vaccination with PPSV23 is recommended every 6 years after individual assessment by the physician. This was adopted into the vaccination directive with binding reimbursement and funding. However, additional voluntary services allow statutory health insurances to differentiate from each other. Aim of this study is to estimate the cost-effectiveness of voluntary service scenarios compared to the strategy in place to support informed decision making. METHODS: A microsimulation framework with Markov-type process of a population susceptible to pneumococcal disease over a lifetime horizon was developed to compare effectiveness and cost-effectiveness of different vaccination strategies. We simulated 1,000 iterations for seven scenarios. Assumptions were derived from published literature and probabilistic sensitivity analysis was run to show the robustness of the model. RESULTS: Our study indicates that all voluntary service strategies could prevent further clinical cases compared to the existing policy. Depending on the scenario, 48-142 invasive pneumococcal disease (IPD), 24,000-45,000 hospitalized all-cause nonbacteremic pneumonia (NBP), 15,000-45,000 outpatient NBP cases, and 4,000-8,000 deaths could be avoided on average. This refers to potential savings of €115 Mio. - €187 Mio. for medical and non-medical costs. Additional costs per patient for the payer are €2.48 to €7.13 and for the society €2.20 to €6.85. The ICER per LYG ranged from €3,662 to €23,061 (payer) and €3,258 to €29,617 (societal). All but one scenario was cost-effective in ≥60% of the generated 1,000 simulations. CONCLUSION: Compared to the vaccination strategy in place, the different hypothetical scenarios can be considered cost-effective and suitable as additional voluntary services.

Effect of Emphysema Extent on Serial Lung Function in Patients with Idiopathic Pulmonary Fibrosis.

RATIONALE: Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. OBJECTIVES: In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. METHODS: Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV1/FVC ratios less than 0.8 or greater than 0.9 (<0.7 or >0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8-0.9 and 0.7-0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. MEASUREMENTS AND MAIN RESULTS: Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. CONCLUSIONS: FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.