Impact of Elexacaftor/Tezacaftor/Ivacaftor on Healthcare Resource Utilization and Associated Costs Among People With Cystic Fibrosis in the US: A Retrospective Claims Analysis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a CFTR modulator (CFTRm) that targets the underlying cause of CF. Based on safety and efficacy demonstrated in clinical trials, ELX/TEZ/IVA is approved in the US for the treatment of CF in people aged ≥ 2 years who have ≥ 1 F508del-CFTR mutation or a CFTR mutation that is responsive to ELX/TEZ/IVA based on in vitro data. While ELX/TEZ/IVA demonstrated unprecedented improvements in lung function and dramatic reductions in pulmonary exacerbations (PEx) and associated hospitalizations in clinical trials, a limited number of studies have examined the impact of ELX/TEZ/IVA on healthcare resource utilization (HCRU) and associated costs in a real-world setting. The aim of this retrospective study was to evaluate changes in PEx, HCRU, and associated non-CFTRm healthcare costs following initiation of ELX/TEZ/IVA among people with CF aged ≥ 12 years in the US. METHODS: We evaluated the rates of PEx, HCRU, and associated costs before and after initiation of ELX/TEZ/IVA in people with CF aged ≥ 12 years using data from the Merative MarketScan® Commercial Claims and Encounters Database and the Merative Multi-State Medicaid Database from April 21, 2019 to December 31, 2020. Because the study period included time following the onset of the COVID-19 pandemic, we limited our primary analysis to the period prior to the pandemic (October 21, 2019 to March 12, 2020). Outcomes following the onset of the pandemic (March 13 to December 31, 2020) were examined in an exploratory analysis. RESULTS: In both commercially insured and Medicaid-insured people with CF, ELX/TEZ/IVA was associated with reductions in PEx, hospitalizations, and associated costs prior to the COVID-19 pandemic, and these reductions were maintained following the onset of the pandemic. CONCLUSIONS: These findings suggest that ELX/TEZ/IVA reduces the burden and costs associated with PEx and hospitalizations in people with CF.

Healthcare resource utilization and costs among children with cystic fibrosis in the United States.

BACKGROUND: Adverse health impacts of cystic fibrosis (CF) can be present in children before respiratory complications are observed. Children with CF show progressive health decline, with increasing lung function decline in adolescence. This study aims to quantify the healthcare resource utilization (HCRU) and costs attributable to CF by comparing children with CF with the general pediatric population. METHODS: This retrospective, cross-sectional, observational study compared HCRU and costs among children with CF in the US with demographically similar children without CF (comparison group) over a 12-month period using administrative claims data spanning 2010-2017. Analyses were conducted by insurance type (commercially insured [COM] and Medicaid insured [MED]) and stratified by age (<2 years, 2 to <6 years, 6 to <12 years, and 12-17 years). RESULTS: Children with CF (2831 COM and 1896 MED) were matched to children in the comparison group (8493 COM and 5688 MED). Higher prevalence of comorbidities was seen in children with CF versus the comparison group across all ages. Across all ages, HCRU attributable to CF was substantial (higher hospitalization rates, more outpatient and emergency room visits, and greater use of prescription medications), and there were higher associated costs (all p values < .05), in COM and MED populations. HCRU and costs attributable to CF were highest for children aged 12-17 years. CONCLUSIONS: Substantial HCRU and costs are evident among children with CF across all ages, starting as young as infancy, with highest HCRU and costs among adolescents. Effective treatments from an early age are needed for children with CF.

Cost Effectiveness of the Third-Generation Tyrosine Kinase Inhibitor (TKI) Ponatinib, vs. Second-Generation TKIs or Stem Cell Transplant, as Third-Line Treatment for Chronic-Phase Chronic Myeloid Leukemia.

BACKGROUND AND OBJECTIVES: Third-line treatment options for patients with chronic-phase chronic myeloid leukemia include tyrosine kinase inhibitors and allogeneic hematopoietic stem cell transplantation (alloHSCT). The objective of this study was to develop a Markov model with a lifetime time horizon to assess the cost effectiveness of ponatinib for third-line chronic-phase chronic myeloid leukemia vs. second-generation tyrosine kinase inhibitors (dasatinib, nilotinib, bosutinib) or alloHSCT from the public healthcare system perspective in Germany, Sweden, and Canada. METHODS: Clinical outcomes were derived from the literature, and from patient-level data (phase II PACE trial) for ponatinib. Resource use included drugs, alloHSCT, monitoring and follow-up, adverse events, and end-of-life care; costs were based on national tariffs. Quality-adjusted life-years (QALYs) were calculated using chronic myeloid leukemia health-state utilities from an international time-trade-off study. Costs and benefits were discounted at 3% per annum for Germany and Sweden, and 5% for Canada. RESULTS: Ponatinib yielded more discounted QALYs than any second-generation tyrosine kinase inhibitor/alloHSCT in all three countries, mainly owing to better response rates and longer durations of response. Incremental cost-effectiveness ratios for ponatinib vs. second-generation tyrosine kinase inhibitors were US$21,543-37,755/QALY in Germany, $24,018-38,227/QALY in Sweden, and $43,001-58,515/QALY in Canada. Ponatinib was dominant over alloHSCT in Germany, while incremental cost-effectiveness ratios for ponatinib vs. alloHSCT in Sweden and Canada were $715/QALY and $31,534/QALY, respectively. CONCLUSIONS: Ponatinib may improve outcomes (mainly because of higher response rates and longer response durations) at an acceptable cost level compared with other third-line treatment options for chronic-phase chronic myeloid leukemia in Germany, Sweden, and Canada; however, the lack of an indirect comparison is a limitation of our study.

Mortality and Vascular Events Among Elderly Patients With Chronic Myeloid Leukemia: A Retrospective Analysis of Linked SEER-Medicare Data.

BACKGROUND: Tyrosine-kinase inhibitors (TKIs) can be associated with vascular events (VEs). The expected VE rates in patients with chronic myeloid leukemia (CML) are unknown. The present study examined the event rates and mortality among elderly patients with and without CML. MATERIALS AND METHODS: Linked Surveillance, Epidemiology, and End Results cancer registry and Medicare claims data were used to identify patients aged ≥ 66 years with an incident (index) diagnosis of CML from 2004 to 2009. A comparison cohort of patients without cancer was matched 1:1 to the CML cohort. All patients were followed up from 12 months before the index diagnosis through death or December 31, 2010. The overall survival and rates of myocardial infarction (MI), stroke, pulmonary embolism (PE), and peripheral arterial disease (PAD) were analyzed. RESULTS: A total of 1466 patients with CML (mean age, 78 years; average follow-up period, 25 months) were identified and matched 1:1 to a noncancer cohort (mean age, 78 years; follow-up period, 42 months). Compared with the noncancer patients, those with CML had greater mortality (63% vs. 23% died during the follow-up period; median survival, 23 vs. > 84 months) and greater rates of MI (33.0 vs. 11.9 per 1000 person-years), stroke (83.2 vs. 43.0), PE (6.6 vs. 2.6), and PAD (92.1 vs. 59.3; P < .01 for all). Of the 15% of CML patients with TKI claims, 97% had received imatinib. The event rates were not elevated for TKI-treated patients compared with the overall group of patients with CML. CONCLUSION: Elderly patients with CML had greater mortality and greater rates of MI, stroke, PE, and PAD than did noncancer patients. The event rates were not elevated among the TKI-treated (primary imatinib) patients, suggesting that the VE risk in these patients with CML was driven primarily by the underlying factors associated with CML.

Increasing economic burden of tyrosine kinase inhibitor treatment failure by line of therapy in chronic myeloid leukemia.

OBJECTIVE: To assess the economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML), by assessing all-cause health care resource use (HCRU) and costs in the year after treatment failure by line of therapy (LOT; 1L/2L/3L) using real-world data. METHODS: Treatment episodes initiating a TKI of interest (index TKI) during June 2008-December 2011 were identified from the IMS PharMetrics Plus Health Plan Claims Database for adult patients with CML diagnosis (ICD-9-CM 205.1x), 120 days pre-index continuous enrollment (CE) and no clinical trial participation. Episodes experiencing treatment failure, defined as switch to a non-index TKI or discontinuation of index TKI (gap of ≥ 60 days), and with 1 year CE post-failure, were analyzed. LOT was determined by number of unique TKIs used in the pre-index. All-cause HCRU and costs (2012 USD) in the 1 year post-failure were assessed by LOT, and the comparisons between 1L and 2L failures were also adjusted using multivariate generalized linear models (GLMs) to control for underlying differences. RESULTS: A total of 706 episodes were identified (518 1L; 180 2L; 8 3L). Unadjusted HCRU over 1 year post-failure increased significantly. This was accompanied by a significant increase in unadjusted mean costs for 2L failures vs. 1L failures ($99,624 vs. $78,667, p = 0.021, Δ$20,957). Following the adjustment using GLMs, adjusted mean costs were 38% higher (95% CI 1.14-1.68), driven primarily by use of medical services. In adjusted analyses, compared to 1L, 2L failures had: 45% more ambulatory visits (mean 31 vs. 21, 95% CI 1.26-1.66), 75% higher risk of hospitalization (33% vs. 23% hospitalized, 95% CI 1.16-2.64), and 73% higher medical costs (95% CI 1.31-2.29). Medical costs comprised a greater proportion of total costs in 2L vs. 1L (55% vs. 44%); pharmacy costs did not increase significantly. CONCLUSIONS: The economic burden over 1 year post TKI failure increased with each sequential line of TKI treatment failure.

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.

Cost-effectiveness analysis of universal influenza vaccination with quadrivalent inactivated vaccine in the United States.

To address influenza B lineage mismatch and co-circulation, several quadrivalent inactivated influenza vaccines (IIV4s) containing two type A strains and both type B lineages have recently been approved in the United States. Currently available trivalent inactivated vaccines (IIV3s) or trivalent live attenuated influenza vaccines (LAIV3s) comprise two influenza A strains and one of the two influenza B lineages that have co-circulated in the United States since 2001. The objective of this analysis was to evaluate the cost-effectiveness of a policy of universal vaccination with IIV4 vs. IIV3/LAIV3 during 1 year in the United States. On average per influenza season, IIV4 was predicted to result in 30,251 fewer influenza cases, 3512 fewer hospitalizations, 722 fewer deaths, 4812 fewer life-years lost, and 3596 fewer quality-adjusted life-years (QALYs) lost vs. IIV3/LAIV3. Using the Fluarix Quadrivalent(TM) (GlaxoSmithKline) prices and the weighted average IIV3/LAIV3 prices, the model predicts that the vaccination program costs would increase by $452.2 million, while direct medical and indirect costs would decrease by $111.6 million and $218.7 million, respectively, with IIV4. The incremental cost-effectiveness ratio (ICER) comparing IIV4 to IIV3/LAIV3 is predicted to be $90,301/QALY gained. Deterministic sensitivity analyses found that influenza B vaccine-matched and mismatched efficacies among adults aged ≥65 years had the greatest impact on the ICER. Probabilistic sensitivity analysis showed that the cost per QALY remained below $100,000 for 61% of iterations. In conclusion, vaccination with IIV4 in the US is predicted to reduce morbidity and mortality. This strategy is also predicted to be cost-effective vs. IIV3/LAIV3 at conventional willingness-to-pay thresholds.

Cost-effectiveness of Tdap vaccination of adults aged ≥65 years in the prevention of pertussis in the US: a dynamic model of disease transmission.

OBJECTIVES: In February 2012, the Advisory Committee on Immunization Practices (ACIP) advised that all adults aged ≥65 years receive a single dose of reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap), expanding on a 2010 recommendation for adults >65 that was limited to those with close contact with infants. We evaluated clinical and economic outcomes of adding Tdap booster of adults aged ≥65 to "baseline" practice [full-strength DTaP administered from 2 months to 4-6 years, and one dose of Tdap at 11-64 years replacing decennial Td booster], using a dynamic model. METHODS: We constructed a population-level disease transmission model to evaluate the cost-effectiveness of supplementing baseline practice by vaccinating 10% of eligible adults aged ≥65 with Tdap replacing the decennial Td booster. US population effects, including indirect benefits accrued by unvaccinated persons, were estimated during a 1-year period after disease incidence reached a new steady state, with consequences of deaths and long-term pertussis sequelae projected over remaining lifetimes. Model outputs include: cases by severity, encephalopathy, deaths, costs (of vaccination and pertussis care) and quality-adjusted life-years (QALYs) associated with each strategy. Results in terms of incremental cost/QALY gained are presented from payer and societal perspectives. Sensitivity analyses vary key parameters within plausible ranges. RESULTS: For the US population, the intervention is expected to prevent >97,000 cases (>4,000 severe and >5,000 among infants) of pertussis annually at steady state. Additional vaccination costs are $4.7 million. Net cost savings, including vaccination costs, are $47.7 million (societal perspective) and $44.8 million (payer perspective). From both perspectives, the intervention strategy is dominant (less costly, and more effective by >3,000 QALYs) versus baseline. Results are robust to sensitivity analyses and alternative scenarios. CONCLUSIONS: Immunization of eligible adults aged ≥65, consistent with the current ACIP recommendation, is cost saving from both payer and societal perspectives.

Cost-effectiveness analysis of Tdap in the prevention of pertussis in the elderly.

OBJECTIVES: Health benefits and costs of combined reduced-antigen-content tetanus, diphtheria, and pertussis (Tdap) immunization among adults ≥65 years have not been evaluated. In February 2012, the Advisory Committee on Immunization Practices (ACIP) recommended expanding Tdap vaccination (one single dose) to include adults ≥65 years not previously vaccinated with Tdap. Our study estimated the health and economic outcomes of one-time replacement of the decennial tetanus and diphtheria (Td) booster with Tdap in the 10% of individuals aged 65 years assumed eligible each year compared with a baseline scenario of continued Td vaccination. METHODS: We constructed a model evaluating the cost-effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating pertussis cases averted due to direct vaccine effects only. Results are presented from societal and payer perspectives for a range of pertussis incidences (25-200 cases per 100,000), due to the uncertainty in estimating true annual incidence. Cases averted were accrued throughout the patient 's lifetime, and a probability tree used to estimate the clinical outcomes and costs (US$ 2010) for each case. Quality-adjusted life-years (QALYs) lost to acute disease were calculated by multiplying cases of mild/moderate/severe pertussis by the associated health-state disutility; QALY losses due to death and long-term sequelae were also considered. Incremental costs and QALYs were summed over the cohort to derive incremental cost-effectiveness ratios. Scenario analyses evaluated the effect of alternative plausible parameter estimates on results. RESULTS: At incidence levels of 25, 100, 200 cases/100,000, vaccinating adults aged 65 years costs an additional $336,000, $63,000 and $17,000/QALY gained, respectively. Vaccination has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is >116 cases/100,000 from societal and payer perspectives. Results were robust to scenario analyses. CONCLUSIONS: Tdap immunization of adults aged 65 years according to current ACIP recommendations is a cost-effective health-care intervention at plausible incidence assumptions.

Economic model of a birth cohort screening program for hepatitis C virus.

UNLABELLED: Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus $53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus $39.8 billion); birth-cohort screening produces an incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus risk-based screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs. CONCLUSION: Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness-to-pay thresholds.

All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective.

BACKGROUND: Approximately 3.2-3.9 million U.S. residents are infected with the hepatitis C virus (HCV). Total annual costs (direct and indirect) in the United States for HCV were estimated to be $5.46 billion in 1997, and direct medical costs have been predicted to increase to $10.7 billion for the 10-year period from 2010 through 2019, due in part to the increasing number of HCV patients developing advanced liver disease (AdvLD). OBJECTIVE: To quantify in a sample of commercially insured enrollees (a) total per patient per year (PPPY) all-cause costs to the payer, overall and by the stage of liver disease, for patients diagnosed with HCV; and (b) incremental all-cause costs for patients diagnosed with HCV relative to a matched non-HCV cohort. METHODS: This retrospective, matched cohort study included patients aged at least 18 years and with at least 6 months of continuous enrollment in a large managed care organization (MCO) claims database from July 1, 2001, through March 31, 2010. Patients with a diagnosis of HCV (ICD-9-CM codes 070.54, 070.70) were identified and stratified into those with and without AdvLD, defined as decompensated cirrhosis (ICD-9-CM codes 070.44, 070.71, 348.3x, 456.0, 456.1, 456.2x, 572.2, 572.3, 572.4, 782.4, 789.59); hepatocellular carcinoma (HCC, ICD-9-CM code 155); or liver transplant (ICD-9-CM codes V42.7, 50.5 or CPT codes 47135, 47136). For patients without AdvLD, the index date was the first HCV diagnosis date observed at least 6 months after the first enrollment date, and at least 6 months of continuous enrollment after the index date were required. HCV patients without AdvLD were stratified into those with and without compensated cirrhosis (ICD-9-CM codes 571.2, 571.5, 571.6). For patients with AdvLD, the index date was the date of the first AdvLD diagnosis observed at least 6 months after the first enrollment date, and at least 1 day of enrollment after the index date was required. Cases were matched in an approximate 1:10 ratio to comparison patients without an HCV diagnosis or AdvLD diagnosis who met all other inclusion criteria based on gender, age, hospital referral region state, pre-index health care costs, alcoholism, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and a modified Charlson Comorbidity Index. For the HCV and comparison patient cohorts, PPPY all-cause costs to the payer were calculated as total allowed charges summed across all patients divided by total patient-days of follow-up for the cohort, multiplied by 365, inflation-normalized to 2009 dollars. Because the calculation of PPPY cost generated a single value for each cohort, bootstrapping was used to generate descriptive statistics. Incremental PPPY costs for HCV patients relative to non-HCV patients were calculated as between-group differences in PPPY costs. T-tests for independent samples were used to compare costs between case and comparison cohorts. RESULTS: A total of 34,597 patients diagnosed with HCV, 78.0% with HCV without AdvLD, 4.4% with compensated cirrhosis, 12.3% with decompensated cirrhosis, 2.8% with HCC, and 2.6% with liver transplant, were matched to 330,435 comparison patients. Mean (SD) age of all HCV cases was 49.9 (8.5) years; 61.7% were male. Incremental mean (SD) PPPY costs in 2009 dollars for all HCV patients relative to comparison patients were $ 9,681 ($176) PPPY. Incremental PPPY costs were $5,870 ($157) and $5,330 ($491) for HCV patients without liver disease and with compensated cirrhosis, respectively. Incremental PPPY costs for patients with AdvLD were $27,845 ($ 965) for decompensated cirrhosis, $43,671 ($2,588) for HCC, and $ 93,609 ($4,482) for transplant. Incremental prescription drug costs, including the cost of antiviral drugs, were $2,739 ($37) for HCV patients overall, $2,659 ($41) for HCV without liver involvement, and $3,102 ($157) for HCV with compensated cirrhosis. These between-group differences were statistically significant at P<0.001. CONCLUSIONS: Based on a retrospective analysis of data from a large, MCO claims database, patients diagnosed with HCV had annual all-cause medical costs that were almost twice as high as those of enrollees without a diagnosis of HCV. Health care costs increased dramatically with AdvLD. Data from this study may help MCOs project future HCV costs and facilitate planning for HCV patient management efforts.

Public health and economic impact of the 13-valent pneumococcal conjugate vaccine (PCV13) in the United States.

The 7-valent pneumococcal conjugate vaccine (PCV7) has dramatically decreased pneumococcal disease incidence, and the 13-valent vaccine (PCV13) protects against 6 additional Streptococcus pneumoniae serotypes. A decision-analytic model was constructed to evaluate the impact of infant vaccination with PCV13 versus PCV7 on pneumococcal disease incidence and mortality as well as the incremental benefit of a serotype catch-up program. PCV13 effectiveness was extrapolated from observed PCV7 data, using assumptions regarding serotype prevalence and PCV13 protection against additional serotypes. The model predicts that PCV13 is more effective and cost saving compared with PCV7, preventing 106,000 invasive pneumococcal disease (IPD) cases and 2.9 million pneumonia cases, and saving $11.6 billion over a 10-year period. The serotype catch-up program would prevent an additional 12,600 IPD cases and 404,000 pneumonia cases, and save an additional $737 million compared with no catch-up program.

Economic assessment of doripenem versus imipenem in the treatment of ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP), the most common nosocomial infection in critically ill patients, is associated with significantly longer duration of mechanical ventilation, and increased mortality, hospital days, and health-care costs. A previously published prospective, randomized study established the noninferiority of intravenous (IV) doripenem versus IV imipenem/cilastatin ('imipenem') for VAP. This study compares the economic outcomes of IV therapy with doripenem versus imipenem as first-line treatment for VAP. METHODS: A decision-analytic model of inpatient care and outcomes for VAP was used to estimate costs associated with VAP treatment. The model calculates total hospital costs, comprising costs of initial and concomitant therapy, and costs associated with mechanical ventilation, intensive care unit stays, and total days in hospital. RESULTS: Total treatment costs for doripenem were $10,630 lower than for imipenem ($71,259 vs. 81,889), driven primarily by differences in costs of mechanical ventilation ($45,224 for doripenem, $57,348 for imipenem). Probabilistic sensitivity analyses found doripenem consistently cost saving versus imipenem in 1,000 simulations. Study limitations include use of a simple model to represent a complex disease process and reliance on trial data that may not reflect real-world care and outcomes. CONCLUSIONS: Doripenem is a cost saving first-line treatment for VAP versus imipenem while providing an equivalent rate of cure.

Public health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) in the context of the annual influenza epidemic and a severe influenza pandemic.

BACKGROUND: Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. METHODS: A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. RESULTS: The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. CONCLUSIONS: PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.

Cost effectiveness of thromboprophylaxis with a low-molecular-weight heparin versus unfractionated heparin in acutely ill medical inpatients.

OBJECTIVE: To compare the cost effectiveness of prophylaxis with a low-molecular-weight heparin with that of prophylaxis with unfractionated heparin for the prevention of venous thromboembolism in acutely ill medical inpatients. STUDY DESIGN: Cost-effectiveness analysis based on decision-tree model. PARTICIPANTS AND METHODS: A hypothetical cohort of 10 000 patients was assumed to receive either (1) prophylaxis with enoxaparin, a low-molecular-weight heparin, 40 mg daily; (2) prophylaxis with unfractionated heparin, 5000 IU twice daily; or (3) no prophylaxis. We developed a decision-analytic model with parameter estimates derived from published clinical trials and other secondary sources. Then, for each strategy, we estimated the risks of venous thromboembolism, complications of prophylaxis and treatment (heparin-induced thrombocytopenia and bleeding), mortality, and costs of prophylaxis and treatment within a 30-day period. RESULTS: In a hypothetical cohort of 10 000 inpatients, expected numbers of deaths attributable to venous thromboembolism or drug complications related to both prophylaxis for and treatment of VTE over a 30-day period were 37 with enoxaparin prophylaxis, 53 with unfractionated heparin prophylaxis, and 81 with no prophylaxis. In 2001, corresponding expected costs of prevention, diagnosis, and management of VTE were $3 502 000 for enoxaparin, $3 772 000 for unfractionated heparin, and $3 105 000 for no prophylaxis. The incremental cost per death averted with enoxaparin prophylaxis versus no prophylaxis was $9100. Enoxaparin dominated unfractionated heparin by being both more effective and less costly in the base-case analysis, as well as in sensitivity analyses in which equal efficacy and equal risks of bleeding were assumed. CONCLUSIONS: Thromboprophylaxis with this low-molecular-weight heparin represents a cost-effective use of healthcare resources in acutely ill medical inpatients and dominates thromboprophylaxis with unfractionated heparin.

Outcomes and costs of acute treatment of traumatic brain injury.

BACKGROUND: Although there are nearly a quarter of a million hospitalizations for traumatic brain injury (TBI) in the United States each year, data on the outcomes and costs of TBI treatment in the acute-care setting are limited. METHODS: Using a large, geographically diverse, multihospital database, we examined inpatient records for persons aged 16 years or older who were hospitalized for TBI between January 1, 1997, and June 30, 1999. Patients were stratified by TBI severity using an adaptation of the Abbreviated Injury Scale for administrative data (ICD/AIS), as follows: 2 = "moderate"; 3 = "serious"; 4 = "severe"; and 5 = "critical." Patient characteristics, patterns of treatment, and outcomes and costs were examined by injury severity and mechanism of injury. RESULTS: Of 8,717 study subjects identified, 12.5% had moderate, 44.8% had serious, 29.6% had severe, and 13.2% had critical TBI. Falls were the most common reported cause of injury (40.8%), followed by motor vehicle crashes (39.3%), blows to the head (11.3%), and gunshot wounds (2.4%). Average length of stay in hospital ranged from 6.7 days for moderate TBI to 17.5 days for critical TBI. The overall rate of death in hospital was relatively low among patients with moderate (1.3%), serious (5.7%), and severe (8.7%) TBIs, but much higher among the most critically injured patients (52.0%). Costs of hospitalization averaged 8,189 dollars for moderate, 14,603 dollars for serious, 16,788 dollars for severe, and 33,537 dollars for critical TBI. Costs also varied by injury type, averaging 20,084 dollars for gunshot wounds, 20,522 dollars for motor vehicle crashes, 15,860 dollars for falls, and 19,949 dollars for blows to the head. CONCLUSION: The economic burden of TBI in the acute-care setting is substantial; treatment outcomes and costs vary considerably by TBI severity and mechanism of injury.