Indirect treatment comparisons including network meta-analysis: Lenvatinib plus everolimus for the second-line treatment of advanced/metastatic renal cell carcinoma.

BACKGROUND: In the absence of clinical trials providing direct efficacy results, this study compares different methods of indirect treatment comparison (ITC), and their respective impacts on efficacy estimates for lenvatinib (LEN) plus everolimus (EVE) combination therapy compared to other second-line treatments for advanced/metastatic renal cell carcinoma (a/mRCC). METHODS: Using EVE alone as the common comparator, the Bucher method for ITC compared LEN + EVE with cabozantinib (CAB), nivolumab (NIV), placebo (PBO) and axitinib (AXI). Hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) estimated the impact of applying three versions of the LEN+EVE trial data in separate ITCs. Last, to overcome exchangeability bias and potential violations to the proportional hazards assumption, a network meta-analysis using fractional polynomials was performed. RESULTS: Bucher ITCs demonstrated LEN + EVE superiority over EVE for PFS, indirect superiority to NIV, AXI, and PBO, and no difference to CAB. For OS, LEN + EVE was superior to EVE and indirectly superior to PBO, applying original HOPE 205 data. Using European Medicines Agency data, LEN + EVE was directly superior to EVE for OS. Fractional polynomial HRs for PFS and OS substantially overlapped with Bucher estimates, demonstrating LEN+EVE superiority over EVE, alone, NIV, and CAB. However, there were no statistically significant results as the credible intervals for HR crossed 1.0. CONCLUSIONS: Comparing three Bucher ITCs, LEN + EVE demonstrated superior PFS when indirectly compared to NIV, AXI, and PBO, and mixed results for OS. While fractional polynomial modelling for PFS and OS failed to find statistically significant differences in LEN + EVE efficacy, the overall HR trends were comparable.

Public health impact of comprehensive hepatitis C screening and treatment in the French baby-boomer population.

OBJECTIVE: To estimate the public health impact of comprehensive hepatitis C virus (HCV) screening and access to all-oral, interferon (IFN)-free direct-acting antivirals (DAAs) in the French baby-boomer population (1945-1965 birth cohorts). METHODS: A sequential, multi-cohort, health-state transition model was developed to assess the impact of different hepatitis C screening and treatment strategies on clinical and economic outcomes in the 1945-1965 birth cohorts. Patients newly-diagnosed with chronic HCV were projected each year from 2016 to 2036 under three screening scenarios (70% [low], 75% [intermediate], and 80% [high] HCV awareness in 2036). Healthcare costs and clinical outcomes (number of liver-related deaths, quality-adjusted life-years [QALYs], life-years [LYs] spent in sustained virologic response [SVR] or with decompensated cirrhosis, hepatocellular carcinoma, or liver transplant) were compared among five treatment strategies (no antiviral therapy; IFN + ribavirin + protease inhibitor for fibrosis stages F2-F4, IFN-based DAAs for stages F2-F4, IFN-free DAAs for stages F2-F4, and IFN-free DAAs for stages F0-F4). RESULTS: Diagnosis of HCV genotype 1 was projected for 4,953, 6,600, and 8,368 individuals in the low, intermediate, and high screening scenarios, respectively. In the intermediate scenario, IFN-free DAAs for stages F0-F4 had a favorable cost-effectiveness profile vs IFN-based or IFN-free treatment strategies for F2-F4 and offered the greatest return on investment (0.899 LYs gained in SVR and 0.933 QALYs per €10,000 invested). CONCLUSION: Comprehensive HCV screening and access to all-oral, IFN-free DAAs is a cost-effective strategy that could help diminish the upcoming burden of HCV in the French baby-boomer population.

Cost-Effectiveness of Genotype 1 Chronic Hepatitis C Virus Treatments in Patients Coinfected with Human Immunodeficiency Virus in the United States.

INTRODUCTION: New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients. METHODS: A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R. CONCLUSION: In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV.

Economic evaluation of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic genotype 1 hepatitis c virus infection.

OBJECTIVES: To estimate clinical outcomes and cost-effectiveness of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (OMB/PTV/r + DSV ± RBV) compared with treatment regimens including pegylated interferon (PegIFN) for patients with chronic genotype 1 hepatitis C virus (HCV) infection. METHODS: An Excel spreadsheet Markov model tracking progression through stages of liver disease was developed. Costs and patient utilities for liver disease stages were taken from published studies. Rates of disease progression were based on studies of untreated HCV infection and long-term follow-up of those achieving sustained virologic response (SVR) after drug treatment. Impact of OMB/PTV/r + DSV ± RBV and other drug regimens on progression was estimated through SVR rates from clinical trials. Analyses were performed for treatment-naive and treatment-experienced patients. Impact of alternative scenarios and input parameter uncertainty on the results were tested. RESULTS: For genotype 1 treatment-naive HCV patients, for OMB/PTV/r + DSV ± RBV, PegIFN + ribavirin (PegIFN/RBV), sofosbuvir + PegIFN/RBV, telaprevir + PegIFN/RBV, boceprevir + PegIFN/RBV, lifetime risk of decompensated liver disease was 5.6%, 18.9%, 7.4%, 11.7%, and 14.9%; hepatocellular carcinoma was 5.4%, 9.2%, 5.7%, 7.0%, and 7.4%; and death from liver disease was 8.7%, 22.2%, 10.4%, 14.8%, and 17.6%, respectively. Estimates of the cost-effectiveness of OMB/PTV/r + DSV ± RBV for treatment-naive and treatment-experienced patients indicated that it dominated all other regimens except PegIFN/RBV. Compared with PegIFN/RBV, the incremental cost-effectiveness ratios were £13,864 and £10,258 per quality-adjusted life-year (QALY) for treatment-naive and treatment-experienced patients, respectively. The results were similar for alternative scenarios and uncertainty analyses. LIMITATIONS: A mixed-treatment comparison for SVR rates for the different treatment regimens was not feasible, because many regimens did not have comparator arms; instead SVR rates were based on those from recent trials. CONCLUSIONS: OMB/PTV/r + DSV ± RBV is a cost-effective oral treatment regimen for chronic genotype 1 HCV infection compared with standard treatment regimens and is estimated to reduce the lifetime risks of advanced liver disease.

Cost-effectiveness of currently recommended direct-acting antiviral treatments in patients infected with genotypes 1 or 4 hepatitis C virus in the US.

OBJECTIVE: This study compared the cost-effectiveness of direct-acting antiviral therapies currently recommended for treating genotypes (GT) 1 and 4 chronic hepatitis C (CHC) patients in the US. METHODS: A cost-effectiveness analysis of treatments for CHC from a US payer's perspective over a lifelong time horizon was performed. A Markov model based on the natural history of CHC was used for a population that included treatment-naïve and -experienced patients. Treatment alternatives considered for GT1 included ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± R), sofosbuvir + ledipasvir (SOF/LDV), sofosbuvir + simeprevir (SOF + SMV), simeprevir + pegylated interferon/ribavirin (SMV + PR) and no treatment (NT). For GT4 treatments, ombitasvir/paritaprevir/ritonavir + ribavirin (2D + R), SOF/LDV and NT were compared. Transition probabilities, utilities and costs were obtained from published literature. Outcomes included rates of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver-related death (LrD), total costs, life-years and quality-adjusted life-years (QALYs). Costs and QALYs were used to calculate incremental cost-effectiveness ratios. RESULTS: In GT1 patients, 3D ± R and SOF-containing regimens have similar long-term outcomes; 3D ± R had the lowest lifetime risks of all liver disease outcomes: CC = 30.2%, DCC = 5.0 %, HCC = 6.8%, LT = 1.9% and LrD = 9.2%. In GT1 patients, 3D ± R had the lowest cost and the highest QALYs. As a result, 3D ± R dominated these treatment options. In GT4 patients, 2D + R had lower rates of liver morbidity and mortality, lower cost and more QALYs than SOF/LDV and NT. LIMITATIONS: While the results are based on input values, which were obtained from a variety of heterogeneous sources-including clinical trials, the findings were robust across a plausible range of input values, as demonstrated in probabilistic sensitivity analyses. CONCLUSIONS: Among currently recommended treatments for GT1 and GT4 in the US, 3D ± R (for GT1) and 2D + R (for GT4) have a favorable cost-effectiveness profile.

Pediatricians' preferences for infant meningococcal vaccination.

BACKGROUND: Meningococcal disease is rare but can cause death or disabilities. Although the Advisory Committee on Immunization Practices has recommended meningococcal vaccination for at-risk children aged 9 through 23 months, it has not endorsed universal vaccination. Health insurance payments for the vaccination of children who are not at risk are likely to be limited. Use of infant meningococcal vaccines by these families will thus depend on the preferences of physicians who might recommend vaccination to parents, as well as parents' preferences. OBJECTIVE: To quantify pediatricians' preferences for specific features of hypothetical infant meningococcal vaccines. METHODS: A sample of pediatricians (n = 216) completed a Web-enabled, discrete choice experiment survey in which respondents chose between pairs of hypothetical vaccines in a series of trade-off questions. The questions described vaccines with six attributes. A random-parameters logit regression model was used to estimate the relative importance weights physicians place on vaccine features. These weights were used to calculate the predicted probability that a physician chooses hypothetical vaccines with given characteristics. RESULTS: Pediatricians' choices indicated that increases in vaccine effectiveness were among the most important factors in their vaccine recommendations, followed by increases in the number of injections. The age at which protection begins and the number of additional office visits were less important. Whether a booster was required after 5 years was the least important factor in vaccine recommendations. The results suggest that virtually all (99.9%) physicians in the sample would recommend a vaccine even with the least-preferred features rather than no infant meningococcal vaccine. CONCLUSIONS: Physicians' responses indicate a strong preference for infant meningococcal vaccination.

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.

Influenza-related health care utilization and productivity losses during seasons with and without a match between the seasonal and vaccine virus B lineage.

OBJECTIVE: To assess and compare direct medical costs (incurred by payers) and indirect productivity losses (incurred by employers) associated with influenza seasons with matched or mismatched circulating and vaccine containing influenza B lineages. METHODS: A retrospective analysis, using two MarketScan databases, for the years 2000-2009. Each influenza season was categorized as matched or mismatched after comparing that season's circulating influenza B lineage and the vaccine influenza B lineage. Patients selected had at least one diagnosis claim for influenza (ICD-9-CM code 487.xx [influenza] or 488.1 [H1N1]) during an influenza season. We assessed the incidence of influenza (overall and influenza B), influenza-related medical utilization and associated costs, and productivity losses for each season. RESULTS: The four matched seasons had lower average influenza incidence (overall incidence per 100,000 plan members: 509; 95% confidence interval [CI]: 505-512) than the five mismatched seasons (748; 95% CI: 745-751). The mismatched seasons had lower influenza B incidence (average incidence per 100,000 plan members: 126; 95% CI: 125-128) than the matched seasons (165; 95% CI: 163-167). The average, per-patient, total influenza-related medical costs in the mismatched seasons ($300.83; range: $245.38-$371.58) were approximately $61.00 higher than in the matched seasons ($239.43; range: $201.49-$264.01). The mismatched seasons had greater average per-patient, influenza-related productivity-loss costs than the matched seasons (mean: $237.31 vs. $175.10). CONCLUSION: CDC data showed that influenza A was the predominant circulating strain during seasons in which the circulating influenza B lineage did not match the vaccine influenza B lineage. This resulted in lower influenza B incidence during the mismatched seasons. However, the average, per-patient, influenza-related direct medical costs and indirect productivity losses were higher during the mismatched seasons. Additional research is required to determine if these higher costs can be attributed to influenza B infections and if the influenza severity varies during mismatched seasons.

Annual all-cause healthcare costs among influenza patients with and without influenza-related complications: analysis of a United States managed care database.

BACKGROUND: Several studies have reported that patients with influenza have a high risk of developing complications such as secondary infections, exacerbation of cardiovascular conditions and asthma. However, limited data exists on the healthcare cost burden for influenza patients with and without influenza-related complications. OBJECTIVE: We compared healthcare utilization and costs among influenza patients with related complications versus patients without complications. METHODS: In this retrospective database analysis (LifeLink database: 1998-2009) of a US managed care database, we selected patients diagnosed with influenza during influenza seasons and categorized them as complicated or uncomplicated based on the presence or absence of a diagnosis for a related complication in the year following their influenza diagnosis. Multivariable regression analyses were conducted to compare all-cause utilization and costs (adjusted to 2009 US dollars) between the two groups. RESULTS: We identified 54,469 patients of which ~65 % had evidence for at least one complication. Patients with complicated influenza had a 1.5-fold higher rate of inpatient utilization compared with uncomplicated cases (p < 0.001). Significantly higher covariate-adjusted predicted mean annual costs were also observed among complicated influenza patients across all care (p-values <0.001 for all comparisons). CONCLUSION: Healthcare costs were twice as high among influenza patients with complications versus those without, with inpatient and outpatient services being the primary cost drivers. Now with the universal recommendation for seasonal influenza vaccination for all individuals ≥6 months of age, improvement in coverage rates may help reduce the healthcare utilization and costs associated with influenza and associated complications.

Employer-incurred health care costs and productivity losses associated with influenza.

The primary objective of this study was to assess trends in employer expenditures for both direct medical costs and indirect productivity losses associated with influenza. A retrospective analysis was performed using two of the MarketScan family of databases for 2005-2009. Patients with at least one diagnosis claim for influenza during an influenza season were selected. We estimated seasonal incidence of influenza in the employed population from the MarketScan Commercial Claims and Encounters database. Health care utilization and costs and productivity losses were assessed during the 21-d period following the influenza diagnosis date. Compared with the 2005-2006 season (493 per 100,000 plan members), influenza incidence increased during the 2006-2007 (598 per 100,000 plan members) and 2007-2008 (1,142 per 100,000 plan members) seasons and had a dramatic increase during the pandemic season of 2008-2009 (1,715 per 100,000 plan members) . The total influenza-related employer spending per 100,000 plan members also increased by over 400% during the 2008-2009 influenza season [$623,248; confidence interval (CI]):$601,518-$644,991], compared with 2005-2006 ($145,834; 95% CI: $135,067-$156,603). The primary drivers of the increased costs were emergency room, outpatient and inpatient visits. Total costs associated with influenza-related missed work time per 100,000 plan members increased over 4-fold from $26,479 in the 2005-2006 influenza season to $122,811 in 2008-2009. Overall, as expected, considerably higher direct and indirect costs were observed during the 2008-2009 influenza pandemic season than during other influenza seasons. In recent years, the influenza-related employer burden has increased considerably. In future, employers may need efficient resource allocation in order to address the productivity losses and increasing direct medical costs associated with increased influenza incidence. One of the strategies that employers may consider is increasing influenza vaccination rates among employees, which likely will help lower the influenza incidence and the associated downstream direct and indirect costs.

Inappropriate antibiotic prescribing in managed care subjects with influenza.

OBJECTIVES: To evaluate costs of inappropriate oral antibiotic prescribing in a managed care population with influenza. METHODS: This was a retrospective (January 1, 2005, through December 31, 2009) analysis of the US Impact National Benchmark Database. Patients with an influenza diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 487.xx) and continuous health plan enrollment for >12 months before and 1 month after the index influenza diagnosis date were included. We identified patients with an antibiotic prescription claim within 3 days before or 3 days after the index influenza diagnosis date. Patients were classified as having received appropriate antibiotic treatment if a secondary respiratory infection was observed within the 2-week postindex period or if there was a previous comorbid diagnosis of diabetes, congestive heart failure, chronic obstructive pulmonary disease, asthma, acute myocardial infarction, or sickle cell anemia as identified by ICD-9-CM codes. RESULTS: We identified 270,057 subjects with influenza (mean age, 31.6 years). Antibiotics were prescribed in 58,477 (21.65%) patients. Among patients receiving antibiotics, 99% did not have a follow-up diagnosis for a respiratory bacterial infection and 79% had neither a secondary infection nor evidence of a comorbidity (ie, received inappropriate antibiotic treatment). Based on a conservative annual seasonal influenza rate of 10%, we estimated that inappropriate antibiotic prescribing for influenza costs the United States approximately $211 million annually. CONCLUSIONS: Empiric antibiotics were inappropriately prescribed in a high percentage of influenza patients. This represents a significant financial burden to the US healthcare system and may contribute to increased antibiotic resistance.

Cost impact of complications in meningococcal disease: evidence from a United States managed care population.

OBJECTIVES: To compare health care utilization and associated costs among patients with and without invasive meningococcal disease (IMD)-related sequelae. METHODS: A retrospective analysis of an administrative claims database from 1998-2009 was performed. Patients with an IMD-related inpatient admission and continuous health plan enrollment selected and categorized by presence (complicated-IMD) or absence (uncomplicated-IMD) IMD-related sequelae during the follow-up year. Differences in the follow-up year healthcare utilization and costs between the two groups tested using univariate and multivariable analyses. RESULTS: We identified 173 patients; 41% had at least one diagnosis claim for IMD-related sequelae. Significantly higher predicted total health care costs for complicated-IMD cases (mean: $72,101), compared with uncomplicated cases (mean: $41,883; P < 0.001). CONCLUSIONS: We observed significantly higher health care costs among complicated-IMD cases, compared with uncomplicated cases. The substantially higher costs observed among patients with IMD-related sequelae warrant inclusion of these costs in studies conducting economic evaluations of meningococcal vaccination programs.

Influence of timing of seasonal influenza vaccination on effectiveness and cost-effectiveness in pregnancy.

The purpose of this review was to estimate the impact of timing of seasonal influenza vaccination during pregnancy on health and economic outcomes. Cost-effectiveness analysis with a dynamic model of the US population of pregnant women and infants who were <6 months incorporated seasonal variation in influenza incidence. Compared with no vaccination, seasonal influenza vaccination in pregnancy costs $70,089 per quality-adjusted life year. Most of the benefit for infants was limited to those whose mothers were vaccinated within the first 4 weeks of vaccine availability. Once all women who were pregnant at the time of vaccine availability were vaccinated, vaccination of newly pregnant women had benefits for mothers but not infants. Delay of vaccination beyond November reduced both effectiveness and cost-effectiveness. The greatest population benefit from seasonal influenza vaccination in pregnancy was realized if pregnant women were vaccinated as soon as possible after trivalent inactivated influenza vaccine became available. Efforts to increase vaccine rates should be concentrated early in the influenza season.

Hospital costs, length of stay and mortality associated with childhood, adolescent and young adult meningococcal disease in the US.

BACKGROUND: Assessments of vaccination programmes should account for several important factors, including efficacy, safety and costs of preventing and treating the disease. Because patients with invasive meningococcal disease (IMD) are managed primarily in an inpatient setting, hospital costs and outcomes are central endpoints in health economic evaluations of IMD. OBJECTIVE: The aim of the study was to estimate hospital costs, length of stay (LOS) and mortality associated with IMD among children, adolescents and young adults in the US. METHODS: The study design was a retrospective analysis of discharges from the 2006 Healthcare Cost and Utilization Project Kids' Inpatient Database. Infant (<1 year), childhood (1-10 years), adolescent (11-18 years) and young adult (19-20 years) IMD-related hospitalizations (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code 036) were selected. Regression-adjusted costs ($US, year 2009 values), LOS and mortality risk were compared between IMD hospitalizations and demographically matched (5 : 1) controls. RESULTS: A weighted total of 735 IMD admissions were identified. Among children, adjusted mean LOS and cost per admission was highest for infants (9.0 days and $US36 454 among cases vs 1.9 days and $US5041 for controls; all p < 0.0001). Adjusted costs and case fatality was highest among infants with meningococcal sepsis ($US49 626 and 11.6%, respectively). Versus controls, adjusted risks of death in IMD cases were 4.6- and 10.3-fold higher, respectively, for infants and adolescents (both p < 0.05). CONCLUSIONS: While the advent of vaccines for Haemophilus influenzae and Streptococcus pneumoniae has curtailed invasive bacterial infection rates, IMD continues to be a public health concern that presents greatly increased hospital costs, LOS and mortality risk, particularly for infants and adolescents.

Cost of acute hospitalization and post-discharge follow-up care for meningococcal disease in the US.

The combined costs of acute hospitalization and post-discharge follow-up care in patients with meningococcal disease have not been widely documented. In this study, data were retrospectively analyzed from three large databases of hospital discharge records and commercial insurance claims in the US. Cases of meningococcal disease were defined as admissions with an ICD-9-CM diagnosis code in the range of 036.x. From the 2005 HCUP Nationwide Inpatient Sample, 349 (weighted N=1,710) meningococcal-related hospitalizations were identified with a mean facility cost (in 2009 dollars) of $19,526 per admission. Similar estimates ($18,119 and $20,066, respectively) were obtained from 268 admissions identified in the LifeLink (formerly PharMetrics) database during 1999-2007 and from 1,058 hospitalizations in the Perspective Comparative Database (PCD) during 2000-2007. Using insurance claims from LifeLink, we estimated that payers incur an additional $26,178 in non-facility (professional and other ancillary) costs during the course of a meningococcal admission, as well as $22,230 in additional medical and pharmacy expenses for post-discharge care during the ensuing year. The majority of follow-up costs ($14,637) were attributed to repeat hospitalizations. Mean length of stay for meningococcal disease was consistently estimated across databases at 8 to 9 days. Data from the PCD further suggested that meningococcal disease carries, on average, nearly 2 days of intensive care unit utilization. In conclusion, hospital admissions for meningococcal disease are costly to payers. These costs are heightened when non-facility services and post-discharge care are also considered. Awareness of the full cost burden of meningococcal disease is needed when evaluating vaccination programs targeting the disease.

Exenatide bid observational study (ExOS): baseline population characteristics of a prospective research study to evaluate the clinical effectiveness of exenatide bid use in patients with type 2 diabetes in a real-world setting.

OBJECTIVES: To describe the Exenatide Observational Study (ExOS) and patients initiating exenatide therapy in a real-world clinical practice setting. METHODS: ExOS is a prospective, single-arm, multicenter, observational study to assess the effectiveness of up to 24 months of exenatide therapy in patients with type 2 diabetes (T2D). Patients with T2D ≥18 years of age, who initiated exenatide therapy, were eligible. The primary effectiveness endpoint is achieving or maintaining hemoglobin A1C of ≤7.0%, or an absolute drop of 0.5% from baseline. Secondary objective measures evaluate the absolute and percentage changes from baseline for a variety of clinical measures (lipid markers, weight, BMI, etc.) and quality of life (QOL) is assessed using the Impact of Weight on Quality of Life (IWQOL)-Lite. RESULTS: On average, the baseline population (n = 531) was aged 55 years, predominantly female (62%), white (79%), educated, obese (mean BMI 39 kg/m(2)), with mean HbA(1c), blood pressure, total cholesterol, and triglyceride values of 8.0%, 129/76 mmHg, 174 mg/dL, and 197 mg/dL, respectively. A total of 28% entered the study with HbA(1c) ≤7.0% and 67% were being treated with oral antihyperglycemic drug(s) (OAD) only [1 (28.4%), 2 (28.4%), >2 (10.2%)], or some form of insulin ±OADs (19%), and ≥50% were on a cholesterol-lowering drug(s) ± antihypertensive medication(s). The single-arm design of this study is a limitation; however, the overall objective of the ongoing study is to observe patients on exenatide therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies. CONCLUSIONS: Patients treated with exenatide tended to be obese, middle-aged women on various combinations of OADs and/or insulin who often had hypertension and/or dyslipidemia. Further planned analyses will provide the largest sample of prospective data on outcomes of exenatide therapy for up to 24 months in this usual-care population.

Long-term sequelae of childhood bacterial meningitis: an underappreciated problem.

BACKGROUND: Numerous sequelae have been noted in survivors of bacterial meningitis; however, few studies document sequelae for several years following a childhood episode of bacterial meningitis. In addition, studies generally focus on the more commonly found sequelae. To review the known information and highlight this gap, this article presents a comprehensive literature review of the long-term (≥ 5 years of follow-up) sequelae of childhood bacterial meningitis. METHODS: A systematic literature search was conducted between December 2009 and February 2010. English-language articles published between January 1970 and January 2010 were selected for screening. Articles were included if the subjects were between the ages of 1 month and <18 years at the time of diagnoses of meningitis. RESULTS: A total of 1433 children who were survivors of childhood bacterial meningitis were evaluated for sequelae after the time of discharge. Of these children, 705 (49.2%) were reported to have 1 or more long-term sequelae. A majority of reported sequelae were behavioral and/or intellectual disorders (n 455, 45.0%). Hearing changes accounted for 6.7% (n 68) of sequelae and gross neurologic deficits accounted for 14.3% (n 145). DISCUSSION: A majority of childhood bacterial meningitis survivors with long-term sequelae that are documented in the literature have academic and behavioral limitations. While neurologic deficits may resolve over time, subtle behavioral deficits may not be appreciated initially and may continue to affect survivors for many years. Further studies are needed to quantify the true societal and economic burden of long-term sequelae as well as fully understand the breadth of types of sequelae that survivors experience.

A comparison of costs among patients with type 2 diabetes mellitus who initiated therapy with exenatide or insulin glargine.

BACKGROUND: Exenatide (Byetta) and insulin glargine (Lantus) are antidiabetic agents that are typically used after lack of response to an oral antidiabetic agent(s). Although previous research has examined the impact of these medications on glycaemic control, there is little information about the relative costs associated with the medications. OBJECTIVE: To compare costs among patients with type 2 diabetes mellitus treated with exenatide or insulin glargine from a US third-party payer perspective. METHODS: Data from a large, national administrative claims database were used in this study. The intent-to-treat (ITT) cohort included adults who were diagnosed with type 2 diabetes and initiated therapy with either exenatide (n = 4090) or insulin glargine (n = 1660). In addition, included patients were required to have no diagnoses of type 1 diabetes, to have received at least two prescriptions for an oral antidiabetic agent in the 6 months prior to first use of either exenatide or insulin glargine and to have continuous insurance coverage from 6 months before, to 12 months after, initiation on ITT medication. Annual total medical costs and total diabetes-related medical costs, in $US, year 2007 values, were estimated using stepwise multivariate regressions. Major cost components were also examined using either stepwise multivariate regressions or a two-part model that controlled for the probability of using the service. Smearing estimates were used to transform estimated log costs into costs. The analysis controlled for the potential impact of patient demographics, general health, prior resource use, co-morbidities and complications, and timing of treatment initiation. RESULTS: Compared with insulin glargine, initiation of exenatide was associated with significantly lower total direct medical costs ($US19,293 vs $US23,782; p < 0.0001), inpatient costs ($US4121 vs $US7532; p < 0.0001), outpatient costs ($US9501 vs $US12,885; p < 0.0001), emergency department (ED) costs ($US82 vs $US131; p < 0.0001), total diabetes-related medical costs ($US7833 vs $US8536; p < 0.0001), diabetes-related inpatient costs ($US2172 vs $US3538; p < 0.0001) and diabetes-related outpatient costs ($US2739 vs $US3249; p < 0.0001). Initiation of exenatide was associated with significantly higher total overall drug costs ($US6885 vs $US5936; p < 0.0001) and diabetes-related drug costs ($US3160 vs $US2422; p < 0.0001). CONCLUSIONS: Compared with the use of insulin glargine, use of exenatide was associated with significantly lower annual total direct medical costs and significantly lower total diabetes-related medical costs, despite higher total drug costs and higher diabetes-related drug costs. In addition, exenatide was associated with significantly lower total inpatient, outpatient, ED, and diabetes-related inpatient and outpatient costs.

Comparison of costs among patients with type 2 diabetes treated with exenatide or sitagliptin therapy.

INTRODUCTION: Exenatide (Byetta, Amylin Pharmaceuticals Inc., CA, USA) and sitagliptin (Januvia, Merck & Co, NJ, USA) are two antidiabetic agents recently approved by the US Food and Drug Administration. The purpose of this analysis was to compare costs among patients with type 2 diabetes (T2D) treated with either of these agents. METHODS: Data with dates of service from September 1, 2005 through August 31, 2007, were obtained from a large US retrospective claims database. Intent-to-treat cohorts of adults diagnosed with T2D who began taking either exenatide (n=1885) or sitagliptin (n=2482) and did not use the alternate medication in the 6-month follow-up period were created. Six-month total medical costs were estimated using stepwise multivariate regressions. Six-month total diabetes-related medical costs, a component of total medical costs, were also estimated using stepwise multivariate regressions. In addition, other cost components were examined using either stepwise multivariate regressions or a two-part model that controlled for the probability of using the medical service. Smearing estimates were used to transform estimated log costs into costs. The analysis controlled for the potential impact of patient demographics, general health, prior resource use, comorbidities, and timing of treatment initiation. RESULTS: Exenatide was associated with lower total 6-month direct medical costs ($9340 vs. $9995; P<0.0001), despite some component costs being slightly higher with exenatide: diabetes-related drug costs ($1765 vs. $1743; P=0.0062), diabetes-related medical costs ($4142 vs. $4002; P<0.0001), and emergency room costs ($43 vs. $29; P=0.0388). Exenatide was associated with lower outpatient costs ($4498 vs. $5942; P<0.0001). CONCLUSIONS: Compared with the use of sitagliptin, exenatide was associated with lower total medical costs (difference of $655) despite higher total diabetes-related costs (difference of $140). As a result, there appears to be overall cost savings associated with the use of exenatide relative to sitagliptin.

Patient characteristics, drug adherence patterns, and hypoglycemia costs for patients with type 2 diabetes mellitus newly initiated on exenatide or insulin glargine.

OBJECTIVE: Examine real-world effectiveness and hypoglycemia cost burden in patients with type 2 diabetes newly initiated on exenatide or insulin glargine. DESIGN AND METHODS: Retrospective cohort study describing patient characteristics, drug adherence patterns, and 1-year hypoglycemia rates with associated costs using an administrative claims database. Adult subjects with type 2 diabetes had an initial claim for exenatide or insulin glargine between May 1, 2005 and June 30, 2007, and had continuous eligibility for >or= 6 months pre- and >or= 12 months post-initiation. RESULTS: The exenatide cohort (n = 3262) was 53 +/- 10 years (+/-SD); 54% female. The insulin glargine cohort (n = 3038) was 56 +/- 12 years; 41% female. The mean Deyo-Charlson comorbidity index score was 1.45 for exenatide versus 1.82 for insulin glargine (p < 0.001). Baseline OAD use rates for exenatide and insulin glargine, respectively, were 77% versus 69% metformin; 47% versus 65% sulfonylurea; 50% versus 49% thiazolidinedione; 56% versus 60% multiple OAD. For patients with two or more pharmacy claims for exenatide or insulin glargine, the 12-month medication possession ratio (MPR) was 68 +/- 29% for exenatide and 58 +/- 28% for insulin glargine (p < 0.001). MPR >or= 80% was higher for exenatide (p < 0.001) and fewer patients discontinued therapy (p < 0.001). The probability of a hypoglycemic event was significantly lower for exenatide (p < 0.005), resulting in lower associated annual costs. CONCLUSIONS: This study provides the first real-world observational comparison of type 2 diabetes patients newly initiated on exenatide or insulin glargine. Exenatide patients had a lower comorbidity burden, better drug adherence, and a lower rate of hypoglycemic events with associated costs. Retrospective database analyses examine medical care utilization in large populations using a relatively inexpensive and expedient approach. However, data are only representative of a commercial health-care plan with limited information on multiple variables usually collected during clinical trials.