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.

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.

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.

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.

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.

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.

Direct medical costs for type 2 diabetes mellitus complications in the US commercial payer setting: a resource for economic research.

BACKGROUND: Medical complications are the key drivers of the direct medical costs of treating patients with type 2 diabetes mellitus. However, the published literature shows great variability across studies in the number and type of sources from which these costs for diabetes are obtained. OBJECTIVE: To provide to researchers a set of costs for type 2 diabetes complications, originally developed for input into an established diabetes model, that are empirically based, clearly and consistently defined and applicable to a large segment of managed care patients in the US. METHODS: Patients with 1 of 24 diabetes-related complications between 1 January 2003 and 31 December 2004 and with evidence of type 2 diabetes were identified using a nationally representative US commercial insurance claims database. Therapy utilization and complication cost data were extracted for all patients for the 12 months following the first identified complication; data for months 13-24 were obtained for a subset of patients with at least 24 months of follow-up enrollment. Medical costs included both the amounts charged by medical providers and the health plan contracted allowed amounts. Costs were expressed as $US, year 2007 values. RESULTS: A total of 44 021 patients with a minimum of 12 months of continuous follow-up enrollment were identified, with a mean age of 56 years; a subset of 32 991 patients with at least 24 months of continuous health-plan enrollment was also identified. Among the aggregate sample, 74% of patients were receiving oral antidiabetics, 26% were receiving insulin, 43% were receiving ACE inhibitors and 50% were receiving antihyperlipidaemics/HMG-CoA reductase inhibitors (statins) during the first 12 months following the index complication. The majority of patients had at least one physician office visit (99.8%), laboratory diagnostic test (96.2%) and other outpatient visit (97.5%). Six complications (angina pectoris, heart failure, peripheral vascular disease, renal disease, nonproliferative retinopathy and neuropathy) had a prevalence of at least 10%. Allowed amounts for most complications were 30-45% of charges. Myocardial infarction, heart failure and renal disease had the greatest fiscal impact because of the total number of patients experiencing them (7.2%, 14.0% and 11.0%, respectively) and their associated costs; 12-month mean allowed amounts were $US 14,853, $US 11,257 and $US 13,876, respectively, and 12-month mean charged amounts were $US 41,695, $US 30, 066 and $US 34,987, respectively. Similarly, in the subset of 32 991 patients, these three complications had higher allowed and charged amounts over months 13-24 compared with the majority of other complications of interest. CONCLUSION: These costing results provide an important resource for economic modelling and other types of costing research related to treating diabetes-related complications within the US managed care system.

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.

Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis.

UNLABELLED: Increases in lumbar spine BMD account for 30-41% of the vertebral fracture risk reduction with teriparatide treatment. The remaining fracture risk reduction is caused by improvements in non-BMD determinants of bone strength. INTRODUCTION: Changes in BMD account for a small percentage of the fracture risk reduction seen in patients treated with antiresorptive drugs. The relationship between changes in lumbar spine BMD and vertebral fracture risk reduction with teriparatide treatment has not been assessed. MATERIALS AND METHODS: The relationship between spine BMD and the risk of new vertebral fractures after teriparatide treatment was assessed using data from the Fracture Prevention Trial. Postmenopausal women with osteoporosis (n = 1637) were randomized to placebo or teriparatide 20 or 40 microg/day for a median of 19 months. Spine BMD was assessed at baseline and 18 months. Vertebrae whose fracture status changed during the trial were removed from the calculation of BMD. Baseline and endpoint lateral spine radiographs were assessed using a visual semiquantitative technique. RESULTS: Both the baseline and change in spine BMD were contributors to vertebral fracture risk. The mean spine BMD increase in teriparatide-treated patients was 0.09 g/cm(2) across tertiles of baseline spine BMD. Compared with placebo, teriparatide significantly reduced the risk of new vertebral fracture for all endpoint BMD values. Teriparatide-mediated increases in spine BMD accounted for 30% (in the low baseline spine BMD tertile) to 41% (in the high baseline spine BMD tertile) of the reduction in vertebral fracture risk. CONCLUSIONS: Increases in BMD account for approximately one third of the vertebral fracture risk reduction seen with teriparatide. The majority of the risk reduction, however, results from improvements in non-BMD determinants of bone strength.

Initial experience with teriparatide in the United States.

Teriparatide has been commercially available in the United States (US) for over 3 years. This summary spans the early experience with this therapy. As of December 31, 2005, over 235 000 patients had filled a prescription for teriparatide world-wide. Data collected from July to December 2004, from 15,000 retail pharmacies in the US, indicated that the mean age of patients was 67.5 years, and more recent data collected from January through October 2005 indicated that 90% of patients were female. According to market research conducted with prescribing physicians from February through March of 2005, it is estimated that over 80% of patients receiving prescriptions for teriparatide had already experienced one or more prior fractures. Since teriparatide is administered subcutaneously, it is important that patients receive training on the use of the teriparatide injection device (i.e., the pen device). Educational programs are available for those who have been prescribed teriparatide therapy. Patients may also contact a customer care program regarding a variety of topics, including pen device use. Based on patient feedback, design changes have been implemented in the pen device to facilitate optimal use. Updates have also been made to the prescribing information to reflect the post-marketing surveillance experience. Adverse experiences reported to date have been consistent with the current product label and with cumulative teriparatide clinical trial experience. As of December 31, 2005 no reports of pathology-confirmed osteosarcoma have been received for individuals who have been treated with teriparatide, either with the commercially available drug or in clinical trials. We are unaware of any reports of osteosarcoma in association with other preparations of teriparatide, or other peptides of parathyroid hormone, either in the setting of clinical trials or from marketed drug experience.

New or worsening lumbar spine vertebral fractures increase lumbar spine bone mineral density and falsely suggest improved skeletal status.

Changes in lumbar spine bone mineral density (BMD) are determined by follow-up dual-energy x-ray absorptiometry (DXA) assessments. Inclusion of new or worsening vertebral fractures in follow-up measurements may increase BMD. To test this hypothesis, we examined pooled data from the placebo groups of two clinical trials that involved postmenopausal women with osteoporosis. DXA measurements of lumbar spine BMD, bone mineral content (BMC), and area were obtained at baseline and at two years in the Multiple Outcomes of Raloxifene Evaluation (MORE) Trial and at baseline and study endpoint in the Fracture Prevention Trial. In these trials, fractured vertebrae identified by expert radiologists during posterioranterior (PA) spine DXA assessment were excluded from the BMD assessment. Lateral spine radiographs were graded using a semi-quantitative (SQ) scale. Most new or worsening vertebral fractures (84%) diagnosed from lateral spine radiographs were not identified by PA spine DXA. While the follow-up BMD of vertebrae without new or worsening fractures did not change significantly, each unit increase in SQ grade was associated with an approximate 7.0% increase in the BMD of affected vertebrae (p < 0.001). Increases in BMD were highly correlated with increases in BMC (r = 0.87, p < 0.001). Inclusion of new or worsening vertebral fractures increased PA spine BMD measurements at follow-up, with the impact being related to the magnitude of change in SQ score. It is difficult to reliably identify vertebral fractures from PA spine DXA assessments. Inclusion of new or worsening vertebral fractures in follow-up DXA measurements may falsely suggest an improvement in spine BMD. Our suggestion is to perform lateral spine imaging concurrently with any assessment of PA spine BMD in patients who, in the opinion of the health care provider, may have vertebral fractures.

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 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.

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.

Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis.

UNLABELLED: The relationship between early changes in biochemical markers of bone turnover and the subsequent BMD response to daily teriparatide therapy in women with postmenopausal osteoporosis was studied. Changes in five biochemical markers, obtained from a subset of women enrolled in the Fracture Prevention Trial, were examined. Early increases in the PICP and the PINP were the best predictors of BMD response to teriparatide in this analysis. INTRODUCTION: Early reductions in biochemical markers of bone turnover with antiresorptive therapy negatively correlate with subsequent increases in BMD. We undertook this analysis to determine if early changes in biochemical markers with teriparatide therapy predict subsequent increases in BMD. MATERIALS AND METHODS: In the Fracture Prevention Trial, 1637 postmenopausal women with osteoporosis were randomized to receive daily, self-administered, subcutaneous injections of placebo, teriparatide 20 microg/day, or teriparatide 40 microg/day. Serum concentrations of two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and the carboxy-terminal extension peptide of procollagen type 1 [PICP]) and urinary concentrations of two bone resorption markers (free deoxypyridinoline [DPD] and N-terminal telopeptide [NTX]) were assessed in a trial population subset (n = 520) at baseline and at 1, 3, 6, and 12 months. We also assessed serum concentrations of another bone formation marker, the amino-terminal extension peptide of procollagen type 1 (PINP), in a subset of 771 women at baseline and 3 months. Lumbar spine (LS) BMD was measured by DXA at baseline and 18 months. Femoral neck BMD was measured at baseline and 12 months. RESULTS AND CONCLUSION: Baseline bone turnover status correlated positively and significantly with BMD response. The highest correlations occurred for the LS BMD response to teriparatide 20 microg/day. Among all studied biochemical markers, increases in PICP at 1 month and PINP at 3 months correlated best with increases in LS BMD at 18 months (0.65 and 0.61, respectively; p < 0.05). The relationships between these two biochemical markers and the LS BMD response were stronger than the corresponding relationships for the femoral neck BMD response. Using receiver operator curve analysis, we determined that the increases in PICP at 1 month and PINP at 3 months were the most sensitive and accurate predictors of the LS BMD response.

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.

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.

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.

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.