Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV-2.

To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

Clinical Management of Hospitalized Coronavirus Disease 2019 Patients in the United States.

BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.

Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort.

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO. RESULTS: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Practice patterns and incidence of adenovirus infection in allogeneic hematopoietic cell transplant recipients: Multicenter survey of transplant centers in the United States.

BACKGROUND: Adenovirus (AdV) is increasingly recognized as a threat to successful outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Guidelines have been developed to inform AdV screening and treatment practices, but the extent to which they are followed in clinical practice in the United States is still unknown. The incidence of AdV in the United States is also not well documented. The main objectives of the AdVance US study were thus to characterize current AdV screening and treatment practices in the United States and to estimate the incidence of AdV infection in allo-HCT recipients across multiple pediatric and adult transplant centers. METHODS: Fifteen pediatric centers and 6 adult centers completed a practice patterns survey, and 15 pediatric centers and four adult centers completed an incidence survey. RESULTS: The practice patterns survey results confirm that pediatric transplant centers are more likely than adult centers to routinely screen for AdV, and are also more likely to have a preemptive AdV treatment approach compared to adult centers. Perceived risk of AdV infection is a determining factor for whether routine screening and preemptive treatment are implemented. Most pediatric centers screen higher-risk patients for AdV weekly, in blood, and have a preemptive AdV treatment approach. The incidence survey results show that from 2015 to 2017, a total of 1230 patients underwent an allo-HCT at the 15 pediatric transplant centers, and 1815 patients underwent an allo-HCT at the 4 adult transplant centers. The incidences of AdV infection, AdV viremia, and AdV viremia ≥ 1000 copies/mL within 6 months after the first allo-HCT were 23%, 16%, and 9%, respectively, for patients at pediatric centers, and 5%, 3%, and 2%, respectively, for patients at adult centers. CONCLUSIONS: These findings provide a more recent estimate of the incidence of AdV infection in the United States, as well as a multicenter view of practice patterns around AdV infection screening and intervention criteria, in pediatric and adult allo-HCT recipients.

Treatment Patterns and Health Resource Use Among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Treated at a Tertiary Referral Center.

BACKGROUND: Although an increasing number of treatments have become available for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), there remains little consensus on treatment sequence and its impact on health care resource use (HRU). We sought to describe treatment patterns and HRU, in a cohort of patients with metastatic GEP-NETs treated at a tertiary referral center in the U.S. MATERIALS AND METHODS: We identified patients with a well-differentiated, metastatic GEP-NET evaluated at Dana-Farber Cancer Institute between July 2003 and May 2015. For these patients, we describe the sequence of treatment regimens received for their disease, together with associated HRU. RESULTS: We identified 682 patients with advanced GEP-NETs. Of these patients, 597 (87.0%) initiated ≥1 treatment over the follow-up period. The mean age at diagnosis was 58.5 years, 50.2% were men, and 94.0% were white. A total of 83.1% initiated a somatostatin analog (SSA) as their first-line treatment, with 55% and 31% of patients continuing with second- and third-line therapies. A total of 31.2% of patients with SSAs underwent dose escalation to above standard dose. In this setting, patients with pancreatic neuroendocrine tumors were more commonly treated with cytotoxic regimens than other NET tumor types and also had higher HRU. CONCLUSION: Our study suggests that, at a tertiary referral center, patients with advanced NETs commonly received multiple courses of treatments. Our data suggest a clear preference for use of SSAs as a first-line treatment for patients with advanced NETs, with SSAs commonly escalated and continued throughout the course of treatment in combination with other regimens. IMPLICATIONS FOR PRACTICE: The current study demonstrates the common use of somatostatin analog as a first-line therapy for patients with advanced gastroenteropancreatic neuroendocrine tumors as well as the incorporation of multiple different treatment regimens in the treatment course of patients with this disease.

Moving Towards Accountability for Reasonableness - A Systematic Exploration of the Features of Legitimate Healthcare Coverage Decision-Making Processes Using Rare Diseases and Regenerative Therapies as a Case Study.

BACKGROUND: The accountability for reasonableness (A4R) framework defines 4 conditions for legitimate healthcare coverage decision processes: Relevance, Publicity, Appeals, and Enforcement. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide decision-making towards legitimacy. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer therefore a useful case study. METHODS: Features operationalizing each A4R condition as well as three different approaches to address these features (cost-per-QALY-focused and multicriteria-based) were defined and organized into a matrix. Seven experts explored these features during a panel run under the Chatham House Rule and provided general and RDRT-specific recommendations. Responses were analyzed to identify converging and diverging recommendations. RESULTS: Regarding Relevance, recommendations included supporting deliberation, stakeholder participation and grounding coverage decision criteria in normative and societal objectives. Thirteen of 17 proposed decision criteria were recommended by a majority of panelists. The usefulness of universal cost-effectiveness thresholds to inform allocative efficiency was challenged, particularly in the RDRT context. RDRTs raise specific issues that need to be considered; however, rarity should be viewed in relation to other aspects, such as disease severity and budget impact. Regarding Publicity, panelists recommended transparency about the values underlying a decision and value judgements used in selecting evidence. For Appeals, recommendations included a life-cycle approach with clear provisions for re-evaluations. For Enforcement, external quality reviews of decisions were recommended. CONCLUSION: Moving coverage decision-making processes towards enhanced legitimacy in general and in the RDRT context involves designing and refining approaches to support participation and deliberation, enhancing transparency, and allowing explicit consideration of multiple decision criteria that reflect normative and societal objectives.

Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison.

BACKGROUND: Nivolumab and cabozantinib, two new treatment options for previously-treated advanced/metastatic renal cell carcinoma (aRCC), have recently been approved. METHODS: Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Indirect treatment comparisons were carried out by directly assessing HR differences and statistical modeling of Kaplan-Meier curves from these two trials. RESULTS: Publications identified showed that no head-to-head comparisons had been carried out. Two indirect treatment comparisons used agreed that there was no significant difference in OS between cabozantinib and nivolumab and that cabozantinib significantly improved PFS compared to nivolumab. CONCLUSIONS: The field of aRCC treatments is evolving rapidly, creating opportunities for individualized treatments and challenges for clinicians to keep up with the evidence. In lieu of availability of direct comparisons of all options, advanced modeling results presented herein can help to inform and improve personalized treatments.

Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England.

PURPOSE: The aim of this study was to compare the cost-effectiveness of cabozantinib with the standard of care in England in adult patients with advanced renal cell carcinoma (aRCC), following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy. METHODS: We developed a partitioned-survival model with three health states to assess the cost-effectiveness of cabozantinib and its comparators. The model time horizon was 30 years. Efficacy and safety data were derived from pivotal clinical trials (METEOR: NCT01865747, CheckMate025: NCT01668784, and AXIS: NCT00678392). METEOR data were used for a direct comparison of cabozantinib and everolimus. Cabozantinib and nivolumab were compared indirectly, whereas equal efficacy for axitinib and everolimus was assumed based on a previously published expert opinion. For all efficacy endpoints, the best-fitting log-logistic or fractional polynomial curves were used to estimate outcomes. Utilities were converted from the 5-level EQ-5D version instrument applied during the METEOR study for specific health states. Reductions in utility scores due to adverse events were applied. English costs (eg, drug prices) and resource use (eg, visit to consultant) data were used. RESULTS: The total treatment cost was estimated to be 84,136 Great British Pounds (GBP) per patient treated with cabozantinib. The health gains were 2.26 life-years (LYs) and 1.78 quality-adjusted LYs (QALYs). The incremental cost-effectiveness ratios (ICERs) versus axitinib and everolimus were 98,967 GBP/QALY and 137,450 GBP/QALY, respectively. Cabozantinib was less costly and more effective than nivolumab; the incremental cost was -6,742 GBP and the QALY difference was 0.18. CONCLUSION: Treatment with cabozantinib was more effective than treatment with axitinib or everolimus but was associated with higher total costs. When compared with nivolumab, cabozantinib represents an efficient option with nominally better efficacy and lower costs.

Effect of Diabetes Treatment-Related Attributes on Costs to Type 2 Diabetes Patients in a Real-World Population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) results in a substantial economic burden on patients, health care systems, and society. Most literature assessing the cost of T2DM focuses on the long-term complications of the disease, the association between glucose control and cost, and patient characteristics resulting in poor and costly outcomes. However, it is likely that attributes specific to diabetes therapy can affect the use of costly resources. OBJECTIVE: To estimate the effect of diabetes treatment-related attributes, such as improved efficacy, adherence, and reduced risk for hypoglycemia, on costs to T2DM patients. METHODS: An observational, retrospective study was conducted using the Optum Clinformatics Database, which links medical and pharmacy claims to laboratory results. Patients aged ≥ 18 years with T2DM who had ≥ 1 antidiabetic medication claim; ≥ 1 hemoglobin A1c (A1c) test result; continuous enrollment in the health plan from April 1, 2010, to March 31, 2011; and at least 1 follow-up day were included. Nondiabetes specific total, inpatient, outpatient, emergency room, and other costs (along with antidiabetes medication costs) were defined for each patient. Generalized linear models with logarithm link were used to predict the 1-year and cumulative 3-year costs. Demographic factors and comorbidities were included as covariates in addition to the diabetes treatment-related attributes. RESULTS: In the entire analysis cohort, the average 3-year cost per patient was $74,862. The percentage effect on cost of diabetes treatment-related variables ranged from -18% to 429%. Drug adherence was associated with lower inpatient, outpatient, and emergency room costs and higher drug costs. Hypoglycemia was associated with higher inpatient, outpatient, emergency room, and other direct costs (except antidiabetic drug costs). Compared with A1c values ≤ 7%, patients with higher levels were associated with higher total and drug costs. CONCLUSIONS: Study results demonstrate the association between diabetes treatment-related attributes and costs, including inpatient, outpatient, drug, and total costs. This association raises the question: what would the effect of a new diabetes therapy, with high efficacy, high adherence, and reduced risk of hypoglycemia have on economic outcomes? DISCLOSURES: Funding from Sanofi supported this study. Tong was an employee of ProUnlimited, under contract with Sanofi during the time of the study. Kitio-Dschassi was a Sanofi employee at time of the analysis. Meng, Casciano, Stern, and Gultyaev are employees of LASER Analytica, which received research funds from Sanofi to conduct this database analysis. Lee was an employee at LASER Analytica at the time of the analysis and has received grants from Sanofi. This manuscript was presented as a poster at the American Diabetes Association, 76th Scientific Sessions; New Orleans, Louisiana; June 10-14, 2016. Study concept and design were contributed by Meng, Casciano, Gultyaev, and Kitio-Dschassi. Meng and Stern collected the data, and data interpretation was performed by Casciano, Lee, Tong, and Kitio-Dschassi. The manuscript was written primarily by Lee, along with Meng and Stern, and revised by Stern, Meng, Tong, Kitio-Dschassi, and Lee.

An Indirect Comparison of Everolimus Versus Axitinib in US Patients With Advanced Renal Cell Carcinoma in Whom Prior Sunitinib Therapy Failed.

PURPOSE: The purpose of this study was to perform a weight-adjusted indirect comparison to approximate the relative efficacy of everolimus versus axitinib among patients with second-line metastatic renal cell carcinoma in whom sunitinib therapy previously failed. METHODS: Individual patient data from the RECORD-1 (Renal Cell Cancer Treatment With Oral RAD001 Given Daily) Phase III clinical trial provided information for patients taking everolimus. Summary baseline clinical and demographic characteristics and progression-free survival (PFS) outcomes were available for patients taking axitinib who were included in the AXIS (axitinib versus sorafenib) Phase III clinical trial. A Bayesian latent class mixture model differentiating responders and nonresponders and with imbedded Weibull regression on PFS was used to identify sex, Memorial Sloan-Kettering Cancer Center risk score, and time receiving prior sunitinib therapy as prognostic factors for PFS based on posterior probability >95%. Patients taking everolimus were weighted up or down based on their combination of prognostic variables. Weights were calculated by dividing the proportion of patients observed in AXIS for a given characteristic by the proportion observed in RECORD-1 and taking the product of the values derived for all three weighting variables considered. Weighted PFS distributions were derived with bootstrapped 95% CIs and compared with those reported for the AXIS trial. FINDINGS: After weighting, distributions of the 3 key baseline characteristics were more closely aligned between the 2 studies; however, some differences remained. A slightly lower rate of poor-risk patients was evident in RECORD-1 (30%) versus AXIS (36%), and a 9% lower proportion of males was observed in the everolimus group compared with the axitinib group. Distributions of time receiving prior sunitinib therapy were almost equivalent between the treatment arms. A median PFS of 4.7 months (95% CI, 3.5-10.6 months) was observed for patients in the weighted everolimus group compared with 4.8 months (95% CI, 4.5-6.4 months) in the AXIS trial. IMPLICATIONS: Similar median PFS point estimates and overlapping CIs suggest that everolimus and axitinib have similar efficacy. Although these results do not negate the need for direct comparison, this study may be used to inform clinical and reimbursement decisions until such evidence is available.

Lifetime cost of everolimus vs axitinib in patients with advanced renal cell carcinoma who failed prior sunitinib therapy in the US.

OBJECTIVE: Everolimus and axitinib are approved in the US to treat patients with advanced renal cell carcinoma (RCC) after failure on sunitinib or sorafenib, and one prior systemic therapy (e.g., sunitinib), respectively. Two indirect comparisons performed to evaluate progression-free survival in patients treated with everolimus vs axitinib suggested similar efficacy between the two treatments. Therefore, this analysis compares the lifetime costs of these two therapies among sunitinib-refractory advanced RCC patients from a US payer perspective. RESEARCH DESIGN AND METHODS: A Markov model was developed to simulate a cohort of sunitinib-refractory advanced RCC patients and estimate the cost of treating patients with everolimus vs axitinib. The following health states were included: stable disease without adverse events (AEs), stable disease with AEs, disease progression (PD), and death. The model included the following resources: active treatments, post-progression treatments, adverse events, physician and nurse visits, scans and tests, and palliative care. Resource utilization inputs were derived from a US claims database analysis. Additionally, a 3% annual discount rate was applied to costs, and the robustness of the model results was tested by conducting sensitivity analyses, including those on dosing scheme and post-progression treatment costs. RESULTS: Base case results demonstrated that patients treated with everolimus cost an average of $12,985 (11%) less over their lifetimes than patients treated with axitinib. The primary difference in costs was related to active treatment, which was largely driven by axitinib's higher dose intensity. RESULTS remained consistent across sensitivity analyses for AE and PD treatment costs, as well as dose intensity and discount rates. CONCLUSION: The results suggest that everolimus likely leads to lower lifetime costs than axitinib for sunitinib-refractory advanced RCC patients in the US.

United States-based practice patterns and resource utilization in advanced neuroendocrine tumor treatment.

AIM: To assess advanced neuroendocrine tumor (NET) treatment patterns and resource utilization by tumor progression stage and tumor site in the United States. METHODS: United States Physicians meeting eligibility criteria were provided with online data extraction forms to collect patient chart data on recent NET patients. Resource utilization and treatment pattern data were collected over a baseline period (after diagnosis and before tumor progression), as well as initial and secondary progression periods, with progression defined according to measureable radiographic evidence of tumor progression. Resource categories used in the analysis include: Treatments (e.g., surgery, chemotherapy, radiotherapy, targeted therapies), hospitalizations and physician visits, diagnostic tests (biomarkers, imaging, laboratory tests). Comparisons between categories of resource utilization and tumor progression status were examined using univariate (by tumor site) and multivariate analyses (across all tumor sites). RESULTS: Fifty-five physicians were included in the study and completed online data extraction forms using the charts of 110 patients. The physician sample showed a relatively even distribution for those affiliated with academic versus community hospitals (46% vs 55%). Forty (36.3%) patients were reported to have pancreatic NET (pNET), while 70 (63.6%) patients had gastrointestinal tract (GI)/Lung as the primary NET site. Univariate analysis showed the proportion of patients hospitalized increased from 32.7% during baseline to 42.1% in the progression stages. While surgeries were performed at similar proportions overall at baseline and progression, pNET patients, were more likely than GI/Lung NET patients to have undergone surgery during the baseline (33.3% vs 25.0%) and any progression periods (26.7% vs 23.4%). While peptide-receptor radionuclide and targeted therapy utilization was low across NET types and tumor stages, GI/Lung types exhibited greater utilization of these technologies compared to pNET. Chemotherapy utilization was also greater among GI/Lung types. Multivariate analysis results demonstrated that patients in first progression period were over 3 times more likely to receive chemotherapy when compared to baseline (odds ratio: 3.31; 95%CI: 1.46-7.48, P = 0.0041). Further, progression was associated with a greater likelihood of having a study physician visit [relative risk (RR): 1.54; 95%CI: 1.10-2.17, P = 0.0117], and an increased frequency of other physician visits (RR: 1.84; 95%CI: 1.10-3.10, P = 0.0211). CONCLUSION: Resource utilization in advanced NET in the United States is significant overall and data suggests progression has an impact on resource utilization regardless of NET tumor site.

International practice patterns and resource utilization in the treatment of neuroendocrine tumors.

OBJECTIVES: This study compared resource use and practice patterns in patients with advanced neuroendocrine tumors (NETs) on disease progression, across countries, and by tumor type. METHODS: Physicians in the United States, United Kingdom, Germany, France, Brazil, and Italy completed data extraction forms to extract chart data of patients with NET relating to health care resource utilization and treatment practice. Data were assessed in a cross-sectional manner, by country, and by NET subtype. Univariate and multivariate analyses were performed to compare categories of resource use by disease progression status. RESULTS: A total of 197 physicians provided data on 394 patients. Overall resource utilization was high across tumor types, countries, and progression. Nearly half of all patients received chemotherapy (49%); moreover, high rates of hospitalization (65%), surgery (47%), and use of somatostatin analog (77%) were observed, with lower rates of peptide receptor radionuclide therapy (10%) and targeted therapies (6%). These patterns were consistent across gastrointestinal tract/lung NET and pancreatic NET. However, a certain variation in resource utilization was observed across countries. Disease progression was associated with increasing utilization of chemotherapy, hospitalization, and targeted therapy. CONCLUSIONS: Advanced NET is associated with significant resource use across subtypes and countries, and resource utilization is likely to increase on disease progression. There remains an unmet need for therapeutic options after disease progression.

Cost-effectiveness of everolimus vs sunitinib in treating patients with advanced, progressive pancreatic neuroendocrine tumors in the United States.

BACKGROUND: Everolimus (Afinitor) and sunitinib (Sutent) were recently approved to treat patients with advanced, progressive pancreatic neuroendocrine tumors (pNETs). (Afinitor is a registered trademark of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Sutent is a registered trademark of Pfizer Inc., New York, NY, USA.) This analysis examined the projected cost-effectiveness of everolimus vs sunitinib in this setting from a US payer perspective. METHODS: A semi-Markov model was developed to simulate a cohort of patients with advanced, progressive pNET and to estimate the cost per life-year gained (LYG) and per quality-adjusted life-year (QALY) gained when treating with everolimus vs sunitinib. Efficacy data were based on a weight-adjusted indirect comparison of the agents using phase 3 trial data. Model health states included: stable disease with no adverse events, stable disease with adverse events, disease progression, and death. Therapy costs were based on wholesale acquisition cost. Other costs such as physician visits, tests, hospitalizations, and adverse event costs were obtained from literature and/or primary research. Utility inputs were based on primary research. Sensitivity analyses were conducted to test the model's robustness. RESULTS: In the base-case analysis, everolimus was associated with an incremental 0.448 LYG (0.304 QALYs) at an incremental cost of $12,673, resulting in an incremental cost-effectiveness ratio (ICER) of $28,281/LYG ($41,702/QALY gained). The ICER fell within the cost per QALY range for many widely used oncology drugs. Sensitivity analyses demonstrated that, overall, there is a trend that everolimus is cost-effective compared to sunitinib in this setting. LIMITATIONS: Results of the indirect analysis were not statistically significant (p > 0.05). Assumptions that treatment patterns are the same across therapies may not represent real-world practice. CONCLUSIONS: While the analysis is limited by its reliance on an indirect comparison of two phase 3 studies, everolimus is expected to be cost-effective relative to sunitinib in advanced, progressive pNET.

Economic evaluation of everolimus versus sorafenib for the treatment of metastatic renal cell carcinoma after failure of first-line sunitinib.

BACKGROUND: A recent indirect comparison study showed that sunitinib-refractory metastatic renal cell carcinoma (mRCC) patients treated with everolimus are expected to have improved overall survival outcomes compared to patients treated with sorafenib. This analysis examines the likely cost-effectiveness of everolimus versus sorafenib in this setting from a US payer perspective. METHODS: A Markov model was developed to simulate a cohort of sunitinib-refractory mRCC patients and to estimate the cost per incremental life-years gained (LYG) and quality-adjusted life-years (QALYs) gained. Markov states included are stable disease without adverse events, stable disease with adverse events, disease progression, and death. Transition probabilities were estimated using a subset of the RECORD-1 patient population receiving everolimus after sunitinib, and a comparable population receiving sorafenib in a single-arm phase II study. Costs of antitumor therapies were based on wholesale acquisition cost. Health state costs accounted for physician visits, tests, adverse events, postprogression therapy, and end-of-life care. The model extrapolated beyond the trial time horizon for up to 6 years based on published trial data. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The estimated gain over sorafenib treatment was 1.273 LYs (0.916 QALYs) at an incremental cost of $81,643. The deterministic analysis resulted in an incremental cost-effectiveness ratio (ICER) of $64,155/LYG ($89,160/QALY). The probabilistic sensitivity analysis demonstrated that results were highly consistent across simulations. CONCLUSIONS: As the ICER fell within the cost per QALY range for many other widely used oncology medicines, everolimus is projected to be a cost-effective treatment relative to sorafenib for sunitinib-refractory mRCC.

An adjusted indirect comparison of everolimus and sorafenib therapy in sunitinib-refractory metastatic renal cell carcinoma patients using repeated matched samples.

OBJECTIVE: To date, no trial data exist comparing treatment outcomes for everolimus versus sorafenib. The current analysis indirectly compares the overall survival (OS) benefit of everolimus and sorafenib as second-line treatment options. RESEARCH DESIGN AND METHODS: A single-arm sorafenib study is selected as a basis to match an everolimus sunitinib-refractory subpopulation of the RECORD-1 trial. Only patients with clear cell histology are included. An adjusted matching approach is taken where 1000 repeated random samples matched to the sorafenib population on risk score distribution are produced, and a 95% CI around the mean of all sampled median OS is generated. MAIN OUTCOME MEASURES: The main outcome measures include adjusted median OS and progression-free survival. RESULTS: In all, 45 clear cell histology sorafenib patients and 1000 samples of N=41 sunitinib-refractory everolimus patients are considered for analysis. After adjusted matching, the estimated median OS benefit is 32.0 [corrected] weeks (95% CI: 22, 64) and 81.5 weeks (95% CI:78, 86) for sorafenib and everolimus patients, respectively. CONCLUSION: Results suggest that sunitinib-refractory metastatic renal cell carcinoma patients treated with everolimus may experience significantly improved OS outcomes compared to those treated with sorafenib. However, because this is not a randomized controlled trial, the results should be interpreted as those from an observational study.

The effectiveness of adjustable gastric banding: a retrospective 6-year U.S. follow-up study.

BACKGROUND: This study aimed to assess the efficacy of laparoscopic adjustable gastric banding (LAGB) during a 6-year follow-up period. METHODS: A retrospective database analysis of patients who underwent LAGB at New York University Medical Center between 1 January 2000 and 29 February 2008 was conducted. Patients were included for the efficacy analysis if they were 18 years old or older at the surgery date and had one or more visits with a recorded weight after surgery. Efficacy was assessed using percentage of excess weight loss (%EWL) at 1-year intervals after surgery. Missing weight values were interpolated using a cubic spline function. Linear regression models were used to assess the characteristics that affected the last available %EWL. All patients had implantation of the LAP-BAND system. RESULTS: The inclusion criteria for the efficacy analysis were met by 2,909 patients. The majority of the patients were white (83.3%) and female (68.4%). The mean patient age was 44.6 years, and the mean baseline body mass index (BMI) was 45.3 kg/m2. The %EWL 3 years after surgery was 52.9%, which was sustained thereafter. In multivariate models, increased number of office visits, younger age, female gender, and Caucasian race were significantly associated with a higher maximum %EWL. CONCLUSIONS: The LAP-BAND patients achieved a substantial and sustainable weight loss of approximately 50% at 6 years after surgery.

Economic consequences of severe bleeding in patients with acute coronary syndrome in the USA.

INTRODUCTION: Previous studies have demonstrated increased costs associated with bleeding in clinical trials, but none have yet examined the association of bleeding with costs/charges in a real-world setting. This study examines the association between health care charges and severe bleeding events among patients with acute coronary syndrome (ACS) in a real-world US setting. METHODS: This retrospective study of ACS patients enrolled in a regional, 570,000-member commercial health plan evaluated resource utilization for patients with and without severe bleeding using medical encounter data in health care administrative records. Inclusion criteria were continuous health plan enrollment in the 6 months before initial ACS-related hospitalization, age of at least 18 years, and an inpatient ACS claim between January 1995 and May 2007. Severe bleeding events were defined as having an in-hospital record for: (a) bleeding plus blood transfusion, (b) intracranial hemorrhage, or (c) blood transfusion followed by death. Hospitalizations in which the patient had a nonsevere bleeding event, defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for bleeding without transfusion or death, were removed from analysis. Resource utilization was assessed using hospital charges. Multiple linear regression analyses controlling for key covariates were used to assess the association of severe bleeding during initial hospitalization with an ACS diagnosis/procedure with charges and length of stay (LOS). RESULTS: There were 11,266 ACS patients identified: 928 patients (8.2%) had severe bleeding during initial hospitalization. Severe bleeding events were associated with significantly higher hospital charges and increased LOS than hospitalizations without severe bleeding events. After adjusting for patient characteristics, in-hospital ACS-related procedures, and LOS, patients with severe bleeding incurred initial hospitalization charges that were $48,114 higher than those of patients without bleeding (P<0.001). CONCLUSION: In a real-world setting, hospitalizations with both severe bleeding and an ACS diagnosis or procedure are associated with significantly higher hospitalization charges and resource use compared with ACS-related hospitalizations without bleeding events. However, due to the limitations of retrospective analyses, no causal relationship can be determined as patient comorbidities represent a possible source of confounding.

Economic consequences of ACS-related rehospitalizations in the US.

OBJECTIVE: To examine economic consequences related to rehospitalization following initial acute coronary syndrome (ACS) treatment in United States managed care settings. STUDY DESIGN: Retrospective observational studies. RESEARCH DESIGN AND METHODS: Retrospective observational studies were conducted on two managed care populations to examine medical encounter insurance claims and charges for ACS-related rehospitalizations following an index hospitalization for new onset ACS (2002-2007). All charges were adjusted to year 2007 United States Dollars (USDs). MAIN OUTCOME MEASURES: The main outcomes for this study were the direct charges related to ACS rehospitalizations as captured in two separate medical encounter claims databases. RESULTS: Of the 11,266 ACS patients identified for analysis in the health system plan, 3588 (32%) had at least one ACS rehospitalization. Of the 97,177 ACS patients enrolled in the nationally representative managed care database, 32,578 (34%) had at least one ACS-related rehospitalization. Multivariate analyses demonstrated that coronary artery bypass graft (CABG) was the strongest predictor of increased charges during the recurrence in both populations (p < 0.0001). When controlling for length of stay (LOS) in the model, CABG remained a significant predictor of increased charges, while percutaneous coronary intervention (PCI) and stent insertion became even stronger predictors of increased charges. CONCLUSIONS: The costs associated with ACS-related rehospitalizations in a real-world setting are high, even when controlling for known cost drivers such as length of stay.