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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A pharmacoeconomic evaluation of 7-valent pneumococcal conjugate vaccine in Canada.

The objective of this study was to evaluate the projected health benefits, costs, and cost-effectiveness of pneumococcal conjugate vaccination for infants and children aged <5 years in Canada. A health state model incorporating incidence, vaccine efficacy, costs, and transitional probabilities for the health states (well, meningitis, bacteremia, otitis media, pneumonia, and death) was constructed for a 10-year time horizon. Implementation of a pneumococcal conjugate vaccine program in Canada for each annual birth cohort of 340,000 persons observed over 10 years would be expected to save approximately 12 lives and 100,000 cases of pneumococcal disease over 10 years, resulting in total savings of $67 million (Canadian dollars [Can$]). Vaccination of healthy infants would result in net savings for society if the vaccine costs less than Can$50 per dose. Moreover, for a vaccine purchase price of Can$67.50, infant vaccination would cost society Can$79,000 per life-year gained. Pneumococcal conjugate vaccination is a potentially cost-effective means of pneumococcal disease prevention.

A pharmacoeconomic evaluation of the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study in the United Kingdom.

OBJECTIVE: To determine the short-term healthcare costs associated with intensive lipid lowering with atorvastatin initiated within 24-96 hours of the occurrence of acute coronary syndrome (ACS) in patients in the UK. METHODS: Patient-level clinical outcome data from the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial and standard cost data were used to compare the total expected 16-week cost per patient on atorvastatin 80 mg/day versus placebo. Clinical outcomes assessed included the following: death; cardiac arrest with resuscitation; nonfatal myocardial infarction; worsening angina pectoris with objective evidence of myocardial ischaemia requiring rehospitalisation; surgical or percutaneous coronary revascularisation; nonfatal stroke; hospitalisation for angina without objective evidence of myocardial ischaemia; and new or worsening congestive heart failure requiring rehospitalisation. All relevant direct medical costs from the perspective of the NHS were considered. RESULTS: The total expected cost was pound 784.05 per patient in the placebo cohort and pound 851.59 per patient in the atorvastatin cohort, resulting in an incremental cost of pound 67.54 per patient in the atorvastatin group. The cost per event avoided was pound 1762.04. A third of the cost of atorvastatin treatment was offset within 16 weeks by the cost savings resulting from the reduction in the number of events in the atorvastatin cohort compared with the placebo cohort. CONCLUSION: The clinical benefits of short-term intensive atorvastatin treatment administered after ACS is attainable through a marginal increase in 'upfront' costs.

Economic benefits of amlodipine treatment in patients with coronary artery disease.

OBJECTIVE: To estimate the potential savings in overall cardiovascular disease (CVD) treatment costs for the US population with coronary artery disease (CAD) resulting from the use of amlodipine. STUDY DESIGN AND METHODS: Using patient-level data from a retrospective analysis of the Prospective Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), a randomised, placebo-controlled clinical trial (n = 825), we constructed a Markov cohort simulation model to estimate the health economic outcomes of patients with CAD treated with either amlodipine or placebo. PERSPECTIVE: Healthcare payer perspective. RESULTS: The expected number of CVD events for amlodipine recipients was significantly lower than the number of CVD events in the placebo cohort (p < 0.01). The net present value of the cost per patient for CVD treatment was estimated to be $US14 117 for amlodipine recipients and $US16 683 (1999 values, assuming a 3% discount rate) for placebo recipients over 3 years of follow-up with cost savings realised in the amlodipine cohorts after 6 months. CONCLUSIONS: According to the model, amlodipine results in an expected per patient cost savings of $US2566 over a 3-year period, mainly due to a reduction in hospitalisations for cardiovascular-related events and procedures.

A pharmacoeconomic evaluation of aggressive cholesterol lowering in Sweden.

OBJECTIVE: To estimate the short-term healthcare costs and incremental cost per event avoided, associated with aggressive atorvastatin treatment in patients with acute coronary syndrome in Sweden. METHODS: The total expected 16-week healthcare costs per patient on atorvastatin 80 mg per day and placebo were compared using clinical outcomes data from The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study and Swedish cost data sources. The incremental cost per event avoided was also assessed for. The clinical outcomes measured in this pharmacoeconomic analysis included: death, cardiac arrest, non-fatal myocardial infarction, fatal myocardial infarction, angina pectoris, non-fatal stroke, congestive heart failure, and surgical or percutaneous coronary revascularizations. All direct medical costs were taken into account. RESULTS: The probability of the occurrence of an event was 40.4% per patient in the placebo cohort and 36.6% per patient in the atorvastatin cohort. The total expected cost per patient was SEK 17,887 (1950.21 euro) in the placebo group and SEK 18,465 (2013.06 euro) in the atorvastatin group, resulting in an incremental cost of SEK 578 (63.0137 euro) per patient. The cost per event avoided was SEK 15,076 (1643.64 euro). Sixty six percent of the cost of atorvastatin treatment was offset by the cost savings obtained through the reduction in the number of events in the atorvastatin group compared to the placebo group. CONCLUSIONS: In Sweden, the clinical benefits of aggressive short-term atorvastatin treatment administered within a few days after acute coronary syndrome is associated with a substantial hospitalization cost offset secondary to the clinical benefits of atorvastatin.

A pharmacoeconomic evaluation of results from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES) in Norway and Canada.

INTRODUCTION: The objective of this analysis was to evaluate the health economic benefits of using amlodipine in patients undergoing angioplasty procedures in Canada and Norway. METHODS: A decision tree model was constructed to find the total expected cost per patient for a 4-month time period following an initial angioplasty. The model used clinical data from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES), a prospective, randomized, double blind, placebo-controlled trial conducted to investigate the effects of amlodipine on restenosis and clinical events in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Outcomes of interest to this analysis included MI, repeat PTCA, CABG, and all-cause mortality. Clinical experts from Canada and Norway were enlisted and a modified Delphi study approach was used to quantify healthcare resources consumed for each clinical outcome. RESULTS: The use of amlodipine decreased the rates of MI, PTCA, and CABG by 2.0, 4.7, and 2.7%, respectively. The total expected cost per patient using amlodipine was $6,398.30 (US$4,323) in Canada and kr 59,993.27 (US$6,846) in Norway. The total expected cost per patient not using amlodipine was $6,519.37 (US$4,405) in Canada and kr 64,292.17 (US$7,337) in Norway. The model demonstrated potential cost-savings over a 4-month follow up period resulting from the improved clinical outcomes for patients using amlodipine with PTCA--$121,071 (US$81,844) per 1000 patients in Canada and kr 4,298,899 (US$490,074) per 1000 patients in Norway. CONCLUSIONS: The adjunctive use of amlodipine is a cost-effective therapeutic strategy to achieve more favorable clinical outcomes in patients undergoing PTCAs in Canada and Norway.

A pharmacoeconomic evaluation of the effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes in Spain.

To determine the 16-week health economic outcomes of short-term, intensive lipid-lowering therapy with atorvastatin in patients with acute coronary syndrome (ACS) using unit costs from Spain. The total expected cost per patient and the cost per inpatient event avoided were compared for patients on atorvastatin 80 mg daily versus placebo. The analysis was based on clinical outcome data from the MIRACL study. Clinical outcomes measured in this analysis included: death, cardiac arrest, nonfatal myocardial infarction (MI), fatal MI, angina pectoris, stroke, congestive heart failure (CHF), and surgical or percutaneous coronary revascularizations. Unit costs for outcomes were values using 2001 Diagnosis Related Group (DRG) costs in Spain. The cost of a follow-up visit was added to the cost of each outcome in both groups. In the atorvastatin group, monitoring costs were also added. All direct medical costs were taken from the perspective of the Spanish National Health System during a 16-week period. The hospital cost in the atorvastatin group was 1,921 per patient, compared to 1,853 in the placebo group. The incremental cost per patient in the atorvastatin group was 67.47, corresponding to a cost per inpatient event avoided of 1,760. The cost of atorvastatin for 16 weeks was 128. Forty-seven percent of this cost of atorvastatin was offset by the cost savings obtained through the reduction of number of events in the atorvastatin group. In Spain, the intensive short-term use of atorvastatin in patients with ACS has a favorable cost-effectiveness. The direct cost of the drug was largely offset by the associated reduction in costs for treating fewer cardiovascular events.