Cost-Effectiveness of Oral Nirmatrelvir/Ritonavir in Patients at High Risk for Progression to Severe COVID-19 in the United States.

OBJECTIVES: Nirmatrelvir/ritonavir (NMV/r) is an orally administered antiviral indicated for the outpatient treatment of patients with mild-to-moderate COVID-19 at high risk for disease progression to severe illness. We estimated the cost-effectiveness of NMV/r versus best supportive care for patients with mild-to-moderate COVID-19 at high risk for progression to severe illness from a US health sector perspective. METHODS: A cost-effectiveness model was developed using a short-term decision-tree (1 year) followed by a lifetime 2-state Markov model (alive and dead). The short-term decision-tree captured costs and outcomes associated with the primary infection and healthcare utilization; survivors of the short-term decision-tree were followed until death assuming US quality-adjusted life years (QALYs), adjusted in the short-term for survivors of mechanical ventilation. Baseline rate of hospitalization and NMV/r effectiveness were taken from an Omicron-era US real-world study. Remaining inputs were informed by previous COVID-19 studies and publicly available US sources. Sensitivity analyses were conducted for all model inputs to test the robustness of model results. RESULTS: NMV/r was found to decrease COVID-19 related hospitalizations (-0.027 per infected case) increase QALYs (+0.030), decrease hospitalization costs (-$1110), and increase total treatment cost (+$271), resulting in an incremental cost-effectiveness ratio of $8931/QALY. Results were most sensitive to baseline risk of hospitalization and NMV/r treatment effectiveness parameters. The probabilistic analysis indicated that NMV/r has a >99% probability of being cost-effective at a $100 000 willingness-to-pay threshold. CONCLUSIONS: NMV/r is cost-effective vs best supportive care for patients at high risk for severe COVID-19 from a US health sector perspective.

Treatment intensification with bempedoic acid to achieve LDL-C goal in patients with ASCVD: A simulation model using a real-world patient cohort in the US.

Background and aims: Guidelines recommend that high-risk patients with atherosclerotic cardiovascular disease (ASCVD) be treated with maximally tolerated statins to lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major adverse cardiovascular events. In patients whose LDL-C remains elevated, non-statin adjunct therapies, including ezetimibe (EZE), bempedoic acid (BA), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are recommended. Methods: The impact of BA and EZE in a fixed-dose combination (FDC) on LDL-C goal attainment was evaluated using a simulation model developed for a United States cohort of high-risk adults with ASCVD. Treatment was simulated for 73,056 patients not at goal (LDL-C >70 mg/dL), comparing BA + EZE (FDC), EZE only, and no oral adjunct therapy (NOAT). The addition of PCSK9 inibitors was assumed after 1 year in patients not at LDL-C goal. Treatment efficacy was estimated from clinical trials. Patient-level outcomes were predicted over a 10-year horizon accounting for treatment discontinuation and general mortality. Results: Baseline mean age of the cohort was 67 years, most were White (79%) and male (56%). A majority had established coronary artery disease (75%), 48% had diabetes, and mean LDL-C was 103.0 mg/dL. After 1 year, 79% of patients achieved LDL-C goal (mean, 61.1 mg/dL) with BA + EZE (FDC) compared to 58% and 42% with EZE (71.7 mg/dL) and NOAT (78.4 mg/dL), respectively. Conclusions: This simulation shows that adding BA + EZE (FDC) to maximally tolerated statins would result in more patients achieving LDL-C goal than adding EZE alone or NOAT.

Economic considerations for mid-urethral sling procedures among patients with stress urinary incontinence.

OVERVIEW: Stress urinary incontinence (SUI) is associated with a hefty economic burden. Retropubic and transobturator vaginal slings have become common surgical options for women with SUI. This study examines the costs of transobturator slings for SUI surgeries. METHODS: A model was created to estimate the budget impact to hospitals of transobturator sling surgery in women with SUI. Current practice using transobturator slings including the MonarcTM Subfascial Hammock, Obtryx® Transobturator Mid-Urethral Sling System, Aris® Transobturator Sling System, Align® TO Trans-Obturator Urethral Support System, GYNECARE TVTTM Obturator System Tension-free Support for Incontinence and GYNECARE TVT ABBREVOTM Continence System were modeled. Four surgical complications were considered: re-operation due to failure, revision or removal of sling, urologic complications including urinary obstruction and urinary tract infection, and pelvic complications. This model calculates the average 1-year cost per patient with the use of each sling product and estimates the total budget for sling urinary incontinence surgery associated with each product based on these calculations. RESULTS: Average incremental cost over 1 year ranged from $2,601 (GYNECARE TVTTM Obturator) to $3,132 (Desara®) per patient. In a hypothetical population of 100 patients, a 10% shift from the most to the least expensive option was associated with a 2% decrease in hospital expenditures. With the current market share for transobturator sling products, the expected expenditure is around $285,533 for a surgical population of 100 patients. Sling costs account for approximately $105,526 (37%) of this cost, with complications comprising the remaining majority. CONCLUSION: This study represents the first comparative assessment of the costs of different sling options for stress urinary incontinence surgeries. GYNECARE TVT ABBREVOTM and GYNECARE TVTTM Obturator products represent a sound clinical and economic choice for hospitals. Moreover, the reduction in expenditures is obtained at the benefit of patients, who experience fewer complications and avoid complication-related procedures.

Healthcare resource utilization and costs among patients with post-stroke spasticity before and after spasticity management including onabotulinumtoxina.

BACKGROUND: Real-world data regarding the impact of onabotulinumtoxinA on healthcare resource utilization and costs for post-stroke spasticity are scarce. OBJECTIVE: To compare differences in 12-month healthcare resource utilization and costs before and after post-stroke spasticity management including onabotulinumtoxinA. METHODS: This retrospective claims analysis of IBM MarketScan Commercial and Medicare Supplemental databases included adults with ≥ 1 onabotulinumtoxinA claim for post-stroke spasticity (1 January 2010 to 30 June 2018) and continuous enrolment for ≥ 12 months pre- and post-index (first onabotulinumtoxinA claim date). All-cause and spasticity-related healthcare resource utilization and costs were compared 12 months pre- and post-index (McNemar's χ2 test or paired t-test). A subgroup analysis assessed effect of stroke-to-index interval on costs. RESULTS: Among 735 patients, mean (standard deviation) stroke-date-to-index-date interval was 284.5 (198.8) days. Decreases were observed post-index for mean all-cause outpatient (62.9 vs 60.5; p ≤ 0.05) and emergency department visits (1.1 vs 0.8; p ≤ 0.0001), and hospital admissions (1.5 vs 0.4; p ≤ 0.0001). Increase in prescription fills (43.0 vs 53.7) was seen post-index. Post-index decreases in all-cause (-66%) and spasticity-related (-51%) costs were driven by reduced inpatient care costs. Findings were consistent regardless of stroke-date-to-index-date interval. CONCLUSION: Significant reductions in healthcare resource utilization and costs were observed after 1 year of post-stroke spasticity management including onabotulinumtoxinA. Long-term studies are needed to establish causality.

Estimated impact of ECHELON-1 overall survival on productivity costs in stage III/IV classical Hodgkin lymphoma in the United States.

BACKGROUND: A 2010 study on the impact of cancer mortality on productivity costs found Hodgkin lymphoma to have the second largest productivity cost lost per death in the United States. The ECHELON-1 trial demonstrated that frontline brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) improves overall survival (OS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in stage III/IV classical Hodgkin lymphoma (cHL), reducing the risk of death to 41% (hazard ratio = 0.59; 95% CI = 0.40-0.88; P = 0.009). OBJECTIVES: To assess the estimated impact of frontline treatment choice on mortality and productivity using an oncology simulation model informed by ECHELON-1 data. METHODS: Individual productivity was estimated using the human capital approach and reported via present value lifetime earnings (PVLE) estimates. Deaths avoided and lifeyears saved without and with A+AVD were calculated using a model informed by realworld treatment use, treatment-specific OS, and expert clinicians' opinions. A+AVD use in the base case was 27% (range: 0%-80%). Stage III/IV cHL prevalence over a 10-year period was estimated; downstream lifetime productivity costs were projected without and with A+AVD. RESULTS: In 2031, 3,645 patients were estimated to be newly diagnosed with stage III/IV cHL. Over 10 years with 27% A+AVD vs no A+AVD use, estimates predicted 14% fewer deaths (2,290 vs 2,650) and 14% less total PVLE losses ($1.438 vs $1.664 billion). Results from scenario analyses (40%-80% vs no A+AVD use) showed 20% to 32% decreases in PVLE losses ($1.331-$1.137 billion vs $1.664 billion), saving up to $527 million over 10 years. CONCLUSIONS: Productivity cost losses due to mortality in stage III/IV cHL are high. Increasing A+AVD use for patients with stage III/IV cHL would reduce productivity cost losses as deaths are avoided, based on ECHELON-1 OS results.

Impact of Ruxolitinib Cream on Work Productivity and Activity Impairment and Associated Indirect Costs in Patients with Atopic Dermatitis: Pooled Results From Two Phase III Studies.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease that can negatively impact work productivity and daily activities. Ruxolitinib cream, a Janus kinase inhibitor, demonstrated efficacy and safety in patients with atopic dermatitis in two phase III studies (TRuE-AD1 and TRuE-AD2). OBJECTIVE: This post hoc analysis sought to describe the effects of ruxolitinib cream on work productivity and activity impairment from pooled data from the phase III studies, to estimate indirect costs due to atopic dermatitis, and to estimate the incremental cost savings with ruxolitinib cream versus vehicle cream. METHODS: Patients in both studies were ≥ 12 years old with atopic dermatitis for ≥ 2 years, an Investigator's Global Assessment score of 2 or 3, and a 3-20% affected body surface area at baseline. Patients were randomized 2:2:1 to receive ruxolitinib cream (0.75% or 1.5%) or vehicle cream for 8 weeks. Patient self-reported productivity in the efficacy-evaluable population was assessed at weeks 2, 4, and 8 using the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem version 2.0. Statistical significance for the two doses versus vehicle was calculated using an analysis of covariance. Work Productivity and Activity Impairment overall work impairment scores were converted to a model of costs per employed patient due to lost productivity and incremental cost savings from ruxolitinib cream treatment using a human capital approach. RESULTS: Of 1249 patients enrolled (median age, 32 years; female sex, 61.7%), 1208 were included in the efficacy-evaluable population. Patients applying 0.75% or 1.5% ruxolitinib cream had significant changes in overall work impairment (- 17.9% [0.75% strength] and - 15.0% [1.5% strength] vs - 5.7% for vehicle; p < 0.0001 for both) and daily activity impairment (- 20.6% [0.75% strength] and - 21.5% [1.5% strength] vs - 10.6% for vehicle; p < 0.0001 for both). These corresponded to estimated lost productivity costs in 2021 US dollars of $1313 (0.75% strength) and $1242 (1.5% strength) versus $2008 (vehicle) over the 8-week trial period. Compared with a patient receiving vehicle, incremental annual indirect cost savings were estimated to be $5302 with 0.75% ruxolitinib cream and $4228 with 1.5% ruxolitinib cream. CONCLUSIONS: Ruxolitinib cream therapy is associated with improved work productivity and daily activity compared with vehicle and is estimated to reduce the indirect cost burden on the patient. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03745638 (registered 19 November, 2018) and NCT03745651 (registered 19 November, 2018).

Estimating long-term outcomes in classic Hodgkin lymphoma: a United States population-based oncology simulation model based on overall survival from the ECHELON-1 trial.

The six-year ECHELON-1 update showed a survival advantage for frontline (1 L) A + AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) vs ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage III/IV classic Hodgkin lymphoma (cHL). As clinical trials have limited ability to track patients for extended periods, we developed an oncology simulation model using ECHELON-1 data to estimate population-based cHL outcomes in the US over 10 years (through 2031). The model included a scenario without (64.5% ABVD, 35.5% PET-adapted ABVD utilization) and scenarios with 1 L A + AVD (27%-80%k utilization). At 27%-80% A + AVD utilization, the model estimated 13.6%-31.7% fewer deaths, 2.4%-6.3% more patients ≥5 years progression free, 9.4%-24.4% fewer stem cell transplants (SCTs), and 7.8%-22.5% fewer second cancers over 10 years. These results suggest that the improved outcomes observed in the ECHELON-1 update with A + AVD vs ABVD may translate to more patients alive and fewer with primary relapsed/refractory cHL, SCTs, and second cancers.

Evaluation of the consequences associated with diffuse vascular disease history in patients diagnosed with peripheral arterial disease: estimates from Saskatchewan health data.

BACKGROUND: Peripheral arterial disease (PAD) is caused by narrowing of the arteries in the lower extremities. Limited data exist concerning the impact of diffuse vascular disease (DVD) on prognosis and costs. Thus, the objective of this study is to estimate the impact of DVD on morbidity, mortality and costs. METHODS: PAD was identified between 1985 and 1995 and classified by extent of DVD at diagnosis: none (PAD only, reference group), prior myocardial infarction (MI), prior stroke, prior MI and stroke (MI + stroke), prior transient ischemic attack (TIA). Deaths and hospitalizations were identified through December 2000. Hospitalization costs were estimated from the Ontario Case Cost Project, reported in 2002 $CAD. Proportional hazards analyses measured the impact of vascular involvement on mortality while controlling for risk factors (e.g., age, cardiovascular history). RESULTS: Overall, 16,439 patients with PAD were included; 14.8% had a prior MI, 10.2% a prior stroke, 2.6% prior MI + stroke, 6.4% prior TIA, two-thirds had PAD only. Median survival was shorter for patients with prior MI (9.3 yrs), TIA (6.3), stroke (4.7), and MI+stroke (4.1) versus the reference group (9.9, p < 0.05, all comparisons). Analyses revealed that the death risk was 60% higher in patients with prior stroke and 84% higher for MI + stroke. Atherothrombotic and bleeding event-related costs were $712, $337, $268, and $170 higher per patient/year of follow-up in patients with a history of MI+stroke, MI, stroke, and TIA, respectively. CONCLUSION: Patients diagnosed with PAD with DVD have higher risk of poor outcomes and increased costs.

Cost-Effectiveness of Rifaximin Treatment in Patients with Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis of the liver causing neuropsychiatric abnormalities. Clinical manifestations of overt HE result in increased health care resource utilization and effects on patient quality of life. While lactulose has historically been the mainstay of treatment for acute HE and maintenance of remission, there is an unmet need for additional therapeutic options with a favorable adverse event profile. Compared with lactulose alone, rifaximin has demonstrated proven efficacy in complete reversal of HE and reduction in the incidence of HE recurrence, mortality, and hospitalizations. Evidence suggests the benefit of long-term prophylactic therapy with rifaximin; however, there is a need to assess the economic impact of rifaximin treatment in patients with HE. OBJECTIVE: To assess the incremental cost-effectiveness of rifaximin ± lactulose versus lactulose monotherapy in patients with overt HE. METHODS: A Markov model was developed in Excel with 4 health states (remission, overt HE, liver transplantation, and death) to predict costs and outcomes of patients with HE after initiation of maintenance therapy with rifaximin ± lactulose to avoid recurrent HE episodes. Cost-effectiveness of rifaximin was evaluated through estimation of incremental cost per quality-adjusted life-year (QALY) or life-year (LY) gained. Analyses were conducted over a lifetime horizon. One-way deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in results. RESULTS: The rifaximin ± lactulose regimen provided added health benefits despite an additional cost versus lactulose monotherapy. Model results showed an incremental benefit of $29,161 per QALY gained and $27,762 per LY gained with rifaximin ± lactulose versus lactulose monotherapy. Probabilistic sensitivity analyses demonstrated that the rifaximin ± lactulose regimen was cost-effective ~99% of the time at a threshold of $50,000 per QALY/LY gained, which falls within the commonly accepted threshold for incremental cost-effectiveness. CONCLUSIONS: The clinical benefit of rifaximin, combined with an acceptable economic profile, demonstrates the advantages of rifaximin maintenance therapy as an important option to consider for patients at risk of recurrent HE. DISCLOSURES: This analysis was funded by Salix Pharmaceuticals, a division of Bausch Health US. Salix and Xcenda collaborated on the methods, and Salix, Xcenda, Jesudian, and Ahmad collaborated on the writing of the manuscript and interpretation of results. Bozkaya and Migliaccio-Walle are employees of Xcenda. Ahmad reports speaker fees from Salix Pharmaceuticals, unrelated to this study. Jesudian reports consulting and speaker fees from Salix Pharmaceuticals, unrelated to this study. The results from this model were presented at AASLD: The Liver Meeting 2014; November 7-11; Boston, MA.

NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right question posed? Were the best tools used?

The National Institute for Health and Clinical Excellence (NICE) recently issued updated guidance on the use of cholinesterase inhibitors in the treatment of Alzheimer's disease. NICE initially recommended that cholinesterase inhibitors no longer be used, but final guidance restricted treatment to patients with disease of a moderately severe stage. This decision was based largely on results from a heavily criticised economic evaluation that used an adaptation of the Assessment of Health Economics in Alzheimer's Disease (AHEAD) model. As the developers of the AHEAD model, we examined the appropriateness of NICE's economic analyses and presentation of results. We attempted to replicate NICE's results by modifying the original AHEAD model. Sensitivity analyses were then run using the modified AHEAD model to evaluate the extent of uncertainty in predictions. The AHEAD(NICE) analyses resulted in an incremental cost-effectiveness ratio for galantamine of 82,000 pound per QALY gained (year 2003 values) from the perspective of the UK NHS and Personal Social Services. This was later revised to 46,000 pound per QALY, compared with < 9000 pound per discounted QALY gained (year 2001 values) in the original AHEAD model. Using our modified AHEAD with effectiveness estimates matching those of AHEAD(NICE), we show that NICE's choice and presentation of sensitivity analyses obscured the instability of their estimates. In the final NICE evaluation, the recommendation to delay treatment with cholinesterase inhibitors until patients have moderately severe disease was based on critical assumptions in the economic analyses that had little evidence to support them. The case of NICE's guidance on cholinesterase inhibitors highlights the importance of transparent and valid economic evaluations and the dangers of using inappropriate modelling technologies, basing analyses on a limited subset of the available data, and insufficiently reflecting the uncertainty in estimates that are intended to inform decision makers.

The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis.

BACKGROUND: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs. AIMS: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US. MATERIALS AND METHODS: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20 mg daily), and subcutaneous interferon beta-1a (IFN, 44 mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses. RESULTS: Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs. LIMITATIONS: Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed). CONCLUSIONS: The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.

The time course of subsequent hospitalizations and associated costs in survivors of an ischemic stroke in Canada.

BACKGROUND: Documentation of the hospitalizations rates following a stroke provides the inputs required for planning health services and to evaluate the economic efficiency of any new therapies. METHODS: Hospitalization rates by cause were examined using administrative data on 18,695 patients diagnosed with ischemic stroke (first or subsequent, excluding transient ischemic attack) in Saskatchewan, Canada between 1990 and 1995. Medical history was available retrospectively to January 1980 and follow-up was complete to March 2000. Analyses evaluated the rate and timing of all-cause and cardiovascular hospitalizations within discrete periods in the five years following the index stroke. Cardiovascular hospitalizations included patients with a primary diagnosis of ischemic stroke, transient ischemic attack, myocardial infarction, stable or unstable angina, heart failure or peripheral arterial disease. RESULTS: One-third (36%) of patients were identified by a hospitalized stroke. Mean age was 70.5 years, 48.0% were male, half had a history of stroke or a transient ischemic attack at the time of their index stroke. Three-quarters of the patients (72.7%) were hospitalized at least once during a mean follow-up of 4.6 years, accruing CAD $24 million in the first year alone. Of all hospitalizations, 20.4% were related to cardiovascular disease and 1.6% to bleeds. In the month following index stroke, 12.5% were admitted, an average of 1.04 times per patient hospitalized. Strokes accounted for 33% of all hospitalizations in the first month. The rate diminished steadily throughout the year and stabilized in the second year when approximately one-third of patients required hospitalization, at a rate of about one hospitalization for every two patient-years. Mean lengths of stay ranged from nine days to nearly 40 days. Close-fitting Weibull functions allow highly specific probability estimates. Other cardiovascular risk factors significantly increased hospitalization rates. CONCLUSION: After stroke, there are frequent hospitalizations accounting for substantial additional costs. Though these rates drop after one year, they remain high over time. The number of other cardiovascular causes of hospitalization confirms that stroke is a manifestation of disseminated atherothrombotic disease.

Costs and medical care consequences associated with the diagnosis of peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is increasingly recognised as an indicator of disseminated atherothrombosis, but its impact on use of healthcare resources is not well understood. OBJECTIVE: To provide a quantitative description of the resource utilisation and costs incurred following PAD. METHODS: Hospitalisations, physician visits and the corresponding direct medical costs were examined in 16,440 patients with a diagnosis of PAD (1985--1995) in Saskatchewan, Canada, and compared with 15,590 reference patients with a diagnosis of myocardial infarction (MI) [1990--1995]. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up to December 2000. Rates and timing of all-cause and cardiovascular hospitalisations and physician visits within discrete periods in the 10 years following PAD diagnosis, and 5 years following MI, were evaluated, as were lengths of stay and predictors of hospitalisation. RESULTS: Average follow-up was 5.9 years among patients with PAD and 3.6 years for MI. Half (55%) of patients with PAD were male versus 64% of reference patients. The mean ages were 67.3 and 66.9 years, respectively. Patients with PAD were hospitalised most frequently soon after diagnosis, with rates subsequently decreasing to 0.14 per month. These rates were similar in the reference group except for the period immediately following MI. The average 5-year cost post-diagnosis (2002 Can dollars) per patient was 41,968 Can dollars vs 48,578 Can dollars for the reference population. CONCLUSIONS: A diagnosis of PAD not only imposes a severe burden on patients and their families, but it also significantly increases the use of healthcare resources and the associated costs. By the end of year 1, this burden is comparable with a diagnosis of MI.

The morbidity and mortality following a diagnosis of peripheral arterial disease: long-term follow-up of a large database.

BACKGROUND: Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. METHODS: Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. CONCLUSION: A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased.

Economic Impact of the Use of an Absorbable Adhesion Barrier in Preventing Adhesions Following Open Gynecologic Surgeries.

We used an economic model to assess the impact of using the GYNECARE INTERCEED absorbable adhesion barrier for reducing the incidence of postoperative adhesions in open surgical gynecologic procedures. Caesarean section surgery, hysterectomy, myomectomy, ovarian surgery, tubal surgery, and endometriosis surgery were modeled with and without the use of GYNECARE INTERCEED absorbable adhesion barrier. Incremental GYNECARE INTERCEED absorbable adhesion barrier material costs, medical costs arising from complications, and adhesion-related readmissions were considered. GYNECARE INTERCEED absorbable adhesion barrier use was assumed in 75% of all procedures. The economic impact was reported during a 3-year period from a United States hospital perspective. Assuming 100 gynecologic surgeries of each type and an average of one GYNECARE INTERCEED absorbable adhesion barrier sheet per surgery, a net savings of $540,823 with GYNECARE INTERCEED absorbable adhesion barrier during 3 years is estimated. In addition, GYNECARE INTERCEED absorbable adhesion barrier use resulted in 62 fewer cases of patients developing adhesions. Although the use of GYNECARE INTERCEED absorbable adhesion barrier added $137,250 in material costs, this was completely offset by the reduction in length of stay ($178,766 savings), fewer adhesion-related readmissions ($458,220 savings), and operating room cost ($41,078 savings). Adoption of the GYNECARE INTERCEED absorbable adhesion barrier for appropriate gynecologic surgeries would likely result in significant savings for hospitals, driven primarily by clinical patient benefits in terms of decreased length of stay and adhesion-related readmissions.

Estimating the Costs of Therapy in Patients with Relapsed and/or Refractory Multiple Myeloma: A Model Framework.

BACKGROUND: Multiple myeloma is a progressive cancer for which there is no cure. Despite treatment, almost all patients eventually experience periods of disease relapse and remission. With the increasing use of novel therapies, including bortezomib, lenalidomide, carfilzomib, pomalidomide, and panobinostat, benchmarks for assessing the value of these therapies in treating patients with relapsed or refractory multiple myeloma (RRMM) are needed for physicians and payers alike. OBJECTIVES: To develop a model framework and to calculate an annual estimate of the total costs per patient for the treatment of patients with RRMM using 7 common treatment regimens, including bortezomib plus dexamethasone; panobinostat, bortezomib, and dexamethasone; lenalidomide plus dexamethasone; lenalidomide, bortezomib, and dexamethasone; carfilzomib; carfilzomib, lenalidomide, and dexamethasone; and pomalidomide plus dexamethasone. METHODS: The expenditures for drugs and their administration, for prophylaxis and adverse event monitoring, and for the treatment of grade 3 or 4 adverse events were included in the calculations of the total pharmacy and medical costs. The drug costs were based on published pricing and labeled dosing schedules; the adverse event prophylaxis and monitoring costs were obtained from peer-reviewed publications; and the adverse event incidence rates were obtained from each regimen's prescribing information and from clinical trials. All the costs were summed over the duration of therapy for which the drugs were administered and were calculated separately for commercial and Medicare plans. The duration of therapy for each regimen was the time for which a patient had to be receiving the regimen to obtain 12 months of progression-free survival based on the duration-of-therapy to progression-free survival ratio observed from published clinical trials and/or the drug's labeling. RESULTS: The pharmacy costs were highest for pomalidomide plus dexamethasone, whereas the medical costs were highest for the combination of carfilzomib, lenalidomide, and dexamethasone. The total cost associated with available treatments for RRMM was highest for regimens that included lenalidomide (approximate range, $126,000-$256,000). Only bortezomib plus dexamethasone and the combination of panobinostat, bortezomib, and dexamethasone had total costs that were lower than $125,000 per patient. CONCLUSION: This study represents the first model developed to comprehensively estimate the costs of managing RRMM with all currently approved and guideline-recommended regimens in the United States. As such, it provides the framework and basis for further budget impact analyses and for cost-effectiveness comparisons with these regimens.

Economic evaluation of galantamine in the treatment of mild to moderate Alzheimer's disease in the United States.

BACKGROUND: Alzheimer's disease (AD) is estimated to affect up to 11% of those aged > or =65 years in the United States, and the number of patients with AD is predicted to increase over the next few decades as the population ages. The substantial social and economic burden associated with AD is well established, with the cost of management increasing as the disease progresses. OBJECTIVE: The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care (FTC). METHODS: Calculations were made using the Assessment of Health Economics in Alzheimer's Disease model, which applies predictive equations to estimate the need for FTC and the associated costs. The predictive equations were developed from longitudinal data on patients with AD. Inputs to the equations were derived by analyzing the data from 2 randomized, placebo-controlled, galantamine clinical trials. Resource use (from a payer perspective) was estimated from US clinical trial data, and costs were estimated from several US databases. Analyses were carried out over 10 years, and costs and benefits were discounted at 3%. RESULTS: In the base case, 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC, depending on dose. Treated patients spent 7% to 8% more time pre-FTC and 12% to 14% less time requiring FTC, resulting in savings of 2408 to 3601 US dollars. Time horizons below 3 years, very high discontinuation rates, or increased survival with galantamine reversed the savings. Conversely, limiting treatment to responders delayed FTC by 6 to 7 months, with savings of approximately 9097 to 11,578 US dollars. CONCLUSIONS: These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly resources such as formal home care and nursing homes, leading to cost savings over time.

To what degree does cognitive impairment in Alzheimer's disease predict dependence of patients on caregivers?

BACKGROUND: Patients with Alzheimer's disease experience a progressive loss of cognitive function, and the ability to independently perform activities of daily life. Sometimes a dependent stage is reached quite early in the disease, when caregivers decide that the patients can no longer be left alone safely. This is an important aspect of Alzheimer's for patients, their families, and also health care providers. Understanding the relationship between a patient's current cognitive status and their need for care may assist clinicians when recommending an appropriate management plan. In this study, we investigated the relationship of cognitive function to dependence on caregivers before the patients reach a severe stage of the disease. METHODS: Data were obtained on 1,289 patients with mild-to-moderate Alzheimer's disease studied in two randomised clinical trials of galantamine (ReminylcircledR;). Cognition was assessed using the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Mini-Mental State Examination (MMSE). Patients were considered dependent if they required >12 hours of supervision each day or had high care needs. The Disability Assessment for Dementia (DAD) scale was also used as a measure of dependence. Disability was predicted directly using MMSE and ADAS-cog and compared to predictions from converted scores. RESULTS: The odds ratio of dependence was significantly higher amongst the patients with worse cognitive impairment, adjusting for age, gender and antipsychotic medication use. For example, a 4-point difference in ADAS-cog score was associated with an increase of 17% (95% CI 11-23) in the adjusted odds for >12 hours of supervision, and of 35% (95% CI 28-43) for dependence. Disability predicted directly using actual ADAS-cog and scores converted from MMSE values had close agreement using the models developed. CONCLUSION: In patients with mild-to-moderate Alzheimer's disease, even relatively small degrees of poorer cognitive function increased the risk of losing the ability to live independently.

Assessing the health and economic impact of galantamine treatment in patients with Alzheimer's disease in the health care systems of different countries.

INTRODUCTION: Cholinesterase inhibitors have been shown to improve cognitive function and improve or maintain global function. OBJECTIVE: To estimate the long-term economic impact of treating patients with Alzheimer's disease with galantamine in seven healthcare systems: Australia, Canada, Finland, New Zealand, Sweden, the Netherlands and the UK. METHODS: The time until patients require full-time care (FTC), defined as the consistent requirement for a significant amount of care giving and supervision each day, and the associated costs were evaluated using the 'Assessment of Health Economics in Alzheimer's Disease (AHEAD)' model. Efficacy data were obtained from three clinical trials comparing galantamine with placebo and local cost and resource use data were determined for each country. Forecast costs reported in Euros (2001 value), were made for up to 10 years in each healthcare system. All costs were determined from a perspective somewhat broader than that of a comprehensive payer, including social services. Both benefits and costs were discounted at 3%. RESULTS: Galantamine (16 mg/day) is predicted to delay the need for FTC by 6.8%, thus the cumulative cost of care over 10 years is expected to be reduced, and this offsets much or all of the cost of galantamine. Approximately five patients need to be treated to avoid 1 year of FTC. In each healthcare system, FTC was estimated to account for 61-92% of the cost. Savings were estimated for most of the countries. For those countries with an expected expense, there were reasonable costs per FTC month avoided (euro553, discounted) and costs per quality-adjusted life year gained (euro25,000). CONCLUSION: In addition to the clinical benefits associated with galantamine treatment, the savings predicted from delaying FTC may offset the treatment costs.

Rational choice of cholinesterase inhibitor for the treatment of Alzheimer's disease in Canada: a comparative economic analysis.

BACKGROUND: Cholinesterase inhibitors, such as galantamine, donepezil and rivastigmine are approved for symptomatic treatment of Alzheimer's Disease (AD) in Canada. In making choices amongst these drugs, one should consider their clinical merits and their economic implications. METHODS: Each drug's short-term efficacy was estimated based on independent Cochrane reviews of the clinical trials. Long-term clinical and economic outcomes were estimated using the Assessment of Health Economics in Alzheimer's Disease (AHEAD) model. RESULTS: While all treatments reduced the need for full-time care, only galantamine and donepezil 10 mg reduced the overall management costs of AD patients. The somewhat greater cognitive effect provided over six months by galantamine leads to the longest estimated delay before full-time care is required and, consequently to lower overall costs, with savings estimated at between 323 dollars and 4,246 dollars. CONCLUSION: Although there is uncertainty in estimated results, the best information currently available suggests that the first choice for treatment of AD should be galantamine. These results should be interpreted with caution, however, as results are not based on direct comparisons among the drugs and the differences emerging from meta-analyses of the trials are relatively small.