Longitudinal evaluation of treatment patterns, risk factors and outcomes in patients with cardiovascular disease treated with lipid-lowering therapy in the UK.

OBJECTIVES: To compare treatment patterns, risk factors and cardiovascular disease (CVD) event rates in the UK from 2008 to 2017. DESIGN: Retrospective cohort study using the Clinical Practice Research Datalink. SETTING: UK primary care. PARTICIPANTS: We selected 10 annual cohorts of patients with documented CVD receiving lipid-lowering therapy and the subsets with myocardial infarction (MI). Each cohort included patients ≥18 years old, with ≥1 year of medical history and ≥2 lipid-lowering therapy prescriptions in the prior year. PRIMARY AND SECONDARY OUTCOME MEASURES: For each annual cohort, we identified cardiovascular risk factors and lipid-lowering therapy and estimated the 1-year composite rate of fatal and non-fatal MI, ischaemic stroke (IS) or revascularisation. RESULTS: The documented CVD cohort mean age was 71.6 years in 2008 (N=173 424) and 72.5 (N=94 418) in 2017; in the MI subset, mean age was 70.1 years in 2008 (N=38 999) and 70.4 in 2017 (N=25 900). Both populations had larger proportions of men. In the documented CVD cohort, the proportion receiving high-intensity lipid-lowering therapy from 2008 to 2017 doubled from 16% to 32%; in the MI subset, the increase was 20% to 48%. In the documented CVD cohort, the proportion of patients with low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L increased from 28% to 38%; in the MI subset, the proportion with LDL-C <1.8 mmol/L increased from 32% to 42%. The composite event rate per 100 person-years declined over time, from 2.5 to 2.0 in the documented CVD cohort, and from 3.7 to 2.8 in the MI subset. After excluding revascularisation from the composite outcome, the decline in the event rate in both populations was substantially attenuated. CONCLUSIONS: Despite an increase in high-intensity therapy use and a decline in revascularisation, more than half of patients did not receive high-intensity lipid-lowering therapy by 2017 and incidence rates of MI and IS remained virtually unchanged.

Treatment patterns and outcomes in older patients with advanced malignant pleural mesothelioma: Analyses of Surveillance, Epidemiology, and End Results-Medicare data.

BACKGROUND: Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant pleural mesothelioma (MPM) is important to understand the unmet needs of this population. AIM: To evaluate the demographic and clinical characteristics, treatment patterns, and outcomes among older patients diagnosed with advanced MPM in the United States between 2007 and 2013. METHODS: This was a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims. We included patients who were age 66 or older at the time of their primary MPM diagnosis between 2007 and 2013 and followed them through 2014. Treated patients who received first-line chemotherapy with pemetrexed and platinum within 90 days of diagnosis, second-line, or third-line therapy were identified for evaluation of outcomes. RESULTS: There were 666 older patients with advanced MPM, of whom 82% were male, 87% White, 78% stage IV, and 70% had no mobility limitation indicators at diagnosis. There were 262 patients who received first-line chemotherapy for advanced MPM, most of whom (80%; n = 209) received pemetrexed-platinum. Of these 209 patients, 41% (n = 86) initiated second-line therapy, and 26% (n = 22) initiated third-line therapy. Median overall survival for the cohort of 209 patients was 7.2 months. Patients with epithelioid histology had better median overall survival (12.2 months) compared with other histologies (4.4-5.6 months). Within 90 days of diagnosis of advanced MPM, 78% of patients were hospitalized, 52% visited an emergency department, and 21% had hospice care. The 2-year cost of care was over $100 000 for all patients with advanced MPM treated with first-line pemetrexed-platinum. CONCLUSIONS: Although first-line systemic anticancer treatment was generally consistent with guidelines (e.g., pemetrexed-platinum), poor patient outcomes highlight the need for effective treatment options for older patients with advanced MPM.

Real World Use and Effects of Calcimimetics in Treating Mineral and Bone Disorder in Hemodialysis Patients.

BACKGROUND: Calcimimetics are used to treat mineral and bone disorder by reducing parathyroid hormone (PTH), calcium (Ca), and phosphorus (Phos). The study objectives were to assess the control of PTH, Ca, and Phos over time in patients receiving cinacalcet or etelcalcetide as well as dosing and time to discontinuation for etelcalcetide. METHODS: This was a retrospective cohort study using electronic medical records from small and independent dialysis centers. Adults ≥18 years of age were identified as cinacalcet or etelcalcetide users based on the first calcimimetic received in 2018 (index date). Patients were followed from the index date until parathyroidectomy, kidney transplant, death, or end of data (December 31, 2018). Analyses of mean PTH, Ca, and Phos, as well as target achievement of PTH, Ca, and Phos were conducted over a 9-month period. Discontinuation with etelcalcetide was measured with the Kaplan-Meier estimator. RESULTS: There were 1,346 cinacalcet patients (mean age 60.5 years, 43.5% female, and 47.1% Black) and 1,255 etelcalcetide patients (mean age 63.4 years, 46.6% female, and 38.5% Black). At baseline, the proportions in target were similar for etelcalcetide versus cinacalcet: 36 versus 38% for PTH, 79 versus 80% for Ca, and 43 versus 44% for Phos. Overall, 40-47% of cinacalcet users and 48-62% of etelcalcetide users were observed to be in target for PTH over 9 months. The proportion in target for Phos ranged from 41 to 46% for cinacalcet and 46-51% for etelcalcetide. The proportion in target for Ca ranged from 74 to 78% for cinacalcet and 60-73% for etelcalcetide. Etelcalcetide 12-month discontinuation was 37.4%. CONCLUSION: Both calcimimetics were effective in keeping PTH, Ca, and Phos levels within target. Patients receiving etelcalcetide tended to have lower laboratory values for PTH, Ca, and Phos over time, while patients receiving cinacalcet tended to be more likely to be in target for Ca over time.

Estimated Life Expectancy and Income of Patients With Sickle Cell Disease Compared With Those Without Sickle Cell Disease.

Importance: Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD. Objective: To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD. Design, Setting, and Participants: Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018. Main Outcomes and Measures: Life expectancy, quality-adjusted life expectancy, and projected lifetime income. Results: The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates. Conclusions and Relevance: In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.

Quality adjusted life year gains associated with administration of recombinant tissue-type plasminogen activator for treatment of acute ischemic stroke: 1998-2011.

BACKGROUND: Intravenous recombinant tissue-type plasminogen activator (r-tPA) is an approved treatment for select patients with acute ischemic stroke (AIS). Data indicate r-tPA improves functional outcome three months after AIS compared with placebo. This study models the increase in quality adjusted life years (QALYs) associated with r-tPA compared with similar patients not treated with r-tPA. METHODS: Hospital discharge data for AIS and r-tPA were obtained from the Nationwide Inpatient Sample from 1998 to 2011. Discharge location (home, rehabilitation, long-term care, death) was mapped to modified Rankin Scale (mRS) scores based on National Institute of Neurological Disorders and Stroke (NINDS) Study Group Part 1 and 2 clinical studies. The mRS scores were mapped to relative risk of death and QALYs obtained from the literature. The model estimated expected survival and QALYs by age, gender and mRS for patients receiving r-tPA. Life expectancy and QALYs for patients not receiving r-tPA were estimated based on discharge location and mRS for placebo patients in the NINDS study. RESULTS: AIS discharges declined from over 635,000 in 1998 to over 593,000 in 2011. A total of 183,235 patients received r-tPA. Utilization of r-tPA increased from 1% of AIS patients in 1998 to over 4% in 2011. Estimated projections for QALYs gained from utilization of r-tPA to QALYS without r-tPA were just under 240,000 for the 13 years and with no discounting, and just over 165,000 assuming 3% annual discounting. In the most conservative scenario, assuming no difference in proportional discharge status (i.e. patients not treated with r-tPA are discharged in the same manner as r-tPA patients), the estimated life years gained are approximately 35,000 and QALYS gained are approximately 90,000. CONCLUSIONS: r-tPA for AIS has resulted in estimated gains in quality-adjusted life years due to reduction in disability and improvement in functioning since its introduction in 1998.

Progression of autosomal dominant kidney disease: measurement of the stage transitions of chronic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. METHODS: This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000-2/28/2013 and ≥6 months of previous continuous enrollment (baseline) within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD) patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. RESULTS: ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. CONCLUSIONS: These results suggest that distribution of patients by age at transition to next stage may be useful for identification of ADPKD patients at risk of rapid progression. The results also suggest that medical claims with diagnosis codes for "unspecified PKD", in absence of a diagnosis code for autosomal recessive polycystic kidney disease, may be a good proxy for ADPKD.

Hospital-based inpatient resource utilization associated with autosomal dominant polycystic kidney disease in the US.

OBJECTIVE: Polycystic kidney disease (PKD) is a clinically and genetically heterogeneous class of genetic disorders characterized by development of renal cysts leading to renal failure and end stage renal disease (ESRD). Autosomal dominant polycystic kidney disease (ADPKD) accounts for the majority of PKD cases and is the predominant monogenic cause of ESRD. Limited information on patient characteristics and healthcare resource utilization is available in this population. This study assessed hospital-based inpatient utilization of patients with ADPKD in the US to help further understand the disease, which may lead to treatments that delay progression and reduce healthcare resource utilization. METHODS: A cross-sectional analysis was conducted using MedAssets Health System Data to investigate inpatient resource utilization for a total of 1876 patients hospitalized with ADPKD or chronic kidney disease (CKD). Patient characteristics and inpatient resource utilization were compared between hospitalized patients with ADPKD and CKD, including demographic and clinical characteristics, overall health, rates of complications and surgical interventions, and average length of hospital and intensive care unit stay. RESULTS: Compared with patients with CKD, patients with ADPKD were more likely to have commercial insurance as their primary payer (36.1 vs 17.8%) and were significantly younger (mean age 57.9 vs 69.5 years) and generally healthier (Charlson Comorbidity Score of 2.0 vs 3.3). Patients with ADPKD also had a substantially shorter average length of hospital stay (6.3 vs 10.3 days). However, patients with ADPKD experienced more kidney-related complications and a higher surgical procedure rate (mainly for transplant and complete nephrectomy). CONCLUSIONS: Although patients with ADPKD were generally healthier than patients with CKD, specific kidney function complications were more frequent. Patients with ADPKD had a higher rate of major kidney procedures, which may contribute to the high burden of ADPKD-related hospital-based inpatient resource utilization.

The economic impact of improving phosphate binder therapy adherence and attainment of guideline phosphorus goals in hemodialysis patients: a Medicare cost-offset model.

INTRODUCTION: Hyperphosphatemia (serum phosphorus >5.5 mg/dL) in hemodialysis patients is a key factor in mineral and bone disorders and is associated with increased hospitalization and mortality risks. Treatment with oral phosphate binders offers limited benefit in achieving target serum phosphorus concentrations due to high daily pill burden (7-10 pills/day) and associated poor medication adherence. The economic value of improving phosphate binder adherence and increasing percent time in range (PTR) for target phosphorus concentrations has not been previously assessed in dialysis patients. The current retrospective analysis was conducted to summarize health care cost savings to United States (US) payers associated with improved phosphate binder adherence and increased PTR for target phosphorus concentrations in adult end-stage renal disease (ESRD) patients receiving hemodialysis therapy. METHODS: Phosphate binder adherence and PTR were derived from hemodialysis patients who were treated at a large dialysis organization between January 2007 and December 2011. Cost model inputs were derived from US Renal Data System data between July 2007 and December 2009. A cost-offset model was constructed to estimate monthly and annual incremental health care costs (total Medicare; inpatient, outpatient, and Medicare Part B) associated with different levels of phosphate binder adherence and PTR. Model inputs included number of ESRD patients, population adherence to phosphate binders, PTR associated with adherence to phosphate binders, and per-patient per-month cost associated with PTR. A base case model estimated monthly and annual costs of phosphate binder therapy in the population using estimated model inputs. The estimated adherence rate was used to determine number of patients in compliant and noncompliant groups. Monthly costs were calculated as the sum of per-patient per-month cost times the number of patients in adherent and nonadherent groups. Annual costs were monthly costs times 12 and assumed the same level of adherence, PTR, and per-patient per-month costs over time. To study the impact of improving phosphate binder adherence and PTR on cost outcomes, we hypothetically and simultaneously increased both base phosphate binders adherence and PTR for adherent patients (adherence/PTR: 10/20%, 20/40%, 30/60%). Monthly and annual costs were derived for each scenario and compared against the results of the base case model. One-way sensitivity analysis was performed to test model robustness. RESULTS: The base case model estimated total Medicare and inpatient costs of $5,152,342 and $1,435,644, respectively (N = 1,000). When base case model costs were compared to results of each extended model scenario, overall Medicare cost savings (range 0.3-1.9%) and inpatient cost savings (range 1.2-5.7%) were observed. The one-way sensitivity analysis indicated that results were sensitive to PTR for adherent and nonadherent patients and the factor used to increase adherence rate and PTR associated with adherence in the hypothetical scenarios. However, cost savings in overall Medicare costs and inpatient costs were still noted. CONCLUSION: Increasing phosphate binder adherence and improving phosphorus control were associated with increased cost savings in total Medicare costs and inpatient costs.

Patterns of care in community-based oncology practices for anemia associated with myelosuppressive chemotherapy.

Use of erythropoiesis-stimulating agents in the treatment of myelosuppresive chemotherapy-induced anemia has been shown to increase hemoglobin levels and reduce the need for transfusions in patients with cancer.

Budget impact model of adding erlotinib to a regimen of gemcitabine for the treatment of locally advanced, nonresectable or metastatic pancreatic cancer.

OBJECTIVE: The aim of this study was to determine the budget impact of adding erlotinib to a US health plan insurer's formulary as a combination therapy with gemcitabine for the treatment of nonresectable pancreatic cancer. METHODS: An Excel-based budget impact model was developed to evaluate the costs for National Comprehensive Cancer Network guideline-recommended treatment options for patients with locally advanced, nonresectable or metastatic pancreatic cancer from the perspective of a US managed care plan. The model compared treatment with gemcitabine alone and in combination with erlotinib, including the costs of treatment, adverse events (AEs), and administration. Inputs for the model were derived from the Surveillance, Epidemiology and End Results Cancer Registry, clinical trials, and publicly available sources and were varied in sensitivity analyses to identify influential inputs. The model addressed first-line use in a single indication and assumed that the proportion of patients aged >or=65 years in a managed care organization was the same as in the general population. The model did not account for patient copayments for oral medications, a factor that could lower a plan's overall cost further than estimated herein. RESULTS: For a hypothetical managed care plan with 500,000 members, the model estimated 43 newly diagnosed pancreatic cancer cases each year, of which 56% (n=24) would be treated with gemcitabine as first-line therapy. Assuming that erlotinib were added to the treatment regimen in 40% (n=10) of gemcitabine-treated patients for 15.7 weeks of therapy per patient, the expected 1-year cost in 2006 dollars would be US $466,700 compared with $346,700 had all patients been treated with gemcitabine alone. Administration costs accounted for 10% to 12% of total costs, while AE management costs made up 14% to 16% of total costs. These estimates corresponded to an incremental cost of $120,000, or $0.020 per member per month (PMPM). The results were relatively insensitive to drug costs, drug administration costs, and costs of treatment of AEs based on sensitivity analyses. CONCLUSIONS: In this analysis of the budget impact of adding to the health plan formulary erlotinib to a regimen of gemcitabine as first-line treatment of locally advanced, nonresectable or metastatic pancreatic cancer in the United States, the budget impact was $0.020 PMPM. The relatively low incidence of pancreatic cancer and the assumption of treating only 23% of these patients with erlotinib were likely the principal reasons for the low budgetary impact of erlotinib. In this model and using these reasonable assumptions, the results suggested that the incremental cost impact on a PMPM basis may be small.

Second-line and third-line chemotherapy for lung cancer: use and cost.

OBJECTIVES: To identify commonly prescribed first-, second-, and third-line chemotherapy regimens for persons with lung cancer and to evaluate the utilization patterns and costs of care associated with receiving these regimens. STUDY DESIGN: Retrospective data analysis. METHODS: Using health insurance claims from January 1, 2002, through December 31, 2006, patients with lung cancer were identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. An algorithm was developed to identify first-, second-, and third-line chemotherapy. Patients were stratified by the number of discrete regimens received or by their specific chemotherapy agent or combination of agents. Data were analyzed for up to 2 years from the date of the initial first-line regimen and for 1 year from the second and third lines. Patient costs were based on total reimbursements for each group during the observation period. RESULTS: Of patients receiving first-line chemotherapy, 25% and 10% received second-line and third-line chemotherapy, respectively. Docetaxel, gefitinib, and erlotinib hydrochloride were the most commonly prescribed second-line regimens; gefitinib and docetaxel were the most commonly prescribed third-line regimens. The most commonly prescribed second- and third-line agents changed substantially over time. Total costs and costs per patient per month increased as the number of lines of chemotherapy prescribed increased. CONCLUSIONS: Second- and third-line chemotherapy is prescribed infrequently, and patterns of prescribing are changing over time. Direct medical care costs increase substantially with additional lines of therapy.

Watchful waiting and health related quality of life for patients with localized prostate cancer: data from CaPSURE.

PURPOSE: Watchful waiting is an alternative to active treatment for men with low risk prostate cancer but it is unclear how health related quality of life (HRQoL) may change over time for men who select this option. We report on HRQoL in men with localized prostate cancer who selected watchful waiting. MATERIALS AND METHODS: HRQoL outcomes were reviewed for 310 men diagnosed with prostate cancer from 1990 to 2001 within Cancer of the Prostate Strategic Urological Research Endeavor who chose watchful waiting. The UCLA Prostate Cancer Index and RAND 36-Item Health Survey were completed at enrollment and approximately every 6 months. A random slopes model was developed to assess time trends in HRQoL for up to 5 years after diagnosis, adjusting for age at diagnosis and specific comorbidities. RESULTS: Significant decreases with time were observed in 7 domains of the RAND 36-Item Health Survey and 4 of the UCLA Prostate Cancer Index scales. CONCLUSIONS: Men with prostate cancer who chose watchful waiting in the current study had better or similar HRQoL outcomes compared to men without prostate cancer at the start of the study. Many of these scores were significantly affected by increasing age and decreased with time. The physical domain scores as well as sexual function scores decreased more than expected from the aging process alone.

Insurance and quality of life in men with prostate cancer: data from the Cancer of the Prostate Strategic Urological Research Endeavor.

OBJECTIVE: To evaluate the effect of medical insurance coverage on health-related quality of life (HRQoL) outcomes in men newly diagnosed with prostate cancer, as insurance status has been shown to be related to clinical presentation, and types of treatments received for localized prostate cancer, but the relationship of insurance and QoL has not been explored sufficiently. PATIENTS AND METHODS: Data from the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE), a national longitudinal database registry of men with prostate cancer, were used for this study. Men who were newly diagnosed at entry to CaPSURE and completed one questionnaire before treatment, and one or more afterwards, were included. Insurance groups specific to age distribution of the study population were assessed, i.e. Medicare, preferred provider organizations (PPOs), health maintenance organizations (HMOs), fee for service (FFS), and the Veterans Administration (VA) for the younger group, and Medicare only, Medicare plus supplement (+S), and HMO/PPO for the older group. Associations between patients' clinical and sociodemographic characteristics and insurance status were evaluated by chi-square and analysis of variance. Relationships between insurance status and HRQoL outcomes over time were evaluated by multivariate mixed model. RESULTS: Of 2258 men who met the study criteria, 1259 were younger and 999 were older than 65 years. More than half of the younger patients belonged to an HMO or PPO (42.2% and 32.5%, respectively), with the remainder distributed between Medicare, FFS and VA. In the older group most men belonged to Medicare only and the Medicare +S groups (22.4% and 58.8%, respectively). There was greater variation in clinical risk categories at presentation by insurance groups in the younger group. In the multivariate analysis, insurance status was significantly associated with changes in most HRQoL outcomes over time in the younger group, while in the older patients the effect of insurance diminished. Men in the VA and Medicare systems had lower scores at baseline and a steeper decline in Physical Function, Role Physical, Role Emotional, Social Function, Bodily Pain, Vitality, and General Health domains over time, controlling for type of initial treatment received, timing of HRQoL assessment, number of comorbidities, clinical risk at presentation, and income. CONCLUSION: Insurance was independently related to changes in a wide range of HRQoL outcomes in men aged <65 years treated for prostate cancer. With the latest advances in early diagnosis and treatment of prostate cancer, clinicians and researchers should be aware of the specific groups of patients who are more vulnerable to the adverse effects of treatment and subsequent decline in functioning. The present findings could provide important tools for understanding the process of recovery after treatment for prostate cancer, and identifying needs for specific services.

Comparative clinical and economic outcomes of treatments for refractory non-small cell lung cancer (NSCLC).

BACKGROUND: Various drug therapies are available for treatment of refractory stage IIIB/IV non-small cell lung cancer (NSCLC), but their comparative economic value is unclear. METHODS: We developed a decision analytic model to evaluate the incremental costs and quality-adjusted life-years (QALYs) of erlotinib, docetaxel, or pemetrexed in a cohort of refractory advanced stage NSCLC patients 60 years of age from a US payer perspective. Mean progression-free and overall survival were assumed equal for the three treatments based on published clinical trials, from which adverse event rates were also derived. Costs and utilities were obtained from publicly available sources. We performed sensitivity analyses to evaluate uncertainty in the results. RESULTS: Treatment with erlotinib, docetaxel, and pemetrexed yielded 0.42, 0.41, and 0.41 quality-adjusted life-years (QALYs), respectively. The slightly increased QALYs for erlotinib compared to docetaxel and pemetrexed resulted from less severe treatment complications and oral vs. IV administration. Total costs were US$ 37,000, US$ 39,100 and US$ 43,800 for erlotinib, docetaxel and pemetrexed, respectively. In the probabilistic sensitivity analyses, erlotinib was cost-saving in 65 and 87% of the simulations compared to docetaxel and pemetrexed, respectively, and had improved QALYs and decreased costs or was cost-effective in 42 and 55% of simulations. Estimates of treatment duration were among the most influential parameters in the analyses. CONCLUSIONS: The results of our analysis suggest treatment of refractory NSCLC with erlotinib is less costly compared with alternative treatments, and suggested improvements in QALYs should be confirmed in controlled clinical trials.

Economic evaluation of rituximab plus cyclophosphamide, vincristine and prednisolone for advanced follicular lymphoma.

The addition of rituximab to cyclophosphamide, vincristine and prednisolone (CVP) for advanced follicular lymphoma increases median time to progression by 17 months. A US societal cost-effectiveness of R-CVP versus CVP is estimated for a representative 50-year-old patient. Progression-free survival (PFS) and overall survival are based on a randomized Phase III trial. Costs are estimated using Medicare reimbursement rates and published drug price data, and include drug and administration costs, adverse events, treatment of relapses, and end-of-life care. Utility estimates are derived from the literature and a 3% discount rate is employed. Mean overall survival is projected to be 1.51 years longer for patients assigned to R-CVP versus CVP. The cost per quality-adjusted year of life gained is $28,565. The utility associated with stable or progressive disease and the unit drug cost of rituximab most influence the findings. The cost-effectiveness ratio of R-CVP compared with CVP is projected to be cost-effective in the United States under a range of sensitivity analyses.

Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer.

BACKGROUND: Adding trastuzumab to adjuvant chemotherapy provides significant clinical benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A cost-effectiveness analysis was performed to assess clinical and economic implications of adding trastuzumab to adjuvant chemotherapy, based upon joint analysis of NSABP B-31 and NCCTG N9831 trials. METHODS: A Markov model with 4 health states was used to estimate the cost utility for a 50-year-old woman on the basis of trial results through 4 years and estimates of long-term recurrence and death based on a meta-analysis of trials. From 6 years onward, rates of recurrence and death were assumed to be the same in both trastuzumab and chemotherapy-only arms. Incremental costs were estimated for diagnostic and treatment-related costs. Analyses were from payer and societal perspectives, and these analyses were projected to lifetime and 20-year horizons. RESULTS: Over a lifetime, the projected cost of trastuzumab per quality-adjusted life year (QALY; discount rate 3%) gained was 26,417 dollars (range 9,104 dollars-69,340 dollars under multiway sensitivity analysis). Discounted incremental lifetime cost was 44,923 dollars, and projected life expectancy was 3 years longer for patients who received trastuzumab (19.4 years vs 16.4 years). During a 20-year horizon, the projected cost of adding trastuzumab to chemotherapy was 34,201 dollars per QALY gained. Key cost-effectiveness drivers were discount rate, trastuzumab price, and probability of metastasis. The cost-effectiveness result was robust to sensitivity analysis. CONCLUSIONS: Trastuzumab for adjuvant treatment of early stage breast cancer was projected to be cost effective over a lifetime horizon, achieving a cost-effectiveness ratio below that of many widely accepted oncology treatments.

Assessment of prognosis with the total illness burden index for prostate cancer: aiding clinicians in treatment choice.

BACKGROUND: Among the most pressing challenges that face physicians who care for men with prostate cancer is evaluating the patient's potential for benefiting from treatment. Because prostate cancer often follows an indolent course, the presence and severity of comorbidities may influence the decision to treat the patient aggressively. The authors adapted the Total Illness Burden Index (TIBI) for use in decision-making among men with prostate cancer at the time of the visit. METHODS: An observational study was performed of 2894 participants in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national disease registry of men with prostate cancer, to examine how well the adapted TIBI for prostate cancer (TIBI-CaP) predicted mortality over the subsequent 3.5 years and health-related quality of life over the subsequent 6 months. RESULTS: The men who had the highest global TIBI-CaP scores were 13 times more likely to die of causes other than prostate cancer over a 3.5-year period than the men who had the lowest scores (hazard ratio, 13.1, 95% confidence interval, 6.3-27.4) after controlling for age, education, income, and race/ethnicity. Patients who had the highest TIBI-CaP scores had 44% mortality compared with 4.9% mortality for patients who had the lowest scores. Demographic variables explained 16% of the variance in future physical function; TIBI-CaP scores explained an additional 19% of the variance. CONCLUSIONS: The TIBI-CaP, a patient-reported measure of comorbidity, identified patients at high risk for nonprostate cancer mortality. It predicted both mortality and future quality of life. The TIBI-CaP may aid physicians and patients in making appropriate treatment decisions.

Clinical and psychosocial characteristics of men with erectile dysfunction: baseline data from ExCEED.

INTRODUCTION: Erectile dysfunction (ED) is associated with psychological impairment, and further research is required to understand their relationship. AIM: We present descriptive baseline results from a longitudinal observational study of North American men seeking treatment for ED. METHODS: Patients completed clinical and health-related quality-of-life information at baseline and three follow-up points over 12 months; 162 patients had usable baseline data, including clinical history and current status, sociodemographic information, and standard paper-and-pencil scales of psychosocial characteristics. Scores on the International Index of Erectile Functioning erectile functioning subscale were collapsed into mild (N = 27), moderate (N = 41), or severe (N = 94) categories. Using chi-square, anova, and logistic regression, we identified baseline characteristics associated with ED severity. MAIN OUTCOME MEASURE: The main outcome measure was the degree of psychosocial impairment associated with mild, moderate, and severe ED. RESULTS: Severe ED was significantly associated with not having a regular sex partner; a history of prostate cancer; and worse scores on measures of positive affect, belonging/loneliness, sexual self-efficacy-strength, psychological adjustment, marital happiness, anxiety at last intercourse, and depression. In a multivariate logistic regression model, poorer sexual self-efficacy was most closely associated with severe ED. The model rescaled R(2) was 0.63 (area-under-the-curve, 0.91). CONCLUSIONS: Severe ED is related to impairment across a broad range of psychosocial domains, and clinicians should consider offering patients assistance in dealing with its psychosocial impact.

Longitudinal differences in psychological outcomes for men with erectile dysfunction: results from ExCEED.

INTRODUCTION: The direction of the relationship between psychological adjustment and erectile dysfunction (ED) is unclear and may differ for different men, and few studies have examined psychological outcomes for men receiving ED treatment. AIM: This study assessed the impact of ED therapy at baseline and 12-month follow-up, using standard psychological measures. METHODS: Using an observational ED registry, we collected clinical and psychosocial data at baseline and 3, 6, and 12 months. Participants had (i) a patient-reported outcomes questionnaire at baseline and at least one follow-up; and (ii) data about ED treatments received during the study. Treated men were classified as responders based on improvements in International Index of Erectile Function scores from baseline to 12 months. MAIN OUTCOME MEASURES: The main outcome measures were changes in psychological outcomes in relation to treatment status and baseline ED severity. RESULTS: Of 153 patients, 40 responded to treatment, 49 did not respond to treatment, and 64 did not receive treatment. Treatment responders reported significant improvements in 12-month sexual self-efficacy but only small improvements or no change across five other psychological domains, whereas nonresponders reported small decrements. There was a trend for differences in sexual self-efficacy to vary by baseline ED severity, as well as by treatment response. CONCLUSIONS: Diagnosing and successfully treating ED significantly affects patient psychological adjustment, so providers should actively diagnose and treat ED.

Evaluation of erlotinib in advanced non-small cell lung cancer: impact on the budget of a U.S. health insurance plan.

BACKGROUND: Lung cancer is the most common non-skin cancer and the leading cause of cancer death among men and women in North America. More than half of all patients diagnosed with lung cancer are diagnosed with advanced disease. Most cases of lung cancer are non-small cell lung cancer (NSCLC). Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least 1 prior chemotherapy regimen. OBJECTIVE: To assess the budgetary impact, from the health plan perspective, of covering erlotinib for treating patients with NSCLC stage IIIb/IV who have failed at least 1 prior chemotherapy regimen. METHODS: An Excel-based model was developed to evaluate costs for U.S. Food and Drug Administration-approved and National Comprehensive Cancer Network guideline-recommended treatment options for second- and third-line NSCLC from the perspective of a U.S. health insurer. In particular, the model compares a formulary with erlotinib and a formulary without erlotinib, including the costs of treatment, drug administration, and adverse effects. The incidence of advanced NSCLC is based on the Surveillance, Epidemiology, and End Results Cancer Registry and adverse effects related to treatment (all agents) in published results of clinical trials. Drug and treatment costs were obtained from publicly available sources in 2005. RESULTS: The base case considers a health plan of 500,000 enrollees. Assuming that erlotinib comprises 30% of second-line treatments and 90% for third-line, total costs of treating stage IIIb/IV NSCLC patients over 1 year are Dollars 382,418 with erlotinib and Dollars 380,968 without erlotinib (difference: Dollars 1,450; 90% confidence interval, -Dollars 61,376 to Dollars 29,855), less than Dollars 0.01 per member per month (PMPM) in 2005. Erlotinib direct cost is offset by reductions in standard chemotherapy-related infusion costs and adverse events. CONCLUSIONS: Based on the analysis, the inclusion of erlotinib on a formulary appears to have a relatively small impact on the annual health care budget or PMPM expenditures if it is used consistent with the product label indications.