Outcomes of erythropoiesis-stimulating agents in cancer patients with chemotherapy-induced anemia.

PURPOSE: To assess the clinical and economic outcomes among patients with chemotherapy-induced anemia (CIA) treated with United States Food and Drug Administration-approved fixed dosing regimens of erythropoiesis-stimulating agents (ESA). METHODS: Data were employed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) registry to evaluate CIA patients who were initiated on either epoetin alfa (EPO) 40,000 Units (U) or darbepoetin alfa (DARB) 500 micrograms (mcg) between January 1, 2006 and May 8, 2009. Study measurements included ESA treatment dose and dose ratio, changes in hemoglobin (Hb) levels from baseline, and cumulative ESA costs. RESULTS: Five hundred forty patients treated in 44 clinical centers were evaluated, of which 420 were initiated on EPO 40,000 U and 120 were initiated on DARB 500 mcg. Both cohorts had similar baseline characteristics, although EPO patients were less likely than DARB patients to have received iron supplementation before ESA initiation (11.4% EPO vs. 20.0% DARB, p = 0.015). The EPO-to-DARB dose ratio based on cumulative ESA dose was 169:1 (U EPO: mcg DARB). EPO patients showed statistically greater Hb improvement compared to DARB patients, and compared to EPO patients, a greater proportion of DARB patients required a blood transfusion (13.9% EPO vs. 22.5% DARB, p = 0.026). Mean cumulative ESA cost was significantly lower for EPO patients than DARB patients ($4,261 EPO vs. $8,643 DARB, p < 0.0001). CONCLUSIONS: These findings reported that patients with CIA achieved more favorable clinical and economic outcomes if initiated with EPO 40,000 U vs. DARB 500 mcg.

Hematologic outcomes and blood utilization in cancer patients with chemotherapy-induced anemia (CIA) pre- and post-national coverage determination (NCD): results from a multicenter chart review.

PURPOSE: In July 2007, the Centers for Medicare and Medicaid Services (CMS) limited coverage of erythropoiesis-stimulating agents (ESAs) in cancer patients with chemotherapy-induced anemia (CIA) through a National Coverage Determination (NCD). The primary objective of this study was to compare transfusion rates in patients with CIA with lung, breast, or colorectal cancer before and after the NCD. METHODS: Adult Medicare patients with CIA treated at 49 community oncology clinics were selected from two time periods based on clinics' NCD implementation date. Chart data were abstracted for 12 weeks post-CIA episode start, defined as hemoglobin (Hb) level <11 g/dL while receiving chemotherapy or within 60 days of the last chemotherapy dose. Multivariate analyses were used to calculate the odds of transfusion and to assess the units of blood transfused, controlling for differences in demographics, clinical history, and chemotherapy. RESULTS: Eight hundred pre-NCD and 994 post-NCD patients from 49 sites were selected. Of the patients, 56% used ESAs post-NCD vs. 88% pre-NCD (p < 0.0001). The duration of ESA use decreased in the post-NCD (32.1 days) vs. pre-NCD (48.4 days, p < 0.0001) group. The post-NCD group reported significantly lower Hb levels, higher odds of receiving a transfusion (odds ratio: 1.41, 95% CI 1.05-1.89, p = 0.0238) and increased blood utilization of 53% (units transfused: OR 1.53, 95% CI 1.15-2.04, p = 0.0034). CONCLUSIONS: Decreased frequency and duration of ESA administration were reported in the post-NCD vs. pre-NCD period. Findings were accompanied by a modest but statistically significant increase in transfusions and a decrease in Hb values.

Disease and treatment burden of psoriasis: examining the impact of biologics.

Plaque psoriasis is a chronic, inflammatory skin disease that can be difficult to treat. Traditional systemic agents, topical agents, phototherapy and biologic therapies can be used for patients with psoriasis. The authors reviewed published results from a variety of sources in order to better understand the effects of psoriasis treatments on patient satisfaction, patient adherence, healthcare resource utilization and productivity. Patients with psoriasis consider many factors when evaluating therapies, including the time for the therapy to be effective, cosmetic issues common with topical therapies and travel to and from phototherapy centers. Satisfaction with and adherence to biologic therapies appears to be greater than for traditional therapies. Although biologic therapies are generally more expensive than are traditional, these agents may contribute to decreased healthcare utilization and increased productivity.

Good research practices for measuring drug costs in cost-effectiveness analyses: a managed care perspective: the ISPOR Drug Cost Task Force report--Part III.

OBJECTIVES: The objective of this report is to provide guidance and recommendations on how drug costs should be measured for cost-effectiveness analyses conducted from the perspective of a managed care organization (MCO). METHODS: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (DCTF) was appointed by the ISPOR Board of Directors. Members were experienced developers or users of CEA models. The DCTF met to develop core assumptions and an outline before preparing a draft report. They solicited comments on drafts from external reviewers and from the ISPOR membership at ISPOR meetings and via the ISPOR Web site. RESULTS: The cost of a drug to an MCO equals the amount it pays to the dispenser for the drug's ingredient cost and dispensing fee minus the patient copay and any rebates paid by the drug's manufacturer. The amount that an MCO reimburses for each of these components can differ substantially across a number of factors that include type of drug (single vs. multisource), dispensing site (retail vs. mail order), and site of administration (self-administered vs. physician's office). Accurately estimating the value of cost components is difficult because they are determined by proprietary and confidential contracts. CONCLUSION: Estimates of drug cost from the MCO perspective should include amounts paid for medication ingredients and dispensing fees, and net out copays, rebates, and other drug price reductions. Because of the evolving nature of drug pricing, ISPOR should publish a Web site where current DCTF costing recommendations are updated as new information becomes available.

Impact of limiting erythropoiesis-stimulating agent use for chemotherapy-induced anemia on the United States blood supply margin.

BACKGROUND: Recently, the Centers for Medicare and Medicaid Services issued a national coverage determination that limited erythropoiesis-stimulating agents (ESAs) utilization in patients with chemotherapy-induced anemia (CIA). This study evaluated the impact of limiting the use of ESAs for CIA on the US blood supply margin. STUDY DESIGN AND METHODS: A modeling simulation was employed to compare the number of red blood cell (RBC) units transfused in CIA patients treated with ESAs to the number of RBC units that would be transfused if ESAs were limited or discontinued. The excess number of RBC units that would be required with limited ESA treatment was contrasted with the available marginal blood supply from 2004 and 2008. Model inputs were obtained from published literature or empirical evidence when published information was unavailable. RESULTS: The model predicted that up to 18 and 15 percent of the respective 2004 and 2008 marginal US blood supply would be required to cover the incremental demand for blood that would arise from a 25 percent decrease in ESA use. For ESA use reductions of 50 and 75 percent, the model predicted 17 to 21 percent (134,667 units) and 26 to 31 percent (202,001 units) of the 2008 and 2004 marginal US blood supply would be required, respectively. CONCLUSION: This study showed that limiting ESA use in CIA patients would impose considerable pressure on the available blood supply margin given the small margin between usable blood and transfusion demand. The public health consequences of such an outcome should be taken into account when revisions to ESA use are being considered.

Direct all-cause health care costs associated with chronic kidney disease in patients with diabetes and hypertension: a managed care perspective.

BACKGROUND: Diabetes and hypertension are the 2 major causes of endstage renal disease. The rate of chronic kidney disease (CKD) secondary to diabetes and/or hypertension is on the rise, and the related health care costs represent a significant economic burden. OBJECTIVE: To quantify from a health system perspective the incremental direct all-cause health care costs associated with a diagnosis of CKD in patients with diabetes and/or hypertension. METHODS: An analysis was conducted of medical claims and laboratory data with dates of service between January 1, 2000, and February 28, 2006, from a managed care database for approximately 30 million members enrolled in 35 health plans. Each patient's observation period began on the date of the first diabetes or hypertension diagnosis (index date) and ended on the earlier of the health plan disenrollment date or February 28, 2006. Inclusion criteria were continuous insurance coverage in the 6 months prior to the index date and during the observation period, age at least 18 years, and at least 2 claims less than 90 days apart with a primary or secondary diagnosis for diabetes or hypertension. Exclusion criteria were cancer, lupus, or organ transplantation or chemotherapy at any time during the observation period. CKD was defined as at least 1 claim with a primary or secondary diagnosis for CKD and at least 2 glomerular filtration rate values of below 60 milliliters per minute per 1.73 square meters of body surface area (60 mL/min/1.73 m(2)) at any time during the observation period. Bivariate and Tobit regression analyses were conducted to compare patients who developed CKD versus those who did not for annualized (per patient per month [PPPM] multiplied by 12) direct, all-cause, health care costs, defined as standardized net provider payments after subtraction of member cost-share. These costs consisted of outpatient services, inpatient services, and pharmacy claims. A subset analysis of the post-versus pre- CKD medical costs was also conducted for cohorts of patients with at least 60 days of observation before and after the development of CKD; that analysis measured both all-cause costs and costs for services directly related to CKD treatment (i.e., claims with a primary or secondary diagnosis of CKD or claims for dialysis services). RESULTS: 11,531 patients with diabetes, 74,759 patients with hypertension, and 4,779 patients with both conditions were identified, of whom 123 (1.1%), 1,137 (1.5%), and 712 (14.9%), respectively, developed CKD during the observation period. The CKD group was older than the no-CKD group in each cohort (mean ages for CKD vs. no-CKD were, respectively, diabetes only cohort: 60.7 vs. 49.9 years, P < 0.001; hypertension only cohort: 63.6 vs. 53.6 years, P < 0.001; diabetes and hypertension cohort: 63.4 vs. 61.8 years, P < 0.001). CKD was associated with significantly higher total direct all-cause health care costs, with unadjusted annualized per patient mean [median] cost differences of $11,814 [$6,895], $8,412 [$4,115], and $10,625 [$7,203], respectively (diabetes: $18,444 [$11,025] vs. $6,631 [$4,131], P < 0.001; hypertension: $14,638 [$7,817] vs. $6,226 [$3,703], P < 0.001; diabetes and hypertension: $21,452 [$13,840] vs. $10,827 [$6,637], P < 0.001). The largest driver of the all-cause mean cost difference associated with CKD for each cohort was hospitalization cost (diabetes: $6,410, P < 0.001; hypertension: $5,498, P < 0.001; diabetes and hypertension: $6,467, P < 0.001). Among patients developing CKD, all-cause mean [median] annualized costs increased significantly following CKD onset (increases for patients with diabetes: $8,829 [$4,899], P = 0.026; hypertension: $4,175 [$2,741], P = 0.004; diabetes and hypertension: $9,397 [$7,240], P < 0.001). In the post-CKD period, costs directly related to treatment of CKD accounted for 9%--19% of all-cause medical service costs--9.2% for patients with diabetes, 11.6% for patients with hypertension, and 18.8% for patients with both diabetes and hypertension. CONCLUSION: CKD was associated with significantly higher all-cause health care costs in managed care patients with diabetes and/or hypertension.

Anaemia and the risk of injurious falls in a community-dwelling elderly population.

BACKGROUND: Anaemia in the elderly is associated with a number of health-related functional declines, such as frailty, disability and muscle weakness. These may contribute to falls which, in the elderly, result in serious injuries in perhaps 10% of cases. OBJECTIVE: To investigate whether anaemia increases the risk of injurious falls in an elderly population. METHOD: Health insurance claims and laboratory test results data from January 1999 to April 2004 for 47 530 individuals >or=65 years of age enrolled in over 30 managed care plans were analysed. An open-cohort design was employed to classify patients' observation periods by anaemia status (based on the WHO definition) and haemoglobin (Hb) level category. Injurious falls outcomes were defined as an injurious event claim, within 30 days after a fall claim, for fractures of the hip/pelvis/femur, vertebrae/ribs, humerus or lower limbs; Colles' fracture; or head injuries/haematomas. Univariate and multivariate (adjusted for age, gender, health plan, history of falls, co-morbidities and concomitant medications) analyses were conducted. Subset analyses based on injurious falls of the hip and head were also conducted. RESULTS: In the univariate analysis, anaemia increased the risk of injurious falls by 1.66 times (95% CI 1.41, 1.95) compared with no anaemia. The incidence of injurious falls increased from 6.5 to 15.8 per 1000 person-years when Hb levels decreased from >or=13 to <10 g/dL (trend test: p < 0.001). Multivariate analysis confirmed that Hb levels were significantly associated with the risk of injurious falls (rate ratio = 1.47, 1.39 and 1.14 for Hb levels of <10, 10-11.9 and 12-12.9 g/dL, respectively, compared with Hb >or=13 g/dL; p < 0.001). Even stronger linear negative trends were observed in the subsets of hip and head injurious falls. CONCLUSION: Anaemia was significantly and independently associated with a risk increase for injurious falls. Furthermore, the risk of injurious falls increased as the degree of anaemia worsened. Correction of anaemia, a modifiable risk factor, warrants further investigation as a means of preventing falls in the elderly.

Current management of anemia in critically ill patients: analysis of a database of 139 hospitals.

PURPOSE: This analysis focused on three objectives: 1) to measure packed red blood cell (pRBC) use across different critical care settings; 2) to characterize transfused and nontransfused critically ill patients; and (3) to identify potential predictors of transfusion use. METHODS: A retrospective analysis of critically ill patients from 139 hospitals across the United States was conducted. Hospital administrative and laboratory data were collected for patients 18 years of age and older admitted to the intensive care unit (ICU) (including coronary care unit and intermediate care units) from January 1, 2004, to May 31, 2005. Multivariate analyses controlling for patient and hospital heterogeneity evaluated the association between pRBC transfusions and patients' ICU or hospital length of stay. RESULTS: A total of 180,221 patients met all inclusion criteria, with 29,331 (16.3%) receiving pRBCs during their ICU stay. There was differential use of pRBCs by ICU/coronary care unit setting (ie, 23% of general ICU patients versus 7% of intermediate coronary care unit patients). Increasing age [odds ratio (OR), 1.007; 95% confidence interval (CI), 1.006-1.008], declining hemoglobin concentrations (OR, 2.315; 95% CI, 2.288-2.342), mechanical ventilation (OR, 1.338; 95% CI, 1.287-1.392), dialysis (OR, 2.071; 95% CI, 1.913-2.242), and presence of acute renal failure (OR, 1.259; 95% CI, 1.193-1.329), congestive heart failure (OR, 1.156; 95% CI, 1.106-1.208), or septicemia (OR, 1.143; 95% CI, 1.071-1.221) were associated with a higher likelihood of pRBC use. Each pRBC transfusion significantly increased hospital length of stay (1.6, 0.5, and 2.7 additional days for patients with 1, 2, and 3 or more transfusions, respectively, P < 0.0001) as compared with nontransfused patients. CONCLUSIONS: Multiple factors increased the likelihood of pRBC use in ICU patients. In addition, pRBC transfusion was associated with increased length of stay. Clinicians should evaluate the risk-benefit ratio and consider interventions to limit any unnecessary pRBC use in the critically ill.

Cost analytic model to determine the least costly inpatient erythropoiesis stimulating therapy regimen.

BACKGROUND: Unlike in outpatient settings, the comparative costs of epoetin alpha (EPO) and darbepoetin alpha (DARB) have not been evaluated broadly from the inpatient hospital perspective. OBJECTIVE: To develop a cost analytic model comparing hospital inpatient costs for erythropoiesis stimulating therapies within the nephrology and oncology settings. METHODS: A cost analytic model incorporating erythropoietic drug, pharmacy, and nursing costs was developed from the inpatient hospital perspective to evaluate comparative costs of EPO and DARB. Erythropoietic drug costs were calculated using unit wholesale acquisition cost multiplied by the number of units or micrograms while comparing the following dosing regimens: EPO 3 times weekly, EPO once weekly, and DARB once weekly. Pharmacy costs included dispensing and delivery costs, while nursing costs incorporated administration time costs; all were calculated by estimated fractional hours per activity multiplied by hourly wages. The total frequency of erythropoiesis stimulating therapy administrations was determined based on the average hospital length of stay. The first erythropoiesis stimulating therapy dose was assumed to occur on day 3 of hospitalization. For total inpatient costs, a weighted average was calculated across disease states. One-way sensitivity analyses were conducted by varying length of stay, day of initial erythropoiesis stimulating therapy dose, pharmacy and nursing costs, and once-weekly DARB dose. RESULTS: EPO 3 times weekly was the least costly regimen across all disease states evaluated. Threshold analysis indicated that the cost of once-weekly DARB regimens would have to be reduced by 37% to equal the cost of EPO 3 times weekly for an average length of stay. Sensitivity analyses did not considerably affect the results. CONCLUSIONS: EPO 3 times weekly was found to be the least costly erythropoiesis stimulating therapy regimen for nephrology and oncology inpatients for the average length of stay as well as most other lengths of stay considered. Once-weekly EPO was the least costly erythropoiesis stimulating therapy regimen for several other lengths of stay, while once-weekly DARB was never found to be the least costly regimen.

Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) : a registry for characterizing anaemia management and outcomes in oncology patients.

BACKGROUND AND OBJECTIVE: To report the design, methodology, implementation and initial results of the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry, the first US patient registry to collect and report on practice patterns and outcomes associated with erythropoiesis-stimulating therapy (EST) for anaemia management in oncology patients. METHODS: DOSE is a prospective ongoing registry of oncology patients treated with epoetin-alpha or darbepoetin-alpha. Patients from either community or academic centres who meet prespecified entry criteria are eligible for inclusion in the registry. Data collected include patient demographic and clinical characteristics, EST administration, haematological parameters, patient-reported outcomes and medical resource utilization. Patients are followed from EST initiation through to the end of therapy or 16 weeks, whichever is earlier. RESULTS: Initial results from 45 sites for 861 patients (epoetin-alpha, n = 312; darbepoetin-alpha, n = 549) showed that baseline demographic and disease characteristics were similar between the two treatment groups. Administration of EST at both weekly and > or =2-weekly intervals was observed in both groups, with similar numbers of haemoglobin determinations. However, the mean number of office visits was higher in the darbepoetin-alpha group despite more frequent administration of therapy at > or =2-weekly intervals in this group. Mean treatment duration was approximately 8 weeks for both groups. Mean post-baseline haemoglobin levels of 11-12 g/dL were achieved and maintained at all timepoints assessed with epoetin-alpha but not with darbepoetin-alpha. Both groups had similar rates of packed red blood cell transfusions. CONCLUSIONS: The DOSE Registry is a valuable source of data relating to anaemia management, practice patterns and outcomes in oncology patients from the perspective of actual clinical practice. Results from this registry should provide patients, clinicians and healthcare decision makers with a better understanding of the relationship between EST dosage and outcomes in the clinical setting.

The economic impact of epoetin alfa therapy on delaying time to dialysis in elderly patients with chronic kidney disease.

The aim of this study was to evaluate the impact of epoetin alfa (EPO) therapy on delaying progression to renal dialysis and quantify the associated medical cost savings in elderly chronic kidney disease (CKD) patients. Elderly (>/=65 years) dialysis patients who had >/=1 hemoglobin (Hb) value and >/=1 glomerular filtration rate (GFR) value of <60 mL/min/1.73 m(2) were identified using health claims and laboratory data from the period January 1999 to February 2005. Exclusion criteria included: organ transplantation, blood transfusion, use of darbepoetin alfa, and dialysis for reasons other than CKD. Each EPO patient was matched by Hb and GFR to one control patient. The time from when matched patients had the same GFR value to dialysis was compared. The economic impact of EPO on delaying dialysis was monetized using standardized health plan payments, and adjusted to 2005 United States dollars. Sixty-eight patients (34 EPO and 34 matched controls) formed the study population. The average time to dialysis was 156 days longer for the EPO group compared to the matched control group (p = 0.003). Analysis by CKD severity revealed that EPO therapy in less severe CKD patients offered a greater delay in time to dialysis (Stage 4: 213 days difference, p = 0.003; Stage 5: 104 days difference, p = 0.160). EPO treatment resulted in cost savings of $43,374-$59,222 per patient compared to non-EPO matched controls. This retrospective matched cohort study suggests that EPO therapy has a beneficial impact on delaying progression to dialysis in elderly CKD patients, especially in those with less severe CKD.

Dosing patterns, treatment costs, and frequency of physician visits in adults with cancer receiving erythropoietic agents in managed care organizations.

OBJECTIVE: To investigate the dosing patterns and treatment costs of erythropoietic agents in adult (>or= 18 years of age) cancer patients newly initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB) in managed care organizations. METHODS: An analysis of US medical claims (30 million lives in over 35 health plans) in the period July 1, 2002-February 28, 2005 was conducted. Patients with >or= 1 cancer claim within 90 days prior to initiating EPO or DARB, and who received at least two doses of the same erythropoietic agent, were included in this analysis. Weighted average weekly dosing, cumulative treatment dose, associated drug cost, dosing frequency patterns, and the frequency of outpatient visits were evaluated. The EPO:DARB dose ratio, based on average cumulative treatment doses, was assessed. RESULTS: 5639 EPO and 2166 DARB patients met the inclusion and exclusion criteria. The EPO group was older (EPO 59.1 years; DARB 57.6 years; p < 0.001) with a higher proportion of men (EPO 38.1%; DARB 33.1%; p < 0.001). Variable dosing frequency was observed with similar treatment durations for the two groups (days: EPO 55.6; DARB 57.7; p = 0.122). A dose ratio of 236:1 was observed (average cumulative dose: EPO 252 856 U; DARB 1072 mcg). Average drug cost was significantly higher in the DARB group (drug cost: EPO 3077 dollars; DARB 4674 dollars; p < 0.001). The average number of hematology/oncology outpatient visits per patient (visits: EPO 7.4; DARB 7.3; p = 0.676) and outpatient visits for hemoglobin determination (visits: EPO 6.7; DARB 6.4; p = 0.093) during treatment was similar between the two groups. LIMITATIONS: The results were based on medical claims only. The absence of information on actual injection dates in pharmacy claims prevented their incorporation in the analysis. CONCLUSIONS: Based on the average cumulative doses, the EPO:DARB dose ratio was 236:1 (Units EPO: mcg DARB) with 52% greater drug cost in the DARB group. Despite the variable administration frequency observed between the two agents, the number of hematology/oncology outpatient visits was not different.

Dosing patterns, hematologic outcomes, and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia.

OBJECTIVE: Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting. METHODS: This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for > or = 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24-week study period. RESULTS: A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (> or = Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (> or = 11 g/dL) (p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24-week cumulative doses were EPO 279 336 +/- 68 302 units and DARB 1084 +/- 246 microg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = 3400 US dollars, DARB = 4726 US dollars; FSS: EPO = 1528 US dollars, DARB = 2379 US dollars). CONCLUSIONS: Extended dosing (Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39-56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.

Dosing patterns and treatment costs of erythropoietic agents in elderly patients with pre-dialysis chronic kidney disease in managed care organisations.

OBJECTIVES: To investigate dosing patterns and drug costs of erythropoietic agents and assess the frequency of outpatient nephrologist visits in an elderly population with pre-dialysis chronic kidney disease (pCKD) newly initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB). METHODS: An analysis of medical claims from more than 30 healthcare plans covering all census regions of the US in the period July 2002 through February 2005 was conducted. Patients were included if they were > or = 65 years of age, had at least one claim for CKD within 90 days prior to the initiation of any erythropoietic agent, were newly commenced on either EPO or DARB, and had received at least two treatment doses. If a patient received renal dialysis, data were censored 30 days prior to the first date of dialysis. Patients diagnosed with cancer or those who had undergone chemotherapy were excluded from the analysis. The average dosing interval for both EPO and DARB was calculated and classified as once weekly (qw), every 2 weeks (q2w) or every 3 weeks or less frequently (> or = q3w). Weighted average weekly doses were scaled based on treatment duration. The frequency of outpatient nephrologist visits was analysed. Average weekly treatment costs were calculated and presented using the May 2005 Wholesale Acquisition Costs. RESULTS: A total of 293 EPO and 102 DARB patients met the inclusion criteria. The two groups of patients had similar mean age (74.4 years for EPO vs 74.3 years for DARB) and gender distribution (47.4% female for EPO vs 51.0% for DARB). Extended dosing (every 2 weeks or less frequently: > or = q2w) during treatment was observed in both groups (EPO: qw 49.8%, q2w 31.7%, > or = q3w 18.4%; DARB: qw 19.6%, q2w 52.9%, > or = q3w 27.5%). The average dosing interval between injections was 13.6 days for the EPO group and 17.3 days for the DARB group. The weighted average weekly dose was 12,748 units for EPO and 43.5 microg for DARB. The average weekly erythropoietic treatment cost was significantly greater for DARB compared with EPO (190 US dollars vs 155 US dollars per week [2005 values]; p = 0.028). After controlling for covariates, the cost difference between the two groups was more pronounced and remained statistically significant (adjusted cost difference 41 US dollars/week higher for DARB patients; p = 0.013). The frequency of outpatient nephrologist visits during treatment was similar between the two groups (EPO 3.4 vs DARB 3.0 visits). CONCLUSIONS: Based on this analysis of claims data from more than 30 US healthcare plans, extended dosing (> or = q2w) of EPO and DARB was common in elderly pCKD patients treated with erythropoietic agents, with significantly higher weekly drug costs observed in the DARB group compared with the EPO group. The number of outpatient nephrologist visits was not significantly different between EPO and DARB patients. This study was the first to evaluate the dosing patterns of EPO and DARB in elderly pCKD patients in a large managed care population.

Impact of non-medical switching on clinical and economic outcomes, resource utilization and medication-taking behavior: a systematic literature review.

OBJECTIVE: To evaluate current knowledge of the impact of non-medical switching on clinical and economic outcomes, resource utilization and medication-taking behavior. METHODS: The literature was searched (Medline and Web of Science, January 2000-November 2015) to identify United States' studies evaluating ≥25 patients and measuring the impact of non-medical switching of drugs (switching to a chemically distinct but similar medication for reasons other than lack of clinical efficacy/response, side effects or poor adherence) on ≥1 clinical, economic, resource utilization or medication-taking behavior outcome. The direction of association between non-medical switching and outcomes was classified as negative or positive if a statistically significant worsening or improvement was reported, or neutral if no significant difference was observed. RESULTS: Twenty-nine studies contributed 96 outcomes (60.4% clinical; 21.9% resource utilization; 13.5% economic; 4.2% medication-taking behavior) within six disease categories (cardio-metabolic, immune-mediated, acid suppression, psychiatric, hormone replacement therapy and pain). The direction of association was more frequently negative (33.3%) or neutral (55.2%) than it was positive (11.5%). Stratified by outcome type, non-medical switching was negatively associated with clinical, economic, healthcare utilization and medication-taking behavior outcomes in 20.7%, 69.2%, 38.1% and 75.0% of cases, respectively; and positively in only 4.8%-17.2% of outcomes subgroups. Of 32 outcomes in patients demonstrating stable/well controlled disease, 68.8% and 31.3% had a negative and neutral direction of association. In patients without demonstrated disease stability, outcomes were negatively, neutrally and positively impacted by non-medical switching in 15.6%, 67.2% and 17.2% of 64 outcomes. LIMITATIONS: Our inability to evaluate specific disease state categories and studies/outcomes received equal weight regardless of sample size or magnitude of effect. CONCLUSIONS: Non-medical switching was more often associated with negative or neutral effects than positive effects on an array of important outcomes. Among patients with stable/well controlled disease, non-medical switching was associated with mostly negative effects.

Retrospective observational study of patients with chemotherapy-related anemia receiving erythropoietic agents.

OBJECTIVE: Epoetin alfa (EPO) and darbepoetin alfa (DARB) are approved for the treatment of chemotherapy-related anemia (CRA) in patients with nonmyeloid malignancies. This study examined dosing and hematologic outcomes with these agents in community oncology clinics. METHODS: Medical charts were abstracted retrospectively for 1005 patients (527 EPO, 478 DARB) with CRA (hemoglobin [Hb] < or = 11 g/dL) who received EPO or DARB at 10 U.S. oncology clinics between January 2002 and March 2003. MAIN OUTCOME MEASURES: Outcome measures included dose and frequency of erythropoietic therapy, change in Hb at 4, 8, and 12 weeks after initiation of therapy, and transfusion of packed red blood cells. RESULTS: Baseline characteristics were generally similar between groups. Most EPO-treated patients received EPO once weekly, but 25% received EPO every 2-3 weeks, with 40,000 U the predominant dose. DARB was usually given every 1-2 weeks in doses ranging from 200-400 mcg/injection. Mean treatment duration was relatively short (< 8 weeks) in both groups, with a similar number of Hb determinations and similar incidence of red blood transfusion between groups. Hb increased from baseline in the EPO and DARB groups at 4 weeks (0.99 vs. 0.69 g/dL, p = 0.003), 8 weeks (1.39 vs. 1.06 g/dL, p = 0.011), and 12 weeks (1.43 vs. 1.11 g/dL, p = 0.055). Early Hb response (> or = 1 g/dL increase by 4 weeks) was more common with EPO than DARB (48% vs. 38%, p = 0.008). CONCLUSIONS: EPO was superior to DARB for early hematologic outcomes in patients with CRA in community oncology clinics. Retrospective data collection and relative inexperience with DARB at the time of the study may limit the generalization of these results. Randomized, controlled trials comparing EPO and DARB are warranted.

Dose conversion and cost effectiveness of erythropoietic therapies in chemotherapy-related anaemia : a meta-analysis.

OBJECTIVE: To estimate a dose-conversion ratio (DCR) between epoetin alfa (EPO) and darbepoetin alfa (DARB) and compare the costs of both drugs at the estimated DCRs using average wholesale prices (AWPs). METHODS: A search of PUBMED, CANCERLIT and references for papers and abstracts reporting on clinical trials of DARB or EPO for chemotherapy-related anaemia (CRA) identified 56 publications. A meta-analysis was conducted on the 12 eligible papers to estimate a DCR at which the two drugs were equally effective as measured by the area under the curve of haemoglobin (Hb) change (Hb AUC) at weeks 4 and 13. The DCR is based on the ratio of the coefficients of DARB and EPO doses in a regression of Hb AUC on those two variables, baseline Hb, Hb change calculation method, tumour type, and dosing frequency. Studies were frequency-weighted by the number of subjects. DCRs with confidence intervals (CIs) were calculated using a Monte-Carlo approach. Results from the regression were used to calculate DCRs for different dosing regimen comparisons - EPO three times weekly (TIW) versus DARB once weekly (QW), EPO TIW versus DARB once every 2 weeks (Q2W), EPO QW versus DARB QW, and EPO QW versus DARB Q2W. Relative cost effectiveness (RCE) was assessed by comparing drug costs at the estimated DCRs at $US 2003 AWPs [RCE = DCR . ($/U EPO)/($/mug DARB)]. RESULTS: The regression results suggest an EPO QW : DARB QW DCR of 187 (95% CI 183, 191). Depending on the assumed starting dose, the DCR ranges from 126 to 137 for EPO TIW : DARB QW; from 128 to 139 for EPO TIW : DARB Q2W; and equals 191 for EPO QW : DARB Q2W. RCE was 2.0 for the main regression. CONCLUSION: The DCR of 330 : 1 estimated for the 2004 Hospital Outpatient Prospective Payment System by the Centers for Medicare and Medicaid Services is greater than the DCRs estimated based on Hb AUC. The DCR estimated in the primary regression suggests that based on AWPs, EPO is 2.0 times more cost effective than DARB.

Self-reported frequency and severity of disease flares, disease perception, and flare treatments in patients with ulcerative colitis: results of a national internet-based survey.

OBJECTIVES: The purpose of this study was to better understand the characteristics and patterns of treatment of flares of ulcerative colitis (UC) from the patient's perspective. A secondary objective was to determine the predictive value of disease characteristics, particularly disease flares, on current use of biologic therapy. METHODS: Study participants were recruited from an Internet panel of self-identified individuals with inflammatory bowel disease (UC or Crohn's disease). The present analysis was limited to individuals who reported having a diagnosis of UC, were aged >or=18 years, resided in the United States, and could speak and write English. Cross-sectional data (demographic characteristics, insurance coverage, incidence of flares, patient experiences, treatment patterns) were collected via a self-reported Internet-based questionnaire during the third quarter of 2008. RESULTS: A total of 505 individuals with UC completed the survey (72.7% female; 16.6% non-white; 37.2% college graduates; mean [SD] age, 48.6 [2.8] years). The mean time since the diagnosis of UC was 11.9 (10.1) years, and 76.6% of respondents characterized their disease as controlled. Overall, 27.9% of the sample reported >or=1 flare per week, and an additional 25.1% reported >or=1 flare per month. Most disease flares (76.5%) lasted or=1 flare per week, 30.5% classified their overall disease severity as mild, 56.0% as moderate, and 13.5% as severe. The majority of respondents with >or=1 flare per week currently used 5-aminosalicylic acids (5-ASAs) (41.1%) or corticosteroids (49.6%), whereas 19.1% used immunomodulators and 17.0% used biologics. Disease flares were most commonly treated by increasing the dose of the current medication (60.4%) or adding a corticosteroid to the treatment regimen (34.5%). CONCLUSIONS: More than half of these individuals with UC reported experiencing disease flares >or=1 time per week or month. The majority reported using 5-ASAs or corticosteroids as maintenance medications and increasing the dose or adding corticosteroids to control flares in the short term.

Healthcare costs associated with nephrology care in pre-dialysis chronic kidney disease patients.

OBJECTIVE: To compare the healthcare costs of pre-dialysis chronic kidney disease (CKD) patients cared for in a nephrology clinic setting versus other care settings. METHODS: An analysis of health claims between 01/2002 and 09/2007 from the Ingenix Impact Database was conducted. Inclusion criteria were ≥ 18 years of age, ≥ 1 ICD-9 claim for CKD, and ≥ 1 estimated glomerular filtration rate (eGFR) value of < 60 mL/min/1.73 m(2). Patients were classified in the nephrology care cohort if they were treated in a nephrology clinic setting at least once during the study period. Univariate and multivariate analyses were conducted to compare average annualized healthcare costs of patients in nephrology care versus other care settings. RESULTS: Among the 20,135 patients identified for analysis, 1,547 patients were cared for in a nephrology clinic setting. Nephrology care was associated with lower healthcare costs with an unadjusted cost savings of $3,049 ($11,303 vs. $14,352, p = 0.0014) and a cost ratio of 0.8:1 relative to other care settings. After adjusting for covariates, nephrology care remained associated with lower costs (adjusted cost savings: $2,742, p = 0.006). LIMITATIONS: Key limitations included potential inaccuracies of claims data, the lack of control for patients' ethnicity in the calculation of eGFR values, and the presence of potential biases due to the observational design of the study. CONCLUSIONS: The current study demonstrated that pre-dialysis CKD patients treated in nephrology clinics were associated with significantly lower healthcare costs compared with patients treated in other healthcare settings.

An examination of productivity and resource utilization associated with epoetin alfa treatment in employees with predialysis chronic kidney disease.

OBJECTIVE: This study assessed the employer cost burden of predialysis CKD-related anemia for a major US manufacturer, by examining indirect and direct costs before and after initiation of epoetin alfa (EPO). METHODS: Hemoglobin (Hb) levels, direct costs, and indirect costs for employees with CKD-related anemia were collected for 15 months (9 months pre-EPO and 6 months concurrent/post-EPO treatment). Indirect costs (absenteeism and presenteeism) and direct costs (medical and pharmacy) were compared for the pre- and post-EPO treatment periods. RESULTS: Treating CKD-related anemia with EPO increased Hb levels from 9.4 (1 to 3 months pre-EPO)to 12.2 g/dL (4 to 6 months post-EPO), decreased absenteeism by 52.3 days per patient per year (PPPY), increased productivity by 91.5% PPPY, and reduced health care costs by approximately $4417 PPPY. CONCLUSION: Among employees with predialysis CKD-related anemia, EPO treatment was associated with increased Hb levels, improved productivity, and decreased direct employer costs.