A retrospective study of patients' out-of-pocket costs for granulocyte colony-stimulating factors.

OBJECTIVE: With rising healthcare costs, there is an increasing concern with the burden of out-of-pocket costs on cancer patients. This study examined patients' out-of-pocket expenditures for granulocyte colony-stimulating factors, pegfilgrastim and filgrastim, which are given to cancer patients receiving myelosuppressive chemotherapy and have been shown to decrease the incidence of febrile neutropenia. METHODS: Adult patients who received chemotherapy and granulocyte colony-stimulating factors in the outpatient setting in the United States between January 2007 and June 2010 were evaluated using medical and pharmacy claims data from two healthcare data sources, the MarketScan(®) Commercial and Medicare Supplemental Databases and the HealthCore Integrated Research Database(SM). The distribution of out-of-pocket costs for granulocyte colony-stimulating factors per patient and per administration was described for each quarter. Longitudinal analyses of out-of-pocket costs for granulocyte colony-stimulating factors were also performed for patients with continuous health plan eligibility during each calendar year from 2007 to 2009. RESULTS: The pattern of out-of-pocket expenditures for pegfilgrastim and filgrastim was generally consistent between the databases and over time. On average, about 65%-75% of patients had zero quarterly out-of-pocket costs for granulocyte colony-stimulating factors. Across the years, the mean quarterly out-of-pocket costs per patient were $100-$150 and $50-$80 for pegfilgrastim and filgrastim, respectively. The mean quarterly out-of-pocket costs for granulocyte colony-stimulating factors per administration were $40-$70 and $8-$10, respectively. CONCLUSION: In this retrospective analysis of medical and pharmacy claims data, most patients who received chemotherapy and granulocyte colony-stimulating factors in 2007 to 2010 had incurred no quarterly out-of-pocket costs associated with G-CSF use.

Mealtimes on eating disorder wards: a two-study investigation.

OBJECTIVE: This research had two aims. First, to assess the current mealtime practices within UK eating disorders units. Second, to investigate staff perspectives of these mealtimes, including their involvement and understanding of patients' experience. METHOD: Study 1 involved a survey to assess mealtime protocols across 22 eating disorders units. In Study 2, sixteen semistructured interviews were conducted with staff at three eating disorders units. RESULTS: Between and within-unit variation exist regarding the implementation of mealtimes. Thematic analysis revealed that staff perceived their provision of mealtimes to be influenced by their own interpersonal difficulties created by the meals. Additionally, they perceived that these issues could be aided by forward planning, successful teamwork, and focused staff training. DISCUSSION: There is a need for specialized mealtime implementation training. Furthermore, research is required to evaluate current mealtime practices from patient perspectives and to determine the impact of modified mealtime approaches on treatment outcome.

Effects of distraction and focused attention on actual and perceived food intake in females with non-clinical eating psychopathology.

The aim of this study was to determine the effects of distraction and focused attention on both food intake and accuracy of perceived intake in women with non-clinical levels of disordered eating. In a laboratory study, twenty-seven young women consumed three identical pasta meals once a week for three consecutive weeks. Meals were eaten ad libitum during a control and two test conditions, in which attention was either diverted away from (distraction condition) or directed towards food-related stimuli (focused attention condition). They also completed the drive for thinness, bulimia and body dissatisfaction subscales of the Eating Disorders Inventory-2. Intake was significantly higher in the distraction than in the control or focused attention conditions, but was not related to eating psychopathology. A measure of accuracy of perceived intake indicated that drive for thinness was associated with overestimation of food intake in the focused attention condition. This study suggests that distraction could promote food intake in all non-clinical consumers, irrespective of individual differences in eating behaviours. Furthermore, it suggests that those with a high drive for thinness may overestimate intake when required to focus on their food. These findings could have implications for mealtime interventions in the treatment of eating disorders.

The impact of methodological approach on cost findings in comparison of epoetin alfa with darbepoetin alfa.

BACKGROUND: Two erythropoiesis-stimulating agents (ESAs), epoetin alfa and darbepoetin alfa, are approved for the treatment of chemotherapy-induced anemia in patients with cancer. Randomized controlled trials indicate that the drugs are similarly efficacious, but that the duration of clinical benefit (DCB) ranges from 2 to 7 days for epoetin alfa and from 7 to 21 days for darbepoetin alfa, depending on dose. Given equivalent efficacy, payers are increasingly interested in understanding the cost differences for these 2 drugs. OBJECTIVE: To examine the impact of different methodological approaches on the cost comparison between epoetin alfa and darbepoetin alfa users, with cancer from a payer perspective. METHODS: Episodes of care (episode) were constructed for cancer patients treated with ESAs, using MarketScan claims data. Episodes started with the first ESA claim and ended on the last ESA claim or the claim before a 42-day or longer gap in ESA therapy. Each episode was augmented with an estimated DCB based on the last dose in the episode. Cost was reimbursed amount observed in the claims database. Adjusted weekly cost was estimated using generalized linear models to control for difference in clinical and demographic differences across epoetin alfa and darbepoetin alfa episodes. RESULTS: Episodes were created in 324 darbepoetin alfa and 342 epoetin alfa users. Darbepoetin alfa users tended to be younger, had more comorbidities, and had advanced cancer (all p < 0.001). After accounting for DCB, the average weekly cost of darbepoetin alfa was significantly lower than that of epoetin alfa ($619 vs $940; p < 0.001). After multivariate adjustment, darbepoetin alfa had lower costs than epoetin alfa in the base case and all alternative approaches. CONCLUSIONS: To reduce the risk of potential bias, DCB and different patient characteristics should be taken into account when using retrospective claims data to conduct cost comparisons between agents that have significant differences in dosing schedule.

Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates.

BACKGROUND: Both raloxifene and bisphosphonates are indicated for the prevention and treatment of postmenopausal osteoporosis, however these medications have different efficacy and safety profiles. It is plausible that physicians would prescribe these agents to optimize the benefit/risk profile for individual patients. The objective of this study was to compare demographic and clinical characteristics of patients initiating raloxifene with those of patients initiating bisphosphonates for the prevention and treatment of osteoporosis. METHODS: This study was conducted using a retrospective cohort design. Female beneficiaries (45 years and older) with at least one claim for raloxifene or a bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified using a collection of large national commercial, Medicare supplemental, and Medicaid administrative claims databases (MarketScan). Patients were divided into two cohorts, a combined commercial/Medicare cohort and a Medicaid cohort. Within each cohort, characteristics (demographic, clinical, and resource utilization) of patients initiating raloxifene were compared to those of patients initiating bisphosphonate therapy. Group comparisons were made using chi-square tests for proportions of categorical measures and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used to simultaneously examine factors independently associated with initiation of raloxifene versus a bisphosphonate. RESULTS: Within both the commercial/Medicare and Medicaid cohorts, raloxifene patients were younger, had fewer comorbid conditions, and fewer pre-existing fractures than bisphosphonate patients. Raloxifene patients in both cohorts were less likely to have had a bone mineral density (BMD) screening in the previous year than were bisphosphonate patients, and were also more likely to have used estrogen or estrogen/progestin therapy in the previous 12 months. These differences remained statistically significant in the multivariate model. CONCLUSION: In this sample of patients enrolled in commercial, Medicare, and Medicaid plans, patients who initiated raloxifene treatment differed from those initiating bisphosphonates. Raloxifene patients were younger, had better overall health status and appeared to be less likely to have risk factors for new osteoporotic fractures than bisphosphonate patients. Differences in the clinical profiles of these agents may impact prescribing decisions. Investigators using observational data to make comparisons of treatment outcomes associated with these medications should take these important differences in patient characteristics into consideration.

The Degradation Chemistry of Farglitazar and Elucidation of the Oxidative Degradation Mechanisms.

The chemical degradation of farglitazar (1) was investigated using a series of controlled stress testing experiments. Farglitazar drug substance was stressed under acidic, natural pH, basic, and oxidative conditions in solution. In the solid state, the drug substance was stressed with heat, high humidity, and light. Farglitazar was found to be most labile toward oxidative stress. A series of mechanistic experiments are described in which the use of 18O-labelled oxygen demonstrated that oxidative degradation of farglitazar is caused primarily by singlet oxygen formed under thermal conditions. Major degradation products were isolated and fully characterized. Mechanisms for the formation of degradation products are proposed. Drug product tablets were also stressed in the solid state with heat, high humidity, and light. Stressed tablets afforded many of the same degradation products observed during drug substance stress testing, with oxidation again being the predominant degradation pathway. Evidence for the activity of singlet oxygen, formed during thermal stress testing of the solid oral dosage form, is presented. The degradation pathways observed during stress testing matched those observed during long-term stability trials of the drug product.

Medical costs associated with non-Hodgkin's lymphoma in the United States during the first two years of treatment.

OBJECTIVES: To determine the direct costs of medical care associated with aggressive and indolent non-Hodgkin's lymphoma (NHL) in the United States; to show how costs for aggressive NHL change over time by examining costs related to initial, secondary and palliative treatment phases; and to evaluate the economic consequences of treatment failure in aggressive NHL. PATIENTS AND METHODS: A retrospective cohort analysis of 1999 - 2000 direct costs in newly diagnosed NHL patients and controls (subjects without any cancer) was conducted using the MarketScan medical and drug claims database of large employers across the United States. Treatment failure analysis was conducted for aggressive NHL patients, and was defined by the need for secondary treatment or palliative care after initial therapy. Cost of treatment failure was calculated as difference in regression-adjusted costs between patients with initial therapy only and patients experiencing initial treatment failure. RESULTS: Patients with aggressive (n = 356) and indolent (n = 698) NHL had significantly greater health service utilization and associated costs (all P < 05) than controls (n = 1068 for aggressive, n = 2094 for indolent). Mean monthly costs were 5871 dollars for aggressive NHL vs. 355 dollars for controls (P < 0001) and 3833 dollars for indolent NHL vs. 289 dollars for controls (P < 0001). The primary cost drivers were hospitalization (aggressive NHL = 44% of total costs, indolent NHL = 50%) and outpatient office visits (aggressive NHL = 39%, indolent NHL = 34%). For aggressive NHL, mean monthly initial treatment phase costs (10,970 dollars) and palliative care costs (9836 dollars) were higher than costs incurred during secondary phase (3302 dollars). The mean cost of treatment failure in aggressive NHL was 14,174 dollars per month, and 85,934 dollars over the study period. CONCLUSION: The treatment of NHL was associated with substantial health care costs. Patients with aggressive lymphomas tended to accrue higher costs, compared with those with indolent lymphomas. These costs varied over time, with the highest costs occurring during the initial treatment and palliative care phases. Treatment failure was the most expensive treatment pattern. New strategies to prevent or delay treatment failure in aggressive NHL could help reduce the economic burden of NHL.

Estimating the cost of cancer: results on the basis of claims data analyses for cancer patients diagnosed with seven types of cancer during 1999 to 2000.

PURPOSE: Cancer accounts for 60.9 billion dollars in direct medical costs and 15.5 billion dollars for indirect morbidity costs. These estimates are derived primarily from national surveys or Federal databases. We derive estimates of the costs of cancer using administrative databases, which include claims and employment-related information on individuals insured by private or Medicare supplemental health plans. METHODS: A retrospective matched-cohort control analysis was performed using 1998 to 2000 databases with information on insurance claims, benefits, and health productivity for 3 million privately insured employees, their dependents, and early retirees. Study patients had new diagnoses of one of seven types of cancer (n = 12,709). Controls without cancer were matched at a 3:1 ratio by demographics. A variable follow-up length was used (maximum of 2 years). Direct costs included health care costs for patients and deductibles and copayments for caregivers. Indirect costs of work absence and short-term disability (STD) were calculated for a subgroup of cancer patients and caregivers. RESULTS: Mean monthly health care costs ranged from 2,187 dollars for prostate cancer to 7,616 dollars for pancreatic cancer, most often driven by hospitalization. Costs for controls were 329 dollars per month. Indirect morbidity costs to employees with cancer averaged 945 dollars, a result of a mean monthly loss of 2.0 workdays and 5.0 STD days. CONCLUSION: The economic burden of cancer is substantial. It is feasible to derive tumor-specific estimates of direct and indirect costs for large numbers of cancer patients using administrative databases. Policy makers charged with providing annual cost-of-cancer estimates should incorporate data obtained from a broad range of sources.

The economic burden of lung cancer and the associated costs of treatment failure in the United States.

The economic burden of lung cancer was examined with a retrospective case-control cohort study on a database containing inpatient, outpatient and drug claims for employees, dependents and retirees of multiple large US employers with wide geographic distribution. Patients were followed for maximum of 2 years from first cancer diagnosis until death, health benefits dis-enrollment or study end (31 December 2000). Compared with controls (subjects without any cancer), patients with lung cancer (n = 2040) had greater health care service utilization and costs for hospitalization, emergency room visits, outpatient office visits, radiology procedures, laboratory procedures and pharmacy-dispensed drugs (all P < 0.05). Regression-adjusted mean monthly total costs were US dollar 6520 for patients versus US dollar 339 for controls (P < 0.0001), and overall costs across the study period (from diagnosis to death or maximum of 2 years) were US dollar 45,897 for patients and US dollar 2907 for controls (P < 0.0001). The main cost drivers were hospitalization (49.0% of costs) and outpatient office visits (35.2% of costs). Monthly initial treatment phase costs (US dollar 11,496 per patient) were higher than costs during the secondary treatment phase (US dollar 3733) or terminal care phase (US dollar 9399). Failure of initial treatment was associated with markedly increased costs. Compared with patients requiring only initial treatment, patients experiencing treatment failure accrued an additional US dollar 10,370 per month in initial treatment phase costs and US dollar 8779 more per month after starting the secondary and/or terminal care phase. Over the course of the study period, these patients had total costs of US dollar 120,650, compared with US dollar 45,953 for those receiving initial treatment only. Thus, the incremental costs associated with treatment failure were US dollar 19,149 per month and US dollar 74,697 across the study period. Other types of clinical and epidemiological analysis are needed to identify risks for treatment failure. The economic burden of lung cancer on the US health care system is significant and increased prevention, new therapies or adjuvant chemotherapy may reduce both resource use and healthcare costs. New strategies for lung cancer that reduce hospitalizations and/or prevent or delay treatment failure could offset some of the economic burden associated with the disease.

The direct cost of stress urinary incontinence among women in a Medicaid population.

OBJECTIVE: To describe health care utilization and costs for women diagnosed with stress urinary incontinence in a Medicaid population. STUDY DESIGN: We utilized a pooled database of claims for women enrolled in Medicaid in 1 of 3 states. Health care utilization and costs were compared for 12 months before and 12 months after a woman's urinary incontinence diagnosis. Additional analyses utilized data from a fourth state. RESULTS: Of 13,672 women with diagnosed stress urinary incontinence, average urinary incontinence-related costs were approximately 800 dollars in the 12-month study period, less than 0.1% of total Medicaid spending. Thirteen percent of women underwent a surgery for stress urinary incontinence in the study period, with sling procedures performed most commonly. CONCLUSION: Although population prevalence estimates of any stress urinary incontinence symptoms often are high, diagnosis and health care utilization in the Medicaid population is low. Overall costs of stress urinary incontinence treatment in Medicaid currently are minimal. Further efforts to understand the appropriate detection, diagnosis, and treatment of women with stress urinary incontinence are needed.

The impact of anaemia and its treatment on employee disability and medical costs.

OBJECTIVE: Anaemia is a common haematological complication of cancer and cytotoxic treatment. The incremental economic burden associated with medical care and short-term disability of anaemia in patients with malignancy and receiving chemotherapy has not been well documented. This study evaluates the effect of anaemia on the costs associated with cancer treated with chemotherapy. METHODS: Patients receiving chemotherapy within 6 months of their initial cancer diagnosis were identified in a commercial claims database for 1999-2000. Data for these individuals were linked to their employers' short-term disability records via unique encrypted personal identification numbers provided by employers. Patients with anaemia were identified by a diagnosis of anaemia or treatment with transfusion or erythropoietin alfa (EPO). Healthcare expenditure and short-term disability leave were observed for up to 6 months following initial cancer diagnosis and were summarised into monthly averages. Exponential conditional mean models and zero-inflated negative binomial models were used to analyse mean monthly healthcare expenditures and short-term disability days. RESULTS: Twenty-five percent of the 619 newly diagnosed cancer patients treated with chemotherapy had anaemia. The presence of anaemia and longer length of transfusion therapy were associated with increased expenditures, while longer length of EPO treatment was associated with lower expenditures. The incremental costs due to anaemia among patients receiving chemotherapy were US$5,538 (year 2001 values) per month in the first 6 months following cancer diagnosis, 10.8% of which were costs related to short-term disability leave. CONCLUSION: Anaemia in patients undergoing chemotherapy presents a substantial burden to employers and payers. The findings also suggest that patients with anaemia treated with erythropoietin alfa can achieve expenditure levels similar to those patients without anaemia.

Design of potent, selective, and orally bioavailable inhibitors of cysteine protease cathepsin k.

Osteoclast-mediated bone matrix resorption has been attributed to cathepsin K, a cysteine protease of the papain family that is abundantly and selectively expressed in osteoclast. Inhibition of cathepsin K could potentially be an effective method to prevent osteoporosis. Structure-activity studies on a series of reversible ketoamides based inhibitors of cathepsin K have led to identification of potent and selective compounds. Crystallographic studies have given insights into the mode of binding of these inhibitors. A series of ketoamides with varying P1 moieties were first synthesized to find an optimum group that would fit into the S1 subsite of the cysteine protease, cathepsin K. With a desired P1 group in place a variety of heterocyclic analogues in the P' region were synthesized to study their steric and electronic effects. In the process of exploring these P' heterocyclic variations, excellent selectivity was gained over other highly homologous cysteine proteases, including cathepsins L, S, and V. The favorable pharmacokinetic properties of some of these cathepsin K inhibitors in rats make them suitable for evaluation in rodent osteoporosis models. A representative cathepsin K inhibitor was shown to attenuate PTH-stimulated hypercalcemia in the TPTX rat model. These inhibitors provide a viable lead series in the discovery of new therapies for the prevention and treatment of osteoporosis

Severity of premenstrual symptoms in a health maintenance organization population.

OBJECTIVE: To describe severity of emotional and physical symptoms in a large diverse sample; to examine demographic, health status, and behavioral correlates of symptom severity; and to describe use of medications and alternative remedies for premenstrual symptoms. METHODS: A total of 1194 women, ages 21-45, selected from members of a large northern California health maintenance organization, completed daily ratings of symptom severity for two menstrual cycles. An empirically derived algorithm defined symptom severity groups as minimal (n = 186), moderate (n = 801), severe (n = 151), or premenstrual dysphoric disorder (n = 56). Symptom severity as a continuous variable was defined by the two-cycle mean symptom ratings in the luteal phase. Demographic, health status, and behavioral factors and use of treatments for premenstrual symptoms were assessed by self-report. RESULTS: Luteal phase symptom-specific ratings were generally significantly greater in the premenstrual dysphoric disorder group than in the other groups (P <.001). Symptom severity score increased with each comorbidity and decreased with each year of age. Symptom severity was also inversely associated with oral contraceptive use (emotional symptoms) and better perceived health (physical symptoms). Hispanics reported greater severity of symptoms, and Asians less, relative to whites. Use of herbal and nutritional supplements for premenstrual symptoms steadily increased from 10.8% in the minimal group to 30.4% in the premenstrual dysphoric disorder group (P <.01). CONCLUSION: The degree of premenstrual symptom severity varies in the population, is relatively constant within each woman over two consecutive cycles, particularly for emotional symptoms, and is influenced by age, race/ethnicity, and health status.

Developing Performance Measures for Prescription Drug Management.

Prescription drug management plans are outpatient drug benefit programs that strive to manage the cost effective and clinically appropriate delivery of prescription drugs to beneficiaries. The demand for accountability and a means to evaluate performance of drug benefit management programs is growing; nevertheless, a set of valid, standardized indicators for evaluating performance does not exist. We review drug management program activities and identify available measures for assessing performance. Additionally, we note recent efforts to develop performance indicators for prescription drug management. We conclude by raising key questions that should be addressed before a comprehensive set of performance measures can be implemented.

The application of two health and productivity instruments at a large employer.

We applied two productivity instruments (the Work Productivity Short Inventory and the Work Limitations Questionnaire) to the same employees working at a large telecommunications firm. In this work we note differences in productivity metrics obtained from these instruments and offer reasons for those differences that may be related to their design. Within this sample, average at-work productivity (presenteeism) losses were 4.9% as measured by the WLQ and 6.9% as measured by the WPSI. These translated into losses of approximately $2000 to $2800 per employee per year, respectively. Total productivity losses were usually not associated with demographics or job type but were associated with perceived health status and the existence of particular medical conditions. Both instruments may be useful for employers who want to estimate productivity losses and learn where to focus their energy to help stem those losses.

Development and reliability analysis of the Work Productivity Short Inventory (WPSI) instrument measuring employee health and productivity.

The Work Productivity Short Inventory (WPSI), also known as the Wellness Inventory, was developed to quickly assess the prevalence of medical problems that may influence work productivity and the financial implications of those problems. The WPSI asks respondents to note the amount of time missed from work resulting from 15 medical conditions and the amount of unproductive time spent at work when affected by the condition. Three versions of the WPSI were compared that differed according to the length of the recall period (12 months, 3 months, or 2 weeks). The reliability of the financial metrics generated from the WPSI was assessed for each version and found to be adequate, ranging from 0.66-0.74 in this application. The WPSI was found to be a highly reliable tool for estimating the prevalence of medical conditions that influence work productivity. The dollar impact of the associated productivity losses were found to be reliable enough to meet the instrument's intended purpose, which is to help employers understand relationships between disease and productivity, thereby contributing to the design of interventions to relieve these problems. The needs of the researcher should dictate which version of the WPSI to use.

A validity analysis of the Work Productivity Short Inventory (WPSI) instrument measuring employee health and productivity.

The Work Productivity Short Inventory (WPSI) was developed to quickly estimate decrements in productivity associated with 15 common disease conditions. Three versions of the WPSI were developed that differed according to the length of the recall period (12 months, 3 months, or 2 weeks). The content, predictive, and construct validity of metrics generated from the WPSI were assessed based on response patterns found in the 3 versions and via comparison to information in national data sources or in the subject company's medical care claims and short-term disability program files. The WPSI provided evidence of content and construct validity to support its intended purpose. Evidence for predictive validity was weaker but still present. The WPSI can be used to provide information on the relative importance of health conditions that affect productivity at work for a large group of employees.

Health, absence, disability, and presenteeism cost estimates of certain physical and mental health conditions affecting U.S. employers.

Evidence about the total cost of health, absence, short-term disability, and productivity losses was synthesized for 10 health conditions. Cost estimates from a large medical/absence database were combined with findings from several published productivity surveys. Ranges of condition prevalence and associated absenteeism and presenteeism (on-the-job-productivity) losses were used to estimate condition-related costs. Based on average impairment and prevalence estimates, the overall economic burden of illness was highest for hypertension ($392 per eligible employee per year), heart disease ($368), depression and other mental illnesses ($348), and arthritis ($327). Presenteeism costs were higher than medical costs in most cases, and represented 18% to 60% of all costs for the 10 conditions. Caution is advised when interpreting any particular source of data, and the need for standardization in future research is noted.

"All eyes are on you": anorexia nervosa patient perspectives of in-patient mealtimes.

The aim of this qualitative study was to investigate in-patient perceptions of mealtimes on eating disorders units. Individual interviews were conducted with 12 women with anorexia nervosa. Using thematic analysis, three themes emerged as important: 1) Mealtime delivery (logistical factors influencing meals); 2) Individual outcomes (cognitions, emotions, behaviours and physical sensations during meals); and 3) Mealtime characteristics (including disengagement, perceived battlegrounds, and a desire for involvement in mealtimes). Future research should focus on areas of treatment delivery identified as important by patients. Recommendations are made regarding mealtime protocols based on patients' views, with increased recognition of behavioural, cognitive, physical and emotional aspects.