Estimating Productivity Loss from Breast and Non-Small-Cell Lung Cancer among Working-Age Patients and Unpaid Caregivers: A Survey Study Using the Multiplier Method.

Background. Traditional approaches to capturing health-related productivity loss (e.g., the human capital method) focus only on the foregone wages of affected patients, overlooking the losses caregivers can incur. This study estimated the burden of productivity loss among breast cancer (BC) and non-small-cell lung cancer (NSCLC) patients and individuals caring for such patients using an augmented multiplier method. Design. A cross-sectional survey of BC and NSCLC patients and caregivers measured loss associated with time absent from work (absenteeism) and reduced effectiveness (presenteeism). Respondents reported pre- and postcancer diagnosis income, hours worked, and time to complete tasks. Exploratory multivariable analyses examined correlations between respondents' clinical/demographic characteristics-including industry of employment-and postdiagnosis productivity. Results. Of 204 patients (104 BC, 100 NSCLC) and 200 caregivers (100 BC, 100 NSCLC) who completed the survey, 319 participants (162 BC, 157 NSCLC) working ≥40 wk/y prediagnosis were included in the analysis. More than one-third of the NSCLC (33%) and BC (43%) patients left the workforce postdiagnosis, whereas only 15% of caregivers did. The traditional estimate for the burden of productivity loss was 66% lower on average than the augmented estimate (NSCLC patients: 60%, BC patients: 69%, NSCLC caregivers: 59%, and BC caregivers: 73%). Conclusions. Although patients typically experience greater absenteeism, productivity loss incurred by caregivers is also substantial. Failure to account for such impacts can result in substantial underestimation of productivity gains novel cancer treatments may confer by enabling patients and caregivers to remain in the workforce longer. Our results underscore the importance of holistic approaches to understanding this impact on both patients and their caregivers and accounting for such considerations when making decisions about treatment and treatment value. Highlights: Cancer can have a profound impact on productivity. This study demonstrates how the disease affects not only patients but also the informal or unpaid individuals who care for patients.An augmented approach to calculating health-related productivity loss suggests that productivity impacts are much larger than previously understood.A more comprehensive understanding of the economic burden of cancer for both patients and their caregivers suggests the need for more support in the workplace for these individuals and a holistic approach to accounting for these impacts in treatment decision making.

Cost-Effectiveness of Cetuximab as First-line Treatment for Metastatic Colorectal Cancer in the United States.

PURPOSE: We conducted a cost-effectiveness analysis incorporating recent phase III clinical trial (FIRE-3) data to evaluate clinical and economic tradeoffs associated with first-line treatments of KRAS wild-type (WT) metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: A cost-effectiveness model was developed using FIRE-3 data to project survival and lifetime costs of FOLFIRI plus either cetuximab or bevacizumab. Hypothetical KRAS-WT mCRC patients initiated first-line treatment and could experience adverse events, disease progression warranting second-line treatment, or clinical response and hepatic metastasectomy. Model inputs were derived from FIRE-3 and published literature. Incremental cost-effectiveness ratios (ICERs) were reported as US$ per life year (LY) and quality-adjusted life year (QALY). Scenario analyses considered patients with extended RAS mutations and CALGB/SWOG 80405 data; 1-way and probabilistic sensitivity analyses were conducted. RESULTS: Compared with bevacizumab, KRAS-WT patients receiving first-line cetuximab gained 5.7 months of life at a cost of $46,266, for an ICER of $97,223/LY ($122,610/QALY). For extended RAS-WT patients, the ICER was $77,339/LY ($99,584/QALY). Cetuximab treatment was cost-effective 80.3% of the time, given a willingness-to-pay threshold of $150,000/LY. Results were sensitive to changes in survival, treatment duration, and product costs. CONCLUSIONS: Our analysis of FIRE-3 data suggests that first-line treatment with cetuximab and FOLFIRI in KRAS (and extended RAS) WT mCRC patients may improve health outcomes and use financial resources more efficiently than bevacizumab and FOLFIRI. This information, in combination with other studies investigating comparative effectiveness of first-line options, can be useful to clinicians, payers, and policymakers in making treatment and resource allocation decisions for mCRC patients.

Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia.

AIM: A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US. METHODS: A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs. RESULTS: In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs = 0.2-2.0), QALYs (ΔQALYs = 0.2-1.9), and accrue highest CML-related costs (ΔCosts = $64,000-$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population. CONCLUSIONS: This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.

The Effectiveness of Tyrosine Kinase Inhibitors and Molecular Monitoring Patterns in Newly Diagnosed Patients With Chronic Myeloid Leukemia in the Community Setting.

BACKGROUND: Clinical outcomes of patients with chronic myeloid leukemia (CML) treated in clinical trials, including response to therapy, may not be representative of those treated in a community setting. Thus, we sought to determine the real-world effectiveness of first-line tyrosine kinase inhibitors in CML by evaluating response rates, all-cause discontinuation, and adherence. Response monitoring patterns were also analyzed. PATIENTS AND METHODS: This retrospective observational study, using the McKesson Specialty Health/US Oncology Network (MSH/USON) iKnowMed electronic health record database and medical charts, identified newly diagnosed CML patients who received first-line imatinib, dasatinib, or nilotinib from July 2007 to March 2011, and were then followed for ≥ 18 months. RESULTS: Three hundred patients met study criteria (222 imatinib-treated, 34 dasatinib-treated, and 44 nilotinib-treated in the first-line). Molecular and cytogenetic response assessments were conducted less frequently than recommended (40% never had cytogenetic or molecular monitoring at any time). Patients treated with either dasatinib or nilotinib experienced higher response rates by 6, 12, and 18 months, faster time to major molecular response, and a significantly lower rate of all-cause treatment discontinuation within 18 months relative to imatinib-treated patients. Approximately 56% of all patients were adherent to tyrosine kinase inhibitor therapy. CONCLUSION: Dasatinib and nilotinib were more effective than imatinib as first-line therapy for CML in a community setting, as observed in descriptive and univariate analyses. The frequency of cytogenetic and molecular monitoring was lower than that recommended by current guidelines, including patients with no molecular or cytogenetic assessments during the 18-month follow-up. Therefore, MSH/USON is working toward improving compliance with response monitoring guidelines.

Development and validation of the Economic Assessment of Glycemic Control and Long-Term Effects of diabetes (EAGLE) model.

BACKGROUND: The Economic Assessment of Glycemic control and Long-term Effects of diabetes (EAGLE) model was developed to provide a flexible and comprehensive tool for the simulation of the long-term effects of diabetes treatment and related costs in type 1 and type 2 diabetes. METHODS: EAGLE simulations are based on risk equations, which were developed using published data from several large studies including the Diabetes Control and Complications Trial, the United Kingdom Prospective Diabetes Study, and the Wisconsin Epidemiological Study of Diabetic Retinopathy. Risk equations for the probability of complications (including hypoglycemia, retinopathy, macular edema, end-stage renal disease, neuropathy, diabetic foot syndrome, myocardial infarction, and stroke) were based on regression analyses, using linear, exponential, and quadratic regression formulae. Subsequent cost calculations are made from the simulated event rates. Internal validation of the EAGLE model was completed by comparing simulated event rates with the published event rates used as the basis for the model. RESULTS: EAGLE provides microsimulations of virtual patient cohorts for type 1 and type 2 diabetes over n years in 1-year cycles. Complications include microvascular and macrovascular events and death, which are calculated over time as cumulative incidences. Glycosylated hemoglobin levels over time are simulated in relation to treatment regimen. Internal validation demonstrated that each mean event rate simulated by EAGLE overlapped with the published mean event (within a range of +/-10%). CONCLUSIONS: The EAGLE model is an evidence-based, internally valid tool for the assessment of the long-term effects of diabetes treatment and related costs.

Prevalence of inadequate glycemic control among patients with type 2 diabetes in the United Kingdom general practice research database: A series of retrospective analyses of data from 1998 through 2002.

BACKGROUND: Since the mid-1990s, the development of new oral antidiabetic agents (OAs) and treatment guidelines have created an opportunity to improve glycemic control in patients with type 2 diabetes. OBJECTIVES: This study aimed to assess the prevalence of good and inadequate glycemic control across a 5-year period among patients with diabetes in the United Kingdom. It also investigated the factors associated with achieving glycemic targets. METHODS: This was a retrospective, cross-sectional analysis of data from the General Practice Research Database. Three limits were used to assess glycosylated hemoglobin (HbA1c): 6.5%, 7.0%, or 7.5%. Values above the cutoffs indicated inadequate control of HbA1c; those at or below the cutoffs indicated good control. The study evaluated clinical and pharmacy data from the years 1998 to 2002 for patients with type 2 diabetes, > or =2 years of follow-up, and > or =2 HbA1c measurements during the first year. Five independent cross-sectional analyses were conducted, grouping data by year. Statistical significance was determined by Student t and chi2 tests. RESULTS: Data were analyzed for 10,663 patients aged 17 to 98 years. The number of total eligible type 2 diabetes patients increased over the course of the study period: 5674 patients in 1998, 6553 in 1999, 7314 in 2000, 7323 in 2001, and 6192 in 2002. Overall, the study population had a mean (SD) age of 66 (11.0) years, was 53% male (3033/5674), and had a body mass index of 29 kg/m(2). Seventy-six percent of patients had HbA1c >7.0% and 37% were taking > or =2 oral agents. In 1998 and 2002, 79% (4482/5674) and 76% (4732/6192) of patients, respectively, had inadequate glycemic control, defined as HbA1c >7.0%. When defined as HbA1c >7.5%, 69% (3923/5674) and 62% (3814/6192) of patients, respectively, had inadequate control. Finally, when defined as HbA1c >6.5%, 88% (5011/5674) of patients in both 1998 and 2002 had inadequate control. Compared with patients with good disease control (HbA1c < or =7.0%), patients with inadequate control were approximately 2 years younger (P < 0.001) and had been prescribed more OAs: 41% received > or =2 OAs in 1998 and 52% in 2002, compared with 23% and 34% (both, P = 0.001), respectively, of patients with good glycemic control (P < 0.02). Sex, number of diabetes complications, and number of comorbidities did not differ between groups (P = NS). CONCLUSIONS: Despite the introduction of new OAs and treatment guidelines, the prevalence of inadequate glycemic control remains high (>60%) in patients with type 2 diabetes in the United Kingdom. Regardless of the HbA1c cutoff, patients with inadequate control were younger and received prescriptions for more OAs than patients with good control.

Cost of hypoglycemia in patients with Type 2 diabetes in Sweden.

OBJECTIVES: Hypoglycemia is a common side effect of antidiabetic therapy. In addition to reducing well-being, hypoglycemic events may lead to substantial costs of medical care and lost productivity. The cost of hypoglycemia is, however, not well identified, particularly in patients with Type 2 diabetes. The purpose of this study was to assess the cost of hypoglycemia in Type 2 diabetes in Sweden. METHODS: A cost-of-illness approach, based on an incidence methodology, was used to estimate the cost of hypoglycemia in patients with Type 2 diabetes. A hypoglycemic event was defined as an episode with symptoms of low blood glucose levels during which the patient required assistance from another person. The events were divided into mild, moderate, and severe, and the incidence and costs of the different events were estimated based on data in the literature. RESULTS: Assuming that there are 300,000 patients with Type 2 diabetes in Sweden, it was estimated that 26,942 hypoglycemic events would occur annually in these patients, corresponding to a rate of 0.09 events per patient-year. The total cost of hypoglycemia was, in base case, estimated at about Euro 4,250,000 (Euro 14 per patient with Type 2 diabetes) per year. Moderate hypoglycemia contributed the largest proportion of these costs. CONCLUSIONS: The results indicate that hypoglycemic events lead to substantial costs, but data are scarce and more studies are needed to better understand the cost and consequences of hypoglycemia.

Real-world trials to answer real-world questions.

Currently, there is a discrepancy between clinical trials designed to assess the efficacy and safety of a new medication under investigation and the real-life questions that need to be addressed regarding the clinical use of the medication by patients, healthcare professionals and society. The data necessary to obtain regulatory approval may be of limited relevance to policy makers when calculating economic parameters such as value for money or cost effectiveness. 'Real-world' studies examine questions relevant to health policy and reimbursement. There are many different forms of clinical trials, but in designing trials incorporating realistic budget impact estimates the important issue is to ensure we are asking a sensible question and attempting to answer it with an appropriate experimental design. As an example, a real-world trial currently underway that examines scenarios of introducing inhaled insulin into clinical practice is described.

The economic and quality of life impact of hypoglycemia.

Hypoglycemia is an often underrecognized side effect of type 2 diabetes therapy. This study assessed the burden of hypoglycemia in this population in Sweden and included 309 patients aged 35 years or older and treated with insulin and/or oral antidiabetic agents. Data were gathered through patient questionnaires/interviews and chart reviews. The results showed that 115 patients (37%) reported symptoms of hypoglycemia during the preceding month. Patients with hypoglycemia were more affected by their diabetes, reported lower general health, and were more anxious about hypoglycemia than those without hypoglycemia. The direct and indirect costs of hypoglycemia per patient with hypoglycemic symptoms were estimated to be U.S. $12.9 and $14.1, respectively, for a 1-month period. The results indicate that hypoglycemia is common, and that a reduction in these symptoms, without reducing glycemic control, may improve patient well-being and possibly also reduce cost.

Patient satisfaction and glycemic control after 1 year with inhaled insulin (Exubera) in patients with type 1 or type 2 diabetes.

OBJECTIVE: The aim of this study was to determine patient satisfaction in patients with type 1 or type 2 diabetes receiving an inhaled insulin or subcutaneous insulin regimen, as assessed by pooled analysis of two 12-week parent studies and 1-year extension studies. RESEARCH DESIGN AND METHODS: In the 12-week parent studies, patients with type 1 (n = 70) or type 2 (n = 51) diabetes were randomized to an inhaled insulin or subcutaneous insulin regimen. In the 1-year extension studies, patients were allowed to select either treatment regimen. Patient satisfaction was assessed at baseline, week 12, and 1 year using the Patient Satisfaction with Insulin Therapy questionnaire. RESULTS: Of the 60 patients who received inhaled insulin during the parent studies, 85.0% (n = 51) chose to continue treatment, 13.3% (n = 8) switched to subcutaneous insulin, and 1.7% (n = 1) did not continue. Of the 61 patients who received subcutaneous insulin, 21.3% (n = 13) chose to continue treatment, 75.4% (n = 46) switched to inhaled insulin, and 3.3% (n = 2) did not continue. From baseline (parent studies) to 1 year (extension studies), HbA(1c) reductions of 0.8% were sustained, and greater improvements were observed in the inhaled insulin group compared with the subcutaneous insulin group in terms of overall satisfaction (37.9 vs. 3.1%; P < 0.01) and ease of use (43.2 vs. -0.9%; P < 0.01). CONCLUSIONS: Inhaled insulin was preferred over subcutaneous insulin, which resulted in greater patient satisfaction up to 1 year in patients with type 1 or type 2 diabetes with durable effects on HbA(1c) levels.