Trends and predictors of first-line chemotherapy use among elderly patients with advanced non-small cell lung cancer in the United States.

PURPOSE: This study assessed first-line chemotherapy treatment patterns over time and identified predictors of chemotherapy use and treatment selection among elderly patients with newly diagnosed Stage IIIB/IV non-small cell lung cancer (NSCLC) in the United States. METHODS: Patients aged 65 years and older newly diagnosed with Stage IIIB/IV NSCLC between 1997 and 2002 were identified and followed through 2003 using the Surveillance, Epidemiology and End Results (SEER)-Medicare database to evaluate temporal trends in chemotherapy treatment. Multivariate logistic regression models were estimated to identify predictors of chemotherapy treatment and factors associated with use of cisplatin/carboplatin (platinum) and either a taxane or gemcitabine versus other treatments. RESULTS: Chemotherapy use increased from approximately 28% of Stage IIIB/IV NSCLC patients diagnosed in 1997 to 36% of patients diagnosed in 2002. Doublet therapy was most commonly used as first-line therapy, received by 74% of chemotherapy-treated patients across all study years. Use of doublet therapy with platinum and either a taxane or gemcitabine also increased over time (with the largest increase for gemcitabine combinations from 0.3% in 1997 to 11.8% in 2002). Males were more likely than females to be treated with chemotherapy (odds ratios [95% CI]: 1.14 [1.06-1.22]), as were patients in the Northeast and South relative to patients in the West (1.24 [1.13-1.36] and 1.33 [1.20-1.47], respectively). CONCLUSION: Use of first-line chemotherapy treatment among elderly Stage IIIB/IV NSCLC patients is low, but appears to be increasing, with potential regional and gender differences in treatment. These findings are likely to be of interest to clinicians and policymakers.

Costs of first-line doublet chemotherapy and lifetime medical care in advanced non-small-cell lung cancer in the United States.

OBJECTIVES: The purpose of this study was to identify total lifetime medical-care costs and costs associated with first-line chemotherapy treatment among older patients with stage IIIB/IV non-small-cell lung cancer treated with commonly used two-drug chemotherapy ("doublet") regimens in the United States. METHODS: Study patients included individuals aged 65 years and older who received a diagnosis of stage IIIB/IV non-small-cell lung cancer in a Surveillance, Epidemiology and End Results cancer registry between 1997 and 2002 and who received first-line treatment with commonly used doublet regimens. Patients were followed retrospectively in the Surveillance, Epidemiology and End Results-Medicare database to evaluate lifetime medical-care costs and costs while on first-line chemotherapy treatment. Pairwise comparisons of treatment costs were estimated by using nonparametric bootstrap methods. RESULTS: Lifetime medical-care costs totaled approximately $70,000 and on-treatment costs for first-line chemotherapy totaled approximately $30,000 among study patients and were dominated by hospitalization and physician costs. Lifetime costs were significantly higher among patients treated with first-line cisplatin/carboplatin (platinum) plus a taxane compared with those who received platinum plus gemcitabine [difference: $4781 ($1558-$8039)] or other doublet therapy [difference: $5961 ($2333-$9614)]. Total on-treatment costs for first-line chemotherapy were significantly higher among patients treated with platinum plus a taxane compared with those who received platinum plus gemcitabine [difference: $5825 ($3872-$7770)], platinum plus another agent [difference: $5968 ($3995-$7975)], or another doublet therapy [difference: $3663 ($1620-$5740)]. CONCLUSIONS: There is a cost differential between first-line doublet regimens in terms of lifetime and on-treatment costs. Although doublet therapy with platinum and a taxane was the most frequently utilized regimen, it was associated with the highest lifetime and on-treatment costs.

Neutropenia-related costs in patients treated with first-line chemotherapy for advanced non-small cell lung cancer.

BACKGROUND: Neutropenia is a major adverse event often associated with chemotherapy administration. Neutropenia-related complications often lead to increased use of costly health care including inpatient and outpatient services. Monitoring and treatment of neutropenia thus place an economic burden on the health care system. OBJECTIVES: To evaluate (a) costs and medical resource use for chemotherapy- related afebrile and febrile neutropenia in an elderly population with Stage IIIB or Stage IV non-small cell lung cancer (NSCLC), and (b) costs unrelated to neutropenia and total all-cause health care costs during first-line chemotherapy. METHODS: Study patients in this retrospective database analysis were aged 65 years or older with a diagnosis of Stage IIIB or Stage IV NSCLC in the Surveillance, Epidemiology and End Results (SEER) cancer registry from 1998 through 2002. Neutropenia was identified by the presence of a primary or secondary diagnosis code for diseases of white blood cells (ICD-9-CM = 288.xx) during a period of first-line chemotherapy treatment. Febrile neutropenia was defined by (a) an inpatient hospitalization with a primary or secondary diagnosis for neutropenia occurring at any time during first-line chemotherapy or (b) intravenous or intramuscular antibiotic administration occurring after the initial neutropenia diagnosis and during first-line chemotherapy. Patients with neutropenia without these events were considered to have afebrile neutropenia. Patients were followed in the SEER-Medicare database to evaluate costs (defined as all Medicare payments, primary insurer payments, and patient copayments and deductibles) and resource use associated with afebrile or febrile neutropenia while on first-line chemotherapy. If a patient switched to second-line chemotherapy, the day prior to the switch was defined as the end of first-line treatment. If a switch to second-line therapy did not occur, then first-line therapy was assumed to end 30 days following administration of the last first-line agent. Costs were summed for 2 main types of cost measures: neutropenia-related costs, defined as costs for claims with either a primary or secondary diagnosis of neutropenia, and costs unrelated to neutropenia. Costs were classified using ICD-9-CM diagnosis and procedure codes appearing on the claims, with confidence intervals [CIs] for cost measures estimated by using nonparametric bootstrapping methods. Group comparisons of patient characteristics, medical utilization, and cost study measures were made using 2-sided Pearson chi-square and t-test statistics for categorical and continuous measures, respectively. The no neutropenia group was used as the reference category for comparisons involving patient characteristic, medical utilization, and total all-cause health care cost study measures. For total neutropenia-related costs, afebrile and febrile neutropenia study groups were compared. RESULTS: Among elderly patients treated first-line for advanced NSCLC, 5,138 met inclusion criteria, of whom 1,228 (23.9%) developed afebrile (n = 740, 14.4%) or febrile neutropenia (n = 488, 9.5%) while on first-line chemotherapy. Mean per patient costs for treating neutropenia during first-line chemotherapy were $12,148 (standard deviation [SD] = $15,432, 95% confidence interval [CI] = $10,915-$13,607) for patients with febrile neutropenia and $3,099 (SD = $4,541, 95% CI = $2,796-$3,431) for patients with afebrile neutropenia (P<0.001), with mean (SD) length of follow-up (duration of first-line chemotherapy) of 4.5 (4.8) and 5.5 (7.0) months, respectively. Expressed as a percentage of total all-cause health care costs during first-line chemotherapy, neutropenia-related costs accounted for 32.2% of total costs for patients with febrile neutropenia (mean [SD] = $37,694 [$26,078]) and 9.1% of total costs for patients with afebrile neutropenia (mean [SD] = $34,204 [$26,317]). Mean neutropenia-related costs per patient per month (PPPM) during first-line chemotherapy were $2,700 for patients with febrile neutropenia and $563 for patients with afebrile neutropenia. PPPM costs unrelated to neutropenia for patients with afebrile neutropenia, febrile neutropenia, and no neutropenia, respectively, were $5,655, $5,677, and $6,146. In sensitivity analyses, results were highly sensitive to the definition of neutropenia (i.e., claims with primary diagnosis only vs. primary or secondary diagnosis) but insensitive to the type of chemotherapy regimen. CONCLUSION: Neutropenia is a major adverse event that places patients at an increased risk of infection and subsequent morbidity and mortality. For elderly patients undergoing first-line chemotherapy for NSCLC, neutropenia, particularly febrile neutropenia, is associated with substantially higher total all-cause health care costs.

Quality of life of adolescent males with attention-deficit hyperactivity disorder.

Most psychosocial research on attention-deficit/hyperactivity disorder (ADHD) has focused on deficits in school, family, or behavioral functioning without incorporating perceived quality of life (QoL) or the adolescents' perspective. The Youth Quality of Life Instrument--Research Version (YQOL-R), was used to assess self-perceived QoL in a community sample of adolescents aged 11-18 years. Fifty-five adolescent males with a clinical diagnosis of ADHD were compared to a group of 107 adolescents with no chronic conditions (NCC) and a group of 52 adolescents with mobility impairments (MI). The adolescents with ADHD reported significantly lower perceived QoL scores, particularly in the Self and Relationship domains, than the NCC group. Their scores were similar to those from the group with MI, a group previously shown to have a substandard QoL. Interventions to improve self-esteem and social interactions might use QoL outcomes in evaluating effectiveness.

Field testing the ENSEMBLE Minimum Dataset: performance of an instrument to address heterogeneity of treatment effects.

AIM: To assess the ability of ENterprising SElective Multi-instrument BLend for hEterogeneity analysis (ENSEMBLE) Minimum Dataset instrument dimensions to discriminate among subgroups of patients expected to have differential outcomes. MATERIALS & METHODS: Patients with Type 2 diabetes, knee osteoarthritis, ischemic heart disease or heart failure completed a survey designed to represent three dimensions (health, personality and behavior). Health-related outcomes and utilization were investigated using claims data. Discriminant validity and associations between the dimensions and outcomes were assessed. RESULTS: A total of 2625 patients completed the survey. The dimensions discriminated 50-100% of the outcome levels across disease cohorts; behavior dimension scores did not differ significantly among the healthcare utilization level subgroups in any disease cohort. CONCLUSION: ENSEMBLE Minimum Dataset dimensions discriminated health-related outcome levels among patients with varied diseases.

Pragmatic clinical trials: U.S. payers' views on their value.

BACKGROUND: Randomized controlled trials (RCTs) reflect priorities established by regulators. Recently, pragmatic clinical trials (PCTs) have begun to attract interest. Unlike RCTs, PCTs aim to better inform post-regulatory decision making by using head-to-head comparisons of alternative treatments, diverse patient populations, and outcomes meaningful to patients, prescribers, and payers. OBJECTIVES: To describe how U.S. insurers and public payers perceive the value of PCTs for assessment of new prescription drugs. STUDY DESIGN: Criterion-based sample of U.S. insurers and public payers. METHODS: We gathered qualitative evidence from intensive interviews with formulary decision makers at 15 payers, representing 10 major types of U.S. payers. Prior literature and exploratory interviews informed our question selection. RESULTS: Payers viewed PCTs favorably despite wariness of drug company-sponsored trials. Payers would accept results from PCTs as part of payers' synthesis of multiple sources of evidence. Payers were enthusiastic about 2 PCT features-a diverse population (compared with the more homogeneous populations typical of RCTs) and an active comparator drug (not placebo). Payers did not anticipate that PCTs would displace their own analyses of internal data. Pharmaceutical companies' financial interest in obtaining trial results that favor their own drugs reduces PCTs' perceived value and dampens their appeal to payers; nonetheless, payers would seek PCT results and review them carefully, as they do other evidence. CONCLUSIONS: Recommendations to trial designers based on payers' views include tailoring different types of PCTs to different disease conditions, building in head-to-head comparisons in phase IIIb PCTs, and designing phase IV PCTs to include broader populations.

The role of private industry in pragmatic comparative effectiveness trials.

Comparative effectiveness research (CER) includes pragmatic clinical trials (PCTs) to address 'real-world' effectiveness. CER interest would be expected to stimulate biopharmaceutical manufacturer PCT investment; however, this does not seem to be the case. In this article we identify all industry-sponsored PCT studies from 1996 to 2010; analyze them across a variety of characteristics, including sponsor, research question, design, comparators and results; and suggest methodological and policy changes to spur future manufacturer PCT investment. Nine 'naturalistic', head-to-head versus standard of care or similar agent PCTs were identified. Two included a 'usual care' arm. Chronic care trials' length averaged 12 months (range: 6-24 months), six of which reported equivocal or no difference in effectiveness; results of two chronic and the single acute care PCTs favored the sponsor drug. None reported the sponsor drug inferior. Of seven that evaluated utilization or costs, six reported no differences and four of five studies comparing brand-generic drugs reported no difference. Whereas private investment in PCTs is in the public interest, manufacturers apparently have not yet seen the business case. To induce investment, we propose several methodological and regulatory policy innovations designed to reduce business risk by decreasing outcome variability and increasing trial efficiency, flexibility and market applicability.

Direct costs associated with initiating NPH insulin versus glargine in patients with type 2 diabetes: a retrospective database analysis.

AIMS: To compare total costs and risk of hypoglycemia in patients with type 2 diabetes (T2D) initiated on NPH insulin versus glargine in a real-world setting. METHODS: This study used claims data (10/2001 to 06/2005) from a privately insured U.S. population of adult T2D patients who were initiated on NPH or glargine following a 6-month insulin-free period. A sample of 1698 glargine-treated and 400 NPH-treated patients met the inclusion criteria. Total and diabetes-related costs (inflation-adjusted to 2006) were calculated for 6-month pre- and post-index periods and compared between 400 patient pairs matched by a propensity score method. RESULTS: In the post-index 6-month period, glargine patients incurred higher diabetes-related drug costs than NPH patients ($785 versus $632, p<0.0001) but there were no significant differences in diabetes-related medical or total costs, or all other total cost categories. Compared to the pre-index period, glargine patient costs declined by $2420 (p=0.058) whereas NPH patient costs declined by $4200 (p=0.046), with no statistically significant group differences (p=0.469). Among patients with hypoglycemia-related claims (0.75% in both groups), mean hypoglycemia-related costs were $85 and $202 for NPH and glargine patients, respectively (p=0.564). CONCLUSION: Initiation of either NPH or glargine was associated with major cost reductions and infrequent hypoglycemia-related claims.

Cardiovascular events and insulin therapy: a retrospective cohort analysis.

To investigate the impact of insulin plus other risk factors on cardiovascular disease (CVD) events in patients with type 2 diabetes (T2D), we conducted a retrospective study among patients with T2D from a U.S. managed care plan (n=342,692). Date of first CVD event was defined as index date. For patients without events, index date was date of last-observed claim. CVD event rates were calculated; odds of CVD event were compared for patients with/without insulin use. Events analyzed included stroke, MI, other cardiac/cerebrovascular events. Among insulin group (n=14,167), 22 patients/1000 patient-years experienced a CVD event, compared with 19/1000 patient-years in non-insulin group (n=328,077). Adjusting for risk factors and comorbidities, odds of event for insulin group compared to non-insulin group was 0.66, ranging from 25% lower for patients aged 65+ to 42% lower for patients aged 31-45. Insulin treatment of T2D was associated with reduced risk of CVD events compared to other or no therapy.

Cross-sectional 7-year follow-up of anxiety in primary care patients.

We describe the longitudinal patterns of anxiety symptoms and mental health treatment among patients recruited from a primary care clinic, and provide a naturalistic view of anxiety symptoms, disorders, and treatment at two time periods 7 years apart. Study participants were originally identified in a primary care setting in 1992 as positive but untreated for the presence of anxiety and/or depressive symptoms and disorders. Data were collected through telephone interviews assessing current psychological status for anxiety and depression symptoms, disorders, and general functioning and well being. There were no planned interventions. Participants were re-interviewed after 7 years. Two hundred seventy-one of the identified 1992 population of 784 patients were followed up by interview in 1999. Comparisons of the scores demonstrated that respondents were less symptomatic in 1999 than in 1992, with 45% of respondents reporting no symptoms whatsoever at follow-up. Severity of symptom status in 1992 was indicative of follow-up symptom severity. Most respondents (68%) had not received mental health treatment over the 7 years, largely because they wanted to handle problems on their own. This study demonstrates the tendency of anxiety to remain or reappear years after originally identified, with 55% of patients reporting symptoms after 7 years. Initially untreated and underdiagnosed anxiety is associated with continued impairment in functional status and quality of life and continued underrecognition and undertreatment.

Functional status and somatization as predictors of medical offset in anxious and depressed patients.

OBJECTIVE: Certain anxious/depressed primary care patients decrease medical utilization after mental health treatment. Previous research has established demo-graphic and medical comorbidities as distinguishing these patients. We asked whether characteristics such as symptom severity, somatization, or health-related quality of life (HRQoL) could also distinguish patients who reduce or increase primary care utilization after mental health care. METHODS: Primary care patients in a mixed-model HMO were screened for untreated anxiety with and without depression, using the Symptom Checklist (SCL-90-R) and medical records abstractions, and also for HRQoL (SF-36). We identified 165 symptomatic patients who subsequently received mental health treatment and then defined two subgroups: 1) offset patients (reduced medical utilization the year after initiation of mental health treatment) (N=97); and 2) no-offset patients (increased utilization) (N =68). RESULTS: Three HRQoL domains (general health perceptions, physical functioning, and role functioning- physical) predicted increased offset savings in the year after initiation of mental health treatment. Each point of improved functioning in these domains was associated with 4 dollars to 10 dollars of additional offset savings. Somatization-related comorbidities were predictive of greater additional costs (230 dollars). CONCLUSION: Using models to predict individual patient costs, we found that HRQoL and somatic comorbidities did not predict by anxiety/depression symptom severity or medical comorbidities, but by increasing or decreasing utilization after mental health care. Patients with higher functioning levels and no somatic comorbidities were most likely to reduce utilization. These findings support growing evidence for the need of inclusion of reliable indicators of somatization and patients' functioning in offset research and inpatient care.