Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race.

BACKGROUND: Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC. METHODS: We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007-2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk. RESULTS: Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks. CONCLUSIONS: Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.

The economic impact of poor sample quality in clinical chemistry laboratories: results from a global survey.

Background Despite advances in clinical chemistry testing, poor blood sample quality continues to impact laboratory operations and the quality of results. While previous studies have identified the preanalytical causes of lower sample quality, few studies have examined the economic impact of poor sample quality on the laboratory. Specifically, the costs associated with workarounds related to fibrin and gel contaminants remain largely unexplored. Methods A quantitative survey of clinical chemistry laboratory stakeholders across 10 international regions, including countries in North America, Europe and Oceania, was conducted to examine current blood sample testing practices, sample quality issues and practices to remediate poor sample quality. Survey data were used to estimate costs incurred by laboratories to mitigate sample quality issues. Results Responses from 164 participants were included in the analysis, which was focused on three specific issues: fibrin strands, fibrin masses and gel globules. Fibrin strands were the most commonly reported issue, with an overall incidence rate of ∼3%. Further, 65% of respondents indicated that these issues contribute to analyzer probe clogging, and the majority of laboratories had visual inspection and manual remediation practices in place to address fibrin- and gel-related quality problems (55% and 70%, respectively). Probe maintenance/replacement, visual inspection and manual remediation were estimated to carry significant costs for the laboratories surveyed. Annual cost associated with lower sample quality and remediation related to fibrin and/or gel globules for an average US laboratory was estimated to be $100,247. Conclusions Measures to improve blood sample quality present an important step towards improved laboratory operations.

Health care resource utilization and costs associated with nonfatal major adverse cardiovascular events.

BACKGROUND: Risk of recurrent cardiovascular events following an initial cardiovascular-related hospitalization remains high despite available interventions. Rates of cardiovascular events as well as associated health care resource utilization and costs are needed to assess the value of treatments. OBJECTIVE: To quantify, in patients with previous hospitalization for acute coronary syndrome (ACS), rates of nonfatal major adverse cardiovascular events (MACE) and secondary coronary events (SCE), as well as health care utilization and costs associated with a first MACE. METHODS: Administrative data from a large population of commercial managed care and managed Medicare enrollees in the United States were retrospectively analyzed. Patients with an ACS-related hospitalization from 2006 to 2011 were followed for 12 months to assess subsequent MACE and SCE rates. Patients were aged ≥ 18 years at initial ACS hospitalization (the index episode) and had ≥ 12 months of continuous health plan enrollment before and after the end of the index episode. Resource utilization and costs during a first MACE were assessed. Multivariable analyses were used to assess the associations between cardiovascular risk factors and the occurrence of a MACE, as well as the costs incurred during a first MACE. RESULTS: Of 75,231 study patients identified, 3.3% had a MACE and 8.3% had an SCE during the 12-month follow-up. Median time to first MACE and SCE from end of the index episode was 4.6 and 3.7 months, respectively. Mean MACE-related cost incurred during the first MACE was $19,642. Logistic analyses showed that age and diabetes were associated with increased odds of a MACE, while index ACS episodes involving ST-elevation myocardial infarction were associated with reduced odds. Findings from generalized linear models indicated that statin use and age were associated with lower episode-related costs and that MACE occurrence within 3 months of ACS hospitalization was associated with increased episode-related costs. CONCLUSIONS: MACEs and SCEs represent a common and costly burden in the year following ACS hospitalization. Our findings may inform future economic assessments of new therapies aimed at prevention of MACEs and SCEs.

Health and economic consequences of fragile X syndrome for caregivers.

OBJECTIVE: To describe the health and economic burden experienced by caregivers of individuals with fragile X syndrome (FXS) and test the assumption that burden is associated with specific dimensions of problem behavior. METHODS: Three hundred fifty caregivers rated their son or daughter's problem behavior and reported the use of medical services, caregiving time, impact on employment, financial burden, caregiver injuries, caregiver mental health, and prescription drug use. RESULTS: The son's FXS posed a significant burden for caregivers in a number of areas. Visits to medical specialists were common for both males (5.4 per year) and females (5.1 per year). Caregivers reported 9.2 hours per day of family caregiving for males with FXS and an additional 5.5 hours of paid help. Most families reported that FXS had at least some financial impact on the family, and caregivers had to take an average of 19.4 hours from work each month to care for their child's needs. Almost one third of the caregivers had been injured by their child at least once in the past year; when injuries occurred, the frequency was high (14.7 per year), of which 2.7 required medical care. Approximately one third of the caregivers had seen a professional for anxiety, stress, or depression during the past year, and one fourth were taking medication to help with these symptoms. Caregiver burden was highly associated with problem behavior, most commonly irritability. CONCLUSION: Problem behavior is a strong contributor to burden experienced by caregivers of children and adults with FXS. Clinicians should be aware of the role problem behavior plays in family adaptation and help families access appropriate medical and social support services.

Association between oral 5-ASA adherence and health care utilization and costs among patients with active ulcerative colitis.

BACKGROUND: Observational cohort study to assess the association between adherence to oral 5-aminosalicylates (5-ASAs) and all-cause costs and health care utilization among patients with active ulcerative colitis (UC) in the United States. METHODS: Retrospective analysis of insurance claims from June 1997 to August 2006 in the LifeLink Database. Patient criteria: aged 18 or older with one or more claim(s) between June 1997 and August 2005 for a UC diagnosis and at least one oral 5-ASA prescription on or after the first observed UC diagnosis; continuous enrollment for at least 6 months prior to and 12 months following 5-ASA initiation (index date). As a proxy for active disease, patients needed to have at least two UC-specific non-pharmacy claims, at least 30 days of 5-ASA treatment and at least one corticosteroid prescription within the 12-month post-index period. Cumulative exposure to oral 5-ASAs over the 12-month period was calculated using the medication possession ratio (MPR). Patients with an MPR of at least 0.80 were classified as adherent. All-cause medical and pharmacy resource utilization and costs were computed over the 12-month post-index period and compared between adherent and nonadherent patients. RESULTS: 1,693 UC patients met study inclusion criteria: 72% were nonadherent to 5-ASA treatment (n=1,217) and 28% were adherent (n=476) in the 12-month study period. Compared with nonadherent patients, adherent patients had 31% fewer hospitalizations (P=0.0025) and 34% fewer emergency department admissions (P=0.0016). Adherent patients had 25% more pharmacy prescriptions overall (P <0.0001) and 71% more UC-related pharmacy prescriptions (P <0.0001) than did nonadherent patients. Total all-cause health care utilization was 1.13 times higher for adherent patients than for nonadherent patients (P=0.0002). After adjusting for covariates, total all-cause costs were 29% higher for nonadherent patients than for adherent patients (mean [95% confidence interval]: $13,465 [$13,094, $13,835] vs $17,339 [$17,033, $17,645]). CONCLUSIONS: Approximately three-quarters of patients with active UC were not adherent with their prescribed doses of oral 5-ASA. Nonadherence was associated with higher total all-cause costs. The key driver of decreased costs among adherent patients was inpatient hospitalizations, which more than offset these patients' expected higher pharmacy costs.

All-cause health care charges among managed care patients with constipation and comorbid irritable bowel syndrome.

OBJECTIVE: Chronic idiopathic constipation and irritable bowel syndrome (IBS) are common gastrointestinal conditions with potentially significant burden on managed care systems. Our objective was to examine all-cause resource utilization and charges associated with constipation alone (C-only) and with IBS with comorbid constipation (IBS+C). METHODS: Administrative claims from a US health plan between January 1, 2003 and December 31, 2005 were analyzed. Patients with C-only (n = 48 585) and IBS+C (n = 10 952) were identified using International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Outcomes were compared with demographically matched controls and with a benchmark group of patients with migraine (N = 48 759). An index date was defined as the date 3 months prior to first observed diagnosis of the condition of interest. Outcomes were evaluated over a 12-month period before and after the index date. RESULTS: The pre-to-post increase in total charges for subjects with C-only was substantially higher than that for the comparison group ($8837 vs $1717; P < 0.001) or the migraine group ($8837 vs $ 4804; P < 0.001). Subjects with IBS+C also had a greater pre-to-post increase in total charges than did comparison group members ($6192 vs $1319; P < 0.001) and subjects with migraine ($6192 vs $4804; P = 0.0120). CONCLUSIONS: Both C-only and IBS+C impose substantial economic burden on third-party payers.

Direct economic burden of chronic hepatitis C virus in a United States managed care population.

GOALS AND BACKGROUND: To estimate all-cause and disease-related resource utilization and costs among managed care enrollees with chronic hepatitis C virus (HCV). STUDY: A large United States claims database was analyzed (1/1/2002 to 12/31/2006). Inclusion criteria were: diagnosis of chronic HCV; no hepatitis B diagnoses; ≥6 and ≥12 months of continuous plan enrollment prediagnosis and postdiagnosis, respectively. Use and costs of medical services and prescription drugs over a 12-month period postdiagnosis were evaluated. Outcomes were assessed in controls without HCV matched (1:1) on age, sex, and plan enrollment. All cost estimates were generated using multivariate generalized linear models to adjust for additional covariates and skewness common in health care cost data. RESULTS: Of the 20,662 patients who met all inclusion criteria, mean age was 49 years; 61% were male. Adjusted all-cause costs were $20,961 per HCV patient, compared with $5451 per control (P<0.0001). Hospitalization occurred in 24% of HCV patients compared with 7% of controls (P<0.0001). Mean inpatient costs were $5892 and $1159 per patient, respectively (P<0.0001). Patients with HCV had higher prescription costs compared with controls ($6191 vs. $1315; P<0.0001). At $6864 per patient, disease-related costs were nearly one-third of all costs in patients with HCV, which exceeded all-cause costs among controls by 26% (P<0.0001). CONCLUSIONS: Chronic HCV is a costly disease to managed care organizations. Disease-related costs in HCV exceed all-cause costs in demographically matched controls. Increased efforts in HCV screening and early treatment, particularly before progression to liver cirrhosis, may lead to long-term cost savings in HCV management for managed care systems.

Treatment patterns and adherence among patients with chronic hepatitis C virus in a US managed care population.

OBJECTIVE: The purpose of this study was to document real-world treatment patterns, medication adherence, and the impact of adherence on disease-specific and all-cause health-care costs among chronic hepatitis C virus (HCV) patients in a US managed care population. METHODS: Commercial insurance claims data between January 1, 2002 and December 31, 2006 from the Ingenix Impact (formerly Integrated Health Care Information Services) database were retrospectively analyzed. Chronic HCV patients with one or more prescriptions for an HCV-specific treatment within 6 months before or at any time after their first observed diagnosis of chronic HCV were selected. Prescribing patterns, treatment cost, and duration of treatment were assessed over the entire therapy period. Medication adherence rates and the relationship between adherence and health-care costs were assessed over the 24-week period after treatment initiation. The results were stratified by key clinical characteristics such as genotype, sustained virologic attainment, and disease severity. RESULTS: Results showed that peginterferon and ribavirin combination regimens were the most common treatments for chronic HCV. The patients underwent treatment for approximately 30-32 weeks on average, and treatment costs were over $20,000 per patient. Adherence to medication was suboptimal, especially among patients with severe disease. Adherent patients had higher pharmacy costs but significantly lower total costs when pharmacy was excluded. CONCLUSIONS: New and improved treatments that promote better adherence and impose a lower cost burden on patients and payers are needed.

Direct economic burden of high-risk and metastatic melanoma in the elderly: evidence from the SEER-Medicare linked database.

BACKGROUND: While the clinical implications of advanced melanoma have been extensively documented, little is known about the direct medical costs associated with the disease, particularly for elderly patients who carry the highest disease incidence and morbidity. OBJECTIVES: To document resource utilization and costs to the Medicare system for elderly patients with high-risk (stages IIB/C, IIIA/B, IIIC) or metastatic (stage IV) melanoma. METHODS: Data were taken from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database combining clinical information on incident cancer cases in the US between 1991 and 2002 with longitudinal (1991-2005) administrative Medicare claims. Subjects aged > or =65 years with at least one stage IIB or higher melanoma diagnosis were selected. An index date was identified corresponding to the first observed stage IIB or higher diagnosis. Subjects were then categorized into mutually exclusive index disease stages, based on the SEER-reported melanoma stage observed at the index date. All subsequent analyses were stratified according to the index disease stage. Subjects without a record of death were required to have at least 6 months of continuous Medicare Part A and Part B benefits coverage before and after their index date. Subjects who died <6 months after their index date were retained for analysis. Resource utilization and costs were evaluated for each patient from index date until death, benefits cessation or end of the database (31 December 2005). Cost data were inflated to 2007 $US and stratified by the care setting in which they were incurred: inpatient hospital, skilled nursing facility, emergency room, physician office, home healthcare, hospice and other ancillary. RESULTS: 6470 subjects met all inclusion criteria. Index stage distribution was: IIB/C (38%), IIIA/B (46%), IIIC (1%) and IV (15%). Median follow-up was 56, 39, 16 and 6 months, respectively. Patients with stage IV disease had 3.1 hospital days per month, compared with 0.5, 0.6 and 1.1 days for stage IIB/C, IIIA/B and IIIC patients, respectively. Adjusted inpatient costs for stage IV subjects were $US5565 per patient per month versus $US1031, $US1440 and $US2275 for stage IIB/C, IIIA/B and IIIC patients, respectively (p < 0.0001). Adjusted total costs were $US11 471 per month for stage IV subjects, compared with $US2338, $US3395 and $US6885 for stages IIB/C, IIIA/B and IIIC, respectively (p < 0.0001). CONCLUSIONS: The per-patient cost of advanced melanoma is high. Hospital services are the largest component of these costs. Monthly costs for subjects with stage IV melanoma were 67% higher than costs for subjects with stage IIIC disease and >3-fold higher than costs for patients with stages IIIA/B and IIB/C. However, when combining estimated monthly costs with median follow-up duration (a proxy for survival time), total costs incurred by Medicare appear to be highest for patients diagnosed at stage IIIA/B.

Cost and cost-effectiveness of the COMBINE study in alcohol-dependent patients.

CONTEXT: The COMBINE (Combined Pharmacotherapies and Behavioral Intervention) clinical trial recently evaluated the efficacy of medications, behavioral therapies, and their combinations for the outpatient treatment of alcohol dependence. The costs and cost-effectiveness of these combinations are unknown and of interest to clinicians and policy makers. OBJECTIVE: To evaluate the costs and cost-effectiveness of the COMBINE Study interventions after 16 weeks of treatment. DESIGN: A prospective cost and cost-effectiveness study of a randomized controlled clinical trial. SETTING: Eleven US clinical sites. PARTICIPANTS: One thousand three hundred eighty-three patients having a diagnosis of primary alcohol dependence. INTERVENTIONS: The study included 9 treatment groups; 4 groups received medical management for 16 weeks with naltrexone, 100 mg/d, acamprosate, 3 g/d, or both, and/or placebo; 4 groups received the same therapy as mentioned earlier with combined behavioral intervention; and 1 group received combined behavioral intervention only. MAIN OUTCOMES MEASURES: Incremental cost per percentage point increase in percentage of days abstinent, incremental cost per patient of avoiding heavy drinking, and incremental cost per patient of achieving a good clinical outcome. RESULTS: On the basis of the mean values of cost and effectiveness, 3 interventions are cost-effective options relative to the other interventions for all 3 outcomes: medical management (MM) with placebo ($409 per patient), MM plus naltrexone therapy ($671 per patient), and MM plus combined naltrexone and acamprosate therapy ($1003 per patient). CONCLUSIONS: To our knowledge, this is only the second prospective cost-effectiveness study with a randomized controlled clinical trial design that has been performed for the treatment of alcohol dependence. Focusing only on effectiveness, MM-naltrexone-acamprosate therapy is not significantly better than MM-naltrexone therapy. However, considering cost and cost-effectiveness, MM-naltrexone-acamprosate therapy may be a better choice, depending on whether the cost of the incremental increase in effectiveness is justified by the decision maker.

Measuring economic outcomes of alcohol treatment using the Economic Form 90.

OBJECTIVE: This article assesses the ability of the economic outcome measures in the Economic Form 90 to detect differences across levels of alcohol dependence as measured by the Alcohol Dependence Scale. METHOD: We used baseline data from the Combining Medications and Behavioral Interventions (COMBINE) Study, a large, multisite clinical trial, to assess the extent to which the economic items on the Economic Form 90 instrument can detect differences across levels of alcohol dependence. RESULTS: After adjusting for differences in demographic characteristics, the Economic Form 90 can detect significant differences across a range of dependence severity levels for the economic outcomes of inpatient medical care, emergency-department medical care, behavioral health care, being on parole or probation, and missed workdays, conditional on being employed. We did not detect significant differences across dependence severity for employment status, outpatient medical care, other criminal justice involvement, or motor vehicle accidents. CONCLUSIONS: The Economic Form 90 can identify differences in many economic outcomes associated with differing levels of alcohol dependence. This suggests that the Economic Form 90 may be useful in assessing changes in economic outcomes that result from changes in alcohol dependence.

The effect of screening and brief intervention for risky drinking on health care utilization in managed care organizations.

OBJECTIVE: We sought to estimate the effect of screening and brief intervention (SBI) for risky alcohol use on the health care utilization of risky drinkers in 4 managed care organizations. RESEARCH DESIGN: A quasi-experimental group design was implemented in which 12 participating primary care clinics randomly were assigned to 1 of 3 study conditions. In one condition, physicians, physician assistants, and nurse practitioners delivered the brief intervention. In another condition, midlevel professionals (usually nurses) performed the brief intervention. In the third condition, SBI was not performed. Using administrative claims data, we estimated the effect of SBI on individual-level annual days of total and inpatient health care utilization; annual outpatient visits; annual emergency room visits; and annual visits related to alcohol, drug, or mental health conditions. Negative binomial regression models were used to control for other factors that may affect health care utilization. RESULTS: Across all categories of care, the pre- to postintervention change in average health care utilization among risky drinkers in the intervention clinics was not significantly different from that of risky drinkers in the comparison clinics. CONCLUSIONS: Our findings suggest that there is no effect of SBI on the health care utilization of risky drinkers in the year following the intervention. Although SBI does not appear to reduce health care utilization, previous studies find that it significantly reduces the alcohol consumption of risky drinkers. Because these reductions presumably improve patients' overall health and well-being, managed care organizations may still find it beneficial to implement SBI on a broad scale.

Cost methodology of COMBINE.

OBJECTIVE: This article describes the methodology used in estimating the mean cost per patient of the interventions delivered in COMBINE, a randomized controlled trial (RCT) comparing pharmacotherapies and behavioral interventions for outpatient treatment of alcohol dependence. METHOD: Our methodology identifies a broad list of nonresearch activities necessary to implement the COMBINE interventions in standard clinical practice. For each activity, we include the time costs of clinical assessments and interventions by staff, the cost of space, laboratory charges and the cost of medical supplies. We also estimate the patients' time used for each of these activities. RESULTS: We present the estimated cost per activity for 15 intake assessments plus the Medical Management (MM) and Combined Behavioral Intervention (CBI) sessions for 9 of the 11 COMBINE sites. Labor costs represent the bulk of the total cost for all activities. The Form 90 AIR/ED is the most expensive intake activity both in terms of labor and space costs. The CBI session is more expensive than the MM session. CONCLUSIONS: Our methodology estimates the cost to treatment providers and to patients of implementing the COMBINE intervention in standard practice. Compared with previous methods, the prospective design of our methodology allows for higher quality data, and the detailed activity costing helps identify key cost drivers. Future analyses will present actual COMBINE intervention cost estimates based on trial data. Although this cost study is specific to the COMBINE interventions, the concepts, instruments and methods used here can be applied to any RCT.