Cost of Bleeding in Trauma and Complex Cardiac Surgery.

PURPOSE: Trauma and complex cardiac surgery are associated with a high risk of bleeding complications. The difference in costs between patients who require bleeding control measures and those who do not is poorly understood. Our goal was to assess the cost of care and outcomes for patients in these settings. METHODS: Patients >18 years of age, who were discharged between January 2010 and December 2012, were retrospectively identified in the Premier Hospital Database based on International Classification of Disease, Ninth Revision codes. These patients were categorized as having received blood products ("bleeding patients") or not ("nonbleeding patients"). Patients with costs and length of stay (LOS) of zero were excluded. Differences in treatment costs and outcomes were assessed using univariate analysis and multivariate modeling. FINDINGS: Bleeding trauma patients (n = 8800) had a 150% higher total cost of care (P < 0.001; 146% after excluding costs of agents used for bleeding control, P < 0.001), an 81.3% longer hospital LOS (P < 0.001), and a 65.2% longer intensive care unit (ICU) LOS (P < 0.001) than nonbleeding patients (n = 53,727). Bleeding complex cardiac surgery patients (n = 82,832) had a 133.2% higher total cost of care (P < 0.001; 128.7% after excluding costs of agents used for bleeding control, P < 0.001), a 155.6% longer hospital LOS (P < 0.001), and an 89.3% longer ICU LOS (P < 0.001) than nonbleeding patients (n = 380,902). IMPLICATIONS: Trauma and cardiac surgery patients who experienced bleeding and received allogeneic blood product transfusions had significantly worse outcomes, including longer LOS, greater inpatient mortality, and higher costs of care (even when excluding costs of agents used for bleeding control) than those who did not.

Comparing antipsychotic treatments for schizophrenia: a health state approach.

The overall impact of first and second generation antipsychotics on quality of life and symptoms of people with schizophrenia remains controversial. We applied health state modeling to data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia study, a randomized trial of antipsychotic medications, and evaluated the likelihood of patients moving to more favorable health states over time. We applied K-means clustering to the data to create discrete groupings of patients with symptom and side effect characteristics that were then validated using quality of life measures. We compared cluster distributions across medications at baseline and 6 months after randomization. 1,049 patients were included in the initial cluster analysis. Five health states were identified: (1) low symptoms and low side effects (LS + LSE) (2) low symptoms and obesity (LS + Ob) (3) high symptoms and low side effects (HS + LSE) (4) high symptoms with depression and akathisia (HS + Dp + Ak) and (5) moderate symptoms and high side effects (MS + HSE). Six-month outcomes among patients randomly assigned to perphenazine, olanzapine, risperidone and quetiapine were compared. At baseline, almost 20% of patients were in the worst health state (HS + Dp + Ak), with greater decreases at 6 months in this health state for perphenazine (9.2% decrease) and olanzapine (11.1%) groups compared to risperidone (4.7%) and quetiapine (6.7%). This study demonstrated that health state analysis can provide insight into the overall clinical state of patients beyond the mere comparison of average scores and largely confirmed original CATIE findings.

Fiscal implications of newborn screening in the diagnosis of severe combined immunodeficiency.

In the United States, newborn screening (NBS) is currently recommended for identification of 31 debilitating and potentially fatal conditions. However, individual states determine which of the recommended conditions are screened. The addition of severe combined immunodeficiency (SCID) screening to the recommended NBS panel has been fully instituted by 18 states, with another 11 states piloting programs or planning to begin screening in 2014. Untreated, SCID is uniformly fatal by 2 years of age. Hematopoietic stem cell transplantation usually is curative, but the success rate depends on the age at which the procedure is performed. Short-term implementation costs may be a barrier to adding SCID to states' NBS panels. A retrospective economic analysis was performed to determine the cost-effectiveness of NBS for early (<3.5 months) versus late (≥3.5 months) treatment of children with SCID at 3 centers over 5 years. The mean total charges at these centers for late treatment were 4 times greater than early treatment ($1.43 million vs $365,785, respectively). Mean charges for intensive care treatments were >5 times higher ($350,252 vs $66,379), and operating room-anesthesia charges were approximately 4 times higher ($57,105 vs $15,885). The cost-effectiveness of early treatment for SCID provides a strong economic rationale for the addition of SCID screening to NBS programs of other states.

Use of blood products in patients with anticoagulant-related major bleeding: an analysis of inhospital outcomes.

PURPOSE: The impact of correcting elevated International Normalized Ratio (INR) values on inhospital mortality in patients with warfarin-associated major bleeding is presented. METHODS: Using patient information from the database of a large U.S. health system, a retrospective analysis was conducted to (1) evaluate inpatient practice patterns in correcting INR elevations among patients hospitalized with warfarin-related intracranial hemorrhage (ICH) or non-ICH bleeding and (2) test the hypothesis that achieving INR correction, defined as an INR of ≤1.5, at any point during the hospital stay is correlated with lower inhospital mortality. Cox proportional hazards models were constructed to assess predictors of inhospital death. RESULTS: Among the 354 patients who met the study selection criteria, INR correction was achieved in 87.9% overall (92.5% and 85.5% of patients with ICH and non-ICH bleeds, respectively). Patients whose elevated INR values were corrected had significantly lower inhospital death rates than those with uncorrected elevations: 15.3% versus 55.6% (p = 0.010) among patients with ICH and 2.0% versus 11.8% (p = 0.017) among those with non-ICH bleeds. After adjusting for baseline demographics and comorbidities, the correlation between failure to correct INR elevations and increased mortality risk was significant only for patients with ICH (hazard ratio, 8.04; 95% confidence interval, 2.07-31.18; p = 0.003). CONCLUSION: Results of this study indicated that correction of elevated INR values was associated with a lower likelihood of inhospital death among warfarin-treated patients hospitalized for ICH or non-ICH major bleeding.

Economic impact of infections among patients with primary immunodeficiency disease receiving IVIG therapy.

PURPOSE: There are limited data on the cost of infections among patients with primary immunodeficiency disease (PIDD) in clinical practice. The purpose of this study was to assess the economic impact, from the US commercial payer perspective, of infections in a cohort of patients with PIDD who were administered intravenous immunoglobulin (IVIG) therapy. METHODS: This study used administrative claims from the MarketScan(®) Database. Patients with a PIDD diagnosis, one or more prescription(s) for IVIG therapy between January 1, 2008 and February 28, 2010, and one or more prescription(s) for IVIG at least 3 months following first IVIG prescription, were selected. The study period consisted of a 7-month window following first IVIG prescription. Study measures included infection-related medical resource use and expenditures. Adjusted infection-related hospitalization expenditures were estimated using a generalized linear model, controlling for demographics, comorbidities, and infection type. RESULTS: A total 1,742 patients with PIDD and consistent IVIG use were identified, with 490 patients (mean age 43; 58.8% female) having one or more infection(s) during the 7-month study period. Infection-related inpatient hospitalizations were the most expensive component of care (US$38,574 per hospitalized patient). In multivariate modeling, the presence of a blood infection during the hospitalization (versus [vs] no blood infection), having diabetes, and younger age (<18 vs 55-64) were associated with significant increases in infection-related hospitalization expenditures (49.3%, 55.3%, and 76.5%, respectively) (P<0.05). CONCLUSION: Health care expenditures for infections in PIDD patients receiving IVIG therapy can be substantial, particularly for inpatient care. Future evaluations assessing the incremental cost of optimizing IVIG therapy should include evaluation of the effects on infection-related medical expenditures.

Implications to payers of switch from hospital-based intravenous immunoglobulin to home-based subcutaneous immunoglobulin therapy in patients with primary and secondary immunodeficiencies in Canada.

BACKGROUND: Switching primary/secondary immunodeficiency (PID/SID) patients from intravenous immunoglobulin (IVIg) to home-based subcutaneous immunoglobulin (SCIg) therapy reduces nurse time. A nurse shortage in Canada provides an important context to estimate the net economic benefit, the number of patients needed to switch to SCIg to recoup one full-time equivalent (FTE), and potential population-wide savings of reduced nurse time to a payer. METHODS: The net economic benefit was estimated by multiplying the hourly compensation for nurses in Canada by the hours required for each administration route. The number needed to switch to SCIg to gain one nurse FTE was estimated by dividing the work hours in a year by the average annual savings in nursing time in a PID population in Canada. The prevalence of treated PID/SID in Canada was calculated using provincial IgG audit data to extrapolate the potential population-wide savings of switching patients to SCIg therapy. FINDINGS: The net economic gain from switching one patient to home-based SCIg care would be C$2,603 (Canadian Dollars) in year 1 and C$2,948 each year thereafter. Switching 37 IVIg patients to SCIg would gain one nurse FTE. Switching 50% of the estimated 5,486 PID and SID patients in Canada receiving IVIg therapy to SCIg has the potential to save 223.3 nurse FTEs (C$23.2 million in labor costs). CONCLUSIONS: A shift from IVIg to less labor-intensive SCIg has the potential to help alleviate nurse shortages and reduce overall health care costs in Canada. Health care professionals might consider advocating for home-based SCIg therapy for PID/SID patients when clinically appropriate.

Validation of electronic systems to collect patient-reported outcome (PRO) data-recommendations for clinical trial teams: report of the ISPOR ePRO systems validation good research practices task force.

Outcomes research literature has many examples of high-quality, reliable patient-reported outcome (PRO) data entered directly by electronic means, ePRO, compared to data entered from original results on paper. Clinical trial managers are increasingly using ePRO data collection for PRO-based end points. Regulatory review dictates the rules to follow with ePRO data collection for medical label claims. A critical component for regulatory compliance is evidence of the validation of these electronic data collection systems. Validation of electronic systems is a process versus a focused activity that finishes at a single point in time. Eight steps need to be described and undertaken to qualify the validation of the data collection software in its target environment: requirements definition, design, coding, testing, tracing, user acceptance testing, installation and configuration, and decommissioning. These elements are consistent with recent regulatory guidance for systems validation. This report was written to explain how the validation process works for sponsors, trial teams, and other users of electronic data collection devices responsible for verifying the quality of the data entered into relational databases from such devices. It is a guide on the requirements and documentation needed from a data collection systems provider to demonstrate systems validation. It is a practical source of information for study teams to ensure that ePRO providers are using system validation and implementation processes that will ensure the systems and services: operate reliably when in practical use; produce accurate and complete data and data files; support management control and comply with any existing regulations. Furthermore, this short report will increase user understanding of the requirements for a technology review leading to more informed and balanced recommendations or decisions on electronic data collection methods.

The effect of a large regional health plan's value-based insurance design program on statin use.

BACKGROUND: Cost-sharing requirements employed by health insurers to discourage the unnecessary use of medications may lead to underutilization of recommended treatment regimens and suboptimal quality of care. Value-based insurance design (VBID) programs seek to address these problems by lowering copayments to promote adherence to "high-value" medications that have been proven to be clinically beneficial. VBID evaluations to date have focused on programs implemented by self-insured employers. This study is among the first to assess the VBID program of a health plan. METHODS: We examined a VBID program for statins implemented by a large regional health plan in 2008 and assessed its effect on medication adherence. Copayments on VBID brand statins were reduced by 42.9% for employer-sponsored plans (the treatment group) and increased by 16.7% for state-sponsored plans (the control group) between the preintervention and postintervention periods. Propensity score weights were used to balance the treatment and control groups on observed characteristics. We evaluated the impact of the VBID program on adherence using an econometric model with a difference-in-difference design. RESULTS: Medication adherence increased 2.7 percentage points (P=0.033) among VBID brand statin users in the treatment group relative to the control group. With a baseline adherence rate of 77.6%, nonadherence was reduced by 11.9%. CONCLUSIONS: Copayment reductions on selected statin medications contributed to improvements in adherence. As one of the first studies to evaluate a health plan's VBID program, our findings demonstrate that insurer-based VBID programs may yield results similar to those achieved by employer-based programs.

The economic burden of Medicare-eligible patients by multiple sclerosis type.

OBJECTIVE: Although the global rate of multiple sclerosis (MS) is low, a few studies have documented high costs. Costs are highly variable depending on MS stage. This study was designed to assess the economic burden of Medicare-eligible patients by MS type in the United States using a claims-based classification algorithm to examine cost variation by disease stage. METHODS: A sample of 2003 to 2006 Medicare patients was selected. Cases were classified as pre-existing progressive MS or pre-existing relapsing-remitting MS (RRMS); the latter were further subdivided into relapsing, remitting, or stable. RESULTS: The sample had 5044 MS subjects, of whom 34.4% had prevalent progressive MS and 65.6% had prevalent RRMS. There were many chronic, comorbid conditions. The mean all-cause Medicare expenditures (not including self-administered medications) per person-year for MS in 2006 were $23,630 for prevalent progressive patients and $5887 for prevalent RRMS patients. Within the RRMS type, Medicare expenditures per person per month in 2006 were $1418 for relapsing patients, $608 for remitting patients, and $331 for stable patients. CONCLUSIONS: There are substantial cost advantages to Medicare for keeping RRMS patients in a stable health state and in keeping them from advancing in disability severity. The overall cost advantage would be diminished by the large cost burden of comorbidity, which would likely remain fixed with improved MS therapies.

Estimation and validation of a multiattribute model of Alzheimer disease progression.

OBJECTIVES: To estimate and validate a multiattribute model of the clinical course of Alzheimer disease (AD) from mild AD to death in a high-quality prospective cohort study, and to estimate the impact of hypothetical modifications to AD progression rates on costs associated with Medicare and Medicaid services. DATA AND METHODS: The authors estimated sex-specific longitudinal Grade of Membership (GoM) models for AD patients (103 men, 149 women) in the initial cohort of the Predictors Study (1989-2001) based on 80 individual measures obtained every 6 mo for 10 y. These models were replicated for AD patients (106 men, 148 women) in the 2nd Predictors Study cohort (1997-2007). Model validation required that the disease-specific transition parameters be identical for both Predictors Study cohorts. Medicare costs were estimated from the National Long Term Care Survey. RESULTS: Sex-specific models were validated using the 2nd Predictors Study cohort with the GoM transition parameters constrained to the values estimated for the 1st Predictors Study cohort; 57 to 61 of the 80 individual measures contributed significantly to the GoM models. Simulated, cost-free interventions in the rate of progression of AD indicated that large potential cost offsets could occur for patients at the earliest stages of AD. CONCLUSIONS: AD progression is characterized by a small number of parameters governing changes in large numbers of correlated indicators of AD severity. The analysis confirmed that the progression of AD represents a complex multidimensional physiological process that is similar across different study cohorts. The estimates suggested that there could be large cost offsets to Medicare and Medicaid from the slowing of AD progression among patients with mild AD. The methodology appears generally applicable in AD modeling.

Q-TWiST analysis of patients receiving temsirolimus or interferon alpha for treatment of advanced renal cell carcinoma.

BACKGROUND AND OBJECTIVES: For patients with advanced cancers, it is important that treatment improves the quality as well as the quantity of survival. This quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) analysis provides a combined measure of both the overall survival interval and the quality of survival for patients with advanced renal cell carcinoma (RCC) receiving temsirolimus, interferon (IFN)-alpha or the combination of these agents, using data from a phase III clinical trial. METHODS: Overall survival was partitioned into three distinct health states: time with serious toxicity (TOX), time after progression (REL) and time without symptoms of progression or toxicity (TWiST). Health states were quality weighted by patient-reported EQ-5D measures collected while receiving treatment. RESULTS: All 626 patients from the trial were included in computation of health-state durations. EQ-5D questionnaires were obtained from 260 patients upon progression and from 230 after a grade 3 or 4 adverse event, and from 278 patients in the TWiST state. Patients receiving temsirolimus had 38% longer TWiST than those receiving IFNalpha (6.5 vs 4.7 months, respectively; p = 0.0005). Patients receiving temsirolimus had 25% longer quality-adjusted survival in terms of Q-TWiST than those receiving IFNalpha (7.0 vs 5.6 months, respectively; p = 0.0015). Differences between the combination (temsirolimus + IFNalpha) and IFNalpha groups were not statistically significant. Threshold utility analysis indicated that temsirolimus was the preferred alternative for all possible utility weights for REL and TOX health states. CONCLUSION: Temsirolimus resulted in significantly longer Q-TWiST (quality-adjusted survival) in patients with advanced RCC than IFNalpha therapy.

Baseline differences and trajectories of change for deceased, placed, and community residing Alzheimer disease patients.

This study identifies predictors of placement or death in a large ethnically/racially diverse sample of moderately impaired Alzheimer disease patients residing in the community. Patients and caregivers were followed for 18 months with 4 assessments at 6-month intervals. Multinomial regression was used to identify caregiver and patient baseline characteristics and changes over time as predictors of patient placement in a long-term care facility (n=180), patient death (not preceded by placement, n=187), or remaining in the community at home (n=583). Our findings reveal important differences between death and placement when compared with continued home care. Both death and placement are significantly associated with increased activities of daily living limitations (Exp(B)=1.285, P=0.017; Exp(B)=0.1.202, P=0.038, for death and placement, compared with home care, respectively), having a nonspouse caregiver [Exp(B)=0.325, P=0.026; Exp(B)=0.386, P=0.050, for death and placement, respectively], and being a male patient [Exp(B)=0.367, P=0.003; Exp(B)=0.439, P=0.016, for death and placement, respectively]. Death and placement differ with respect to health service use, race, and group assignment. Whites are more likely to be placed rather than remain at home when compared with African American [Ex(B)=0.520, P=0.028] or Hispanic [Exp(B)=0.338, P<0.005] patients, whereas being assigned to the control condition as opposed to active treatment [Exp(B)=0.515, P=0.008], having a male caregiver [Exp(B)=0.482, P=0.043], and increasing patient health service use [Exp(B)=1.105, P=0.015] are associated with increased mortality. Placed and deceased patients are further differentiated from each other by the fact that caregivers of placed patients report an increase in being bothered by memory problems when compared with caregivers of deceased patients [Exp(B)=0.577, P=0.006]. Patients who are placed, died, or remain at home have unique trajectories, which vary as a function of the reference group used for comparison. Increasing bother with memory problems is uniquely associated with placement relative to death while increasing health service use in the form of physician contacts and nurses visits is uniquely associated with death among community residing Alzheimer disease patients.

Willingness-to-pay for reductions in care need: estimating the value of informal care in Alzheimer's disease.

OBJECTIVE: To estimate the value of informal care in Alzheimer's disease using contingent valuation. METHODS: A questionnaire was administered to 517 primary carers in four countries (UK, Spain, Sweden, and US). Dichotomous choice and bidding game methods were used to elicit their willingness to pay for a reduction in care burden by 1 h per day, or a total elimination of care needs. Further, the relationship between carer willingness to pay and carer and patient characteristics including disease severity and income was examined. RESULTS: Carers spend on average about 7-9 h per day on giving care to their patient, of which 4-5 h constituted basic and instrumental ADL tasks. For a 1 h reduction in need for care per day, carers in the UK, Spain, Sweden, and US said that they were willing to pay pound105, pound121, pound59, and pound144 per month respectively. The willingness to pay was higher for carers with higher disposable income while the influence of other determinants varied across countries. About one-third of carers were not willing to pay anything for a reduction in care. CONCLUSIONS: Carers' stated willingness to pay for reductions in care giving time is substantial and comparable to the prices currently paid for treatments that achieve this benefit. Its determinants seem more directly related to carer status than directly to patient status and may vary by region and by cultural and sociologic factors.

Patient dependence and longitudinal changes in costs of care in Alzheimer's disease.

BACKGROUND/AIMS: To examine the incremental effect of patients' dependence on others, on cost of medical and nonmedical care, and on informal caregiving hours over time. METHODS: Data are obtained from 172 patients from the Predictors Study, a large, multicenter cohort of patients with probable Alzheimer disease (AD) followed annually for 4 years in 3 University-based AD centers in the USA. Enrollment required a modified Mini-Mental State Examination score >or=30. We examined the effects of patient dependence (measured by the Dependence Scale, DS) and function (measured by the Blessed Dementia Rating Scale, BDRS) on medical care cost, nonmedical care cost, and informal caregiving time using random effects regression models. RESULTS: A one-point increase in DS score was associated with a 5.7% increase in medical cost, a 10.5% increase in nonmedical cost, and a 4.1% increase in caregiving time. A one-point increase in BDRS score was associated with a 7.6% increase in medical cost, a 3.9% increase in nonmedical cost and an 8.7% increase in caregiving time. CONCLUSIONS: Both functional impairment and patient dependence were associated with higher costs of care and caregiving time. Measures of functional impairment and patient dependence provide unique and incremental information on the overall impact of AD on patients and their caregivers.

Sociodemographic and clinical correlates of utility scores in Alzheimer's disease.

OBJECTIVES: To examine the relationship between psychiatric symptoms, cognitive performance, functional capacity and quality of life in Alzheimer's disease (AD), and change in the Health Utilities Index (HUI)-Mark III, a widely used generic, multiattribute preference-based health-status classification system. METHODS: Follow-up data were obtained from caregiver proxy raters at 3, to 6, and 9-months postrandom assignment concerning 421 patients with AD, living with at least one caregiver in a noninstitutional setting, who participated in the Clinical Antipsychotic Trial of Intervention Effectiveness-AD of antipsychotic medication. Spearman rank correlations, multivariate linear regression, and mixed modeling were used to examine the correlates of change in the HUI. RESULTS: HUI scores decreased by an average of -0.061 over 9 months. Analysis revealed weak bivariate, and largely, nonsignificant multivariate relationships between change in HUI scores and sociodemographic characteristics, psychiatric symptoms, and cognitive performance. There were highly significant associations between decreases in health utilities and change in the AD Cooperative Study for Activities of Daily Living scale (ADCS-ADL) and AD-Related Quality of Life (ADRQoL) (both P < 0.001), even after controlling for other factors. Adjusted R(2) values ranged from 0.14 to 0.20. CONCLUSION: In AD patients requiring antipsychotic treatment, only weak relationships were found between changes in the HUI and sociodemographic and clinical indicators. While functional capability and quality of life showed more significant associations, less than 20% of the variance in health utility could be explained. Significant cognitive impairment and the need to rely on proxy raters may limit the usefulness of utility measurement in AD patients with serious behavioral symptoms.

Development and testing of a new outcome measure of relationship between patients with Alzheimer's disease and their partners.

In mild Alzheimer's disease (AD), loss of relationship with the patient is a significant consequence for the partner (relative) and may be amenable to improvement with effective intervention. To evaluate relationship dynamics, the authors developed and tested content and discriminative validity of the self-administered Partner-Patient Questionnaire for Shared Activities among 100 partners of patients with mild to moderate Alzheimer's disease. Principal component analysis confirmed that interference in 17 activities derived from the literature and partner-specified activities comprised a relationship factor; internal consistency was very high. Time spent caregiving, caregiver esteem, lack of family support, and impact on partner health and activities were significant predictors of the Partner-Patient Questionnaire for Shared Activities, but the patient's cognitive and mood states were not. The Partner-Patient Questionnaire for Shared Activities warrants additional psychometric testing as a measure of Alzheimer's disease outcome.