A framework for addressing Alzheimer's disease: Without a frame, the work has no aim.

Confronting Alzheimer's disease (AD) involves patients, healthcare professionals, supportive services, caregivers, and government agencies interacting along a continuum from initial awareness to diagnosis, treatment, support, and care. This complex scope presents a challenge for health system transformation supporting individuals at risk for, or diagnosed with, AD. The AD systems preparedness framework was developed to help health systems identify specific opportunities to implement and evaluate focused improvement programs. The framework is purposely flexible to permit local adaptation across different health systems and countries. Health systems can develop solutions tailored to system-specific priorities considered within the context of the overall framework. Example metric concepts and initiatives are provided for each of ten areas of focus. Examples of funded projects focusing on screening and early detection are provided. It is our hope that stakeholders utilize the common framework to generate and share additional implementation evidence to benefit individuals with AD.

Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials.

INTRODUCTION: This study estimated the minimal clinically important difference (MCID) for Mini Mental State Examination, Clinical Dementia Rating Scale sum of boxes, and Functional Activities Questionnaire across the Alzheimer's disease (AD) spectrum. METHODS: Retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (9/2005-9/2016) and MCID for clinical outcomes were estimated using anchor-based (clinician's assessment of meaningful decline) and distribution-based (1/2 baseline standard deviation) approaches, stratified by severity of cognitive impairment. RESULTS: On average, a 1-3 point decrease in Mini Mental State Examination, 1-2 point increase in Clinical Dementia Scale sum of boxes, and 3-5 point increase in Functional Activities Questionnaire were indicative of a meaningful decline. The MCID values generally increased by disease severity; the effect size and standardized response mean for those with meaningful decline were consistently in the acceptable ranges for MCID. DISCUSSION: These findings can inform design and interpretation of future clinical trials.

Retrospective assessment of patient characteristics and healthcare costs prior to a diagnosis of Alzheimer's disease in an administrative claims database.

BACKGROUND: The objective of this study was to examine patient characteristics and health care resource utilization (HCRU) in the 36 months prior to a confirmatory diagnosis of Alzheimer's disease (AD) compared to a matched cohort without dementia during the same time interval. METHODS: Patients newly diagnosed with AD (with ≥2 claims) were identified between January 1, 2013 to September 31, 2015, and the date of the second claim for AD was defined as the index date. Patients were enrolled for at least 36 months prior to index date. The AD cohort was matched to a cohort with no AD or dementia codes (1:3) on age, gender, race/ethnicity, and enrollment duration prior to the index date. Descriptive analyses were used to summarize patient characteristics, HCRU, and healthcare costs prior to the confirmatory AD diagnosis. The classification and regression tree analysis and logistic regression were used to identify factors associated with the AD diagnosis. RESULTS: The AD cohort (N = 16,494) had significantly higher comorbidity indices and greater odds of comorbid mental and behavioral diagnoses, including mild cognitive impairment, mood and anxiety disorders, behavioral disturbances, and cerebrovascular disease, heart disease, urinary tract infections, and pneumonia than the matched non-AD or dementia cohort (N = 49,482). During the six-month period before the confirmatory AD diagnosis, AD medication use and diagnosis of mild cognitive impairment, Parkinson's disease, or mood disorder were the strongest predictors of a subsequent confirmatory diagnosis of AD. Greater HCRU and healthcare costs were observed for the AD cohort primarily during the six-month period before the confirmatory AD diagnosis. CONCLUSION: The results of this study demonstrated a higher comorbidity burden and higher costs for patients prior to a diagnosis of AD in comparison to the matched cohort. Several comorbidities were associated with a subsequent diagnosis of AD.

Patient Characteristics and Outcomes Associated with Receiving an Earlier Versus Later Diagnosis of Probable Alzheimer's Disease.

BACKGROUND: Effectiveness of Alzheimer's disease (AD) treatments may depend critically on the timeliness of intervention. OBJECTIVE: To compare characteristics and outcomes of patients diagnosed with probable AD (prAD) based on time elapsed from first onset of cognitive decline. METHODS: Patients with ≥1 prAD diagnosis and ≥1 follow-up visit were selected from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS; 9/2005-6/2015) and stratified based on the time between the perceived onset of cognitive decline at baseline and first prAD diagnosis (i.e., earlier versus later diagnosis). Characteristics at baseline and prAD diagnosis, clinically meaningful progression, and medication use following prAD diagnosis were compared. RESULTS: Median time from perceived onset of cognitive decline to prAD diagnosis was 4.5 years (earlier diagnosis: ≤3.46; later diagnosis: >5.71). Earlier-diagnosed patients (n = 1,476) were younger at baseline (74.3 versus 76.3 years) and had better cognitive and functional scores than later-diagnosed patients (n = 1,474). At first prAD diagnosis, earlier-diagnosed patients had lower mean global Clinical Dementia Rating (CDR) score (0.8 versus 1.1), higher mean Mini-Mental State Examination (MMSE) (22.6 versus 20.0), and lower mean Functional Activities Questionnaire (11.6 versus 17.3). Earlier- and later-diagnosed patients experienced similar time to a decrease of ≥3 points in MMSE (median 23.2 versus 23.1 months, p = 0.83), but earlier-diagnosed patients had longer time to a CDR score of ≥2 points, and longer times to initiation of AD medication and antipsychotic agents (all p < 0.01). CONCLUSION: Earlier prAD diagnosis in NACC data is associated with higher cognitive function and lower functional impairment at diagnosis.

A Claims-Based Examination of Health Care Costs Among Spouses of Patients With Alzheimer's Disease.

BACKGROUND: Spouses of Alzheimer's disease patients (AD spouses) may experience substantial health effects associated with their partner's chronic cognitive and behavioral dysfunction. Studies examining associations between the medical experiences of AD spouses in the period before and after their partner's AD diagnosis are limited, particularly those which measure health care resource use and cost. METHODS: AD patients were identified through multiple Medicare claims containing an AD diagnostic code. Their spouses were identified through special coding in the Medicare eligibility records. The AD spouses were matched demographically to the spouses of Medicare beneficiaries without a history of AD. Longitudinal and annual cross-sectional Medicare cost comparisons utilized log-transformed linear regression. The longitudinal period of observation began 12 months before the AD patient's initial claim listing AD and continued for up to 38 months afterwards. RESULTS: The study identified 16,322 AD spouses. Total per person costs were 24% higher in AD spouses than in the controls ($694/month vs $561/month). AD spouses' excess costs began 3 months before their partners' AD diagnoses and continued for ≥30 months. Being an AD spouse predicted 29% higher Medicare costs after adjustment for chronic health status (P < .001). Increasing AD patient care complexity had a substantial impact on AD spouse Medicare costs (P < .001). CONCLUSIONS: This study documents a link between the health status of AD spouses and AD patients. Additional research is required to elicit the mechanism behind the association between AD spouse and AD patient diagnosis.

Treatment patterns and cost-effectiveness of first line treatment of advanced non-squamous non-small cell lung cancer in Medicare patients.

AIM: To assess the cost-effectiveness of first-line pemetrexed/platinum and other commonly administered regimens in a representative US elderly population with advanced non-squamous non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This study utilized the Surveillance Epidemiology and End Results (SEER) cancer registry linked to Medicare claims records. The study population included all SEER-Medicare patients diagnosed in 2008-2009 with advanced non-squamous NSCLC (stages IIIB-IV) as their only primary cancer and who started chemotherapy within 90 days of diagnosis. The study evaluated the four most commonly observed first-line regimens: paclitaxel/carboplatin, platinum monotherapy, pemetrexed/platinum, and paclitaxel/carboplatin/bevacizumab. Overall survival and total healthcare cost comparisons as well as incremental cost-effectiveness ratios (ICERs) were calculated for pemetrexed/platinum vs each of the other three. Unstratified analyses and analyses stratified by initial disease stage were conducted. RESULTS: The final study population consisted of 2,461 patients. Greater administrative censorship of pemetrexed recipients at the end of the study period disproportionately reduced the observed mean survival for pemetrexed/platinum recipients. The disease stage-stratified ICER analysis found that the pemetrexed/platinum incurred total Medicare costs of $536,424 and $283,560 per observed additional year of life relative to platinum monotherapy and paclitaxel/carboplatin, respectively. The pemetrexed/platinum vs triplet comparator analysis indicated that pemetrexed/platinum was associated with considerably lower total Medicare costs, with no appreciable survival difference. LIMITATIONS: Limitations included differential censorship of the study regimen recipients and differential administration of radiotherapy. CONCLUSIONS: Pemetrexed/platinum yielded either improved survival at increased cost or similar survival at reduced cost relative to comparator regimens in the treatment of advanced non-squamous NSCLC. Limitations in the study methodology suggest that the observed pemetrexed survival benefit was likely conservative.

Frequency of skeletal-related events and associated healthcare resource use and costs in US patients with multiple myeloma.

OBJECTIVE: A potential complication for all new multiple myeloma (MM) patients is the clinical presentation of osteolytic lesions which increase the risk for skeletal-related events (SREs). However, the contribution of SREs to the overall economic impact of MM is unclear. The impact of SREs on healthcare resource utilization (HCRU) and costs for US patients with MM was analyzed in Truven Health Marketscan Commercial Claims and Medicare Supplemental Databases. METHODS: Adults diagnosed with MM between January 1, 2005 and December 31, 2010 with ≥2 claims ≥30 days apart (first claim = index date) were included. SREs included: hypercalcemia, pathologic fracture, surgery for the prevention and treatment of pathologic fractures or spinal cord compression, and radiation for bone pain. Rates of HCRU (outpatient [OP], inpatient [IP], emergency room [ER], orthopedic consultation [OC], and ancillary) and healthcare costs were compared between MM patients with and without SREs. Inverse propensity weighting was applied to adjust for potential bias. RESULTS: Of 1028 MM patients (mean age = 67, standard deviation = 13.2), 596 patients with ≥1 SRE and 432 without SREs were assessed. HCRU rates in IP, ER, and ancillary (p < 0.01) and mean total costs of OP, IP, and ER were significantly higher (p < 0.05) for patients with vs without SREs during follow-up. HCRU rates also increased with SRE frequency (p < 0.05 in OP, IP, ER, OC, and ancillary), as did mean total healthcare costs, except for OC (p < 0.001). LIMITATIONS: A broad assessment of pharmacotherapy for the treatment of MM was not an objective of the current study. Bisphosphonate use was evaluated; however, results were descriptively focused on frequency of utilization only and were not included in the broader cost and HCRU analysis. CONCLUSIONS: Among US patients with MM, higher SRE frequency was associated with a significant trend of higher HCRU and total healthcare costs in several settings.

Metastatic Pancreatic Adenocarcinoma Treatment Patterns, Health Care Resource Use, and Outcomes in France and the United Kingdom Between 2009 and 2012: A Retrospective Study.

PURPOSE: In Europe, pancreatic cancer (PC) accounts for approximately 2.6% of all new cancer cases and is the fourth leading cause of cancer-related death. Despite substantial morbidity and mortality, limited data are available describing real-world treatment patterns and health care resource use in any European country. We evaluated PC-related treatment patterns and associated health care resource use among patients with metastatic PC in the United Kingdom and France. METHODS: One hundred three oncology specialists (53 in France and 50 in the United Kingdom) abstracted data from medical records of 400 patients whom they treated for metastatic PC. Eligible patients had a diagnosis of metastatic PC at age 18 years or older between January 1, 2009, and December 31, 2012; had ≥3 months of follow-up time beginning at metastatic diagnosis; and received at least 1 cancer-directed therapy for metastatic disease. Information on patient demographics, Eastern Cooperative Oncology Group performance status, location of primary tumor, presence of comorbidities, adverse events, and complications were collected. Data on cancer-directed treatments and supportive care measures were evaluated. All analyses were descriptive. FINDINGS: Approximately two thirds of patients were men, and median age at metastatic disease diagnosis was 62.2 years. Nearly all patients (97.3%) received chemotherapy to treat metastatic disease, 9.3% received radiation therapy, and 7.8% received a targeted therapy. Overall, the most frequently administered first-line regimens for metastatic disease were gemcitabine alone (46.0%), a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX; 20.1%); gemcitabine/capecitabine (10.8%); and gemcitabine/oxaliplatin (9.5%). Approximately 40% of patients in France and 15% of patients in the United Kingdom received second-line systemic therapy, whereas 20% of patients in France and 3.4% of patients in the United Kingdom received third-line systemic therapy for metastatic disease. Overall, 52.5% of patients experienced at least one complication of PC. More than two thirds of patients had ≥1 office visit unrelated to chemotherapy administration, 54.0% had ≥1 inpatient hospitalization, 36.8% had ≥1 emergency department visit, and 25.3% had ≥1 pain management clinic visit. A total of 26.5% of patients in France and 42.5% in the United Kingdom entered hospice or long-term care. IMPLICATIONS: This study provides new, detailed information for patients with metastatic PC in real-world settings in 2 European countries. A small proportion of patients received >1 line of systemic therapy for metastatic disease, which is likely due to the aggressiveness of this disease and the lack of effective therapeutic options.

Using U.S. Medicare records to evaluate the indirect health effects on spouses: a case study in Alzheimer's disease patients.

BACKGROUND: The burden experienced by spouses of patients with Alzheimer's disease (AD) may have negative consequences for their physical health. We describe here a method for analyzing United States Medicare records to determine the changes in health service use and costs experienced by spouses after their marital partner receives an AD diagnosis. METHODS: We initially identified all beneficiaries in the 2001-2005 Medicare 5% sample who had multiple claims listing the ICD-9 diagnostic code for AD, 331.0. The 5% sample includes spouses who share a Medicare account with their marital partners because they lack a sufficient work history for full eligibility on their own. A matched cohort study assessed incremental health costs in the spouses of AD patients versus a control group of spouses of non-AD patients. Longitudinal and cross-sectional analyses tracked the impact of a patient's AD diagnosis on his or her spouse's healthcare costs. RESULTS: Our method located 54,593 AD patients of whom 11.5% had spouses identifiable via a shared Medicare account. AD diagnosis in one member of a couple was associated with significantly higher monthly Medicare payments for the other member's healthcare. The spouses' elevated costs commenced 2 to 3 months before their partners' AD diagnosis and persisted over the follow-up period. After 31 months, the cumulative additional Medicare reimbursements totaled a mean $4,600 in the spouses of AD patients. This excess was significant even after accounting for differences in baseline health status between the cohorts. CONCLUSION: The study methodology provides a framework for comprehensively evaluating medical costs of both chronically ill patients and their spouses. This method also provides monthly data, which makes possible a longitudinal evaluation of the cost effects of specific health events. The observed correlations provide a coherent demonstration of the interdependence between AD patients' and spouses' health. Future research should examine caregiving burden and other possible factors contributing to the AD spouses' health outcomes. It should also extend the method presented here to evaluations of other chronic diseases of the elderly.

Estimating the incremental net health benefit of requirements for cardiovascular risk evaluation for diabetes therapies.

PURPOSE: To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. METHODS: We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. RESULTS: The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was -1.80 million LYs, attributable to delayed access to diabetes therapies (-0 .18 million LYs) and fewer drugs (-1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. CONCLUSION: The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or for gone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result.

Persistence with biologic therapies in the Medicare coverage gap.

OBJECTIVES: To describe persistence with teriparatide and other biologic therapies in Medicare Part D plans with and without a coverage gap. STUDY DESIGN: Retrospective (2006) cohort study of Medicare Part D prescription drug plan beneficiaries from a large benefits company. Two plans with a coverage gap (defined as "basic") were combined and compared with a single plan with coverage for generic and branded medications (defined as "complete"). METHODS: Patients taking alendronate (nonbiologic comparator), teriparatide, etanercept, adalimumab, interferon ß-1a, or glatiramer acetate were selected for the study. For patients with complete coverage, equivalent financial thresholds were used to define the "gap."The definition of discontinuation was failure to fill the index prescription after reaching the gap. RESULTS: For alendronate, 27% of 133,260 patients had enrolled in the complete plan. Patients taking biologic therapies had more commonly enrolled in complete plans: teriparatide (66% of 6221), etanercept (58% of 1469), adalimumab (52% of 824), interferon ß-1a (60% of 438), and glatiramer acetate (53% of 393). For patients taking either alendronate or teriparatide, discontinuation rates were higher in the basic, versus complete, plan (adjusted odds ratios, 2.02 and 3.56, respectively). Discontinuation did not significantly vary by plan type for etanercept, adalimumab, interferon ß-1a, or glatiramer acetate. CONCLUSIONS: For patients who reached the coverage gap, discontinuation was more likely for patients taking osteoporosis (OP) medication. Not having a coverage gap was associated with improved persistence with OP treatment.

Increased olanzapine discontinuation and health care resource utilization following a Medicaid policy change.

OBJECTIVE: To assess the short-term impact of Florida Medicaid's policy change on olanzapine discontinuation and health care resource utilization among olanzapine-treated patients with schizophrenia or bipolar diagnoses. The announced policy change, effective on July 11, 2005, but rescinded on September 9, 2005, reclassified olanzapine as nonpreferred and gave physicians 60 days to change antipsychotics for current users. METHOD: Prescription patterns, health care resource utilization, and Medicaid payments were compared between patients using olanzapine on July 11, 2005, and matched prior-year controls. For reference, parallel analyses were conducted in New Jersey Medicaid, where access to olanzapine remained constant. The effect of Florida's policy change was also estimated among policy-sensitive olanzapine users by treating year (2004 vs 2005) as an instrumental variable. RESULTS: Matched Florida cohorts (N = 4,255) showed increases from 2004 to 2005 in 6-month rates of switching from olanzapine (+326%), hospitalization (+19.8%), and emergency room visits (+19.7%) (all P values < .001). Concurrently in the matched New Jersey cohorts (N = 2,680), there were no significant changes in these outcomes from 2004 to 2005. Among matched Florida policy-sensitive olanzapine users, an additional 9.3% experienced hospitalization in 2005 versus 2004 (P < .001), and increased payments for medical services and other antipsychotics largely offset decreased payments for olanzapine. CONCLUSIONS: The announced reclassification of olanzapine to nonpreferred status substantially disrupted the continuity of olanzapine therapy for many Florida Medicaid recipients diagnosed with schizophrenia or bipolar disorder and was associated with increased hospitalization and emergency room visits. During the 6 months following the policy change, increased payments for medical services largely offset reduced payments for olanzapine.

Costs associated with attempted suicide among individuals with bipolar disorder.

BACKGROUND: Bipolar disorder is a chronic mood disorder associated with a high risk for suicide attempts, which carry personal, societal, and economical consequences. No information is available on the economic costs associated with suicide attempts among patients with bipolar disorder or the change in economic costs from before to following the suicide attempt. AIMS OF THE STUDY: The primary objective of this study was to estimate the total health care costs and cost components (inpatient, outpatient, emergency services, and medication) incurred by patients diagnosed with bipolar disorder who attempt suicide. Cost data included psychiatric and non-psychiatric costs. A secondary objective was to compare patients with and without attempted suicide on demographic and clinical characteristics. METHODS: Data for this retrospective study were obtained from the PharMetrics Integrated Outcomes Database (1995-2005). Patients diagnosed with bipolar disorder with (N = 352) and without (N = 15,102) a suicide attempt were identified and compared on demographics and psychiatric and medical comorbidities. T-tests and chi-square tests were used for group comparisons of patient characteristics. Among patients who attempted suicide and were continuously enrolled in the year before and following the suicide attempt (N = 352), Wilcoxon signed-rank tests were used to compare health care costs between the year prior and the year following the first suicide attempt. RESULTS: The average total health care cost for the year following the suicide attempt (N = 352) was $25,012, which was more than 2 times higher than the $11,476 incurred in the prior 1-year period (p. < 001). The total health care cost in the first month following the suicide attempt accounted for 28.9% of the total annual cost. The cost distribution over time showed a large spike for inpatient and emergency services costs in the month following the attempt with sustained increases in medication and outpatient costs. Patients with suicide attempt (N = 1,147) were significantly more likely than patients without (N = 15,102) to be younger, female, and to have comorbid psychiatric and medical diagnoses, especially depressive and substance use disorders. DISCUSSION: The substantial economic costs incurred by patients with bipolar disorder who attempt suicide are marked by an increase in costs of crisis services during the first month following the suicide attempt, along with sustained increases in medication and outpatient costs during the year following the suicide attempt. Limitations of the study include reliance on claims data and potential lack of generalizability beyond private payer data. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Interventions designed to reduce the risk of suicide attempts among patients diagnosed with bipolar disorder may help decrease the related high economic costs, in addition to helping decrease adverse personal and societal consequences. IMPLICATIONS FOR HEALTH POLICIES: Cost-benefit analyses of treatment methods for bipolar disorder need to include the considerable expenses associated with suicide attempts. Current findings may also be of value for modeling the cost-effectiveness of treatment for bipolar disorder and of interest to payers and other health care decision makers, especially those involved in developing Medicare capitation models for patients with chronic conditions such as bipolar disorder. IMPLICATIONS FOR FURTHER RESEARCH: Additional research is needed on the cost of attempted suicide in the treatment of patients with bipolar disorder, especially studies that capture societal costs.

Antipsychotic adherence, switching, and health care service utilization among Medicaid recipients with schizophrenia.

OBJECTIVE: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to different treatments. METHODS: Adults with schizophrenia in the California Medicaid (MediCal) database who initiated treatment with index medications in 1998-2001, were classified as having: 1) abandoned antipsychotic medications; 2) switched to another medication; or 3) continued with the index antipsychotic, for up to 6 months after the index date. RESULTS: Of 2300 patients meeting eligibility criteria, 1382 (60.1%) continued index medications, 480 (20.9%) switched, and 438 (19.0%) abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications). These included using psychiatric (24.2% vs 14.5%; P < 0.001) or nonpsychiatric (31.5% vs 24.3%; P < 0.05) emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05); making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05) or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05); and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001) or nonpsychiatric (82.7% vs 74.6%; P < 0.001) services. CONCLUSIONS: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment).

Involvement in the US criminal justice system and cost implications for persons treated for schizophrenia.

BACKGROUND: Individuals with schizophrenia may have a higher risk of encounters with the criminal justice system than the general population, but there are limited data on such encounters and their attendant costs. This study assessed the prevalence of encounters with the criminal justice system, encounter types, and the estimated cost attributable to these encounters in the one-year treatment of persons with schizophrenia. METHODS: This post-hoc analysis used data from a prospective one-year cost-effectiveness study of persons treated with antipsychotics for schizophrenia and related disorders in the United States. Criminal justice system involvement was assessed using the Schizophrenia Patients Outcome Research Team (PORT) client survey and the victimization subscale of the Lehman Quality of Life Interview (QOLI). Direct cost of criminal justice system involvement was estimated using previously reported costs per type of encounter. Patients with and without involvement were compared on baseline characteristics and direct annual health care and criminal justice system-related costs. RESULTS: Overall, 278 (46%) of 609 participants reported at least 1 criminal justice system encounter. They were more likely to be substance users and less adherent to antipsychotics compared to participants without involvement. The 2 most prevalent types of encounters were being a victim of a crime (67%) and being on parole or probation (26%). The mean annual per-patient cost of involvement was $1,429, translating to 6% of total annual direct health care costs for those with involvement (11% when excluding crime victims). CONCLUSIONS: Criminal justice system involvement appears to be prevalent and costly for persons treated for schizophrenia in the United States. Findings highlight the need to better understand the interface between the mental health and the criminal justice systems and the related costs, in personal, societal, and economic terms.

Use of atypical antipsychotic drugs for schizophrenia in Maine Medicaid following a policy change.

More than one-third of Medicaid programs and Medicare Part D plans use prior authorization (PA) policies to control the use of atypical antipsychotics (AAs). We used Medicaid and Medicare claims data to investigate how Maine's PA policy affected AA use, treatment discontinuities, and spending among schizophrenia patients initiating AA therapy. Patients initiating AAs during Maine's policy experienced a 29 percent greater risk of treatment discontinuity than patients initiating AAs before the policy took effect; no change occurred in a comparison state. AA spending was slightly lower in both states. Observed increases in treatment discontinuities without cost savings suggest that AAs should be exempt from PA for patients with severe mental illnesses.

The economic burden of schizophrenia in the United States in 2002.

OBJECTIVE: This study quantifies excess annual costs associated with schizophrenia patients in the United States in 2002 from a societal perspective. METHOD: Annual direct medical costs associated with schizophrenia were estimated separately for privately (N = 1090) and publicly (Medicaid; N = 14,074) insured patients based on administrative claims data, including a large private claims database and the California Medicaid program (MediCal) database, and compared separately to demographically/geographically matched control samples (1 case:3 controls). Medicare costs of patients over age 65 years were imputed using the Medicare/MediCal dual-eligible patients (N = 1491) and published statistics. Excess annual direct non-health care costs were estimated for law enforcement, homeless shelters, and research/training related to schizophrenia. Excess annual indirect costs were estimated for 4 components of productivity loss: unemployment, reduced workplace productivity, premature mortality from suicide, and family caregiving using a human capital approach based on market wages. All costs were adjusted to 2002 dollars using the Medical Care Consumer Price Index and were based on the reported prevalence in the National Comorbidity Survey Replication. RESULTS: The overall U.S. 2002 cost of schizophrenia was estimated to be $62.7 billion, with $22.7 billion excess direct health care cost ($7.0 billion outpatient, $5.0 billion drugs, $2.8 billion inpatient, $8.0 billion long-term care). The total direct non-health care excess costs, including living cost offsets, were estimated to be $7.6 billion. The total indirect excess costs were estimated to be $32.4 billion. CONCLUSION: Schizophrenia is a debilitating illness resulting in significant costs. The indirect excess cost due to unemployment is the largest component of overall schizophrenia excess annual costs.

The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis.

OBJECTIVE: To determine long-term survival for subjects with severe sepsis enrolled in the previous multiple-center trial (PROWESS) of drotrecogin alfa (activated) (DrotAA) vs. placebo. DESIGN: Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial. SETTING: One hundred sixty-four tertiary care institutions in 11 countries. PARTICIPANTS: The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1,220 were alive at 28 days (the end of the original PROWESS follow-up). INTERVENTIONS: DrotAA (n = 850), 24 mug/kg/hr for 96 hrs, or placebo (n = 840). MEASUREMENTS AND MAIN RESULTS: Long-term survival data were collected. We had follow-up information on 100% of subjects at 28 days, 98% at hospital discharge, 94% at 3 months, and 93% at 1 yr. The longest follow-up was 3.6 yrs. Hospital survival was higher with DrotAA vs. placebo (70.3% vs. 65.1%, p = .03). There was no statistically significant difference in duration of survival time or in landmark survival rates in subjects who received DrotAA compared with those who received placebo (median duration of survival = 1113 days vs. 846 days for DrotAA vs. placebo, p = .10; landmark survival rates for DrotAA vs. placebo, 66.1% vs. 62.4% at 3 months [p = .11], 62.2% vs. 60.3% at 6 months [p = .44], 58.9% vs. 57.2% at 1 yr [p = .49], and 52.6% vs. 49.3% at 2(1/2) yrs [p = .21]). There was a significant interaction (p = .0008) between treatment assignment and baseline Acute Physiology and Chronic Health Evaluation (APACHE) II scores, suggesting qualitative differences in treatment effect with severity of illness. Subjects with APACHE II >/=25 had better survival time with DrotAA (median duration of survival: 450 vs. 71 days, p =.0005). Survival rates were also higher at landmark time points (DrotAA vs. placebo, 58.9% vs. 48.4% at 3 months [p = .003], 55.2% vs. 45.3% at 6 months [p = .005], 52.1% vs. 41.3% at 1 yr [p = .002], and 45.6% vs. 33.8% at 2(1/2) yrs [p = .001]). In the APACHE II <25 group there was no significant difference in survival time or survival rates at landmark time points except at 1 yr (DrotAA vs. placebo, 65.5% vs. 72.0% at 1 yr, p = .04). CONCLUSIONS: The acute survival benefit observed in subjects with severe sepsis who received DrotAA persists to hospital discharge. The survival benefit loses statistical significance thereafter. Post hoc analysis suggests the effect of DrotAA varies by APACHE II score with improved long-term survival in subjects with APACHE II scores >/=25 but no benefit in those with lower scores.

Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial.

OBJECTIVE: To compare differences in hospital mortality and resource use in adult severe sepsis subjects randomized to receive drotrecogin alfa (activated) (DrotAA) or placebo in the PROWESS trial. DESIGN: Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial. SETTING: One hundred sixty-four tertiary care institutions in 11 countries. PARTICIPANTS: The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1,220 were alive at 28 days (the end of the original PROWESS follow-up). INTERVENTIONS: DrotAA (n = 850), 24 microg/kg/hr for 96 hrs, or placebo (n = 840). MEASUREMENTS AND MAIN RESULTS: New follow-up data through hospital discharge were merged with existing 28-day follow-up data. Hospital mortality was calculated for designated subgroups. Intensive care unit and hospital length of stay and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) scores were calculated overall and in designated subgroups. Hospital discharge location was recorded. The 95% confidence interval of most subgroups contained the relative risk estimate for overall 28-day and hospital mortality. Median hospital length of stay and intensive care unit length of stay were similar in both treatment groups: 16 vs. 17 days (p = .22) and 9 vs. 9 days (p = .7) for placebo vs. DrotAA. No significant difference in TISS-28 scores was observed between treatment groups overall or in subgroups of disease severity. In subjects for whom discharge destination was reported, 42.8% of placebo subjects and 46.8% of DrotAA subjects (two thirds of survivors in each group) were discharged directly to home. CONCLUSIONS: Reduction in hospital mortality with DrotAA in most of the subgroups of PROWESS is consistent with the reduction in 28-day and hospital mortality observed in the overall PROWESS population. Additional survivors created with DrotAA treatment did not increase per-patient resource use or intensive care unit or hospital length of stay.

Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis.

OBJECTIVE: To assess the cost-effectiveness of drotrecogin alfa (activated) therapy, which was recently shown to reduce mortality in severe sepsis. DESIGN: Estimates of effectiveness and resource use were based on data collected prospectively as part of a multicenter international trial. Estimates of hospital costs were based on a subset of the patients treated in the United States (33% of all enrolled patients). Lifetime projections were modeled from published sources and tested in sensitivity analyses. Analyses were conducted from the United States societal perspective, limited to healthcare costs, and using a 3% annual discount rate. SETTING: A total of 164 medical institutions in 11 countries. PATIENTS: Adults > or = 18 yrs of age with severe sepsis INTERVENTIONS: Eligible patients were randomly assigned to receive a 96-hr intravenous infusion of drotrecogin alfa (activated) at 24 microg/kg/hr (n = 850) or placebo (n = 840). MEASUREMENTS AND MAIN RESULTS: Base Case: incremental short-term (days 1-28) healthcare costs per day-28 survivor; Panel on Cost-Effectiveness in Health and Medicine Reference Case: incremental lifetime healthcare costs per quality-adjusted life-year. Over the first 28 days (short-term Base Case), drotrecogin alfa (activated) increased the costs of care by $9,800 and survival by 0.061 lives saved per treated patient. Thus, drotrecogin alfa (activated) cost $160,000 per life saved (with 84.7% probability that ratio is <$250,000 per life saved). Projected to lifetime (lifetime Reference Case), drotrecogin alfa (activated) increased the costs of care by $16,000 and quality-adjusted survival by 0.33 quality-adjusted life-years per treated patient. Thus, drotrecogin alfa (activated) cost $48,800 per quality-adjusted life-year (with 82% probability that ratio is <$100,000 per quality-adjusted life-year). Estimates were generally robust to sensitivity analyses, although cost-effectiveness deteriorated to >$100,000 per quality-adjusted life-year if survivors lived <4.6 yrs on average. Drotrecogin alfa (activated) cost $27,400 per quality-adjusted life-year when limited to patients with an Acute Physiology and Chronic Health Evaluation II score > or = 25 and was cost-ineffective when limited to patients with a score <25. CONCLUSIONS: Drotrecogin alfa has a cost-effectiveness profile similar to that of many well-accepted healthcare strategies and below commonly quoted thresholds.