Provider imaging practices and outcomes of advanced colorectal cancer.

PURPOSE: To explore the real-world utilization of computerized tomography (CT) in patients with advanced colorectal cancer (CRC) and the associated outcomes. METHODS: Using Optum's de-identified Clinformatics® Data Mart Database (2008-2016), we identified patients with CRC receiving combination of chemotherapies (fluoropyrimidines with either oxaliplatin or irinotecan, or capecitabine with either oxaliplatin or irinotecan) combined with bevacizumab as the initial treatment, and its starting date was registered as the index date. End of treatment was defined by the presence of a gap in therapy > 60 days or treatment switch. We assessed the CT scan utilization during the period between 60 days pre-index and 30 days post-end of treatment. Cox regressions were performed to assess the impact of intensity of follow-up CT scans, measured by time to the first scan from the index date, on likelihood of treatment switch and survival. RESULTS: Among included 4,810 patients, the median (standard deviation) time to the first follow-up scan was 57 (45) days. The mean and median number of CT scans was 4 and 3, respectively. An earlier follow-up scan was associated with significantly greater chance of treatment switch (hazard ratio = 0.99 for each day of delay, P < 0.01), and greater likelihood of death (hazard ratio = 0.99 for each day of delay, P < 0.01). CONCLUSION: More intense follow-up increased the likelihood of treatment switch, yet it was not associated with better survival outcome. Further analysis in populations with longer follow-up period is warranted to elucidate the link between CT scan utilization and outcomes.

Impact of Adding Pharmacists and Comprehensive Medication Management to a Medical Group's Transition of Care Services.

OBJECTIVES: Evaluate the impact of pharmacist-provided transition of care (TOC) services on hospital readmissions. METHODS: Starting March 2014, TOC services were provided to all hospitalized patients from an at-risk medical group. Data covering all inpatient and outpatient services and prescription drugs were retrieved for all adult patients discharged between January 2010 and December 2018. The overall impact of TOC was estimated using a generalized estimating equation with logistic regression. Longitudinal TOC effects were estimated using generalized estimating equation in an interrupted time series model. Parallel analyses were conducted using data from an affiliated medical group in a neighboring county without access to the TOC intervention. RESULTS: The study included 13,256 hospital discharges for adult patients for the 30-day readmission analysis and 10,740 discharges for the 180 days analysis. The TOC program reduced 30-day readmission risk by 34.9% [odds ratio (OR)=0.651 (range, 0.590-0.719)] and 180-day readmissions by 33.4% [OR=0.666 (range, 0.604-0.735)]. The interrupted time series results found the 30-day readmission rate to be stable over the pre-TOC period (OR=0.00; not significant) then to decreased by 1.5% per month in the post-TOC period [OR=0.985 (range, 0.980-0.991)]. For 180-day readmissions, risk decreased by 1% per month after TOC implementation [OR=0.990 (range, 0.984-0.996)]. Referral to the medical group's pre-existing Priority Care clinic also reduced readmission risk. Results from the comparison medical group found 180-day readmission declined by 1% per month after March 2014 [OR=0.990 (0.891-1.00)]. CONCLUSIONS: Adding a pharmacist-led TOC program to the medical group's existing outpatient services reduced 30- and 180-day readmissions by "bending the curve" for readmission risk over time.

Complications and hospital costs during hematopoietic stem cell transplantation for non-Hodgkin lymphoma in the United States.

While the initial hospitalization accounts for 75% of total healthcare costs during the first 100 days following hematopoietic stem cell transplantation (HSCT), there is a lack of studies evaluating the considerable variation in cost estimates. Using the National Inpatient Sample (NIS) database from 2012-2014, we identified 1832 adult non-Hodgkin lymphoma (NHL) patients who received autologous or allogeneic HSCT and examined complications as predictors of hospital cost. Complications occurred in >70% of patients, and the presence of one or more complications was associated with an increase in mean hospital costs of 46% in autologous HSCT and 81% in allogeneic HSCT. The most common complications (∼40%) were mucositis, febrile neutropenia, and infection. Acute organ failure, acute graft-versus-host disease, and death were less frequent (∼10%) but had a greater impact on increasing hospital costs and length of stays. Despite recent advances in supportive care and pre-conditioning regimens, complications are common and costly during HSCT.

Primary Prevention Using Cholesterol-Lowering Medications in Patients Meeting New Treatment Guidelines: A Retrospective Cohort Analysis.

BACKGROUND: The American College of Cardiology and American Heart Association (ACC/AHA) issued new cholesterol treatment guidelines in 2013. Two of the groups designated for primary prevention were analyzed: patients with a low-density lipoprotein cholesterol (LDL-C) level ≥ 190 mg per dL and diabetic patients aged 40-75 years. OBJECTIVE: To estimate the effects of primary prevention as specified in the 2013 guidelines on cardiovascular event risk and cost. METHODS: Primary prevention patients were identified using laboratory and diagnostic data for Humana members from 2007 to 2013. Potential study patients were classified into 3 risk groups: elevated LDL-C, diabetes, and elevated LDL-C and diabetes. Patients receiving cholesterol-lowering medications before their index date were excluded. Eligible patients were divided into 2 treatment groups: (1) primary prevention patients who initiated treatment before experiencing any cardiovascular disease (CVD)-related event, and (2) patients who either did not initiate treatment until after experiencing a CVD event or never initiated treatment. The associations between initiating cholesterol-lowering medications for primary prevention and the risk for acute myocardial infarction, stroke, coronary angioplasty, or coronary artery bypass graft surgery were estimated using Cox proportional hazards models. The effect of primary prevention on health care costs was estimated using generalized linear models. RESULTS: 91,066 patients met study selection criteria. Primary prevention rates were the lowest in diabetic patients (35%), who were newly designated for treatment in the 2013 guidelines. Primary prevention rates were higher for patients designated for treatment under earlier guidelines: 65% for patients with elevated LDL-C and 78% for the combined LDL-C and diabetes group. Primary prevention treatment was associated with significant reductions in cardiovascular event risk (up to 37%) and lower total all-cause costs (by $673) in the first post-index year. CONCLUSIONS: Initiating cholesterol-lowering medications for primary prevention, as specified in the ACC/AHA 2013 guidelines, for patients with high LDL-C and diabetes is associated with reduced CVD event risks and lower health care costs. DISCLOSURES: No outside funding supported this study. Han received fellowship support from the Pharmaceutical Research and Manufacturers Association Foundation (PhRMA) during the conduct of this study. Dougherty is employed by PhRMA. The authors have nothing to disclose.

Reduction of healthcare costs through a transitions-of-care program.

PURPOSE: Results of an evaluation of the impact of a pharmacy-based transitional care program on healthcare costs in a population of high-risk patients are reported. METHODS: A nonrandomized, observational cohort study was conducted to compare cost outcomes in a group of patients discharged from a single hospital who were referred to an ambulatory care pharmacy-based transitions-of-care (TOC) program and a control group of patients discharged from neighboring hospitals who received usual care; all patients were members of the same managed Medicaid plan. The intervention and control groups were matched by number of hospitalizations during the 180 days preceding the index admission and by index admission length of stay. In the intervention group, all matched patients referred for TOC services (including those who did not qualify for services, could not be contacted, or declined services) were included in an intent-to-treat analysis. Thirty- and 180-day inpatient, outpatient, prescription, emergency room, and total costs were analyzed by ordinary least-squares and generalized linear model regressions, with selected costs further analyzed using two-part regression models. RESULTS: Among 830 patients referred to the TOC program, total healthcare costs at 180 days after discharge were an average of $2,139 lower than costs in the control group, yielding estimated savings of nearly $1.8 million for the managed care plan. CONCLUSION: Compared with usual postdischarge care, use of TOC services was associated with a significant reduction in 180-day total healthcare costs.

Budget Impact Analysis of a Pharmacist-Provided Transition of Care Program.

BACKGROUND: Postdischarge medication management services have been shown to reduce the incidence of medication-related problems during the transition from inpatient to outpatient care. A pharmacist-run transition of care (TOC) program has been developed to reduce the unplanned readmissions of a high-risk managed Medicaid population after hospitalization. OBJECTIVE: To estimate the budget impact of adding an outpatient pharmacy-based TOC program to a medical benefit from the payer perspective. METHODS: A budget impact analysis was conducted using a decision-tree model developed in Microsoft Excel. The effect on inpatient and total health care costs from the payer perspective was estimated for the 2-year period following initial hospital discharge. Inputs were based on a total plan population of 240,000 lives, with a high-risk population of 7.5%, of whom 37% were hospitalized and potentially qualified for TOC services, resulting in an eligible population of 6,660 patients. The TOC program was assumed to initially cover 30% of the eligible population, with expansion to 60% over the 2 years. We previously reported that this program reduced the risk of readmission by 32% within 6 months and saved the health plan $2,139 per patient referred to the program, inclusive of program cost, compared with patients receiving usual discharge care. Sensitivity analyses were performed to test the impact of uncertainty of model inputs on the results, with the cost of TOC services ranging from $99 to $2,000 per patient referred. RESULTS: The model showed that the TOC program was cost saving at over $3 per member per month in the first 6 months, which translates to over $25 million in total health care cost savings over 2 years. These results were primarily driven by the estimated reduction in inpatient costs associated with the program, which were estimated at $20 million over the 2 years. Sensitivity analyses illustrated that within all the reasonable ranges of model input parameters, including the upper limit of TOC services set to $2,000 per patient referred, the TOC program resulted in cost savings to the health plan. CONCLUSIONS: The TOC program resulted in potential cost savings of over $25 million to the managed Medicaid plan over a period of 2 years, corresponding to over $4 per member per month. DISCLOSURES: Funding for this study was contributed by the Komoto Family Foundation, which provided fellowships to Ni and McCombs during the time of this study. Colayco is employed by Synergy Pharmacy Solutions and by the Komoto Family Foundation. Hashimoto and Komoto are employed by Synergy Pharmacy Solutions. Gowda and Wearda report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. Study concept and design were contributed by Ni, Colayco, and McCombs, along with the other authors. Hashimoto, Komoto, and Wearda took the lead in data collection, assisted by Ni, Colayco, and Gowda. Data interpretation was performed by Ni, Colayco, and McCombs, along with the other authors. The manuscript was written by Ni and Colayco and revised by Gowda and McCombs, along with the other authors.

Impact of a pharmacy-based transitional care program on hospital readmissions.

OBJECTIVES: Avoidable readmissions of patients discharged from hospitals are a major concern. This study evaluates the impact of pharmacist-provided postdischarge services on hospital readmissions for members of a US managed Medicaid health plan. STUDY DESIGN: Prospective cohort study. METHODS: Synergy Pharmacy Solutions (SPS) initiated a transition of care (TOC) service for high-risk members of the Kern Health Systems (KHS) managed Medicaid plan. Over 1100 patients were referred to SPS between April 2013 and March 2015. KHS classified hospitalized members as high risk for readmission based on prior healthcare utilization, a health risk assessment questionnaire, and the use of the Johns Hopkins predictive modeler. This study compares SPS TOC recipients with a matched sample of KHS members discharged from nonintervention hospitals. Thirty-day and 180-day readmissions and time-to-readmission were defined as outcomes. Logistic regression and Cox model were estimated, controlling for demographics, diagnostic and drug profiles, and prior hospital utilization. RESULTS: KHS identified 1763 high-risk discharges from nonintervention hospitals, of which 1005 and 669 were matched to 830 and 558 selected SPS patients in 30-day and 180-day populations, respectively. The SPS postdischarge intervention reduced the risk of readmission within 30 days by 28% (odds ratio [OR], 0.720; 95% confidence interval [CI], 0.526-0.985) and within 180 days by 31.9% (OR, 0.681; 95% CI, 0.507-0.914). The estimated effect of the SPS intervention from the Cox model was a reduction in risk of 25% (hazard ratio, 0.749; 95% CI, 0.566-0.992). CONCLUSIONS: A community pharmacy-based postdischarge TOC program can significantly reduce readmission rates at 30 and 180 days compared with usual discharge care.

A Retrospective Cohort Study of Acute Kidney Injury Risk Associated with Antipsychotics.

BACKGROUND: A recent large database analysis raised concerns of potential acute kidney injury (AKI) risk associated with antipsychotics. However, whether individual atypical and typical antipsychotics are associated with differential AKI risks has not been investigated. OBJECTIVE: The current study compared the risks of AKI and known causes of AKI associated with a broad range of atypical and typical antipsychotics. METHOD: This retrospective cohort analysis used January 2007-June 2013 US nationwide Humana claims data to define episodes of antipsychotic drug therapy for patients with schizophrenia and bipolar disorder. Study drugs were aripiprazole, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Study outcomes were hospitalizations with AKI, and known causes of AKI, i.e., hypotension, acute urinary retention, neuroleptic malignant syndrome/rhabdomyolysis, and pneumonia. AKI was the primary outcome of the study. Cox regressions using haloperidol as the baseline comparator were used to estimate the impact of alternative antipsychotics on the risks of study adverse events following the initiation of treatment. The Cox models controlled for treatment history, comorbidities, and concomitant drug use in the prior 6 months. They also controlled for patient demographics and dose of current treatment. RESULTS: The overall incidence of AKI was 25.0 per 1000 person-years. According to our multivariate regression results, the risk of AKI was significantly increased in patients taking olanzapine [hazard ratio (HR) 1.344, 95% confidence interval (CI) 1.057-1.708], quetiapine (HR 1.350, 95% CI 1.082-1.685), and ziprasidone (HR 1.338, 95% CI 1.035-1.729) relative to haloperidol. Aripiprazole (HR 1.152, 95% CI 0.908-1.462) and risperidone (HR 1.147, 95% CI 0.923-1.426) had insignificantly higher risks of AKI compared with haloperidol, whereas fluphenazine (HR 0.729, 95% CI 0.483-1.102) had an insignificantly lower risk of AKI. When compared between drug classes, atypical antipsychotics had a significantly higher risk of AKI (HR 1.313, 95% CI 1.083-1.591) than typical antipsychotics. CONCLUSIONS: Antipsychotics are associated with differential AKI risks, with several atypical antipsychotics having higher risks than haloperidol. However, the overall incidence of AKI was moderate, and AKI risk should only raise concern for clinicians with elderly patients or patients who are vulnerable to kidney disease.

Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: Data from the Veterans administration.

BACKGROUND AND AIMS: Data addressing real world effectiveness of direct acting antiviral agents in hepatitis C infected patients are now emerging. This study compared the sustained virologic response rates achieved 12 weeks post-treatment in patients treated with three such agents by the Veterans Health Administration. METHODS: A retrospective cohort study was conducted using patients who terminated treatment by July 1, 2015. Data were retrieved from the Veterans Health Administration electronic medical records system. Patients were included if sufficient viral load laboratory data were available to determine sustained virologic response. Applying an intention to treat approach and logistic regression analysis, the sustained virologic response rates achieved were compared across drug regimens. RESULTS: A total of 11 464 patients met study selection criteria. Without controlling for other risk factors, sustained virologic response at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients. After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate sustained virologic response. Human immunodeficiency virus, hepatitis B infection, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact sustained virologic response rates. Sustained virologic response rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a sustained virologic response. CONCLUSIONS: All three direct acting antiviral regimens appear highly effective in achieving sustained virologic response.

The Impact of Delayed Hepatitis C Viral Load Suppression on Patient Risk: Historical Evidence from the Veterans Administration.

BACKGROUND: The high cost of new hepatitis C (HCV) treatments has resulted in "watchful waiting" strategies being developed to safely delay treatment, which will in turn delay viral load suppression (VLS). OBJECTIVE: To document if delayed VLS adversely impacted patient risk for adverse events and death. METHODS: 187,860 patients were selected from the Veterans Administration's (VA) clinical registry (CCR), a longitudinal compilation of electronic medical records (EMR) data for 1999-2010. Inclusion criteria required at least 6 months of CCR/EMR data prior to their HCV diagnosis and sufficient data post-diagnosis to calculate one or more FIB-4 scores. Primary outcome measures were time-to-death and time-to-a composite of liver-related clinical events. Cox proportional hazards models were estimated separately using three critical FIB-4 levels to define early and late viral response. RESULTS: Achieving an undetectable viral load before the patient's FIB-4 level exceed pre-specified critical values (1.00, 1.45 and 3.25) effectively reduced the risk of an adverse clinical events by 33-35% and death by 21-26%. However, achieving VLS after FIB-4 exceeds 3.25 significantly reduced the benefit of viral response. CONCLUSIONS: Delaying VLS until FIB-4 >3.25 reduces the benefits of VLS in reducing patient risk.

Clozapine revisited: Impact of clozapine vs olanzapine on health care use by schizophrenia patients on Medicaid.

BACKGROUND: Our purpose was to evaluate health care use and cost patterns for clozapine compared with olanzapine in the treatment of schizophrenia. METHODS: Health care outcomes were measured over a 1-year posttreatment period for episodes of antipsychotic therapy initiated between 1997 and 2002. Four episode categories were defined: restart after lapse in therapy, switch after break, switch without break, and augmentation. We estimated the impact of clozapine or olanzapine using mixed model regression for costs by type of service and days of uninterrupted drug therapy. Time to admission in an acute hospital, psychiatric hospital, or longterm care facility, and time to suicide attempt were compared using Cox proportional hazards models. RESULTS: Clozapine increased duration of therapy and decreased risk of psychiatric hospitalization or suicide attempts compared to olanzapine. However, increased drug costs and use of community mental health centers (CMHC) for complete blood count (CBC) monitoring overwhelmed any offsetting savings. CONCLUSIONS: Clozapine is more expensive than olanzapine over the first year of treatment, primarily due to frequent CMHC visits required for CBC monitoring. However, fewer psychiatric hospitalizations, reduced suicide attempts, and longer duration of treatment should generate more benefits over time, which could eventually outweigh clozapine's higher first-year costs.

The risk of long-term morbidity and mortality in patients with chronic hepatitis C: results from an analysis of data from a Department of Veterans Affairs Clinical Registry.

IMPORTANCE: The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV. OBJECTIVE: To describe the natural history of HCV in real-world clinical practice. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study. Patients with a detectable viral load (>25 IU/mL) and a recorded baseline genotype were selected from the Veterans Affairs (VA) HCV clinical registry (CCR), which compiles electronic medical records data from 1999 to present. EXPOSURES: Risk factors included genotype, race, age, sex, and time to achieving an observed undetected viral load. MAIN OUTCOMES AND MEASURES: The primary outcomes were time to death and time to a composite of liver-related clinical events. Secondary outcomes included the components of the composite clinical outcome. Outcomes were measured using a time-to-event format and were analyzed using Cox proportional hazards models. RESULTS A total of 28,769 of 360,857 unique HCV CCR patients met all study criteria. Only 24.3% of patients received treatment, and 16.4% of treated patients (4.0% of all patients) achieved an undetectable viral load. The unadjusted death rates were 6.8 (95% CI, 6.0-7.7) per 1000 person-years for patients who achieved viral load suppression vs 21.8 (95% CI, 21.5-22.2) deaths per 1000 person-years in patients who did not achieve this goal. Cox model results found that achieving viral suppression reduced risk of the composite clinical end point by 27% (hazard ratio [HR], 0.73 [95% CI, 0.66-0.82]) and the risk of death by 45% (HR, 0.55 [95% CI, 0.47-0.64]). Genotype 2 patients were at significantly lower risk, and genotype 3 patients were at higher risk for all study outcomes relative to genotype 1. Black patients were at lower risk for all liver events than white patients. CONCLUSION AND RELEVANCE: Achieving an undetectable viral load was associated with decreased hepatic morbidity and mortality. It remains to be determined whether newer treatment regimens can offer higher response rates with fewer adverse effects in real-world settings.

Primary nonadherence to medications in an integrated healthcare setting.

OBJECTIVES: To measure primary nonadherence (PNA) rates for 10 therapeutic drug groups and identify factors associated with PNA to chronic and acute medications. STUDY DESIGN: Retrospective cohort study. METHODS: New prescriptions written in an integrated healthcare system for study drugs were identified between December 1, 2009, and February 28, 2010. PNA was defined as the failure to fill a prescription within 14 days of when it was written. PNA rates were calculated by drug group and descriptive statistics were performed. Multivariable logistic regression was used to identify significant patient, provider, and prescription characteristics associated with PNA. Results were stratified by acute versus chronic treatment. RESULTS: A total of 569,095 new prescriptions were written during the 3-month period. Across all drug groups, the PNA rate was 9.8%. PNA rates for individual drug groups varied and were highest for osteoporosis medications (22.4%) and antihyperlipidemics (22.3%). Patients who filled at least 1 prescription in the prior year (odds ratio [OR], 95% confidence interval [CI] for acute = 0.06 [0.06-0.07], for chronic = 0.11 [0.10-0.12]) or had a prescription for a symptomatic disease (OR = 0.51 [0.48-0.53]) were more likely to fill their prescription. Patients were more likely to be primary nonadherent if they were black (OR acute = 1.30 [1.25-1.36], chronic = 1.26 [1.18-1.33]) or treatment-naive to therapy (OR acute = 2.52 [2.36-2.7], chronic=1.07 [1.03-1.12]). CONCLUSIONS: Overall PNA was 9.8% but individual PNA rates varied by therapeutic drug group. Factors of PNA were mostly consistent across drug groups, but some depended on whether the treatment was acute or chronic.

Effect of exenatide, pen insulin, and vial insulin on patient outcomes: a retrospective database analysis of persistence and first-year costs in a commercially insured population.

OBJECTIVE: We compared health care costs and medication persistence for patients with type 2 diabetes initiating treatment using exenatide, pen insulin, or vial insulin. METHODS: Commercial health plan data (2004-2008) were used to identify episodes of antidiabetic drug therapy, which were then classified according to treatment history: first observed treatment, restarting a previous therapy (90-day gap in all treatment), switching therapy, and augmentation therapy. Three time periods were defined for each episode: the month in which the episode was initiated (index month), 6 months before the index month (preindex period), and 12 months after the index month (postindex period). All exenatide and insulin episodes were selected for this analysis of persistence and first-year costs. Multivariate statistical methods were adjusted for demographic characteristics, drug use history, previous medical care use, comorbid medical conditions, and prescription drug profile. Several sensitivity analyses were conducted. RESULTS: A total of 213,701 episodes of antidiabetic drug therapy were identified, of which 7031 patients were initiated using exenatide, 21,011 used vial insulin, and 422 used pen insulin. Time to all-cause discontinuation (TTAD) was measured for the index drug and all diabetic-related drugs. Pen insulin was discontinued 91 days earlier than exenatide, whereas vial insulin was continued 18 days longer than exenatide. Patients using pen insulin discontinued all antidiabetic drugs 34 days earlier than patients on exenatide, whereas patients using exenatide and vial insulin exhibited similar TTAD for all drugs. Exenatide use was estimated to significantly reduce medical costs of the first posttreatment year sufficient to offset higher prescription drug costs. These results were confirmed using propensity score matching estimation and were robust across episode type. CONCLUSIONS: Patients initiating drug therapy using exenatide might incur lower posttreatment costs than similar patients who initiated treatment using insulin.

Economic burden associated with patients diagnosed with hepatitis C.

BACKGROUND: New therapies for Hepatitis C virus (HCV) are under development that will augment pegylated interferon-alpha plus ribavirin to improve patient outcomes. Data documenting the incremental economic and health burden of patients with HCV relative to those who are not infected with HCV will be required to evaluate the comparative effectiveness of these new therapies. OBJECTIVE: The objective of this study was to estimate the incremental impact of HCV infection on health care costs and risk of adverse health events. METHODS: Paid claims data for commercially insured patients in the United States were used to identify 2 matched cohorts of 8861 patients with and without HCV infection. Propensity score matching was used to adjust for patient demographics, diagnostic mix, prior use, and drug profile. Patients with prior cirrhosis, liver cancer, or liver transplantation were excluded. Differences in the first postindex year associated with the diagnosis of an HCV infection were estimated for adverse event risk (logistic regression), costs (ordinary least square regression), and utilization counts (generalized linear models), controlling for patient demographics, prior use, comorbidity profile, and prescription drug profile. RESULTS: The costs of treating patients infected with HCV and a matched sample not infected with HCV were $37,390 and $13,575, respectively. The incremental cost of HCV infection was estimated at +$23,406, primarily because of higher costs for ambulatory care (+$6531), hospital services (+$1827), and prescription drugs (+$6935). The presence of HCV was associated with a significantly higher risk of hospitalization (odds ratio [OR] = 2.5) and number of hospital admissions (+186%); depression (OR = 2.2); cirrhosis (OR = 65.8); hepatic cancer (OR = 28.1), and liver transplantation (OR = 46.1; P < 0.0001 for all estimates). CONCLUSIONS: A diagnosis of HCV infection was correlated significantly with increased adverse event risk and increased health care costs. New alternative treatments are needed that are more efficacious and less burdensome for the patient. Limitations of this study are that only 1 year was used to screen for preexisting conditions and events and that paid claims data do not capture indirect HCV infection costs such as time lost from work.

Impact of drug treatment history on comparative effectiveness research in schizophrenia.

OBJECTIVES: Randomized clinical trials frequently attract volunteer patients who were either non-compliant or seeking to switch therapies. Patients on active therapies often undergo a washout period after which a single medication is initiated. Observational research has the potential to compare alternative treatments under a wider range of clinical situations if care is taken to document each patient's treatment history. METHODS: This study used paid claims data from a large commercial insurer to investigate drug therapy outcomes in schizophrenia. Episodes of drug therapy were defined each time a patient initiated or restarted drug therapy using an antipsychotic, antidepressant or mood stabilizing medication. Episode definitions were based on calculations of continuous drug therapy using a 15-day gap definition. A total of 21,570 episodes of drug therapy were included in the analysis, some of which used two drugs as initial therapy. RESULTS: Most episodes were initiated using a mood stabilizing drug (27%) or an antidepressant (38%). Over 62% of all episodes were augmentation therapy in which a psychotropic drug was added to an existing psychotropic medication, followed by switching episodes (22%) and restart episodes (16%). Patient outcomes measured by either duration of uninterrupted therapy or one-year post-treatment cost varied significantly with patient treatment history, especially episode type. The comparative effectiveness of alternative therapies is sensitive to the extent to which treatment history is taken into account. CONCLUSIONS: Observational comparative effectiveness research should capture and evaluate patient outcomes across a wide range of patients taking into account the patient's treatment history.

The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system.

BACKGROUND: Preventing fetal exposure to isotretinoin is widely acknowledged as an important safety issue. The iPLEDGE program is the latest in a series of Food and Drug Administration-mandated risk management programs designed to prevent pregnancies in female patients of childbearing potential (FCBP) taking isotretinoin. OBJECTIVE: We sought to evaluate the effect of iPLEDGE relative to the prior risk management program (system to manage Accutane-related teratogenicity [SMART]) on the risk of isotretinoin fetal exposure in FCBP in a managed care setting. METHODS: All FCBP at Kaiser Permanente Southern and Northern California who filled at least one prescription for isotretinoin during a 4-year period (March 1, 2004, to February 29, 2008) were included in this retrospective cohort study (n = 8344). Chart review was performed to confirm fetal exposures and outcomes. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals. RESULTS: There were a total of 29 fetal exposures and 9912 isotretinoin treatment courses. After iPLEDGE was implemented, the unadjusted rate of fetal exposure decreased from 3.11 to 2.67 per 1000 treatment courses (P = .69). The hazard ratio = 0.76 (95% confidence interval 0.36-1.61) for fetal exposures to isotretinoin during treatment courses filled after iPLEDGE implementation compared with SMART. LIMITATIONS: Limitations include limited generalizability of results, small sample size (n = 29 total documented fetal exposures), and potential uncontrolled confounders. CONCLUSION: Evaluating the impact of iPLEDGE on isotretinoin fetal exposures is important in understanding the full risks and benefits of isotretinoin treatment. We found no evidence that iPLEDGE significantly decreased the risk of fetal exposure in FCBP compared to the SMART program.

A1C and cardiovascular outcomes in type 2 diabetes: a nested case-control study.

OBJECTIVE: Type 2 diabetes is associated with increased cardiovascular risk. The role of aggressive glycemic control in preventing cardiovascular events is unclear. A nested case-control study design was used to evaluate the association between average A1C and cardiovascular outcomes. RESEARCH DESIGN AND METHODS: Adults with type 2 diabetes were identified among members of Kaiser Permanente Southern California. Type 2 diabetes was identified based on ICD-9 diagnosis codes and either A1C >7.5% or prescriptions for hypoglycemic agents. Case subjects were defined based on nonfatal myocardial infarction, nonfatal stroke, or death attributed to cardiovascular events during a 3-year window. Four type 2 diabetes control subjects were matched to each case subject based on age, sex, and index date for the corresponding case. A conditional logistic regression model was used to estimate the odds ratio of cardiovascular events and compare three patient groups based on average A1C measured in the preindex period (≤6, >6-8, >8%). RESULTS: A total of 44,628 control subjects were matched to 11,157 case subjects. Patients with an average A1C ≤6% were 20% more likely to experience a cardiovascular event than the group with an average A1C of >6-8% (P < 0.0001). Patients with an average A1C >8% experienced a 16% increase in the likelihood of a cardiovascular event (P < 0.0001). We found evidence of statistical interaction with A1C category and LDL level (P = 0.0002), use of cardiovascular medications (P = 0.02), and use of antipsychotics (P = 0.001). CONCLUSIONS: High-risk patients with type 2 diabetes who achieved mean A1C levels of ≤6% or failed to decrease their A1C to <8% are at increased risk for cardiovascular events.

Applying comparative effectiveness research methods in bipolar disorders.

BACKGROUND: Randomized clinical trials [RCT] are the Gold Standard of medical evidence. However, observational comparative effectiveness research [CER] based on real-world data is receiving national attention. This paper demonstrates how observational CER can fill important gaps in clinical knowledge left behind by RCT approaches. An example of CER in bipolar disorders is presented. METHODS: Paid claims data from a large commercial insurer were used to identify episodes of drug therapy. Episodes were defined each time a patient initiated or restarted therapy using an antipsychotic, antidepressant or mood stabilizing medication. Episode definitions were based on calculations of continuous days of drug therapy using a 15 day gap definition. 105,440 episodes of drug therapy were included in the analysis. RESULTS: Most episodes were initiated using a mood stabilizing drug (40%) or an antidepressant (40%). Over 59% of all episodes were for augmentation therapy, followed by switching episodes (25%) and restart episodes (16%). Patient outcomes measured by either duration of uninterrupted therapy or one-year post-treatment cost varied significantly with patient treatment history, especially episode type. The comparative effectiveness of alternative therapies was sensitive to the extent to which treatment history is taken into account. CONCLUSIONS: Observational research can evaluate patient outcomes across a wide range of clinical presentations with regard to the patient's treatment history. Treatment history is a major determinant of patient compliance and future treatment costs. Failure to account for treatment history can introduce bias into comparative effectiveness results. Observational CER research can also uncover important questions that require future research.