Building Research Infrastructure to Develop Greater Learning Efficiencies (BRIDGE).

In this manuscript, we outline our developed version of a Learning Health System (LHS) in oncology implemented at the Department of Veterans Affairs (VA). Transferring healthcare into an LHS framework has been one of the spearpoints of VA's Central Office and given the general lack of evidence generated through randomized control clinical trials to guide medical decisions in oncology, this domain is one of the most suitable for this change. We describe our technical solution, which includes a large real-world data repository, a data science and algorithm development framework, and the mechanism by which results are brought back to the clinic and to the patient. Additionally, we propose the need for a bridging framework that requires collaboration between informatics specialists and medical professionals to integrate knowledge generation into the clinical workflow at the point of care.

Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Differences in treatment effect among clinical subgroups in a randomized clinical trial of long-acting injectable risperidone and oral antipsychotics in unstable chronic schizophrenia.

A long-term randomized trial of unstable patients with schizophrenia found no benefit of long-acting injectable (LAI) risperidone over oral treatment in preventing or delaying time to psychiatric hospitalizations or on clinical outcomes. The initial analyses did not examine whether benefits of LAI emerged in selected subgroups.Patients with schizophrenia or schizoaffective disorder who had been hospitalized within the past 2 years or judged to be at risk for hospitalization because of increasing psychiatric service use were randomly assigned to LAI risperidone 12.5 to 50 mg per injection biweekly or to the psychiatrist's choice of oral antipsychotics and followed for up to 2 years. The primary endpoint was psychiatric rehospitalization. Symptoms, quality of life, and global functioning were assessed through blinded videoconference interviews. Cox's regression and mixed effects models were used to assess difference in treatment effect within 12 subgroups defined by hospitalization at study entry, substance abuse, race, symptom severity, quality of life, body mass index, age, race or sex, or reported medication compliance.Mixed models and Cox's regression using up to 24 months of follow-up data showed no significant differences in treatment effect in 10 of 12 subgroups on psychiatric symptoms, quality of life, or time to hospitalization. With adjustment for multiple comparisons, treatment effect differed by race on substance use outcomes, with white participants showing more benefit from LAI than other groups.LAI risperidone showed no superiority to psychiatrist's choice of oral treatment in most clinically defined subgroups, although the white patients benefited more than the other groups on substance abuse outcomes.

Assessment of the minimum clinically important difference in quality of life in schizophrenia measured by the Quality of Well-Being Scale and disease-specific measures.

This study examines the psychometric properties of the Quality of Well Being Scale (QWB), the Positive and Negative Syndrome Scale (PANSS), the Heinrich-Carpenter Quality of Life Scale (QOLS), and the Lenert PANSS-based utility measure in a cohort of patients with schizophrenia and identifies threshold values of clinically meaningful change using the Clinical Global Impressions scale (CGI), as the anchor. The correlation of these measures at baseline and change at 6 and 12 months post enrollment in a comparative effectiveness trial was evaluated in 350 veterans with schizophrenia or schizoaffective disorder. An equipercentile method was used to estimate the minimum clinically important difference (MCID) for each measure. Effect size of 0.30-0.50 for baseline quality of life associated with inpatient status supported concurrent validity. The QWB was moderately correlated with disease-specific measures. The MCID as detected by the CGI at 6 months was 0.17 for QWB, 0.15 for the Lenert utility score, 1.13 for the QOLS, and 20.2 for the PANSS. These differences were stable at 12 months. The QWB is significantly correlated with disease specific measures of health related quality of life in schizophrenia.

Long-acting risperidone and oral antipsychotics in unstable schizophrenia.

BACKGROUND: Long-acting injectable risperidone, a second-generation antipsychotic agent, may improve adherence to treatment and outcomes in schizophrenia, but it has not been tested in a long-term randomized trial involving patients with unstable disease. METHODS: We randomly assigned patients in the Veterans Affairs (VA) system who had schizophrenia or schizoaffective disorder and who had been hospitalized within the previous 2 years or were at imminent risk for hospitalization to 25 to 50 mg of long-acting injectable risperidone every two weeks or to a psychiatrist's choice of an oral antipsychotic. All patients were followed for up to 2 years. The primary end point was hospitalization in a VA or non-VA psychiatric hospital. Symptoms, quality of life, and functioning were assessed in blinded videoconference interviews. RESULTS: Of 369 participants, 40% were hospitalized at randomization, 55% were hospitalized within the previous 2 years, and 5% were at risk for hospitalization. The rate of hospitalization after randomization was not significantly lower among patients who received long-acting injectable risperidone than among those who received oral antipsychotics (39% after 10.8 months vs. 45% after 11.3 months; hazard ratio, 0.87; 95% confidence interval, 0.63 to 1.20). Psychiatric symptoms, quality of life, scores on the Personal and Social Performance scale of global functioning, and neurologic side effects were not significantly improved with long-acting injectable risperidone as compared with control treatments. Patients who received long-acting injectable risperidone reported more adverse events at the injection site and more extrapyramidal symptoms. CONCLUSIONS: Long-acting injectable risperidone was not superior to a psychiatrist's choice of oral treatment in patients with schizophrenia and schizoaffective disorder who were hospitalized or at high risk for hospitalization, and it was associated with more local injection-site and extrapyramidal adverse effects. (Supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs; ClinicalTrials.gov number, NCT00132314.).

Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia.

BACKGROUND: The introduction of antipsychotic medication has been a major advance in the treatment of schizophrenia and allows millions of people to live outside of institutions. It is generally believed that long-acting intramuscular antipsychotic medication is the most effective approach to increasing medication adherence and thereby reduce relapse in high-risk patients with schizophrenia, but the data are scant. PURPOSE: To report the design of a study to assess the effect of long-acting injectable risperidone in unstable patients and under more realistic conditions than previously studied and to evaluate the effect of this medication on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs. METHODS: The trial was an open randomized clinical comparative effectiveness trial in patients with schizophrenia or schizo-affective disorders in which parenteral risperidone was compared to an oral antipsychotic regimen selected by each control patient's psychiatrist. Participants had unstable psychiatric disease defined by recent hospitalization or exhibition of unusual need for psychiatric services. The primary endpoint was hospitalization for psychiatric indications; the secondary endpoint was psychiatric symptoms. RESULTS: Overall, 382 patients were randomized. Determination of a persons' competency to understand the elements of informed consent was addressed. The use of a closed-circuit TV interview for psychosocial measures provided an economical, high quality, reliable means of collecting data. A unique method for insuring that usual care was optimal was incorporated in the follow-up of all subjects. LIMITATIONS: Patients with schizophrenia or schizo-affective disorders and with the common co-morbid illnesses seen in the VA are a challenging group of subjects to study in long-term trials. Some techniques unique in the VA and found useful may not be generalizable or applicable in other research or treatment settings. CONCLUSIONS: The trial tested a new antipsychotic medication early in its adoption in the Veterans Health Administration. The VA has a unique electronic medical record and database which can be used to identify the endpoint, that is, first hospitalization due to a psychiatric problem, with complete ascertainment. Several methodologic solutions addressed competency to understand elements of consent, the costs and reliability of collecting interview data gathering, and insuring usual care.

Competition among hospitals for HMO business: effect of price and nonprice attributes.

OBJECTIVE: To investigate patterns of competition among hospitals for the business of health maintenance organizations (HMOs). The study focused on the relative importance of hospital price and nonprice attributes in the competition for HMO business. DATA SOURCES/STUDY SETTING: The study capitalized on hospital cost reports from Florida that are unique in their inclusion of financial data regarding HMO business activity. The time frame was 1992 to 1997. STUDY DESIGN: The study was designed as an observational investigation of acute care hospitals. PRINCIPAL FINDINGS: Results indicated that a hospital's share of HMO business was related to both its price and nonprice attributes. However, the importance of both price and nonprice attributes diminished as the number of HMOs in a market increased. Hospitals that were market share leaders in terms of HMO business (i.e., 30 percent or more market share) were superior, on average, to their competitors on both price and nonprice attributes. CONCLUSIONS: Study results indicate that competition among hospitals for HMO business involves a complex set of price and nonprice attributes. The HMOs do not appear to focus on price alone. Hospitals likely to be the most attractive to HMOs are those that can differentiate themselves on the basis of nonprice attributes while being competitive on price as well.

The financial experience of hospitals with HMO contracts: evidence from Florida.

In this paper, we report results from the first study to systematically examine trends in the financial experience of hospitals with health maintenance organization (HMO) contracts. The longitudinal analysis (1990 through 1997) focused on hospitals in Florida. Hospital operating margins for HMO contracts grew tighter toward the end of the study period when the median margin was less than 1%. Teaching hospitals had operating margins that on average were below that of their nonteaching counterparts. The continued growth of HMOs and other managed care entities may have important implications for the future financial viability of U.S. hospitals.