Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator.

BACKGROUND: Adoption of high-throughput, gene panel-based, next-generation sequencing (NGS) into routine cancer care is widely supported, but hampered by concerns about cost. To inform policies regarding genomic testing strategies, we propose a simple metric, cost per correctly identified patient (CCIP), that compares sequential single-gene testing (SGT) vs. multiplex NGS in different tumor types. MATERIALS AND METHODS: A genomic testing cost calculator was developed based on clinically actionable genomic alterations identified in the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets. Using sensitivity/specificity data for SGTs (immunohistochemistry, polymerase chain reaction, and fluorescence in situ hybridization) and NGS and marker prevalence, the number needed to predict metric was monetarized to estimate CCIP. RESULTS: At base case, CCIP was lower with NGS than sequential SGT for advanced/metastatic non-squamous non-small cell lung cancer (NSCLC), breast, colorectal, gastric cancers, and cholangiocarcinoma. CCIP with NGS was also favorable for squamous NSCLC, pancreatic, and hepatic cancers, but with overlapping confidence intervals. CCIP favored SGT for prostate cancer. Alternate scenarios using different price estimates for each test showed similar trends, but with incremental changes in the magnitude of difference between NGS and SGT, depending on price estimates for each test. CONCLUSIONS: The cost to correctly identify clinically actionable genomic alterations was lower for NGS than sequential SGT in most cancer types evaluated. Decreasing price estimates for NGS and the rapid expansion of targeted therapies and accompanying biomarkers are anticipated to further support NGS as a preferred diagnostic standard for precision oncology.

Modification of existing patient-reported outcome measures: qualitative development of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM).

PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung pleura. The MD Anderson Symptom Inventory (MDASI) is a patient-reported outcome (PRO) measure of symptom burden, the combined impact of disease-related and treatment-related symptoms on functioning. Validated PRO measures may require modification for use in specific study populations. We sought to modify the MDASI for patients with MPM and create a fit-for-purpose symptom-burden measure for use in a clinical trial, according to US Food and Drug Administration guidance on PRO utilization to support labeling claims. METHODS: A literature review for MPM symptoms was conducted. Patients with MPM were qualitatively interviewed about experiences of disease and treatment. Descriptive analysis identified symptoms and interference with functioning to define MPM-related symptom burden. An expert panel rated the relevance of identified symptoms to patients with MPM. Patients who received the investigational drug in a previous Phase I study were interviewed for drug-specific symptoms. RESULTS: Literature review and interviews of 20 patients identified 31 MPM-related symptoms. A conceptual model of MPM-related symptom burden was developed. After expert-panel relevance review, five MPM-specific items and the 13 core MDASI symptoms met criteria for inclusion in a provisional MDASI-MPM for psychometric testing. Interviews with six patients identified six drug-specific symptoms; three were mentioned by multiple patients. Of these three, one was not in the core MDASI. CONCLUSIONS: The MDASI-MPM has established content validity and, with the addition of one symptom item, is ready for psychometric testing as fit-for-purpose for a clinical trial of an investigational agent.

Developing a fit-for-purpose composite symptom score as a symptom burden endpoint for clinical trials in patients with malignant pleural mesothelioma.

We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92-0.94) and the Lung Cancer Symptom Scale-Mesothelioma (0.79-0.87) at each co-administration of the scales. The CSS also had good sensitivity to worsening disease and global quality-of-life ratings. The MDASI-MPM CSS can be used as an outcome in MPM clinical trials, including in responder analyses and at the individual patient level. It is brief enough to administer frequently, including electronically, to better capture symptom trajectories during and after a trial and in clinical practice. As a single score, the CSS addresses multiplicity issues that can arise when several symptoms increase due to worsening disease. Our process can be adapted to produce a CSS for other advanced-cancer trials.

Transforming approaches to treating TRK fusion cancer: historical comparison of larotrectinib and histology-specific therapies.

OBJECTIVE: The results from basket trials utilized to gain regulatory approval of tumor-agnostic therapies can be difficult to interpret without the context of a comparator arm. We describe the role and efficacy of histology-based treatments to provide a historical comparison with larotrectinib. METHODS: A systematic literature review (SLR) was conducted on the clinical outcomes of current histology-based standard of care treatments used in non-small cell lung cancer, colorectal cancer, thyroid cancer, gliomas, soft tissue sarcoma, salivary gland cancer, and infantile fibrosarcoma (7 of the 21 tumor histologies in the larotrectinib trials). The review focused on advanced stage/metastatic disease to make a historical comparison with larotrectinib. RESULTS: Larotrectinib provides positive outcomes in both adult and pediatric patients with advanced or metastatic solid tumors known to harbor NTRK gene fusions across a wide range of tumor types. Although the numbers of patients per tumor type are limited, the results of this historical comparison demonstrated that larotrectinib is an efficacious treatment option when naïvely indirectly compared with historical treatments across all 7 reviewed tumor types, especially in comparison to later lines of therapy. CONCLUSIONS: Utilizing larotrectinib as a case example across these types of historical comparisons shows that larotrectinib provides positive efficacy outcomes in TRK fusion cancer across tumor histologies known to harbor NTRK gene fusions that may be preferable to historical treatments.

Dose trends for second-generation antipsychotic treatment of schizophrenia and bipolar disorder.

BACKGROUND: Antipsychotic dosing used in clinical practice can differ from dosing originally recommended in product labeling. This has been reported for olanzapine and quetiapine, where higher doses are commonly used. This may be the case for ziprasidone as well. METHOD: To characterize changes over time in dosing for the initial and subsequent prescriptions of first-line second-generation antipsychotics used during treatment episodes for outpatients with schizophrenia and bipolar disorder, the 2001-2005 Thomson MarketScan Medicaid Database (Medicaid) and the 2001-2006 MarketScan Commercial Claims and Encounters Database (Commercial) were analyzed. Dose trends were evaluated using autoregressive time-series models. RESULTS: Data were available for 49180 treatment episodes of schizophrenia (4683 Commercial and 44497 Medicaid) and 83289 treatment episodes of bipolar disorder (57961 Commercial and 25328 Medicaid). The initial prescription mean daily and overall mean daily doses of ziprasidone in schizophrenia episodes significantly increased across the Medicaid and Commercial populations, with similar trends observed for bipolar episodes. The first (May 2001) and last (December 2005) observed 3-month mean daily doses for ziprasidone were 112 mg/d and 138 mg/d for patients with schizophrenia and 93 mg/d and 113 mg/d for those with bipolar disorder in the Medicaid cohort, with similar findings for the Commercial cohort. Consistently significant trends in dose changes were not observed for the other medications, although quetiapine and olanzapine doses generally increased while aripiprazole and risperidone doses generally decreased. CONCLUSIONS: There remains a need for controlled randomized clinical trials that test fixed doses of antipsychotics to ascertain the dose-response relationship within the dose range used in contemporary clinical practice.

Metabolic risk status and second-generation antipsychotic drug selection: a retrospective study of commercially insured patients.

BACKGROUND: Routine metabolic screening and consideration of patient metabolic status in the choice of a second-generation antipsychotic (SGA) medication are recommended. This study evaluated the association between abnormal blood glucose and lipid values and SGA prescribing patterns. MATERIALS AND METHODS: A retrospective cohort study using administrative data from 2 managed care plans in the United States evaluated 7904 adults initiating SGA therapy between 2001 and 2004. Baseline serum glucose, total cholesterol, and triglyceride values were available for 989 patients (12.5%), and follow-up assessments were done in 699 patients (8.8%). Abnormal values were defined as the following: total cholesterol, 200 mg/dL or higher; triglycerides, 200 mg/dL or higher; and glucose, 126 mg/dL or higher. The likelihood of abnormal laboratory values being associated with selection of a lower metabolic risk SGA drug (aripiprazole or ziprasidone) and with switching decisions was assessed using multivariate logistic regression models. RESULTS: Thirteen percent of the patients had glucose and lipid tests within 6 months of starting SGA therapy. The likelihood of starting a patient on an SGA drug with lower metabolic risk (ziprasidone: odds ratio, 3.26; 95% confidence interval, 1.25-8.47; aripiprazole: odds ratio, 2.13; 95% confidence interval, 0.77-5.88) was higher if the patient had elevated glucose values but was not associated with elevated cholesterol or triglyceride values or if the patient had preexisting diabetes or dyslipidemia. Abnormal glucose and lipid values were not associated with switching SGA medications in the first 6 months of therapy. Among patients who did switch SGA medications, elevated glucose and lipid values were not associated with a greater likelihood of switching to aripiprazole or ziprasidone. CONCLUSIONS: Low rates of recommended monitoring were observed. Abnormal metabolic parameters among those who were tested were not consistently associated with the selection of an SGA drug with lower metabolic risk.

Evaluation of the psychometric properties and minimally important difference of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM).

BACKGROUND: Symptom assessment requires psychometrically validated questionnaires that are easy to use, relevant to the disease, and quick to administer. The MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM) was adapted from the general (core) MDASI to assess the severity of cancer-related and treatment-related symptoms specific to patients with this condition. The MDASI-MPM includes the 13 core MDASI symptoms, which are experienced by most cancer patients, and 6 MPM-specific items developed via qualitative interviewing, a method favored by the US Food and Drug Administration for instrument item generation and development. Qualitative interviewing that summarizes the item generation and development for the MDASI-MPM is detailed in a separate report. The psychometric study reported here was the next step in developing the validation dossier for the MDASI-MPM. RESULTS: In this secondary analysis of data from a Phase II trial, 248 patients provided MDASI-MPM data at multiple timepoints during therapy. Over time, fatigue, pain, shortness of breath, feeling of malaise, and muscle weakness were consistently the worst symptoms reported; symptoms interfered most with work and general activity and least with relations with others. Cronbach coefficient alpha values for all MDASI-MPM subscales were at least 0.88 at baseline and 0.91 during treatment, indicating good internal consistency reliability. Intraclass correlations of at least 0.86 for all MDASI-MPM subscales administered a cycle apart (n = 82) were indicative of good test-retest reliability. Correlations between MDASI-MPM subscales and LCSS-Meso scores were at least 0.70 (P < 0.001 for all comparisons). Patients with good performance status had significantly lower scores than did patients with poor performance status (all P < 0.05), supporting evidence for known-group validity and sensitivity. Effect-size differences were 0.69 and higher, indicating medium-to-large effects. The minimally important difference in the MDASI-MPM subscales ranged from 1.0 to 1.5 points on a 0-10 scale. CONCLUSIONS: Symptoms specific to a particular cancer, treatment method, or treatment site can be added to the core MDASI to create a tailored, "fit for purpose" instrument. We found the MDASI-MPM to be a valid, reliable, and responsive (sensitive) instrument for assessing the severity of symptoms of patients with MPM and their interference in patients' daily functioning.

Risk of discontinuation of atypical antipsychotic agents in the treatment of schizophrenia.

OBJECTIVES: To compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia. METHOD: Adult Maryland Medicaid patients with schizophrenia were categorized based on initial atypical antipsychotic drug received: aripiprazole (n=446); olanzapine (n=1705); quetiapine (n=1467); risperidone (n=1580); and ziprasidone (n=700). Discontinuation was measured using refill patterns, allowing 14-day gaps between refill dates. Using olanzapine as the reference drug, the hazard of discontinuation within the first year of follow-up was compared across atypicals using Cox proportional hazard models adjusted for demographic and clinical covariates. Sensitivity analysis tested the robustness of results by using different definitions of the index date. RESULTS: At one-year follow-up, most patients discontinued their antipsychotic medication (90.4% adjusted mean discontinuation). The hazard ratio (HR) for discontinuing therapy in patients starting treatment on aripiprazole, risperidone, or ziprasidone was not significantly different from olanzapine [HR 1.047, 0.973 and 0.990, respectively]. Quetiapine was associated with significantly higher hazard of discontinuation [HR 1.130] than olanzapine. Covariates associated with significantly lower discontinuation were being male [HR 0.899], older age [HR 0.997] and being on concurrent medication when initiating therapy [HR 0.225]; having a previous hospitalization was associated with significantly higher discontinuation hazard [HR 1.276]. Results were robust in the sensitivity analysis. CONCLUSIONS: Discontinuation rates were high at one-year follow-up and did not differ significantly for patients on aripiprazole, olanzapine, risperidone, or ziprasidone. The higher hazard of discontinuation associated with quetiapine when compared to olanzapine is consistent with that observed in Phase I of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis: a systematic comparison.

The treatment of relapsing-remitting multiple sclerosis (RRMS) has become more effective over the last decade with the advent of the currently available disease-modifying therapies (DMTs). Pivotal clinical studies differ in many characteristics, such that cross-comparisons of relative risk reductions are of limited value and can be misleading. Our objective was to compare the clinical efficacy of currently approved first-line DMTs in patients with RRMS, applying an evidence-based medicine approach. We reviewed all phase III pivotal trials of DMTs. Six clinical trials of Avonex, Betaseron, Copaxone, Rebif and Tysabri in patients with RRMS were identified for analysis. Only randomized, placebo-controlled, double-blind studies were included. The clinical efficacy endpoints compared were: proportion of relapse-free patients at 1 and 2 years; annualized relapse rate at 2 years; proportion of progression-free patients at 2 years, and proportion of patients free of gadolinium-enhancing lesions at 1 year or 9 months. Based on these analyses, Betaseron, Rebif, and Tysabri show comparable effects, whereas for several endpoints Avonex or Copaxone did not significantly differ from placebo. In the absence of head-to-head studies for all products used to treat RRMS, it still may be possible to compare treatment effects by applying evidence-based medicine principles.

Comparison of cholinesterase inhibitor utilization patterns and associated health care costs in Alzheimer's disease.

BACKGROUND: Sustained treatment with a cholinesterase inhibitor (ChEI) is used in the management of the symptoms of Alzheimer's disease (AD). However, the characteristic declines in learning and memory seen in AD may erode the patient's ability to adhere to medication regimens with or without caregiver support. OBJECTIVES: To examine differences by type of ChEI in (1) monthly prevalence of use, (2) nonpersistence, (3) switching from the index drug to another ChEI, (4) number of days on therapy, (5) medication possession ratio (MPR), and (6) an estimate of the relationship of these characteristics to total annual health care expenditures. METHODS: Data were from the MarketScan Medicare Supplemental and Coordination of Benefits 2001-2003 database, which comprised 1.47 million Medicare beneficiaries during this 3-year time period. Inclusion criteria were: (1) aged 65 years or older; (2) at least 1 claim with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 331.0 for AD in any of 15 diagnosis fields on outpatient claims or any of 2 diagnosis fields on inpatient claims at any time during 18 months of observation; (3) at least 1 pharmacy claim for donepezil, galantamine, or rivastigmine preceded by a 6-month period without a ChEI claim; and (4) at least 12 months of follow-up data, for a minimum 18 months continuous enrollment. Multivariate analyses, including logistic regression and exponential conditional mean models, tested for cohort differences in ChEI utilization, controlling for demographics, region of the country, type of insurer, and the Charlson Comorbidity Index (comorbid diagnoses). Using exponential conditional mean models, we also examined the relationship between utilization characteristics and all-cause (i.e., not specific to AD) health care expenditures for a 12-month period, including inpatient and outpatient (physician) care, laboratory and radiology services, emergency room (ER) use, prescription drugs, and long-term care services (e.g., nursing home care, home health visits) paid by Medicare or private insurance, but excluding long-term care services paid by Medicaid. Expenditure was defined as allowed charge (i.e., the total payment received by the service provider including plan and patient paid amounts.) RESULTS: More than 70% of the patients who received ChEI therapy and who otherwise met the inclusion criteria were excluded from this study due to the absence of at least 1 claim with a diagnosis for AD. Of the 3,177 patients included in the study, the index ChEI was donepezil for 62.8% of the patients (n=1,994); 17.2% received galantamine (n=546) and 20.1% received rivastigmine (n=637). The total number of days of index therapy dispensed was greater for those starting on donepezil (mean [median, SD] days=226 [263, 115]) compared with rivastigmine (206 [233, 120], P<0.001), but was not significantly different compared with galantamine (216 [250, 119], P=0.085). Monthly prevalence of use was similar for the 3 drugs until month 5 when a smaller proportion of rivastigmine patients had index medication on hand (65.9%) compared with 72.1% of donepezil patients (P=0.003) and 72.7% of galantamine patients (P=0.012). At 12 months, the likelihood of receiving the index ChEI was higher for donepezil (61.1%) than for either rivastigmine (50.1%, P<0.001) or galantamine (56.4%, P=0.048) and was higher for galantamine than for rivastigmine (P=0.030). The rate of switching for donepezil patients was significantly lower (14.5%) than the switch rate for rivastigmine patients (21.5%, P<0.001) and was similar to the switch rate for galantamine patients (15.0%, P=0.781 for donepezil vs. galantamine; P=0.004 for galantamine vs. rivastigmine). Rates of nonpersistence, measured as having at least 1 gap in therapy of 30 days or more during the 1-year follow-up, were 63.5% for donepezil, 63.7% for galantamine (P=0.933 for donepezil vs. galantamine), and 68.0% for rivastigmine (P=0.042 for donepezil vs. rivastigmine). MPRs and total days supply of any ChEI did not significantly differ among the 3 drugs. Results of multivariate models showed that, controlling for index ChEI drug, each additional month of ChEI treatment was associated with a reduction of 1% in total all-cause health care costs. The mean (SD) total all-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different: $12,112 ($16,437) for donepezil, $12,137 ($19,154) for galantamine (P=0.978), and $12,853 ($14,543) for rivastigmine (P=0.278). CONCLUSIONS: During the first year following initiation of ChEI therapy, patients initiated on donepezil had a greater days supply of the index medication than did patients initiated on rivastigmine. At 12 months following treatment initiation, the proportion of patients in therapy was higher for donepezil than for either rivastigmine or galantamine and was higher for galantamine than for rivastigmine. Patients treated with either donepezil or galantamine were less likely to switch from the index drug to another ChEI than were patients treated with rivastigmine. All-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different.

Change in framingham risk score in patients with schizophrenia: a post hoc analysis of a randomized, double-blind, 6-week trial of ziprasidone and olanzapine.

OBJECTIVE: To examine the change in Framingham risk score (FRS) arising from short-term treatment with ziprasidone or olanzapine. METHOD: Hospitalized adults with a primary DSM-IV diagnosis of schizophrenia or schizo-affective disorder were randomly assigned to 6 weeks of double-blind treatment with ziprasidone or olanzapine from November 21, 1998 to September 28, 2000. Data on fasting lipid levels were collected at screening and endpoint, and blood pressure was measured at screening and baseline and weekly until week 6 of treatment (or last visit). FRS for patients aged ≥30 years was calculated using an algorithm derived from the Framingham Heart Study. Baseline-to-endpoint least-squares mean changes in age-adjusted FRS by gender were compared using analysis of covariance (baseline adjusted). RESULTS: Men who received olanzapine demonstrated a mean increase in their total cholesterol levels (+18.5 mg/dL; N = 53) and low-density lipoprotein cholesterol levels (+13.0 mg/dL; N = 45), whereas men who received ziprasidone demonstrated a mean decrease in their total cholesterol levels (-8.5 mg/dL; N = 44) and low-density lipoprotein cholesterol levels (-7.2 mg/dL; N = 40) (p = .0006 and p = .004, respectively). Additionally, men who received olanzapine showed an increase in baseline FRS (+7.69%; N = 53), whereas men who received ziprasidone showed a decrease in baseline FRS (-11.06%; N = 42) (p = .09). In women, treatment differences in FSR numerically favored ziprasidone but were not statistically significant. Neither treatment had a significant effect on blood pressure. CONCLUSION: In short-term treatment, olanza-pine was associated with a significant worsening of lipid profile compared with ziprasidone, with a consequent increase in FRS versus ziprasidone. These findings, coupled with the significant weight gain in patients treated with olanzapine versus ziprasidone, warrant investigation in longer-term trials.

The acceptability and effectiveness of patient-reported assessments and feedback in a managed behavioral healthcare setting.

OBJECTIVE: To determine whether providing clinicians with the results of a patient-reported mental health assessment would have a significant impact on patients' mental health outcomes. STUDY DESIGN: The study used a portion of the SCL-90 (Symptom Checklist-90) to track the perceived mental health of 1374 patients in a managed behavioral healthcare system over 6 weeks. METHODS: Participants were randomized into a feedback group whose clinicians received clinical feedback reports at intake and at 6 weeks, and a control group whose clinicians received no report. RESULTS: Patients in the feedback group achieved statistically significant improvement in clinical status relative to controls. CONCLUSIONS: Overall, the study suggests that patient-reported mental health assessments have the potential both to become acceptable to clinicians and to improve the effectiveness of clinical care.

Remission, residual symptoms, and nonresponse in the usual treatment of major depression in managed clinical practice.

BACKGROUND: Although published guidelines recommend the continuation of treatment for depression until full remission of symptoms and restoration of functioning, little is known about how often remission is achieved in usual practice and the precipitants of treatment termination when treatment outcome has not been optimal. METHOD: A naturalistic study design examined 1859 patients receiving treatment for DSM-III-R major depression between 1995 and 1997 in the national provider network of a managed behavioral health organization (MBHO). Symptom and impairment ratings by clinicians were used to group patients into full remission, partial remission, and no response. Claims data were used to characterize treatment and identify comorbid medical conditions. RESULTS: According to clinician ratings, approximately 27% to 39% of patients achieved full remission. Medical and substance use comorbidity and hospital admission were more common in those with a partial response to treatment. Only half of patients without a treatment response received a trial of medication during their treatment. Patient choice was the most common reason for termination of treatment, although nearly 40% of clinicians concurred with patients' decisions even when symptoms had not improved. CONCLUSION: Although rates of full remission were comparable to those in clinical trials of antidepressants, results suggest that clinicians may fail to recommend continuation and maintenance treatment consistent with best practice guidelines and that unsuccessful treatment often does not include antidepressant medication.

Two-year outcomes of fee-for-service and capitated medicaid programs for people with severe mental illness.

OBJECTIVE: To examine the effects of two models of capitation on the clinical outcomes of Medicaid beneficiaries in the state of Colorado. DATA SOURCE: A large sample of adult, Medicaid beneficiaries with severe mental illness drawn from regions where capitation contracts were (1) awarded to local community mental health agencies (direct capitation), (2) awarded to a joint venture between local community mental health agencies and a large, private managed behavioral health organization, and (3) not awarded and care continued to be reimbursed on a fee-for-service basis. STUDY DESIGN: The three samples were compared on treatment outcomes assessed over 2 years (total n = 591). DATA COLLECTION METHODS: Study participants were interviewed by trained, clinical interviewers using a standardized protocol consisting of the GAF, BPRS, QOLI, and CAGE. PRINCIPAL FINDINGS: Outcomes were comparable across most outcome measures. When outcome diffrences were evident, they tended to favor the capitation samples. CONCLUSIONS: Medicaid capitation in Colorado does not appear to have negatively affected the outcomes of people with severe mental illness during the first 2 years of the program. Furthermore, the type of capitation model was unrelated to outcomes in this study.

Mental health costs and access under alternative capitation systems in Colorado.

OBJECTIVE: To examine service cost and access for persons with severe mental illness under Medicaid mental health capitation payment in Colorado. Capitation contracts were made with two organizational models: community mental health centers (CMHCs) that manage and deliver services (direct capitation [DC]) and joint ventures between CMHCs and a for-profit managed care firm (managed behavioral health organization, [MBHO]) and compared to fee for service (F.F.S.). DATA SOURCES/STUDY SETTING: Both primary and secondary data were collected for the year prior to the new financing policy and the following two years (1995-1998). STUDY DESIGN: A stratified random sample of 522 severely mentally ill subjects was selected from comparable geographic areas within the capitated and FFS regions of Colorado. Major variables include service cost, utilization, and access (probability of service use) derived from secondary claims data, subject reported access collected at six-month intervals, and baseline outcomes (symptoms, functioning, and quality of life). PRINCIPAL FINDINGS: In comparison to the FFS area, cost per person was reduced in the capitated areas in each of the two years following implementation. By the end of year two, cost per person was reduced by two-thirds in the MBHO areas and by one-fifth in the DC areas. Reductions in access were found for both capitated areas, although reductions in utilization for those receiving service were found only in the MBHO model. CONCLUSIONS: Medicaid mental health capitation in Colorado resulted in cost reducing service changes for persons with severe mental illness. Assessment of outcome change is necessary to identify cost effectiveness.

Treatment for substance use disorders in a privately insured population under managed care: costs and services use.

The study investigated the relationship of substance use disorders, concurrent psychiatric disorders, and patient demographics to patterns of treatment use and spending in behavioral health and medical treatment sectors. We examined claims data for individuals covered by the same organization. Services spending and use were examined for 1899 individuals who received substance use disorder treatment in 1997. Medical and pharmacy spending was assessed for 590 individuals (31.1%). The most prevalent services were outpatient, intensive outpatient, residential, and detoxification. Average mental health/substance abuse (MHSA) care spending conditional on use was highest for those with concurrent alcohol and drug disorders (US 5235 dollars) compared to those with alcohol (US 2507 dollars) or drugs (US 3360 dollars) alone; other psychiatric illness (US 4463 dollars) compared to those without (US 1837 dollars); and employees' dependents (US 4138 dollars) compared to employees (US 2875 dollars) or their spouses (US 2744 dollars). A significant minority also sought MHSA services in the medical sector. Understanding services use and associated costs can best be achieved by examining services use across treatment sectors.

A four-year study of enhancing outpatient psychotherapy in managed care.

OBJECTIVES: This study was a first step in explicitly attempting to open, at least partially, the "black box" of specialty managed mental health care by examining qualitative as well as quantitative aspects of managed outpatient mental health treatment. The Goal Focus Treatment Planning and Outcomes (GFTPO) program was studied as an example of a relatively simple, patient-specific, structured educational intervention with a modest capacity to affect practice patterns and care over time among network clinicians. METHODS: Four years of data from an enhanced care management program (N=28,741) designed to facilitate focused, goal-oriented, accountable outpatient psychotherapy and appropriate use of medications were used to illustrate what was actually done in one large national managed behavioral health organization. Random samples of persons from seven matched pairs of GFTPO (N=17,752) and non-GFTPO (N=10,989) employer groups from 1995 to 1998 were studied in a quasi-experimental design. The effects of GFTPO were tested by analyzing samples compared on five measures of outpatient psychotherapy: errors in prescribing medication, continuity of therapists, early termination of treatment, likelihood of multiple treatment episodes, and the use and cost of services. RESULTS: The GFTPO sample showed a lower incidence of medication prescribing errors and therapist switching as well as shorter treatment episodes in the year after the start of outpatient treatment. No differences were observed in the likelihood of early termination or of having multiple treatment episodes. Cost savings did not appear to be at the expense of quality of care. CONCLUSIONS: It is possible to enhance the potential for measuring and influencing the quality of care in large organized systems.

Predictive models and the effectiveness of strategies for improving outpatient follow-up under managed care.

OBJECTIVES: This study tested the accuracy of models for predicting rehospitalization in a managed behavioral health organization and tested the effectiveness of different care management strategies for enhancing outpatient treatment follow-up. METHODS: In a controlled study, patients with an inpatient mental health or substance use admission received one of three types of care management, distinguished by the level of care managers' involvement in discharge planning and postdischarge outreach: usual (N=31), enhanced (N=94), and intensive (N=74). The groups were compared with each other and with a cohort admitted in the year before the study that received usual care management (N=192) to determine whether differences existed in time to outpatient follow-up, amount of postdischarge care, and rehospitalization at 30, 60, and 180 days. RESULTS: No differences between groups were found. The majority of patients (69 percent) received outpatient care within 30 days of discharge. Prediction models using logistic regression suggested that the number of clinical and sociodemographic risk factors identified by care managers was related to the rate of rehospitalization at 60 and 180 days. Patients authorized to receive intermediate care (partial hospitalization or residential care) and those who failed to attend intermediate care if it was authorized were more likely than other patients to be rehospitalized at 30, 60, and 180 days. CONCLUSIONS: Outpatient follow-up after psychiatric hospitalization did not improve with increasingly intensive discharge planning and outreach. Improvement in prediction of risk of rehospitalization may increase opportunities to provide intensive interventions for difficult-to-engage patients.

Clinical practice variations in prescribing antipsychotics for patients with schizophrenia.

Few studies have examined the variations among individual physicians in prescribing antipsychotics for schizophrenia. This study examined clinical practice variations in the route and dosage of antipsychotic medication prescribed for inpatients with schizophrenia by 11 different psychiatrists. The sample consisted of 130 patients with a DSM-III-R diagnosis of schizophrenia who had received inpatient care at a state hospital or Veterans Affairs medical center in the southeastern United States in 1992-1993. Mixed-effects regression models were developed to explore the influence of individual physicians and hospitals on route of antipsychotic administration (oral or depot) and daily antipsychotic dose, controlling for patient case-mix variables (age, race, sex, duration of illness, symptom severity, and substance-abuse diagnosis). The average daily antipsychotic dose was 1092 +/- 892 chlorpromazine mg equivalents. Almost half of the patients (48%) were prescribed doses above or below the range recommended by current practice guidelines. The proportion of patients prescribed depot antipsychotics was significantly different at the 2 hospitals, as was the antipsychotic dose prescribed at discharge. Individual physicians and patient characteristics were not significantly associated with prescribing practices. These data, which were obtained before clinical practice guidelines were widely disseminated, provide a benchmark against which to examine more current practice variations in antipsychotic prescribing. The results raise several questions about deviations from practice guidelines in the pharmacological treatment of schizophrenia. To adequately assess quality and inform and possibly further develop clinical practice guideline recommendations for schizophrenia, well-designed research studies conducted in routine clinical settings are needed.

Mental health costs and outcomes under alternative capitation systems in Colorado: early results.

BACKGROUND: This study presents preliminary findings for the first nine months of the State of Colorado USA Medicaid capitation Pilot Project. Two different models of capitation (model I and model II) are compared with fee for service (FFS) in providing services to severely and persistently mentally ill adults. In model I the state's mental health authority contracts with community mental health centers (CMHCs) who both manage the care and deliver mental health services, while in model II the state contracted with a joint venture between a for-profit managed care firm who manage the care with either a single CMHC or an alliance of CMHCs who deliver the mental health services. AIMS: Our objective is to examine utilization, cost and outcomes of inpatient and outpatient (including community based) services before and after the implementation of a capitated payment system for Colorado's Medicaid mental health services compared to services that remained under FFS reimbursement. METHODS: The stratified, random sample includes 513 consumers (188 for model I, 179 for model II, and 146 for FFS). Consumer outcomes were collected by trained interviewers and include 17 measures of symptoms, health status, functioning, quality of life and consumer satisfaction. Utilization and cost of services are from the Medicaid claims data and a shadow billing data system (post-capitation) designed by Colorado. The first step of the two-step regression procedure adjusts for the presence of individuals with use or no service use during the specified time while the second step, ordinary least-squares regression, is applied to the sample who utilized services. RESULTS: These preliminary findings indicate consistent reductions in inpatient user costs and probability of outpatient use under capitation. Combining all services, there are consistent reductions in the probability of use in both models: model I had significantly higher initial probability of use for any service. Only model II showed a statistically significant decrease in post-capitation overall user costs, but they were initially higher than model I or FFS. Estimated total cost per person for model I suggests virtually no change from the pre- to post-capitation period. Model II had the highest pre-capitation and the lowest post-capitation estimated cost per person. Examination of pre measures of outcomes across capitated areas suggest that samples drawn from the FFS, model I and model II areas were comparable in severity of psychiatric symptoms, functioning, health status and quality of life. No changes were found in outcomes. DISCUSSION: These early findings are consistent with the limited literature on capitation. Both studies of capitation integrated with medical care and those specific to mental health settings did not find adverse changes in outcomes compared to FFS. Limitations include the short follow-up period, lack of detail and possible under-reporting of outpatient services provided by the shadow billing data system. CONCLUSIONS: For the short term, it is concluded that capitation can reduce service cost per person without significant change in clinical status. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Implications are unclear until we can determine whether (i) reductions in the numbers receiving service indicates favorable consumer outcomes or reductions in access and (ii) lack of change in consumer outcomes is due to the benefits of capitation or the lack of sensitivity of the outcome measures. IMPLICATIONS FOR HEALTH CARE POLICY FORMULATION: Implications are premature for these early findings. IMPLICATIONS FOR FUTURE RESEARCH: Future research should include longer follow-up as well as analysis of long-term consequences for both cost savings and clinical outcomes.