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.

Outcome assessment of an antipsychotic drug algorithm: effects of the Mississippi State Hospital algorithm project.

OBJECTIVE: This study evaluated a state psychiatric hospital's algorithm for prescribing antipsychotic drugs for inpatients with schizophrenia to determine whether its emphasis on cost efficiency is compatible with quality of care. METHODS: Outcomes were compared for patients who received medication that was algorithm adherent or nonadherent. Risperidone and ziprasidone were first-step oral antipsychotics. Documentation of clinical rationale was acceptable for nonpreferred drug use. Outcomes of interest were length of hospitalization and "much improved" or "very much improved" status on the Clinical Global Impression severity scale (CGI-S). RESULTS: Of 401 patients, 70% were male. The CGI-S modal rating of severity was "markedly ill." Duration of illness was longer for patients given algorithm-nonadherent (17.6±9.7 years) versus -adherent (14.9±11.6 years, p=.013) medication. No statistically significant between-group differences were observed for mean length of stay (51.4±35.5 days versus 43.8±27.4 days, adjusted difference p=.18) or median improvement time (adherent, 41 days; nonadherent, 42 days; CI=34-48 days for both group medians). CONCLUSIONS: Prescription algorithm adherence was not associated with significantly increased length of inpatient stay or delayed time to improvement.

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.

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.

Monitoring patient improvement and treatment outcomes in managed behavioral health.

This study examined the use of outcome reports sent to clinicians by a managed behavioral healthcare organization to monitor patient progress and its relation to treatment outcome. Results showed that clinicians who reported using outcome information had patients who also reported greater improvement at 6 months from baseline. Improvement per session was greatest among patients whose clinicians reported reading the outcome report and using outcome measures in their clinical practice. Using baseline and ongoing measures to assess patient improvement can provide clinicians with feedback during treatment, which may lead to better clinical outcomes and enable quality management systems in managed care to flag high-risk cases and identify failure of adequate improvement.

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.

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.

Patterns of medical resource and psychotropic medicine use among adult depressed managed behavioral health patients.

Medical and pharmacy utilization patterns were examined among 782 depressed patients seen by independent clinicians through a Managed Behavioral Health Organization using behavioral, medical and pharmacy claims spanning 2 years. Two-thirds received psychiatric care in the medical and mental health sector concurrently, 43% had comorbid medical disorders, 61% received psychotropic medications, and 54% were on antidepressants. Fewer depressed medically comorbid patients used medical services while in mental health treatment than before or after treatment, while the per patient costs remained the same. For those with chronic conditions, medical utilization and costs remained the same. A quarter of depressed patients received mental health treatment before seeing a mental health specialist, and a quarter remained in treatment in the medical sector after treatment in the mental health sector. Despite increases in mental health services access made available through managed behavioral health organizations, patients continue receiving mental health treatment in the medical sector.

Profiling hospitals for length of stay for treatment of psychiatric disorders.

Managed behavioral health care organizations (MBHOs) often profile hospitals on length of stay (LOS) and other performance measures. However, previous research has suggested that most of the variation in utilization for general medical conditions is attributable to case-mix indicators and random sources rather than individual providers. Hospital discharge data are used to estimate hierarchical linear models, where hospitals and physicians within hospitals are treated as a random effect. The goal was to determine the intraclass correlation coefficient (ICC) for psychiatric LOS for hospitals and for physicians before and after making case-mix adjustments. After controlling for case-mix, the hospital ICCs for depression, schizophrenia, and bipolar disorder show that 32%, 36%, and 11% of the variation in LOS, respectively, can be attributed to hospitals, while 7%, 5%, and 6% of the variation in LOS, respectively, can be attributed to physicians or provider practice. Unlike health services for other conditions, the variation in LOS for inpatient psychiatric treatment of depression and schizophrenia is quite dependent upon hospitals.

Advanced practice psychiatric nurses as a treatment resource: survey and analysis.

Access to behavioral health services, particularly pharmacotherapy, continues to be a significant problem. This is particularly the case for public sector beneficiaries and managed care members. The greater use of advanced practice psychiatric nurses (APPNs) with prescribing privileges could help. To better understand the availability and competence of APPNs to prescribe, the authors conducted 1) a national survey of APPNs' availability and prescribing practices, 2) a comparative analysis of pharmacy claims data generated by APPNs and psychiatrists, and 3) a comprehensive clinical record review comparing APPNs to psychiatrists. About 25% of the sample of APPNs reported having prescription authority and a private practice. The analysis of prescribing practices between APPNs and psychiatrists showed that with a few exceptions, there were no differences between the groups, as did a retrospective clinical record review. These results lead the authors to recommend greater efforts to increase the supply of APPNs.

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.

The impact of evidence-based guideline dissemination for the assessment and treatment of major depression in a managed behavioral health care organization.

This study tests whether a managed behavioral health care organization can influence adherence to practice guidelines for the treatment of major depression in a randomized trial of guideline dissemination. Guidelines were disseminated to mental health clinicians (N = 443) under one of three conditions: (1) a general mailing of guidelines to clinicians, (2) a mailing in which guidelines were targeted to a patient starting treatment with the clinician, and (3) no mailing of guidelines. The results showed no effects of guideline dissemination as measured by self-report of patients and clinicians and through episode characteristics derived from claims data, despite sentinel effects. Results also showed high rates of clinician-reported guideline adherence that were not detected in the claims data, indicating significant undertreatment of depression. Results suggest that mental health systems must look to other dissemination strategies to improve adherence to standards of care and raise the performance of independent practicing clinicians.

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.

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.

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 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.