Factors associated with second-line triplet therapy in routine care in relapsed/refractory multiple myeloma.

WHAT IS KNOWN AND OBJECTIVE: Second-line therapy (SLT) trials in relapsed/refractory multiple myeloma (RRMM) report superior outcomes with triplet combinations. We sought to determine factors associated with triplet SLT in routine practice. METHODS: A retrospective cohort with claims for MM between 01/01/2008 and 03/31/2015 was grouped by 1-2 ("doublet") or 3+ ("triplet") agent therapy. Charlson comorbidity index (CCI) and disability status; CRAB symptoms (hypercalcaemia, renal/bone disease, anaemia); and relapse risk were determined. RESULTS: Among 623 patients, the triplet group (n=146 [23%]) was younger (65.2 vs 69.8 years) and more likely to have high-risk relapse (67% vs 50%), CRAB symptoms (94.5% vs 81.1%), triplet first-line treatment (75% vs 51%) and frontline stem cell transplant (38% vs 20%) (P<0.001 for all). In multivariate analyses, CRAB symptoms (OR: 3.22, 95% CI: 1.47, 7.10), high-risk relapse (OR: 1.71, 95% CI: 1.12, 2.62) and prior triplet therapy (OR: 2.16, 95% CI: 1.38, 3.40), but neither CCI nor disability, were associated with triplet SLT. A trend towards triplets among younger patients (<65 vs >75 years, OR: 1.73, 95% CI: 0.99, 3.04) was observed. WHAT IS NEW AND CONCLUSION: The majority of patients did not receive triplet regimens. Treatment selection with triplet therapy for RRMM should carefully consider comorbidities and patient-specific characteristics.

Comparative effectiveness of pegfilgrastim, filgrastim, and sargramostim prophylaxis for neutropenia-related hospitalization: two US retrospective claims analyses.

OBJECTIVE: Few studies have compared the effectiveness of filgrastim (FIL), pegfilgrastim (PEG), and sargramostim (SAR) to reduce the risk of febrile neutropenia (FN) associated with myelosuppressive chemotherapy (M-CT). Two large commercial database analyses were separately conducted to examine the incidence of neutropenia-related and all-cause hospitalizations associated with FIL, PEG, and SAR prophylaxis for patients receiving M-CT for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, or solid tumors. METHODS: Separate retrospective US claims database analyses utilized patient data from January 1, 2004 to April 30, 2010 using the HealthCore Integrated Research Database (HIRD(SM)) and January 1, 2001 to August 31, 2009 using OptumInsight's (formerly Ingenix) database. Patients were ≥18 years old and treated with M-CT for NHL, Hodgkin lymphoma, and solid tumors. All identified M-CT cycles with prophylactic (first 5 days of cycle) FIL, PEG, or SAR were included in the analysis. Patterns of administration and incidence rates of all-cause and neutropenia-related hospitalization were examined on a per-cycle basis. RESULTS: In total, 9330 and 8762 patients with cancer, representing 30,264 and 24,215 chemotherapy cycles (28,189 and 22,649 (PEG), 1669 and 1351 (FIL), 406 and 215 (SAR)) from the HIRD(SM) and OptumInsight databases, respectively, were included in the separate database analyses. Both the HIRD(SM) and OptumInsight analysis showed that SAR and FIL prophylaxis had a higher risk of neutropenia-related hospitalization (SAR: OR = 3.48 [95%CI = 2.11, 5.74] and 2.81 [1.62, 4.87]; FIL: 1.78 [1.28, 2.48] and 2.36 [1.82, 3.06], respectively) and all-cause hospitalization (SAR: 2.18 [1.41, 3.36] and 2.41 [1.58, 3.68]; FIL:1.57 [1.25, 1.97] and 1.95 [1.60, 2.38], respectively) vs PEG. LIMITATIONS: Medical claims do not contain information about chemotherapy dose, and hospitalizations were not validated against the patient's chart. CONCLUSION: In this comparative effectiveness study, use of PEG was associated with a lower risk of neutropenia-related and all-cause hospitalizations compared to use of FIL or SAR prophylaxis.

The economics of upper gastrointestinal bleeding in a US managed-care setting: a retrospective, claims-based analysis.

OBJECTIVE: To assess 12-month healthcare resource utilization and costs associated with upper gastrointestinal (UGI) bleeding events. METHODS: Patients hospitalized with a UGI bleeding event were identified in US national health-plan claims data (1999-2003) and propensity matched to control patients without UGI bleeding in the same health plan. Matching criteria included age, gender, index date, Charlson Comorbidity Index score, geographic region, and prior medical utilization. RESULTS: A total of 9,033 UGI-bleed patients and 579,018 control patients met the inclusion criteria, yielding 4,651 matched pairs. After matching, differences between the UGI bleed and general population cohorts remained for office visits, ER visits, and ER costs during the 6-month baseline period prior to the index date. During the 12 months following the index date, both UGI-related healthcare utilization and total healthcare, medical, and pharmacy costs incurred by the UGI-bleed cohort were significantly greater (p< 0.0001) than those incurred by the general population cohort (mean of $20,405 vs. 3,652), even after excluding the initial hospitalization costs (mean of $11,228 vs. 3,652). Costs were primarily due to inpatient hospitalizations (mean of $13,059 for the UGI-bleed cohort vs. $729 for the general population cohort) and ambulatory services (mean of $4,037 for the UGI-bleed cohort vs. $1,537 for the general population cohort). Sixteen percent of the UGI-bleed cohort had a GI-related hospitalization, and about 40% of total costs occurred after the initial hospitalization. CONCLUSIONS: Patients with UGI bleeds experienced significantly higher (p< 0.0001) 12-month health-resource utilization and costs than patients without UGI bleeds. This study provides empirical evidence of the long-term economic burden associated with UGI bleeding. Interpretation of the results should take into account the lack of available information in claims data that could have an effect on study outcomes, such as particular clinical and disease-specific parameters that are not mitigated by propensity score and comorbidity index matching. In addition, this study is limited by the intensive demographic matching that was done between the two cohorts, which may have eliminated the sickest UGI patients and the healthiest general health-plan population patients.

Impact of generalized social anxiety disorder in managed care.

OBJECTIVE: The authors determined the costs associated with generalized social anxiety disorder in a managed care setting. METHOD: A three-phase mail and telephone survey was conducted from July to October 1998 in two outpatient clinics of a large health maintenance organization (HMO). The survey assessed direct costs, indirect costs, health-related quality of life, and clinical severity associated with generalized social anxiety disorder, both alone and with comorbid psychopathology. RESULTS: The weighted prevalence rate of current generalized social anxiety disorder was 8.2%. In the past year, only 0.5% of subjects with generalized social anxiety disorder had been accurately diagnosed. Yet 44.1% had a mental health specialty visit or had been prescribed an antidepressant, and psychiatric comorbidity was found in 43.6%. Noncomorbid generalized social anxiety disorder was associated with significantly lower health-related quality of life, work productivity, and earnings and greater utilization of health services; generalized social anxiety disorder with comorbid psychopathology was even more disabling. Suicide was attempted by 21.9% of subjects with noncomorbid generalized social anxiety disorder. Persons with average-severity generalized social anxiety disorder had probabilities of graduating from college that were 10 percentage points lower, earned wages that were 10% lower, and had probabilities of holding a technical, professional, or managerial job that were 14 percentage points lower than the comparison group. CONCLUSIONS: In a community cohort of HMO members, generalized social anxiety disorder was rarely diagnosed or treated despite being highly prevalent and associated with significant direct and indirect costs, comorbid depression, and impairment.

A comparison of asthma-related expenditures for patients started on montelukast versus fluticasone propionate as monotherapy.

BACKGROUND: The prevalence of asthma is increasing, and this chronic condition imposes a substantial economic burden worldwide. It is not known whether newer therapies, such as leukotriene receptor antagonists (LTRAs), can ease this burden. OBJECTIVE: This analysis examined the association between choice of first-line asthma control therapy and health care resource utilization and expenditures in patients with mild asthma. METHODS: A retrospective cohort analysis of claims data for patients who started therapy with fluticasone propionate or montelukast between January 1, 1997, and February 28, 1999, was performed, adjusting for baseline differences. RESULTS: Data from 343 patients (229 fluticasone; 114 montelukast) were analyzed. Patients starting therapy with fluticasone were significantly older (33.3 vs 27.6 years; P = 0.015) and significantly less likely than patients starting therapy with montelukast to have been started on control therapy by an asthma specialist (52.0% vs 69.3%; P = 0.007). There were no significant differences in mean changes in total asthma-related health care expenditures, oral steroid and antibiotic prescriptions, hospitalizations, or emergent care visits. The mean increase in total asthma-related pharmacy expenses was significantly greater for patients who were prescribed montelukast than for those prescribed fluticasone (P < 0.001). Treatment adherence was better in patients prescribed montelukast versus fluticasone (5.1 vs 3.1 prescriptions filled per year, respectively; P < 0.001). Montelukast patients had a significantly lower increase in the number of beta-agonist prescriptions filled per year than fluticasone patients (0.19 vs 0.66; P = 0.03). In the subsequent year, 4% (10/229) of fluticasone patients added or switched to an LTRA. No montelukast patients added to or switched control therapy. CONCLUSION: The mean change in total asthma-related health care expenditures was not significantly different in patients started on fluticasone propionate versus montelukast. Montelukast patients had better adherence to their treatment regimen and required fewer beta-agonist prescriptions, which is an indicator of asthma control and possibly therapeutic effectiveness.

Cost-effectiveness of systematic depression treatment for high utilizers of general medical care.

BACKGROUND: Expanding access to high-quality depression treatment will depend on the balance of incremental benefits and costs. We examine the incremental cost-effectiveness of an organized depression management program for high utilizers of medical care. METHODS: Computerized records at 3 health maintenance organizations were used to identify adult patients with outpatient medical visit rates above the 85th percentile for 2 consecutive years. A 2-step screening process identified patients with current depressive disorders, who were not in active treatment. Eligible patients were randomly assigned to continued usual care (n = 189) or to an organized depression management program (n = 218). The program included patient education, antidepressant pharmacotherapy initiated in primary care (when appropriate), systematic telephone monitoring of adherence and outcomes, and psychiatric consultation as needed. Clinical outcomes (assessed using the Hamilton Depression Rating Scale on 4 occasions throughout 12 months) were converted to measures of "depression-free days." Health services utilization and costs were estimated using health plan-standardized claims. RESULTS: The intervention program led to an adjusted increase of 47.7 depression-free days throughout 12 months (95% confidence interval [CI], 28.2-67.8 days). Estimated cost increases were $1008 per year (95% CI, $534-$1383) for outpatient health services, $1974 per year for total health services costs (95% CI, $848-$3171), and $2475 for health services plus time-in-treatment costs (95% CI, $880-$4138). Including total health services and time-in-treatment costs, estimated incremental cost per depression-free day was $51.84 (95% CI, $17.37-$108.47). CONCLUSIONS: Among high utilizers of medical care, systematic identification and treatment of depression produce significant and sustained improvements in clinical outcomes as well as significant increases in health services costs.

Randomized trial of a depression management program in high utilizers of medical care.

BACKGROUND: High utilizers of nonpsychiatric health care services have disproportionally high rates of undiagnosed or undertreated depression. OBJECTIVE: To determine the impact of offering a systematic primary care-based depression treatment program to depressed "high utilizers" not in active treatment. DESIGN: Randomized clinical trial. SETTING: One hundred sixty-three primary care practices in 3 health maintenance organizations located in different geographic regions of the United States. PATIENTS: A group of 1465 health maintenance organization members were identified as depressed high utilizers using a 2-stage telephone screening process. Eligibility criteria were met by 410 patients and 407 agreed to enroll: 218 in the depression management program (DMP) practices and 189 in the usual care (UC) group. INTERVENTION: The DMP included patient education materials, physician education programs, telephone-based treatment coordination, and antidepressant pharmacotherapy initiated and managed by patients' primary care physicians. MAIN OUTCOME MEASURES: Depression severity was measured using the Hamilton Depression Rating Scale (Ham-D) and functional status using the Medical Outcomes Study 20-item short form (SF-20) subscales. Outpatient visit and hospitalization rates were measured using the health plan's encounter data. RESULTS: Based on an intent-to-treat analysis, at least 3 antidepressant prescriptions were filled in the first 6 months by 151 (69.3%) of 218 of DMP patients vs 35 (18.5%) of 189 in UC (P < .001). Improvements in Ham-D scores were significantly greater in the intervention group at 6 weeks (P = .04), 3 months (P = .02), 6 months (P < .001), and 12 months (P < .001). At 12 months, DMP intervention patients were more improved than UC patients on the mental health, social functioning, and general health perceptions scales of the SF-20 (P < .05 for all). CONCLUSION: In depressed high utilizers not already in active treatment, a systematic primary care-based treatment program can substantially increase adequate antidepressant treatment, decrease depression severity, and improve general health status compared with usual care.

Depression among high utilizers of medical care.

OBJECTIVE: To determine the prevalence of unrecognized or unsuccessfully treated depression among high utilizers of medical care, and to describe the relation between depression, medical comorbidities, and resource utilization. DESIGN: Survey. SETTING: Three HMOs located in different geographic regions of the United States. PATIENTS: A total of 12,773 HMO members were identified as high utilizers. Eligibility criteria for depression screening were met by 10,461 patients. MEASUREMENTS AND MAIN RESULTS: Depression status was assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Depression screening was completed in 7,203 patients who were high utilizers of medical care, of whom 1,465 (20.3%) screened positive for current major depression or major depression in partial remission. Among depressed patients, 621 (42.4%) had had a visit with a mental health specialist or a diagnosis of depression or both within the previous 2 years. The prevalence of well-defined medical conditions was the same in patients with and patients without evidence of depression (41.5% vs 41.5%, p = .87). However, high-utilizing patients who had not made a visit for a nonspecific complaint during the previous 2 years were at significantly lower risk of depression (13.1% vs 22.4%, p < .001). Patients with current depression or depression in partial remission had significantly higher numbers of annual office visits and hospital days per 1,000 than patients without depression. CONCLUSIONS: Although there was evidence that mental health problems had previously been recognized in many of the patients, a large percentage of high utilizers still suffered from active depression that either went unrecognized or was not being treated successfully. Patients who had not made visits for nonspecific complaints were at significantly lower risk of depression. Depression among high utilizers was associated with higher resource utilization.

Behavioral versus pharmacological treatments of obsessive compulsive disorder: a meta-analysis.

The goal of the study was to provide a quantitative analysis of the relative efficacy of all five currently available serotonin reuptake inhibitors (SRIs) and behavior therapy [exposure and response prevention (ERP)] for obsessive compulsive disorder. The relationship between effect size and methodological characteristics was also empirically examined. A search was conducted of several computerized databases covering the dates from 1973 to 1997. Seventy-seven studies were identified, yielding 106 treatment comparisons involving 4641 patients. Effect sizes were analyzed between individual interventions and between intervention class [SRI, ERP or the combined treatment of an SRI with ERP(ERP/SRI)]. Data were analyzed both before and after controlling for methodological variables. The effect size for clomipramine (CMI) was significantly greater than the other SRIs, with the exception of fluoxetine (FLX). CMI was not significantly greater than ERP or ERP/SRI. As a class, ERP was significantly greater than SRIs as a whole. Effect sizes were larger for studies without a control group or random assignment, for self-reported outcome measures, and varied significantly by method of effect size calculation. Year of publication was significantly related to effect size. When controlling for these methodological variables, CMI was not significantly greater than FLX or fluvoxamine (FLV), and ERP was no longer significantly greater than the SRIs as a whole. No significant difference was found between CMI and the other SRIs as a group in head to head trials. No differences in drop-out rates were found. CMI stands out from the other SRIs. This difference is probably not clinically significant enough to warrant first choice treatment, given CMI's greater lethality in overdose. The choice between an SRI or ERP is dominated primarily by the infrequent availability of ERP and to a lesser degree by personal preference. Methodological differences significantly impact effect size.

A computer-administered telephone interview to identify mental disorders.

CONTEXT: Common mental disorders are often not identified in primary care settings. OBJECTIVE: To evaluate the validity and clinical utility of a telephone-assisted computer-administered version of Primary Care Evaluation of Mental Disorders (PRIME-MD), a brief questionnaire and interview instrument designed to identify psychiatric disorders in primary care patients. DESIGN: Comparison of diagnoses obtained by computer over the telephone using interactive voice response (IVR) technology vs those obtained by a trained clinician over the telephone using the Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID). A subsample also received the clinician-administered version of PRIME-MD. PATIENTS: Outpatients (N=200) from 4 primary care clinics, an eating disorders clinic, an alcohol treatment facility, psychiatric outpatients, and community controls. SETTING: Interviews conducted by telephone, except for face-to-face administration of PRIME-MD, which was conducted at either the primary care clinic or a research clinic. MEASUREMENTS AND MAIN RESULTS: Prevalence rates for any psychiatric disorder were similar between diagnoses made by the computer and those made by a mental health professional using the SCID (60.0% vs 58.5%). Prevalence rates for individual diagnoses were generally similar across versions. However, primary care patients reported twice as much alcohol abuse on the computer (15.0%) as on either the SCID (7.5%) or the clinician-administered PRIME-MD (7.5%). Using the SCID as the criterion, both the computer- and clinician-administered versions of PRIME-MD demonstrated high and roughly equivalent levels of sensitivity and specificity. Overall agreement (K) for any diagnosis was 0.67 for the computer-administered PRIME-MD and 0.70 for the clinician-administered PRIME-MD. CONCLUSIONS: The computer-administered PRIME-MD appears to be a valid instrument for assessing psychopathology in primary care patients. Interactive voice response technology allows for increased availability, and provides primary care physicians with information that will increase the quality of patient care without additional physician time and at minimal expense.

Effect of primary care treatment of depression on service use by patients with high medical expenditures.

OBJECTIVE: The study examined the impact of identifying and treating depression among patients who had a history of high medical expenditures. Effects on service use, disability, and quality of life were measured. METHODS: A total of 786 high users of services from two primary care clinics and an equal number of randomly selected patients who were not high users were screened for depression using the Medical Outcomes Study (MOS) depression screen. High-user patients who screened positive were subsequently seen by their primary care physician for a diagnostic interview. The 20 patients with a confirmed diagnosis of depression were offered open-label antidepressant treatment by their primary care physician for six months. RESULTS: All 20 patients completed the six-month study. Treatment resulted in significant reductions in depression and significant improvements in quality of life in the areas of social functioning, general health, mental health, physical functioning, emotional role functioning, and vitality. Days of missed work per month were reduced, and the percentage of patients who reported not being at all impaired by their depression at work increased. Costs for service use fell from $13.28 to $6.75 per day; when costs for the treatment study were added, the daily service use cost was $12.55. CONCLUSIONS: Identification and treatment of depression among patients with a history of high medical expenditures improved depression and increased work productivity and quality of life. Service use decreased with treatment. A larger sample and control group are needed to determine if treatment is associated with a statistically significant decrease in medical expenditures.

Medical costs attributed to depression among patients with a history of high medical expenses in a health maintenance organization.

BACKGROUND: While previous studies have compared medical utilization between depressed and nondepressed patients, we conducted a study that focused specifically on patients who had a history of high medical expenditures. METHODS: This study was designed to determine whether a positive screen for depression is predictive of continued high medical expenditures. Medical utilization data were obtained on 50,000 patients enrolled in the DeanCare health maintenance organization for 2 consecutive years. Consistent high utilizers were identified based on the medical utilization costs (paid by the health maintenance organization) for those 2 consecutive years, 1992 and 1993. A depression screen based on the Medical Outcomes Survey was mailed to 786 high utilizers. Their costs were determined for 1994. Regression analyses identified 1994 costs associated with depression, adjusting for age, sex, benefits package, and medical comorbidity. RESULTS: Depressed high utilizers were more likely than nondepressed high utilizers to have higher medical costs in 1994. Among high utilizers, depressed patients' 1994 costs were significantly higher ($5764 vs $4227; P < .001), although expenditures for depressed and nondepressed high utilizers were similar for the previous 2 years. The total medical cost associated with depression in 1994, adjusted for age, sex, benefits package, and medical comorbidity, was $1498 per patient. CONCLUSIONS: In the third year (1994), a positive Medical Outcomes Survey screen for depression in high utilizers was associated with $1498 in higher medical costs. The average actual amount spent on depression treatment accounted for only a small portion of total medical costs for depressed high utilizers in the third year.