John Fastenau

Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE)

Abstract Background: Schizophrenia affects ∼1.1% of the United States population, resulting in substantial direct, indirect and societal costs. Objective: To evaluate hospitalization rates associated with use of paliperidone palmitate (PP). Methods: Data were from a variable-duration double-blind (DB), randomized, relapse-prevention comparison (NCT00111189) of PP vs. placebo (Pbo), followed by a 1-year open-label extension (OLE). Between-phase change in schizophrenia-related hospitalizations was evaluated using data from an investigator-completed questionnaire. Change in hospitalizations using patients before enrollment who participated in the OLE phase was also analyzed. Poisson regression was used to evaluate changes in incidence density within exposure category and by schizophrenia duration. Results: A total of 160 patients in the PP-PP group and 153 in the Pbo-PP group from the DB to the OLE phase were included. Mean age (standard deviation [SD]), gender, and duration of schizophrenia were similar at the start of the DB phase (Pbo: 38.5 years [10.6], 51.0% male, 68.0% ≥5 years’ duration; PP: 37.3 years [11.4] (p = 0.342); 51.9% male (p = 0.874); 70.0% ≥5 years’ duration (p = 0.698), respectively. From the DB to the end of the OLE phase, the number of hospitalizations per person-year for patients treated during the DB phase with Pbo significantly declined from 0.27 to 0.06 (78% reduction; p = 0.005). A statistically nonsignificant difference was observed for PP patients treated during the DB phase with PP (0.11–0.04; 63.6% reduction; p = 0.076), compared with the OLE phase. Change from before enrollment to the end of the OLE phase (n = 381) produced similar results (0.35–0.04; 88.6% reduction; p < 0.001). Patients who enroll in a clinical trial may be different from the general population and this may affect the generalizability of results. Conclusion: From the double-blind to the open-label phase and from prior to the trial until the end of the open-label phase, hospitalizations significantly decreased for patients with schizophrenia treated with PP.

Retrospective observational study of patients with chemotherapy-related anemia receiving erythropoietic agents

ABSTRACT Objective: Epoetin alfa (EPO) and darbepoetin alfa (DARB) are approved for the treatment of chemotherapy-related anemia (CRA) in patients with nonmyeloid malignancies. This study examined dosing and hematologic outcomes with these agents in community oncology clinics. Methods: Medical charts were abstracted retrospectively for 1005 patients (527 EPO, 478 DARB) with CRA (hemoglobin [Hb] ≤ 11 g/dL) who received EPO or DARB at 10 U.S. oncology clinics between January 2002 and March 2003. Main outcome measures: Outcome measures included dose and frequency of erythropoietic therapy, change in Hb at 4, 8, and 12 weeks after initiation of therapy, and transfusion of packed red blood cells. Results: Baseline characteristics were generally similar between groups. Most EPO-treated patients received EPO once weekly, but 25% received EPO every 2–3 weeks, with 40 000 U the predominant dose. DARB was usually given every 1–2 weeks in doses ranging from 200–400 mcg/injection. Mean treatment duration was relatively short(< 8 weeks) in both groups, with a similar number of Hb determinations and similar incidence of red blood transfusion between groups. Hb increased from baseline in the EPO and DARB groups at 4 weeks (0.99 vs. 0.69 g/dL, p = 0.003), 8 weeks (1.39 vs. 1.06 g/dL, p = 0.011), and 12 weeks (1.43 vs. 1.11 g/dL, p = 0.055). Early Hb response (≥ 1 g/dL increase by 4 weeks) was more common with EPO than DARB (48% vs. 38%, p = 0.008). Conclusions: EPO was superior to DARB for early hematologic outcomes in patients with CRA in community oncology clinics. Retrospective data collection and relative inexperience with DARB at the time of the study may limit the generalization of these results. Randomized, controlled trials comparing EPO and DARB are warranted.

Systematic review of long-acting injectables versus oral atypical antipsychotics on hospitalization in schizophrenia

Abstract Objective: To assess the impact of long-acting injectables (LAIs) versus oral antipsychotics (OAs) on hospitalizations among patients with schizophrenia by conducting a systematic literature review of studies with different study designs and performing a meta-analysis. Methods: Using the PubMed database and major psychiatric conference proceedings, a systematic literature review for January 2000 to July 2013 was performed to identify English-language studies evaluating schizophrenia patients treated with atypical antipsychotics. Studies reporting hospitalization rates as a percentage of patients hospitalized or as the number of hospitalizations per person per year were selected. The primary meta-analysis assessed the percentage decrease in hospitalization rates before and after treatment initiation for matched time periods. The secondary meta-analysis assessed the absolute rate of hospitalization during follow-up. Pooled treatment-effect estimates were calculated using random-effects models. To account for differences in patient and study-level characteristics between studies, meta-regression analyses were used. Subset analyses further explored the heterogeneity across study designs. Results: Fifty-eight studies evaluating 25 arms (LAIs: 13 arms, 4516 patients; OAs: 12 arms, 23,516 patients) in the primary meta-analysis and 78 arms (LAIs: 12 arms, 4481 patients; OAs: 66 arms, 96,230 patients) in the secondary meta-analysis were identified. Reduction in hospitalization rates for LAIs was 20.7 percentage points higher than that of OAs (random-effects estimates: LAIs = 56.2% vs. OAs = 35.5%, P = 0.023). Controlling for patient and study characteristics, the adjusted percentage reduction in hospitalization rates for LAIs was 26.4 percentage points higher than for OAs (95% CI: 3.3–49.5, P = 0.027). As for the secondary meta-analysis, no significant difference between LAIs and OAs was observed (random-effects estimate: −8.6, 95% CI: −18.1–1.0, P = 0.077). Subset analyses across type of study yielded consistent results. Limitations of this analysis include the long observation period, which may not reflect current treatment patterns, the use of all-cause hospitalization, which may not be solely related to schizophrenia, and the fact that most studies in the LAI cohort evaluated risperidone. Conclusion: The primary results of this meta-analysis, including studies with both interventional and non-interventional designs and using meta-regressions, suggest that LAIs are associated with higher reductions in hospitalization rates for schizophrenia patients compared to OAs.

Patterns of relapse and associated cost burden in schizophrenia patients receiving atypical antipsychotics

Objective: To identify relapse in schizophrenia and the main cost drivers of relapse using a cost-based algorithm. Methods: Multi-state Medicaid data (1997–2010) were used to identify adults with schizophrenia receiving atypical antipsychotics (AP). The first schizophrenia diagnosis following AP initiation was defined as the index date. Relapse episodes were identified based on (1) weeks during the � 2 years post-index associated with high cost increase from baseline (12 months before the index date) and (2) high absolute weekly cost. A compound score was then calculated based on these two metrics, where the 54% of patients associated with higher cost increase from baseline and higher absolute weekly cost were considered relapsers. Resource use and costs of relapsers during baseline and relapse episodes were compared using incidence rate ratios (IRRs) and bootstrap methods.

Dose conversion and cost effectiveness of erythropoietic therapies in chemotherapy-related anaemia : a meta-analysis.

AbstractObjective: To estimate a dose-conversion ratio (DCR) between epoetin alfa (EPO) and darbepoetin alfa (DARB) and compare the costs of both drugs at the estimated DCRs using average wholesale prices (AWPs). Methods: A search of PUBMED, CANCERLIT and references for papers and abstracts reporting on clinical trials of DARB or EPO for chemotherapy-related anaemia (CRA) identified 56 publications. A meta-analysis was conducted on the 12 eligible papers to estimate a DCR at which the two drugs were equally effective as measured by the area under the curve of haemoglobin (Hb) change (Hb AUC) at weeks 4 and 13. The DCR is based on the ratio of the coefficients of DARB and EPO doses in a regression of Hb AUC on those two variables, baseline Hb, Hb change calculation method, tumour type, and dosing frequency. Studies were frequency-weighted by the number of subjects. DCRs with confidence intervals (CIs) were calculated using a Monte-Carlo approach. Results from the regression were used to calculate DCRs for different dosing regimen comparisons — EPO three times weekly (TIW) versus DARB once weekly (QW), EPO TIW versus DARB once every 2 weeks (Q2W), EPO QW versus DARB QW, and EPO QW versus DARB Q2W. Relative cost effectiveness (RCE) was assessed by comparing drug costs at the estimated DCRs at

Early hemoglobin response and alternative metrics of efficacy with erythropoietic agents for chemotherapy-related anemia

US 2003 AWPs [RCE = DCR · (

The threshold rate of oral atypical anti-psychotic adherence at which paliperidone palmitate is cost saving

/U EPO)/(

Burden of schizophrenia on selected comorbidity costs

/μg DARB)]. Results: The regression results suggest an EPO QW: DARB QW DCR of 187 (95% CI 183, 191). Depending on the assumed starting dose, the DCR ranges from 126 to 137 for EPO TIW: DARB QW; from 128 to 139 for EPO TIW: DARB Q2W; and equals 191 for EPO QW: DARB Q2W. RCE was 2.0 for the main regression. Conclusion: The DCR of 330: 1 estimated for the 2004 Hospital Outpatient Prospective Payment System by the Centers for Medicare and Medicaid Services is greater than the DCRs estimated based on Hb AUC. The DCR estimated in the primary regression suggests that based on AWPs, EPO is 2.0 times more cost effective than DARB.

Effectiveness versus convenience: patient preferences for an erythropoietic agent to treat cancer-related anemia

ABSTRACT Objective: To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia. Research design and methods: Preliminary data from an ongoing randomized, multicenter, 16‐week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (≥ 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion. Main outcome measures: Efficacy measures included: the proportion of patients with a ≥ 1 g/dL increase in hemoglobin by 4 weeks or a ≥ 2 g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL; and proportion of patients who never had a hemoglobin level within this range. Results: A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 ± 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred. Conclusions: Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.

Evaluation of the relationship between early hemoglobin rise during epoetin alfa treatment and improved patient-reported quality of life

Abstract Objective: To identify, estimate, and compare ‘real world’ costs and outcomes associated with paliperidone palmitate compared with branded oral atypical anti-psychotics, and to estimate the threshold rate of oral atypical adherence at which paliperidone palmitate is cost saving. Methods: Decision analytic modeling techniques developed by Glazer and Ereshefsky have previously been used to estimate the cost-effectiveness of depot haloperidol, LAI risperidone, and, more recently, LAI olanzapine. This study used those same techniques, along with updated comparative published clinical data, to evaluate paliperidone palmitate. Adherence rates were based on strict Medication Event Monitoring System (MEMS) criteria. The evaluation was conducted from the perspective of US healthcare payers. Results: Paliperidone palmitate patients had fewer mean annual days of relapse (8.7 days; 6.0 requiring hospitalization, 2.7 not requiring hospitalization vs 17.8 days; 12.4 requiring hospitalization, 5.4 not requiring hospitalization), and lower annual total cost (