Jacqueline Brown

Three-year antipsychotic effectiveness in the outpatient care of schizophrenia: observational versus randomized studies results.

Antipsychotic discontinuation rates are a powerful indicator of medication effectiveness in schizophrenia. We examined antipsychotic discontinuation in the Schizophrenia Outpatient Health Outcomes (SOHO) study, a 3-year prospective, observational study in outpatients with schizophrenia in 10 European countries. Patients (n=7728) who started antipsychotic monotherapy were analyzed. Medication discontinuation for any cause ranged from 34% and 36% for clozapine and olanzapine, respectively, to 66% for quetiapine. Compared to olanzapine, the risk of treatment discontinuation before 36 months was significantly higher for quetiapine, risperidone, amisulpride, and typical antipsychotics (oral and depot), but similar for clozapine. Longer medication maintenance was associated with being socially active and having a longer time since first treatment contact for schizophrenia, whereas higher symptom severity, treatment with mood stabilizers, substance abuse, having hostile behaviour were associated with lower medication maintenance. Antipsychotic maintenance in SOHO was higher than the results of previous randomized studies.

The cost of relapse in patients with schizophrenia in the European SOHO (Schizophrenia Outpatient Health Outcomes) study.

BACKGROUND Relapse in schizophrenia is one of the greatest burdens of the illness. AIMS To estimate the costs associated with relapse in a pan-European naturalistic setting. METHOD The SOHO study is a 3-year, prospective, observational study of 10,972 outpatients with schizophrenia across 10 European countries. The cost of resource use (inpatient stay, day care, psychiatrist visits and medication) for those who ever relapsed in three years was compared to those who never relapsed. One-year costs for both groups were also compared for a more stringent comparison. The analyses were adjusted for patient characteristics and took account of non-normality of the cost data by using a log-link function. UK unit costs were applied to resource use. The analysis was repeated after multiple imputation for missing data. RESULTS Costs incurred by patients who ever relapsed ( pound14,055) during three years were almost double to those incurred by patients who never relapsed ( pound7417). 61% of the cost difference was accounted for by hospital stay. The impact of relapse was even greater in the 1-year cost comparison. Results from the additional analysis with imputed missing data remained largely consistent. CONCLUSIONS Our findings confirm the significant economic burden of relapse, and show such costs were mainly due to hospital stay. Nevertheless, the use of UK unit costs requires caution when interpreting this costing in the context of a specific country, as resource use and their associated costs will differ by country.

Health-Related Quality of Life (HRQL) and Continuous Antipsychotic Treatment: 3-year Results from the Schizophrenia Health Outcomes (SOHO) Study

OBJECTIVES We investigated the association between continuous antipsychotic use and health-related quality of life (HRQL) 3-year change in the European Schizophrenia Outpatients Health Outcomes (EU-SOHO) study. METHODS EU-SOHO is an observational study of outcomes associated with antipsychotic treatment for schizophrenia in an outpatient setting. HRQL was assessed at study entry and at 6, 12, 18, 24, 30, and 36 months using the EuroQol-5D (EQ-5D). UK population time trade-off (TTO) tariffs were applied to the self-rated EQ-5D health states to calculate HRQL ratings (0 = death, 1 = best). An epoch analysis approach was used as a conceptual framework to analyze the longitudinal data. Follow-up was divided into epochs or periods of continuous treatment. When a patient changed antipsychotic treatment, he or she was considered to have a new observation. Multilevel models were employed to evaluate the association of HRQL with medication and other clinical and sociodemographic variables for each epoch. A total of 9340 patients were analyzed (42.1% women; mean age 40 years). RESULTS Mean EQ-5D scores increased over time; the largest improvement occurred in the first 6 months (mean increase of 0.19). Longer duration of illness and older age at first treatment were associated with worse baseline EQ-5D scores. Improvements in EQ-5D scores were greater for more socially active patients or those in paid employment. Few significant differences were found between antipsychotic medications. Olanzapine and clozapine were associated with higher HRQL increases. CONCLUSIONS Continuous antipsychotic treatment is associated with important HRQL benefits at 3 years, most of which occurs during the first 6 months. Although some medications are associated with better HRQL outcomes, differences are small.

Cost-utility analysis of treatment with Olanzapine compared with other antipsychotic treatments in patients with schizophrenia in the Pan-European SOHO study

ObjectiveTo determine the cost utility of treating schizophrenic patients with olanzapine compared with other antipsychotics in a naturalistic outpatient setting.MethodsThe pan-European SOHO study is a 3-year, prospective, outpatient, observational study of outcomes associated with antipsychotic treatment, focusing on olanzapine, in ten European countries. For the cost-utility analysis, healthcare resource use (inpatient care, day care, outpatient psychiatric consultations and antipsychotic and concomitant medication use) and EQ-5D data were collected at baseline and at 3, 6 and 12 months. The perspective was that of the health service payer. UK healthcare unit costs (year 2004 values) were applied to the resource use data for the ten countries. UK population tariffs were applied to the EQ-5D data to determine utility values.An Epoch analysis was used to analyze the longitudinal data. Multivariate regression analyses that adjusted for baseline covariates were used to estimate the incremental cost and utility gains for patients treated with olanzapine compared with each of the other antipsychotics (risperidone, quetiapine, amisulpride, clozapine and oral or depot typical antipsychotics).ResultsA total of 10 972 patients were enrolled at baseline, of which 9107 completed the 12-month study period. Treatment with olanzapine was more effective in terms of QALYs gained than all of the other antipsychotic treatments. Treatment with olanzapine dominated quetiapine and amisulpride. The incremental cost for olanzapine compared with risperidone was £226 per patient over 12 months and the incremental cost per QALY gained was £5156, with bootstrap analyses showing 100% of the replications falling below a £30 000 per QALY gained threshold. Compared with treatment with clozapine, olanzapine was found to be marginally more effective, at an additional cost of £13 per patient over 12 months and to have an incremental cost per QALY gained of £775. Bootstrap analyses showed that 81% of replications fell below a £30 000 per QALY gained threshold. Comparing olanzapine with oral and depot typical antipsychotics, the incremental cost was £849 and £1106 per patient over 12 months and the incremental cost per QALY gained was £15 696 and £23 331, respectively. Bootstrap analyses showed that 98% of the replications fell below a £30 000 per QALY gained threshold for the comparison with oral typical antipsychotics, and 79% of replications for the comparison with depot preparations.ConclusionsAmong SOHO patients, if a funding threshold of £30 000 per QALY gained is assumed, this analysis suggests that olanzapine has a high probability of being the most cost-effective treatment compared with other antipsychotic treatments. However, comparison of olanzapine with clozapine and typical depot antipsychotics should be viewed with caution because clozapine is a second-line treatment and depot treatment is used for patients who do not adhere to their oral medication.

A Randomised Phase 2 Study Combining LY2181308 Sodium (Survivin Antisense Oligonucleotide) with First-line Docetaxel/Prednisone in Patients with Castration-resistant Prostate Cancer

Castration-resistant prostate cancer (CRPC) is partially characterised by overexpression of antiapoptotic proteins, such as survivin. In this phase 2 study, patients with metastatic CRPC (n=154) were randomly assigned (1:2 ratio) to receive standard first-line docetaxel/prednisone (control arm) or the combination of LY2181308 with docetaxel/prednisone (experimental arm). The primary objective was to estimate progression-free survival (PFS) for LY2181308 plus docetaxel. Secondary efficacy measures included overall survival (OS), several predefined prostate-specific antigen (PSA)-derived end points, and Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores. The median PFS of treated patients for the experimental arm (n=98) was 8.64 mo (90% confidence interval [CI], 7.39-10.45) versus 9.00 mo (90% CI, 7.00-10.09) in the control arm (n=51; p=0.755). The median OS for the experimental arm was 27.04 mo (90% CI, 19.94-33.41) compared with 29.04 mo (90% CI, 20.11-39.26; p=0.838). The PSA responses (≥ 50% PSA reduction), BPI, and FACT-P scores were similar in both arms. In the experimental arm, patients had a numerically higher incidence of grades 3-4 neutropenia, anaemia, thrombocytopenia, and sensory neuropathy. In conclusion, this study failed to detect a difference in efficacy between the two treatment groups.

Real-world treatment patterns and costs in a US Medicare population with metastatic squamous non-small cell lung cancer

OBJECTIVES Despite advances in the treatment of nonsquamous non-small cell lung cancer (NSCLC), therapeutic choices and overall disease course for squamous NSCLC have remained relatively unchanged over the past several years. We provide a detailed account of current treatment patterns, healthcare use, and survival in real-world clinical settings for metastatic squamous NSCLC. MATERIALS AND METHODS Patients aged ≥65 years with metastatic squamous NSCLC diagnosed 2001-2009 were identified and followed through 2010 using the Surveillance, Epidemiology and End Results-Medicare database. Treatment patterns were descriptively analyzed. Multivariate logistic regressions were estimated to identify predictors of treatment pattern events; generalized linear models were estimated for total all-cause and NSCLC-related costs to assess cost drivers. RESULTS Of 17,133 patients, 72% received cancer-directed therapy (surgery, radiation, chemotherapy, or biologic therapy), whereas 28% received only supportive care. Median survival was significantly longer in patients receiving cancer-directed therapy (8 months) than in patients receiving supportive care only (2 months) (P<0.0001). An agent-specific first-line chemotherapy regimen was identified for 91% of the 7700 patients who received chemotherapy. Among these, the most common first-line regimen was carboplatin-paclitaxel combination therapy (46%). Common second-line regimens were gemcitabine monotherapy (16%) and pemetrexed monotherapy (11%). Factors associated with decreased odds of receiving cancer-directed treatment were black versus white race (OR, 0.72; 95% CI, 0.64-0.82), residence in the West versus South (OR, 0.73; 95% CI, 0.66-0.81), and metastatic disease at initial diagnosis versus progression to metastatic disease (OR, 0.77; 95% CI, 0.70-0.84). CONCLUSIONS Our study shows that prognosis remains poor for patients with metastatic squamous NSCLC, even among those receiving treatment, but particularly for patients limited to supportive care only, highlighting the continuing unmet medical need in this population. Additionally, our analysis indicates that selections for second-line and third-line chemotherapies are not necessarily consistent with National Comprehensive Cancer Network guidelines.

Methodological approach for assessing the cost-effectiveness of treatments using longitudinal observational data: the SOHO study

OBJECTIVES The objective of this study was to develop a method to allocate treatment effects when patients switch medication frequently in longitudinal observational studies and apply the approach to assess the cost-effectiveness of treatments in the Schizophrenia Outpatient Health Outcomes (SOHO) study. METHODS Data were collected on patients at entry to the SOHO study at 3, 6, and 12 months. The 12-month follow-up period was considered as three epochs: 0-3 months, 3-6 months, and 6-12 months. Patients who switched treatment at 3 months had their new treatment considered as a new baseline observation, as these two 3-month observations provide two sets of information on the cost-effectiveness of a drug in the first 3 months after initiation. Multivariate regression analysis was used to adjust for baseline covariates. The model allowed for flexible functional forms, and the cost data were modeled using an exponential mean function. Bootstrapping assessed the uncertainty of the estimated parameters and incremental cost-effectiveness analysis decision rule. RESULTS AND CONCLUSIONS We show the feasibility of the epoch analysis approach using data from the SOHO study comparing two antipsychotics. Estimates for the incremental cost and effectiveness per epoch over the full 12-month period are presented. Using the estimates of 200 bootstrap samples, we demonstrate how one drug is cost-effective compared with another.

The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial

Introduction: Necitumumab, a second‐generation, recombinant human immunoglobulin G1 epidermal growth factor receptor antibody in the phase 3 SQUIRE trial (NCT00981058), increased survival benefit for patients randomized to receive necitumumab plus gemcitabine‐cisplatin compared with those who received gemcitabine‐cisplatin. Here we characterize health‐related quality of life (HRQoL) and tolerability results. Methods: A total of 1093 patients with stage IV squamous non–small cell lung cancer were randomized 1:1 to receive necitumumab (800 mg absolute dose intravenously [IV]) plus gemcitabine‐cisplatin (gemcitabine = 1250 mg/m2 IV on days 1 and 8; cisplatin = 75 mg/m2 IV on day 1) or gemcitabine‐cisplatin alone (every 21 days) for up to six cycles. Patients receiving necitumumab plus gemcitabine‐cisplatin without disease progression continued necitumumab until progression. HRQoL was measured by Eastern Cooperative Oncology Group performance status, the Lung Cancer Symptom Scale (LCSS), and the European Quality of Life Five‐Dimensions questionnaire. Efficacy and LCSS outcomes were analyzed using the baseline maximum severity score of the LCSS. Tolerability was measured in terms of exposure to the study treatment and adverse events. Hospitalization rates were collected. Results: Most patients in both study arms similarly maintained Eastern Cooperative Oncology Group performance status and comparable LCSS and European Quality of Life Five‐Dimensions questionnaire assessments. Patients with a higher baseline LCSS had a greater survival benefit on the necitumumab arm. Chemotherapy exposure was similar in both treatment arms; 51% of patients on the necitumumab plus gemcitabine‐cisplatin arm continued on single‐agent necitumumab. The most frequent grade 4 adverse events were neutropenia (6.1% versus 7.9%) and thrombocytopenia (3.2% versus 4.3%) in the necitumumab plus gemcitabine‐cisplatin versus gemcitabine‐cisplatin arms, respectively. Hospitalizations were slightly higher with necitumumab plus gemcitabine‐cisplatin (36.4%) than with gemcitabine‐cisplatin (34.0%). Conclusions: The addition of necitumumab to gemcitabine‐cisplatin was well tolerated, did not negatively affect HRQoL or toxicity, and particularly benefited patients with more severe baseline symptoms or lower HRQoL.

Utility values associated with advanced or metastatic non-small cell lung cancer: data needs for economic modeling

ABSTRACT Introduction: Cost-effectiveness analyses often inform healthcare reimbursement decisions. The preferred measure of effectiveness is the quality adjusted life year (QALY) gained, where the quality of life adjustment is measured in terms of utility. Areas covered: We assessed the availability and variation of utility values for health states associated with advanced or metastatic non-small cell lung cancer (NSCLC) to identify values appropriate for cost-effectiveness models assessing alternative treatments. Our systematic search of six electronic databases (January 2000 to August 2015) found the current literature to be sparse in terms of utility values associated with NSCLC, identifying 27 studies. Utility values were most frequently reported over time and by treatment type, and less frequently by disease response, stage of disease, adverse events or disease comorbidities. Expert commentary: In response to rising healthcare costs, payers increasingly consider the cost-effectiveness of novel treatments in reimbursement decisions, especially in oncology. As the number of therapies available to treat NSCLC increases, cost-effectiveness analyses will play a key role in reimbursement decisions in this area. Quantifying the relationship between health and quality of life for NSCLC patients via utility values is an important component of assessing the cost effectiveness of novel treatments.

Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE).

Background: In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors. Patient and Methods: Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)). Results: The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N). Conclusion: The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population.