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BACKGROUND: The safety and efficacy of paliperidone extended-release tablets (paliperidone ER) in patients with acute symptoms of schizophrenia have been described in 3 randomized, double-blind, 6-week, placebo-controlled, fixed-dose, Phase III clinical trials. The validity and reliability of the Personal and Social Performance (PSP) scale, both in patients with acute symptoms of schizophrenia and those with stabilized symptoms, have also been reported. OBJECTIVE: The aim of this work was to estimate the treatment benefit of paliperidone ER compared with placebo in terms of improvements in personal and social functioning as measured by the PSP scale in 3 controlled clinical trials. METHODS: Data were derived from 3 paliperidone ER multicenter Phase III pivotal studies of patients with acute symptoms of schizophrenia. Each study included a randomized, double-blind, placebo- and active-controlled, parallel-group, 6-week treatment period with an open-label extension of paliperidone ER treatment. Patients were randomized to receive paliperidone ER, olanzapine 10 mg, or placebo once daily. Paliperidone ER doses were 3, 9, and 15 mg/d in 1 study; 6, 9, and 12 mg/d in another; and 6 and 12 mg/d in the third. Collectively, 1306 intent-to-treat patients received placebo or paliperidone ER in these 3 trials. Most (61.7%) were white; 21.6% were black, 8.8% were Asian, and 7.9% were of another race. The mean age ranged from 36.3 to 39.4 years across treatment groups. Multiple analyses were applied to PSP data (for which higher scores indicate better personal and social functioning) from these paliperidone ER studies: between-group minimum important difference (MID) estimates; responder analyses; between-group cumulative frequency comparisons of PSP change from baseline to end point; and number-needed-to-treat (NNT) estimates. RESULTS: Standardized differences and effect sizes between paliperidone ER and placebo in PSP mean change from baseline to end point ranged from 0.52 to 0.85 for all paliperidone ER doses. Observed between-group differences (paliperidone ER minus placebo) in PSP mean change from baseline to end point exceeded the between-group MID of 7 points at all paliperidone ER doses. The percentage of patients achieving at least one 10-point category improvement in the PSP was higher with all paliperidone ER doses (range, 49.6%-63.6%) than placebo (33.1%) (P < 0.005). Across the distribution of all possible PSP scores, the percentage of patients achieving any level of change appeared to be greater for paliperidone ER than for placebo at all doses. Derived NNTs for improved personal and social functioning based on paliperidone ER trials ranged from 3.3 to 6.1. The improvement in personal and social functioning achieved by patients receiving paliperidone ER during the double-blind studies was maintained throughout the 52-week, open-label extension studies, as assessed using multiple definitions of response; subjects in the placebo arm during doubleblind treatment appeared to achieve and maintain improved functioning when switched to paliperidone ER for the extension studies. CONCLUSION: These results suggest that paliperidone ER had a meaningful treatment benefit with respect to improving personal and social functioning in these patients with acute symptoms of schizophrenia.

Objective: To assess the economic impact of two polychemotherapy regimens for patients with advanced ovarian cancer from the perspective of the Belgian health insurance and financing system. Design: An economic evaluation was integrated in an intergroup randomised controlled trial (EORTC 55931) in which patients were randomised to receive the new treatment of paclitaxel and cisplatin or the standard therapy of cyclophosphamide and cisplatin. Data on the use of medical resources were collected prospectively for the 231 European Organization for Research and Treatment of Cancer (EORTC) patients in the trial and costs were valued by using unit prices. The outcome for the economic evaluation was mean survival time as determined by the so-called restricted means method, with the time point of restriction fixed by statistical criteria. A correction of censoring of the cost data collected in the trial was also performed. Main outcome measures and results: The paclitaxel and cisplatin group experienced a statistically significant improvement in mean survival time of 4 months, which was associated with an increase in the average total cost per patient of 6795 euros (EUR; 1998 values), when costs were assessed over the same period as the gain in mean survival time. This corresponds to a point estimate of the incremental cost-effectiveness ratio of EUR20 385 per life-year gained. The impact of uncertainty was assessed by using a bias-corrected and accelerated bootstrap method with 5000 resamples, and the final results of the analysis are expressed in terms of a cost-effectiveness acceptability curve. Conclusions: The present economic evaluation has shown that the substitution of paclitaxel for cyclophosphamide in the chemotherapy regimen for women with advanced ovarian cancer leads to a significant improvement in patient survival, which is associated with an increase in costs for the Belgian health insurance system.

The AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) clinical trial examined the efficacy and safety of two ritonavir-boosted protease inhibitors (PI/r), darunavir/r 800/100 mg once daily (QD) and lopinavir/r 800/200 mg daily, both used in combination with tenofovir disoproxil fumarate/emtricitabine. This study aimed to assess the cost effectiveness of the darunavir/r regimen compared with the lopinavir/r regimen in treatment-naive adults with HIV-1 infection in Canada. A Markov model with a 3-month cycle time and six CD4 cell-count-based health states (>500, 351–500, 201–500, 101–200, 51–100, and 0–50 cells/mm3) followed a cohort of treatment-naive adults with HIV-1 infection through initial darunavir/r or lopinavir/r combination therapy and a common set of subsequent regimens over the course of their remaining lifetimes. Population characteristics and transition probabilities were estimated from the ARTEMIS clinical trial and other trials. Costs (in 2014 Canadian dollars), utilities, and mortality were estimated from Canadian sources and published literature. Costs and health outcomes were discounted at 5 % per year. One-way and probabilistic sensitivity analyses were performed, including a simple indirect comparison of the darunavir/r initial regimen with an atazanavir/r-based regimen. In the base-case lifetime analysis, individuals receiving initial therapy with the darunavir/r regimen experienced 0.25 more quality-adjusted life-years (QALYs) with lower antiretroviral drug costs (−$14,246) and total costs (−$18,402) than individuals receiving the lopinavir/r regimen, indicating that darunavir/r dominated lopinavir/r. In an indirect comparison with an atazanavir/r-based regimen, the darunavir/r regimen remained the dominant choice, but with lower cost savings (−$2,303) and QALY gains (0.02). Results were robust to a wide range of other changes in input parameter values, population characteristics, and modeling assumptions. The probabilistic sensitivity analysis demonstrated that the darunavir/r regimen was cost effective compared with the lopinavir/r regimen in over 86 % of simulations for willingness-to-pay thresholds between $0 and $100,000 per QALY gained. Darunavir/r 800/100 mg QD may be a cost-effective PI/r component of initial antiretroviral therapy for treatment-naive adults with HIV-1 infection in Canada.

OBJECTIVE: To describe the measurement properties of the Personal and Social Performance scale (PSP), a clinician-reported measure of severity of personal and social dysfunction, in subjects with acute symptoms of schizophrenia. METHODS: Pooled data from three paliperidone extended-release clinical studies (n = 1665) and data from a separate noninterventional, cross-sectional, validation study (n = 299) were analyzed. RESULTS: The PSP showed good interrater (intraclass correlation coefficient [ICC] = 0.87) and test-retest (ICCs > 0.90) reliability. Pearson correlation coefficient for association between baseline PSP and Positive and Negative Syndrome Scale (PANSS) total scores was -0.32 for subjects assessed by the same rater and -0.29 for subjects assessed by different raters, suggesting low overlap in measurement constructs between the PANSS and PSP. Spearman Rank correlation coefficient for association between baseline PSP and Clinical Global Impression-Severity (CGI-S) scores was -0.51 with the same rater and -0.15 with different raters. Hypothesized relationships between the PSP and the PANSS or CGI-S based on levels of disease severity were prospectively defined. These hypotheses were confirmed by analyses showing statistically significant differences between baseline mean PSP scores in subjects grouped by severity rating on the CGI-S (mild or less vs. at least moderate) (p < 0.001) and the PANSS ('low symptom severity' vs. 'high symptom severity') (p = 0.005). The PSP was sensitive to change based on statistically significant correlations between change in the PSP and change in the CGI-S (p < 0.001) and the PANSS (p < 0.001). Limitations of analyses include pooling data across studies, interrater reliability assessment in the validation study only, post hoc assessment of test-retest reliability in the paliperidone ER studies, different raters for the PSP and PANSS not specified in the paliperidone ER studies, PSP validity assessment based on the PANSS and the CGI-S as comparators rather than another social function instrument. CONCLUSION: These initial reliability and validity assessments suggest the PSP has promise as a measure of social functioning in patients with acute symptoms of schizophrenia.