Christophe Sapin

Development and validation of a perioperative satisfaction questionnaire.

Background:Satisfaction is considered a valuable measure of outcome of healthcare processes. Only a few anesthesia-related validated questionnaires are reported. Because their scope is restricted to specific clinical contexts, their use remains limited. The objective of the current study was to develop and validate a self-reported questionnaire, Evaluation du Vécu de l’Anesthésie Générale (EVAN-G), assessing the satisfaction of the perioperative period surrounding general anesthesia. Methods:Development of the EVAN-G questionnaire comprised a phase of item generation and a phase of psychometric validation. The patient sample was generated to be proportionally matched to the population of patients undergoing general anesthesia in France. The structure of the questionnaire was identified studying interitem, item–dimension, and interdimension correlations and factor analyses. Data were concurrently gathered to assess external validity. The discriminant validity was determined by comparison of scores across well known patient groups. Reliability was assessed by computation of Cronbach α coefficients and by test–retest. Results:Eight hundred seventy-four patients were recruited in eight anesthesia departments. The EVAN-G includes 26 items; six specific scores and one global index score are available. Correlations between EVAN-G scores and other concurrent measures supported convergent validity. The EVAN-G correlated poorly with age, American Society of Anesthesiologists physical status, total anesthesia time, and number of previous anesthesias. Significantly higher satisfaction was reported by patients older than 65 yr, belonging to the laryngeal mask group. Reliability and reproducibility were shown. Conclusion:The EVAN-G adds important information oriented toward patients’ perceptions. The authors’ approach provides a novel, valid, and reliable tool that may be used in anesthesia practice.

Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia

OBJECTIVE To directly compare aripiprazole once-monthly 400mg (AOM 400) and paliperidone palmitate once-monthly (PP) on the Heinrichs-Carpenter Quality-of-Life Scale (QLS), a validated health-related quality of life and functioning measure in schizophrenia. METHOD This 28-week, randomized, non-inferiority, open-label, rater-blinded, head-to-head study (QUALIFY) of AOM 400 and PP in adult patients (18-60 years) comprised oral conversion, initiation of AOM 400 or PP treatment, and continuation with intramuscular injections every 4weeks. The primary endpoint assessed non-inferiority and superiority on QLS total score analyzed using a mixed model for repeated measurements. RESULTS Of 295 randomized patients, 100/148 (67.6%) of AOM 400 and 83/147 (56.5%) of PP patients completed 28weeks of treatment. A statistically significant least squares mean difference in change from baseline to week 28 on QLS total score (4.67 [95%CI: 0.32;9.02], p=0.036) confirmed non-inferiority and established superiority of AOM 400 vs PP. There were also significant improvements in Clinical Global Impression - Severity scale and the Investigators Assessment Questionnaire for AOM 400 vs PP, and pre-defined sub-group analyses revealed a consistent pattern of significance favoring AOM 400 in patients ≤35years. Common treatment-emergent adverse events in the treatment continuation phase were more frequent with PP vs AOM 400, and adverse events were the most frequent reason for discontinuation (27/137 [19.7%] for PP and 16/144 [11.1%] for AOM 400). All-cause discontinuation was numerically lower with AOM 400. CONCLUSION Superior improvements on clinician-rated health-related quality of life and a favorable tolerability profile suggest greater overall effectiveness for aripiprazole once-monthly vs paliperidone palmitate. ClinicalTrials.gov identifier:NCT01795547.

The Sertindole Safety Survey: A retrospective analysis under a named patient use programme in Europe

BackgroundAfter sertindoles suspension, health authorities established a specific named-patient use (NPU) programme in order to supply sertindole to patients who did not respond to or did not tolerate alternative treatments. This programme provided the possibility of prospectively following an exhaustive cohort of patients treated with sertindole after its suspension. A survey was performed to assess sertindoles modalities of prescription, assess and document any serious adverse events (SAEs), and assess the mortality rate within the NPU cohort.MethodsThe study comprised a survey of sertindole-treated patients in eleven European countries. All patients treated with sertindole within the NPU programme were eligible for the study.Results1,432 patients were included in the study. The reason for sertindole prescription was lack of efficacy (approximately 50%) or adverse events (approximately 20%) of other antipsychotic treatments. The mean sertindole dose was 13.4 mg daily. Lack of efficacy and adverse events were reported as reasons for sertindole discontinuation.A total of 97 SAEs were recorded, including ten fatal outcomes, which occurred during the study period or within thirty days after sertindole discontinuation. The all-cause mortality rate was 0.51 per 100 Person-Years of Exposure (95% Poisson confidence interval: 0.23–0.97). QTc prolongation was reported in 15 patients (1.05% of total patients), being a rate of 0.85 per 100 Person-Years of Exposure [95% CI: 0.48–1.41].ConclusionAlthough prescribing and supplying sertindole were subject to administrative constraints, a significant number of patients were treated with sertindole, thus supporting the need for sertindole in specific cases.Trial registration numberNot applicable.

A pharmacoeconomic analysis of sertindole in the treatment of schizophrenia in Sweden

Background: Atypical antipsychotics have similar clinical efficacy in the treatment of schizophrenia; variability in their tolerability represents the discerning factor in treatment choices. Sertindole has a relatively good tolerability profile that favours long-term patient adherence and, therefore, is associated with lower rates of relapse and rehospitalization. Aim: A model was developed to compare the cost-effectiveness of a 5-year treatment strategy starting with sertindole versus olanzapine, risperidone, aripiprazole or the typical antipsychotic agent, haloperidol. Methods: The model was based on published trials and local clinical practice, and considered costs from the perspective of the Swedish National Health Insurance Board. Results: All atypical agents were clinically superior and more cost-effective than haloperidol with a cost per quality-adjusted life year gained of approximately 490,000 Swedish kroner. Sertindole was associated with the lowest direct and indirect medical costs, driven by its tolerability profile. Conclusions: Sertindole represents a useful alternative to the current treatment options available in Sweden. Clinical implications: The relatively good tolerability profile of sertindole translates into lower costs of schizophrenia management, primarily driven by substantially lower direct and indirect costs. Sertindole appears to be a clinically and cost-effective alternative in the management of patients with schizophrenia in Sweden.

Shortening the VSP-A: preliminary development of the VSP-A12, a 12-item short-form.

The ‘Vécu et Santé Perçue des Adolescents’ (VSP-A) questionnaire is a French generic self-administered health-related quality of life (HRQL) instrument for adolescents which comprises 40 items, allowing the calculation of six dimensions as well as an index. Regression methods were used to select 12 items from the VSP-A to reproduce its HRQL index. The resulting 12-item short-form (VSP-A12) achieved an adjusted R2 of 0.907 in prediction of the VSP-A index. Scoring algorithm used to score this 12-item index achieved a R2 of 0.901 with the VSP-A index when cross-validated in the validation sample (n = 2941). Numerous tests of empirical validity previously published for the VSP-A were replicated for the VSP-A12, including comparisons between groups known to differ in terms of gender, age or health status. All the significant results shown by the VSP-A index were also encountered by the VSP-A12 summary measure. The ability of VSP-A12 to discriminate between healthy and ill adolescents was also proven. A test–retest correlation (4 weeks) of 0.745 was observed for the 12-item HRQL index in the target population (n = 664). Average score for this shorter index closely mirrored VSP-A index, although standard deviation was always greater for the VSP-A12.

Defining the minimal clinically important difference (MCID) of the Heinrichs–carpenter quality of life scale (QLS)

To determine the Minimal Clinically Important Difference (MCID) of the Heinrichs–Carpenter Quality of Life Scale (QLS). Data from the “Schizophrenia Trial of Aripiprazole” (STAR) study were used in this analysis. The MCID value of the QLS total score was estimated using the anchor‐based method. These findings were substantiated/validated by comparing the MCID estimate to other measurements collected in the study. Half of the patients (49%) showed improvement in Clinical Global Impressions of Severity (CGI‐S) during the trial. The estimated MCID of the QLS total score was 5.30 (standard error: 2.60; 95% confidence interval: [0.16; 10.43]; p < 0.05). Patients were divided into two groups: “QLS improvers” (QLS total score increased ≥ six points) and “non‐improvers”. The QLS improvers had significantly better effectiveness and reported significantly higher levels of preference for their current medications. There was a statistically significant difference between the two groups in the change in two of the four domains of QLS; “Interpersonal relations” and “Intrapsychic foundations” domains during the study. These findings support the value of the estimated MCID for the QLS and may be a useful tool in evaluating antipsychotic treatment effects and improving long‐term patient outcomes in schizophrenia. Copyright

Cost-effectiveness of aripiprazole once-monthly compared with paliperidone palmitate once-monthly injectable for the treatment of schizophrenia in the United States.

Abstract Objective: To develop a decision-analytic model to estimate the cost-effectiveness of initiating maintenance treatment with aripiprazole once-monthly (AOM) vs paliperidone long-acting injectable (PLAI) once-monthly among patients with schizophrenia in the US. Methods: A decision-analytic model was developed to evaluate a hypothetical cohort of patients initiating maintenance treatment with AOM or PLAI. Rates of relapse, adverse events (AEs), and direct medical costs were estimated for 1 year. Patients either remained on initial treatment or discontinued treatment due to lack of efficacy, AEs, or other reasons, including non-adherence. Data from placebo-controlled pivotal trials and product prescribing information (PI) were used to estimate treatment efficacy and AEs. Analyses were performed assuming dosing of clinical trials, real-world practice, PIs, and highest therapeutic dose available, because of variation in practice settings. The main outcome of interest was incremental cost per schizophrenia hospitalization averted with AOM vs PLAI. Results: Based on placebo-controlled pivotal trials’ dosing, AOM improved clinical outcomes by reducing schizophrenia relapses vs PLAI (0.181 vs 0.277 per person per year [pppy]) at an additional cost of US

Comparison of escitalopram and citalopram in outpatients with severe major depressive disorder: a prospective, naturalistic, 8-week study

1276 pppy, resulting in an incremental cost-effectiveness ratio (ICER) of US

Reduced sexual dysfunction with aripiprazole once-monthly versus paliperidone palmitate: results from QUALIFY

13,280/relapse averted. When PI dosing was assumed, this ICER increased to US

Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials

19,968/relapse averted. When real-world dosing and highest available dosing were assumed, AOM was associated with fewer relapses and lower overall treatment costs vs PLAI. Conclusions: AOM consistently provided favorable clinical benefits. Under various dosing scenarios, AOM results indicated fewer relapses at lower overall costs or a reasonable cost-effectiveness threshold (i.e., less than the cost of a hospitalization relapse) vs PLAI. Given the heterogeneous nature of schizophrenia and variability in treatment response, health plans may consider open access for treatments like AOM. Since model inputs were based on data from separate placebo-controlled trials, generalization of results to the real-world setting is limited.