Aurélie Millier

Background: Schizophrenia negative symptoms (SNS) contribute substantially to poor functional outcomes, loss in productivity and poor quality of life. It is unclear which instruments may be used for assessing quality of life in patients with SNS. Objective: The objective of this review was to identify instruments assessing health-related quality of life (HRQoL) validated in patients with SNS and to assess their level of validation. Data sources: We conducted a systematic literature review in Medline and the ISPOR database in March 2016 to identify studies on the quality of life in patients with SNS published by March 2016. Data extraction: Psychometric properties and validation steps. Data synthesis: After applying inclusion/exclusion criteria, 49 studies were selected for the analysis of HRQoL instruments; however, none of these instruments only addressed patients with SNS. Of these, 19 HRQoL instruments used in patients with schizophrenia or including patients with SNS among others, in the context of instrument validation, were identified (4 generic, 10 non-specific mental health, 5 schizophrenia-specific). Conclusion: No HRQoL instrument has been validated in patients with SNS only; for the remaining instruments identified, it remains unclear whether they were intended to capture HRQoL in patients with SNS.

The introduction of the orphan drug legislation led to the increase in the number of available orphan drugs, but the access to them is often limited due to the high price. Social preferences regarding funding orphan drugs as well as the criteria taken into consideration while setting the price remain unclear. The study aimed at identifying the determinant of orphan drug prices in France using a regression analysis. All drugs with a valid orphan designation at the moment of launch for which the price was available in France were included in the analysis. The selection of covariates was based on a literature review and included drug characteristics (Anatomical Therapeutic Chemical (ATC) class, treatment line, age of target population), diseases characteristics (severity, prevalence, availability of alternative therapeutic options), health technology assessment (HTA) details (actual benefit (AB) and improvement in actual benefit (IAB) scores, delay between the HTA and commercialisation), and study characteristics (type of study, comparator, type of endpoint). The main data sources were European public assessment reports, HTA reports, summaries of opinion on orphan designation of the European Medicines Agency, and the French insurance database of drugs and tariffs. A generalized regression model was developed to test the association between the annual treatment cost and selected covariates. A total of 68 drugs were included. The mean annual treatment cost was €96,518. In the univariate analysis, the ATC class (p = 0.01), availability of alternative treatment options (p = 0.02) and the prevalence (p = 0.02) showed a significant correlation with the annual cost. The multivariate analysis demonstrated significant association between the annual cost and availability of alternative treatment options, ATC class, IAB score, type of comparator in the pivotal clinical trial, as well as commercialisation date and delay between the HTA and commercialisation. The orphan drug pricing is a multivariate phenomenon. The complex association between drug prices and the studied attributes and shows that payers integrate multiple variables in decision making when setting orphan drug prices. The interpretation of the study results is limited by the small sample size and the complex data structure.

Background: It is unclear if the burden associated with schizophrenia is affected by the type and severity of patient's symptoms. Objective: This study aims to quantify healthcare resource use associated with different profiles of schizophrenia symptoms. Study design: Post-hoc analysis of data from a naturalistic follow-up study. Setting: Secondary psychiatric services in France, Germany and the UK. Patients: EuroSC cohort:, representative sample of 1,208 schizophrenia patients Main outcome measure: We classified patients into eight health states, according to the Lenert classification (HS1-HS8), and estimated 6-month healthcare resource use (outpatient and day clinic visits, and hospitalisations) across the health states. Results: Approximately half of the patients were classed as having mild symptoms (HS1), with around 20% experiencing moderate, predominantly negative symptoms (HS2). The remaining health states were represented by <10% of patients each. Very few patients experienced extremely severe symptoms (HS8). No health state was associated with excess utilisation across all resource types. In terms of outpatient visits, patients were estimated to see a psychiatrist most often (3.01-4.15 visits over 6 months). Hospital admission was needed in 11%(HS1) - 35%(HS8) of patients and inpatient stays were generally prolonged for all health states (39-57 days). The average number of inpatient days was highest for patients in HS8 (18.17 days), followed by patients with severe negative symptoms (HS4; 13.37 days). In other health states characterised by severe symptoms (HS5-HS7), the average number of inpatient days was approximately half of those seen for HS4 (6.09-7.66). Conclusion: While none of the symptom profiles was associated with excess resource usage, hospitalization days were highest for HS with severe, predominantly negative or extremely severe symptoms. Patients with predominantly negative, moderate or severe symptoms appeared to have a high number of psychologist visits - an interesting finding that may reflect a specific therapeutic approach to the treatment of these patients.

There is controversy as to whether use of statistical clustering methods to identify common disease patterns in schizophrenia identifies patterns generalizable across countries. The goal of this study was to compare disease states identified in a published study (Mohr/Lenert, 2004) considering US patients to disease states in a European cohort (EuroSC) considering English, French, and German patients. Using methods paralleling those in Mohr/Lenert, we conducted a principal component analysis (PCA) on Positive and Negative Syndrome Scale items in the EuroSC data set (n=1,208), followed by k-means cluster analyses and a search for an optimal k. The optimal model structure was compared to Mohr/Lenert by assigning discrete severity levels to each cluster in each factor based on the cluster center. A harmonized model was created and patients were assigned to health states using both approaches; agreement rates in state assignment were then calculated. Five factors accounting for 56% of total variance were obtained from PCA. These factors corresponded to positive symptoms (Factor 1), negative symptoms (Factor 2), cognitive impairment (Factor 3), hostility/aggression (Factor 4), and mood disorder (Factor 5) (as in Mohr/Lenert). The optimal number of cluster states was six. The kappa statistic (95% confidence interval) for agreement in state assignment was 0.686 (0.670–0.703). The patterns of schizophrenia effects identified using clustering in two different data sets were reasonably similar. Results suggest the Mohr/Lenert health state model is potentially generalizable to other populations.

Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption. Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness. Shifting from >220 HDDs per year to 120–140 HDDs and shifting from 36,000-39,000 g TAC per year (120–130 g/day) to 15,000–18,000 g TAC per year (50–60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses. This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health.

Objective The clinical symptoms of schizophrenia are associated with serious social, quality of life and functioning alterations. Typically, data on health utilities are not available in clinical studies in schizophrenia. This makes the economic evaluation of schizophrenia treatments challenging. The purpose of this article was to provide a mapping function to predict unobserved utility values in patients with schizophrenia from the available clinical and socio-demographic information. Methods The analysis was performed using data from EuroSC, a 2-year, multi-centre, cohort study conducted in France (N = 288), Germany (N = 618), and the UK (N = 302), totalling 1208 patients. Utility was calculated based on the EQ-5D questionnaire. The relationships between the utility values and the patients’ socio-demographic and clinical characteristics (Positive and Negative Syndrome Scale—PANSS, Calgary Depression Scale for Schizophrenia—CDSS, Global Assessment of Functioning—GAF, extra-pyramidal symptoms measured by Barnes Akathisia Scale—BAS, age, sex, country, antipsychotic type) were modelled using a random and a fixed individual effects panel linear model. Results The analysis demonstrated the prediction ability of the used parameters for estimating utility measures in patients with schizophrenia. Although there are small variations between countries, the same variables appear to be the key predictors. From a clinical perspective, age, gender, psychopathology, and depression were the most important predictors associated with the EQ-5D. Conclusion This paper proposed a reliable, robust and easy-to-apply mapping method to estimate EQ-5D utilities based on demographic and clinical measures in schizophrenia.

Triptans have been safely and effectively used in the management of migraine for more than fifteen years, and it seems reasonable to wonder what would be the economic impact of moving a specific triptan to OTC availability. The objective of this study was then to examine the economic impact of payer policies of a triptan Rx-to-OTC switch in six EU countries (France, UK, Spain, Italy, Germany and Poland). A decision model was used to model the budgetary impact of a triptan Rx-to-OTC switch from the third-party payer (TPP) and the societal perspectives, using a one-year timeframe. From the TPP perspective, it is estimated that the current overall direct spending on the management of migraine attacks across the 6 EU Member States is €582 million annually, and that the savings would reach €75 million (13% of the overall direct economic burden of migraine). From the societal perspective, €86 million annually would be added. Given evidence of effectiveness and safety, and given the potential savings, a triptan Rx-to-OTC switch is a reasonable public policy decision.

Background: In their study ‘Mental Health in the General Population: Images and Realities’ Jean-Luc Roelandt et al. found a huge divide between the French public’s conceptualizations of insanity and depression. The study aims to examine whether such differences can be replicated using modern operationalized diagnostic criteria for schizophrenia and major depressive disorder.Methods: In 2012, an online survey was conducted using a representative sample drawn from the adult French population (N = 1600). After presentation of a case-vignette depicting a person with either schizophrenia or major depressive disorder a fully structured interview was carried out.Results: Despite some similarities marked differences between both disorders emerge regarding beliefs and attitudes. While respondents presented with the schizophrenia vignette more frequently defined symptoms as the expression of an illness with a stronger biological component and a less favorable prognosis, demanding psychiatric treatment, respondents presented with the depression vignette considered the occurrence of symptoms more frequently as the consequence of current psychosocial stress, benefitting not only from established but also from alternative treatments. People with schizophrenia were more frequently perceived as unpredictable and dangerous, there was a stronger need to separate one-self from them, they were more frequently met with fear and less frequently reacted to with pro-social feelings, and they also faced more rejection.Conclusions: The French public draws a clear line between schizophrenia and major depressive disorder. This applies equally to beliefs about both disorders and to attitudes towards the persons afflicted. There is a need for interventions trying to reduce existing misconceptions in order to improve the care of patients.