Predictors of Employment for People With Mental Illness: Results of a Multicenter Randomized Trial on the Effectiveness of Placement Budgets for Supported Employment.

Background: Individual placement and support (IPS) has proven to be effective for vocational outcomes in people with mental illness. The original concept of IPS requires temporally unlimited provision of support. Using limited placement budgets and investigating factors that predict their effectiveness may inform decisions about resource allocation. Methods: A range of patient characteristics were tested as predictors of employment outcomes in participants who attended six outpatient psychiatric clinics in Switzerland between June 2010 and May 2011. Overall, 116 patients with the full spectrum of psychiatric conditions were randomly assigned and started an IPS intervention, which was provided by three different placement budgets. Support lasted 2 years for those who found a job, and outcomes were repeatedly assessed over 3 years. The intervention ended for those who failed to find competitive employment by the time their placement budget had run out. Results: Of the 15 variables tested, only Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) scores were predictors for obtaining work (for ≥1 day) and for maintaining it over a longer period (>3 months). Higher GAF and lower CGI scores increased the odds of obtaining employment and keeping it for at least 3 months. Functional role impairment, quality of life, self-esteem, or education level did not predict employment. Conclusion: Our data suggest that, if time-restricted budgets are offered to a wide range of patients, such as those included in this study, better functioning and lower symptom severity at baseline are predictive of better employment outcomes (finding and maintaining work) on the first (competitive) labor market in Switzerland. It remains to be investigated whether this holds true under different environmental factors. Clinical Trial Registration: ISRCTN, trial number: ISRCTN89670872.

Sleep Disturbances and Suicidality-A Longitudinal Analysis From a Representative Community Study Over 30 Years.

Study objectives: Associations between sleep problems and suicidality are increasingly acknowledged, but prospective data from well-controlled long-term community studies are lacking. Methods: We analyzed data from a longitudinal cohort study with n = 591 young adults from Zurich, Switzerland, prospectively followed from 1979 (age 20/21 years) to 2008 (age 49/50 years). Twelve-month prevalence of various mental disorders, socio-environmental confounders and sleep problems were carefully assessed with semi-structured interviews at 7 assessment waves spanning overall a 30-year observation period. Interviews were conducted with the "Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology" (SPIKE). The 12-month prevalence of sleep problems was graded according to frequency and associated distress of reported symptoms. 12-month prevalence of suicidality was classified as either mild (transient suicidal ideation) or severe (self-harm, suicide attempts). Results: Concurrently, and fully adjusted for several covariates, including mental disorders, relative to no sleep problems there was an odds ratio (OR) of OR = 1.9 (95% confidence interval 1.4-2.5), OR = 3.3 (2.5-4.4), and OR = 1.9 (1.3-2.8) for mild, moderate and severe sleep problems in association with suicidality. There was no evidence for a prospective effect of broad sleep problems on subsequent suicidality. Mild suicidality, but not severe suicidality, prospectively predicted subsequent broad sleep problems in the fully adjusted multivariate model (adjusted OR = 1.5; 1.1-1.9). Disturbed sleep initiation, a proxy for insomnia, significantly predicted subsequent suicidality (OR = 1.5; 1.1-1.9), whereas mild suicidality, but not severe suicidality, significantly predicted subsequent insomnia (OR = 1.5; 1.1-2.0). Conclusions: Sleep problems and suicidality are longitudinally inter-related, which has important implications for clinical practice. Most importantly, the causal pathways appear to be bi-directional and independent of socio-demographics and concomitant mental disorders. More research is needed to examine the possible biopsychosocial etiological mechanisms linking suicidality to sleep problems.

Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation.

PURPOSE: The pivotal trials for stroke prevention in non-valvular atrial fibrillation (NVAF) compared rivaroxaban, dabigatran, and apixaban with warfarin, as did most claims-based studies. Comparisons with phenprocoumon, the most frequently used vitamin K antagonist (VKA) in Germany, are scarce. METHODS: Risk of bleeding, ischemic stroke, and all-cause mortality in patients with NVAF were analyzed using data for 2010 to 2014 from a large German claims database. New users of oral anticoagulants from January 2012 to December 2013 were included and observed over 1 year. Baseline characteristics were adjusted using propensity score matching and logistic regression. Several sensitivity analyses were carried out. RESULTS: Fifty-nine thousand four hundred forty-nine rivaroxaban, 23,654 dabigatran, 4894 apixaban, and 87,997 matched phenprocoumon users were included. Adjusted hazard ratios (95% confidence intervals) compared with phenprocoumon were as follows: hospitalized bleedings: rivaroxaban 1.04 (0.97; 1.11), dabigatran 0.87 (0.77; 0.98), and apixaban 0.65 (0.50; 0.86); ischemic stroke: rivaroxaban 1.05 (0.94; 1.17), dabigatran 1.14 (0.96; 1.35), and apixaban 1.84 (1.20; 2.84); all-cause mortality: rivaroxaban 1.17 (1.11; 1.22), dabigatran 1.04 (0.95; 1.13), and apixaban 1.14 (0.97; 1.34). CONCLUSIONS: With rivaroxaban, no significant differences were observed compared to phenprocoumon with regard to hospitalized bleedings or ischemic strokes. Dabigatran was associated with fewer bleedings and a similar risk of ischemic strokes compared to phenprocoumon. Apixaban was also associated with fewer bleedings but was unexpectedly associated with more ischemic strokes, possibly reflecting selective prescribing. The association of rivaroxaban with higher all-cause mortality unrelated to bleedings or strokes has been described previously but remains to be explained.

[The costs of new drugs compared to current standard treatment]. / Die Preise neuer Arzneimittel im Vergleich zu ihren therapeutischen Alternativen.

BACKGROUND: Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. METHOD: We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. RESULTS: If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions.

New drugs: evidence relating to their therapeutic value after introduction to the market.

BACKGROUND: Drug approval is based on three criteria: quality, efficacy, and safety. We investigated the types of study design and statistical methods employed to demonstrate safety and efficacy of proprietary medicinal products (PMPs) that were approved for use in the European Union through the centralized procedure. METHODS: We retrospectively analyzed the European Public Assessment Reports of PMPs that the European Medicinal Agency approved, either initially or for extended indications, in 2009 and 2010. RESULTS: Data were analyzed for 39 PMPs: 64% of these were new active substances, and 36% were approved for extended indications. 46% of the PMPs had been studied in an active-control trial. In only 28%, superiority of the new PMPs compared to active control had been tested. 46% of the approvals included testing of a patient-relevant primary endpoint. The median size of population used to demonstrate safety was 1700 persons. CONCLUSION: The centralized procedure does not require comparative information from active-control trials. Accordingly, as our descriptive analysis revealed, this information is often not available at the time of market introduction. Pivotal studies only rarely clearly demonstrate an added therapeutic value of a new PMP compared to existing alternatives.