Clinical implications and cost-effectiveness analysis of rivaroxaban in patients with coronary artery disease or peripheral arterial disease in the Netherlands.

BACKGROUND: Patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD) are at substantial risk of atherothrombotic events. The COMPASS trial showed that patients with stable CAD or PAD experienced significant benefits after treatment with rivaroxaban in combination with acetylsalicylic acid (ASA) compared with ASA alone. This paper aims to provide insight into the clinical and economic consequences of treatment with rivaroxaban from a Dutch societal perspective. METHODS: The clinical and economic implications of rivaroxaban in terms of the number of events prevented, costs, the incremental cost per life-years gained (LYG), and incremental cost per quality-adjusted life-years (QALYs) were determined based on a cost-effectiveness model for patients with stable CAD or PAD and in high-risk subgroups (i.e. patients with CAD and PAD, CAD and prior myocardial infarction and renal impairment, CAD and heart failure) using results from the Cardiovascular OutcoMes for People Using Anticoagulation Strategies (COMPASS) trial. RESULTS: Patients treated with rivaroxaban have an expected increased discounted life expectancy of 0.67 years. In high-risk groups discounted incremental life expectancy ranged from 1.33 to 1.90 years. The incremental cost-effectiveness ratio for the full COMPASS population was €9,760/LYG and €12,033/QALY, whereas, for high-risk subgroups of patients with underlying conditions, incremental cost-effectiveness ratios ranged from €2,966/LYG to €5,052/LYG and from €3,940/QALY to €6,815/QALY. Results from the sensitivity analyses revealed that the model results were robust to variations in single or multiple input parameters at once. CONCLUSIONS: The cost-effectiveness analysis showed that rivaroxaban in combination with ASA is a cost-effective treatment option in stable CAD or PAD patients. Rivaroxaban in combination with ASA is even more cost-effective in high-risk subgroups.

Direct healthcare cost of schizophrenia - European overview.

PURPOSE: To provide an overview on the magnitude of the impact of schizophrenia on the healthcare system in Europe and to gain a better understanding on the most important factors influencing the variation of costs. METHODS: Studies reporting costs and healthcare utilization among patients with schizophrenia were searched in MEDLINE (via Scopus), EMBASE (via Scopus) and Cochrane Database of Systematic Reviews on 19th January 2017. RESULTS: Twenty-three studies, from the 1075 references initially identified, were included in this review. The annual cost per patient ranged from €533 in Ukraine to €13,704 in the Netherlands. Notably drug costs contributed to less than 25% of the direct healthcare cost per patient in every country, which might be explained by similar pharmaceutical prices among countries due to the reference pricing system applied in Europe. Inpatient costs were the largest component of health service costs in the majority of the countries. Despite methodological heterogeneity across studies, four major themes could be identified (age, severity of symptoms, continuation of treatment/persistence, hospitalization) that have substantial impact on the costs of schizophrenia. CONCLUSIONS: Schizophrenia represents a substantial cost for the healthcare system in Europe driven by the high cost per patient. Substantial savings could potentially be achieved by increasing investment in the following areas: (1) reducing the number of hospitalizations e.g. by increasing the efficiency of outpatient care; (2) working out interventions targeted at specific symptoms; (3) improving patient persistence and adherence in antipsychotic therapy.

Healthcare resource use in schizophrenia, EuroSC findings.

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.

Utility decrements associated with side effects in schizophrenia.

OBJECTIVE: Most of the existing studies investigating the impact of schizophrenia on utility have focused on the different stages of the disease. The objective of this study was to describe and quantify the impact of treatment-related side-effects on utility in patients with schizophrenia, using data from an observational study. METHODS: This study used data from the European Schizophrenia Cohort (EuroSC), a multi-center 2-year cohort study conducted in France, England, and Germany. The EQ-5D questionnaire was completed every 6 months, as well as the Subjective Side Effect Rating Scale, assessing patient distress over extrapyramidal symptoms (EPS), weight gain, sedation, and sexual dysfunction, used to assess whether or not the patient experienced the side-effect. At first a bivariate analysis was conducted to describe utility values with and without side-effects. Then, a random effects regression analysis was performed on utility, where random effects were controlled for repeated measures on the same subjects, with potential confounding factors. Finally, findings were compared with those of previous publications. RESULTS: This sample consisted of 1208 patients with schizophrenia. At the baseline visit, the most reported side-effect was EPS (almost 60% of patients), followed by sedation and weight gain (∼50% of patients for each), and sexual dysfunction (almost 30% of patients). Significant association with severity of symptoms, functioning abilities, and utility were found. Patients reporting none of the studied side-effects had an average EQ-5D index score of 0.81, found to be higher than scores of patients reporting EPS (0.70), sexual dysfunction (0.67), sedation (0.70), or weight gain (0.72). The random effects model reported a utility decrement of 0.042 for EPS, 0.022 for weight gain, 0.022 for sexual dysfunction, and 0.019 for sedation. Although the external validation was difficult due to the different methods or definitions of the side-effects, as well as the paucity of data for weight gain, sedation and sexual dysfunction, the results were generally consistent with previous studies. CONCLUSION: This study aimed at quantifying the direct impact of main side-effects associated with antipsychotics on patients' utility. RESULTS suggested a significant direct impact of side-effects, with EPS being the most impactful.

Humanistic burden in schizophrenia: a literature review.

OBJECTIVES OF THE STUDY AND BACKGROUND: Schizophrenia is a complex disease that affects 1% of the population. This disease has a considerable impact not only on patients' health and well-being but also on their surrounding environment. The costs of the disease's management remain large for individuals and society. While literature on the economic impact of schizophrenia is abundant, few studies have focused on its humanistic burden. This does not only concern patients, but also caregivers, relatives, neighbours and others in a patient's daily life. This burden appears through several dimensions, including treatment side effects and the impact on caregivers and features of the patient's environment. The aim of this review is to consider, compile and describe the humanistic burden of schizophrenia as documented in the literature. MATERIALS AND METHODS: We conducted a literature review assessing the worldwide disease burden of schizophrenia, taking into account all humanistic burden topics. The search considered several databases, including Embase, Medline, Cochrane Library, The German Institute of Medical Documentation and Information (DIMDI) and the ISPOR conference websites. RESULTS: The search identified 200 literature reviews, covering several dimensions of humanistic burden and documenting many issues. Main findings included the high death rates that may be explained by long-lasting negative health habits, disease- and treatment-related metabolic disorders, and consequent increased frequencies of cardiovascular diseases. Co-existing depression was found to have adverse consequence on the course of schizophrenia progression, morbidity and mortality. Cognitive impairment also adds to the burden of schizophrenia. Social impairment is worsened by underestimated stigmatisation and lack of corresponding awareness within the professional and social spheres. Finally, caregiver burden was found to be considerable. DISCUSSION: Humanistic burden among patients with schizophrenia is substantial potentially impacted by co-morbid depressive symptoms, caregiver burden and cognitive impairment. Effects of treatment on humanistic burden in addition to economic burden need to be explored in future trials.

Evaluation of different approaches for confounding in nonrandomised observational data: a case-study of antipsychotics treatment.

Although randomised controlled trials are regarded as the gold standard for treatments efficacy, evidence from observational studies remains relevant. To address the problem of possible confounding in these studies, investigators must employ analysis methods that adjust for confounders and lead to an unbiased estimation of the treatment effect. In this paper, the authors describe two relevant statistical methods. The first method represents the classical approach consisting of a multiple regression model including the effects of treatment and covariates. This approach considers the relation between prognostic factors and the outcome variable as a relevant criterion for adjustment. The second method is based on the propensity score, and focuses on the relation between prognostic factors and treatment assignment. These approaches were applied to a cohort of 183 French schizophrenic patients who were followed for a 2-year period (from 1998 to 2000). The probability of relapse according to antipsychotic treatment exposure was modelled using Cox regression models with the two statistical methods. Goodness-of-fit criteria were used to compare the modelling approaches. This study demonstrates that the propensity score, a predicted probability, has an important balancing property that underscores its value in strengthening the results of nonrandomised observational studies.

Assessing the economic impact of Rx-to-OTC switches: systematic review and guidelines for future development.

INTRODUCTION: Switching drugs from prescription to non-prescription status (Rx-to-OTC) presents a unique set of challenges and opportunities to policy-makers and the industry in terms of managing health outcomes, pharmaceutical spending, and steering of consumer choices of therapy. Decision-analytic models are used to address uncertainty and produce reasonable estimates of the economic impact of switches for payers. This article presents a critical literature review of existing models which assess the economic impact of Rx-to-OTC switches, and provides guidelines in which future economic evaluations of Rx-to-OTC switches could be improved. METHODS: A comprehensive search strategy was implemented in Medline and Embase, to retrieve published economic evaluations on Rx-to-OTC switches from 1995-2010. The research digest of the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) was reviewed for potentially relevant abstracts for the past 3 years. Each model used was critically evaluated in terms of structure, relevance of inputs, methodology used, and robustness of results. RESULTS: Worldwide, the economic impact of Rx-to-OTC switches has only been evaluated in a total of 12 peer-reviewed publications. Ten out of 12 studies were US-based, and two European-based. The models covered various disease categories, including allergy, hypercholesterolemia, gastroenterology, contraception, pulmonology, and virology. Seventy-five per cent of the models predicted cost savings for payers and patients. Limitations of the models mainly included use of strong assumptions and non-inclusion of specific populations due to lack of data. Guidelines were developed to help future model development. They cover structural issues on decision context, health states, and clinical outcomes, and other considerations for model specifications. CONCLUSIONS: Although reviewed studies lacked quality, this review of economic evidence of Rx-to-OTC switches suggests that switches may produce cost savings to public and private payers. This is especially important in light of the trend towards more switches.