Cost-effectiveness of dapagliflozin (Forxiga®) added to metformin compared with sulfonylurea added to metformin in type 2 diabetes in the Nordic countries.

AIMS: The aim of this study was to assess the long-term cost-effectiveness of dapagliflozin (Forxiga(®)) added to metformin, compared with sulfonylurea (SU) added to metformin, in Nordic Type 2 diabetes mellitus (T2DM) patients inadequately controlled on metformin. METHODS: Data from a 52-week clinical trial comparing dapagliflozin and SU in combination with metformin was used in a Cardiff simulation model to estimate long term diabetes-related complications in a cohort of T2DM patients. Costs and QALYs were calculated from a healthcare provider perspective and estimated over a patient's lifetime. RESULTS: Compared with metformin+SU, the cost per QALY gained with dapagliflozin+metformin was €7944 in Denmark, €5424 in Finland, €4769 in Norway, and €6093 in Sweden. Metformin+dapagliflozin was associated with QALY gains ranging from 0.236 in Norway to 0.278 in Sweden and incremental cost ranging from €1125 in Norway to €1962 in Denmark. Results were robust across both one-way and probabilistic sensitivity analyses. Results were driven by weight changes associated with each treatment. CONCLUSIONS: Results indicate that metformin+dapagliflozin is associated with gains in QALY compared with metformin+SU in Nordic T2DM patients inadequately controlled on metformin. Dapagliflozin treatment is a cost-effective treatment alternative for Type 2 diabetes in all four Nordic countries.

Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review.

BACKGROUND: Nonadherence to medication is a recognized problem and may be the most challenging aspect of treatment. METHODS: We performed a systematic review of factors that influence adherence and the consequences of nonadherence to the patient, healthcare system and society, in patients with schizophrenia. Particular attention was given to the effect of nonadherence on hospitalization rates, as a key driver of increased costs of care. A qualitative systematic literature review was conducted using a broad search strategy using disease and adherence terms. Due to the large number of abstracts identified, article selection was based on studies with larger sample sizes published after 2001. Thirty-seven full papers were included: 15 studies on drivers and 22 on consequences, of which 12 assessed the link between nonadherence and hospitalization. RESULTS: Key drivers of nonadherence included lack of insight, medication beliefs and substance abuse. Key consequences of nonadherence included greater risk of relapse, hospitalization and suicide. Factors positively related to adherence were a good therapeutic relationship with physician and perception of benefits of medication. The most frequently reported driver and consequence were lack of insight and greater risk of hospitalization respectively. CONCLUSIONS: Improving adherence in schizophrenia may have a considerable positive impact on patients and society. This can be achieved by focusing on the identified multitude of factors driving nonadherence.

The societal cost of bipolar disorder in Sweden.

PURPOSE: There is a lack of comprehensive cost-of-illness studies in bipolar disorder, in particular studies based on patient-level data. The purpose of this study was to estimate the societal cost of bipolar disorder and to relate costs to disease severity, depressive episodes, hospitalisation and patient functioning. METHODS: Retrospective resource use data in inpatient and outpatient care during 2006-2008, as well as ICD-10 diagnoses and Global Assessment of Functioning (GAF) scores, were obtained from the Northern Stockholm psychiatric clinic with a catchment area including 47% of the adult inhabitants in Stockholm. This dataset was combined with national register data on prescription pharmaceuticals and sick leave to estimate the societal cost of bipolar disorder. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. RESULTS: The average annual cost per patient was 28,011 in 2008 (n = 1,846). Indirect costs due to sick leave and early retirement represented 75%, inpatient costs 13%, outpatient costs 8%, pharmaceuticals 2% and community care another 2% of the total cost. Total costs were considerably higher during mood episodes (six times higher than in remission), for hospitalised patients (55,500 vs. 22,200) and for patients with low GAF scores. CONCLUSIONS: The high cost of bipolar disorder is driven primarily by indirect costs. Costs were strongly associated with mood episodes, hospitalisations and low GAF scores. This suggests that treatment that reduces the risk for relapses and hospitalizations and improve functioning may decrease both the societal cost of bipolar disorder and patient suffering.

The societal cost of schizophrenia in Sweden.

BACKGROUND: Schizophrenia is a disabling psychiatric disorder that has severe consequences for patients and their families. Moreover, the expensive treatment of schizophrenia imposes a burden on health care providers and the wider society. Existing cost estimates for Sweden, however, are based on relatively small patient populations and need to be confirmed in a large register-based study. AIMS OF THE STUDY: To investigate the health care resource utilization and cost-of-illness in patients with schizophrenia in Sweden and to relate the costs to hospitalizations and global assessment of functioning (GAF). METHODS: Hospital-based registry data were combined with national registry data from a large patient population to get reliable estimates of the costs of schizophrenia in Sweden. Schizophrenia was defined by ICD-10 codes F20; F21; F23.1,2,8,9; F25.1,8,9. Registry data on socio-demographics and disease-related healthcare resource use in outpatient and inpatient care were obtained from Northern Stockholm Psychiatry. Data on pharmaceuticals were obtained from the National Board of Health and Welfare, and data on sick leave and early retirement were obtained from the Swedish Social Insurance Agency. Costs for community mental health care were not available at the individual level, but were estimated based on previous studies and aggregate cost data from Stockholm. Resource use data from the registries were combined with unit costs from publicly available sources. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. RESULTS: The average annual psychiatric cost per patient with schizophrenia in 2008 was EUR 42700 (95% CI: EUR 41500-44000), based on a sample of 2161 patients. To this should be added costs for community mental health care of EUR 12400 per patient, giving a total cost of EUR 55100 per patient. The two largest cost items in the total costs were indirect costs due to lost productivity (60%) and community mental health care (22% of the total cost). Patients who were hospitalized in 2008 had greater psychiatric costs than those who were not, EUR 71700 vs. EUR 37700 (p<0.0001). Psychiatric costs were significantly and negatively correlated with GAF (p<0.001). DISCUSSION: The major strengths of the study are the relatively large sample, and the linkage of patient-level clinical data on inpatient and outpatient care with national registry data on prescription pharmaceuticals, and days on social insurance. A limitation was that costs for informal care and primary care were not included in the data, but previous studies suggest that these costs items are small compared to other costs for schizophrenia. IMPLICATIONS FOR HEALTH POLICIES AND FUTURE RESEARCH: Costs were strongly related to hospitalization and GAF, suggesting that attempts to improve global functioning and avoid hospitalizations by means of effective treatment and rehabilitation might not only decrease suffering for patients and relatives, but also reduce the societal cost of schizophrenia. A detailed knowledge of the societal costs can also be helpful in evaluating the cost-effectiveness of new treatment strategies to improve the care for patients with schizophrenia.

Dosing frequency and adherence in chronic psychiatric disease: systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to investigate the impact of dosing frequency on adherence in severe chronic psychiatric and neurological diseases. METHODS: A systematic literature review was conducted for articles in English from medical databases. Diseases were schizophrenia, psychosis, epilepsy, bipolar disorder, and major depressive disorder. RESULTS: Of 1420 abstracts screened, 12 studies were included. Adherence measures included Medication Event Monitoring System (MEMS(®)), medication possession ratio, medication persistence, and refill adherence. Three schizophrenia and one epilepsy study used MEMS, and all showed a trend towards higher adherence rates with less frequent dosing regimens. Three depression and one schizophrenia study used the medication possession ratio; the pooled odds ratio of being adherent was 89% higher (ie, 1.89, 95% credibility limits 1.71-2.09) on once-daily versus twice-daily dosing. Two studies in depression and one in all bupropion patients assessed medication persistence and refill adherence. The pooled odds ratio for the two depression studies using medication persistence was 2.10 (95% credibility limits 1.86-2.37) for once-daily versus twice-daily dosing. For refill adherence after 9 months, 65%-75% of patients on once-daily versus 56% on twice-daily dosing had at least one refill. In all but one of the studies using other measures of adherence, adherence rates were higher with once-daily dosing compared with more frequent dosing regimens. No relevant studies were identified for bipolar disorder or psychosis. CONCLUSION: Differences in study design and adherence measures used across the studies were too large to allow pooling of all results. Despite these differences, there was a consistent trend of better adherence with less frequent dosing.

Cost-effectiveness of candesartan versus losartan in the primary preventive treatment of hypertension.

BACKGROUND: Although angiotensin receptor blockers have different receptor binding properties, no comparative randomized studies with cardiovascular event endpoints have been performed for this class of drugs. The aim of this study was to assess the long-term cost-effectiveness of candesartan (Atacand(®)) versus generic losartan in the primary preventive treatment of hypertension. METHODS: A decision-analytic model was developed to estimate costs and health outcomes over a patient's lifetime. Data from a clinical registry study were used to estimate event rates for cardiovascular complications, such as myocardial infarction and heart failure. Costs and quality of life data were from published sources. Costs were in Swedish kronor and the outcome was quality-adjusted life-years (QALYs). RESULTS: Due to reduced rates of cardiovascular complications, candesartan was associated with a QALY gain and lower health care costs compared with generic losartan (0.053 QALYs gained and reduced costs of approximately 4700 Swedish kronor for women; and 0.057 QALYs gained and reduced costs of approximately 4250 Swedish kronor for men). This result was robust in several sensitivity analyses. CONCLUSION: When modeling costs and health outcomes based on event rates for cardiovascular complications from a real-world registry study, candesartan appears to bring a QALY gain and a reduction in costs compared with generic losartan in the primary preventive treatment of hypertension in Sweden.

Differential use of extended and immediate release quetiapine: a retrospective registry study of Finnish inpatients with schizophrenia spectrum and bipolar disorders.

OBJECTIVE: Extended release (XR) and immediate release (IR) quetiapine have differing dosing, titration and plasma concentration profiles. The authors assessed whether the use of quetiapine XR and IR in schizophrenia spectrum disorders (SCZ) and bipolar disorder (BD) differ. DESIGN: Retrospective non-interventional registry study. SETTING: Secondary healthcare. PARTICIPANTS: All SCZ and BD (ICD-10 codes F20-F29, F30-F31) patients discharged between June 2008 and June 2010 from a Finnish psychiatric hospital with any use of quetiapine during their inpatient stay. PRIMARY AND SECONDARY OUTCOME MEASURES: Differences in patient characteristics between quetiapine XR and IR users were tested. To assess the profile of XR versus IR patients, logistic regressions were performed. RESULTS: 43 patients used quetiapine XR, 58 used quetiapine IR and 55 used both formulations (n=156). 102 patients were diagnosed with SCZ and 54 with BD, with no significant differences between the quetiapine formulations. The mean daily dose of quetiapine XR was significantly higher than that of quetiapine IR (542 mg vs 328 mg; p<0.001). This was also true for the SCZ subgroup (XR: 593 mg vs IR: 338 mg; p<0.001) and the BD subgroup (XR: 466 mg vs IR: 308 mg; p=0.009). 48% of all quetiapine IR patients used a mean dose of ≤200 mg compared with 2% of XR patients. Injectable antipsychotics were combined with quetiapine IR but not with quetiapine XR (12% vs 0%; p=0.019). At discharge, quetiapine XR was used as monotherapy to a greater extent than IR (79% vs 44%; p=0.003). The odds for quetiapine XR use in hospital were lower with advancing age, substance abuse diagnosis and prior IR use. CONCLUSIONS: Among SCZ and BD inpatients, quetiapine XR was more often used as monotherapy and in significantly higher doses than quetiapine IR. Differential use of the quetiapine formulations appears to depend, at least in part, on patient characteristics.

Cost-effectiveness of saxagliptin (Onglyza®) in type 2 diabetes in Sweden.

AIM: The objective of this study was to investigate the cost-effectiveness of saxagliptin (Onglyza(®)), a DPP-4 inhibitor, plus metformin compared with a sulphonylurea (SU) (Glipizide) plus metformin in Swedish patients not well controlled on metformin alone. METHODS: Data from a 52-week clinical trial comparing saxagliptin and glipizide in combination with metformin was used in a simulation model to estimate long term complications in a cohort of type 2 diabetes patients. The model estimates the incidence of microvascular and macrovascular complications, diabetes-specific mortality, all-cause mortality, and ultimately, costs and quality-adjusted life years (QALYs) associated with the investigated treatment strategies. Costs and QALYs were estimated for a lifetime time horizon. RESULTS: Compared with SU+metformin, the cost per QALY gained with saxagliptin+metformin is approximately SEK 91,000. Patients on saxagliptin+metformin gain 0.10 QALYs on average, at an incremental cost of around SEK 9500. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSIONS: This study demonstrates that, over a patient's lifetime, the addition of saxagliptin to metformin is associated with improvements in quality-adjusted life years compared with SU in patients with type 2 diabetes. Saxagliptin treatment is a cost-effective treatment alternative for type 2 diabetes in patients not well-controlled on metformin alone.