Treatment persistence and adherence and their consequences on patient outcomes of generic versus brand-name statins routinely used to treat high cholesterol levels in Spain: a retrospective cost-consequences analysis.

BACKGROUND: High blood lipoprotein concentrations are one of the major risk factors for cardiovascular diseases. Drug therapy is the base of treatment; statins in particular. Both brand-name and generic presentations are available for statin therapy of high cholesterol levels. Factors that may influence their use in routine medical practice include, among others, patient persistence and adherence to treatment as prescribed by physicians. The aim of this retrospective analysis was to provide real-world evidence of treatment persistence and adherence and their consequences on economic and patient outcomes of generic versus brand-name statins routinely used to treat high cholesterol levels in Spain. METHODS: Existing real-world electronic medical records abstracted from a database of two regions in Spain were analyzed. The analysis compared generic versus brand-name statins data from subjects' who started treatment between July 1, 2010 and June 30, 2012. Treatment persistence, adherence expressed as medication possession ratio (MPR), healthcare resource utilization and their costs were analyzed together with patient's at-goal rates of low-density-lipoprotein-cholesterol (LDL-c), incidence of any major cardiovascular event (CVE) and all-cause mortality during a 5-year follow-up period. Multivariate analyses were applied. RESULTS: A total of 13,244 records were included. Persistence was lower with generics; adjusted hazard ratio -HR- [95% confidence interval]: 0.86 [0.82-0.91], p < 0.001) and MPR was also lower: 61.5% vs. 65.1% (p < 0.001). Less patients with generics reached their LDL-c goal: 39.2% [38.3-40.2%] vs. 42.0% [40.2-43.7%]; adjusted odds ratio; 0.87 [0.80-0.95], p = 0.003. Compared to brand-name statins, the observed probability of occurrence of a CVE; HR: 1.31 [1.15-1.50], p < 0.001, and also all-cause deaths; HR: 1.36 [1.15-1.62], was significantly higher with generics; p < 0.001 in both cases. Adjusted mean total healthcare cost per patient was also higher with generic than with brand-name statins: €9118 (9059-9176) vs. €7980 (7853-8808) [adjusted difference: €1137 (997-1277), p < 0.001]. CONCLUSION: This retrospective cost-consequences analysis found poorer treatment persistence and adherence in patients who first started therapy with generic instead of brand-name statins in routine medical practice in Spain. Also, patients receiving generics were more unlikely to reach LDL-c goals, showed increased probability of having CVE and all-cause mortality at a higher cost to payers.

Relationship between global severity of patients with Alzheimer's disease and costs of care in Spain; results from the co-dependence study in Spain.

OBJECTIVE: The objectives of this analysis were to examine how patients' global severity with Alzheimer's disease (AD) relates to costs of care and explore the incremental effects of global severity measured by the clinical dementia rating (CDR) scale on these costs for patients in Spain. METHODS: The Codep-EA study is an 18-multicenter, cross-sectional, observational study among patients (343) with AD according to the CDR score and their caregivers in Spain. The data obtained included (in addition to clinical measures) also socio-demographic data concerning the patient and its caregiver. Cost analyses were based on resource use for medical care, social care, caregiver productivity losses, and informal caregiver time reported in the resource utilization in dementia (RUD). Lite instrument and a complementary questionnaire. Multivariate regression analysis was used to model the effects of global severity and other socio-demographic and clinical variables on cost of care. RESULTS: The mean (standard deviation) costs per patient over 6 months for direct medical, social care, indirect and informal care costs, were estimated at €1,028.1 (1,655.0), €843.8 (2,684.8), €464.2 (1,639.0) and €33,232.2 (30,898.9), respectively. Dementia severity, as having a CDR score 0.5, 2, or 3 with CDR score 1 being the reference group were all independently and significantly associated with informal care costs. Whereas having a CDR score of 2 was also significantly related with social care costs, a CDR score of 3 was associated with most cost components including direct medical, social care, and total costs, all compared to the reference group. CONCLUSIONS: The costs of care for patients with AD in Spain are substantial, with informal care accounting for the greatest part. Dementia severity, measured by CDR score, showed that with increasing severity of the disease, direct medical, social care, informal care and total costs augmented.

Patient preferences for osteoporosis in Spain: a discrete choice experiment.

UNLABELLED: In Spain, various treatments are available to prevent osteoporotic fractures. A discrete choice experiment (DCE) was used to investigate the importance of different treatment aspects and its influence on patients' preferences. All attributes included as type and place of drug administration as well as costs showed to be significant predictors of choice. Spanish osteoporosis patients have well-defined preferences and accept trade-offs among attributes. INTRODUCTION: This study was designed to identify patient preferences for different aspects of osteoporosis treatments in Spain. METHODS: Main attributes of severe osteoporosis treatments were determined by literature review and consultations with nurses. The discrete choice experiment included three attributes: type of drug administration, place of administration, plus a cost attribute in order to estimate willingness to pay for improvements in attribute levels. A pilot study with 50 patients was performed to identify the areas of misunderstanding. One hundred sixty-six patients with a diagnosis of osteoporosis and severe osteoporosis were presented with pairs of hypothetical treatment profiles with different type of administration levels, places of administration and costs. Questions to collect socio-demographic and disease-related treatment data were also included. Data were analysed using a random effects probit model. RESULTS: All attributes had the expected polarity and were significant predictors of choice. Patients were willing to pay 183 euro/month to have a subcutaneous injection once per day rather than an intravenous injection once per year. Patients with osteoporosis were willing to pay 121 euro/month to have medical support when administering the drug treatment at home rather than being admitted several hours to a hospital for drug administration. CONCLUSION: Spanish osteoporosis patients have well-defined preferences among treatment attributes and are willing to accept trade-offs among attributes. Participants indicated that they are willing to accept self medication with medical support rather than being hospitalised for several hours. The perspective of the patients should be taken into account when making treatment decisions.

Assessment of potential measures in models of progression in Alzheimer disease.

BACKGROUND: In estimating the potential benefits of treatment, it is often necessary to extrapolate beyond clinical trial results using economic modeling. Previous attempts in Alzheimer disease (AD) were primarily based on the Mini-Mental State Examination (MMSE) due to its widespread use. These models were criticized as not accurately reflecting the total impact of the disease, providing untrustworthy estimates of treatment benefit. We compared 3 alternatives to the MMSE with respect to bridging between clinical outcomes needed for regulatory approval and economic and quality of life (QOL) outcomes important to reimbursement agencies. METHODS: The MMSE, Disability Assessment in Dementia (DAD) scale, Clinical Dementia Rating (CDR) scale, and Dependence Scale (DS) were compared in their ability to explain variation in cognitive, functional, and behavioral measures as well as economic and QOL outcomes using univariate (Pearson correlations) and multivariate (linear regression) analyses of data from research sites in the United States and Europe. RESULTS: Subjects with mild to moderate AD (n = 196; mean 75.9 years; 56% female) were evaluated. The DS, DAD, and CDR were moderately correlated with the MMSE (Pearson correlations, range 0.54-0.58) but performed better (higher adjusted R(2)) than the MMSE in explaining variations in subject behavior, QOL, and health status. The DS and DAD performed better in explaining variation in medical costs, caregiver QOL, and caregiver time. CONCLUSIONS: Measures of function (DAD) or dependence on others (DS), or global measures (CDR), appear to be better candidates than the MMSE for modeling AD progression.

A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of quetiapine, olanzapine and valproate semisodium in the treatment of mania associated with bipolar disorder. DATA SOURCES: Electronic databases; industry submissions made to the National Institute for Clinical Excellence. REVIEW METHODS: Randomised trials and economic evaluations that evaluated the effectiveness of quetiapine, olanzapine or valproate semisodium in the treatment of mania associated with bipolar disorder were selected for inclusion. Data were extracted by one reviewer into a Microsoft Access database and checked for quality and accuracy by a second. The quality of the cost-effectiveness studies was assessed using a checklist updated from that developed by Drummond and colleagues. Relative risk and mean difference data were presented as Forest plots but only pooled where this made sense clinically and statistically. Studies were grouped by drug and, within each drug, by comparator used. Chi-squared tests of heterogeneity were performed for the outcomes if pooling was indicated. A probabilistic model was developed to estimate costs from the perspective of the NHS, and health outcomes in terms of response rate, based on an improvement of at least 50% in a patient's baseline manic symptoms derived from an interview-based mania assessment scale. The model evaluated the cost-effectiveness of the alternative drugs when used as part of treatment for the acute manic episode only. RESULTS: Eighteen randomised trials met the inclusion criteria. Aspects of three of the quetiapine studies were commercial-in-confidence. The quality of the included trials was limited and overall, key methodological criteria were not met in most trials. Quetiapine, olanzapine and valproate semisodium appear superior to placebo in reducing manic symptoms, but may cause side-effects. There appears to be little difference between these treatments and lithium in terms of effectiveness, but quetiapine is associated with somnolence and weight gain, whereas lithium is associated with tremor. Olanzapine as adjunct therapy to mood stabilisers may be more effective than placebo in reducing mania and improving global health, but it is associated with more dry mouth, somnolence, weight gain, increased appetite, tremor and speech disorder. There was little difference between these treatments and haloperidol in reducing mania, but haloperidol was associated with more extrapyramidal side-effects and negative implications for health-related quality of life. Intramuscular olanzapine and lorazepam were equally effective and safe in one very short (24 hour) trial. Valproate semisodium and carbamazepine were equally effective and safe in one small trial in children. Olanzapine may be more effective than valproate semisodium in reducing mania, but was associated with more dry mouth, increased appetite, oedema, somnolence, speech disorder, Parkinson-like symptoms and weight gain. Valproate semisodium was associated with more nausea than olanzapine. The results from the base-case analysis demonstrate that choice of optimal strategy is dependent on the maximum that the health service is prepared to pay per additional responder. For a figure of less than 7179 British pounds per additional responder, haloperidol is the optimal decision; for a spend in excess of this, it would be olanzapine. Under the most favourable scenario in relation to the costs of responders and non-responders beyond the 3-week period considered in the base-case analysis, the incremental cost-effectiveness ratio of olanzapine is reduced to 1236 British pounds. CONCLUSIONS: In comparison with placebo, quetiapine, olanzapine and valproate semisodium appear superior in reducing manic symptoms, but all drugs are associated with adverse events. In comparison with lithium, no significant differences were found between the three drugs in terms of effectiveness, and all were associated with adverse events. Several limitations of the cost-effectiveness analysis exist, which inevitably means that the results should be treated with some caution. There remains a need for well-conducted, randomised, double-blind head-to-head comparisons of drugs used in the treatment of mania associated with bipolar disorder and their cost-effectiveness. Participant demographic, diagnostic characteristics, the treatment of mania in children, the use of adjunctive therapy and long-term safety issues in the elderly population, and acute and long-term treatment are also subjects for further study.

Parallel imports of pharmaceuticals in the European Union.

Parallel importing has existed on a small scale in Europe for many years and has been upheld by the European Court of Justice as consistent with standard principles of free trade. However, the potential impact of parallel trade has increased significantly with the launch of the European Medicines Evaluation Agency in 1995, the accession to the European Union (EU) of countries with traditionally low prices, such as Spain, and the possible accession of Eastern European countries. This article examines the current state of parallel trade in medicines in the EU (different modalities and the medicines affected), analyses some policy implications associated with parallel trade (who gains and who loses) and explores the effects of several policy scenarios affecting parallel trade. The main conclusion is that a single European price is probably not the best solution from a European welfare point of view. A solution to the present situation could be achieved by separating the market price (at which any agent is allowed to buy a product either for consumption or for resale) and the price actually paid by a final consumer. Discounts and reference pricing may present two of the most feasible options.