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Abstract Background Epidemiological studies have shown that microalbuminuria is an important risk factor for arteriosclerosis, coronary heart disease and other vascular diseases in persons with type 2 diabetes. In the present study we examined the prevalence and risk factors for micro- and macroalbuminuria and examined glycemic control as well as treatment of modifiable cardiovascular risk factors in persons with known type 2 diabetes in Germany. Methods The presented data were derived from the 'KORA Augsburg Diabetes Family Study', conducted between October 2001 and September 2002. Participants were adults aged 29 years and older with previously diagnosed type 2 diabetes (n = 581). Microalbuminuria was defined as an albumin-creatinine ratio of 30 to 300 mg/g, and macroalbuminuria as an albumin-creatinine ratio of more than 300 mg/g. Results Microalbuminuria was revealed in 27.2% and macroalbuminuria in 9.0% of the 581 included diabetic persons. Multivariable regression analysis identified HBA1c, duration of diabetes, systolic blood pressure, serum creatinine, smoking and waist circumference as independent risk factors associated with albuminuria (micro- or macroalbuminuria). Relatively few persons with type 2 diabetes achieved treatment targets of HbA1c < 7% (46.6%), total cholesterol < 200 mg/dl (44.1%), and LDL cholesterol < 100 mg/dl (16.0%). Optimal HDL cholesterol values (> 45 mg/dl in men, > 55 mg/dl in women) were found in 55.8%, and blood pressure values < 130 and < 85 mmHg in 31.3% of the persons Conclusion Albuminuria is common among German persons with known type 2 diabetes. Despite evidence-based guidelines, only a small proportion of type 2 diabetic persons achieved the recommended levels of glycemic control and control of cardiovascular risk factors.

Evidence from randomized controlled trials available for timely health technology assessments of new pharmacological treatments and regulatory decision making may not be generalizable to local patient populations, often resulting in decisions being made under uncertainty. In recent years, several reweighting approaches have been explored to address this important question of generalizability to a target population. We present a case study of the Innovative Medicines Initiative to illustrate the inverse propensity score reweighting methodology, which may allow us to estimate the expected treatment benefit if a clinical trial had been run in a broader real‐world target population. We learned that identifying treatment effect modifiers, understanding and managing differences between patient characteristic data sets, and balancing the closeness of trial and target patient populations with effective sample size are key to successfully using this methodology and potentially mitigating some of this uncertainty around local decision making. [ABSTRACT FROM AUTHOR]

Objective: Amyloid beta (Aβ) positron emission tomography (PET) imaging helps estimate Aβ neuritic plaque density in patients with cognitive impairment who are under evaluation for Alzheimer's disease (AD). This study aims to evaluate the cost-effectiveness of the Aβ-PET scan as an adjunct to standard diagnostic assessment for diagnosis of AD in France, using florbetapir as an example.Methods: A state-transition probability analysis was developed adopting the French Health Technology Assessment (HTA) perspective per guidance. Parameters included test characteristics, rate of cognitive decline, treatment effect, costs, and quality of life. Additional scenarios assessed the validity of the analytical framework, including: (1) earlier evaluation/treatment; (2) cerebrospinal fluid (CSF) as a comparator; and (3) use of other diagnostic procedures. Outputs included differences in quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). All benefits and costs were discounted for time preferences. Sensitivity analyses were performed to assess the robustness of findings and key influencers of outcomes.Results: Aβ-PET used as an adjunct to standard diagnostic assessment increased QALYs by 0.021 years and 10 year costs by €470 per patient. The ICER was €21,888 per QALY gained compared to standard diagnostic assessment alone. When compared with CSF, Aβ-PET costs €24,084 per QALY gained. In other scenarios, Aβ-PET was consistently cost-effective relative to the commonly used affordability threshold (€40,000 per QALY). Over 95% of simulations in the sensitivity analysis were cost-effective.Conclusion: Aβ-PET is projected to affordably increase QALYs from the French HTA perspective per guidance over a range of clinical scenarios, comparators, and input parameters. [ABSTRACT FROM AUTHOR]

Background: Country differences in resource use and costs of Alzheimer's disease (AD) may be driven by differences in health care systems and resource availability.Objective: To compare country resource utilization drivers of societal costs for AD dementia over 18 months.Methods: GERAS is an observational study in France (n = 419), Germany (n = 550), and the UK (n = 526). Resource use of AD patients and caregivers contributing to >1% of total societal costs (year 2010) was assessed for country differences, adjusting for participant characteristics.Results: Mean 18-month societal costs per patient were France €33,339, Germany €38,197, and UK €37,899 (£32,501). Caregiver time spent on basic and instrumental activities of daily living (ADL) contributed the most to societal costs (54% France, 64% Germany, 65% UK). Caregivers in France spent less time on ADL than UK caregivers and missed fewer work days than in other countries. Compared with other countries, patients in France used more community care services overall and were more likely to use home aid. Patients in Germany were least likely to use temporary accommodation or to be institutionalized at 18 months. UK caregivers spent the most time on instrumental ADL, UK patients used fewest outpatient resources, and UK patients/caregivers were most likely to receive financial support.Conclusion: Caregiver time on ADL contributed the most to societal costs and differed across countries, possibly due to use of community care services and institutionalization. Other resources had different patterns of use across countries, reflecting country-specific health and social care systems. [ABSTRACT FROM AUTHOR]

Background: Prior diagnosis of Alzheimer's disease (AD) among patients later diagnosed with vascular dementia (VaD) has been associated with excess costs, suggesting potential benefits of earlier rule-out of AD diagnosis.Objective: To investigate whether prior diagnosis with AD among patients with VaD is associated with excess costs in the UK.Methods: Patients with a final VaD diagnosis, continuous data visibility for≥6 months prior to index date, and linkage to Hospital Episode Statistics data were retrospectively selected from de-identified Clinical Practice Research Datalink data. Patients with AD diagnosis before a final VaD diagnosis were matched to similar patients with no prior AD diagnosis using propensity score methods. Annual excess healthcare costs were calculated for 5 years post-index, stratified by time to final diagnosis.Results: Of 9,311 patients with VaD, 508 (6%) had prior AD diagnosis with a median time to VaD diagnosis exceeding 2 years from index date. Over the entire follow-up period, patients with prior AD diagnosis had accumulated healthcare costs that were approximately GBP2,000 higher than those for matched counterparts (mostly due to higher hospitalization costs). Cost differentials peaked particularly in the period including the final VaD diagnosis, with excess costs quickly declining thereafter.Conclusion: Potential misdiagnosis of AD among UK patients with VaD resulted in substantial excess costs. The decline in excess costs following a final VaD diagnosis suggests potential benefits from earlier rule-out of AD. [ABSTRACT FROM AUTHOR]

Background: Missing data are a common problem in prospective studies with a long follow-up, and the volume, pattern and reasons for missing data may be relevant when estimating the cost of illness. We aimed to evaluate the effects of different methods for dealing with missing longitudinal cost data and for costing caregiver time on total societal costs in Alzheimer's disease (AD).Methods: GERAS is an 18-month observational study of costs associated with AD. Total societal costs included patient health and social care costs, and caregiver health and informal care costs. Missing data were classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Simulation datasets were generated from baseline data with 10-40 % missing total cost data for each missing data mechanism. Datasets were also simulated to reflect the missing cost data pattern at 18 months using MAR and MNAR assumptions. Naïve and multiple imputation (MI) methods were applied to each dataset and results compared with complete GERAS 18-month cost data. Opportunity and replacement cost approaches were used for caregiver time, which was costed with and without supervision included and with time for working caregivers only being costed.Results: Total costs were available for 99.4 % of 1497 patients at baseline. For MCAR datasets, naïve methods performed as well as MI methods. For MAR, MI methods performed better than naïve methods. All imputation approaches were poor for MNAR data. For all approaches, percentage bias increased with missing data volume. For datasets reflecting 18-month patterns, a combination of imputation methods provided more accurate cost estimates (e.g. bias: -1 % vs -6 % for single MI method), although different approaches to costing caregiver time had a greater impact on estimated costs (29-43 % increase over base case estimate).Conclusions: Methods used to impute missing cost data in AD will impact on accuracy of cost estimates although varying approaches to costing informal caregiver time has the greatest impact on total costs. Tailoring imputation methods to the reason for missing data will further our understanding of the best analytical approach for studies involving cost outcomes. [ABSTRACT FROM AUTHOR]

Background To identify the main factors associated with societal costs of Alzheimer's disease (AD) in community-dwelling patients across three European countries. Methods Baseline cost data from a prospective, observational study were used. Assessments included patients' cognition, activities of daily living (ADLs) and behavioral symptoms, and caregiver burden. Cost calculations (2010) from the societal perspective were based on patient/caregiver resource use. Generalized linear models estimated factors associated with costs. Results Mean monthly costs per patient differed for France (€1881), Germany (€2349), and the UK (€2016), with informal care costs accounting for 50% to 61%. Independent factors associated with costs across all countries were ADL total score, patient living arrangements, caregiver working status, and caregiver burden (all P < .05). Additional factors were significant for the pooled cohort or individual countries. Conclusions Several patient and caregiver factors, including factors associated with informal care, should be included when evaluating care options for patients with AD. [ABSTRACT FROM AUTHOR]

Background: In schizophrenia, medication adherence is critical to achieve better patient outcomes and to avoid relapses, which are responsible for a significant proportion of total healthcare costs for this chronic illness. The aim of this study was to assess the cost-effectiveness of olanzapine long-acting injection (OLAI) compared with risperidone long-acting injection (RLAI) in patients with schizophrenia in Spain. Methods: A discrete event simulation (DES) model was developed from a Spanish healthcare system perspective to estimate clinical and economic outcomes for patients with schizophrenia over a five-year period. Patients who had earlier responded to oral medication and have a history of relapse due to adherence problems were considered. Identical model populations were treated with either OLAI or RLAI. In the absence of a head-to-head clinical trial, discontinuation and relapse rates were obtained from open-label studies. The model accounted for age, gender, risks of relapse and discontinuation, relapse management, hospitalization, treatment switching and adverse events. Direct medical costs for the year 2011 and outcomes including relapse avoided, life years (LYs), and quality-adjusted life years (QALYs) were discounted at a rate of 3%. Results: When comparing RLAI and OLAI, the model predicts that OLAI would decrease 5-year costs by €2,940 (Standard Deviation between replications 300.83), and result in a QALY and LY gains of 0.07 (SD 0.019) and 0.04 (SD 0.025), respectively. Patients on OLAI had fewer relapses compared to RLAI (1.392 [SD 0.035] vs. 1.815 [SD 0.035]) and fewer discontinuations (1.222 [SD 0.031] vs. 1.710 [SD 0.039]). Sensitivity analysis indicated that the study was robust and conclusions were largely unaffected by changes in a wide range of parameters. Conclusions: The present evaluation results in OLAI being dominant over RLAI, meaning that OLAI represents a more effective and less costly alternative compared to RLAI in the treatment of patients with schizophrenia in the Spanish setting. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of Alzheimer's disease (AD) is crucial to implement the latest treatment strategies and management of AD symptoms. Diagnostic procedures play a major role in this detection process but evidence on their respective accuracy is still limited. Objective: To conduct a systematic literature on the sensitivity and specificity of different test modalities to identify AD patients and perform meta-analyses on the test accuracy values of studies focusing on autopsy-confirmation as the standard of truth. Methods: The systematic review identified all English papers published between 1984 and 2011 on diagnostic imaging tests and cerebrospinal fluid biomarkers including results on the newest technologies currently investigated in this area. Meta-analyses using bivariate fixed and random-effect models and hierarchical summary receiver operating curve (HSROC) random-effect model were applied. Results: Out of the 1,189 records, 20 publications were identified to report the accuracy of diagnostic tests in distinguishing autopsy-confirmed AD patients from other dementia types and healthy controls. Looking at all tests and comparator populations together, sensitivity was calculated at 85.4% (95% confidence interval [CI]: 80.9%-90.0%) and specificity at 77.7% (95% CI: 70.2%-85.1%). The area under the HSROC curve was 0.88. Sensitivity and specificity values were higher for imaging procedures, and slightly lower for CSF biomarkers. Test-specific random-effect models could not be calculated due to the small number of studies. Conclusion: The review and meta-analysis point to a slight advantage of imaging procedures in correctly detecting AD patients but also highlight the limited evidence on autopsy-confirmations and heterogeneity in study designs. [ABSTRACT FROM AUTHOR]

Background This study examined medical resource utilisation patterns in the United Kingdom (UK) prior to and following Alzheimer's disease (AD) diagnosis. Methods A patient cohort aged 65 years and older with newly diagnosed AD between January 2008 and December 2010 was identified through the UK's Clinical Practice Research Datalink (CPRD). Patients with a continuous record in the CPRD (formerly the General Practice Research Database [GPRD]) for both the 3 years prior to, and the 1year following, AD diagnosis were eligible for inclusion. A control cohort was identified by matching general older adult (GOA) patients to patients with AD based on year of birth, gender, region, and Charlson Comorbidity Index at a ratio of 2:1. Medical resource utilisation was calculated in 6-month intervals over the 4-year study period. Comparisons between AD and GOA control cohorts were conducted using conditional logistic regression for patient characteristics and a generalised linear model for resource utilisation. Results Data for the AD cohort (N = 3,896) and matched GOA control cohort (N = 7,792) were extracted from the CPRD. The groups were 65% female and the AD cohort had a mean age of 79.9 years (standard deviation 6.5 years) at the date of diagnosis. Over the entire study period, the AD cohort had a significantly higher mean primary care consultation rate than the GOA cohort (p < .0001). While the GOA cohort primary care consultation rate gradually increased over the 4-year period (ranging from 5 to 7 consultations per 6-month period), increases were more pronounced in the AD cohort (ranging from 6 to 11 consultations per 6-month period, peaking during the 6-month periods immediately prior to and post diagnosis). The AD cohort also had a higher overall specialty referral rate than the GOA cohort over the 4-year period (37% vs. 25%, respectively; p < .0001); the largest difference was during the 6-months immediately prior to AD diagnosis (17% vs. 5%, respectively; p < .0001). Conclusions In the UK, AD diagnosis is associated with significant increases in primary and secondary care resource utilisation, continuing beyond diagnosis. This evidence may be important to health care commissioners to facilitate effective mobilisation of appropriate AD-related health care resources. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis. Methods: A systematic literature review of English language articles was performed in PUBMED, EMBASE, MedLine In-Process, Cochrane Library, and ClinicalTrials.gov between January 1985 and March 2013. Randomized controlled trials of duloxetine and all oral non-steroidal anti-inflammatory drugs and opioids were included if treatment was ⩾12 weeks and the Western Ontario and McMaster Universities Index (WOMAC) total score was available. Studies were assessed for quality using the assessment tool from the National Institute for Health and Clinical Excellence guidelines for single technology appraisal submissions. WOMAC baseline and change from baseline total scores were extracted and standardized. A frequentist meta-analysis, meta-regression, and indirect comparison were performed using the DerSimonian-Laird and Bucher methods. Bayesian analyses with and without adjustment for study-level covariates were performed using noninformative priors. Results: Thirty-two publications reported 34 trials (2 publications each reported 2 trials) that met inclusion criteria. The analyses found all treatments except oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more effective than placebo. Indirect comparisons to duloxetine found no significant differences for most of the compounds. Some analyses showed evidence of a difference with duloxetine for etoricoxib (better), tramadol and oxycodone (worse), but without consistent results between analyses. Forest plots revealed positive trends in overall efficacy improvement with baseline scores. Adjusting for baseline, the probability duloxetine is superior to other treatments ranges between 15% to 100%. Limitations of this study include the low number of studies included in the analyses, the inclusion of only English language publications, and possible ecological fallacy associated with patient level characteristics. Conclusions: This analysis suggests no difference between duloxetine and other post-first line oral treatments for osteoarthritis (OA) in total WOMAC score after approximately 12 weeks of treatment. Significant results for 3 compounds (1 better and 2 worse) were not consistent across performed analyses. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost effectiveness of duloxetine compared to other oral postacetaminophen treatments for osteoarthritis (OA) from a Quebec societal perspective.Methods: A cost-utility analysis was performed enhancing the Markov model from the 2008 OA guidelines of the National Institute for Health and Clinical Excellence (NICE). The NICE model was extended to include opioid and antidepressant comparators, adding titration, discontinuation, and relevant adverse events (AEs). Comparators included duloxetine, celecoxib, diclofenac, naproxen, hydromorphone, and oxycodone extended release (oxycodone). AEs included gastrointestinal and cardiovascular events associated with nonsteroidal antiinflammatory drugs (NSAIDs), as well as fracture, opioid abuse, and constipation, among others. Costs and incremental cost-effectiveness ratios (ICERs) were estimated in 2011 Canadian dollars. The base case modeled a cohort of 55-year-old patients with OA for a 12-month period of treatment, followed by treatment from a basket of post-discontinuation oral therapies until death. Sensitivity analyses (one-way and probabilistic) were conducted.Results: Overall, naproxen was the least expensive treatment, whereas oxycodone was the most expensive. Duloxetine accumulated the highest number of quality-adjusted life years (QALYs), with an ICER of $36,291 per QALY versus celecoxib. Duloxetine was dominant over opioids. In subgroup analyses, ICERs for duloxetine versus celecoxib were $15,619 and $20,463 for patients at high risk of NSAID-related AEs and patients ages >65 years, respectively.Conclusion: Duloxetine was cost effective for a cohort of 55-year-old patients with OA, and more so in older patients and those with greater AE risks. [ABSTRACT FROM AUTHOR]

Purpose: To determine the incidence of diabetic peripheral neuropathic pain (DPNP) in the United Kingdom (UK) primary care population using the General Practice Research Database (GPRD). Patients and methods: This retrospective cohort study identiied incident cases of DPNP in the UK GPRD between July 1, 2002 and June 30, 2011, using diagnostic codes. Trends in the incidence rate were examined by dividing the study period into 3-year periods: (1) July 1, 2002-June 30, 2005; (2) July 1, 2005-June 30, 2008; and (3) July 1, 2008-June 30, 2011. Patient characteristics (age, sex, comorbidities) and initial pharmacological treatment were described; the proportion of patients with incident DPNP, who had previously been screened for neuropathic symptoms, was determined. Results: Among almost 7.5 million persons contributing 38,118,838 person-years of observations in the GPRD, 6,779 new cases of DPNP were identified (45.5%, women), giving an incidence rate of 17.8 per 100,000 person-years (95% confidence interval [CI] 17.4-18.2). The incidence of DPNP increased with age, but it was stable over the three consecutive 3-year periods: 17.9, 17.2, and 18.4 cases per 100,000 person-years. Of the 6,779 patients with incident DPNP, 15.5% had prior neuropathic screening during the study period. The majority of patients with incident DPNP (84.5%) had a treatment for pain initiated within 28 days of first diagnosis. The most common first-line treatments prescribed were tricyclic antidepressants (27.2%), anticonvulsants (17.0%), and nonsteroidal anti-inflammatory drugs (14.9%), with 26.6% of patients receiving combination therapy as their initial treatment. Conclusion: The incidence of DPNP in UK primary care has remained steady over the past 10 years. Our results suggest that DPNP is underdiagnosed, and initial treatment prescribed does not follow clinical guidelines. [ABSTRACT FROM AUTHOR]

To address socioeconomic challenges associated with its increasing prevalence, data are needed on country-level resource use and costs associated with Alzheimer's disease (AD). GERAS is an 18-month observational study being conducted in France, Germany, and the UK (with an 18-month extension in France and Germany), aimed at determining resource use and total costs associated with AD, stratified by AD severity at baseline. Resource use information and time spent on informal care by non-professional caregivers was obtained using the Resource Utilization in Dementia instrument. Total baseline societal costs were based on four cost components: patient health care costs, patient social care costs, caregiver health care costs, and caregiver informal care costs. Overall, 1,497 community-dwelling patients with AD were analyzed at baseline. Estimated mean monthly total societal costs per patient at baseline differed significantly between groups with mild, moderate, and moderately severe/severe AD (p < 0.001 in each country): $\euro$1,418, $\euro$1,737, and $\euro$2,453 in France; $\euro$1,312, $\euro$2,412, and $\euro$3,722 in Germany; and $\euro$1,621, $\euro$1,836, and $\euro$2,784 in the UK, respectively. All cost components except caregiver health care costs increased with AD severity. Informal caregiver costs were the largest cost component accounting for about half to just over 60% of total societal costs, depending on country and AD severity group. In conclusion, GERAS study baseline results showed that country-specific costs increase with AD severity. Informal care costs formed the greatest proportion of total societal costs, increasing with AD severity independent of costing method. Longitudinal data will provide information on cost trends with disease progression. [ABSTRACT FROM AUTHOR]

Data on inability to work from an observational study in patients treated with duloxetine for major depressive disorder in clinical practice in Germany were collected. Ability to work was compared between baseline and up to 6 months after initiation of duloxetine. All patients with a working status at baseline other than retired or retired early were included. 2,825 patients were analyzed, 54.8% were able to work at baseline increasing to 83.8% at 6months. Of those patients unable to work at baseline, 72.7% were able to work after 6 months. A relevant reduction of inability to work was also found for patient subgroups with moderate to severe pain at baseline and those with and without MDD pretreatment. As inability to work is one of the main cost drivers for depressive patients in Germany, the reduction of inability to work could potentially result in considerable cost savings for health insurance companies and society. [ABSTRACT FROM AUTHOR]

Background. Knowledge about real-world use of duloxetine and venlafaxine XR to treat depression in the UK is limited. Aims. To identify predictors of duloxetine or venlafaxine XR initiation. Method. Adult depressed patients who initiated duloxetine or venlafaxine XR between January 1, 2006 and September 30, 2007 were identified in the UK's General Practice Research Database. Demographic and clinical predictors of treatment initiation with duloxetine and venlafaxine XR were identified using logistic regression. Results. Patients initiating duloxetine (n = 909) were 4 years older than venlafaxine XR recipients (n = 1286).Older age, preexisting unexplained pain, respiratory disease, and pre-period use of anticonvulsants, opioids, and antihyperlipidemics were associated with increased odds of initiating duloxetine compared to venlafaxine XR. Pre-period anxiety disorder was associated with decreased odds of receiving duloxetine. Conclusion. Initial treatment choice with duloxetine versus venlafaxine XR was primarily driven by patient-specific mental and medical health characteristics. General practitioners in the UK favor duloxetine over venlafaxine XR when pain conditions coexist with depression. [ABSTRACT FROM AUTHOR]

Whose preferences are to be used for cost-effectiveness analysis? It has been recommended that community preferences for health states are the most appropriate ones for use in a reference case analysis. However, critics maintain that persons are not able properly to judge a health state if they have not experienced the condition themselves. This problem is analyzed here in the framework of Prospect Theory. It can be argued that the differing reference points of patients and the general public are responsible for deviating results. In addition, we argue that risk attitudes with respect to health-related quality of life are an indicator of reference points. If patients and the general public refer to the same reference point, i.e., they have the same risk attitude, the hypothesis is that deviations no longer significantly differ. Evaluations of the health condition of tinnitus by 210 patients and 210 unaffected persons were compared. The Time Tradeoff and Standard Gamble methods were applied to elicit preferences. Risk attitude was measured with the question of whether participants would undergo a treatment that could either improve or worsen their health condition, both with an equal chance (five possible answers between “in no case” and “in any case”). Affected persons indicated significantly higher values for tinnitus-related quality of life according to the Standard Gamble method. The difference between Time Tradeoff values was less dramatic but still significant. In addition, nonaffected persons are more risk-averse than affected persons. However, differences in evaluations are not significant considering single risk groups (e.g., those who answered “in no case”). Prospect Theory is a reasonable framework for considering the question of whose preferences count. If this result can be generalized for other diseases as well, it allows the mathematical combination of “objective” evaluations by the general public with the illness experience of patients. These evaluations should be weighted with patients' risk attitudes, i.e., community preferences can be used if they are corrected for risk attitudes. [ABSTRACT FROM AUTHOR]

A recently published article suggested that factor prices within the EU converged between 1980 and 1992 but diverged between 1992 and 1994. However, these findings largely reflect inflation differentials and exchange rate adjustments. Markov chain analysis on the basis of an alternative income aggregate, GDP per capita measured in Purchasing Power Standards, leads to different results: Convergence was close to non-existent from 1980 to 1994 but resumed significantly thereafter. This is likely to be attributable to the establishment of the Single Market and subsequent integration steps. [ABSTRACT FROM AUTHOR]

In light of increasing attention towards the use of real-world evidence (RWE) in decision making in recent years, this commentary aims to reflect on the experiences gained in accessing and using RWE for comparative effectiveness research as a part of the Innovative Medicines Initiative GetReal Consortium and discuss their implications for RWE use in decision-making.

Background: To identify the main factors associated with societal costs of Alzheimer's disease (AD) in community-dwelling patients across three European countries., Methods: Baseline cost data from a prospective, observational study were used. Assessments included patients' cognition, activities of daily living (ADLs) and behavioral symptoms, and caregiver burden. Cost calculations (2010) from the societal perspective were based on patient/caregiver resource use. Generalized linear models estimated factors associated with costs., Results: Mean monthly costs per patient differed for France (€1881), Germany (€2349), and the UK (€2016), with informal care costs accounting for 50% to 61%. Independent factors associated with costs across all countries were ADL total score, patient living arrangements, caregiver working status, and caregiver burden (all P < .05). Additional factors were significant for the pooled cohort or individual countries., Conclusions: Several patient and caregiver factors, including factors associated with informal care, should be included when evaluating care options for patients with AD., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: The rising prevalence of Alzheimer's disease (AD), and other diseases associated with dementia, imposes significant burden to various stakeholders who care for the elderly. Management of AD is complicated by multiple factors including disease-specific features which make it difficult to diagnose accurately during milder stages. Florbetapir F18 positron emission tomography (florbetapir-PET) is an approved imaging tool used to capture beta-amyloid neuritic plaque density in brains of cognitively impaired adults undergoing evaluation for AD and other causes of cognitive impairment. It has the potential to help improve healthcare outcomes as it may help clinicians identify patients with AD early so that treatments are initiated when most effective., Aims of the Study: Evaluate the potential long-term clinical and economic outcomes of adopting florbetapir-PET--adjunctive to standard clinical evaluation (SCE)--versus SCE alone in the diagnostic assessment of cognitively impaired patients with suspected AD., Methods: A decision analysis with a ten-year time horizon was developed in compliance with Good Research Practices and CHEERS guidelines. The target population was comprised of Spanish patients who were undergoing initial assessment for cognitive impairment (Mini-Mental State Examination [MMSE] score=20). Diagnostic accuracy, rate of cognitive decline, effect of drugs on cognition and dwelling status, economic burden (direct and indirect costs), and quality of life (QoL) were based on relevant clinical studies and published literature. Scenario analysis was applied to explore outcomes under different conditions, which included: (i) use of florbetapir-PET earlier in disease progression (MMSE score=22); and (ii) the addition of fluorodeoxyglucose (FDG)-PET to SCE., Results: Adjunctive florbetapir-PET increased quality-adjusted life years (QALYs) by 0.008 years and increased costs by 36 compared to SCE alone (incremental cost-effectiveness ratio [ICER], 4,769). Use of florbetapir-PET was dominant in alternate scenarios. Sensitivity analyses indicated rates of institutionalization (by MMSE) and MMSE score upon initiation of acetylcholinesterase inhibitor (AChEI) treatment most influenced the primary outcome (ICER) in the base case scenario. Over 82% of probabilistic simulations were cost-effective using the Spanish threshold (30,000/QALY)., Discussion: The addition of florbetapir-PET to SCE is expected to improve the accuracy of AD diagnoses for patients experiencing cognitive impairment; it is cost-effective due to decreased healthcare costs and caregiver burden. Prospective studies of the clinical utility of florbetapir-PET are necessary to evaluate the long-term implications of adopting florbetapir-PET on clinical outcomes and costs in real-world settings., Implications for Health Care Provision and Use: Florbetapir-PET is expected to improve decision-making regarding appropriate and sufficient care for cognitively impaired patients with suspected AD, while cost-effective., Implications for Health Policies: Earlier and more accurate diagnosis of AD may help to improve patient's health status and reduce treatment costs by effectively allocating healthcare resources and maximizing the benefit of treatments and supportive services., Implications for Further Research: Use of florbetapir-PET may help accurately identify patients with AD. The development of novel therapeutics for use with companion diagnostics may provide additional benefits by slowing or halting progressive cognitive decline with AD, increase QoL and prolong survival.

Objective: This post hoc analysis aimed to determine whether patients with major depressive disorder (MDD) in duloxetine trials who were antidepressant naive or who were previously exposed to antidepressants exhibited differences in efficacy and functioning., Method: Data were pooled from 15 double-blind, placebo- and/or active-controlled duloxetine trials of adult patients with MDD conducted by Eli Lilly and Company. The individual studies took place between March 2000 and November 2009. Data were analyzed using 4 pretreatment subgroups: first-episode never treated, multiple-episode never treated, treated previously only with selective serotonin reuptake inhibitors (SSRIs), and previously treated with antidepressants other than just SSRIs. Measures included the 17-item Hamilton Depression Rating Scale (HDRS-17) total and somatic symptom subscale scores, Montgomery-Asberg Depression Rating Scale (MADRS) total score, and Sheehan Disability Scale total score. Response rates (50% and 30%) were based on the HDRS-17 total score and remission rates on either the HDRS-17 or MADRS total score., Results: Response and remission rates were significantly greater (P < .05 in 11 of 12 comparisons) for duloxetine versus placebo in the 4 subgroups. A trend of greater response and remission occurred for first-episode versus multiple-episode patients; both groups were generally higher than the antidepressant-treated groups. Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores., Conclusions: Duloxetine was generally superior to placebo on response and remission rates and in mean change on efficacy measures. Response and remission rates were numerically greater for first-episode versus multiple-episode and drug-treated patients. Mean change differences on efficacy measures among the 4 subgroups were inconsistent. Duloxetine showed a similar therapeutic effect independent of episode frequency and antidepressant pretreatment.

Purpose: To assess the impact of pain severity and time to diagnosis of depression on health care costs for primary care patients with pre-existing unexplained pain symptoms who subsequently received a diagnosis of depression., Patients and Methods: This retrospective cohort study analyzed 4000 adults with unexplained pain (defined as painful physical symptoms [PPS] without any probable organic cause) and a subsequent diagnosis of depression, identified from the UK General Practice Research Database using diagnostic codes. Patients were categorized into four groups based on pain severity (milder or more severe; based on number of pain-relief medications and use of opioids) and time to diagnosis of depression (≤1 year or>1 year from PPS index date). Annual health care costs were calculated (2009 values) and included general practitioner (GP) consultations, secondary care referrals, and prescriptions for pain-relief medications for the 12 months before depression diagnosis and in the subsequent 2 years. Multivariate models of cost included time period as a main independent variable, and adjusted for age, gender, and comorbidities., Results: Total annual health care costs before and after depression diagnosis for the four patient groups were higher for the groups with more severe pain (£819-£988 versus £565-£628; P < 0.001 for all pairwise comparisons) and highest for the group with more severe pain and longer time to depression diagnosis in the subsequent 2 years (P < 0.05). Total GP costs were highest in the group with more severe pain and longer time to depression diagnosis both before and after depression diagnosis (P < 0.05). In the second year following depression diagnosis, this group also had the highest secondary care referral costs (P < 0.01). The highest drug costs were in the groups with more severe pain (P < 0.001), although costs within each group were similar before and after depression diagnosis., Conclusion: Among patients with unexplained pain symptoms, significant pain in combination with longer time from pain symptoms to depression diagnosis contribute to higher costs for the UK health care system.

Objective: Duloxetine is indicated for treatment of major depressive disorders in the UK. While clinical trials have documented its clinical effectiveness, little is known regarding the relationship between duloxetine use and healthcare utilization in community practice. This study quantifies the impact of treatment with duloxetine on healthcare utilization among patients with depression and those with depression and co-existing pain., Methods: Depressed adults initiating duloxetine during 1/1/2006-9/30/2007 were identified from the General Practice Research Database (GPRD). All-cause hospitalization, accident/emergency visits, specialist referrals, and analgesic use in the 12 months before (pre-period) and after (post-period) duloxetine initiation were compared. Generalized Estimating Equation models evaluated the pre-post change in the odds of hospitalization., Results: Nine hundred and nine patients were identified, 413 had pre-period unexplained pain (UPain). Rates of hospitalization declined from the pre- to the post-period. Fewer UPain patients received analgesics post-duloxetine initiation. Multivariate analyses confirmed that the odds of hospitalization were lower after duloxetine initiation. UPain patients with pre-period anticonvulsant use had lower odds of hospitalization in the post-period and the reduction in odds was significantly larger than that of patients without pre-period anticonvulsants. While patients with pre-period anxiolytic use, alcohol/drug dependence, or sleep disorders did not show statistically significant pre-post change in the odds of hospitalization, these changes were significantly different from patients without these conditions., Limitations: The study did not include a comparison group of patients who were non-users of duloxetine. Prevalence of chronic conditions might be under-estimated due to coding in the GPRD. Medications were assumed to be taken as prescribed. Study results are not generalizable beyond the population covered by the UK's primary care system., Conclusions: All-cause hospitalization rates lowered among depressed patients and fewer UPain patients received analgesics post-duloxetine initiation. The reduction in the odds of hospitalization was most pronounced among UPain patients receiving pre-period anticonvulsants.

Background: The use of rapid-acting insulin analogs and regular insulin differs considerably in countries throughout the world. We therefore studied how glycemic control has been affected by using insulin lispro in clinical practice over 5 years in 14 hospitals in Sweden., Methods: We used a time period when most patients had not changed the basal insulin, but only the mealtime insulin. Accordingly the most recent years were not suitable since many patients had changed basal insulin from NPH to glargine or determir. We therefore analyzed the metabolic consequences on glycosylated hemoglobin (HbA1c) when changing from regular insulin to insulin lispro from 1997 and during the following 5 years. We studied 1,069 patients with diabetes taking NPH insulin as basal insulin and at least three daily injections of regular insulin, of whom 423 changed their mealtime insulin to insulin lispro and 646 controls who continued with regular insulin., Results: Patients changing to insulin lispro on average decreased by 0.19% units more in HbA1c than those remaining on regular insulin. The effect was most pronounced in patients with high HbA1c even after controlling for regression to the mean. A beneficial effect of insulin lispro was also indicated since patients had the same level of HbA1c during a long period of time with regular insulin but then dropped when changing to insulin lispro., Conclusions: This study indicates that insulin lispro has had a beneficial and persisting effect on glycemic control when used in patients with diabetes on multiple daily injections of insulin in clinical practice.