Stated Preferences for Attributes of a CYP2C19 Pharmacogenetic Test Among the General Population Presented with a Hypothetical Acute Coronary Syndrome Scenario.

BACKGROUND: Pharmacogenetic (PGx) testing identifies pharmacotherapeutic risks to permit personalized therapy. Identifying the genetic profile of patients with acute coronary syndrome (ACS) who are considered for therapy with clopidogrel (P2Y12 receptor blockers) and acetylsalicylic acid (ASA) contributes to the treatment paradigm. Patient preferences would inform a collaborative framework and by extension inform healthcare policy formulation. PURPOSE: To quantify stated preferences (willingness to pay) for attributes of a novel point-of-care PGx (CYP2C19) test using a discrete choice experiment (DCE) from the general public in Ontario, Canada, and to identify starting point bias of the cost attribute. METHODS: A web survey was created and included a questionnaire, decision board, and a DCE. DCE choice sets include the following attributes (levels): sample collection (blood, finger prick, and cheek swab), turnaround time for results (1 hr, 3 days, and 1 week), and cost in additional insurance premiums. The presence of starting point bias (cost attribute levels of $0, $1, $5 or $0, $2, $10) in the estimation of willingness to pay (WTP) was tested. RESULTS: Estimates for turnaround time and cost attributes were statistically significant. Coefficients related to the starting point bias were also significant. Approximately 67% of survey participants chose the PGx test compared to status quo treatment options. WTP for a 1 hr turnaround time compared to a 1-week turnaround time was $10.77 (95% CI 9.58 -12.25). CONCLUSION: This translational study shows preference for a point of care PGx test.

Cost-effectiveness of 3-month paliperidone therapy for chronic schizophrenia in the Netherlands.

BACKGROUND: A new depot formulation of paliperidone has been developed that provides effective treatment for schizophrenia for 3 months (PP3M). It has been tested in phase-3 trials, but no data on its cost-effectiveness have been published. PURPOSE: To determine the cost-effectiveness of PP3M compared with once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT), risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating chronic schizophrenia in The Netherlands. METHODS: A previous 1-year decision tree was adapted, based on local inputs supplemented with data from published literature. The primary analysis used DRG costs in 2016 euros from the insurer perspective, as derived from official lists. A micro-costing analysis was also conducted. For the costing scenario, official list prices were used. Clinical outcomes included relapses (treated as outpatients, requiring hospitalization, total), and quality-adjusted life-years (QALYs). Rates and utility scores were derived from the literature. Economic outcomes were the incremental cost/QALY-gained or relapse-avoided. Model robustness was examined in scenario, 1-way, and probability sensitivity analyses. RESULTS: The expected cost was lowest with PP3M (8,781€), followed by PP1M (10,325€), HAL-LAT (11,278€), RIS-LAT (11,307€), and oral-OLZ (13,556€). PP3M had the fewest total relapses/patient (0.36, 0.94, 1.39, 1.21, and 1.70, respectively), hospitalizations (0.11, 0.46, 0.40, 0.56, and 0.57, respectively), emergency room visits (0.25, 0.48. 0.99, 0.65, and 1.14, respectively) and the most QALYs (0.847, 0.735, 0.709, 0.719, and 0.656, respectively). In both cost-effectiveness and cost-utility analyses, PP3M dominated all other drugs. Sensitivity analyses confirmed base case findings. In the costing analysis, total costs were, on average, 31.9% higher than DRGs. CONCLUSIONS: PP3M dominated all commonly used drugs. It is cost-effective for treating chronic schizophrenia in the Netherlands. Results were robust over a wide range of sensitivity analyses. For patients requiring a depot medication, such as those with adherence problems, PP3M appears to be a good alternative anti-psychotic treatment.

Cost-effectiveness of 3-month paliperidone treatment for chronic schizophrenia in Spain.

BACKGROUND: A 3-month long treatment of paliperidone palmitate (PP3M) has been introduced as an option for treating schizophrenia. Its cost-effectiveness in Spain has not been established. AIMS: To compare the costs and effects of PP3M compared with once-monthly paliperidone (PP1M) from the payer perspective in Spain. METHODS: This study used the recently published trial by Savitz et al. as a core model over 1 year. Additional data were derived from the literature. Costs in 2016 Euros were obtained from official lists and utilities from Osborne et al. The authors conducted both cost-utility and cost-effectiveness analyses. For the former, the incremental cost per quality-adjusted life-year (QALY) gained was calculated. For the latter, the outcomes were relapses and hospitalizations avoided. To assure the robustness of the analyses, a series of 1-way and probability sensitivity analyses were conducted. RESULTS: The expected cost was lower with PP3M (4,780€) compared with PP1M (5,244€). PP3M had the fewest relapses (0.080 vs 0.161), hospitalizations (0.034 v.s 0.065), and emergency room visits (0.045 v.s 0.096) and the most QALYs (0.677 v.s 0.625). In both cost-effectiveness and cost-utility analyses, PP3M dominated PP1M. Sensitivity analyses confirmed base case findings. For the primary analysis (cost-utility), PP3M dominated PP1M in 46.9% of 10,000 simulations and was cost-effective at a threshold of 30,000€/QALY gained. CONCLUSIONS: PP3M dominated PP1M in all analyses and was, therefore, cost-effective for treating chronic relapsing schizophrenia in Spain. For patients who require long-acting therapy, PP3M appears to be a good alternative anti-psychotic treatment.

Dose escalation of biologics in Crohn's disease: critical review of observational studies.

BACKGROUND: Biologics used to treat Crohn's disease (CD) may lose their effect over time, requiring dose escalation. Little information is available on this topic. AIM: To summarize rates of dose escalation, duration, de-escalation in observational studies of CD in adults treated with adalimumab, infliximab, and vedolizumab in Europe. METHODS: Two independent investigators searched Medline and Embase for observational studies published in 1998-2015 and proceedings from four major scientific meetings. Rates were summarized descriptively. RESULTS: In total, 58 articles from 12 European countries were analyzed (49 full articles, nine abstracts), providing 65 reports with 7,850 patients; 35 reported on 3,830 patients with adalimumab (ADA), and 30 on 4,020 patients with infliximab (IFX). Overall, 29.9% ± 3.5% of patients required dose escalation; 32.8% ± 6.2% with ADA and 25.2% ± 2.4% with IFX (p = .35 between drugs). Rates increased according to line of treatment: 19% for first line, 37% second, and 41% third. The median time to loss of response was 12 months, and the weighted average was 15.1 ± 5.9 months. Median time to escalation was 6.7 months; 6.7 months for ADA and 7.5 for IFX (p = .86). Short-term response rates to escalation were 63% for ADA and 45% for IFX (p = .08). There were no papers available for vedolizumab. CONCLUSIONS: A substantial proportion of patients receiving ADA or IFX for Crohn's disease require dose escalation after a short period of time.

Comparative effectiveness of interferons in relapsing-remitting multiple sclerosis: a meta-analysis of real-world studies.

BACKGROUND: Differences between interferons have been evaluated for over 20 years. While randomized controlled trial (RCT) data is mainly used for assessments and strong data for causal inferences, it does not necessarily reflect everyday practice. Real-world data may provide additional information. PURPOSE: To assess the results, quality, and representativeness of observational studies directly comparing interferons (IFNs) in RRMS. METHODS: Medline and Embase were searched for observational studies comparing IFN-beta-1a 30 mcg IM (Avonex 1 ), IFN-beta-1a 44 mcg SC (Rebif 2 ) and/or IFN-beta-1b 250 mcg SC (Betaseron 3 ). Outcomes included annualized relapse rate (ARR), proportions relapse free, confirmed progression free, treatment persistence, and neutralizing antibodies rates (NABs) measured up to 5 years of treatment. Data was combined using random effects meta-analyses. Categorical values were analyzed using chi-squared and Mann-Whitney tests. RESULTS: Thirty-six studies examining 32,026 patients (72.5% females, age = 39.2 ± 3.7 years, disease duration = 5.6 ± 2.0 years) were identified. Thirty-three studies investigated IFN-beta-1a IM (N = 11,925), 30 IFN-beta-1a SC (N = 10,684) and 34 IFN-beta-1b SC (N = 9417). Baseline ARRs were similar (1.37 ± 0.35, 1.51 ± 0.27 and 1.55 ± 0.23, respectively; P = .101) as were EDSS scores (2.24 ± 0.39, 2.33 ± 0.30, 2.55 ± 0.38; P = .070) and >75% were naïve to IFNs. On treatment, ARRs were comparable (IFN-beta-1a IM 0.52 ± 0.27, IFN-beta-1a SC 0.51 ± 0.24, IFN-beta-1b SC 0.55 ± 0.23; P = .595). Proportions of relapse-free patients were similar between drugs (P > .05 for all data points), except that IFN-beta-1a SC was superior to IFN-beta-1b SC in years 3-5 (all P ≤ .001). After 1 year, EDSS scores were comparable; after 2 years, IFN-beta-1a IM and IFN-beta-1a SC incurred less disease progression than IFN-beta-1b SC (P < .02). Confirmed progression-free rates and persistence were similar over 5 years. Fewer patients developed NABs with IFN-beta-1a IM (4.7 ± 1.5%) versus IFN-beta-1a SC (21.4 ± 2.8%) (P < 0.001) or IFN-beta-1b SC (32.2% ± 3.3%) (P < .001). CONCLUSIONS: In this comprehensive meta-analysis of real-world studies in RRMS, IFN-beta-1a IM, IFN-beta-1a SC and IFN-beta-1b SC had similar clinical profiles. When selecting an IFN, practitioners should consider observational data in their decision making process.

Systematic literature review of the health economic implications of early detection by screening populations at risk for type 2 diabetes.

BACKGROUND: Undetected/uncontrolled diabetes is associated with substantial morbidity and mortality and consequent costs. Early detection through screening identifies patients at risk, allowing for earlier treatment initiation. OBJECTIVES: To determine the economic impact of screening for type 2 diabetes (T2DM). DATA SOURCES: We systematically reviewed health economic analyses of screening programs for T2DM/pre-diabetes. STUDY ELIGIBILITY CRITERIA: Published between 2000 and 2015 in any language. Articles must have reported costs of screening, test/patient outcomes and cost-effectiveness. PARTICIPANTS AND INTERVENTIONS: Any type of screening (universal, targeted, opportunistic) was accepted. METHODS: Data were extracted from Scopus/Medline/Embase, then tabulated. RESULTS: There were 137 studies identified, 108 rejected; 29 were analyzed. Screening types included 18 universal, 8 targeted and 8 opportunistic. One study screened for pre-diabetes, 16 for T2DM and 12 examined both. Fourteen (48%) reported costs of screening only, 9 (31%) costs of screening combined with interventions and 6 (21%) presented all costs separately. Screening was compared to no screening in 13 studies (45%); screening was cost-effective in 8 (62%), not cost-effective in 4 (31%) and neither in 1 (8%). When comparing different screening methods, 6 found targeted screening was cost-effective compared with universal screening (none found the opposite), 2 found opportunistic superior to universal. Sensitivity analyses generally confirmed primary findings. Cost drivers included prevalence of T2DM/pre-diabetes, type of blood test used and uptake of testing. For optimal cost-effectiveness, screening for both T2DM and pre-diabetes should be initiated around age 45-50, with repeated testing every 5 years. CONCLUSIONS/IMPLICATIONS: Targeted screening appears to be cost-effective compared to universal screening.

Economic analysis of paliperidone long-acting injectable for chronic schizophrenia in Portugal.

OBJECTIVE: Patients with chronic schizophrenia suffer a huge burden, as do their families/caregivers. Treating schizophrenia is costly for health systems. The European Medicines Agency has approved paliperidone palmitate (PP-LAI; Xeplion), an atypical antipsychotic depot; however, its pharmacoeconomic profile in Portugal is unknown. A cost-effectiveness analysis was conducted from the viewpoint of the Portuguese National Health Service. METHODS: PP-LAI was compared with long acting injectables risperidone (RIS-LAI) and haloperidol (HAL-LAI) and oral drugs (olanzapine; oral-OLZ) adapting a 1-year decision tree to Portugal, guided by local experts. Clinical information and costs were obtained from literature sources and published lists. Outcomes included relapses (both requiring and not requiring hospitalization) and quality-adjusted life-years (QALYs). Costs were expressed in 2014 euros. Economic outcomes were incremental cost-effectiveness ratios (ICERs); including cost-utility (outcome = QALYs) and cost-effectiveness analyses (outcomes = relapse/hospitalization/emergency room (ER) visit avoided). RESULTS: The base-case cost of oral-OLZ was 4447€ (20% drugs/20% medical/60% hospital); HAL-LAI cost 4474€ (13% drugs/13% medical/74% hospital); PP-LAI cost 5326€ (49% drugs/12% medical/39% hospital); RIS-LAI cost 6223€ (44% drugs/12% medical/44% hospital). Respective QALYs/hospitalizations/ER visits were oral-OLZ: 0.761/0.615/0.242; HAL-LAI: 0.758/0.623/0.250; PP-LAI: 0.823/0.288/0.122; RIS-LAI: 0.799/0.394/0.168. HAL-LAI was dominated by oral-OLZ and RIS-LAI by PP-LAI for all outcomes. The ICER of PP-LAI over oral-OLZ was 14,247€/QALY, well below NICE/Portuguese thresholds (≈24,800€/30,000€/QALY). ICERs were 1973€/relapse avoided and 2697€/hospitalization avoided. Analyses were robust against most variations in input values, as PP-LAI was cost-effective over oral-OLZ in >99% of 10,000 simulations. CONCLUSION: In Portugal, PP-LAI dominated HAL-LAI and RIS-LAI and was cost-effective over oral-OLZ with respect to QALYs gained, relapses avoided, and hospitalizations avoided.

Pharmacoeconomics of long-acting atypical antipsychotics for acutely relapsed chronic schizophrenia in Finland.

BACKGROUND: Atypical long-acting injectable (LAI) antipsychotics are increasingly available for treating chronic schizophrenia in patients chronically non-adherent to prescribed regimens. Few economic studies have compared these products. PURPOSE: To determine the cost-effectiveness of aripiprazole (ARI-LAI), paliperidone (PP-LAI), olanzapine (OLZ-LAI), and risperidone (RIS-LAI) in patients with chronic schizophrenia in Finland. METHODS: A 1-year decision tree model was adapted with guidance from an expert panel. Patients started hospitalized in relapse; those who responded continued treatment, others were switched to secondary drugs, then clozapine in the event of 2nd line failure. Rates of adherence, stable disease, relapse, and hospitalization were taken from pivotal trials, and utilities from published research. Included were direct costs paid by the Finnish Ministry of Health, in 2015 euros. Outcomes included quality-adjusted life-years (QALYs), hospitalization rates, and rates of relapse not requiring hospitalization. Model robustness was assessed using a series of 1-way and multivariate sensitivity analyses. RESULTS: Expected costs were lowest for PP-LAI at 41,148€, followed by 41,543€ for ARI-LAI, 42,067€ for RIS-LAI and 45,406€ for OLZ-LAI. Respective QALYs were 0.683, 0.671, 0.666, and 0.672. Re-hospitalization rates and non-admitted relapses were 23.6% and 3.9% for PP-LAI, 28.5% and 4.1% for ARI-LAI, 28.8% and 5.0% for RIS-LAI, 28.3% and 5.2% for OLZ-LAI. PP-LAI treatment was associated with the most days with stable disease (132.0), followed by OLZ-LAI (125.5), ARI-LAI (122.6), and RIS-LAI (114.4). Sensitive inputs between PP-LAI and ARI-LAI included rates of adherence, dropouts, and relapses plus drug prices; dropout and relapse rates for RIS-LAI; OLZ-LAI results were insensitive. In probability sensitivity analyses, PP-LAI dominated ARI-LAI in 75.8% of the 10,000 iterations, RIS-LAI in 83.1% and OLZ-LAI in 95.7%. CONCLUSIONS: PP-LAI dominated the other atypicals. It appears to be the preferred option for treating chronic relapsing schizophrenia.

Systematic review of models used in economic analyses in moderate-to-severe asthma and COPD.

BACKGROUND: Respiratory diseases exert a substantial burden on society, with newer drugs increasingly adding to the burden. Economic models are often used, but seldom reviewed. PURPOSE: To summarize economic models used in economic analyses of drugs treating moderate-to-severe/very severe asthma or chronic obstructive pulmonary disease (COPD). METHODS: This study searched Medline and Embase from inception to the end of February 2015 for cost-effectiveness/utility analyses that examined at least one drug against placebo, another drug, or other standard therapy in asthma or COPD. Two reviewers independently searched and extracted data with differences adjudicated via consensus discussion. Data extracted included model used and its qualities, validation methods, treatments compared, disease severity, analytic perspective, time horizon, data collection (pro- or retrospective), input rates and sources, costs and sources, planned sensitivity analyses, criteria for cost-effectiveness, reported outcomes, and sponsor. RESULTS: This study analyzed 53 articles; 14 (25%) on asthma and 39 (75%) COPD. Markov models were commonly used for both asthma and COPD-related economic evaluations. Relatively few studies validated their model. For asthma-related studies, 10 examined inhaled corticosteroids and nine studied omalizumab. Placebo or standard therapy was the comparison in 11 studies and active drugs in the remainder. CONCLUSIONS: Few studies include validation of their models. Furthermore, controversy concerning some results was uncovered in this study, which needs to be avoided in the future.

Patient preferences in severe COPD and asthma: a comprehensive literature review.

BACKGROUND: Management of chronic incurable diseases such as chronic obstructive pulmonary disease (COPD) and asthma is difficult. Incorporation of patient preferences is widely encouraged. PURPOSE: To summarize original research articles determining patient preference in moderate-to-severe disease. METHODS: Acceptable articles consisted of original research determining preferences for any aspect of care in patients with COPD/asthma. The target population included those with severe disease; however, articles were accepted if they separated outcomes by severity or if the majority had at least moderate-to-severe disease. We also accepted simulation research based on scenarios describing situations involving moderate-to-severe disease that elicited preferences. Two reviewers searched Medline and Embase for articles published from the date of inception of the databases until the end of November 2014, with differences resolved through consensus discussion. Data were tabulated and analyzed descriptively. RESULTS: About 478 articles identified, 448 were rejected and 30 analyzed. There were 25 on COPD and five on asthma. Themes identified as most important in COPD were symptom relief (dyspnea/breathlessness), a positive patient-physician relationship, quality-of-life impairments, and information availability. Patients strongly preferred sponsors' inhalers. At end-of-life, 69% preferred receiving CPR, 70% wanted noninvasive, and 58% invasive mechanical intervention. While patients with asthma preferred treatments that increased symptom-free days, they were willing to trade days without symptoms for a reduction in adverse events and greater convenience. Asthma patients were willing to pay for waking up once and not needing their inhaler over waking up once overnight and needing their inhaler. CONCLUSION: Few studies have examined patient preference in these diseases. More research is needed to fill in knowledge gaps.

Utilities for asthma and COPD according to category of severity: a comprehensive literature review.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are incurable diseases that impact quality-of-life. OBJECTIVE: To summarize original research articles that measured or utilized preference-based utilities or disutilities according to disease severity. METHODS: Medline and Embase were searched from inception until the end of November 2014. Two reviewers independently searched the literature with differences settled through discussion. Data extracted included utility scores as determined in original research categorized according to disease severity as well as disutilities associated with exacerbations or comorbidities. Data were tabulated and analyzed descriptively. RESULTS: In total, 862 articles were identified, 790 were rejected, and 69 analyzed. There were 44 dealing with COPD and 25 with asthma. Average utilities determined by research were 0.828 ± 0.062, 0.765 ± 0.090, 0.711 ± 0.120, and 0.607 ± 0.120 for mild, moderate, severe, and very severe COPD, respectively. Utilities used in economic analyses were 0.866 ± 0.038, 0.770 ± 0.024, 0.739 ± 0.045, and 0.596 ± 0.075, respectively. Disutilities (annual) ranged from 0.002-0.378; major and minor exacerbations had respective disutilities of 0.287 and 0.108. For asthma patients, utilities were for 0.86 ± 0.32, 0.83 ± 0.065, and 0.74 ± 0.029, for mild, moderate, and severe disease, respectively. CONCLUSIONS: Utilities have been summarized according to severity category of asthma and COPD. These values should be useful for researchers undertaking economic analyses of these diseases.

Evidence-based review of clinical outcomes of guideline-recommended pharmacotherapies for generalized anxiety disorder.

OBJECTIVE: To quantify the rates of clinical outcomes of Canadian Psychiatric Association (CPA) guideline-recommended pharmacotherapies for generalized anxiety disorder (GAD) by drug classification within each treatment line. METHODS: Evidence from original research cited by the CPA was included. Pooled analyses, duplicates, and studies with nonextractable data were excluded. Response, remission, and baseline-endpoint or mean reductions scores of the Hamilton Anxiety Rating Scale (HARS) were extracted. The Cochrane Collaboration's computer program, Review Manager, version 5, with a random effects model, was used to pool results. RESULTS: A total of 50 articles were cited as evidence for managing GAD by the CPA. There was sufficient evidence of remission with first- or third-line agents to pool reported rates, and with agents from all 3 treatment lines to pool response rates and reduction in HARS scores. The mean range of effect size varied considerably from study to study within each treatment line. Comparison of pooled remission rates between first- and second-line agents was not possible. While the range of values by drug and drug class overlapped, the summary results for the probability of response and reduction in HARS scores was greater for first-line, compared with second-line, treatments. Drug components for third-line treatments were heterogeneous and produced mixed results. CONCLUSION: Despite the abundance of evidence in its totality presented in the CPA guidelines, there is inadequate evidence to formulate recommendations based on the pooled results from this study alone. However, such analysis provides an additional resource for clinicians to make more effective treatment decisions for individual patients with GAD.

A markov model approach assessing the cost of illness of generalized anxiety disorder in Canada.

INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic disease with waxing and waning of symptoms. This is the first comprehensive economic model developed to reflect the nature and course of GAD. METHODS: An incidence-based probabilistic Markov model was developed reflecting nine GAD health states (HS): clinical assessments (three HS), maintenance therapies (four HS), discontinuation (one HS), and death (one HS). A probability curve of the GAD onset (ages 18-80) determined entry into the model and assumed patients retained the diagnoses until death. Canadian Psychiatric Association (CPA) guidelines determined pharmacotherapy, with revisions/validation by an expert panel. Direct costs (clinician, pharmacotherapy, hospitalization) were retrieved from government publications. Remission was based on pooled-analysis of CPA-cited evidence. Remaining clinical rates, absenteeism, and hospitalization were retrieved from the literature. Direct costs were attributed throughout the model except for the discontinuation and death HS. Indirect costs (wage rate) were retrieved from government publications and the literature (absenteeism), and were attributed to patients with GAD ≤65 years of age. Results were discounted at 5% and results expressed in 2008 Canadian dollars. RESULTS: The mean lifetime cost of illness (COI) was estimated to be $31,213 (SD $9,100) per patient. The cost of absenteeism accounted for 96% of the mean COI. The mean age of onset was 31 years and approximately 19% did not respond to pharmacotherapy. Over 85% of patients discontinued treatment by the fourth cycle (2nd year of therapy). Over the course of the model, a mean of 53% of patients relapsed, with an average rate of 0.79 relapses per patient. On average and over a lifetime, the disorder went unmanaged over a period of 14 (SD 9) years. The model was most sensitive to absenteeism. CONCLUSION: GAD is a costly disease with a lifetime COI <$32k/patient, with absenteeism exerting a significant impact.

Financial burden of household out-of-pocket expenditures for prescription drugs: cross-sectional analysis based on national survey data.

BACKGROUND: Commentaries on the adequacy of insurance coverage for prescription drugs available to Canadians have emphasized differences in the coverage provided by different provincial governments. Less is known about the actual financial burden of prescription drug spending and how this burden varies by province of residence, affluence and source of primary drug coverage. METHODS: We used data from a nationally representative household expenditure survey to analyze the financial burden of prescription drugs. We focused on the drug budget share (defined as the share of the household budget spent on prescription drugs), considering how it varied by province, total household budget and likely primary source of drug insurance coverage (i.e., provincial government plan for senior citizens, social assistance plan or private coverage). We examined both "typical" households (at the median of the distribution of the drug budget share) and households with relatively large shares (in the top 5%). Finally, we estimated the percentage of households with catastrophic drug expenditures (defined as a drug budget share of 10% or more) and the average catastrophic drug expenditures. RESULTS: Senior, social assistance and general population households accounted for 21.1%, 8.9% and 69.9% of the sample of 14,430 respondents to the 2006 Survey of Household Spending, respectively. The median drug budget share in Canada was 1.1% for senior households (range 0.4% [Ontario] to 3.6% [Saskatchewan]) and 0.1% for both social assistance households and general population households, with little appreciable variation across provinces for these latter 2 categories. The 95th percentile drug budget share in Canada was 7.4% for senior households (range 3.5% [Ontario] to 12.7% [Saskatchewan]), 5.4% for social assistance households (range 2.3% [British Columbia] to 13.0% [Prince Edward Island]) and 2.6% for general population households (range 2.1% [Ontario] to 5.4% [Prince Edward Island]). The interprovincial range of the 95th percentile drug budget share was 10.7 percentage points for social assistance households, 9.2 percentage points for senior households and 3.3 percentage points for general population households. INTERPRETATION: For most households, the financial burden of prescription drug expenditures appeared to be relatively small, with little interprovincial variation. However, a small number of households incurred catastrophic drug costs. These households were concentrated in the groups that traditionally benefit from provincial government drug plans. It is likely that some households did not purchase needed prescription drugs because of the expense, so our estimates of the financial burden of catastrophic prescription drug expenditures therefore represent a lower bound.

Systematic review and quality assessment of economic evaluations and quality-of-life studies related to generalized anxiety disorder.

BACKGROUND: The objectives of this article were to systematically review, summarize the results of, and assess the quality of economic evaluations and humanistic studies related to patients with generalized anxiety disorder (GAD). METHODS: EMBASE, EBM Reviews, MEDLINE, and HealthSTAR databases were searched (from the time of inception through April 2008). Full-text publications describing full economic evaluations (cost-benefit, cost-minimization, cost-effectiveness, and cost-utility analyses), partial economic evaluations (cost, burden-of-illness, and resource-utilization analyses), and humanistic outcomes (utilities, preferences, and willingness-to-pay analyses) were included. GAD diagnoses per official publications (eg, Diagnostic and Statistical Manual of Mental Disorders) and associated comorbid conditions were included; anxiety-related symptoms without a diagnosis of GAD were excluded. Study quality was assessed with a 38-point checklist of criteria previously developed by the Panel on Cost-Effectiveness in Health and Medicine. RESULTS: Thirty-six articles were included. Full economic evaluations (n = 5) were based on conventional decision-making modeling or population-summary data, using time horizons < or =12 months. Cognitive-behavioral therapy by a public-salaried psychologist and evidence-based care generated savings compared with current care. Pharmacotherapy with extended-release venlafaxine treatment was cost-effective compared with diazepam; escitalopram was cost-effective compared with paroxetine because of productivity gains. Full economic evaluations addressed 55.3% to 68.4% of the 38 items on the quality-assessment checklist. Partial evaluations were reported; GAD incurred larger mean marginal health care costs compared with other anxiety disorders (a difference of US $2138 in year-1999 values). GAD patients with severe pain interference incurred significantly higher costs than did patients with pain but no GAD. Furthermore, GAD patients used more services from a primary care provider or specialist than did patients with other psychiatric disorders. Comorbidities were associated with greater absenteeism than was having a diagnosis of GAD alone. Mean (SE) utility scores for quality-of-life assessments among patients with GAD (15D, 0.783 [0.019]; EuroQoL EQ-5D, 0.589 [0.038]) were similar to those for patients who were 20 years older and reported somatic conditions such as Parkinson's disease or heart failure. CONCLUSIONS: Current evidence suggests that GAD is associated with substantial economic and humanistic impact on patients and health care systems. Future research should address economic evaluations from the private-payer perspective, studies related to the cost of underdiagnosed or untreated GAD, and full economic evaluations that incorporate longer clinical courses of the disorder.

Assessing the reporting and scientific quality of meta-analyses of randomized controlled trials of treatments for anxiety disorders.

BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) constitute the highest level of evidence, but their usefulness depends on their quality. OBJECTIVE: To assess the reporting and scientific quality of meta-analyses of RCTs on treatments for anxiety disorders. METHODS: Criteria for peer-reviewed, full-text retrieval included meta-analyses of RCTs of drugs versus active ingredient placebo, standard care, or psychotherapy. Sample populations were required to meet Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases and Related Health Problems diagnostic criteria for anxiety disorders. Two reviewers independently searched EMBASE, EBM Reviews, Ovid MEDLINE, Ovid HealthSTAR, and International Pharmaceutical Abstracts from inception to August 2007. Search terms included meta-analysis, randomized controlled trials, anxiety, anxiolytic, anti-depressant/antidepressant, and pharmacotherapy, without language restrictions. References and reviews were searched manually. Quality was assessed independently by 2 raters, using the Quality of Reporting of Meta-analyses (QUOROM) and the Overview Quality Assessment Questionnaire (OQAQ). The QUOROM was used to assess the reporting quality of the study, using an 18-item checklist, and the scientific quality was assessed with the OQAQ's 10-item checklist. Kendall's tau measured interrater reliability with statistical significance at p less than or equal to 0.01. Means and standard deviations described the overall quality. A time series analysis was performed. RESULTS: A total of 136 titles and abstracts were reviewed; 48 were retrieved, including 6 from the manual search. Thirty-two were excluded (not pooled analyses, inappropriate condition/treatment, duplications), leaving 16 studies published between 1995 and 2007. Agreement was high: tau = 0.801 (p < 0.01) for QUOROM and 0.834 (p < 0.01) for OQAQ. QUOROM quality scored 61% +/- 19%. Overall, the results sections of the studies scored lowest, while the introduction and discussion sections scored highest. The overall scientific quality was 58% +/- 28%. Most studies appropriately linked results to primary objectives but did not report how bias was avoided or how study validity was assessed. Quality increased nonsignificantly over time. CONCLUSIONS: Reporting/scientific quality was considered less than fair-to-good. Stakeholders should strive for higher scientific quality of meta-analyses.

Cost-effectiveness of escitalopram for generalized anxiety disorder in Canada.

BACKGROUND: Generalized Anxiety Disorder (GAD) is a common chronic disease with a lifetime prevalence estimated to range from 4.2% to 12.7%. GAD places a substantial burden upon patients and healthcare resources. OBJECTIVE: To determine the cost-effectiveness of escitalopram for GAD in a Canadian primary care setting from two perspectives [Ministry of Health (MoH) and society (SOC)]. METHODS: A 24-week decision-analytic model was constructed using Data/TreeAge software. Patients were treated with escitalopram or generic paroxetine. Clinical rates were determined from the literature; expert opinion guided model pathway development. Effectiveness was measured as 'symptom-free days' (SFDs). Analyses from MoH perspective focused on direct costs of treatment (drugs, physician visits), while SOC also accounted for indirect costs associated with workdays lost due to GAD. Unit costs of healthcare services and wage rates were obtained from standard Canadian sources (2005 Canadian $ values). Cost-effectiveness was expressed as the incremental cost-effectiveness ratio (ICER). Extensive one-way and probabilistic sensitivity analyses were conducted. RESULTS: Escitalopram was associated with higher expected number of SFDs than paroxetine (86.4 vs. 77.0 SFD, respectively). From the MoH perspective, expected costs were Can$724 and Can$663 for escitalopram and paroxetine arms, respectively, resulting in the ICER for escitalopram vs. paroxetine of Can$6.56/SFD (Can$2362/symptom free year). From the SOC perspective, escitalopram dominated paroxetine as more effective on SFDs and less costly. Sensitivity analyses demonstrated robustness of the model. Limitations include the absence of comorbidities, which are common in practice, lack of long-term data, and assuming that dropouts in trials reflect those in practice. CONCLUSION: Escitalopram was found to be cost-effective compared with paroxetine in treatment of GAD from the Canadian MoH perspective, and dominating paroxetine from the SOC perspective. Therefore, a possible advantage may exist at the population level in the treatment of GAD with escitalopram in Canada.

Pain due to multiple sclerosis: analysis of the prevalence and economic burden in Canada.

BACKGROUND: Multiple sclerosis (MS) is a neurological disease affecting approximately 50,000 Canadians. Although studies have described overall MS costs, none have focused specifically on MS-related pain. OBJECTIVES: To estimate the prevalence of MS-related pain in Canada, the proportion of patients treated and responding to treatment for MS-related pain, and the associated economic burden. METHODS: Results were captured through physician and patient surveys. Patients were recruited through MS clinics and the MS Society. Patient-reported outcomes and resource utilization over the previous six months were collected by telephone interview. Costs were measured in 2004 Canadian dollars. The economic burden was extrapolated to the population using national demographics and prevalence. Spearman's rho assessed the relationship between cost and pain severity. RESULTS: Physicians estimated that 46% of their MS patients experienced MS-related pain, and that 35% received treatment for pain. Pain was reported to be relieved somewhat in 29%+/-10% of their patients, adequately in 26%+/-19% and poorly in 27%+/-13%, while 17%+/-9% received no relief. Two hundred ninety-seven participants completed the patient survey. Seventy-one per cent (211 of 297 patients) experienced MS-related pain. Eighty per cent of patients reported taking some type of medication to manage their pain, and of these, 82% reported some reduction in pain. The mean +/- SD direct cost per patient of MS-related pain was dollars 2,528+/-5,695. The mean +/- SD indirect cost per patient was dollars 669+/-875. Total costs were positively correlated with levels of self-reported pain (rho=0.291, rho<0.0001). The estimated six-month burden of pain of MS patients in Canada was dollars 79,444,888. CONCLUSIONS: The prevalence of pain is high in MS patients. This condition may be underdiagnosed and undertreated, and results in a significant economic burden on society.