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Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain

ABSTRACT Objective: Debilitating pain, occurring in 50–70% of multiple sclerosis (MS) patients, is poorly understood and infrequently studied. We summarized efficacy and safety data of cannabinoid-based drugs for neuropathic pain. Data sources: Studies were identified from Medline, Embase, and Cochrane databases; Bayer Healthcare provided additional trials. Study selection: Accepted were randomized, double-blinded placebo-controlled trials of cannabinoid-based treatments for MS-related/neuropathic pain in adults ≥ 18 years of age. Data extraction: Two reviewers identified studies and extracted data; a third adjudicated disagreements. Data included baseline and endpoint pain scores on visual analog or 11-point ordinal scales. Data synthesis: Of 18 articles and three randomized controlled trial (RCT) reports identified, 12 articles and two reports were rejected (9 = inappropriate disease or outcome, 1 = duplicate, 1 = review, and 1 = abstract); six accepted articles and one RCT-report involved 298 patients (222 treated, 76 placebo); four examined Sativex* (a cannabidiol/delta-9-tetrahydrocannabinol (THC) buccal spray) (observations = 196), five cannabidiol (n = 41), and three dronabinol (n = 91). Homogeneity χ2 values were non-significant, allowing data combination. Analyses focused on baseline-endpoint score differences. The cannabidiol/THC buccal spray decreased pain 1.7 ± 0.7 points ( p = 0.018), cannabidiol 1.5 ± 0.7 ( p = 0.044), dronabinol 1.5 ± 0.6 ( p = 0.013), and all cannabinoids pooled together 1.6 ± 0.4 ( p < 0.001). Placebo baseline-endpoint scores did not differ (0.8 ± 0.4 points, p = 0.023). At endpoint, cannabinoids were superior to placebo by 0.8 ± 0.3 points ( p = 0.029). Dizziness was the most commonly observed adverse event in the cannabidiol/THC buccal spray arms (39 ± 16%), across all cannabinoid treatments (32.5 ± 16%) as well as in the placebo arms (10 ± 4%). Conclusion: Cannabinoids including the cannabidiol/THC buccal spray are effective in treating neuropathic pain in MS. Limitations: This review was based on a small number of trials and patients. Pain related to MS was assumed to be similar to neuropathic pain.

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

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

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 Parkinsons 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.

Evidence-Based Review of Clinical Outcomes of Guideline-Recommended Pharmacotherapies for Generalized Anxiety Disorder

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. Spearmans 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.

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

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 Collaborations 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.

Assessing the Reporting and Scientific Quality of Meta-Analyses of Randomized Controlled Trials of Treatments for Anxiety Disorders:

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.

Willingness to Pay for a Treatment for Pain in Multiple Sclerosis

Background: Mela-analyses of randomized controlled trials (RCTs) constitute the highest level of evidence, but their usefulness depends on their quality. Objective: To assess tho 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-anatyses (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 OQAQs 10-item checklist, Kendalls - 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: t = 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 qualify was 58% ± 28%. Most studies appropriately linked results to priman/ 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.

AbstractBackground: Multiple sclerosis (MS) is a chronic neurological disease that affects 240 per 100 000 Canadians. Of these patients, 10–80% (average 70%) experience pain. Sativex® is a cannabis-based drug recently approved for neuropathic pain. Objectives: In this study, we determine individuals’ preferences between two treatment options as well as the willingness to pay (WTP) for Sativex®, expressed as the amount they would pay in insurance premiums to have access to that treatment. Methods: The WTP instrument comprised a decision board as a visual aid, and a questionnaire. A decision board helps clinicians standardize the presentation of treatment information. In this study, the decision board described two treatment options: a three-drug combination (gabapentin, amytriptyline, acetaminophen [paracetamol] {i.e. pills}) and the three-drug combination plus Sativex® (i.e. ‘pills and oral spray’). Information on efficacy and adverse effects was taken from trial data; wording was guided by a panel of neurologists and tested for clarity on lay people. The instrument was administered to 500 participants from Canada’s general population using the bidding game approach. Descriptive statistics were calculated. Results: Mean (SD) age of participants was 39 (13) years, with a female: male distribution of 56: 44. The decision board was presented in both English (85%) and French (15%). Of 500 interviewees, 253 (50.6%) chose the ‘pills and oral spray’. Mean monthly WTP for the insurance premium for those who chose the ‘pills and oral spray’ was

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

Can8 (SD ± 15, median 4, range 0–200). Conclusions: Assuming that 51% of the general population are willing to pay additional premiums as reported in this study, the premiums collected would cover the cost of Sativex® for all Canadian MS patients experiencing pain, with a surplus.

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

ABSTRACT 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