Direct costs associated with adverse events of systemic therapies for advanced melanoma: Systematic literature review.

BACKGROUND: Treatments for advanced melanoma are associated with different adverse events (AEs), which may be costly to manage. This study aimed to evaluate direct costs associated with managing treatment-related AEs for advanced melanoma through a systematic literature review. METHODS: Systematic searches were conducted of the PubMed, Embase, Cochrane, BIOSIS, and EconLit medical literature databases to identify studies providing estimates of direct costs and health care resource utilization for the management of AEs of melanoma treatments, published between January 1, 2007, and February 23, 2017. Gray literature searches also were conducted. Studies reporting direct costs for patients with advanced melanoma that were published in English between 2007 and 2017 were eligible. Studies were systematically screened in 2 phases by 2 independent reviewers. Study design details and data on direct costs by country were extracted. RESULTS: Seven studies evaluating the cost of AEs in patients with advanced melanoma were included; most estimated the costs for grade 3 or 4 events. In a United States study, monthly AE costs constituted 36.9% of overall health care costs for dacarbazine, 30.3% for paclitaxel, 9.2% for temozolomide, 6.4% for vemurafenib, and 4.0% for ipilimumab. A multicountry study found the greatest cost per event to be for grade 3 or 4 AEs associated with ipilimumab, including colitis (A$1471 [Australia]-&OV0556;3313 [France]) and diarrhea (£2836 [United Kingdom]), and chemotherapy (neutropenia/leukopenia in Germany [&OV0556;1744] and Italy [&OV0556;804]). Across studies, cost drivers for the most expensive AEs to manage were requiring hospitalization or use of expensive outpatient medications and/or procedures (eg, erythropoietin and blood transfusions for anemia). Some currently available therapies were not available during the research period, and their associated AEs are not reflected. Results may not be comparable across countries. For some studies, resource-use estimates reflect practice patterns from a limited number of centers, limiting generalizability. CONCLUSION: Costs for managing each type of AE associated with the treatment of advanced melanoma are substantial. Effective treatments with improved safety profiles may help reduce total AE management costs.

A cost-effectiveness analysis of lisdexamfetamine dimesylate in the treatment of adults with attention-deficit/hyperactivity disorder in the UK.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder in children that may persist into adulthood. Lisdexamfetamine dimesylate (LDX) is approved in many countries for ADHD treatment in children, adolescents, and adults. OBJECTIVES: Estimate the cost-effectiveness of LDX as a first- or second-line treatment for adults with ADHD from the United Kingdom (UK) National Health Service (NHS) perspective compared with methylphenidate extended release (MPH-ER) and atomoxetine (ATX). METHODS: A 1-year decision-analytic model was developed. Health outcomes included response, non-response and inability to tolerate. Efficacy data were obtained from a mixed-treatment comparison (MTC). Response was a score of 1 or 2 on the Clinical Global Impression-Improvement scale. Tolerability was assessed by discontinuation rates due to adverse events. Utilities were identified via a systematic literature review. Health care resource use estimates were obtained via a survey of clinicians. Daily drug costs were estimated from mean doses reported in the trials used in the MTC. One-way and probabilistic sensitivity analyses (PSAs) were performed. RESULTS: LDX dominated MPH-ER and ATX; reducing mean per-patient annual cost by £5 and £200, and increasing mean quality-adjusted life years (QALYs) by 0.005 and 0.009, respectively. In the PSA, the probability of cost-effectiveness for LDX vs. MPH-ER and ATX at a threshold of £20,000 per QALY was 61% and 80%, respectively. CONCLUSIONS: From the perspective of the UK NHS, LDX is likely to provide a cost-effective treatment for adults with ADHD. This conclusion may be drawn with more certainty in comparison with ATX than with MPH-ER.

Humanistic and cost burden of systemic sclerosis: A review of the literature.

BACKGROUND: Systemic sclerosis (SSc), or systemic scleroderma, is a chronic multisystem autoimmune disease characterised by widespread vascular injury and progressive fibrosis of the skin and internal organs. Patients with SSc have decreased survival, with pulmonary involvement as the main cause of death. Current treatments for SSc manage a range of symptoms but not the cause of the disease. Our review describes the humanistic and cost burden of SSc. METHODS: A structured review of the literature was conducted, using predefined search strategies to search PubMed, Embase, and the Cochrane Library. Grey literature searches also were conducted. RESULTS: In total, 2226 articles were identified in the databases and 52 were included; an additional 10 sources were included from the grey literature. The review identified six studies reporting relevant cost estimates conducted in five different countries and four studies that assessed the humanistic burden of SSc. Total direct annual medical costs per patient for Europe varied from €3544 to €8452. For Canada, these costs were reported to be from Can$5038 to Can$10,673. In the United States, the total direct health care costs were reported to be US$17,365 to US$18,396. Different key drivers of direct costs were reported, including hospitalisations, outpatients, and medication. The total annual costs per patient were reported at Can$18,453 in Canada and varied from €11,074 to €22,459 in Europe. Indirect costs represented the largest component of the total costs. EQ-5D utility scores were lower for patients with SSc than those observed in the general population, with reported mean values of 0.49 and 0.68, respectively. The average value of the Health Assessment Questionnaire for patients with SSc was significantly higher than the control population (0.94), and the average value of the SF-36 was significantly lower than the control population: 49.99 for the physical dimension and 58.42 for the mental dimension. CONCLUSIONS: Overall, there is a paucity of information on the burden of SSc. Nonetheless, our review indicates that the quality of life of patients with SSc is considerably lower than that of the general population. In addition, SSc places a considerable economic burden on health care systems and society as a whole.

A Cost-Utility Analysis of Lisdexamfetamine Versus Atomoxetine in the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Inadequate Response to Methylphenidate.

BACKGROUND: An economic analysis from the perspective of the UK National Health Service (NHS) evaluated the cost effectiveness of lisdexamfetamine dimesylate (LDX) compared with atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder who have had an inadequate response to methylphenidate. METHODS: A 1-year decision-analytic model was constructed, with the health outcomes "response", "nonresponse", and "unable to tolerate". Clinical data were taken from a head-to-head, randomized controlled trial in inadequate responders to methylphenidate. Response to treatment was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement subscale. Tolerability was assessed by discontinuation rates owing to adverse events. Utility weights were identified via a systematic literature review. Healthcare resource use estimates were obtained via a survey of clinicians. Daily drug costs were derived from British National Formulary 2012 costs and mean doses reported in the trial. One-way and probabilistic sensitivity analyses (PSAs) were performed. RESULTS: The comparison of LDX with atomoxetine resulted in an estimate of an incremental cost-effectiveness ratio of £1802 per quality-adjusted life-year (QALY). The result was robust in a wide range of sensitivity analyses; results were most sensitive to changes in drug costs and efficacy. In the PSA, assuming a maximum willingness to pay of £20,000 per QALY, LDX versus atomoxetine had an 86 % probability of being cost effective. In 38 % of PSA runs, LDX was more effective and less costly than atomoxetine. CONCLUSIONS: From the perspective of the UK NHS, LDX provides a cost-effective treatment option for children and adolescents who are inadequate responders to methylphenidate.

Methodologies used in cost-effectiveness models for evaluating treatments in major depressive disorder: a systematic review.

BACKGROUND: Decision makers in many jurisdictions use cost-effectiveness estimates as an aid for selecting interventions with an appropriate balance between health benefits and costs. This systematic literature review aims to provide an overview of published cost-effectiveness models in major depressive disorder (MDD) with a focus on the methods employed. Key components of the identified models are discussed and any challenges in developing models are highlighted. METHODS: A systematic literature search was performed to identify all primary model-based economic evaluations of MDD interventions indexed in MEDLINE, the Cochrane Library, EMBASE, EconLit, and PsycINFO between January 2000 and May 2010. RESULTS: A total of 37 studies were included in the review. These studies predominantly evaluated antidepressant medications. The analyses were performed across a broad set of countries. The majority of models were decision-trees; eight were Markov models. Most models had a time horizon of less than 1 year. The majority of analyses took a payer perspective. Clinical input data were obtained from pooled placebo-controlled comparative trials, single head-to-head trials, or meta-analyses. The majority of studies (24 of 37) used treatment success or symptom-free days as main outcomes, 14 studies incorporated health state utilities, and 2 used disability-adjusted life-years. A few models (14 of 37) incorporated probabilities and costs associated with suicide and/or suicide attempts. Two models examined the cost-effectiveness of second-line treatment in patients who had failed to respond to initial therapy. Resource use data used in the models were obtained mostly from expert opinion. All studies, with the exception of one, explored parameter uncertainty. CONCLUSIONS: The review identified several model input data gaps, including utility values in partial responders, efficacy of second-line treatments, and resource utilisation estimates obtained from relevant, high-quality studies. It highlighted the differences in outcome measures among the trials of MDD interventions, which can lead to difficulty in performing indirect comparisons, and the inconsistencies in definitions of health states used in the clinical trials and those used in utility studies. Clinical outcomes contributed to the uncertainty in cost-effectiveness estimates to a greater degree than costs or utility weights.

A review of cost-effectiveness of varenicline and comparison of cost-effectiveness of treatments for major smoking-related morbidities.

RATIONALE: This review aims to examine economic evaluations of varenicline, to compare the reported cost-effectiveness of varenicline with that of treatments for major smoking-related diseases and to evaluate the findings for decision making. METHODS: A literature search was performed to identify published articles in English indexed in MEDLINE and the Cochrane Library (Issue 1, 2009), which includes the Economic Evaluation Database. Additional sources also were searched to identify unpublished varenicline studies, including conference abstracts. The search for varenicline studies was limited from 2006 to October 2009; searches for all other types of studies were limited from 1990 to October 2009. RESULTS: The search yielded a total of 20 relevant economic evaluations of varenicline. In addition, 37 reviews of economic evaluations in chronic obstructive pulmonary disease, non-small cell lung cancer and cardiovascular disease, as well as studies evaluating the impact of economic rewarding were considered in this review. From these identified economic evaluations, the incremental cost-effectiveness ratios for varenicline ranged from dominance (more effective and cost saving) to €18,582 per quality-adjusted life-year (including indirect costs). These estimates appeared substantially lower when compared with incremental cost-effectiveness ratios reported for secondary prevention of smoking-related diseases, which in some cases were as high as €66,218 per quality-adjusted life-year. CONCLUSIONS: Varenicline appears to be cost-effective from the perspective of both health care payers and employers, because of reduced health care consumption and costs. The cost-effectiveness of varenicline also compares favourably to that of interventions recommended for the treatment and prevention of smoking-related diseases.

Efficacy and safety of treatments for refractory generalized anxiety disorder: a systematic review.

This study systematically collated clinical evidence on refractory generalized anxiety disorder (GAD). Refractory GAD patients are those who have failed to respond adequately to at least one earlier treatment for GAD. MEDLINE, EMBASE, The Cochrane Library and conference proceedings were searched to identify trials. Four placebo-controlled trials (pregabalin, olanzapine, quetiapine, risperidone) and four single-arm studies (aripiprazole, risperidone, quetiapine, ziprasidone) evaluated the add-ons to initial treatment(s) or switch of treatment(s) because of inadequate efficacy. The most robust trial was the pregabalin study, with a study duration of 8 weeks and a largest sample size that consists of 356 patients. A significant reduction in the Hamilton Anxiety Scale (HAM-A) score was found for pregabalin and risperidone augmentation compared with placebo. Olanzapine augmentation resulted in a significantly higher proportion of responders (using HAM-A scores) compared with placebo. Quetiapine augmentation did not result in significantly greater mean reductions in the HAM-Ascores compared with placebo. There is a need for effective and safe augmentation treatments for patient's refractory to initial treatments for GAD. This study has located one large robust trial assessing the add-on to pregabalin. All other trials were small and unpowered studies with less than 50 patients. Further high-quality trials of augmentation treatment on refractory GAD are required.