Posts Tagged Cost-effectiveness

[ARTICLE] Levetiracetam for epilepsy: an evidence map of efficacy, safety and economic profiles – Full Text

Objective: To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.
Materials and methods: PubMed, Scopus, the Cochrane Library, and were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.
Results: A total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50–1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79–1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34–5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51–2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90–1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41–0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.

LEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness


Epilepsy ranks fourth after tension-type headache, migraine and Alzheimer disease in the world’s neurological disorders burden.1 A systematic review (SR) and meta-analysis of international studies reported that the point prevalence of active epilepsy was 6.38 per 1,000 people, while the lifetime prevalence was 7.60 per 1,000 people. The annual cumulative incidence of epilepsy was 67.77 per 100,000 people, while the incidence rate was 61.44 per 100,000 person-years.2 As a fairly common clinical condition affecting all ages and requiring long-term, sometimes lifelong, treatment, epilepsy incurs high health care costs for the society.1 In 2010, the total annual cost for epilepsy was 13.8 billion and the total cost per patient was €5,221 in Europe.3 Meanwhile, in the USA, epilepsy-related costs ranged from $1,022 to $19,749 per person annually.4 What is more, drug-refractory epilepsy was a major cost driver,5 with main costs from anticonvulsants, hospitalization and early retirement.6

Currently, antiepileptic drugs (AEDs) are the main treatment method for epilepsy patients, and it was reported that approximately two-thirds of epileptic seizures were controlled by AEDs.7 Conventional AEDs such as carbamazepine (CBZ) and sodium valproate (VPA) have been proven to have good therapeutic effects and low treatment cost. However, some adverse events (AEs) related to these drugs, such as Stevens–Johnson syndrome, menstrual disorder and memory deterioration seriously affect the tolerance and compliance of patients. Compared with conventional AEDs, new AEDs have the potential to be safer, but also more expensive.8

Levetiracetam (LEV) is a novel AED that has been approved as an adjunctive therapy for adults with focal epilepsy since 1999 in the US. In 2006, it was licensed as monotherapy for adults and adolescents above 16 years of age with newly diagnosed focal-onset seizures with or without secondary generalization in Europe. Also, it has been indicated as an adjunctive therapy for partial-onset seizures in patients above 4 years of age in China since 2007. Although the precise mechanism of LEV is still unclear, current researches suggest that its pharmacological mechanism is different from those of other AEDs. It may bind to the synaptic vesicle protein 2A (SV2A), which presents on the synaptic vesicles and some neuroendocrine cells. SV2A may participate in the exocytosis of synaptic vesicles and regulate the release of neurotransmitters, especially the release of excitatory amino acids, and thus depress the epilepsy discharge.9,10 Other possible mechanisms of LEV include the following: selective inhibition of voltage-dependent N-type calcium channels in hippocampal pyramidal cells and reduction of the negative allosteric agents’ inhibition, such as zinc ions and B-carbolines, on glycine and γ-aminobutyric acid neurons, which results in indirectly increasing central nervous system inhibition.11

LEV is almost completely absorbed after oral administration and the absorption is unaffected by food. The bioavailability is nearly 100% and the steady-state concentrations are achieved in 2 days if LEV is taken twice daily. Sixty-six percent of LEV is renally excreted unchanged and its major metabolic pathway is enzymatic hydrolysis of the acetamide group, which is independent of liver CYP/CYP450; so, no clinically meaningful drug–drug interactions with other AEDs were found.12 One published SR of LEV suggested LEV has an equal efficacy compared with conventional AEDs and it is well tolerated for long-term therapy without significant effect on the immune system.13 But in recent years, apart from the most frequent AEs of LEV, such as nausea, gastrointestinal symptoms, dizziness, irritability and aggressive behavior, some rare AEs of LEV have been reported, including eosinophilic pneumonia, rhabdomyolysis, thrombocytopenia, elevated kinase and reduced sperm quality.1417

Thus, we conducted a mapping review to evaluate the efficacy, safety and economic profiles of LEV compared with all other AEDs for epilepsy, to provide evidence-based information for the rational use of LEV and research agendas.



Continue —>  [Full text] Levetiracetam for epilepsy: an evidence map of efficacy, safety and ec | NDT

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[ARTICLE] Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial – Full Text


Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY) gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER) of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.

1. Introduction

Stroke is a major cause of mortality and morbidity and imposes a significant burden on both health services and society [1,2,3]. In the United Kingdom (UK) it is estimated that the annual direct costs of stroke are approximately £4 billion, which constitutes around 5.5% of the total UK expenditure on health care [3]. If the costs of lost productivity and informal care are taken into account, the total annual societal costs of stroke are estimated to be around £9 billion [3]. In England, over 900,000 people are living with the consequences of stroke, 300,000 of whom are moderately or severely disabled [4]. As the proportion of older people in society increases, so the burden of stroke is likely to grow.

Upper limb spasticity after stroke is an important clinical problem and its identification and treatment are key components of stroke rehabilitation [5]. Upper limb spasticity may cause deformity, reduced function and pain [6]. Botulinum toxin type A, which when given by intramuscular injection causes temporary local muscle paresis by blocking neuromuscular transmission [7], has become an established treatment for spasticity due to stroke. Randomised controlled trials have shown that botulinum toxin reduces muscle tone [8] and improves the performance of basic upper limb functional tasks such as hand opening for cleaning and ease of dressing [9,10,11]. However, the impact on active upper limb function (e.g., reaching and grasping) and the efficacy of repeated treatment is less clear.

The BoTULS trial was a pragmatic multi-centre randomised controlled trial to evaluate the clinical and cost-effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. The clinical results indicated that botulinum toxin type A did not improve active upper limb function (as measured by the Action Research Arm Test (ARAT)), but that there may be benefits in terms of decreased muscle tone, improved upper limb strength, improved ease of performance of basic upper limb functional activities and reduction in pain [12]. This article describes the results of the cost-effectiveness analysis. […]

Continue —> Toxins | Free Full-Text | Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial | HTML

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[ARTICLE] Caregiver-mediated exercises with e-health support for early supported discharge after stroke (CARE4STROKE): study protocol for a randomized controlled trial – Full Text HTML


Background: Several systematic reviews have shown that additional exercise therapy has a positive effect on functional outcome after stroke. However, there is an urgent need for resource-efficient methods to augment rehabilitation services without increasing health care costs. Asking informal caregivers to do exercises with their loved ones, combined with e-health services may be a cost-effective method to promote early supported discharge with increased functional outcome.

The primary aim of the CARE4STROKE study is to evaluate the effects and cost-effectiveness of a caregiver-mediated exercises program combined with e-health services after stroke in terms of self-reported mobility and length of stay.

Methods: An observer-blinded randomized controlled trial, in which 66 stroke-patients admitted to a hospital stroke unit, rehabilitation center or nursing home are randomly assigned to either 8 weeks of the CARE4STROKE program in addition to usual care (i.e., experimental group) or 8 weeks of usual care alone (i.e., control group). The CARE4STROKE program is compiled in consultation with a trained physical therapist. A tablet computer is used to present video-based exercises for gait and gait-related activities in which a caregiver acts as an exercise coach.

Primary outcomes are the mobility domain of the Stroke Impact Scale and length of stay. Secondary outcomes are the other domains of the Stroke Impact Scale, motor impairment, strength, walking ability, balance, mobility, (Extended) Activities of Daily Living, psychosocial functioning, self-efficacy, fatigue, health-related quality of life of the patient as well as the experienced strain, psychosocial functioning and quality of life of the caregiver. An economic evaluation will be conducted from the societal and health care perspective.

Discussion: The main aspects of the CARE4STROKE program are

  1. increasing intensity of training by doing exercises with a caregiver in addition to usual care and
  2. e-health support.

We hypothesize this program leads to better functional outcome and early supported discharge, resulting in reduced costs.

Source: Caregiver-mediated exercises with e-health support for early supported discharge after stroke (CARE4STROKE): study protocol for a randomized controlled trial – Springer

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