On the Analysis and Interpretation of Outcome Measures in Stroke Clinical Trials

Koziol, James A.; Feng, Anne C.

doi:10.1161/01.str.0000241106.81293.2b

Cited by 51 publications

(17 citation statements)

References 21 publications

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“…It has been suggested that a moderate effect size of 0.5, or equivalently, a "onehalf standard deviation" rule, is clinically significant. 25 The mean differences and observed effect sizes based on parametric tests of both raw and rank-transformed data found in this study were well below these general guidelines (Table 3), and suggest that any differences between the two groups were clinically insignificant. …”

Section: Discussionmentioning

confidence: 44%

Randomized, Double-Blind Clinical Trial of Two Different Modes of Positive Airway Pressure Therapy on Adherence and Efficacy in Children

Marcus

Beck

Traylor

et al. 2012

Journal of Clinical Sleep Medicine

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Study Objectives:To determine the effects of bilevel positive airway pressure with pressure release technology (Bi-Flex) on adherence and effi cacy in children and adolescents compared to standard continuous positive airway pressure (CPAP) therapy. We hypothesized that Bi-Flex would result in improved adherence but similar effi cacy to CPAP. Methods: This was a randomized, double-blinded clinical trial. Patients with obstructive sleep apnea were randomized to CPAP or Bi-Flex. Repeat polysomnography was performed on pressure at 3 months. Objective adherence data were obtained at 1 and 3 months. Results: 56 children and adolescents were evaluated. There were no signifi cant differences in the number of nights the device was turned on, or the mean number of minutes used at pressure per night for CPAP vs Bi-Flex (24 ± 6 vs 22 ± 9 nights, and 201 ± 135 vs 185 ± 165 min, respectively, for Month 1). The apnea hypopnea index decreased signifi cantly from 22 ± 21/h to 2 ± 3/h on CPAP (p = 0.005), and 18 ± 15/h to 2 ± 2/h on Bi-Flex (p < 0.0005), but there was no signifi cant difference between groups (p = 0.82 for CPAP vs Bi-Flex). The Epworth Sleepiness Scale decreased from 8 ± 5 to 6 ± 3 on CPAP (p = 0.14), and 10 ± 6 to 5 ± 5 on Bi-Flex (p < 0.0005; p = 0.12 for CPAP vs Bi-Flex). Conclusions: Both CPAP and Bi-Flex are effi cacious in treating children and adolescents with OSAS. However, adherence is suboptimal with both methods. Further research is required to determine ways to improve adherence in the pediatric population. keywords: CPAP, obstructive sleep apnea, Bi-Flex Citation: Marcus CL; Beck SE; Traylor J; Cornaglia MA; Meltzer LJ; DiFeo N; Karamessinis LR; Samuel J; Falvo J; DiMaria M; Gallagher PR; Beris H; Menello MK. Randomized, double-blind clinical trial of two different modes of positive airway pressure therapy on adherence and effi cacy in children.

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Section: Discussionmentioning

confidence: 44%

Randomized, Double-Blind Clinical Trial of Two Different Modes of Positive Airway Pressure Therapy on Adherence and Efficacy in Children

Marcus

Beck

Traylor

et al. 2012

Journal of Clinical Sleep Medicine

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“…This finding has implications for outcome measurement in stroke intervention trials. In the past, the mRS has been treated as an ordinal scale and the interpretation of mRS scores and ranges has been the subject of a number publications [28][29][30] . We recommend that future costeffectiveness evaluations of new ischemic stroke therapies focus on mRS distributions.…”

Section: Discussionmentioning

confidence: 99%

Impact of Disability Status on Ischemic Stroke Costs in Canada in the First Year

Mittmann

Seung

Hill

et al. 2012

Can. J. Neurol. Sci.

105

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Background: Longitudinal, patient-level data on resource use and costs after an ischemic stroke are lacking in Canada. The objectives of this analysis were to calculate costs for the first year post-stroke and determine the impact of disability on costs. Methodology: The Economic Burden of Ischemic Stroke (BURST) Study was a one-year prospective study with a cohort of ischemic stroke patients recruited at 12 Canadian stroke centres. Clinical history, disability, health preference and resource utilization information was collected at discharge, three months, six months and one year. Resources included direct medical costs (2009 CAN$) such as emergency services, hospitalizations, rehabilitation, physician services, diagnostics, medications, allied health professional services, homecare, medical/assistive devices, changes to residence and paid caregivers, as well as indirect costs. Results were stratified by disability measured at discharge using the modified Rankin Score (mRS): nondisabling stroke (mRS 0-2) and disabling stroke (mRS 3-5). Results: We enrolled 232 ischemic stroke patients (age 69.4 ± 15.4 years; 51.3% male) and 113 (48.7%) were disabled at hospital discharge. The average annual cost was $74,353; $107,883 for disabling strokes and $48,339 for non-disabling strokes. Conclusions: An average annual cost for ischemic stroke was calculated in which a disabling stroke was associated with a two-fold increase in costs compared to NDS. Costs during the hospitalization to three months phase were the highest contributor to the annual cost. A "back of the envelope" calculation using 38,000 stroke admissions and the average annual cost yields $2.8 billion as the burden of ischemic stroke.RÉSUMÉ: Impact du degré d'invalidité sur les coûts reliés à l'accident vasculaire cérébral ischémique au cours de la première année au Canada. Contexte : Nous n'avons pas de données longitudinales sur l'utilisation des ressources par les patients et les coûts ainsi engendrés suite à un accident vasculaire cérébral (AVC) ischémique au Canada. Les buts de cette analyse étaient de calculer les coûts engendrés au cours de la première année après un AVC et de déterminer l'impact de l'invalidité sur ces coûts. Méthode : Le Economic Burden of Ischemic Stroke (BURST) Study est une étude prospective d'une durée de un an chez une cohorte de patients ayant subi un AVC ischémique qui ont été recrutés dans 12 centres canadiens de traitement de l'AVC. Des informations ont été recueillies sur l'histoire clinique, l'invalidité, les choix de santé et l'utilisation des ressources au moment du congé hospitalier, trois mois, six mois et un an plus tard. Les ressources incluaient les coûts médicaux directs (en $ canadiens 2009) comme les services d'urgence, les hospitalisations, la réadaptation, les frais médicaux, diagnostiques et thérapeutiques, les autres services professionnels, les soins à domicile, les équipements médicaux/accessoires fonctionnels, les changements effectués au lieu de résidence et les aidants rémunérés ainsi que les ...

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“…In this author's view, the "positive" results of SAINT I are likely to have occurred by chance. Other authors have critically analyzed the design-and statistical weaknesses of SAINT I (Koziol et al, 2006;Saver, 2007). One curious design feature was the inclusion of both tPA-treated and non-tPA-treated subjects (tPA fraction, 29% in SAINT I, 44% in SAINT II) without adequately powering these subgroups for analysis of the primary outcome Shuaib et al, 2007).…”

Section: Magnesiummentioning

confidence: 99%

Neuroprotection for ischemic stroke: Past, present and future

2008

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Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. Rigorously conducted experimental studies in animal models of brain ischemia provide incontrovertible proof-of-principle that high-grade protection of the ischemic brain is an achievable goal. Nonetheless, many agents have been brought to clinical trial without a sufficiently compelling evidence-based pre-clinical foundation. At this writing, around 160 clinical trials of neuroprotection for ischemic stroke have been initiated. Of the approximately 120 completed trials, two-thirds were smaller early-phase safetyfeasibility studies. The remaining one-third were typically larger (>200 subjects) phase II or III trials, but, disappointingly, only fewer than one-half of these administered neuroprotective therapy within the 4-6 hour therapeutic window within which efficacious neuroprotection is considered to be achievable. This fact alone helps to account for the abundance of "failed" trials.This review presents a close survey of the most extensively evaluated neuroprotective agents and classes and considers both the strengths and weakness of the pre-clinical evidence as well as the results and shortcomings of the clinical trials themselves. Among the agent-classes considered are calcium channel blockers; glutamate antagonists; GABA agonists; antioxidants/radical scavengers; phospholipid precursor; nitric oxide signal-transduction down-regulator; leukocyte inhibitors; hemodilution; and a miscellany of other agents. Among promising ongoing efforts, therapeutic hypothermia, high-dose human albumin therapy, and hyperacute magnesium therapy are considered in detail. The potential of combination therapies is highlighted. Issues of clinical-trial funding, the need for improved translational strategies and clinical-trial design, and "thinking outside the box" are emphasized. Part I: Neuroprotection -from Past to the PresentNeuroprotection for ischemic brain injury has emerged only recently as a topic of serious biomedical inquiry. A MEDLINE survey (PubMed, 2007) reveals virtually no publications on this topic until the early 1990's but a remarkable surge in publications over the past 10 years Correspondence and reprint requests to:

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On the Analysis and Interpretation of Outcome Measures in Stroke Clinical Trials

Cited by 51 publications

References 21 publications

Randomized, Double-Blind Clinical Trial of Two Different Modes of Positive Airway Pressure Therapy on Adherence and Efficacy in Children

Randomized, Double-Blind Clinical Trial of Two Different Modes of Positive Airway Pressure Therapy on Adherence and Efficacy in Children

Impact of Disability Status on Ischemic Stroke Costs in Canada in the First Year

Neuroprotection for ischemic stroke: Past, present and future

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