An Improved Method for Simple, Assumption-Free Ordinal Analysis of the Modified Rankin Scale Using Generalized Odds Ratios

Чурилов, Леонид; Arnup, Sarah; Johns, Hannah; Leung, Tiffany; Roberts, S. A.; Campbell, Bruce C.V.; Davis, Stephen M.; Donnan, Geoffrey A.

doi:10.1111/ijs.12364

Cited by 55 publications

(64 citation statements)

References 17 publications

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“…However, logistic regression permits use of both continuous and categorical covariates. Even so, there are several approaches to describing the effect size that do not invoke the proportionality assumption 10–12 and also several circumstances where any violation of the assumption has limited impact.…”

Section: Outcome Measure Selectionmentioning

confidence: 99%

Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke

Lees

Khatri

2016

Stroke

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Pooled analysis of individual patient data from stroke trials can deliver more precise estimates of treatment effect, enhance power to examine pre-specified subgroups, and facilitate exploration of treatment-modifying influences. Analysis plans should be declared, and preferably published, before trial results are known. For pooling trials that used diverse analytic approaches, an ordinal analysis is favoured, with justification for considering deaths and severe disability jointly. Since trial pooling is an incremental process, analyses should follow a sequential approach, with statistical adjustment for iterations. Updated analyses should be published when revised conclusions have a clinical implication. However, caution is recommended in declaring pooled findings that may prejudice ongoing trials, unless clinical implications are compelling. All contributing trial teams should contribute to leadership, data verification, and authorship of pooled analyses. Development work is needed to enable reliable inferences to be drawn about individual drug or device effects that contribute to a pooled analysis, versus a class effect, if the treatment strategy combines two or more such drugs or devices. Despite the practical challenges, pooled analyses are powerful and essential tools in interpreting clinical trial findings and advancing clinical care.

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Section: Outcome Measure Selectionmentioning

confidence: 99%

Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke

Lees

Khatri

2016

Stroke

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“…51,52 This provided a measure of effect size with confidence interval (CIs), which was stratified by age and stroke severity. Time (days) taken to achieve unassisted walking of 50 m was analysed using the Cox regression model with treatment group as the independent variable, the time to unassisted walking (censored at 3 months) as the dependent variable, and age and baseline NIHSS as covariates.…”

Section: Methodsmentioning

confidence: 99%

A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial

Langhorne

Rodgers

et al. 2017

Health Technol Assess

121

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BackgroundMobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit.ObjectivesWe assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke.DesignWe conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation.SettingThe trial took place in 56 acute stroke units in five countries.ParticipantsWe included adult patients with a first or recurrent stroke who met physiological inclusion criteria.InterventionsPatients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke.Main outcome measuresThe primary outcome was good recovery [modified Rankin scale (mRS) score of 0–2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose–response analysis.Data sourcesPatients, outcome assessors and investigators involved in the trial were blinded to treatment allocation.ResultsWe recruited 2104 (UK,n = 610; Australasia,n = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours;p < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5;p < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group (n = 480, 46%) had a favourable outcome than in the UC group (n = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90;p = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose–response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day).LimitationsUC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction.ConclusionsPatients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable outcome at 3 months cautioning against very early high-dose mobilisation. At 12 months, health-related QoL was similar regardless of group. Shorter, more frequent mobilisation early after stroke may be associated with a more favourable outcome.Future workThese results informed a new trial proposal [A Very Early Rehabilitation Trial – DOSE (AVERT–DOSE)] aiming to determine the optimal frequency and dose of EM.Trial registrationThe trial is registered with the Australian New Zealand Clinical Trials Registry number ACTRN12606000185561, Current Controlled Trials ISRCTN98129255 and ISRCTN98129255.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 54. See the NIHR Journals Library website for further project information. Funding was also received from the National Health and Medical Research Council Australia, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, and the Stroke Association. In addition, National Health and Medical Research Council fellowship funding was provided to Julie Bernhardt (1058635), who also received fellowship funding from the Australia Research Council (0991086) and the National Heart Foundation (G04M1571). The Florey Institute of Neuroscience and Mental Health, which hosted the trial, acknowledges the support received from the Victorian Government via the Operational Infrastructure Support Scheme.

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“…18,19 The proportions of patients with a modified Rankin scale score of 0 or 1 (or no change from baseline in patients with a preexisting modified Rankin scale score of 2 or 3) and with a score of 0 to 2 (or no change from baseline in patients with a preexisting modified Rankin scale score of 3) were to be compared between the tenecteplase group and the alteplase group of the trial, with adjustment for age and baseline NIHSS score with the use of a logisticregression model. The proportions of patients with early neurologic improvement were compared between the two groups, with adjustment for age and baseline NIHSS score, with the use of logistic regression.…”

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confidence: 99%

“…The differences in the distributions of the NIHSS scores between the tenecteplase group and the alteplase group at 24 hours and at 72 hours were analyzed with the use of Wilcoxon-Mann-Whitney generalized odds ratios, with stratification according to baseline NIHSS score. 18 …”

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Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

Campbell¹,

et al. 2018

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BACKGROUNDIntravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODSWe randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTSOf 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P = 0.002 for noninferiority; P = 0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONSTenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061.) a bs tr ac t

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An Improved Method for Simple, Assumption-Free Ordinal Analysis of the Modified Rankin Scale Using Generalized Odds Ratios

Cited by 55 publications

References 17 publications

Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke

Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke

A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

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