Early Termination of Acute Stroke Randomized Controlled Trials Published Between 2013 and 2020: A Systematic Review

2021 ◽  
Vol 14 (12) ◽  
Author(s):  
Brent Strong ◽  
J. Adam Oostema ◽  
Nadia Nikroo ◽  
Murtaza Hussain ◽  
Mathew J. Reeves
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Acute Stroke ◽  
Sample Size ◽  
Early Termination ◽  
Reporting Guidelines ◽  
Effect Sizes ◽  
Controlled Trials ◽  
Acute Stroke Care ◽  
Randomized Controlled

Background: Termination of a clinical trial before the maximum planned sample size is accrued can occur for multiple valid reasons but has implications for the interpretation of results. We undertook a systematic review of contemporary acute stroke trials to document the prevalence of and reasons for early termination. Methods: We searched MEDLINE for randomized controlled trials of acute stroke therapies published between 2013 and 2020 in 9 major clinical journals. Manuscripts describing the primary results of phase 2 and phase 3 trials of acute stroke care were included. Data on study characteristics and adherence to CONSORT reporting guidelines were abstracted and summarized using descriptive statistics. Where feasible, we compared treatment effect sizes between trials terminated early and those not terminated early. Results: Of 96 randomized controlled trials, 39 (41%) were terminated early, 84 (88%) had a data and safety monitoring board, and 57 (59%) reported a prespecified statistical stopping rule. Among the 39 trials terminated early, 10 were discontinued for benefit, 10 due to logistical issues, 8 for futility, 6 because of newly available evidence, 1 for harm, and 4 for other or a combination of reasons. The median percentage of the maximum planned sample size accrued among trials terminated early was 63% (range, 8%–89%). Only 55% of trials (53 of 96) reported whether interim efficacy analyses were conducted, as recommended by the CONSORT guidelines. When 10 endovascular therapy trials were compared according to early termination status, the effect sizes of trials terminated early for benefit were only modestly larger than those not terminated early. Conclusions: The high prevalence of early termination in combination with the wide variety of reasons underscores the necessity of meticulous trial planning and adherence to methodological and reporting guidelines for early termination. Registration: URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42019128727.

Abstract TP324: Early Termination of Acute Stroke Randomized Controlled Trials Published Between 2013 and 2018: A Systematic Review

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Brent Strong ◽  
John A Oostema ◽  
Nadia Nikroo ◽  
Murtaza Hussain ◽  
Mathew J Reeves
Keyword(s):  
Systematic Review ◽  
North America ◽  
Randomized Controlled Trials ◽  
Acute Stroke ◽  
Sample Size ◽  
Early Termination ◽  
Stopping Rules ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Study Results

Introduction: A priori sample size determination is an essential step in designing randomized controlled trials (RCTs). Failure to reach pre-planned sample size introduces risk of both falsely negative and spuriously positive findings. We undertook a systematic review of contemporary acute stroke trials to document the prevalence and reasons for termination of trials prior to completion of enrollment. Methods: We searched MEDLINE for RCTs of acute stroke therapy published between 2013 and 2018 in 9 major journals. Manuscripts describing the final primary results of phase 3 and large phase 2 trials of any therapeutic intervention were eligible for inclusion. Study characteristics, including the presence of a data monitoring committee (DMC) and stopping rules, risk-of-bias assessment, funding sources and conflicts of interest, were abstracted from published manuscripts and trial protocols by two independent reviewers. The prevalence of and reasons for early termination were quantified. Multivariable logistic regression was used to identify study-level predictors of early termination. Results: Of 756 hits, 60 were eligible for inclusion, 21 (35%) of which were terminated early. Among the trials stopped early, 10 (48%) reported stopping for benefit or newly available evidence while 11 (52%) were terminated for futility; 20 (95%) reported a DMC and 17 (81%) reported the use of a pre-specified statistical stopping rule. Factors associated with early termination included study location in North America, larger planned sample size, and industry funding (Table). Study location in North America and larger planned sample size retained statistical significance in a multivariable model. Conclusions: One in three contemporary stroke trials were terminated prior to completion of enrollment. Reasons for termination were evenly split between benefit and futility. Further study is needed to understand the reasons for and impact of early termination on study results.

scholarly journals Effects of stretching exercises on human gait: a systematic review and meta-analysis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 984
Author(s):  
Thomas Vialleron ◽  
Arnaud Delafontaine ◽  
Sebastien Ditcharles ◽  
Paul Fourcade ◽  
Eric Yiou
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Elderly Population ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Human Gait ◽  
Controlled Trials ◽  
Phase Duration ◽  
Randomized Controlled ◽  
Patient Category

Background: Stretching is commonly used in physical therapy as a rehabilitation tool to improve range of motion and motor function. However, is stretching an efficient method to improve gait, and if so, for which patient category? Methods: A systematic review of randomized and non-randomized controlled trials with meta-analysis was conducted using relevant databases. Every patient category and every type of stretching programs were included without multicomponent programs. Data were meta-analysed where possible. Estimates of effect sizes (reported as standard mean difference (SMD)) with their respective 95% confidence interval (95% CI) were reported for each outcome. The PEDro scale was used for the quality assessment. Results: Twelve studies were included in the analysis. Stretching improved gait performance as assessed by walking speed and stride length only in a study with a frail elderly population, with small effect sizes (both SMD= 0.49; 95% CI: 0.03, 0.96; PEDro score: 3/10). The total distance and the continuous walking distance of the six-minute walking test were also improved only in a study in an elderly population who had symptomatic peripheral artery disease, with large effect sizes (SMD= 1.56; 95% CI: 0.66, 2.45 and SMD= 3.05; 95% CI: 1.86, 4.23, respectively; PEDro score: 5/10). The results were conflicting in healthy older adults or no benefit was found for most of the performance, spatiotemporal, kinetic and angular related variables. Only one study (PEDro score: 6/10) showed improvements in stance phase duration (SMD=-1.92; 95% CI: -3.04, -0.81), swing phase duration (SMD=1.92; 95 CI: 0.81, 3.04), double support phase duration (SMD= -1.69; 95% CI: -2.76, -0.62) and step length (SMD=1.37; 95% CI: 0.36, 2.38) with large effect sizes. Conclusions: There is no strong evidence supporting the beneficial effect of using stretching to improve gait. Further randomized controlled trials are needed to understand the impact of stretching on human gait.

scholarly journals Effects of stretching exercises on human gait: a systematic review and meta-analysis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 984
Author(s):  
Thomas Vialleron ◽  
Arnaud Delafontaine ◽  
Sebastien Ditcharles ◽  
Paul Fourcade ◽  
Eric Yiou
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Elderly Population ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Human Gait ◽  
Controlled Trials ◽  
Phase Duration ◽  
Randomized Controlled ◽  
Patient Category

Background: Stretching is commonly used in physical therapy as a rehabilitation tool to improve range of motion and motor function. However, is stretching an efficient method to improve gait, and if so, for which patient category? Methods: A systematic review of randomized and non-randomized controlled trials with meta-analysis was conducted using relevant databases. Every patient category and every type of stretching programs were included without multicomponent programs. Data were meta-analysed where possible. Estimates of effect sizes (reported as standard mean difference (SMD)) with their respective 95% confidence interval (95% CI) were reported for each outcome. The PEDro scale was used for the quality assessment. Results: Twelve studies were included in the analysis. Stretching improved gait performance as assessed by walking speed and stride length only in a study with a frail elderly population, with small effect sizes (both SMD= 0.49; 95% CI: 0.03, 0.96; PEDro score: 3/10). The total distance and the continuous walking distance of the six-minute walking test were also improved only in a study in an elderly population who had symptomatic peripheral artery disease, with large effect sizes (SMD= 1.56; 95% CI: 0.66, 2.45 and SMD= 3.05; 95% CI: 1.86, 4.23, respectively; PEDro score: 5/10). The results were conflicting in healthy older adults or no benefit was found for most of the performance, spatiotemporal, kinetic and angular related variables. Only one study (PEDro score: 6/10) showed improvements in stance phase duration (SMD=-1.92; 95% CI: -3.04, -0.81), swing phase duration (SMD=1.92; 95 CI: 0.81, 3.04), double support phase duration (SMD= -1.69; 95% CI: -2.76, -0.62) and step length (SMD=1.37; 95% CI: 0.36, 2.38) with large effect sizes. Conclusions: There is no strong evidence supporting the beneficial effect of using stretching to improve gait. Further randomized controlled trials are needed to understand the impact of stretching on human gait.

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