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.

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.

scholarly journals Attention to principles of exercise training: an updated systematic review of randomized controlled trials in cancers other than breast and prostate

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kelcey A. Bland ◽  
Sarah E. Neil-Sztramko ◽  
Kendra Zadravec ◽  
Mary E. Medysky ◽  
Jeffrey Kong ◽  
...  
Keyword(s):  
Systematic Review ◽  
Exercise Training ◽  
Randomized Controlled Trials ◽  
Exercise Intervention ◽  
Exercise Prescription ◽  
Primary Objective ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Initial Values ◽  
Study Results

Abstract Background The primary objective of this systematic review was to update our previous review on randomized controlled trials (RCTs) of exercise in cancers other than breast or prostate, evaluating: 1) the application of principles of exercise training within the exercise prescription; 2) reporting of the exercise prescription components (i.e., frequency, intensity, time, and type (FITT)); and 3) reporting of participant adherence to FITT. A secondary objective was to examine whether reporting of these interventions had improved over time. Methods MEDLINE, EMBASE, CINAHL and SPORTDiscus databases were searched from 2012 to 2020. Eligible studies were RCTs of at least 4 weeks of aerobic and/or resistance exercise that reported on physiological outcomes relating to exercise (e.g., aerobic capacity, muscular strength) in people with cancer other than breast or prostate. Results Eighty-six new studies were identified in the updated search, for a total of 107 studies included in this review. The principle of specificity was applied by 91%, progression by 32%, overload by 46%, initial values by 72%, reversibility by 7% and diminishing returns by 5%. A significant increase in the percentage of studies that appropriately reported initial values (46 to 80%, p < 0.001) and progression (15 to 37%, p = 0.039) was found for studies published after 2011 compared to older studies. All four FITT prescription components were fully reported in the methods in 58% of all studies, which was higher than the proportion that fully reported adherence to the FITT prescription components in the results (7% of studies). Reporting of the FITT exercise prescription components and FITT adherence did not improve in studies published after 2011 compared to older studies. Conclusion Full reporting of exercise prescription and adherence still needs improvement within exercise oncology RCTs. Some aspects of exercise intervention reporting have improved since 2011, including the reporting of the principles of progression and initial values. Enhancing the reporting of exercise prescriptions, particularly FITT adherence, may provide better context for interpreting study results and improve research to practice translation.

scholarly journals Should preventive antibiotics be used in patients with acute stroke? A systematic review and meta-analysis of randomized controlled trials

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186607 ◽  
Author(s):  
Feng Zheng ◽  
Niklas von Spreckelsen ◽  
Xintong Zhang ◽  
Pantelis Stavrinou ◽  
Marco Timmer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Acute Stroke ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled
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