Faculty of 1000 evaluation for A systematic review of power and sample size reporting in randomized controlled trials within plastic surgery.

2013 ◽  
Author(s):  
Jeremy Bordeaux
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Sample Size ◽  
Plastic Surgery ◽  
Controlled Trials ◽  
Randomized Controlled

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.

Estimation of sample size in randomized controlled trials in multiple sclerosis studying annualized relapse rates: A systematic review

2021 ◽  
pp. 135245852110524
Author(s):  
Louis Poncet-Megemont ◽  
Bruno Pereira ◽  
Fabien Rollot ◽  
Maria Pia Sormani ◽  
Pierre Clavelou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Sample Size ◽  
Negative Binomial ◽  
Final Analysis ◽  
Controlled Trials ◽  
Size Estimation ◽  
Randomized Controlled ◽  
Relapse Rates

Background: In multiple sclerosis (MS) studies, the most appropriate model for the distribution of the number of relapses was shown to be the negative binomial (NB) distribution. Objective: To determine whether the sample-size estimation (SSE) and the analysis of annualized relapse rates (ARRs) in randomized controlled trials (RCTs) were aligned and compare the SSE between normal and NB distributions. Methods: Systematic review of phase 3 and 4 RCTs for which the primary endpoint was ARR in relapsing remitting MS published since 2008 in pre-selected major medical journals. A PubMed search was performed on 30 November 2020. We checked whether the SSE and ARR analyses were congruent. We also performed standardized (fixed α/β, number of arms and overdispersion) SSEs using data collected from the studies. Results: Twenty articles (22 studies) were selected. NB distribution (or quasi-Poisson) was used for SSE in only 7/22 studies, whereas 21/22 used it for ARR analyses. SSE relying on NB regression necessitated a smaller sample size in 21/22 of our calculations. Conclusion: SSE was rarely performed using the most appropriate model. However, the use of an NB model is recommended to optimize the number of included patients and to be congruent with the final analysis.

Sign in / Sign up

Export Citation Format

Share Document