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.

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.

Efficacy of probiotics in multiple sclerosis: a systematic review of preclinical trials and meta-analysis of randomized controlled trials

2021 ◽  
Author(s):  
Jinchi Jiang ◽  
Chuanqi Chu ◽  
Caie Wu ◽  
Chen Wang ◽  
Chengcheng Zhang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Potential Role ◽  
Meta Analysis ◽  
Preliminary Evidence ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Preclinical Trials

Preliminary evidence shows the potential role of probiotics in ameliorating multiple sclerosis (MS); however, the effects of probiotics on MS remain unclear.

A systematic review of oral methotrexate for multiple sclerosis

2006 ◽  
Vol 12 (4) ◽  
pp. 507-510 ◽  
Author(s):  
O M Gray ◽  
G V McDonnell ◽  
R B Forbes
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Side Effects ◽  
Randomized Controlled Trials ◽  
Disease Progression ◽  
Allocation Concealment ◽  
Controlled Trials ◽  
Oral Methotrexate ◽  
Randomized Controlled ◽  
Definition Of

Oral methotrexate is a potent immunosuppressant, which could have a beneficial effect on relapse rates and delay disease progression in multiple sclerosis (MS). We performed a systematic review of all randomized controlled trials of oral methotrexate for MS. Of the two randomized controlled trials identified, one was excluded due to its allocation concealment and definition of a relapse and time to sustained disease progression. The other trial studied 60 participants with progressive MS only. This trial reported a non-significant reduction in sustained Expanded Disability Status Scale (EDSS) progression and number of relapses in favour of methotrexate therapy. There were no data on relapse rate and no difference in time to first relapse. Minor side-effects were reported in both methotrexate (87.1%) and placebo groups (89.7%), but there were no major side-effects. Further trials are required in both relapsing-remitting and progressive groups to establish the role of oral methotrexate in MS.

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