Allowing for stratification in sample size planning of two-arm trials with continuous or binary outcome: Overview and tutorial

2021 ◽  
pp. 096228022110510
Author(s):  
Stefan Wellek

More often than not, clinical trials and even nonclinical medical experiments have to be run with observational units sampled from populations to be assumed heterogeneous with respect to covariates associated with the outcome. Relevant covariates which are known prior to randomization are usually categorical in type, and the corresponding subpopulations are called strata. In contrast to randomization which in most cases is performed in a way ensuring approximately constant sample size ratios across the strata, sample size planning is rarely done taking stratification into account. This holds true although the statistical literature provides a reasonably rich repertoire of testing procedures for stratified comparisons between two treatments in a parallel group design. For all of them, at least approximate methods of power calculation are available from which algorithms or even closed-form formulae for required sample sizes can be derived. The objective of this tutorial is to give a systematic review of the most frequently applicable of these methods and to compare them in terms of their efficiency under standard settings. Based on the results, recommendations for the sample size planning of stratified two-arm trials are given.

2015 ◽  
Vol 26 (6) ◽  
pp. 2543-2551 ◽  
Author(s):  
Hong Zhu ◽  
Song Zhang ◽  
Chul Ahn

Split-mouth designs are frequently used in dental clinical research, where a mouth is divided into two or more experimental segments that are randomly assigned to different treatments. It has the distinct advantage of removing a lot of inter-subject variability from the estimated treatment effect. Methods of statistical analyses for split-mouth design have been well developed. However, little work is available on sample size consideration at the design phase of a split-mouth trial, although many researchers pointed out that the split-mouth design can only be more efficient than a parallel-group design when within-subject correlation coefficient is substantial. In this paper, we propose to use the generalized estimating equation (GEE) approach to assess treatment effect in split-mouth trials, accounting for correlations among observations. Closed-form sample size formulas are introduced for the split-mouth design with continuous and binary outcomes, assuming exchangeable and “nested exchangeable” correlation structures for outcomes from the same subject. The statistical inference is based on the large sample approximation under the GEE approach. Simulation studies are conducted to investigate the finite-sample performance of the GEE sample size formulas. A dental clinical trial example is presented for illustration.


Psychometrika ◽  
2021 ◽  
Author(s):  
Gwowen Shieh

A Correction to this paper has been published: https://doi.org/10.1007/s11336-019-09692-3


2005 ◽  
Vol 20 (2) ◽  
pp. 92-95 ◽  
Author(s):  
JR Calabrese ◽  
DJ Rapport ◽  
EA Youngstrom ◽  
K. Jackson ◽  
S. Bilali ◽  
...  

AbstractThe rapid cycling variant of bipolar disorder is defined as the occurrence of four periods of either manic or depressive illness within 12 months. Patients suffering from this variant of bipolar disorder have an unmet need for effective treatment. This review examines two major studies in an attempt to update understanding of the current therapies available to treat rapid cycling patients. The first trial compares lamotrigine versus placebo in 182 patients studied for 6 months. The second is a recently completed, 20-month trial comparing divalproate and lithium in 60 patients. Both trials had a double-blind, randomized parallel-group design. The data from the latter study indicate that there are no large differences in efficacy between lithium and divalproate in the long-term treatment of rapid cycling bipolar disorder. In addition, lamotrigine has the potential to complement the spectrum of lithium and divalproate through its greater efficacy for depressive symptoms.


1981 ◽  
Vol 9 (4) ◽  
pp. 288-291 ◽  
Author(s):  
Hans K Uhthoff ◽  
Jacques A Brunet ◽  
Anand Aggerwal ◽  
Raymond Varin

The efficacy of quazepam (Sch-16134) 15 mg capsules as a hypnotic has been compared with that of placebo in a 9-day study, using a parallel-group design. The physician's global evaluation numerically favoured quazepam 63% (nineteen of thirty) over placebo 50% (fifteen of thirty). Furthermore, it demonstrated greater improvement in Hypnotic Activity Index and Sleep Quality Index from baseline scores, and caused no adverse reactions.


Biometrics ◽  
2004 ◽  
Vol 60 (4) ◽  
pp. 1015-1024 ◽  
Author(s):  
Jianwen Cai ◽  
Donglin Zeng

2017 ◽  
Author(s):  
Stevan Nikolin ◽  
Donel Martin ◽  
Colleen K. Loo ◽  
Tjeerd W. Boonstra

AbstractBackgroundTranscranial direct current stimulation (tDCS) has been found to improve working memory (WM) performance in healthy participants following a single session. However, results are mixed and the overall effect size is small. Interpretation of these results is confounded by heterogeneous study designs, including differences in tDCS dose (current intensity) and sham conditions used.AimsWe systematically investigated the effect of tDCS dose on working memory using behavioural and neurophysiological outcomes.MethodsIn a single-blind parallel group design, 100 participants were randomised across five groups to receive 15 minutes of bifrontal tDCS at different current intensities (2mA, 1mA, and three sham tDCS conditions at 0.034mA, 0.016mA, or 0mA). EEG activity was acquired while participants performed a WM task prior to, during, and following tDCS. Response time, accuracy and an event-related EEG component (P3) were evaluated.ResultsWe found no significant differences in response time or performance accuracy between current intensities. The P3 amplitude was significantly lower in the 0mA condition compared to the 0.034mA, 1mA and 2mA tDCS conditions. Changes in WM accuracy were moderately correlated with changes in the P3 amplitude following tDCS compared to baseline levels (r = 0.34).ConclusionsWorking memory was not significantly altered by tDCS, regardless of dose. The P3 amplitude showed that stimulation at 1mA, 2mA and a sham condition (0.034mA) had biological effects, with the largest effect size for 1mA stimulation. These findings indicate higher sensitivity of neurophysiological outcomes to tDCS and suggests that sham stimulation previously considered inactive may alter neuronal function.


2018 ◽  
Vol 90 (21) ◽  
pp. 12485-12492 ◽  
Author(s):  
Nairveen Ali ◽  
Sophie Girnus ◽  
Petra Rösch ◽  
Jürgen Popp ◽  
Thomas Bocklitz

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