Additional file 1: of Social work after stroke: identifying demand for support by recording stroke patients’ and carers’ needs in different phases after stroke

Recruitment and verbal consent. Description of recruitment as well as obtaining and documentation of consent. Data management. Description of data management and generation of the questionnaire. (DOCX 18 kb

additional information to: Increasing Efficacy of Pre-clinical Research by Group Sequential Designs

supplemental information to the paper: Increasing Efficacy of Pre-clinical Research by Group Sequential Designs<br

Study design and sequential analysis approach allowing two interim analyses.

<p>Stage 1: 33% of samples acquired, stage 2: 66% of samples acquired, and stage 3: 100% of samples acquired. H₀: null hypothesis, P: <i>p</i>-value, Credible interval: specific Bayesian interval of certainty about an estimate, d: effect size Cohen’s d, α_i: significance levels for each stage derived from [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001307#pbio.2001307.ref011" target="_blank">11</a>] α₁ = 0.0006, α₂ = 0.0151, α ₃ = 0.0471. Additionally, we used a Bayes factor approach (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001307#pbio.2001307.t001" target="_blank">Table 1</a>) and Pocock boundaries for the frequentist approach (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001307#pbio.2001307.s002" target="_blank">S1 Table</a>). All sequential approaches used were calibrated by using simulations to get a type I error of about 5%.</p

Predictive capabilities of sequential designs compared to traditional nonsequential design for two different scenarios of potential effect size distributions.

<p>Upper left: “optimistic” scenario with more large effect sizes. Upper right: “pessimistic” scenario with mostly effect sizes of 0. Bottom: Probability of getting a significant test result reflecting a true effect of d ≠ 0 or d ≥ 0.5, respectively, for the two different scenarios of effect size distributions. First, the probabilities P(significant) for getting any significant study results are given, then the corresponding positive predictive values, and, finally, the product of both giving the corresponding overall probability of getting a significant study result that truly represents an effect of d ≠ 0 or d ≥ 0.5 (P_{detect true effect}). Stopping rules that allowed early stopping for futility or success as given in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001307#pbio.2001307.t001" target="_blank">Table 1</a>.</p

Early stopping for significance or futility using nonsequential group sequential designs (examples with <i>n</i> = 36 or <i>n</i> = 72).

<p>Early stopping for significance or futility using nonsequential group sequential designs (examples with <i>n</i> = 36 or <i>n</i> = 72).</p

Database screening results and final study inclusion rate.

<p>In both databases the exclusion criterion with the highest exclusion rate was a stroke-to-imaging-time higher than 12 hours. In the 1.5 T database, the number of patients, which had to be excluded due to insufficient image quality (mainly of FLAIR images), was much higher (17.1%) than in the 3 T database (2.0%).</p

Detailed results of the adjusted ROC analysis for ADC and all 3 raters at 1.5 and 3 T.

a<p>m0: adjusted model, adjusted for lesion volume, sex, thrombolysis, NIHSS).</p>b<p>m1: m0 additionally adjusted for age.</p>c<p>m2: m1 additionally adjusted for time (stroke-to-imaging).</p>d<p>m3: m1 and rater specific ADC-ROI values.</p><p>In contrast to DWI (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092295#pone-0092295-t003" target="_blank">table 3</a>), adding the ADC-ROI-values for each rater (model 3[m3]) as a variable led to only a bad to moderate accuracy for the prediction of FLAIR-hyperintensities for each rater in comparison with the basic models (m0 and m1). The AUC was even inferior to m2, which was based on “time-from-stroke-onset”. Thus, ADC maps cannot reliably predict FLAIR-hyperintensities in contrast to DWI-maps. Please see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092295#pone-0092295-g003" target="_blank">figure 3</a> for the respective ROC-curves for each model. AUC, Area under the curve.</p

Adjusted linear regression analysis to evaluate the association of relative DWI-intensity and time-from-stroke-onset.

<p>Adjusted linear regression analysis was performed to identify a possible association of relative (A) DWI-intensity and (B) ADC-intensity (y-axis,) and time-from-stroke-onset (x-axis) at 1.5 T (blue circles) and 3 T (green circle). At both field strengths, a significant association was found for DWI (A) with moderate adjusted Rsquare values (1.5 T: 0.28; 3 T: 0.44). Adjusted correlation (Spearman's rank correlation) was: 1.5 T = 0.45 (p<0.001), 3 T = 0.69 (p<0.001). In contrast, no association was found for ADC-maps (B) with adjusted Rsquare values near zero (1.5 T: 0.04; 3 T: 0.01) and weak to no adjusted correlation (1.5 T = −0.22, 3 T = 0.05). Plots are shown in logarithmic scale.</p

Clinical data, imaging data and comparison of patient groups.

<p>Data are given as median and IQR (interquartile range); Groups were compared using the Mann-Whitney U rank sum test, significant differences are marked by an asterisk; n, number; h, hours; y, years; ACA: anterior cerebral artery; MCA: middle cerebral artery; PCA: posterior cerebral artery; ICA/CCA: internal/common carotid artery; VA: vertebral artery; BA: basilar artery. ^a =  if patients had occlusion in two different vessels at the same time (e.g. ICA and MCA), occlusion was indicated for both vessels.</p

Adjusted ROC curves for the detection of presence of FLAIR-lesions by a relative DWI- and ADC-threshold.

<p>ROC-curves belonging to the detailed data presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092295#pone-0092295-t003" target="_blank">table 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092295#pone-0092295-t004" target="_blank">4</a> (please see legends of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092295#pone-0092295-t003" target="_blank">table 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092295#pone-0092295-t004" target="_blank">4</a> for further details). DWI-models for Group A (1.5 T) and B (3 T) (A,B) and ADC-models for Group A and B (C,D).</p