Ordinal meta-analysis, based on WMW GenOR, of 5 simulated studies using mock EDSS data.

<p>Ordinal meta-analysis, based on WMW GenOR, of 5 simulated studies using mock EDSS data.</p

Reporting of central tendency for the 6 clinical rating scales.

<p>Reporting of central tendency for the 6 clinical rating scales.</p

Approach to pooling data from the 6 clinical rating scales in systematic reviews.

<p>Approach to pooling data from the 6 clinical rating scales in systematic reviews.</p

Histograms of mock EDSS data in a control group (sample 0) and 5 treatment groups (samples 1–5).

<p>Histograms of mock EDSS data in a control group (sample 0) and 5 treatment groups (samples 1–5).</p

Ordinal meta-analysis, based on WMW GenOR calculated from summary statistics, of 5 simulated studies using mock EDSS data.

<p>Ordinal meta-analysis, based on WMW GenOR calculated from summary statistics, of 5 simulated studies using mock EDSS data.</p

Approach to statistical analysis for the 6 clinical rating scales.

<p>Approach to statistical analysis for the 6 clinical rating scales.</p

Coverage probability plotted against the number of participating laboratories for <i>N</i> = 12 (blue), <i>N</i> = 24 (orange), and <i>N</i> = 48 (grey) for simulated studies for 12 additional intervention studies of mouse models of stroke, myocardial infarction, and breast cancer.

<p>First row: tPA, trastuzumab, FK506, rosiglitazone 2, IL-1RA, cardiosphere DC; second row: estradiol, human MSC, MK-80, TMZ, c-kit CSC, rat BMSC (see Table A in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003693#pbio.2003693.s001" target="_blank">S1 Text</a> for details). BMSC, bone marrow stem cell; CSC, cardiac stem cell; DC, derived cell; IL1-RA, interleukin 1 receptor antagonist; MSC, mesenchymal stem cell; TMZ, temozolomide; tPA, tissue plasminogen activator.</p

Proportion of studies reporting significant and accurate effects.

<p>(A) Schematic of study outcomes. A study reporting both ES estimates and inferential significant statements can lead to 1 of 4 outcomes. (α) The reported CI for the ES estimate (horizontal blue line) includes the true ES, and the CI is not including 0, suggesting the existence of an effect; (β) the CI covers neither 0 nor the true ES, suggesting the existence of an effect, though its magnitude is either over- or underestimated; (γ) the CI covers the true effect but also 0—in this case “no significant” effect would be reported, and the ES estimate would be ignored or treated as nonrelevant (which is often the case in underpowered studies); (δ) the CI includes 0 but not the true ES, leading again to a “nonsignificant” result. Based on this, we can calculate the ratio of studies accurately estimating the true ES as p_sa = α / (α + β + γ + δ). (B) p_sa based on 10⁵ simulated samples for the hypothermia treatment of stroke (blue) and 12 further interventions (grey) for total sample sizes of <i>N</i> = 12, 24, and 48 subjects and <i>k</i> = 1–4 laboratories. ES, effect size.</p

Definitions of key terms used in this manuscript.

<p>Definitions of key terms used in this manuscript.</p

Stratification by animal and tumour model characteristics.

<p>(A) The specific xenograft model used were associated with a significant proportion of the between-study heterogeneity (χ² = 4416, df = 23, P<0.00385). (B) Overexpression of HER2 in breast cancer tumours was associated with greater efficacy (χ² = 160, df = 1, P<0.00385). (C) A greater reduction in tumour volume was observed with subcutaneous inoculation compared to intramammary route (χ² = 810, df = 2, P<0.00385). (D) There is comorbidity related between-study heterogeneity (χ² = 5130, df = 9, P<0.00385). The more commonly used athymic and SCID mice were associated with lower efficacies. (E) A significant proportion of between-study heterogeneity is accounted for by the tumour volume at treatment initiation, with a smaller treatment effect seen at either extreme (χ² = 1042, df = 6, P<0.00385). The grey bands represent global 95% confidence intervals; diamonds (A) and columns (B-E) represent mean±95% CI and diamond size (A) column width (B-E) a measure of number of comparisons within each stratum; the number of comparisons is included inside the y-axis (A) and at the base of each column (B-E). The solid lines in A, C and E represent the level of neutral treatment effect.</p