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9 For each question, relevant data were extracted and appropriate statistics were calculated, including effect sizes, hazard ratios (HR), and standardised mortality ratios with 95% CI.
The most useful circulating biomarkers are likely to be relatively stable across testing conditions, easy to measure precisely and reproducibly (low intra-assay and inter-assay coefficients <5 to 10%) and to have fairly significant effect sizes (hazard ratios >1.5).
The exceptions to this are three genome-wide association studies (GWAS) [ 4- 6] and a study from the Breast Cancer Association Consortium, which had substantial power to detect associated variants with large effect sizes (hazard ratio (HR) >2) [ 7].
As both of the last-mentioned factors showed relatively large effect sizes (hazard ratios) and have been validated in several previous studied, also these factors were included in the final prognostic model.
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While the time to infection differed between children and adults, the effect size (hazard ratios) were very similar (e.g., 3D7 GIA HR = 1.43, 95% CI = 0.85 2.38 for children and HR = 1.60, 95% CI = 0.78 3.28 for adults).. Therefore, age was treated as a confounder in these analyses as it was significantly associated with time-to-infection and growth inhibition (p<0.001).
9p loss had an independent effect on DFS on multivariate analysis model including T-stage, grade, and size (Hazard ratio 6.65; P = 0.021) [ 29].
Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib, 16.5 months; placebo, 3.7 months), although significance was not reached, presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10 1.57; P = 0.067).
In univariate survival analyses, tumour size (hazard ratio (HR) for recurrence 1.75; 95% CI 1.21 2.54; P=0.003), and lymph node status (HR for recurrence 1.46; 95% CI 1.13 1.88; P=0.004) were significantly associated with RFS (Table 2).
A population with GI bleeding 3 times larger than evaluated in this study would be necessary to identify the effect size (hazard ratio of 0.7), as seen in the prospective trial.
Univariate Cox-regression analysis for all clinicopathological characteristics and disease-free survival is shown in Table 2. Multivariate regression analysis for all clinicopathological characteristics showed that only tumour size (hazard ratio (HR)=4.8, 95% CI 1.8 12.3, P=0.001) and lymph node metastasis (HR=5.4, 95% CI 2.3 12.7, P<0.001) were independently associated with disease-free survival.
In this setting, one observes that the use of IPTW in an observational study gives slightly lower statistical power than an RCT in the scenario with both a low prevalence of treatment (10%%) and a low effect size (hazard ratio = 1.1).
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com