a) Patients, treatment and variables | ||||
---|---|---|---|---|
Study and marker | Remarks | |||
Marker | OS = 8-probe-set gene-expression signature | |||
Further variables | v1 = age, v2 = sex, v3 = FISH, v4 = IGVH | |||
Reference | Herold et al. (2011) | |||
Source of the data | GEO (reference: GSE22762) | |||
Patients | n | Remarks | Â | |
 | Assessed for eligibility | 151 | Disease: chronic lymphocytic leukemia | |
 |  |  | Patient source: Department of Internal Medicine III, University of Munich (2001 - 2005) | |
Training set | Excluded | 0 | Â | Â |
 | Included | 151 | Criteria: sample availability | |
 |  |  | Gene expression profiling: 44 Affymetrix HG-U133 A&B microarrays, 107 Affymetrix HG-U133 plus 2.0 microarrays | |
 | With outcome events | 41 | Overall survival | |
 | Assessed for eligibility | 149 | Disease: chronic lymphocytic leukemia | |
 |  |  | Patient source: Department of Internal Medicine III, University of Munich (2005 - 2007) | |
Validation set | Excluded | 18 | Due to missing clinical information | |
 | Included | 131 | Criteria: sample availability | |
 |  |  | Gene expression profiling: 149 qRT-PCR (only selected genes) | |
 | With outcome events | 40 | Overall survival | |
Relevant differences between training and validation sets | ||||
Data source | Same institution, different time (see above) | Â | ||
Measurement of gene expressions | Affymetrix HG-U133 vs. TaqMan LDA (see text) | Â | ||
Survival rate | Lower in the validation set (see Figure 4) | Â | ||
b) Statistical analyses of survival outcomes | ||||
Analysis | n | e | Variables considered | Results/remarks |
F: preliminary analysis (separately on training and validation sets) | ||||
F1: univariate | 151 | 41 | v1 to v4 | Kaplan-Meier curves (Figure 3) |
131 | 40 | |||
G: Multivariate testing of the omics score in the validation data (only validation set involved) | ||||
G1: significance | 131 | 40 | OS, v1 to v4 | Multivariate Cox model (Table 5) |
H: Comparison of the predictive accuracy of clinical and combined models through cross-validation in the validation data (only validation set involved) | ||||
H1: Overall prediction | 131 | 40 | OS, v1 to v4 | Prediction error curves based on cross-validation (Figure 11) |
Integrated Brier score based on cross-validation (text) |