Preface |
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xi | |
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1 | (6) |
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2 | (1) |
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3 | (2) |
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5 | (2) |
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2 Cancer Biology and Genetics for Non-Biologists |
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7 | (16) |
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7 | (3) |
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2.2 DNA, genes, RNA and proteins |
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10 | (4) |
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10 | (2) |
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12 | (1) |
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12 | (2) |
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2.3 Cancer -- DNA gone wrong |
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14 | (2) |
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16 | (2) |
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2.5 Measuring cancer in the patient |
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18 | (5) |
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23 | (42) |
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3.1 The amazing survival equations |
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23 | (9) |
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3.1.1 The survival function |
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23 | (3) |
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3.1.2 The hazard function |
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26 | (1) |
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3.1.2.1 Shapes of Weibull distributions |
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27 | (2) |
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3.1.2.2 Proportional hazards and the hazard ratio |
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29 | (1) |
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3.1.3 The cumulative hazard function |
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29 | (2) |
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3.1.4 Design your own survival function |
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31 | (1) |
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3.2 Non-parametric estimation of survival curves |
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32 | (11) |
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3.2.1 The Kaplan-Meier survival curve |
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33 | (3) |
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3.2.2 Confidence intervals for KM curves |
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36 | (2) |
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3.2.3 Mean and median survival times |
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38 | (2) |
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3.2.4 The Nelson-Aalen cumulative hazard curve |
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40 | (1) |
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3.2.5 Estimating the hazard function |
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41 | (2) |
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3.3 Fitting parametric survival curves to data |
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43 | (4) |
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3.3.1 Parametric survival curves fitted to the lung cancer trial data |
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45 | (2) |
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3.4 Comparing two survival distributions |
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47 | (11) |
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48 | (3) |
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3.4.1.1 Stratified log-rank test |
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51 | (1) |
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3.4.1.2 Log-rank tests for the lung cancer trial |
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52 | (1) |
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53 | (1) |
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3.4.2.1 Checking for proportional hazards |
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54 | (1) |
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3.4.2.2 Weighted log-rank tests |
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55 | (1) |
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3.4.2.3 Log-rank test: three or more arms |
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56 | (2) |
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58 | (5) |
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3.6 Comparing two parametric survival curves |
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63 | (2) |
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4 Designing and Running a Clinical Trial |
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65 | (10) |
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4.1 Types of trials and studies |
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65 | (2) |
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67 | (8) |
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4.2.1 Regulatory and other bodies |
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68 | (1) |
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69 | (3) |
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72 | (3) |
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5 Regression Analysis for Survival Data |
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75 | (48) |
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5.1 A Weibull parametric regression model |
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75 | (2) |
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5.2 Cox proportional hazards model |
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77 | (28) |
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5.2.1 Multiple imputation for missing data |
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82 | (5) |
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5.2.2 Assessing the fit of the Cox model |
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87 | (6) |
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5.2.3 Estimating the baseline hazard function |
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93 | (2) |
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5.2.4 Time dependent predictors |
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95 | (9) |
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104 | (1) |
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105 | (1) |
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5.3 Accelerated failure time (AFT) models |
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105 | (4) |
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5.4 Proportional odds models |
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109 | (2) |
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5.5 Parametric survival distributions for PH and AFT models |
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111 | (2) |
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5.6 Flexible parametric models |
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113 | (10) |
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5.6.1 Parametric models fitted to some colon cancer data |
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115 | (8) |
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6 Clinical Trials: the Statistician's Role |
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123 | (28) |
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6.1 Sample size calculation |
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123 | (7) |
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6.1.1 Normal random variables |
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124 | (1) |
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6.1.2 Binomial random variables |
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125 | (1) |
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6.1.3 Survival random variables |
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126 | (2) |
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6.1.3.1 Number to recruit |
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128 | (2) |
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6.2 Examples of sample size calculations; Phases I to III |
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130 | (4) |
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6.2.1 Phase I trials: dose escalation studies |
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130 | (1) |
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131 | (2) |
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133 | (1) |
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6.3 Group sequential designs |
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134 | (8) |
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6.3.0.1 Stopping for futility |
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139 | (1) |
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6.3.0.2 Group sequential designs for survival endpoints |
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140 | (2) |
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6.4 More statistical tasks for clinical trials |
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142 | (9) |
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6.4.1 Randomisation and recruitment |
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142 | (1) |
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6.4.1.1 Simple randomisation |
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142 | (1) |
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6.4.1.2 Block randomisation |
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143 | (1) |
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6.4.1.3 Stratified randomisation |
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143 | (1) |
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143 | (1) |
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6.4.2 Statistical contribution to the protocol |
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144 | (2) |
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6.4.3 The Statistical Analysis Plan (SAP) |
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146 | (1) |
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146 | (1) |
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6.4.5 Statistical reports |
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147 | (1) |
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6.4.6 Post study analyses |
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148 | (3) |
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151 | (42) |
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152 | (4) |
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7.1.1 Study designs for measuring cancer |
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154 | (2) |
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7.2 Cancer statistics for countries |
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156 | (8) |
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157 | (5) |
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162 | (2) |
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164 | (12) |
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7.3.1 Poisson regression models |
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169 | (4) |
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7.3.2 Two more examples of cohort studies |
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173 | (3) |
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176 | (10) |
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7.4.1 Unmatched case-control study |
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177 | (2) |
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7.4.2 Confounding in case-control studies |
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179 | (2) |
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7.4.3 Logistic regression for unmatched case-control studies |
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181 | (2) |
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7.4.4 Matched case-control studies |
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183 | (3) |
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7.5 Cross-sectional studies |
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186 | (4) |
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190 | (3) |
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193 | (38) |
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8.1 How to carry out a systematic review |
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194 | (3) |
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8.1.1 An oesophageal cancer review |
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196 | (1) |
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197 | (4) |
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201 | (9) |
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8.3.1 Assessing model fit |
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205 | (3) |
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208 | (2) |
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8.4 Bayesian meta-analysis |
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210 | (6) |
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8.5 Network meta-analysis |
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216 | (13) |
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8.5.1 Fixed effects network meta-analysis |
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218 | (2) |
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8.5.2 Network meta-analysis for breast cancer |
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220 | (4) |
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8.5.3 Bayesian network meta-analysis for pancreatic cancer |
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224 | (5) |
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8.6 Individual patient data |
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229 | (2) |
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231 | (24) |
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9.1 Diagnostic biomarkers |
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232 | (11) |
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9.1.1 Measuring prevalence |
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235 | (1) |
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9.1.2 Comparing two tests |
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236 | (2) |
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9.1.3 Receiver Operating Characteristic (ROC) curves |
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238 | (3) |
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241 | (1) |
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242 | (1) |
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243 | (1) |
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9.2 Prognostic biomarkers |
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243 | (5) |
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9.2.1 Prognostic biomakers for HCC |
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244 | (4) |
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9.3 Predictive biomarkers for pancreatic cancer |
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248 | (5) |
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9.4 Biomarker trial design |
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253 | (2) |
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255 | (30) |
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10.1 Producing genetic data |
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256 | (3) |
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10.1.1 Polymerase chain reaction (PCR) |
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257 | (1) |
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257 | (1) |
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10.1.3 Next generation sequencing (NGS) |
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258 | (1) |
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10.2 Analysis of microarray data |
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259 | (15) |
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10.2.1 Preprocessing microarray data, low-level analysis |
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260 | (2) |
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10.2.2 Preprocessing the melanoma microarray data |
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262 | (4) |
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10.2.3 High-level analysis of the melanoma data |
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266 | (8) |
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10.3 Pre-processing NGS data |
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274 | (1) |
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10.4 TCGA-KIRC: Renal clear cell carcinoma |
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275 | (10) |
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10.4.1 Differential expression |
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276 | (2) |
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10.4.2 Genes as biomarkers for survival |
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278 | (2) |
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10.4.3 Single nucleotide variation |
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280 | (5) |
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285 | (22) |
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287 | (1) |
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A.1 Some distribution theory |
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287 | (3) |
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A.1.1 The central limit theorem |
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287 | (1) |
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A.1.2 Transformations of random variables |
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288 | (2) |
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A.2 Statistical inference |
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290 | (3) |
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A.2.1 Parameter estimation |
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290 | (1) |
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291 | (2) |
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293 | (2) |
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A.3.0.1 Choosing a subset of predictor variables |
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294 | (1) |
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295 | (8) |
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A.4.1 MCMC: Markov Chain Monte Carlo |
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296 | (5) |
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301 | (2) |
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A.5 Multivariate data analysis |
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303 | (4) |
Bibliography |
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307 | (8) |
Index |
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315 | |