Table 3.
Evaluation of postoperative plasma neutrophil gelatinase-associated lipocalin as a prognostic enrichment biomarker for the outcome of death within one year of surgery. Biomarker performance and rates of death are estimated from data from the Translational Research Investigating Biomarker Endpoints study, where the area under the receiver operating characteristic curve of the biomarker is 0.63 and the clinical event occurred in 8.7% of observations. A trial of an intervention to help prevent the clinical event is designed to have 90% power to detect a 30% relative reduction in the event rate using one-sided hypothesis testing and α=0.025. The cost of screening is $50 and the per patient trial cost is $1,000. The Screening Threshold is the proportion of patients who will be screened out of the trial. The Event Rate is the rate of the clinical event in the enriched study population not receiving the intervention. The Sample Size is the trial sample size calculated as a function of the event rate and statistical testing specifications. Total Screened is the total number of patients who would need to be screened to enroll the trial, which depends on the sample size and stringency of screening. Total Cost summarizes patient-related costs of different levels of enrichment, specifically the costs of biomarker-based screening and the costs of having a patient in a trial. The results here are also shown in Figure 2.
| Screening Threshold | Event Rate | Sample Size | Total Screened | Total Cost | Percent Reduction in Total Cost |
|---|---|---|---|---|---|
| 0% | 0.09 | 4004 | 4427 | 4003965 | 0% |
|
|
|||||
| 5% | 0.09 | 4004 | 4427 | 4225338 | −5.5% |
|
|
|||||
| 10% | 0.09 | 3983 | 4426 | 4204355 | −5% |
|
|
|||||
| 15% | 0.10 | 3739 | 4403 | 3959482 | 1.1% |
|
|
|||||
| 20% | 0.10 | 3716 | 4645 | 3948378 | 1.4% |
|
|
|||||
| 25% | 0.10 | 3605 | 4811 | 3845575 | 4% |
|
|
|||||
| 30% | 0.10 | 3571 | 5102 | 3826289 | 4.4% |
|
|
|||||
| 35% | 0.10 | 3442 | 5301 | 3707178 | 7.4% |
|
|
|||||
| 40% | 0.11 | 3231 | 5385 | 3500209 | 12.6% |
|
|
|||||
| 45% | 0.12 | 3078 | 5603 | 3357747 | 16.1% |
|
|
|||||
| 50% | 0.12 | 2919 | 5838 | 3210983 | 19.8% |
|
|
|||||
| 55% | 0.12 | 2995 | 6645 | 3327176 | 16.9% |
|
|
|||||
| 60% | 0.13 | 2702 | 6754 | 3039412 | 24.1% |
|
|
|||||
| 65% | 0.14 | 2569 | 7326 | 2935680 | 26.7% |
|
|
|||||
| 70% | 0.14 | 2397 | 7991 | 2796935 | 30.1% |
|
|
|||||
| 75% | 0.13 | 2780 | 11087 | 3334256 | 16.7% |
|
|
|||||
| 80% | 0.12 | 2881 | 14404 | 3600894 | 10.1% |
|
|
|||||
| 85% | 0.14 | 2411 | 15993 | 3210276 | 19.8% |
|
|
|||||
| 90% | 0.14 | 2397 | 23974 | 3596059 | 10.2% |
|
|
|||||
| 95% | 0.14 | 2437 | 48045 | 4839320 | −20.9% |