TABLE 3 ∣.
Simulation results for the comparator frequentist trial design.
| Scenario | Possible final decision |
Overall trial decision rate |
Average sample size |
Average marker prevalence |
|---|---|---|---|---|
| 1: No treat effect, No marker effect | No Marker Detected | 0.713 | N = 254.8 | — |
| Marker Detected | 0.287 | — | 0.505 | |
| Overall Efficacy | 0.010 | |||
| Overall Inferiority | 0.017 | |||
| Overall Futility | 0.846 | |||
| M+ Eff/M− Fut | 0.063 | |||
| M+ Eff/M− Inf | 0.005 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | 0.059 | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 2: Constant treat effect, No marker effect | No Marker Detected | 0.726 | N = 250 | — |
| Marker Detected | 0.274 | — | 0.505 | |
| Overall Efficacy | 0.891 | |||
| Overall Inferiority | — | |||
| Overall Futility | — | |||
| M+ Eff/M− Fut | 0.109 | |||
| M+ Eff/M− Inf | — | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | — | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 3: Prognostic marker effect, No treat effect | No Marker Detected | 0.302 | N = 253.5 | — |
| Marker Detected | 0.698 | — | 0.472 | |
| Overall Efficacy | 0.006 | |||
| Overall Inferiority | 0.008 | |||
| Overall Futility | 0.859 | |||
| M+ Eff/M− Fut | 0.066 | |||
| M+ Eff/M− Inf | 0.001 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | 0.060 | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 4: Predictive marker effect, (perfectly dichotomous) | No Marker Detected | 0.009 | N = 251 | — |
| Marker Detected | 0.991 | — | 0.515 | |
| Overall Efficacy | 0.015 | |||
| Overall Inferiority | — | |||
| Overall Futility | — | |||
| M+ Eff/M− Fut | 0.947 | |||
| M+ Eff/M− Inf | 0.037 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | 0.001 | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 5: Predictive marker effect, (nearly dichotomous) | No Marker Detected | 0.025 | N = 251 | — |
| Marker Detected | 0.975 | — | 0.527 | |
| Overall Efficacy | 0.030 | |||
| Overall Inferiority | — | |||
| Overall Futility | — | |||
| M+ Eff/M− Fut | 0.946 | |||
| M+ Eff/M− Inf | 0.024 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | — | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 6: Predictive marker effect, (linear) | No Marker Detected | 0.189 | N = 254.25 | — |
| Marker Detected | 0.811 | — | 0.545 | |
| Overall Efficacy | 0.229 | |||
| Overall Inferiority | — | |||
| Overall Futility | 0.008 | |||
| M+ Eff/M− Fut | 0.759 | |||
| M+ Eff/M− Inf | 0.004 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | — | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 7: Predictive marker effect, (non-linear and monotone) | No Marker Detected | 0.428 | N = 250.5 | — |
| Marker Detected | 0.572 | — | 0.665 | |
| Overall Efficacy | 0.558 | |||
| Overall Inferiority | — | |||
| Overall Futility | — | |||
| M+ Eff/M− Fut | 0.442 | |||
| M+ Eff/M− Inf | — | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | — | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 8: Predictive marker effect, (nonlinear and monotone) | No Marker Detected | 0.179 | N = 261.5 | — |
| Marker Detected | 0.821 | — | 0.498 | |
| Overall Efficacy | 0.188 | |||
| Overall Inferiority | — | |||
| Overall Futility | 0.024 | |||
| M+ Eff/M− Fut | 0.779 | |||
| M+ Eff/M− Inf | 0.008 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | 0.001 | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 9: Predictive marker effect, (nonlinear and non-monotone) | No Marker Detected | 0.128 | N = 263.25 | — |
| Marker Detected | 0.872 | — | 0.261 | |
| Overall Efficacy | 0.189 | |||
| Overall Inferiority | — | |||
| Overall Futility | 0.058 | |||
| M+ Eff/M− Fut | 0.753 | |||
| M+ Eff/M− Inf | — | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | — | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 10: Predictive marker effect, (nonlinear and non-monotone) | No Marker Detected | 0.177 | N = 251.25 | — |
| Marker Detected | 0.823 | — | 0.767 | |
| Overall Efficacy | 0.173 | |||
| Overall Inferiority | — | |||
| Overall Futility | 0.007 | |||
| M+ Eff/M− Fut | 0.812 | |||
| M+ Eff/M− Inf | 0.007 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | 0.001 | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 11: Constant inferior treat effect, No marker effect | No Marker Detected | 0.763 | N = 250 | — |
| Marker Detected | 0.237 | — | 0.420 | |
| Overall Efficacy | — | |||
| Overall Inferiority | 0.916 | |||
| Overall Futility | — | |||
| M+ Eff/M− Fut | — | |||
| M+ Eff/M− Inf | — | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | 0.084 | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — | |||
| 12: Prognostic and predictive marker effect, (linear; nearly dichotomous) | No Marker Detected | 0.157 | N = 255.75 | — |
| Marker Detected | 0.843 | — | 0.509 | |
| Overall Efficacy | 0.088 | |||
| Overall Inferiority | — | |||
| Overall Futility | 0.104 | |||
| M+ Eff/M− Fut | 0.789 | |||
| M+ Eff/M− Inf | 0.016 | |||
| M+ Fut/M− Eff | — | |||
| M+ Fut/M− Inf | 0.003 | |||
| M+ Inf/M− Eff | — | |||
| M+ Inf/M− Fut | — |