Table 6.
Regression coefficient estimates and permutation test p-values of the multivariate model of probability of achieving each milestone given the phase 1 study characteristics.
| Phase 1 study characteristic | Regression coefficient estimate | Permutation test p-value |
|---|---|---|
| Clinical promise observed in phase 1 | 1.690 | 6.00 × 10−4 |
| Rationale for study of combination based on in vitro evidence of greater activity of the combination | −1.634 | 1.80 × 10−3 |
| Response biomarker-driven objectives included in phase 1 trial | 1.761 | 2.50 × 10−3 |
| Characterizing PK is criterion for phase 1 success | −2.323 | 2.70 × 10−3 |
| Other results observed in phase 1 | −1.893 | 8.30 × 10−3 |
| PK interactions expected | −1.602 | 0.012 |
| Overlapping dose-limiting toxicities expected | −0.970 | 0.015 |
| Rationale for study of combination based on lack of overlapping toxicities | −0.908 | 0.021 |
| 3 + 3 design used for phase 1 | −1.007 | 0.028 |
| Clinical data used for pharmacological or biological rationale for study of the combination | −0.711 | 0.036 |
| Adverse events expected | 0.673 | 0.040 |
| Rationale for study of combination based on in vivo evidence of greater activity of the combination | 0.586 | 0.044 |
| PK observed in phase 1 | 0.727 | 0.046 |
| Optimal dose or schedule established in phase 1 | 0.772 | 0.055 |
| Safe and tolerable dose or schedule established in phase 1 | 0.726 | 0.061 |
| PD biomarker-driven objectives included in phase 1 trial | −0.352 | 0.089 |
The p-values for statistically significant associations after adjustment with Benjamini-Hochberg are indicated in boldface. Characteristics not selected through forward stepwise regression were not included in this table.