Table 4.
Logistic Regression Comparing Initial and Supplementary Indication Approval of New Targeted Multi-Indication Cancer Drugs by the FDA, EMA, HC, and TGA
| Model 1 | Model 2 | Model 3 | Model 4 | |
|---|---|---|---|---|
| Dependent Variable: FDA Approval Sequence (Initial Indication: 1, Supplementary Indication: 0) | ||||
| A) Regulatory Approval | ||||
| Conditional Approval | 3.208* | 2.168 | 2.684* | 2.686* |
| (2.46) | (1.70) | (2.06) | (2.09) | |
| Priority Review | 2.663* | 2.606* | 2.482* | 2.602* |
| (2.38) | (2.50) | (2.27) | (2.35) | |
| Orphan Designation | 2.807* | 3.703** | 3.689** | 3.318** |
| (2.29) | (2.85) | (2.87) | (2.67) | |
| Supporting Trials † | 1.704*** | 1.712*** | 1.703** | 1.654** |
| (3.50) | (3.41) | (3.15) | (3.02) | |
| B) Pivotal Trial Characteristics | ||||
| Phase ‡ | 0.230* | 0.206* | 0.281* | |
| (-2.43) | (-2.55) | (-2.25) | ||
| MCBS Score | 0.853 | 0.607 | ||
| (-0.27) | (-0.81) | |||
| Enrolled Patients (per 100) | 1.153 | 1.195* | 1.186* | |
| (1.85) | (2.15) | (2.14) | ||
| Trial Length (months) | 0.963* | 0.961* | 0.963* | |
| (-2.18) | (-2.31) | (-2.28) | ||
| C) Treatment Characteristics | ||||
| Monotherapy | 7.174* | 5.913* | ||
| (2.25) | (2.12) | |||
| 1st Line Treatment | 1.318 | 1.179 | ||
| (0.48) | (0.30) | |||
| Agency Dummy | ||||
| US (FDA) | 1.000 | 1.000 | 1.000 | 1.000 |
| (Reference) | (Reference) | (Reference) | (Reference) | |
| EU (EMA) | 1.366 | 1.339 | 1.389 | 1.382 |
| (1.37) | (1.21) | (1.31) | (1.34) | |
| Canada (HC) | 1.180 | 1.257 | 1.209 | 1.155 |
| (0.76) | (0.96) | (0.78) | (0.62) | |
| Australia (TGA) | 2.711** | 2.828*** | 3.000*** | 2.891*** |
| (3.20) | (3.27) | (3.29) | (3.29) | |
| No. of Observations | 357 | 357 | 357 | 357 |
| Pseudo-R2 | 13.9% | 19.7% | 22.8% | 22.4% |
| AIC | 374 | 358 | 349 | 349 |
| Wald-Test (p-Value) | 0.0001 | 0.0003 | 0.0001 | 0.0001 |
Regulatory (Model 1), pivotal trial (Model 2), and treatment (Model 3) characteristics were added sequentially. Model 4 optimizes the regression by excluding collinear variables. Odds Ratios are presented. Indication approval sequence was determined by the FDA approval date (initial indication: 1, supplementary indication: 0). t statistics in parentheses
FDA US Food and Drug Administration, EMA European Medicines Agency, HC Health Canada, TGA Therapeutics Goods Administration, MCBS Magnitude of Clinical Benefit Scale (1: low benefit to 5: high benefit)
P-values: * p <0.05; ** p <0.01; *** p <0.001
† Highest phase of supporting trials disclosed in the regulatory approval report (No supporting trial: 0, Phase 1: 1, Phase 2: 2, Phase 3: 3)
‡ Highest phase pivotal trial disclosed in the regulatory approval report (Phase 1: 1, Phase 2: 2, Phase 3: 3)