TABLE 2.
Comparison of parameter estimates of OS submodel using two‐stage or joint modeling approaches.
| Parameter | Unit or Group | Two‐stage model | Joint model | ||||
|---|---|---|---|---|---|---|---|
| Estimate | RSE% | Wald test statistic | Estimate | RSE% | Wald test statistic | ||
| Scale | day | 640 | 3.1 | – | 750 | 3.2 | – |
| Log(K G) | – | 0.73 | 4.1 | 24 | 1.0 | 4.1 | 25 |
| C‐reactive protein | mg/L | 0.26 | 7.5 | 13 | 0.23 | 8.5 | 12 |
| ECOG | 1 vs. 0 | 0.52 | 9.2 | 11 | 0.41 | 9.9 | 10 |
| Treatment line | 2+ vs. 1 | 0.33 | 10 | 9.6 | 0.22 | 18 | 5.6 |
| Neutrophil‐to‐Lymphocyte ratio | – | 0.23 | 15 | 6.7 | 0.21 | 18 | 5.6 |
| Liver metastasis | Yes vs. no | 0.29 | 19 | 5.2 | 0.23 | 24 | 4.2 |
| Asian | Yes vs. no | −0.35 | 20 | 4.9 | −0.36 | 24 | 4.2 |
| Number of metastatic sites | – | 0.22 | 21 | 4.7 | 0.19 | 25 | 4.0 |
| Albumin | g/L | −0.70 | 21 | 4.7 | −0.63 | 27 | 3.7 |
| Lactate dehydrogenase | U/L | 0.18 | 22 | 4.5 | 0.17 | 25 | 4.1 |
| PD‐L1 status | IC or TC >0 vs. IC and TC = 0 | −0.14 | 25 | 4.0 | −0.14 | 29 | 3.4 |
| Shape | – | 1.8 | 1.2 | – | 1.7 | 1.1 | – |
Note: The covariate model for OS for the two‐stage approach was initially developed in R and refitted within Monolix. Of note, all the included covariates in R where still significant when implemented in Monolix. Continuous covariates were log‐transformed and centered around the median. Covariates are ordered from the most to the less significant one using a Wald‐test in the two‐stage setting.
Abbreviations: ECOG, Eastern Cooperative Oncology Group performance status; K G, tumor growth rate constant; OS, overall survival; RSE, relative standard error.