Table 2.
Criteria to enable evaluation of the translational relevance of preclinical models of pediatric cancer (developed by St. Jude Children’s Research Hospital) [51]
| Criteria | Description |
|---|---|
| Randomization | Before the preclinical study begins, the randomization schedule should be designed by biostatisticians and the interim analysis and censure rules specified |
| Double-blind study design | Individuals administering treatment and monitoring responses should have no knowledge of the treatment groups |
| Pharmacokinetics | The murine equivalent dose should be determined based on the recommended pediatric phase 2 dose (RPP2D). In many cases, the RPP2D is not known, so the adult recommended phase 2 dose is used instead |
| Pharmacodynamics | Pharmacodynamic analysis is required to confirm that the drug enters tumor cells and affects the pathway of interest |
| Clinically relevant drug dose | The drug dose used in the preclinical model should correspond to the plasma exposure in pediatric patients (if known) |
| Clinically relevant drug combination | In addition to single-agent studies, drug combinations should be considered for preclinical studies if clinically relevant |
| Clinically relevant drug schedule | The duration of each course of therapy in the preclinical study should be the same as that used in clinical trials |
| Monitoring toxicity relevant to pediatric patients | The hematological and/or organ toxicity expected for a given treatment should be carefully monitored and any relationship between drug exposure and toxicity should be characterized |
| Tumor validation | Preclinical tumor model should be carefully characterized and, where possible, should match patient tumors in terms of histology, genomic features, and tumor location |
| Efficacy measurements relevant to patient outcome | The definitions of progressive disease, stable disease, partial response, and complete response should be specified before the preclinical study begins. As a guide, for a double-blind, placebo-controlled, randomized efficacy study, typically 10–20 mice per group are needed to adequately power the study |