Simulating Colorectal Cancer Trials Using Real-World Data.

TitleSimulating Colorectal Cancer Trials Using Real-World Data.
Publication TypeJournal Article
Year of Publication2022
AuthorsChen Z, Zhang H, George TJ, Guo Y, Prosperi M, Guo J, Braithwaite D, Wang F, Kibbe W, Wagner L, Bian J
JournalJCO Clin Cancer Inform
Date Published2022 Jul
KeywordsAntineoplastic Combined Chemotherapy Protocols, Clinical Trials, Phase III as Topic, Colorectal Neoplasms, Fluorouracil, Humans, Irinotecan, Leucovorin

PURPOSE: Using real-world data (RWD)-based trial simulation approach, we aim to simulate colorectal cancer (CRC) trials and examine both effectiveness and safety end points in different simulation scenarios.

METHODS: We identified five phase III trials comparing new treatment regimens with an US Food and Drug Administration-approved first-line treatment in patients with metastatic CRC (ie, fluorouracil, leucovorin, and irinotecan) as the standard-of-care (SOC) control arm. Using Electronic Health Record-derived data from the OneFlorida network, we defined the study populations and outcome measures using the protocols from the original trials. Our design scenarios were (1) simulation of the SOC fluorouracil, leucovorin, and irinotecan arm and (2) comparative effectiveness research (CER) simulation of the control and experimental arms. For each scenario, we adjusted for random assignment, sampling, and dropout. We used overall survival (OS) and severe adverse events (SAEs) to measure effectiveness and safety.

RESULTS: We conducted CER simulations for two trials, and SOC simulations for three trials. The effect sizes of our simulated trials were stable across all simulation runs. Compared with the original trials, we observed longer OS and higher mean number of SAEs in both CER and SOC simulation. In the two CER simulations, hazard ratios associated with death from simulations were similar to that reported in the original trials. Consistent with the original trials, we found higher risk ratios of SAEs in the experiment arm, suggesting potentially higher toxicities from the new treatment regimen. We also observed similar SAE rates across all simulations compared with the original trials.

CONCLUSION: In this study, we simulated five CRC trials, and tested two simulation scenarios with several different configurations demonstrated that our simulations can robustly generate effectiveness and safety outcomes comparable with the original trials using real-world data.

Alternate JournalJCO Clin Cancer Inform
PubMed ID35839432
PubMed Central IDPMC9848597
Grant ListP30 AG028740 / AG / NIA NIH HHS / United States
R01 CA246418 / CA / NCI NIH HHS / United States
R21 CA253394 / CA / NCI NIH HHS / United States
Institute of Artificial Intelligence for Digital Health
Faculty Publication