2019/09/06 by Lucie Biard, Biard, Lucie, Bin Cheng +5
Biochemistry, Genetics and Molecular Biology · Mathematics · Medicine · #Applications (stat.AP) #Cancer Genomics and Diagnostics #FOS: Computer and information sciences #Lymphoma Diagnosis and Treatment #Statistical Methods in Clinical Trials
paper · pdf · doi:10.48550/arxiv.1909.02913
openalex publication_date 2019/09/06 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
In traditional dose-finding studies, dose-limiting toxicity (DLT) is determined within a fixed time observation window where DLT is often defined as a binary outcome. In the setting of oncology dose-finding trials, often patients in advanced stage of diseases are enrolled. Therefore, disease progression may occur within the DLT observation window leading to treatment discontinuation and rendering the patient unevaluable for DLT assessment. As a result, additional patients have to be enrolled, increasing the sample size. We propose and compare several practical methods for handling disease progression which occurs within the DLT observation window, in the context of the time-to-event continual reassessment method (TITE-CRM) which allows using partial observations. The methods differ on the way they define an evaluable patient and in the way incomplete observations are included. The methods are illustrated and contrasted in the context of a single simulated trial, and compared via simulations under various scenarios of dose-progression relationship, in the setting of advanced soft-tissue sarcoma.