Journal of Data Science

We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on the statistical analysis of time-to-event outcomes in late-phase oncology trials. Using a simulated case study that mimics a Phase III ongoing trial during the pandemic, we evaluated the impact of COVID-19-related deaths, time off-treatment and missed clinical visits due to the pandemic, on overall survival and/or progression-free survival in terms of test size (also referred to as Type 1 error rate or alpha level), power, and hazard ratio (HR) estimates. We found that COVID-19-related deaths would impact both size and power, and lead to biased HR estimates; the impact would be more severe if there was an imbalance in COVID-19-related deaths between the study arms. Approaches censoring COVID-19-related deaths may mitigate the impact on power and HR estimation, especially if study data cut-off was extended to recover censoring-related event loss. The impact of COVID-19-related time off-treatment would be modest for power, and moderate for size and HR estimation. Different rules of censoring cancer progression times result in a slight difference in the power for the analysis of progression-free survival. The simulations provided valuable information for determining whether clinical-trial modifications should be required for ongoing trials during the COVID-19 pandemic.

Abstract: The interest in estimating the probability of cure has been increas ing in cancer survival analysis as the cure of some cancer sites is becoming a reality. Mixture cure models have been used to model the failure time data with the existence of long-term survivors. The mixture cure model assumes that a fraction of the survivors are cured from the disease of interest. The failure time distribution for the uncured individuals (latency) can be mod eled by either parametric models or a semi-parametric proportional hazards model. In the model, the probability of cure and the latency distribution are both related to the prognostic factors and patients’ characteristics. The maximum likelihood estimates (MLEs) of these parameters can be obtained using the Newton-Raphson algorithm. The EM algorithm has been proposed as a simple alternative by Larson and Dinse (1985) and Taylor (1995). in various setting for the cause-specific survival analysis. This approach is ex tended here to the grouped relative survival data. The methods are applied to analyze the colorectal cancer relative survival data from the Surveillance, Epidemiology, and End Results (SEER) program.