In some clinical settings such as the cancer immunotherapy trials, a treatment time-lag effect may be present and the lag duration possibly vary from subject to subject. An efficient study design and analysis procedure should not only take into account the time-lag effect but also consider the individual heterogeneity in the lag duration. In this paper, we present a Generalized Piecewise Weighted Logrank (GPW-Logrank) test, designed to account for the random time-lag effect while maximizing the study power with respect to the weights.
View Article and Find Full Text PDFArming the immune system against cancer has emerged as a powerful tool in oncology during recent years. Instead of poisoning a tumor or destroying it with radiation, therapeutic cancer vaccine, a type of cancer immunotherapy, unleashes the immune system to combat cancer. This indirect mechanism-of-action of vaccines poses the possibility of a delayed onset of clinical effect, which results in a delayed separation of survival curves between the experimental and control groups in therapeutic cancer vaccine trials with time-to-event endpoints.
View Article and Find Full Text PDFThere is considerable interest among pharmaceutical and other medical product developers in adaptive clinical trials, in which knowledge learned during the course of a trial affects ongoing conduct or analysis of the trial. When the FDA released a draft Guidance document on adaptive design clinical trials in early 2010, expectations were high that it would lead to an increase in regulatory submissions involving adaptive design features, particularly for confirmatory trials. A 6-year (2008-2013) retrospective survey was performed within the Center for Biologics Evaluation and Research (CBER) at the FDA to gather information regarding the submission and evaluation of adaptive design trial proposals.
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