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Marina B. Klein

Publications and source records attributed to Marina B. Klein.

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Group Sequential Design with Posterior and Posterior Predictive Probabilities

Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved interventions. Bayesian decision procedures provide a formal and intuitive framework for early stopping using posterior and posterior predictive probabilities. Design parameters including decision thresholds and sample sizes are chosen to control the error probabilities associated with the sequential decision process. These choices are routinely made based on estimating the sampling distribution of posterior summaries via intensive Monte Carlo simulations for each sample size and design scenario considered. In this paper, we propose an efficient method to calibrate decision thresholds to pre-specified alpha- and beta-spending functions and determine minimum sample sizes for Bayesian group sequential designs. We prove theoretical results that enable posterior and posterior predictive probabilities to be modeled as a function of the sample size. Using these functions, we assess error probabilities at a range of sample sizes given simulations conducted at only two sample sizes. The effectiveness of our methodology is highlighted using several substantive examples.

stat.ME

A time-dependent Poisson-Gamma model for recruitment forecasting in multicenter studies

Forecasting recruitments is a key component of the monitoring phase of multicenter studies. One of the most popular techniques in this field is the Poisson-Gamma recruitment model, a Bayesian technique built on a doubly stochastic Poisson process. This approach is based on the modeling of enrollments as a Poisson process where the recruitment rates are assumed to be constant over time and to follow a common Gamma prior distribution. However, the constant-rate assumption is a restrictive limitation that is rarely appropriate for applications in real studies. In this paper, we illustrate a flexible generalization of this methodology which allows the enrollment rates to vary over time by modeling them through B-splines. We show the suitability of this approach for a wide range of recruitment behaviors in a simulation study and by estimating the recruitment progression of the Canadian Co-infection Cohort (CCC).

stat.ME