Enrollment forecast for clinical trials at the portfolio planning phase based on site-level historical data.

ABSTRACT

An accurate forecast of a clinical trial enrollment timeline at the planning phase is of great importance to both corporate strategic planning and trial operational excellence. The naive approach often calculates an average enrollment rate from historical data and generates an inaccurate prediction based on a linear trend with the average rate. Under the traditional framework of a Poisson-Gamma model, site activation delays are often modeled with either fixed initiation time or a simple random distribution while incorporating the user-provided site planning information to achieve good forecast accuracy. However, such user-provided information is not available at the early portfolio planning stage. We present a novel statistical approach based on generalized linear mixed-effects models and the use of non-homogeneous Poisson processes through the Bayesian framework to model the country initiation, site activation, and subject enrollment sequentially in a systematic fashion. We validate the performance of our proposed enrollment modeling framework based on a set of 25 preselected studies from four therapeutic areas. Our modeling framework shows a substantial improvement in prediction accuracy in comparison to the traditional statistical approach. Furthermore, we show that our modeling and simulation approach calibrates the data variability appropriately and gives correct coverage rates for prediction intervals of various nominal levels. Finally, we demonstrate the use of our approach to generate the predicted enrollment curves through time with confidence bands overlaid.