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Pharm Stat. 2019 Jul;18(4):433-446. doi: 10.1002/pst.1934. Epub 2019 Feb 26.

Milestone prediction for time-to-event endpoint monitoring in clinical trials.

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Department of Health Sciences Research, Mayo Clinic Cancer Center, Rochester, MN, USA.
Private Practitioner, Rochester, MN, USA.


Predicting the times of milestone events, ie, interim and final analyses in clinical trials, helps resource planning. This manuscript presents and compares several easily implemented methods for predicting when a milestone event is achieved. We show that it is beneficial to combine the predictions from different models to craft a better predictor through prediction synthesis. Furthermore, a Bayesian approach provides a better measure of the uncertainty involved in prediction of milestone events. We compare the methods through two simulations where the model has been correctly specified and where the models are a mixture of three incorrectly specified model classes. We then apply the methods on two real clinical trial data, North Central Cancer Treatment Group (NCCTG) N0147 and N9841. In summary, the Bayesian prediction synthesis methods automatically perform well even when the data collection is far from homogeneous. An R shiny app is under development to carry out the prediction in a user-friendly fashion.


clinical trial; density forecast combination; event modeling; model stacking; prediction synthesis; trial monitoring

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