A SuperLearner Approach to Predict Run-In Selection in Clinical Trials

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Lanera C., Berchialla P., Lorenzoni G., Acar A. S., Chiminazzo V., Azzolina D., ...More

COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE, vol.2022, 2022 (SCI-Expanded) identifier identifier identifier


A critical early step in a clinical trial is defining the study sample that appropriately represents the target population from which the sample will be drawn. Envisaging a "run-in" process in study design may accomplish this task; however, the traditional run-in requires additional patients, increasing times, and costs. The possible use of the available a-priori data could skip the run-in period. In this regard, ML (machine learning) techniques, which have recently shown considerable promising usage in clinical research, can be used to construct individual predictions of therapy response probability conditional on patient characteristics. An ensemble model of ML techniques was trained and validated on twin randomized clinical trials to mimic a run-in process within this framework. An ensemble ML model composed of 26 algorithms was trained on the twin clinical trials. SuperLearner (SL) performance for the Verum (Treatment) arm is above 70% sensitivity. The Positive Predictive Value (PPP) achieves a value of 80%. Results show good performance in the direction of being useful in the simulation of the run-in period; the trials conducted in similar settings can train an optimal patient selection algorithm minimizing the run-in time and costs of conduction.