A SuperLearner-enforced approach for the estimation of treatment effect in pediatric trials

Randomized Clinical Trials (RCT) represent the gold standard among scientific evidence. RCTs are tailored to control selection bias and the confounding effect of baseline characteristics on the effect of treatment. However, trial conduction and enrolment procedures could be challenging, especially for rare diseases and paediatric research. In these research frameworks, the treatment effect estimation could be compromised. A potential countermeasure is to develop predictive models on the probability of the baseline disease based on previously collected observational data. Machine learning (ML) algorithms have recently become attractive in clinical research because of their flexibility and improved performance compared to standard statistical methods in developing predictive models.

This manuscript proposes an ML-enforced treatment effect estimation procedure based on an ensemble SuperLearner (SL) approach, trained on historical observational data, to control the confounding effect.

The REnal SCarring Urinary infEction trial served as a motivating example. Historical observational study data have been simulated through 10,000 Monte Carlo (MC) runs. Hypothetical RCTs have been also simulated, for each MC run, assuming different treatment effects of antibiotics combined with steroids. For each MC simulation, the SL tool has been applied to the simulated observational data. Furthermore, the average treatment effect (ATE), has been estimated on the trial data and adjusted for the SL predicted probability of renal scar.

The simulation results revealed an increased power in ATE estimation for the SL-enforced estimation compared to the unadjusted estimates for all the algorithms composing the ensemble SL.