Improving Transportability of Randomized Clinical Trial Inference Using Robust Prediction Methods

November 18, 2023
Randomized trials have been the gold standard for assessing causal effects since their introduction by Fisher in the 1920s, since they can eliminate both observed and unobserved confounding. Estimates of causal effects at the population level from randomized controlled trials (RCTs) can still be biased if there are both effect modification and systematic differences between the trial sample and the ultimate population of inference with respect to these modifiers. Recent advances in the survey statistics literature to improve inference in nonprobability samples by using information from probability samples can provide an avenue for improving population causal inference in randomized controlled trials when relevant probability samples of the patient population are available. We propose extending these estimators using either inverse probability weighting (IWPT) or prediction that can accommodate unequal probability of selection in the “benchmark” or population, and use Bayesian additive regression trees (BART) for both IPTW and prediction estimation that do not require specification of functional form or interaction. We also consider how the assumption of ignorability may be assessed from observed data and propose a sensitivity analysis under the failure of this assumption.