Adjustment for "super" or "prognostic" composite covariates has become more popular in randomized trials recently. These prognostic covariates are often constructed from historical data obtained from previous clinical trials or registries by fitting a predictive model of the outcome on the raw covariates. A natural question that we have been asked by applied researchers is whether this can be done without the historical data: can the prognostic covariate be constructed or derived from the trial data itself, possibly using different folds of the data, before adjusting for it? Here we clarify that such "within-trial" prognostic adjustment is nothing more than a form of targeted maximum likelihood estimation (TMLE), a well-studied procedure that typically improves the power of trial analyses. We therefore argue that there is no reason to reinvent the wheel: within-trial prognostic score adjustment should be referred to as TMLE, without qualification.
Højbjerre‐Frandsen et al. (Sun,) studied this question.