# "Within-trial" prognostic score adjustment is targeted maximum likelihood estimation

arXiv: https://arxiv.org/abs/2507.23446 · HTML: https://mlsanity.com/paper/2507.23446/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- First posted on arXiv 31 Jul 2025.

## Built on by (most cited first, 1 of 1)

- [Improving the Efficiency of Subgroup Analysis in Randomized Controlled Trials with TMLE](https://mlsanity.com/paper/2605.15483/) (2026)

## Abstract (arXiv)

Adjustment for ``super'' or ``prognostic'' composite covariates has become more popular in randomized trials recently. These prognostic covariates are often constructed from historical data 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 for optimal inference. We demonstrate the equivalence with a simulation study and discuss the pros and cons of within-trial prognostic adjustment (standard efficient estimation) relative to standard TMLE and standard prognostic adjustment with historical data.