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

Fuente: arXiv
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Main Authors: Højbjerre-Frandsen, Emilie, Schuler, Alejandro
Format: Preprint
Published: 2025
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author Højbjerre-Frandsen, Emilie
Schuler, Alejandro
author_facet Højbjerre-Frandsen, Emilie
Schuler, Alejandro
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2507_23446
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle "Within-trial" prognostic score adjustment is targeted maximum likelihood estimation
Højbjerre-Frandsen, Emilie
Schuler, Alejandro
Methodology
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.
title "Within-trial" prognostic score adjustment is targeted maximum likelihood estimation
topic Methodology
url https://arxiv.org/abs/2507.23446