Targeted maximum likelihood estimation of vaccine effectiveness and immune correlates in test-negative design studies with missing data
Authors: Leah I. B. Andrews, Lars van der Laan, Peter B. Gilbert
Summary
arXiv:2605. 21793v1 Announce Type: cross Abstract: The test-negative design (TND) is a resource-efficient observational study design that can assess vaccine effectiveness and exposure-proximal immune correlates of disease.
Relevance
Read next because Targeted maximum likelihood estimation of vaccine effectiveness and immune correlates in test-negative design studies with missing data overlaps with clean result "LoRA persona trained on alone emits at 23.5% when a co-trained partner learns ..., vs 0% control on Qwen2.5-7B-Instruct (MODERATE confidence)", clean result "Language-mismatch LoRA SFT on Qwen2.5-7B leaks the trained completion language into bystander directives the model was never trained on, absent under same-language SFT (LOW confidence)", clean result "Only continuous soft prefixes hit both EM axes at once on Qwen-2.5-7B-Instruct: discrete prompt searches split between the alignment objective and the distributional objective, and both discretizations of the soft prefix collapse (MODERATE confidence)". Matching terms: marker, under, eval, source, line, compare, control, test. Source: arxiv stat.ML (Machine Learning).
Threat model
Potential threat/caveat for clean result "LoRA persona trained on alone emits at 23.5% when a co-trained partner learns ..., vs 0% control on Qwen2.5-7B-Instruct (MODERATE confidence)": this item discusses confound, negative.
Abstract
arXiv:2605.21793v1 Announce Type: cross Abstract: The test-negative design (TND) is a resource-efficient observational study design that can assess vaccine effectiveness and exposure-proximal immune correlates of disease. The TND enrolls symptomatic individuals seeking diagnostic testing and compares case status by an exposure variable, such as vaccination status or immune marker level, that is measured at testing. While the TND reduces confounding by healthcare-seeking behavior, other sources of confounding may remain. TND studies may also have missing data in the exposure variable due to incomplete records or two-phase sampling designs. We present a targeted maximum likelihood estimation approach involving a semiparametric logistic regression model that targets a causal conditional risk ratio of symptomatic disease in the healthcare-seeking population. Under causal and missing at random assumptions, our method produces an efficient, asymptotically linear estimator that provides flexible, data-driven confounding control and valid causal inference when analyzing TND studies with missing exposure variable data. We evaluate our method's finite sample properties using plasmode simulations of a two-phase TND immune correlates study. We also apply our method to assess COVID-19 vaccine effectiveness and antibody marker correlates of COVID-19 from TND study cohorts derived from the Moderna Coronavirus Efficacy phase 3 trial.