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Statistics in Medicine
Article . 2024 . Peer-reviewed
License: Wiley Online Library User Agreement
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zbMATH Open
Article . 2024
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https://dx.doi.org/10.48550/ar...
Article . 2021
License: CC BY
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Causal mediation analysis with mediator values below an assay limit

Authors: Ariel Chernofsky; Ronald J. Bosch; Judith J. Lok;

Causal mediation analysis with mediator values below an assay limit

Abstract

Causal indirect and direct effects provide an interpretable method for decomposing the total effect of an exposure on an outcome into the indirect effect through a mediator and the direct effect through all other pathways. A natural choice for a mediator in a randomized clinical trial is the treatment's targeted biomarker. However, when the mediator is a biomarker, values can be subject to an assay lower limit. The mediator is affected by the treatment and is a putative cause of the outcome, so the assay lower limit presents a compounded problem in mediation analysis. We propose two approaches to estimate indirect and direct effects with a mediator subject to an assay limit: (1) extrapolation and (2) numerical optimization and integration of the observed likelihood. Since these estimation methods solely rely on the so‐called Mediation Formula, they apply to most approaches to causal mediation analysis: natural, separable, and organic indirect, and direct effects. A simulation study compares the two estimation approaches to imputing with half the assay limit. Using HIV interruption study data from the AIDS Clinical Trials Group described in Li et al 2016, AIDS; Lok and Bosch 2021, Epidemiology, we illustrate our methods by estimating the organic/pure indirect effect of a hypothetical HIV curative treatment on viral suppression mediated by two HIV persistence measures: cell‐associated HIV‐RNA and single‐copy plasma HIV‐RNA.

Keywords

FOS: Computer and information sciences, Likelihood Functions, assay lower limit, Mediation Analysis, Models, Statistical, Anti-HIV Agents, HIV Infections, Applications of statistics to biology and medical sciences; meta analysis, Causality, Methodology (stat.ME), causal mediation analysis, HIV/AIDS, Humans, Computer Simulation, causal inference, indirect and direct effects, Statistics - Methodology, Biomarkers, Randomized Controlled Trials as Topic

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
Green