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• The paper presents a set of relaxed conditions under which the natural direct effect is identifiable despite unobserved baseline confounding of the exposure-mediator pathway.method 95%
• The natural direct and indirect effects have limited practical utility due to stringent identification requirements.limitation 90%
• The paper demonstrates the construction of flexible, multiply robust estimators of the natural direct effect.method 90%
• The paper discusses efficient estimation strategies that do not place restrictive modeling assumptions on nuisance functions.method 85%
• The research is motivated by a secondary aim of a recent non-randomized vaccine prospective cohort study (NCT05168813).technical 95%
• The paper relaxes the commonly used but restrictive cross-world counterfactual independence assumption.method 90%
• The paper discusses strategies for evaluating the natural direct effect in non-randomized settings that arise in vaccine studies.method 85%
• The paper applies the method to investigate the effect mediated by putative immune correlates of protection.result 85%

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