A causal framework for evaluating the total effect of strategies aiming to expand screening and to improve outcomes

Statistics > Methodology [Submitted on 6 Jun 2025 (v1), last revised 17 Jun 2026 (this version, v4)] Title:A causal framework for evaluating the total effect of strategies aiming to expand screening and to improve outcomes View PDF HTML (experimental)Abstract:For many health conditions, there are highly efficacious treatment and prevention products. Maximizing their impact requires strategies that improve the reach of health screening in order to establish who could benefit. For example, HIV prevention strategies aim to expand risk screening and to improve uptake of pre-exposure prophylaxis (PrEP) among those experiencing risk. Often, these strategies induce changes at the group-level (e.g., health clinics or communities) and are evaluated through cluster randomized trials. This scenario creates a complex, multilevel-mediation-missing data problem for the following reasons. First, the strategy is delivered at the cluster-level, while health screening and outcomes are at the individual-level. Second, the strategy improves health outcomes directly and indirectly through improved health screening. Third, everyone has an underlying status, which is only observed among those screened. To formally define the total effect in such settings, we use Counterfactual Strata Effects: causal estimands where the outcome is only relevant for a group whose membership is subject to missingness and/ or impacted by the exposure of interest. To identify and estimate the corresponding statistical estimand, we propose a novel extension of Two-Stage targeted minimum loss-based estimation (TMLE). Simulations demonstrate the practical performance of our approach as well as the limitations of existing approaches. Submission history From: Zora Joy Nakato [view email][v1] Fri, 6 Jun 2025 17:49:44 UTC (76 KB) [v2] Tue, 10 Jun 2025 15:09:50 UTC (76 KB) [v3] Mon, 2 Mar 2026 17:51:46 UTC (168 KB) [v4] Wed, 17 Jun 2026 21:01:15 UTC (166 KB) References & Citations Loading... Bibliographic and Citation Tools Bibliographic Explorer (What is the Explorer?) Connected Papers (What is Connected Papers?) Litmaps (What is Litmaps?) scite Smart Citations (What are Smart Citations?) Code, Data and Media Associated with this Article alphaXiv (What is alphaXiv?) CatalyzeX Code Finder for Papers (What is CatalyzeX?) DagsHub (What is DagsHub?) Gotit.pub (What is GotitPub?) Hugging Face (What is Huggingface?) ScienceCast (What is ScienceCast?) Demos Recommenders and Search Tools Influence Flower (What are Influence Flowers?) CORE Recommender (What is CORE?) arXivLabs: experimental projects with community collaborators arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website. Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them. Have an idea for a project that will add value for arXiv's community? Learn more about arXivLabs.