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

TL;DR

This paper introduces a causal framework using Counterfactual Strata Effects and an extended TMLE method to evaluate the total impact of strategies that expand health screening and improve outcomes, addressing complex multilevel data issues.

Contribution

It develops a novel causal estimand and an extended TMLE approach to accurately estimate total effects in multilevel, missing data, cluster-randomized health intervention studies.

Findings

Simulations show the method's effectiveness in estimating total effects.

The approach outperforms existing methods in complex data scenarios.

Limitations of current approaches are demonstrated.

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.