Causal inference in randomized trials with partial clustering.

Background: Participant dependence, if present, must be accounted for in the analysis of randomized trials. This dependence, also referred to as "clustering," can occur in one or more trial arms. This dependence may predate randomization or arise after randomization. We examine three trial designs:...

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Publicado en:Clinical Trials Vol. 22; no. 5; pp. 547 - 559
Autores principales: Nugent, Joshua R, Kakande, Elijah, Chamie, Gabriel, Kabami, Jane, Owaraganise, Asiphas, Havlir, Diane V, Kamya, Moses, Balzer, Laura B
Formato: equations & formulas research tables/charts Journal Article
Publicado: Sage Publications, Ltd. Oct2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Oct2025
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        atl: Causal inference in randomized trials with partial clustering.
      aug:
        au:
          Nugent, Joshua R
          Kakande, Elijah
          Chamie, Gabriel
          Kabami, Jane
          Owaraganise, Asiphas
          Havlir, Diane V
          Kamya, Moses
          Balzer, Laura B
        affil: Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, USA
      sug:
        subj:
          Randomized Controlled Trials Methods
          Cluster Sample
          Research Subjects
          Control Group
          Models, Statistical
          Machine Learning
          Human
          Uganda
          Health Personnel
          Comparative Studies
          Tuberculosis Prevention and Control
          Multiple Regression
          Descriptive Statistics
          Data Analysis Software
          Funding Source
          Nonparametric Statistics
      ab: Background: Participant dependence, if present, must be accounted for in the analysis of randomized trials. This dependence, also referred to as "clustering," can occur in one or more trial arms. This dependence may predate randomization or arise after randomization. We examine three trial designs: one "fully clustered" (where all participants are dependent within clusters or groups) and two "partially clustered" (where some participants are dependent within clusters and some participants are completely independent of all others). Methods: For these three designs, we (1) use causal models to non-parametrically describe the data generating process and formalize the dependence in the observed data distribution; (2) develop a novel implementation of targeted minimum loss-based estimation for analysis; (3) evaluate the finite-sample performance of targeted minimum loss-based estimation and common alternatives via a simulation study; and (4) apply the methods to real-data from the SEARCH-IPT trial. Results: We show that the two randomization schemes resulting in partially clustered trials have the same dependence structure, enabling use of the same statistical methods for estimation and inference of causal effects. Our novel targeted minimum loss-based estimation approach leverages covariate adjustment and machine learning to improve precision and facilitates estimation of a large set of causal effects. In simulations, we demonstrate that targeted minimum loss-based estimation achieves comparable or markedly higher statistical power than common alternatives for these partially clustered designs. Finally, application of targeted minimum loss-based estimation to real data from the SEARCH-IPT trial resulted in 20%–57% efficiency gains, demonstrating the real-world consequences of our proposed approach. Conclusions: Partially clustered trial analysis can be made more efficient by implementing targeted minimum loss-based estimation, assuming care is taken to account for the dependent nature of the observed data.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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