Simulation-Guided Planning of a Target Trial Emulated Cluster Randomized Trial for Mass Small-Quantity Lipid Nutrient Supplementation Combined with Expanded Program on Immunization in Rural Niger

Fuente: arXiv
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Autores principales: Alam, Shomoita, Dyrkton, Nathaniel, Shepherd, Susan, Sana, Ibrahim, Phelan, Kevin, Park, Jay JH
Formato: Preprint
Publicado: 2025
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author Alam, Shomoita
Dyrkton, Nathaniel
Shepherd, Susan
Sana, Ibrahim
Phelan, Kevin
Park, Jay JH
author_facet Alam, Shomoita
Dyrkton, Nathaniel
Shepherd, Susan
Sana, Ibrahim
Phelan, Kevin
Park, Jay JH
contents Background: Target trial emulation (TTE) that applies trial design principles to improve the analysis of non-randomized studies is increasingly being used. Applications of TTE to emulate cluster randomized trials (RCTs) have been limited. This study explored how to integrate simulation-guided design into the TTE framework to inform planning of a non-randomized cluster trial. Methods: We performed simulations to prospectively plan data collection of a non-randomized study emulating a village-level cluster RCT when cluster-randomization was infeasible. The planned study will assess the impact of mass distribution of nutritional supplements embedded within an existing immunization program to improve pentavalent vaccination rates among children 12-24 months old in Niger. The design included covariate-constrained random selection of villages for outcome ascertainment at follow-up. Simulations used baseline census data on pentavalent vaccination rates and cluster-level covariates to compare the type I error rate and power of four statistical methods: beta-regression; quasi-binomial regression; inverse probability of treatment weighting (IPTW); and naive Wald test. Results: Of the four analytic methods considered, only IPTW and beta-regression controlled the type I error rate at 0.05, but IPTW yielded poor statistical power. Beta-regression that showed adequate statistical power was chosen as our primary analysis. Conclusions: Adopting simulation-guided design principles within TTE can enable robust planning of a group-level non-randomized study emulating a cluster RCT. Lessons from this study also apply to TTE planning of individually-RCTs.
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publishDate 2025
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spellingShingle Simulation-Guided Planning of a Target Trial Emulated Cluster Randomized Trial for Mass Small-Quantity Lipid Nutrient Supplementation Combined with Expanded Program on Immunization in Rural Niger
Alam, Shomoita
Dyrkton, Nathaniel
Shepherd, Susan
Sana, Ibrahim
Phelan, Kevin
Park, Jay JH
Applications
Methodology
Background: Target trial emulation (TTE) that applies trial design principles to improve the analysis of non-randomized studies is increasingly being used. Applications of TTE to emulate cluster randomized trials (RCTs) have been limited. This study explored how to integrate simulation-guided design into the TTE framework to inform planning of a non-randomized cluster trial. Methods: We performed simulations to prospectively plan data collection of a non-randomized study emulating a village-level cluster RCT when cluster-randomization was infeasible. The planned study will assess the impact of mass distribution of nutritional supplements embedded within an existing immunization program to improve pentavalent vaccination rates among children 12-24 months old in Niger. The design included covariate-constrained random selection of villages for outcome ascertainment at follow-up. Simulations used baseline census data on pentavalent vaccination rates and cluster-level covariates to compare the type I error rate and power of four statistical methods: beta-regression; quasi-binomial regression; inverse probability of treatment weighting (IPTW); and naive Wald test. Results: Of the four analytic methods considered, only IPTW and beta-regression controlled the type I error rate at 0.05, but IPTW yielded poor statistical power. Beta-regression that showed adequate statistical power was chosen as our primary analysis. Conclusions: Adopting simulation-guided design principles within TTE can enable robust planning of a group-level non-randomized study emulating a cluster RCT. Lessons from this study also apply to TTE planning of individually-RCTs.
title Simulation-Guided Planning of a Target Trial Emulated Cluster Randomized Trial for Mass Small-Quantity Lipid Nutrient Supplementation Combined with Expanded Program on Immunization in Rural Niger
topic Applications
Methodology
url https://arxiv.org/abs/2510.19077