Modeling treatment effect modification in multidrug-resistant tuberculosis in an individual patientdata meta-analysis

Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and d...

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Vydáno v:Statistical methods in medical research Ročník 31; číslo 4; s. 689
Hlavní autoři: Liu, Yan, Schnitzer, Mireille E, Wang, Guanbo, Kennedy, Edward, Viiklepp, Piret, Vargas, Mario H, Sotgiu, Giovanni, Menzies, Dick, Benedetti, Andrea
Médium: Journal Article
Jazyk:angličtina
Vydáno: England 01.04.2022
Témata:
Biometry
Humans
Observational Studies as Topic
Tuberculosis, Multidrug-Resistant - drug therapy
Conditional average treatment effect
individual patient data
targeted maximum likelihood estimation
meta-analysis
multidrug-resistant tuberculosis
double robustness
marginal structural model
ISSN:1477-0334, 1477-0334
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Shrnutí:Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. However, this task is statistically challenging and typically requires large amounts of data. Investigators may be interested in using the individual patient data from multiple studies to estimate these treatment effect models. Our data arise from a systematic review of observational studies contrasting different treatments for multidrug-resistant tuberculosis, where multiple antimicrobial agents are taken concurrently to cure the infection. We propose a marginal structural model for effect modification by different patient characteristics and co-medications in a meta-analysis of observational individual patient data. We develop, evaluate, and apply a targeted maximum likelihood estimator for the doubly robust estimation of the parameters of the proposed marginal structural model in this context. In particular, we allow for differential availability of treatments across studies, measured confounding within and across studies, and random effects by study.
Bibliografie:ObjectType-Article-1
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ISSN:1477-0334
1477-0334
DOI:10.1177/09622802211046383