Dataset Information

Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

ABSTRACT: Estimation of causal effects of time-varying exposures using longitudinal data is a common problem in epidemiology. When there are time-varying confounders, which may include past outcomes, affected by prior exposure, standard regression methods can lead to bias. Methods such as inverse probability weighted estimation of marginal structural models have been developed to address this problem. However, in this paper we show how standard regression methods can be used, even in the presence of time-dependent confounding, to estimate the total effect of an exposure on a subsequent outcome by controlling appropriately for prior exposures, outcomes, and time-varying covariates. We refer to the resulting estimation approach as sequential conditional mean models (SCMMs), which can be fitted using generalized estimating equations. We outline this approach and describe how including propensity score adjustment is advantageous. We compare the causal effects being estimated using SCMMs and marginal structural models, and we compare the two approaches using simulations. SCMMs enable more precise inferences, with greater robustness against model misspecification via propensity score adjustment, and easily accommodate continuous exposures and interactions. A new test for direct effects of past exposures on a subsequent outcome is described.

SUBMITTER: Keogh RH

PROVIDER: S-EPMC5928464 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

Keogh Ruth H RH Daniel Rhian M RM VanderWeele Tyler J TJ Vansteelandt Stijn S

American journal of epidemiology 20180501 5

Estimation of causal effects of time-varying exposures using longitudinal data is a common problem in epidemiology. When there are time-varying confounders, which may include past outcomes, affected by prior exposure, standard regression methods can lead to bias. Methods such as inverse probability weighted estimation of marginal structural models have been developed to address this problem. However, in this paper we show how standard regression methods can be used, even in the presence of time- ...[more]

PMID: 29020128

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Project description:Longitudinal intervention studies with repeated measurements over time are an important type of experimental design in biomedical research. Due to the advent of “omics”-sciences (genomics, transcriptomics, proteomics, metabolomics), longitudinal studies generate increasingly multivariate outcome data. Analysis of such data must take both the longitudinal intervention structure and multivariate nature of the data into account. The ASCA+-framework combines general linear models with principal component analysis and can be used to separate and visualize the multivariate effect of different experimental factors. However, this methodology has not yet been developed for the more complex designs often found in longitudinal intervention studies, which may be unbalanced, involve randomized interventions, and have substantial missing data. Here we describe a new methodology, repeated measures ASCA+ (RM-ASCA+), and show how it can be used to model metabolic changes over time, and compare metabolic changes between groups, in both randomized and non-randomized intervention studies. Tools for both visualization and model validation are discussed. This approach can facilitate easier interpretation of data from longitudinal clinical trials with multivariate outcomes. Author summary Clinical trials are increasingly generating large amounts of complex biological data. Examples can include measuring metabolism or gene expression in tissue or blood sampled repeatedly over the course of a treatment. In such cases, one might wish to compare changes in not one, but hundreds, or thousands of variables simultaneously. In order to effectively analyze such data, both the study design and the multivariate nature of the data should be considered during data analysis. ANOVA simultaneous component analysis+ (ASCA+) is a statistical method which combines general linear models with principal component analysis, and provides a way to separate and visualize the effects of different factors on complex biological data. In this work, we describe how repeated measures linear mixed models, a class of models commonly used when analyzing changes over time and treatment effects in longitudinal studies, can be used together with ASCA+ for analyzing clinical trials in a novel method called repeated measures-ASCA+ (RM-ASCA+).

Project description:ObjectivesTo adjust for confounding in observational data, researchers use propensity score matching (PSM), but more advanced methods might be required when dealing with longitudinal data and time-varying treatments as PSM might not include possible changes that occurred over time. This study aims to explore which confounding adjustment methods have been used in longitudinal observational data to estimate a treatment effect and identify potential inappropriate use of PSM.DesignMapping review.Data sourcesWe searched PubMed, from inception up to January 2021, for studies in which a treatment was evaluated using longitudinal observational data.Eligibility criteriaMethodological, non-medical and cost-effectiveness papers were excluded, as were non-English studies and studies that did not study a treatment effect.Data extraction and synthesisStudies were categorised based on time of treatment: at baseline (interventions performed at start of follow-up) or time-varying (interventions received asynchronously during follow-up) and sorted based on publication year, time of treatment and confounding adjustment method. Cumulative time series plots were used to investigate the use of different methods over time. No risk-of-bias assessment was performed as it was not applicable.ResultsIn total, 764 studies were included that met the eligibility criteria. PSM (165/201, 82%) and inverse probability weighting (IPW; 154/502, 31%) were most common for studies with a treatment at baseline (n=201) and time-varying treatment (n=502), respectively. Of the 502 studies with a time-varying treatment, 123 (25%) used PSM with baseline covariates, which might be inappropriate. In the past 5 years, the proportion of studies with a time-varying treatment that used PSM over IPW increased.ConclusionsPSM is the most frequently used method to correct for confounding in longitudinal observational data. In studies with a time-varying treatment, PSM was potentially inappropriately used in 25% of studies. Confounding adjustment methods designed to deal with a time-varying treatment and time-varying confounding are available, but were only used in 45% of the studies with a time-varying treatment.

Project description:BACKGROUND:In stroke studies, ordinal logistic regression (OLR) is often used to analyze outcome on the modified Rankin Scale (mRS), whereas the non-parametric Mann-Whitney measure of superiority (MWS) has also been suggested. It is unclear how these perform comparatively when confounding adjustment is warranted. AIMS:Our aim is to quantify the performance of OLR and MWS in different confounding variable settings. METHODS:We set up a simulation study with three different scenarios; (1) dichotomous confounding variables, (2) continuous confounding variables, and (3) confounding variable settings mimicking a study on functional outcome after stroke. We compared adjusted ordinal logistic regression (aOLR) and stratified Mann-Whitney measure of superiority (sMWS), and also used propensity scores to stratify the MWS (psMWS). For comparability, OLR estimates were transformed to a MWS. We report bias, the percentage of runs that produced a point estimate deviating by more than 0.05 points (point estimate variation), and the coverage probability. RESULTS:In scenario 1, there was no bias in both sMWS and aOLR, with similar point estimate variation and coverage probabilities. In scenario 2, sMWS resulted in more bias (0.04 versus 0.00), and higher point estimate variation (41.6% versus 3.3%), whereas coverage probabilities were similar. In scenario 3, there was no bias in both methods, point estimate variation was higher in the sMWS (6.7%) versus aOLR (1.1%), and coverage probabilities were 0.98 (sMWS) versus 0.95 (aOLR). With psMWS, bias remained 0.00, with less point estimate variation (1.5%) and a coverage probability of 0.95. CONCLUSIONS:The bias of both adjustment methods was similar in our stroke simulation scenario, and the higher point estimate variation in the MWS improved with propensity score based stratification. The stratified MWS is a valid alternative for adjusted OLR only when the ratio of number of strata versus number of observations is relatively low, but propensity score based stratification extends the application range of the MWS.

Dataset Information

Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

Publications

Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

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