GfoRmula: An R Package for Estimating the Effects of Sustained Treatment Strategies via the Parametric g-formula.
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ABSTRACT:
SUBMITTER: McGrath S
PROVIDER: S-EPMC7351102 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPolicy decisions regarding climate change mitigation are increasingly incorporating the beneficial and adverse health impacts of greenhouse gas emission reduction strategies. Studies of such co-benefits and co-harms involve modeling approaches requiring a range of analytic decisions that affect the model output.ObjectiveOur objective was to assess analytic decisions regarding model framework, structure, choice of parameters, and handling of uncertainty when modeling health co-benefits, and to make recommendations for improvements that could increase policy uptake.MethodsWe describe the assumptions and analytic decisions underlying models of mitigation co-benefits, examining their effects on modeling outputs, and consider tools for quantifying uncertainty.DiscussionThere is considerable variation in approaches to valuation metrics, discounting methods, uncertainty characterization and propagation, and assessment of low-probability/high-impact events. There is also variable inclusion of adverse impacts of mitigation policies, and limited extension of modeling domains to include implementation considerations. Going forward, co-benefits modeling efforts should be carried out in collaboration with policy makers; these efforts should include the full range of positive and negative impacts and critical uncertainties, as well as a range of discount rates, and should explicitly characterize uncertainty. We make recommendations to improve the rigor and consistency of modeling of health co-benefits.ConclusionModeling health co-benefits requires systematic consideration of the suitability of model assumptions, of what should be included and excluded from the model framework, and how uncertainty should be treated. Increased attention to these and other analytic decisions has the potential to increase the policy relevance and application of co-benefits modeling studies, potentially helping policy makers to maximize mitigation potential while simultaneously improving health.
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Project description:ObjectiveTo compare the effectiveness of dynamic anemia management strategies by applying the parametric g-formula to electronic health records.Data source/study settingPatients with end-stage renal disease from the US Renal Data System who had congestive heart failure or ischemic heart disease and were undergoing hemodialysis in outpatient dialysis facilities between 2006 and 2010.Study designWe explicitly emulated a target trial of three erythropoietin dosing strategies (aimed at achieving a low, middle, or high hematocrit) and estimated the observational analog of the per-protocol effect.ResultsOf 156,945 eligible patients, 41,970 died during the 18-month follow-up. Compared to the low-hematocrit strategy, the estimated risk of death was 4.6 (95% CI 4.4-4.9) percentage points higher under the high-hematocrit strategy and 1.8 (95% CI 1.7-1.9) percentage points higher under the mid-hematocrit strategy. The corresponding risk differences for a composite outcome of death and myocardial infarction were similar.ConclusionAn explicit emulation of a target trial using electronic health records, combined with the parametric g-formula, allowed comparison of real-world dynamic strategies that have not been compared in randomized trials.
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Project description:Many research questions in public health and medicine concern sustained interventions in populations defined by substantive priorities. Existing methods to answer such questions typically require a measured covariate set sufficient to control confounding, which can be questionable in observational studies. Differences-in-differences rely instead on the parallel trends assumption, allowing for some types of time-invariant unmeasured confounding. However, most existing difference-in-differences implementations are limited to point treatments in restricted subpopulations. We derive identification results for population effects of sustained treatments under parallel trends assumptions. In particular, in settings where all individuals begin follow-up with exposure status consistent with the treatment plan of interest but may deviate at later times, a version of Robins' g-formula identifies the intervention-specific mean under stable unit treatment value assumption, positivity, and parallel trends. We develop consistent asymptotically normal estimators based on inverse-probability weighting, outcome regression, and a double robust estimator based on targeted maximum likelihood. Simulation studies confirm theoretical results and support the use of the proposed estimators at realistic sample sizes. As an example, the methods are used to estimate the effect of a hypothetical federal stay-at-home order on all-cause mortality during the COVID-19 pandemic in spring 2020 in the United States.
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Project description:High-resolution methods such as 4C and Capture-C enable the study of chromatin loops such as those formed between promoters and enhancers or CTCF/cohesin binding sites. An important aspect of 4C/CapC analyses is the identification of robust peaks in the data for the identification of chromatin loops. Here we present an R package for the analysis of 4C/CapC data. We generated 4C data for 10 viewpoints in 2 tissues in triplicate to test our methods. We developed a non-parametric peak caller based on rank-products. Sampling analysis shows that not read depth but template quality is the most important determinant of success in 4C experiments. By performing peak calling on single experiments we show that the peak calling results are similar to the replicate experiments, but that false positive rates are significantly reduced by performing replicates.
2018-05-14 | GSE105177 | GEO
Project description:ObjectiveTo demonstrate the performance of methodologies that include machine learning (ML) algorithms to estimate average treatment effects under the assumption of exogeneity (selection on observables).Data sourcesSimulated data and observational data on hospitalized adults.Study designWe assessed the performance of several ML-based estimators, including Targeted Maximum Likelihood Estimation, Bayesian Additive Regression Trees, Causal Random Forests, Double Machine Learning, and Bayesian Causal Forests, applying these methods to simulated data as well as data on the effects of right heart catheterization.Principal findingsIn Monte Carlo studies, ML-based estimators generated estimates with smaller bias than traditional regression approaches, demonstrating substantial (69 percent-98 percent) bias reduction in some scenarios. Bayesian Causal Forests and Double Machine Learning were top performers, although all were sensitive to high dimensional (>150) sets of covariates.ConclusionsML-based methods are promising methods for estimating treatment effects, allowing for the inclusion of many covariates and automating the search for nonlinearities and interactions among variables. We provide guidance and sample code for researchers interested in implementing these tools in their own empirical work.
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Project description:We consider inference for longitudinal data based on mixed-effects models with a non-parametric Bayesian prior on the treatment effect. The proposed non-parametric Bayesian prior is a random partition model with a regression on patient-specific covariates. The main feature and motivation for the proposed model is the use of covariates with a mix of different data formats and possibly high-order interactions in the regression. The regression is not explicitly parameterized. It is implied by the random clustering of subjects. The motivating application is a study of the effect of an anticancer drug on a patient's blood pressure. The study involves blood pressure measurements taken periodically over several 24-h periods for 54 patients. The 24-h periods for each patient include a pretreatment period and several occasions after the start of therapy.
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Project description:BackgroundTopical moisturizing products are widely used to alleviate the problems associated with xerotic skin. Their use affects many properties of the stratum corneum (SC) in a complex and interrelated manner. The range of measurement techniques available to the researcher has increased in recent years. However, few studies have looked for correlations between the different techniques for assessing how aspects of xerotic skin change over time as a result of topical moisturizer usage.ObjectivesA 3-week in vivo study using an oil-in-water based moisturizing product and an untreated site was conducted to determine the clinical significance of and any correlations between a range of different approaches for the measurement of skin lipid content and also skin hydration and visual grading of dry skin.MethodsA range of traditional and more recently developed skin measurement techniques have been used to examine a variety of SC properties in normal and xerotic skin during topical moisturizer usage.ResultsIn vivo confocal Raman spectroscopy and analysis of SC lipids from tape strips both showed an increase in SC lipid level and organization after 3 weeks of moisturizer usage on xerotic skin. Hydration, measured both optically and electrically, also increased and skin barrier function improved, with strong correlations between the different measures of dryness being observed.ConclusionsStrong correlations were observed between the skin measurements for lipid assessment and skin hydration with regard to the assessment of xerotic skin, providing valuable new information for future in vivo clinical research into dry and atopic skin. Keywords biophysical assessment, skin barrier, skin hydration, topical moisturizers, Xerosis.
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