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Russell Steele

Publications and source records attributed to Russell Steele.

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Modifying causal models to distinguish between transient and lasting causal effects

This paper considers how to classify the effects of interventions in causal models for outcomes and exposures observed over time. First, we demonstrate the limitations of the most common uses of potential outcomes and causal directed acyclic graphs for capturing all possible interventions in a time varying framework, particularly in problems where the key question concerns interventions to maintain or change equilibrium behaviour. Second, we adopt a system and state based approach rather than a measurement-based approach to identify the causal parameters. In particular, we discuss how assumptions about the system's equilibrium and the effects of interventions on that equilibrium can allow for more specific causal interpretations and clarify the goals of design and analysis. Third, we show how the ability to identify the the causal parameters of a time varying system depends on the selection of timepoints for measuring the system's states. We address this by proposing a novel version of the null effect, which is designed to distinguish between transient and lasting causal effects.

stat.ME

Meta-analysis of median survival times with inverse-variance weighting

We consider the problem of meta-analyzing outcome measures based on median survival times. Primary studies with time-to-event outcomes often report estimates of median survival times and confidence intervals based on the Kaplan-Meier estimator. However, outcome measures based on median survival are rarely meta-analyzed, as standard inverse-variance weighted methods require within-study standard errors that are typically not reported. In this article, we consider an inverse-variance weighted approach to meta-analyze median survival times that estimates the within-study standard errors from the reported confidence intervals. We show that this method consistently estimates the standard error of median survival when applied to confidence intervals constructed by the Brookmeyer-Crowley method. We conduct a series of simulation studies evaluating the performance of this approach at the study level (i.e., for estimating the standard error of median survival) and the meta-analytic level (i.e., for estimating the pooled median, difference of medians, and ratio of medians) for commonly used confidence intervals for median survival, including the Brookmeyer-Crowley method and nonparametric bootstrap. We find that this approach often performs comparably to a benchmark approach that uses the true within-study standard errors for meta-analyzing median-based outcome measures when within-study sample sizes are moderately large (e.g., above 50). However, when the effective sample sizes are small, the method can yield biased estimates of within-study standard errors. We illustrate an application of this approach in a meta-analysis evaluating survival benefits of being assigned to experimental arms versus comparator arms in randomized trials for non-small cell lung cancer therapies.

stat.ME

Simulation Experiments as a Causal Problem

Simulation methods are among the most ubiquitous methodological tools in statistical science. In particular, statisticians often is simulation to explore properties of statistical functionals in models for which developed statistical theory is insufficient or to assess finite sample properties of theoretical results. We show that the design of simulation experiments can be viewed from the perspective of causal intervention on a data generating mechanism. We then demonstrate the use of causal tools and frameworks in this context. Our perspective is agnostic to the particular domain of the simulation experiment which increases the potential impact of our proposed approach. In this paper, we consider two illustrative examples. First, we re-examine a predictive machine learning example from a popular textbook designed to assess the relationship between mean function complexity and the mean-squared error. Second, we discuss a traditional causal inference method problem, simulating the effect of unmeasured confounding on estimation, specifically to illustrate bias amplification. In both cases, applying causal principles and using graphical models with parameters and distributions as nodes in the spirit of influence diagrams can 1) make precise which estimand the simulation targets , 2) suggest modifications to better attain the simulation goals, and 3) provide scaffolding to discuss performance criteria for a particular simulation design.

stat.ME

metamedian: An R package for meta-analyzing studies reporting medians

When performing an aggregate data meta-analysis of a continuous outcome, researchers often come across primary studies that report the sample median of the outcome. However, standard meta-analytic methods typically cannot be directly applied in this setting. In recent years, there has been substantial development in statistical methods to incorporate primary studies reporting sample medians in meta-analysis, yet there are currently no comprehensive software tools implementing these methods. In this paper, we present the metamedian R package, a freely available and open-source software tool for meta-analyzing primary studies that report sample medians. We summarize the main features of the software and illustrate its application through real data examples involving risk factors for a severe course of COVID-19.

stat.ME

Standard error estimation in meta-analysis of studies reporting medians

We consider the setting of an aggregate data meta-analysis of a continuous outcome of interest. When the distribution of the outcome is skewed, it is often the case that some primary studies report the sample mean and standard deviation of the outcome and other studies report the sample median along with the first and third quartiles and/or minimum and maximum values. To perform meta-analysis in this context, a number of approaches have recently been developed to impute the sample mean and standard deviation from studies reporting medians. Then, standard meta-analytic approaches with inverse-variance weighting are applied based on the (imputed) study-specific sample means and standard deviations. In this paper, we illustrate how this common practice can severely underestimate the within-study standard errors, which results in overestimation of between-study heterogeneity in random effects meta-analyses. We propose a straightforward bootstrap approach to estimate the standard errors of the imputed sample means. Our simulation study illustrates how the proposed approach can improve estimation of the within-study standard errors and between-study heterogeneity. Moreover, we apply the proposed approach in a meta-analysis to identify risk factors of a severe course of COVID-19.

stat.ME

Injury risk increases minimally over a large range of changes in activity level in children

Background: Limited research exists on the association between changes in physical activity levels and injury in children. Objective: To assess how well different variations of the acute:chronic workload ratio (ACWR), a measure of change in activity, predict injury in children. Methods: We conducted a prospective cohort study using data from 1670 Danish schoolchildren measured over 5.5 years (2008 to 2014). Coupled 4-week, uncoupled 4-week, and uncoupled 5-week ACWRs were calculated using activity frequency in the past week as the acute load (numerator), and average weekly activity frequency in the past 4 or 5 weeks as the chronic load (denominator). We modelled the relationship between different ACWR variations and injury using generalized linear and generalized additive models, with and without accounting for repeated measures. Results: The prognostic relationship between the ACWR and injury risk was best represented using a generalized additive mixed model for the uncoupled 5-week ACWR. It predicted an injury risk of ~3% for ACWRs between 0.8 (activity level decreased by 20%) and 1.5 (activity level increased by 50%). When activity decreased by more than 20% (ACWR< 0.8), injury risk was lower (minimum of 1.5% at ACWR=0). When activity increased by more than 50% (ACWR > 1.5), injury risk was higher (maximum of 6% at ACWR = 5). Girls were at significantly higher risk of injury than boys. Conclusion: Increases in physical activity in children are associated with much lower injury risks compared to previous results in adults.

q-bio.QM

Implementing multiple imputation for missing data in longitudinal studies when models are not feasible: A tutorial on the random hot deck approach

Objective: Researchers often use model-based multiple imputation to handle missing at random data to minimize bias while making the best use of all available data. However, there are sometimes constraints within the data that make model-based imputation difficult and may result in implausible values. In these contexts, we describe how to use random hot deck imputation to allow for plausible multiple imputation in longitudinal studies. Study Design and Setting: We illustrate random hot deck multiple imputation using The Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-DK), a prospective cohort study that measured weekly sports participation for 1700 Danish schoolchildren. We matched records with missing data to several observed records, generated probabilities for matched records using observed data, and sampled from these records based on the probability of each occurring. Because imputed values are generated randomly, multiple complete datasets can be created and analyzed similar to model-based multiple imputation. Conclusion: Multiple imputation using random hot deck imputation is an alternative method when model-based approaches are infeasible, specifically where there are constraints within and between covariates.

stat.ME

Causal Simulation Experiments: Lessons from Bias Amplification

Recent theoretical work in causal inference has explored an important class of variables which, when conditioned on, may further amplify existing unmeasured confounding bias (bias amplification). Despite this theoretical work, existing simulations of bias amplification in clinical settings have suggested bias amplification may not be as important in many practical cases as suggested in the theoretical literature.We resolve this tension by using tools from the semi-parametric regression literature leading to a general characterization in terms of the geometry of OLS estimators which allows us to extend current results to a larger class of DAGs, functional forms, and distributional assumptions. We further use these results to understand the limitations of current simulation approaches and to propose a new framework for performing causal simulation experiments to compare estimators. We then evaluate the challenges and benefits of extending this simulation approach to the context of a real clinical data set with a binary treatment, laying the groundwork for a principled approach to sensitivity analysis for bias amplification in the presence of unmeasured confounding.

stat.ME

The acute:chronic workload ratio: challenges and prospects for improvement

Injuries occur when an athlete performs a greater amount of activity (workload) than what their body can absorb. To maximize the positive effects of training while avoiding injuries, athletes and coaches need to determine safe workload levels. The International Olympic Committee has recommended using the acute:chronic workload ratio (ACRatio) to monitor injury risk, and has provided thresholds to minimize risk. However, there are several limitations to the ACRatio which may impact the validity of current recommendations. In this review, we discuss previously published and novel challenges with the ACRatio, and possible strategies to address them. These challenges include 1) formulating the ACRatio as a proportion rather than a measure of change, 2) its use of unweighted averages to measure activity loads, 3) inapplicability of the ACRatio to sports where athletes taper their activity, 4) discretization of the ACRatio prior to model selection, 5) the establishment of the model using sparse data, 6) potential bias in the ACRatio of injured athletes, 7) unmeasured confounding, and 8) application of the ACRatio to subsequent injuries.

stat.AP

Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis

Researchers increasingly use meta-analysis to synthesize the results of several studies in order to estimate a common effect. When the outcome variable is continuous, standard meta-analytic approaches assume that the primary studies report the sample mean and standard deviation of the outcome. However, when the outcome is skewed, authors sometimes summarize the data by reporting the sample median and one or both of (i) the minimum and maximum values and (ii) the first and third quartiles, but do not report the mean or standard deviation. To include these studies in meta-analysis, several methods have been developed to estimate the sample mean and standard deviation from the reported summary data. A major limitation of these widely used methods is that they assume that the outcome distribution is normal, which is unlikely to be tenable for studies reporting medians. We propose two novel approaches to estimate the sample mean and standard deviation when data are suspected to be non-normal. Our simulation results and empirical assessments show that the proposed methods often perform better than the existing methods when applied to non-normal data.

stat.ME

Two-sample aggregate data meta-analysis of medians

We consider the problem of meta-analyzing two-group studies that report the median of the outcome. Often, these studies are excluded from meta-analysis because there are no well-established statistical methods to pool the difference of medians. To include these studies in meta-analysis, several authors have recently proposed methods to estimate the sample mean and standard deviation from the median, sample size, and several commonly reported measures of spread. Researchers frequently apply these methods to estimate the difference of means and its variance for each primary study and pool the difference of means using inverse variance weighting. In this work, we develop several methods to directly meta-analyze the difference of medians. We conduct a simulation study evaluating the performance of the proposed median-based methods and the competing transformation-based methods. The simulation results show that the median-based methods outperform the transformation-based methods when meta-analyzing studies that report the median of the outcome, especially when the outcome is skewed. Moreover, we illustrate the various methods on a real-life data set.

stat.ME

One-sample aggregate data meta-analysis of medians

An aggregate data meta-analysis is a statistical method that pools the summary statistics of several selected studies to estimate the outcome of interest. When considering a continuous outcome, typically each study must report the same measure of the outcome variable and its spread (e.g., the sample mean and its standard error). However, some studies may instead report the median along with various measures of spread. Recently, the task of incorporating medians in meta-analysis has been achieved by estimating the sample mean and its standard error from each study that reports a median in order to meta-analyze the means. In this paper, we propose two alternative approaches to meta-analyze data that instead rely on medians. We systematically compare these approaches via simulation study to each other and to methods that transform the study-specific medians and spread into sample means and their standard errors. We demonstrate that the proposed median-based approaches perform better than the transformation-based approaches, especially when applied to skewed data and data with high inter-study variance. In addition, when meta-analyzing data that consists of medians, we show that the median-based approaches perform considerably better than or comparably to the best-case scenario for a transformation approach: conducting a meta-analysis using the actual sample mean and standard error of the mean of each study. Finally, we illustrate these approaches in a meta-analysis of patient delay in tuberculosis diagnosis.

stat.ME

Bayesian Nonparametric Modeling of Heterogeneous Groups of Censored Data

Datasets containing large samples of time-to-event data arising from several small heterogeneous groups are commonly encountered in statistics. This presents problems as they cannot be pooled directly due to their heterogeneity or analyzed individually because of their small sample size. Bayesian nonparametric modelling approaches can be used to model such datasets given their ability to flexibly share information across groups. In this paper, we will compare three popular Bayesian nonparametric methods for modelling the survival functions of heterogeneous groups. Specifically, we will first compare the modelling accuracy of the Dirichlet process, the hierarchical Dirichlet process, and the nested Dirichlet process on simulated datasets of different sizes, where group survival curves differ in shape or in expectation. We, then, will compare the models on a real-world injury dataset.

stat.ML