scholarly journals Correction to: Graphing and reporting heterogeneous treatment effects through reference classes

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
James A. Watson ◽  
Chris C. Holmes

An amendment to this paper has been published and can be accessed via the original article.

2019 ◽  
Author(s):  
James A. Watson ◽  
Chris C. Holmes

AbstractBackgroundExploration and modelling of individual treatment effects and treatment heterogeneity is an important aspect of precision medicine in randomized controlled trials (RCTs). The usual approach is to develop a predictive model for individual outcomes and then look for an interaction effect between treatment allocation and important patient covariates. However, such models are prone to overfitting and multiple testing, and typically demand a transformation of the outcome measurement, for example, from the absolute risk in the original RCT to log-odds of risk in the predictive model.MethodsWe show how reference classes derived from background information can be used to alleviate this problem through a two-stage approach where we first estimate a key aspect of heterogeneity in the trial population and then explore for an interaction with the treatment effect along this axis of variation. This bypasses the search for interactions, protecting against multiple testing, and allows for exploration of heterogeneous treatment effects on the original outcome scale of the RCT. This would typically be applied to multivariate models of baseline risk to assess the stability of average treatment effects with respect to the distribution of risk in the population studied. We show how ‘local’ and ‘tilting’ schemes based on ranking patients by baseline risk can be used as a general approach for exploring heterogeneity of treatment effect.ResultsWe illustrate this approach using the single largest randomised treatment trial in severe falciparum malaria and show how the estimated treatment effect in terms of absolute mortality risk reduction increases considerably for higher risk strata.


Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
James A. Watson ◽  
Chris C. Holmes

Abstract Background Exploration and modelling of heterogeneous treatment effects as a function of baseline covariates is an important aspect of precision medicine in randomised controlled trials (RCTs). Randomisation generally guarantees the internal validity of an RCT, but heterogeneity in treatment effect can reduce external validity. Estimation of heterogeneous treatment effects is usually done via a predictive model for individual outcomes, where one searches for interactions between treatment allocation and important patient baseline covariates. However, such models are prone to overfitting and multiple testing and typically demand a transformation of the outcome measurement, for example, from the absolute risk in the original RCT to log-odds of risk in the predictive model. Methods We show how reference classes derived from baseline covariates can be used to explore heterogeneous treatment effects via a two-stage approach. We first estimate a risk score which captures on a single dimension some of the heterogeneity in outcomes of the trial population. Heterogeneity in the treatment effect can then be explored via reweighting schemes along this axis of variation. This two-stage approach bypasses the search for interactions with multiple covariates, thus protecting against multiple testing. It also allows for exploration of heterogeneous treatment effects on the original outcome scale of the RCT. This approach would typically be applied to multivariable models of baseline risk to assess the stability of average treatment effects with respect to the distribution of risk in the population studied. Case study We illustrate this approach using the single largest randomised treatment trial in severe falciparum malaria and demonstrate how the estimated treatment effect in terms of absolute mortality risk reduction increases considerably in higher risk strata. Conclusions ‘Local’ and ‘tilting’ reweighting schemes based on ranking patients by baseline risk can be used as a general approach for exploring, graphing and reporting heterogeneity of treatment effect in RCTs. Trial registration ISRCTN clinical trials registry: ISRCTN50258054. Prospectively registered on 22 July 2005.


2017 ◽  
Vol 25 (4) ◽  
pp. 413-434 ◽  
Author(s):  
Justin Grimmer ◽  
Solomon Messing ◽  
Sean J. Westwood

Randomized experiments are increasingly used to study political phenomena because they can credibly estimate the average effect of a treatment on a population of interest. But political scientists are often interested in how effects vary across subpopulations—heterogeneous treatment effects—and how differences in the content of the treatment affects responses—the response to heterogeneous treatments. Several new methods have been introduced to estimate heterogeneous effects, but it is difficult to know if a method will perform well for a particular data set. Rather than using only one method, we show how an ensemble of methods—weighted averages of estimates from individual models increasingly used in machine learning—accurately measure heterogeneous effects. Building on a large literature on ensemble methods, we show how the weighting of methods can contribute to accurate estimation of heterogeneous treatment effects and demonstrate how pooling models lead to superior performance to individual methods across diverse problems. We apply the ensemble method to two experiments, illuminating how the ensemble method for heterogeneous treatment effects facilitates exploratory analysis of treatment effects.


2019 ◽  
Vol 116 (10) ◽  
pp. 4156-4165 ◽  
Author(s):  
Sören R. Künzel ◽  
Jasjeet S. Sekhon ◽  
Peter J. Bickel ◽  
Bin Yu

There is growing interest in estimating and analyzing heterogeneous treatment effects in experimental and observational studies. We describe a number of metaalgorithms that can take advantage of any supervised learning or regression method in machine learning and statistics to estimate the conditional average treatment effect (CATE) function. Metaalgorithms build on base algorithms—such as random forests (RFs), Bayesian additive regression trees (BARTs), or neural networks—to estimate the CATE, a function that the base algorithms are not designed to estimate directly. We introduce a metaalgorithm, the X-learner, that is provably efficient when the number of units in one treatment group is much larger than in the other and can exploit structural properties of the CATE function. For example, if the CATE function is linear and the response functions in treatment and control are Lipschitz-continuous, the X-learner can still achieve the parametric rate under regularity conditions. We then introduce versions of the X-learner that use RF and BART as base learners. In extensive simulation studies, the X-learner performs favorably, although none of the metalearners is uniformly the best. In two persuasion field experiments from political science, we demonstrate how our X-learner can be used to target treatment regimes and to shed light on underlying mechanisms. A software package is provided that implements our methods.


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