Conditional Average Treatment Effect Research Articles

Finding the best subgroup with differential treatment effect with multiple outcomes.

Precision medicine aims to identify specific patient subgroups that may benefit the most from a particular treatment than the whole population. Existing definitions for the best subgroup in subgroup analysis are based on a single outcome and do not consider multiple outcomes; specifically, outcomes of different types. In this article, we introduce a definition for the best subgroup under a multiple-outcome setting with continuous, binary, and censored time-to-event outcomes. Our definition provides a trade-off between the subgroup size and the conditional average treatment effects (CATE) in the subgroup with respect to each of the outcomes while taking the relative contribution of the outcomes into account. We conduct simulations to illustrate the proposed definition. By examining the outcomes of urinary tract infection and renal scarring in the RIVUR clinical trial, we identify a subgroup of children that would benefit the most from long-term antimicrobial prophylaxis.

Heterogeneity of the effect of the COVID-19 pandemic on the incidence of Metabolic Syndrome onset at a Japanese campus.

The coronavirus disease 2019 (COVID-19) outbreak began in China in December 2019, with the World Health Organization declaring a state of emergency in January 2020. Worldwide implementation of lockdown measures to slow the spread of the virus led to reduced physical activity, disrupted eating habits, mental health issues, and sleep disturbances, which increased the risk of lifestyle-related diseases such as metabolic syndrome (MetS). During the COVID-19 pandemic, healthcare workers, especially intensive care workers, experienced longer working hours and burnout, which further increased the risk of lifestyle-related diseases. Accordingly, it is important to identify individuals at a risk of new-onset MetS during a pandemic, which could direct preventive interventions. This study aimed to assess the heterogeneous impact of the COVID-19 pandemic on the incidence of new-onset MetS based on the conditional average treatment effect (CATE) and to identify at-risk populations. This study analyzed health checkup data obtained from Okayama University Shikata Campus workers using paired baseline and follow-up years. Baseline data encompassed 2017 to 2019, with respective follow-up data from 2018 to 2020. Furthermore, as the COVID-19 pandemic in Japan began in January 2020, workers who underwent follow-up health checkups in 2018 to 2019 and 2020 were considered as "unexposed" and "exposed," respectively. As the Shikata campus has several departments, comparisons among departments were made. The primary outcome was new-onset MetS at follow-up. Predictor variables included baseline health checkup results, sex, age, and department (administrative, research, medical, or intensive care department). X-learner was used to calculate the CATE. This study included 3,572 eligible individuals (unexposed, n=2,181; exposed, n=1,391). Among them, 1,544 (70.8%) and 866 (62.3%) participants in the unexposed and exposed groups, respectively, were females. The mean age (±standard deviation) of the unexposed and exposed groups was 48.2 ± 8.2 and 47.8 ± 8.3 years, respectively. The COVID-19 pandemic increased the average probability of new-onset MetS by 4.4% in the overall population. According to the department, the intensive care department showed the highest CATE, with a 15.4% increase. Moreover, there was large heterogeneity according to the department. The high-CATE group was characterized by older age, urinary protein, elevated liver enzymes, higher triglyceride levels, and a history of hyperlipidemia treatment. This study demonstrated that the COVID-19 pandemic increased the incidence of new-onset MetS, with this effect showing heterogeneity at a single Japanese campus. Regarding specific populations, workers in the intensive care department showed an increased risk of new-onset MetS. At-risk populations require specific preventive interventions in case the current COVID-19 pandemic persists or a new pandemic occurs.

Estimating conditional average treatment effects with heteroscedasticity by model averaging and matching

We propose a model averaging approach, combined with a partition and matching method to estimate the conditional average treatment effects under heteroskedastic error settings. The proposed approach has asymptotic optimality and consistency of weights and estimator. Numerical studies show that our method has good finite-sample performances.

다중비교 인과포레스트를 활용한 대학입학전형에 따른 대학생활 성과 분석

Over the years, university admission types have primarily been the subject of social discussions on the
 dimension of fairness. However, considering the original purpose of university admissions system, it is also
 crucial to evaluate how well each type performs in selecting students who can successfully navigate academic
 life at each university. Accordingly, this study aimed to analyze the university life outcomes (sense of
 belonging, adaptability, intention to reselect the university, intention to reselect the major, GPA) according
 to different university admissions types: the admission officer(AO) system, high school grade-focused(HSG)
 selection system, and College Scholastic Ability Test-focused(CSAT) selection system, using the data from the
 Korea Education Longitudinal Study(KELS) 2013 collected in ’20~’21(N=2,011). Assuming the effects may
 vary according to the baseline characteristics, the study employs the Conditional Average Treatment Effects
 (CATE) perspective through the Multi-arm Causal Forest technique(Athey, Tibshirani, & Wager, 2019). The
 main findings are summarized as follows: First, on average, students admitted through AO system exhibit
 superior outcomes across all considered aspects of college life, with a notable emphasis on higher intentions
 to reselect both the university and major. Second, it appears that parental income and education, high
 school academic achievement levels and their university-level average were significant conditioning variables
 predicting heterogeneous treatment effects on college life outcomes. Last, the effect heterogeneity of CSAT
 system, depending on the values of major conditioning variables, was more prominent compared to that of
 AO system. Based on these findings, suggestions for interpreting the research results and directions for
 future studies were provided.

Heterogeneous Association of Tooth Loss with Functional Limitations

Tooth loss is prevalent in older adults and associated with functional capacity decline. Studies on the susceptibility of some individuals to the effects of tooth loss are lacking. This study aimed to investigate the heterogeneity of the association between tooth loss and higher-level functional capacity in older Japanese individuals employing a machine learning approach. This is a prospective cohort study using the data of adults aged ≥65 y in Japan (N = 16,553). Higher-level functional capacity, comprising instrumental independence, intellectual activity, and social role, was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The scale ranged from 0 (lowest function) to 13 (highest function). Doubly robust targeted maximum likelihood estimation was used to estimate the population-average association between tooth loss (having <20 natural teeth) and TMIG-IC total score after 6 y. The heterogeneity of the association was evaluated by estimating conditional average treatment effects (CATEs) using the causal forest algorithm. The result showed that tooth loss was statistically significantly associated with lower TMIG-IC total scores (population-average effect: −0.14; 95% confidence interval, −0.18 to −0.09). The causal forest analysis revealed the heterogeneous associations between tooth loss and lower TMIG-IC total score after 6 y (median of estimated CATEs = −0.13; interquartile range = 0.12). The high-impact subgroup (i.e., individuals with estimated CATEs of the bottom 10%) were significantly more likely to be older and male, had a lower socioeconomic status, did not have a partner, and had poor health conditions compared with the low-impact subgroup (i.e., individuals with estimated CATEs of the top 10%). This study found that heterogeneity exists in the association between tooth loss and lower scores on functional capacity. Implementing tooth loss prevention policy and clinical measures, especially among vulnerable subpopulations significantly affected by tooth loss, may reduce its burden more effectively.

Treatment Allocation with Strategic Agents

There is increasing interest in allocating treatments based on observed individual characteristics: examples include targeted marketing, individualized credit offers, and heterogeneous pricing. Treatment personalization introduces incentives for individuals to modify their behavior to obtain a better treatment. Strategic behavior shifts the joint distribution of covariates and potential outcomes. The optimal rule without strategic behavior allocates treatments only to those with a positive conditional average treatment effect. With strategic behavior, we show that the optimal rule can involve randomization, allocating treatments with less than 100% probability even to those who respond positively on average to the treatment. We propose a sequential experiment based on Bayesian optimization that converges to the optimal treatment rule without parametric assumptions on individual strategic behavior. This paper was accepted by Vivek Farias, data science. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2022.01629 .

Phenotype-based targeted treatment of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes

Aims/hypothesisA precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA).MethodsWe designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA1c) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]). Differences in glycaemic outcome with GLP1-RA by sex seen in clinical data were replicated in clinical trial data (HARMONY programme: liraglutide [n=389] and albiglutide [n=1682]). As secondary outcomes, we evaluated the impacts of targeting therapy based on glycaemic response on weight change, tolerability and longer-term risk of new-onset microvascular complications, macrovascular complications and adverse kidney events.ResultsModel development identified marked heterogeneity in glycaemic response, with 4787 (17.5%) of the development cohort having a predicted HbA1c benefit >3 mmol/mol (>0.3%) with SGLT2i over GLP1-RA and 5551 (20.3%) having a predicted HbA1c benefit >3 mmol/mol with GLP1-RA over SGLT2i. Calibration was good in hold-back validation, and external validation in an independent Scottish dataset identified clear differences in glycaemic outcomes between those predicted to benefit from each therapy. Sex, with women markedly more responsive to GLP1-RA, was identified as a major treatment effect modifier in both the UK observational datasets and in clinical trial data: HARMONY-7 liraglutide (GLP1-RA): 4.4 mmol/mol (95% credible interval [95% CrI] 2.2, 6.3) (0.4% [95% CrI 0.2, 0.6]) greater response in women than men. Targeting the two therapies based on predicted glycaemic response was also associated with improvements in short-term tolerability and long-term risk of new-onset microvascular complications.Conclusions/interpretationPrecision medicine approaches can facilitate effective individualised treatment choice between SGLT2i and GLP1-RA therapies, and the use of routinely collected clinical features for treatment selection could support low-cost deployment in many countries.Graphical

The impact of early childhood education and medical care on children

Causal inference is a statistical approach that aims to understand and quantify the causal relationship between variables, allowing us to determine the impact of one variable on another while accounting for potential confounding factors. In this study, we chose the Infant Health and Development Program (IHDP) dataset to test whether high-quality early childhood education and medical care will enhance their cognitive and academic ability. We use some common and classic algorithms to achieve this study by calculating the CATE (Conditional Average Treatment Effect) of the dataset; if the result is a negative number, that means early treatment doesn’t improve children’s further ability; if the result is a positive number, that means treatment improves it. After fitting the targeted models, BART(Bayesian Additive Regression Trees) and Metalearners, into this dataset, we found out that all the models will get positive CATE, which means that these early treatments positively affect children’s future development. Also, we can judge which model gives us a more accurate result according to the standard variance of TE(treatment effect). The result of this study will provide us with an insightful idea about whether we should give children some treatments regarding education and medical care and which model is more suitable for this casual inference test.

Harnessing Causal Forests for Epidemiologic Research: Key Consideration.

Assessing heterogeneous treatment effects (HTEs) is an essential task in epidemiology. The recent integration of machine learning into causal inference has provided a new, flexible tool for evaluating complex HTEs: causal forest. Jawadekar et al. (Am J Epidemiol. 2023) introduce this innovative approach and offer practical guidelines for applied users. Building on their work, this commentary provides additional insights and guidance to promote the understanding and application of causal forest in epidemiologic research. We start with conceptual clarifications, differentiating between honesty and cross-fitting, and exploring the interpretation of estimated conditional average treatment effects. We then delve into the following practical considerations not addressed by Jawadekar et al., including motivations for estimating HTEs, calibration approaches, and ways to leverage causal forest output with examples from simulated data. We conclude by outlining challenges to consider for future advancements and applications of causal forest in epidemiological research.

BENK: The Beran Estimator with Neural Kernels for Estimating the Heterogeneous Treatment Effect

A method for estimating the conditional average treatment effect under the condition of censored time-to-event data, called BENK (the Beran Estimator with Neural Kernels), is proposed. The main idea behind the method is to apply the Beran estimator for estimating the survival functions of controls and treatments. Instead of typical kernel functions in the Beran estimator, it is proposed to implement kernels in the form of neural networks of a specific form, called neural kernels. The conditional average treatment effect is estimated by using the survival functions as outcomes of the control and treatment neural networks, which consist of a set of neural kernels with shared parameters. The neural kernels are more flexible and can accurately model a complex location structure of feature vectors. BENK does not require a large dataset for training due to its special way for training networks by means of pairs of examples from the control and treatment groups. The proposed method extends a set of models that estimate the conditional average treatment effect. Various numerical simulation experiments illustrate BENK and compare it with the well-known T-learner, S-learner and X-learner for several types of control and treatment outcome functions based on the Cox models, the random survival forest and the Beran estimator with Gaussian kernels. The code of the proposed algorithms implementing BENK is publicly available.

Climate smart agriculture impact on food and nutrition security in Ethiopia

IntroductionThe objective of this study was to analyze how innovations in Climate-smart agriculture (CSA) contribute to improving the food and nutrition security of smallholder households, thereby promoting sustainable food systems.MethodsA cross-sectional household survey was conducted among a multi-stage sample of 424 smallholder farmers drawn from five different agroecosystems. To examine households’ food and nutrition security, we used food consumption score (FCS) and modified household dietary diversity score (HDDS) in propensity score matching (PSM) and endogenous switching regression (ESR) estimation models.ResultsPSM results showed that crop residue management, compost, and agroforestry have a significant effect on improving households’ food and nutrition security by 21.3, 13.6, and 16.6%, respectively, whereas Soil and water conservation (SWC) has reduced adopters’ food security by 12.9%. However, the conditional average treatment effect, or ESR result, reveals that households’ food and nutrition security has improved as a result of the adoption of crop residue management, compost, SWC, and agroforestry.DiscussionAlthough the impact of crop residue management, compost, and agroforestry is positive, the effect of SWC on household food security has been inconclusive. Hence, it is important to upscale the adoption of multiple CSA innovations to improve smallholder household’s food security in the face of climate change.

Dirichlet process mixture models to impute missing predictor data in counterfactual prediction models: an application to predict optimal type 2 diabetes therapy

BackgroundThe handling of missing data is a challenge for inference and regression modelling. A particular challenge is dealing with missing predictor information, particularly when trying to build and make predictions from models for use in clinical practice.MethodsWe utilise a flexible Bayesian approach for handling missing predictor information in regression models. This provides practitioners with full posterior predictive distributions for both the missing predictor information (conditional on the observed predictors) and the outcome-of-interest. We apply this approach to a previously proposed counterfactual treatment selection model for type 2 diabetes second-line therapies. Our approach combines a regression model and a Dirichlet process mixture model (DPMM), where the former defines the treatment selection model, and the latter provides a flexible way to model the joint distribution of the predictors.ResultsWe show that DPMMs can model complex relationships between predictor variables and can provide powerful means of fitting models to incomplete data (under missing-completely-at-random and missing-at-random assumptions). This framework ensures that the posterior distribution for the parameters and the conditional average treatment effect estimates automatically reflect the additional uncertainties associated with missing data due to the hierarchical model structure. We also demonstrate that in the presence of multiple missing predictors, the DPMM model can be used to explore which variable(s), if collected, could provide the most additional information about the likely outcome.ConclusionsWhen developing clinical prediction models, DPMMs offer a flexible way to model complex covariate structures and handle missing predictor information. DPMM-based counterfactual prediction models can also provide additional information to support clinical decision-making, including allowing predictions with appropriate uncertainty to be made for individuals with incomplete predictor data.

Triple/Debiased Lasso for Statistical Inference of Conditional Average Treatment Effects

Triple/Debiased Lasso for Statistical Inference of Conditional Average Treatment Effects

인과 포레스트를 이용한 벤처기업 사회적 활동의 매출액에 대한 효과 분석

The impact of corporate's social activities on sustainable management is increasing, and this is not just for large companies, but also expanding to small and medium-sized companies and venture companies. Accordingly, in this paper, the effect of the social activities of venture companies on sales was empirically analyzed through the Causal Forest method. Causal Forest is a machine learning model that allows the effect (treatment effect) of the variable of interest to be tested through causal reasoning after controlling several other characteristic variables that affect the objective variable through random forest modeling. As a result of empirical analysis using detailed survey data of venture companies from 2015 to 2020, it was confirmed that the social activities of venture companies had a significant average treatment effect (ATE) on sales. In addition, it was confirmed that the difference in the individual conditional average treatment effect (CATE) on the sales of social activities was significant depending on the size of the company's debt and the degree of investment activation. At this time, the treatment effect of companies with low total debt and low investment activation was widely distributed, which can be attributed to the characteristics of venture companies that focus on investment and technological innovation and show various corporate forms.

Revisiting the analysis of matched‐pair and stratified experiments in the presence of attrition

AbstractIn this paper, we revisit some common recommendations regarding the analysis of matched‐pair and stratified experimental designs in the presence of attrition. Our main objective is to clarify a number of well‐known claims about the practice of dropping pairs with an attrited unit when analyzing matched‐pair designs. Contradictory advice appears in the literature about whether or not dropping pairs is beneficial or harmful, and stratifying into larger groups has been recommended as a resolution to the issue. To address these claims, we derive the estimands obtained from the difference‐in‐means estimator in a matched‐pair design both when the observations from pairs with an attrited unit are retained and when they are dropped. We find limited evidence to support the claims that dropping pairs helps recover the average treatment effect, but we find that it may potentially help in recovering a convex‐weighted average of conditional average treatment effects. We report similar findings for stratified designs when studying the estimands obtained from a regression of outcomes on treatment with and without strata fixed effects.

Does informing citizens about the non-meritocratic nature of inequality bolster support for a universal basic income? Evidence from a population-based survey experiment

ABSTRACT Despite citizens’ precarization and policymakers’ enthusiasm for a universal basic income (UBI), this alternative to targeted welfare has, curiously, received limited popular support. We theorize that this is due to people overestimating society’s meritocratic nature. Accordingly, we field a randomized survey experiment with a representative sample of the Dutch population (n = 1,630) to investigate the impact of information provision about the non-meritocratic nature of wealth and ethnic inequality on support for a UBI. Informed by extant research indicating that citizens respond differently to the same information because of material circumstances or different worldviews, we further estimate conditional average treatment effects to explore moderation by (1) income, (2) economic egalitarianism, (3) welfare chauvinism and (4) institutional trust. We find that support for a UBI is higher among individuals with lower incomes and those who are more egalitarian and less welfare chauvinistic. Nonetheless, while exposure to our factual treatment makes participants more concerned about inequality and supportive of economic redistribution in general, it neither directly nor conditionally affects their support for a UBI. Our findings suggest that a UBI may be deemed too radical an approach to addressing inequality. We discuss theoretical and policy implications and provide suggestions for future research.

A groupwise approach for inferring heterogeneous treatment effects in causal inference

Abstract Recently, there has been great interest in estimating the conditional average treatment effect using flexible machine learning methods. However, in practice, investigators often have working hypotheses about effect heterogeneity across pre-defined subgroups of study units, which we call the groupwise approach. The paper compares two modern ways to estimate groupwise treatment effects, a non-parametric approach and a semi-parametric approach, with the goal of better informing practice. Specifically, we compare (a) the underlying assumptions, (b) efficiency and adaption to the underlying data generating models, and (c) a way to combine the two approaches. We also discuss how to test a key assumption concerning the semi-parametric estimator and to obtain cluster-robust standard errors if study units in the same subgroups are correlated. We demonstrate our findings by conducting simulation studies and reanalysing the Early Childhood Longitudinal Study.

2D score-based estimation of heterogeneous treatment effects

Abstract Statisticians show growing interest in estimating and analyzing heterogeneity in causal effects in observational studies. However, there usually exists a trade-off between accuracy and interpretability for developing a desirable estimator for treatment effects, especially in the case when there are a large number of features in estimation. To make efforts to address the issue, we propose a score-based framework for estimating the conditional average treatment effect (CATE) function in this article. The framework integrates two components: (i) leverage the joint use of propensity and prognostic scores in a matching algorithm to obtain a proxy of the heterogeneous treatment effects for each observation and (ii) utilize nonparametric regression trees to construct an estimator for the CATE function conditioning on the two scores. The method naturally stratifies treatment effects into subgroups over a 2d grid whose axis are the propensity and prognostic scores. We conduct benchmark experiments on multiple simulated data and demonstrate clear advantages of the proposed estimator over state-of-the-art methods. We also evaluate empirical performance in real-life settings, using two observational data from a clinical trial and a complex social survey, and interpret policy implications following the numerical results.

Flexible Machine Learning Estimation of Conditional Average Treatment Effects: A Blessing and a Curse.

Causal inference from observational data requires untestable identification assumptions. If these assumptions apply, machine learning methods can be used to study complex forms of causal effect heterogeneity. Recently, several machine learning methods were developed to estimate the conditional average treatment effect (ATE). If the features at hand cannot explain all heterogeneity, the individual treatment effects can seriously deviate from the conditional ATE. In this work, we demonstrate how the distributions of the individual treatment effect and the conditional ATE can differ when a causal random forest is applied. We extend the causal random forest to estimate the difference in conditional variance between treated and controls. If the distribution of the individual treatment effect equals that of the conditional ATE, this estimated difference in variance should be small. If they differ, an additional causal assumption is necessary to quantify the heterogeneity not captured by the distribution of the conditional ATE. The conditional variance of the individual treatment effect can be identified when the individual effect is independent of the outcome under no treatment given the measured features. Then, in the cases where the individual treatment effect and conditional ATE distributions differ, the extended causal random forest can appropriately estimate the variance of the individual treatment effect distribution, whereas the causal random forest fails to do so.

Bayesian multilevel multivariate logistic regression for superiority decision-making under observable treatment heterogeneity

BackgroundIn medical, social, and behavioral research we often encounter datasets with a multilevel structure and multiple correlated dependent variables. These data are frequently collected from a study population that distinguishes several subpopulations with different (i.e., heterogeneous) effects of an intervention. Despite the frequent occurrence of such data, methods to analyze them are less common and researchers often resort to either ignoring the multilevel and/or heterogeneous structure, analyzing only a single dependent variable, or a combination of these. These analysis strategies are suboptimal: Ignoring multilevel structures inflates Type I error rates, while neglecting the multivariate or heterogeneous structure masks detailed insights.MethodsTo analyze such data comprehensively, the current paper presents a novel Bayesian multilevel multivariate logistic regression model. The clustered structure of multilevel data is taken into account, such that posterior inferences can be made with accurate error rates. Further, the model shares information between different subpopulations in the estimation of average and conditional average multivariate treatment effects. To facilitate interpretation, multivariate logistic regression parameters are transformed to posterior success probabilities and differences between them.ResultsA numerical evaluation compared our framework to less comprehensive alternatives and highlighted the need to model the multilevel structure: Treatment comparisons based on the multilevel model had targeted Type I error rates, while single-level alternatives resulted in inflated Type I errors. Further, the multilevel model was more powerful than a single-level model when the number of clusters was higher. A re-analysis of the Third International Stroke Trial data illustrated how incorporating a multilevel structure, assessing treatment heterogeneity, and combining dependent variables contributed to an in-depth understanding of treatment effects. Further, we demonstrated how Bayes factors can aid in the selection of a suitable model.ConclusionThe method is useful in prediction of treatment effects and decision-making within subpopulations from multiple clusters, while taking advantage of the size of the entire study sample and while properly incorporating the uncertainty in a principled probabilistic manner using the full posterior distribution.