Estimation Of Average Treatment Effects Research Articles

Variance estimation for average treatment effects estimated by g-computation

AbstractThe average treatment effect is used to evaluate effects of interventions in a population. Under certain causal assumptions, such an effect may be estimated from observational data using the g-computation technique. The asymptotic properties of this estimator appears not to be well-known and hence bootstrapping has become the preferred method for estimating its variance. Bootstrapping is, however, not an optimal choice for multiple reasons; it is a slow procedure and, if based on too few bootstrap samples, results in a highly variable estimator of the variance. In this paper, we consider estimators of potential outcome means and average treatment effects using g-computation. We consider these parameters for the entire population but also in subgroups, for example, the average treatment effect among the treated. We derive their asymptotic distributions in a general framework. An estimator of the asymptotic variance is proposed and shown to be consistent when g-computation is used in conjunction with the M-estimation technique. The proposed estimator is shown to be superior to the bootstrap technique in a simulation study. Robustness against model misspecification is also demonstrated by means of simulations.

Reducing Interference Bias in Online Marketplace Experiments Using Cluster Randomization: Evidence from a Pricing Meta-experiment on Airbnb

Online marketplace designers frequently run randomized experiments to measure the impact of proposed product changes. However, given that marketplaces are inherently connected, total average treatment effect (TATE) estimates obtained through individual-level randomized experiments may be biased because of violations of the stable unit treatment value assumption, a phenomenon we refer to as “interference bias.” Cluster randomization (i.e., the practice of randomizing treatment assignment at the level of “clusters” of similar individuals) is an established experiment design technique for countering interference bias in social networks, but it is unclear ex ante if it will be effective in marketplace settings. In this paper, we use a meta-experiment or “experiment over experiments” conducted on Airbnb to both provide empirical evidence of interference bias in online marketplace settings and assess the viability of cluster randomization as a tool for reducing interference bias in marketplace TATE estimates. Results from our meta-experiment indicate that at least 20% of the TATE estimate produced by an individual-level randomized evaluation of the platform fee increase we study is attributable to interference bias and eliminated through the use of cluster randomization. We also find suggestive, nonstatistically significant evidence that interference bias in seller-side experiments is more severe in demand-constrained geographies and that the efficacy of cluster randomization at reducing interference bias increases with cluster quality. This paper was accepted by Chris Forman, information systems. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2020.01157 .

Propensity Score Weighting with Missing Data on Covariates and Clustered Data Structure

Propensity score (PS) analyses are increasingly popular in behavioral sciences. Two issues often add complexities to PS analyses, including missing data in observed covariates and clustered data structure. In previous research, methods for conducting PS analyses with considering either issue alone were examined. In practice, the two issues often co-occur; but the performance of methods for PS analyses in the presence of both issues has not been evaluated previously. In this study, we consider PS weighting analysis when data are clustered and observed covariates have missing values. A simulation study is conducted to evaluate the performance of different missing data handling methods (complete-case, single-level imputation, or multilevel imputation) combined with different multilevel PS weighting methods (fixed- or random-effects PS models, inverse-propensity-weighting or the clustered weighting, weighted single-level or multilevel outcome models). The results suggest that the bias in average treatment effect estimation can be reduced, by better accounting for clustering in both the missing data handling stage (such as with the multilevel imputation) and the PS analysis stage (such as with the fixed-effects PS model, clustered weighting, and weighted multilevel outcome model). A real-data example is provided for illustration.

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.

Directed Acyclic Graph Assisted Method For Estimating Average Treatment Effect

ABSTRACT Observational data, such as electronic clinical records and claims data, can prove invaluable for evaluating the Average Treatment Effect (ATE) and supporting decision-making, provided they are employed correctly. The Inverse Probability of Treatment Weighting (IPTW) method, based on propensity scores, has demonstrated remarkable efficacy in estimating ATE, assuming that the assumptions of exchangeability, consistency, and positivity are met. Directed Acyclic Graphs (DAGs) offer a practical approach to assess the exchangeability assumption, which asserts that treatment assignment and potential outcomes are independent given a set of confounding variables that block all backdoor paths from treatment assignment to potential outcomes. To ensure a consistent ATE estimator, one can adjust for a minimally sufficient adjustment set of confounding variables that block all backdoor paths from treatment assignment to the outcome. To enhance the efficiency of ATE estimators, our proposal involves incorporating both the minimally sufficient adjustment set of confounding variables and predictors into the propensity score model. Extensive simulations were conducted to evaluate the performance of propensity score-based IPTW methods in estimating ATE when different sets of covariates were included in the propensity score models. The simulation results underscored the significance of including the minimally sufficient adjustment set of confounding variables along with predictors in the propensity score models to obtain a consistent and efficient ATE estimator. We applied this proposed method to investigate whether tracheostomy was causally associated with in-hospital infant mortality, utilizing the 2016 Healthcare Cost and Utilization Project Kids’ Inpatient Database. The estimated ATE was found to be approximately 2.30%–2.46% with p-value >0.05.

Impact of Pleural Lavage Cytology Positivity on Early Recurrence After Surgery for Non-Small Cell Lung Cancer

ObjectiveThe aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). MethodsThis is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. ResultsOverall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06–2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04–2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14–2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27–3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25–16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25–5.36, p<0.001). ConclusionsPositive pleural lavage cytology was found to be the strongest predictor of early recurrence.

Quantifying and reducing inequity in average treatment effect estimation

BackgroundAcross studies of average treatment effects, some population subgroups consistently have lower representation than others which can lead to discrepancies in how well results generalize.MethodsWe develop a framework for quantifying inequity due to systemic disparities in sample representation and a method for mitigation during data analysis. Assuming subgroup treatment effects are exchangeable, an unbiased sample average treatment effect estimator will have lower mean-squared error, on average across studies, for subgroups with less representation when treatment effects vary. We present a method for estimating average treatment effects in representation-adjusted samples which enables subgroups to optimally leverage information from the full sample rather than only their own subgroup’s data. Two approaches for specifying representation adjustment are offered—one minimizes average mean-squared error for each subgroup separately and the other balances minimization of mean-squared error and equal representation. We conduct simulation studies to compare the performance of the proposed estimators to several subgroup-specific estimators.ResultsWe find that the proposed estimators generally provide lower mean squared error, particularly for smaller subgroups, relative to the other estimators. As a case study, we apply this method to a subgroup analysis from a published study.ConclusionsWe recommend the use of the proposed estimators to mitigate the impact of disparities in representation, though structural change is ultimately needed.

A new method for clustered survival data: Estimation of treatment effect heterogeneity and variable selection.

We recently developed a new method random-intercept accelerated failure time model with Bayesian additive regression trees (riAFT-BART) to draw causal inferences about population treatment effect on patient survival from clustered and censored survival data while accounting for the multilevel data structure. The practical utility of this method goes beyond the estimation of population average treatment effect. In this work, we exposit how riAFT-BART can be used to solve two important statistical questions with clustered survival data: estimating the treatment effect heterogeneity and variable selection. Leveraging the likelihood-based machine learning, we describe a way in which we can draw posterior samples of the individual survival treatment effect from riAFT-BART model runs, and use the drawn posterior samples to perform an exploratory treatment effect heterogeneity analysis to identify subpopulations who may experience differential treatment effects than population average effects. There is sparse literature on methods for variable selection among clustered and censored survival data, particularly ones using flexible modeling techniques. We propose a permutation-based approach using the predictor's variable inclusion proportion supplied by the riAFT-BART model for variable selection. To address the missing data issue frequently encountered in health databases, we propose a strategy to combine bootstrap imputation and riAFT-BART for variable selection among incomplete clustered survival data. We conduct an expansive simulation study to examine the practical operating characteristics of our proposed methods, and provide empirical evidence that our proposed methods perform better than several existing methods across a wide range of data scenarios. Finally, we demonstrate the methods via a case study of predictors for in-hospital mortality among severe COVID-19 patients and estimating the heterogeneous treatment effects of three COVID-specific medications. The methods developed in this work are readily available in the package .

The Finite Sample Performance of Instrumental Variable-Based Estimators of the Local Average Treatment Effect When Controlling for Covariates

AbstractThis paper investigates the finite sample performance of a range of parametric, semi-parametric, and non-parametric instrumental variable estimators when controlling for a fixed set of covariates to evaluate the local average treatment effect. Our simulation designs are based on empirical labor market data from the US and vary in several dimensions, including effect heterogeneity, instrument selectivity, instrument strength, outcome distribution, and sample size. Among the estimators and simulations considered, non-parametric estimation based on the random forest (a machine learner controlling for covariates in a data-driven way) performs competitive in terms of the average coverage rates of the (bootstrap-based) 95% confidence intervals, while also being relatively precise. Non-parametric kernel regression as well as certain versions of semi-parametric radius matching on the propensity score, pair matching on the covariates, and inverse probability weighting also have a decent coverage, but are less precise than the random forest-based method. In terms of the average root mean squared error of LATE estimation, kernel regression performs best, closely followed by the random forest method, which has the lowest average absolute bias.

Early ICD implantation and survival after out-of-hospital cardiac arrest

Abstract Background It is unclear whether an implantable cardioverter-defibrillator (ICD) is generally beneficial in survivors of out-of-hospital cardiac arrest (OHCA) of cardiac etiology. Aim We studied the association between ICD implantation and survival in patients with cardiac etiology or initial shockable rhythm in OHCA, using the Swedish Registry for Cardiopulmonary Resuscitation (SRCR). Methods All cases in the SRCR during 2010 to 2020 with cardiac etiology or initial shockable rhythm who were discharged alive included. We examined the association between ICD and survival using propensity score. Propensity scores (919 candidate predictors before feature selection) were estimated using gradient boosting, Bayesian additive regression trees, neural networks, extreme gradient boosting and logistic regression. Cox regression was used to model survival. The primary outcome was death or recurrent cardiac arrest. Results The 90-days event rate was 25% in the ICD group, compared with 52% in those without ICD. With regards to the average treatment effect (ATE) the overall hazard ratio 0.38 (95% CI 0.26-0.56) for ICD vs. no ICD. The overall average treatment effect on those treated (ATT) was 0.31 (95% CI 0.22-0.44). In the 15 subgroup analyses, every point estimate were below 1, with the most pronounced association noted in those with a history of acute myocardial infarction (HR 0.07 [95% CI 0.02-0.32]). All ATE and ATE estimates were aligned. Conclusions Mortality in survivors of OHCA occurs early after discharge, and prompt implantation of an ICD is associated with 62% lower probability of death and recurrent cardiac arrest overall.

Comparison of Propensity Score Weighting Methods to Remove Selection Bias in Average Treatment Effect Estimates

In this Monte Carlo simulation study, the performance of six different propensity score methods implemented through weighting cases was investigated: inverse probability of treatment weighting, truncated inverse probability of treatment weighting, propensity score stratification, marginal mean weighting through propensity score stratification, optimal full propensity score matching, and marginal mean weighting through optimal full propensity score matching. These methods aim to reduce selection bias in estimates of the average treatment effect (ATE) in observational studies. For the estimation of standard errors of the ATE with weights, three methods were compared: weighted least squares (WLS), Taylor series linearization (TSL), and jackknife (JK). Results indicated that covariance adjustment extensions of the investigated propensity score methods, in combination with TSL and JK standard error estimation methods, remove the selection bias appropriately and provide the most accurate standard errors under the simulated conditions.

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.

Sample Size Requirements to Test Subgroup-Specific Treatment Effects in Cluster-Randomized Trials.

Cluster-randomized trials (CRTs) often allocate intact clusters of participants to treatment or control conditions and are increasingly used to evaluate healthcare delivery interventions. While previous studies have developed sample size methods for testing confirmatory hypotheses of treatment effect heterogeneity in CRTs (i.e., targeting the difference between subgroup-specific treatment effects), sample size methods for testing the subgroup-specific treatment effects themselves have not received adequate attention-despite a rising interest in health equity considerations in CRTs. In this article, we develop formal methods for sample size and power analyses for testing subgroup-specific treatment effects in parallel-arm CRTs with a continuous outcome and a binary subgroup variable. We point out that the variances of the subgroup-specific treatment effect estimators and their covariance are given by weighted averages of the variance of the overall average treatment effect estimator and the variance of the heterogeneous treatment effect estimator. This analytical insight facilitates an explicit characterization of the requirements for both the omnibus test and the intersection-union test to achieve the desired level of power. Generalizations to allow for subgroup-specific variance structures are also discussed. We report on a simulation study to validate the proposed sample size methods and demonstrate that the empirical power corresponds well with the predicted power for both tests. The design and setting of the Umea Dementia and Exercise (UMDEX) CRT in older adults are used to illustrate our sample size methods.

Double robustness for complier parameters and a semi-parametric test for complier characteristics

Summary We propose a semi-parametric test to evaluate (a) whether different instruments induce subpopulations of compliers with the same observable characteristics, on average; and (b) whether compliers have observable characteristics that are the same as the full population, treated subpopulation, or untreated subpopulation, on average. The test is a flexible robustness check for the external validity of instruments. To justify the test, we characterise the doubly robust moment for Abadie’s class of complier parameters, and we analyse a machine learning update to weighting that we call the automatic $\kappa$ weight. We use the test to reinterpret Angrist and Evans' different local average treatment effect estimates obtained using different instrumental variables.

One-Step Weighting to Generalize and Transport Treatment Effect Estimates to a Target Population

The problems of generalization and transportation of treatment effect estimates from a study sample to a target population are central to empirical research and statistical methodology. In both randomized experiments and observational studies, weighting methods are often used with this objective. Traditional methods construct the weights by separately modeling the treatment assignment and study selection probabilities and then multiplying functions (e.g., inverses) of their estimates. In this work, we provide a justification and an implementation for weighting in a single step. We show a formal connection between this one-step method and inverse probability and inverse odds weighting. We demonstrate that the resulting estimator for the target average treatment effect is consistent, asymptotically Normal, multiply robust, and semiparametrically efficient. We evaluate the performance of the one-step estimator in a simulation study. We illustrate its use in a case study on the effects of physician racial diversity on preventive healthcare utilization among Black men in California. We provide R code implementing the methodology.

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.

Selective machine learning of doubly robust functionals

Summary While model selection is a well-studied topic in parametric and nonparametric regression or density estimation, selection of possibly high-dimensional nuisance parameters in semiparametric problems is far less developed. In this paper, we propose a selective machine learning framework for making inferences about a finite-dimensional functional defined on a semiparametric model, when the latter admits a doubly robust estimating function and several candidate machine learning algorithms are available for estimating the nuisance parameters. We introduce a new selection criterion aimed at bias reduction in estimating the functional of interest based on a novel definition of pseudo risk inspired by the double robustness property. Intuitively, the proposed criterion selects a pair of learners with the smallest pseudo risk, so that the estimated functional is least sensitive to perturbations of a nuisance parameter. We establish an oracle property for a multi-fold cross-validation version of the new selection criterion that states that our empirical criterion performs nearly as well as an oracle with a priori knowledge of the pseudo risk for each pair of candidate learners. Finally, we apply the approach to model selection of a semiparametric estimator of average treatment effect given an ensemble of candidate machine learners to account for confounding in an observational study that we illustrate in simulations and a data application.

Robust analyzes for longitudinal clinical trials with missing and non-normal continuous outcomes

Missing data are unavoidable in longitudinal clinical trials, and outcomes are not always normally distributed. In the presence of outliers or heavy-tailed distributions, the conventional multiple imputation with the mixed model with repeated measures analysis of the average treatment effect (ATE) based on the multivariate normal assumption may produce bias and power loss. Control-based imputation (CBI) is an approach for evaluating the treatment effect under the assumption that participants in both the test and control groups with missing outcome data have a similar outcome profile as those with an identical history in the control group. We develop a robust framework to handle non-normal outcomes under CBI without imposing any parametric modeling assumptions. Under the proposed framework, sequential weighted robust regressions are applied to protect the constructed imputation model against non-normality in the covariates and the response variables. Accompanied by the subsequent mean imputation and robust model analysis, the resulting ATE estimator has good theoretical properties in terms of consistency and asymptotic normality. Moreover, our proposed method guarantees the analysis model robustness of the ATE estimation in the sense that its asymptotic results remain intact even when the analysis model is misspecified. The superiority of the proposed robust method is demonstrated by comprehensive simulation studies and an AIDS clinical trial data application.

CausalCmprsk: An R package for nonparametric and Cox-based estimation of average treatment effects in competing risks data

Background and ObjectiveCompeting risks data arise in both observational and experimental clinical studies with time-to-event outcomes, when each patient might follow one of the multiple mutually exclusive competing paths. Ignoring competing risks in the analysis can result in biased conclusions. In addition, possible confounding bias of the treatment-outcome relationship has to be addressed, when estimating treatment effects from observational data. In order to provide tools for estimation of average treatment effects on time-to-event outcomes in the presence of competing risks, we developed the R package causalCmprsk. We illustrate the package functionality in the estimation of effects of a right heart catheterization procedure on discharge and in-hospital death from observational data. MethodsThe causalCmprsk package implements an inverse probability weighting estimation approach, aiming to emulate baseline randomization and alleviate possible treatment selection bias. The package allows for different types of weights, representing different target populations. causalCmprsk builds on existing methods from survival analysis and adapts them to the causal analysis in non-parametric and semi-parametric frameworks. ResultsThe causalCmprsk package has two main functions: fit.cox assumes a semiparametric structural Cox proportional hazards model for the counterfactual cause-specific hazards, while fit.nonpar does not impose any structural assumptions. In both frameworks, causalCmprsk implements estimators of (i) absolute risks for each treatment arm, e.g., cumulative hazards or cumulative incidence functions, and (ii) relative treatment effects, e.g., hazard ratios, or restricted mean time differences. The latter treatment effect measure translates the treatment effect from probability into more intuitive time domain and allows the user to quantify, for example, by how many days or months the treatment accelerates the recovery or postpones illness or death. ConclusionsThe causalCmprsk package provides a convenient and useful tool for causal analysis of competing risks data. It allows the user to distinguish between different causes of the end of follow-up and provides several time-varying measures of treatment effects. The package is accompanied by a vignette that contains more details, examples and code, making the package accessible even for non-expert users.

Improved estimation of average treatment effects under covariate‐adaptive randomization methods

Estimation of the average treatment effect is one of the crucial problems in clinical trials for two or multiple treatments. The covariate‐adaptive randomization methods are often applied to balance treatment assignments across prognostic factors in clinical trials, such as the minimization and stratified permuted blocks method. We propose a model‐free estimator of average treatment effects under covariate‐adaptive randomization methods, which is least square adjustment for the estimator of outcome models. The proposed estimator is not only applicable to the case of binary treatment, but also can be extended to the case of multiple treatment. The proposed estimator is consistent and asymptotically normally distributed. Simulation studies show that the proposed estimator and Ye's estimator are comparable, and it performs better than Bugni's estimator when the outcome model is linear. The proposed estimator has some advantages over targeted maximum likelihood estimator, Bugni's estimator and Ye's estimator in terms of the standard error and root mean squared error when the outcome model is nonlinear. The proposed estimator is stable for the from of outcome model. Finally, we apply the proposed methodology to a dataset that studies the causal effect promotional videos mode on the school‐age children's educational attainment in Peru.