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Ting Ye

Publications and source records attributed to Ting Ye.

At least 55 records · Page 3Linked to original sources

A unified analysis of regression adjustment in randomized experiments

Regression adjustment is broadly applied in randomized trials under the premise that it usually improves the precision of a treatment effect estimator. However, previous work has shown that this is not always true. To further understand this phenomenon, we develop a unified comparison of the asymptotic variance of a class of linear regression-adjusted estimators. Our analysis is based on the classical theory for linear regression with heteroscedastic errors and thus does not assume that the postulated linear model is correct. For a completely randomized binary treatment, we provide sufficient conditions under which some regression-adjusted estimators are guaranteed to be more asymptotically efficient than others. We explore other settings such as general treatment assignment mechanisms and generalized linear models, and find that the variance dominance phenomenon no longer occurs.

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Structural mean models for instrumented difference-in-differences

In the standard difference-in-differences research design, the parallel trends assumption may be violated when the relationship between the exposure trend and the outcome trend is confounded by unmeasured confounders. Progress can be made if there is an exogenous variable that (i) does not directly influence the change in outcome means (i.e. the outcome trend) except through influencing the change in exposure means (i.e. the exposure trend), and (ii) is not related to the unmeasured exposure - outcome confounders on the trend scale. Such exogenous variable is called an instrument for difference-in-differences. For continuous outcomes that lend themselves to linear modelling, so-called instrumented difference-in-differences methods have been proposed. In this paper, we will suggest novel multiplicative structural mean models for instrumented difference-in-differences, which allow one to identify and estimate the average treatment effect on count and rare binary outcomes, in the whole population or among the treated, when a valid instrument for difference-in-differences is available. We discuss the identifiability of these models, then develop efficient semi-parametric estimation approaches that allow the use of flexible, data-adaptive or machine learning methods to estimate the nuisance parameters. We apply our proposal on health care data to investigate the risk of moderate to severe weight gain under sulfonylurea treatment compared to metformin treatment, among new users of antihyperglycemic drugs.

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Testing for Treatment Effect Twice Using Internal and External Controls in Clinical Trials

Leveraging external controls -- relevant individual patient data under control from external trials or real-world data -- has the potential to reduce the cost of randomized controlled trials (RCTs) while increasing the proportion of trial patients given access to novel treatments. However, due to lack of randomization, RCT patients and external controls may differ with respect to covariates that may or may not have been measured. Hence, after controlling for measured covariates, for instance by matching, testing for treatment effect using external controls may still be subject to unmeasured biases. In this paper, we propose a sensitivity analysis approach to quantify the magnitude of unmeasured bias that would be needed to alter the study conclusion that presumed no unmeasured biases are introduced by employing external controls. Whether leveraging external controls increases power or not depends on the interplay between sample sizes and the magnitude of treatment effect and unmeasured biases, which may be difficult to anticipate. This motivates a combined testing procedure that performs two highly correlated analyses, one with and one without external controls, with a small correction for multiple testing using the joint distribution of the two test statistics. The combined test provides a new method of sensitivity analysis designed for data fusion problems, which anchors at the unbiased analysis based on RCT only and spends a small proportion of the type I error to also test using the external controls. In this way, if leveraging external controls increases power, the power gain compared to the analysis based on RCT only can be substantial; if not, the power loss is small. The proposed method is evaluated in theory and power calculations, and applied to a real trial.

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The Role of Placebo Samples in Observational Studies

In an observational study, it is common to leverage known null effect to detect bias. One such strategy is to set aside a placebo sample -- a subset of data immune from the hypothesized cause-and-effect relationship. Existence of an effect in the placebo sample raises concern of unmeasured confounding bias while absence of it corroborates the causal conclusion. This paper establishes a formal framework for using a placebo sample to detect and remove bias. We state identification assumption, and develop estimation and inference methods based on outcome regression, inverse probability weighting, and doubly-robust approaches. Simulation studies and an empirical application illustrate the finite-sample performance of the proposed methods.

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Nonparametric identification of causal effects in clustered observational studies with differential selection

The clustered observational study (COS) design is the observational study counterpart to the clustered randomized trial. In a COS, a treatment is assigned to intact groups, and all units within the group are exposed to the treatment. However, the treatment is non-randomly assigned. COSs are common in both education and health services research. In education, treatments may be given to all students within some schools but withheld from all students in other schools. In health studies, treatments may be applied to clusters such as hospitals or groups of patients treated by the same physician. In this manuscript, we study the identification of causal effects in clustered observational study designs. We focus on the prospect of differential selection of units to clusters, which occurs when the units' cluster selections depend on the clusters' treatment assignments. Extant work on COSs has made an implicit assumption that rules out the presence of differential selection. We derive the identification results for designs with differential selection and that contexts with differential cluster selection require different adjustment sets than standard designs. We outline estimators for designs with and without differential selection. Using a series of simulations, we outline the magnitude of the bias that can occur with differential selection. We then present two empirical applications focusing on the likelihood of differential selection.

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A Negative Correlation Strategy for Bracketing in Difference-in-Differences

The method of difference-in-differences (DID) is widely used to study the causal effect of policy interventions in observational studies. DID employs a before and after comparison of the treated and control units to remove bias due to time-invariant unmeasured confounders under the parallel trends assumption. Estimates from DID, however, will be biased if the outcomes for the treated and control units evolve differently in the absence of treatment, namely if the parallel trends assumption is violated. We propose a general identification strategy that leverages two groups of control units whose outcomes relative to the treated units exhibit a negative correlation, and achieves partial identification of the average treatment effect for the treated. The identified set is of a union bounds form that involves the minimum and maximum operators, which makes the canonical bootstrap generally inconsistent and naive methods overly conservative. By utilizing the directional inconsistency of the bootstrap distribution, we develop a novel bootstrap method to construct uniformly valid confidence intervals for the identified set and parameter of interest when the identified set is of a union bounds form, and we establish the method's theoretical properties. We develop a simple falsification test and sensitivity analysis. We apply the proposed strategy for bracketing to study whether minimum wage laws affect employment levels.

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FIFA: Making Fairness More Generalizable in Classifiers Trained on Imbalanced Data

Algorithmic fairness plays an important role in machine learning and imposing fairness constraints during learning is a common approach. However, many datasets are imbalanced in certain label classes (e.g. "healthy") and sensitive subgroups (e.g. "older patients"). Empirically, this imbalance leads to a lack of generalizability not only of classification, but also of fairness properties, especially in over-parameterized models. For example, fairness-aware training may ensure equalized odds (EO) on the training data, but EO is far from being satisfied on new users. In this paper, we propose a theoretically-principled, yet Flexible approach that is Imbalance-Fairness-Aware (FIFA). Specifically, FIFA encourages both classification and fairness generalization and can be flexibly combined with many existing fair learning methods with logits-based losses. While our main focus is on EO, FIFA can be directly applied to achieve equalized opportunity (EqOpt); and under certain conditions, it can also be applied to other fairness notions. We demonstrate the power of FIFA by combining it with a popular fair classification algorithm, and the resulting algorithm achieves significantly better fairness generalization on several real-world datasets.

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A Focusing Framework for Testing Bi-Directional Causal Effects with GWAS Summary Data

Mendelian randomization (MR) is a powerful method that uses genetic variants as instrumental variables (IVs) to infer the causal effect of a modifiable exposure on an outcome. Although recent years have seen many extensions of basic MR methods to be robust to certain violations of assumptions, few methods were proposed to infer bi-directional causal relationships, especially for phenotypes with limited biological understandings. The presence of horizontal pleiotropy adds another layer of complexity. In this article, we show that assumptions for common MR methods are often impossible or too stringent in the existence of bi-directional relationships. We then propose a new focusing framework for testing bi-directional causal effects between two traits with possibly pleiotropic genetic variants. Our proposal can be coupled with many state-of-art MR methods. We provide theoretical guarantees on the Type I error and power of the proposed methods. We demonstrate the robustness of the proposed methods using several simulated and real datasets.

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Instrumented Difference-in-Differences

Unmeasured confounding is a key threat to reliable causal inference based on observational studies. Motivated from two powerful natural experiment devices, the instrumental variables and difference-in-differences, we propose a new method called instrumented difference-in-differences that explicitly leverages exogenous randomness in an exposure trend to estimate the average and conditional average treatment effect in the presence of unmeasured confounding. We develop the identification assumptions using the potential outcomes framework. We propose a Wald estimator and a class of multiply robust and efficient semiparametric estimators, with provable consistency and asymptotic normality. In addition, we extend the instrumented difference-in-differences to a two-sample design to facilitate investigations of delayed treatment effect and provide a measure of weak identification. We demonstrate our results in simulated and real datasets.

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Semiparametric causal mediation analysis with unmeasured mediator-outcome confounding

Although the exposure can be randomly assigned in studies of mediation effects, any form of direct intervention on the mediator is often infeasible. As a result, unmeasured mediator-outcome confounding can seldom be ruled out. We propose semiparametric identification of natural direct and indirect effects in the presence of unmeasured mediator-outcome confounding by leveraging heteroskedasticity restrictions on the observed data law. For inference, we develop semiparametric estimators that remain consistent under partial misspecifications of the observed data model. We illustrate the proposed estimators through both simulations and an application to evaluate the effect of self-efficacy on fatigue among health care workers during the COVID-19 outbreak.

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Minimax Rates and Adaptivity in Combining Experimental and Observational Data

Randomized controlled trials (RCTs) are the gold standard for evaluating the causal effect of a treatment; however, they often have limited sample sizes and sometimes poor generalizability. On the other hand, non-randomized, observational data derived from large administrative databases have massive sample sizes and better generalizability, but they are prone to unmeasured confounding bias. It is thus of considerable interest to reconcile effect estimates obtained from randomized controlled trials and observational studies investigating the same intervention, potentially harvesting the best from both realms. In this paper, we theoretically characterize the potential efficiency gain of integrating observational data into the RCT-based analysis from a minimax point of view. For estimation, we derive the minimax rate of convergence for the mean squared error, and propose a fully adaptive anchored thresholding estimator that attains the optimal rate up to poly-log factors. For inference, we characterize the minimax rate for the length of confidence intervals and show that adaptation (to unknown confounding bias) is in general impossible. A curious phenomenon thus emerges: for estimation, the efficiency gain from data integration can be achieved without prior knowledge on the magnitude of the confounding bias; for inference, the same task becomes information-theoretically impossible in general. We corroborate our theoretical findings using simulations and a real data example from the RCT DUPLICATE initiative [Franklin et al., 2021b].

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Social Distancing and COVID-19: Randomization Inference for a Structured Dose-Response Relationship

Social distancing is widely acknowledged as an effective public health policy combating the novel coronavirus. But extreme social distancing has costs and it is not clear how much social distancing is needed to achieve public health effects. In this article, we develop a design-based framework to make inference about the dose-response relationship between social distancing and COVID-19 related death toll and case numbers. We first discuss how to embed observational data with a time-independent, continuous treatment dose into an approximate randomized experiment, and develop a randomization-based procedure that tests if a structured dose-response relationship fits the data. We then generalize the design and testing procedure to accommodate a time-dependent, treatment dose trajectory, and generalize a dose-response relationship to a longitudinal setting. Finally, we apply the proposed design and testing procedures to investigate the effect of social distancing during the phased reopening in the United States on public health outcomes using data compiled from sources including Unacast, the United States Census Bureau, and the County Health Rankings and Roadmaps Program. We rejected a primary analysis null hypothesis that stated the social distancing from April 27, 2020, to June 28, 2020, had no effect on the COVID-19-related death toll from June 29, 2020, to August 2, 2020 (p-value < 0.001), and found that it took more reduction in mobility to prevent exponential growth in case numbers for non-rural counties compared to rural counties.

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Toward Better Practice of Covariate Adjustment in Analyzing Randomized Clinical Trials

In randomized clinical trials, adjustments for baseline covariates at both design and analysis stages are highly encouraged by regulatory agencies. A recent trend is to use a model-assisted approach for covariate adjustment to gain credibility and efficiency while producing asymptotically valid inference even when the model is incorrect. In this article we present three considerations for better practice when model-assisted inference is applied to adjust for covariates under simple or covariate-adaptive randomized trials: (1) guaranteed efficiency gain: a model-assisted method should often gain but never hurt efficiency; (2) wide applicability: a valid procedure should be applicable, and preferably universally applicable, to all commonly used randomization schemes; (3) robust standard error: variance estimation should be robust to model misspecification and heteroscedasticity. To achieve these, we recommend a model-assisted estimator under an analysis of heterogeneous covariance working model including all covariates utilized in randomization. Our conclusions are based on an asymptotic theory that provides a clear picture of how covariate-adaptive randomization and regression adjustment alter statistical efficiency. Our theory is more general than the existing ones in terms of studying arbitrary functions of response means (including linear contrasts, ratios, and odds ratios), multiple arms, guaranteed efficiency gain, optimality, and universal applicability.

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FastSeq: Make Sequence Generation Faster

Transformer-based models have made tremendous impacts in natural language generation. However the inference speed is a bottleneck due to large model size and intensive computing involved in auto-regressive decoding process. We develop FastSeq framework to accelerate sequence generation without accuracy loss. The proposed optimization techniques include an attention cache optimization, an efficient algorithm for detecting repeated n-grams, and an asynchronous generation pipeline with parallel I/O. These optimizations are general enough to be applicable to Transformer-based models (e.g., T5, GPT2, and UniLM). Our benchmark results on a set of widely used and diverse models demonstrate 4-9x inference speed gain. Additionally, FastSeq is easy to use with a simple one-line code change. The source code is available at https://github.com/microsoft/fastseq.

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Bridging preference-based instrumental variable studies and cluster-randomized encouragement experiments: study design, noncompliance, and average cluster effect ratio

Instrumental variable methods are widely used in medical and social science research to draw causal conclusions when the treatment and outcome are confounded by unmeasured confounding variables. One important feature of such studies is that the instrumental variable is often applied at the cluster level, e.g., hospitals' or physicians' preference for a certain treatment where each hospital or physician naturally defines a cluster. This paper proposes to embed such observational instrumental variable data into a cluster-randomized encouragement experiment using statistical matching. Potential outcomes and causal assumptions underpinning the design are formalized and examined. Testing procedures for two commonly-used estimands, Fisher's sharp null hypothesis and the pooled effect ratio, are extended to the current setting. We then introduce a novel cluster-heterogeneous proportional treatment effect model and the relevant estimand: the average cluster effect ratio. This new estimand is advantageous over the structural parameter in a constant proportional treatment effect model in that it allows treatment heterogeneity, and is advantageous over the pooled effect ratio estimand in that it is immune to Simpson's paradox. We develop an asymptotically valid randomization-based testing procedure for this new estimand based on solving a mixed integer quadratically-constrained optimization problem. The proposed design and inferential methods are applied to a study of the effect of using transesophageal echocardiography during CABG surgery on patients' 30-day mortality rate.

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On Mendelian Randomization Mixed-Scale Treatment Effect Robust Identification (MR MiSTERI) and Estimation for Causal Inference

Standard Mendelian randomization analysis can produce biased results if the genetic variant defining the instrumental variable (IV) is confounded and/or has a horizontal pleiotropic effect on the outcome of interest not mediated by the treatment. We provide novel identification conditions for the causal effect of a treatment in presence of unmeasured confounding, by leveraging an invalid IV for which both the IV independence and exclusion restriction assumptions may be violated. The proposed Mendelian Randomization Mixed-Scale Treatment Effect Robust Identification (MR MiSTERI) approach relies on (i) an assumption that the treatment effect does not vary with the invalid IV on the additive scale; and (ii) that the selection bias due to confounding does not vary with the invalid IV on the odds ratio scale; and (iii) that the residual variance for the outcome is heteroscedastic and thus varies with the invalid IV. We formally establish that their conjunction can identify a causal effect even with an invalid IV subject to pleiotropy. MiSTERI is shown to be particularly advantageous in presence of pervasive heterogeneity of pleiotropic effects on additive scale, a setting in which two recently proposed robust estimation methods MR GxE and MR GENIUS can be severely biased. In order to incorporate multiple, possibly correlated and weak IVs, a common challenge in MR studies, we develop a MAny Weak Invalid Instruments (MR MaWII MiSTERI) approach for strengthened identification and improved accuracy MaWII MiSTERI is shown to be robust to horizontal pleiotropy, violation of IV independence assumption and weak IV bias. Both simulation studies and real data analysis results demonstrate the robustness of the proposed MR MiSTERI methods.

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Debiased Inverse-Variance Weighted Estimator in Two-Sample Summary-Data Mendelian Randomization

Mendelian randomization (MR) has become a popular approach to study the effect of a modifiable exposure on an outcome by using genetic variants as instrumental variables. A challenge in MR is that each genetic variant explains a relatively small proportion of variance in the exposure and there are many such variants, a setting known as many weak instruments. To this end, we provide a theoretical characterization of the statistical properties of two popular estimators in MR, the inverse-variance weighted (IVW) estimator and the IVW estimator with screened instruments using an independent selection dataset, under many weak instruments. We then propose a debiased IVW estimator, a simple modification of the IVW estimator, that is robust to many weak instruments and doesn't require screening. Additionally, we present two instrument selection methods to improve the efficiency of the new estimator when a selection dataset is available. An extension of the debiased IVW estimator to handle balanced horizontal pleiotropy is also discussed. We conclude by demonstrating our results in simulated and real datasets.

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Inference on Average Treatment Effect under Minimization and Other Covariate-Adaptive Randomization Methods

Covariate-adaptive randomization schemes such as the minimization and stratified permuted blocks are often applied in clinical trials to balance treatment assignments across prognostic factors. The existing theoretical developments on inference after covariate-adaptive randomization are mostly limited to situations where a correct model between the response and covariates can be specified or the randomization method has well-understood properties. Based on stratification with covariate levels utilized in randomization and a further adjusting for covariates not used in randomization, in this article we propose several estimators for model free inference on average treatment effect defined as the difference between response means under two treatments. We establish asymptotic normality of the proposed estimators under all popular covariate-adaptive randomization schemes including the minimization whose theoretical property is unclear, and we show that the asymptotic distributions are invariant with respect to covariate-adaptive randomization methods. Consistent variance estimators are constructed for asymptotic inference. Asymptotic relative efficiencies and finite sample properties of estimators are also studied. We recommend using one of our proposed estimators for valid and model free inference after covariate-adaptive randomization.

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