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Andrew Ying

Publications and source records attributed to Andrew Ying.

24 records · Page 2Linked to original sources

A New Causal Approach to Account for Treatment Switching in Randomized Experiments under a Structural Cumulative Survival Model

Treatment switching in a randomized controlled trial is said to occur when a patient randomized to one treatment arm switches to another treatment arm during follow-up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously dilute the estimated effect of treatment on overall survival. In this paper, we aim to account for the potential impact of treatment switching in a re-analysis evaluating the treatment effect of NucleosideReverse Transcriptase Inhibitors (NRTIs) on a safety outcome (time to first severe or worse sign or symptom) in participants receiving a new antiretroviral regimen that either included or omitted NRTIs in the Optimized Treatment That Includes or OmitsNRTIs (OPTIONS) trial. We propose an estimator of a treatment causal effect under a structural cumulative survival model (SCSM) that leverages randomization as an instrumental variable to account for selective treatment switching. Unlike Robins' accelerated failure time model often used to address treatment switching, the proposed approach avoids the need for artificial censoring for estimation. We establish that the proposed estimator is uniformly consistent and asymptotically Gaussian under standard regularity conditions. A consistent variance estimator is also given and a simple resampling approach provides uniform confidence bands for the causal difference comparing treatment groups overtime on the cumulative intensity scale. We develop an R package named "ivsacim" implementing all proposed methods, freely available to download from R CRAN. We examine the finite performance of the estimator via extensive simulations.

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An Introduction to Proximal Causal Learning

A standard assumption for causal inference from observational data is that one has measured a sufficiently rich set of covariates to ensure that within covariate strata, subjects are exchangeable across observed treatment values. Skepticism about the exchangeability assumption in observational studies is often warranted because it hinges on investigators' ability to accurately measure covariates capturing all potential sources of confounding. Realistically, confounding mechanisms can rarely if ever, be learned with certainty from measured covariates. One can therefore only ever hope that covariate measurements are at best proxies of true underlying confounding mechanisms operating in an observational study, thus invalidating causal claims made on basis of standard exchangeability conditions. Causal learning from proxies is a challenging inverse problem which has to date remained unresolved. In this paper, we introduce a formal potential outcome framework for proximal causal learning, which while explicitly acknowledging covariate measurements as imperfect proxies of confounding mechanisms, offers an opportunity to learn about causal effects in settings where exchangeability on the basis of measured covariates fails. Sufficient conditions for nonparametric identification are given, leading to the proximal g-formula and corresponding proximal g-computation algorithm for estimation. These may be viewed as generalizations of Robins' foundational g-formula and g-computation algorithm, which account explicitly for bias due to unmeasured confounding. Both point treatment and time-varying treatment settings are considered, and an application of proximal g-computation of causal effects is given for illustration.

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On the Asymptotic Distribution of the Scan Statistic for Empirical Distributions

We investigate the asymptotic behavior of several variants of the scan statistic applied to empirical distributions, which can be applied to detect the presence of an anomalous interval with any length. Of particular interest is Studentized scan statistic that is preferable in practice. The main ingredients in the proof are Kolmogorov's theorem, a Poisson approximation, and recent technical results by Kabluchko et al (2014).

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A Scan Procedure for Multiple Testing

In a multiple testing framework, we propose a method that identifies the interval with the highest estimated false discovery rate of P-values and rejects the corresponding null hypotheses. Unlike the Benjamini-Hochberg method, which does the same but over intervals with an endpoint at the origin, the new procedure `scans' all intervals. In parallel with \citep*{storey2004strong}, we show that this scan procedure provides strong control of asymptotic false discovery rate. In addition, we investigate its asymptotic false non-discovery rate, deriving conditions under which it outperforms the Benjamini-Hochberg procedure. For example, the scan procedure is superior in power-law location models.

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Two-Stage Residual Inclusion under the Additive Hazards Model - An Instrumental Variable Approach with Application to SEER-Medicare Linked Data

Instrumental variable is an essential tool for addressing unmeasured confounding in observational studies. Two stage predictor substitution (2SPS) estimator and two stage residual inclusion(2SRI) are two commonly used approaches in applying instrumental variables. Recently 2SPS was studied under the additive hazards model in the presence of competing risks of time-to-events data, where linearity was assumed for the relationship between the treatment and the instrument variable. This assumption may not be the most appropriate when we have binary treatments. In this paper, we consider the 2SRI estimator under the additive hazards model for general survival data and in the presence of competing risks, which allows generalized linear models for the relation between the treatment and the instrumental variable. We derive the asymptotic properties including a closed-form asymptotic variance estimate for the 2SRI estimator. We carry out numerical studies in finite samples, and apply our methodology to the linked Surveillance, Epidemiology and End Results (SEER) - Medicare database comparing radical prostatectomy versus conservative treatment in early-stage prostate cancer patients.

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Detection of Sparse Mixtures: Higher Criticism and Scan Statistic

We consider the problem of detecting a sparse mixture as studied by Ingster (1997) and Donoho and Jin (2004). We consider a wide array of base distributions. In particular, we study the situation when the base distribution has polynomial tails, a situation that has not received much attention in the literature. Perhaps surprisingly, we find that in the context of such a power-law distribution, the higher criticism does not achieve the detection boundary. However, the scan statistic does.

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