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Register a new userA New Causal Approach to Account for Treatment Switching in Randomized Experiments under a Structural Cumulative Survival Model
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Added by
Andrew Ying
Publication date
2021
fields
Mathematical Statistics
and research's language is
English
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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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Analyses of environmental phenomena often are concerned with understanding unlikely events such as floods, heatwaves, droughts or high concentrations of pollutants. Yet the majority of the causal inference literature has focused on modelling means, rather than (possibly high) quantiles. We define a general estimator of the population quantile treatment (or exposure) effects (QTE) -- the weighted QTE (WQTE) -- of which the population QTE is a special case, along with a general class of balancing weights incorporating the propensity score. Asymptotic properties of the proposed WQTE estimators are derived. We further propose and compare propensity score regression and two weighted methods based on these balancing weights to understand the causal effect of an exposure on quantiles, allowing for the exposure to be binary, discrete or continuous. Finite sample behavior of the three estimators is studied in simulation. The proposed methods are applied to data taken from the Bavarian Danube catchment area to estimate the 95% QTE of phosphorus on copper concentration in the river.
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How to measure the incremental Return On Ad Spend (iROAS) is a fundamental problem for the online advertising industry. A standard modern tool is to run randomized geo experiments, where experimental units are non-overlapping ad-targetable geographical areas (Vaver & Koehler 2011). However, how to design a reliable and cost-effective geo experiment can be complicated, for example: 1) the number of geos is often small, 2) the response metric (e.g. revenue) across geos can be very heavy-tailed due to geo heterogeneity, and furthermore 3) the response metric can vary dramatically over time. To address these issues, we propose a robust nonparametric method for the design, called Trimmed Match Design (TMD), which extends the idea of Trimmed Match (Chen & Au 2019) and furthermore integrates the techniques of optimal subset pairing and sample splitting in a novel and systematic manner. Some simulation and real case studies are presented. We also point out a few open problems for future research.
We develop new semiparametric methods for estimating treatment effects. We focus on a setting where the outcome distributions may be thick tailed, where treatment effects are small, where sample sizes are large and where assignment is completely random. This setting is of particular interest in recent experimentation in tech companies. We propose using parametric models for the treatment effects, as opposed to parametric models for the full outcome distributions. This leads to semiparametric models for the outcome distributions. We derive the semiparametric efficiency bound for this setting, and propose efficient estimators. In the case with a constant treatment effect one of the proposed estimators has an interesting interpretation as a weighted average of quantile treatment effects, with the weights proportional to (minus) the second derivative of the log of the density of the potential outcomes. Our analysis also results in an extension of Hubers model and trimmed mean to include asymmetry and a simplified condition on linear combinations of order statistics, which may be of independent interest.
We introduce a numerically tractable formulation of Bayesian joint models for longitudinal and survival data. The longitudinal process is modelled using generalised linear mixed models, while the survival process is modelled using a parametric general hazard structure. The two processes are linked by sharing fixed and random effects, separating the effects that play a role at the time scale from those that affect the hazard scale. This strategy allows for the inclusion of non-linear and time-dependent effects while avoiding the need for numerical integration, which facilitates the implementation of the proposed joint model. We explore the use of flexible parametric distributions for modelling the baseline hazard function which can capture the basic shapes of interest in practice. We discuss prior elicitation based on the interpretation of the parameters. We present an extensive simulation study, where we analyse the inferential properties of the proposed models, and illustrate the trade-off between flexibility, sample size, and censoring. We also apply our proposal to two real data applications in order to demonstrate the adaptability of our formulation both in univariate time-to-event data and in a competing risks framework. The methodology is implemented in rstan.
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