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Zehao Su

Publications and source records attributed to Zehao Su.

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Improving precision of cumulative incidence estimates in randomized controlled trials with external controls

Augmenting the control arm in clinical trials with external data can improve statistical power for demonstrating treatment effects. In many time-to-event outcome trials, participants are subject to truncation by death. Direct application of methods for competing risks analysis on the joint data may introduce bias, for example, due to covariate shifts between the populations. In this work, we consider transportability of the conditional cause-specific hazard of the event of interest under the control treatment. Under this assumption, we derive semiparametric efficiency bounds of causal cumulative incidences. This allows for quantification of the theoretical efficiency gain from incorporating the external controls. We propose triply robust estimators that can achieve the efficiency bounds, where the trial controls and external controls are made comparable through time-specific weights in a martingale integral. We conducted a simulation study to show the precision gain of the proposed fusion estimators compared to their counterparts without utilizing external controls. As a real data application, we used two cardiovascular outcome trials conducted to assess the safety of glucagon-like peptide-1 agonists. Incorporating the external controls from one trial into the other, we observed a decrease in the standard error of the treatment effects on adverse non-fatal cardiovascular events with all-cause death as the competing risk.

stat.ME

Gravitational instability in protoplanetary disk with cooling: 2D global analysis

Self-gravity is important in protoplanetary disks for planet formation through gravitational instability (GI). We study the cooling effect on GI in a thin two-dimensional protoplanetary disk. By solving the linear perturbation equations in global geometry, we obtain all the normal modes. Faster cooling leads to faster growth rate of GI with lower azimuthal wavenumber $m$. According to the spatial structure of normal modes at different mass-averaged Toomre number $\overline{Q}$ and dimensionless cooling timescale $\beta$, we identify three modes: local, transitional and global. The transitional modes are located in the outer disk while the other two modes in the inner disk. At $\beta\approx 1$ (the resonance of dynamical timescale and thermal timescale) the growth rate changes sharply and the transitional modes dominate. The disk $\alpha$ due to GI is much higher in the transitional modes than in the other two. Our result implies that the transitional modes at $\overline{Q}\approx 1$ and $\beta\approx 1$ can plausibly interpret the substructures and planet/brown dwarf formation in the outer disk.

astro-ph.EP

Dynamical Consequence of Shadows Cast to the Outer Protoplanetary Disks: I. Two-dimensional Simulations

There has been increasing evidence of shadows from scattered light observations of outer protoplanetary disks (PPDs) cast from the (unresolved) disk inner region, while in the meantime these disks present substructures of various kinds in the submillimeter. As stellar irradiation is the primary heating source for the outer PPDs, the presence of such shadows thus suggest inhomogeneous heating of the outer disk in azimuth, leading to a "thermal forcing" with dynamical consequences. We conduct a suite of idealized 2D disk simulations of the outer disk with azimuthally-varying cooling prescription to mimic the effect of shadows, generally assuming the shadow is static or slowly-rotating. The linear response to such shadows is two-armed spirals with the same pattern speed as the shadow. Towards the nonlinear regime, we find that shadows can potentially lead to the formation of a variety of types of substructures including rings, spirals and crescents, depending on viscosity, cooling time, etc. We have conducted systematic and statistical characterization of the simulation suite, and as thermal forcing from the shadow strengthens, the dominant form of shadow-induced disk substructures change from spirals to rings, and eventually to crescents/vortices. Our results highlight the importance of properly modeling the dynamical impact of inhomogeneous stellar irradiation, while call for more detailed modeling incorporating more realistic disk physics.

astro-ph.EP

Efficient estimation of the target population average treatment effect from multi-source data

We consider estimation of the target population average treatment effect (TATE) when outcome information is unavailable. Instead, we observe the outcome in multiple source populations and wish to combine the treatment effects therein to make inference on the TATE. In contrast to existing works that assume transportability on the conditional distribution of potential outcomes or conditional treatment-specific means, we work under a weaker form of effect transportability. Following the framework for causally interpretable meta-analysis, we assume transportability of conditional average treatment effects across multiple populations, which may hold with fewer standardization variables. Under this assumption, we derive the semiparametric efficiency bound of the TATE and characterize a class of doubly robust and asymptotically linear estimators. Within this class, an efficient estimator assigns optimal weights to observations from different data sources. Additionally, we suggest estimators of a low-dimensional summary of effect heterogeneity in the target population. We illustrate the use of the proposed estimators on a multicentre weight management clinical trial for semaglutide, a glucagon-like peptide-1 receptor agonist, on overweight or obese patients. Using outcome information from other regions, we estimate the weight loss effect of semaglutide in the United States subgroup.

stat.ME

Proximal indirect comparison

We consider the problem of indirect comparison, where a treatment arm of interest is absent by design in one randomized controlled trial but available in the other. The former is the target trial, and the latter is the source trial. The identifiability of the target population average treatment effect often relies on conditional transportability assumptions. However, it is a common concern whether all relevant effect modifiers are measured and controlled for. We give a new proximal identification result in the presence of shifted, unobserved effect modifiers based on proxies: an adjustment proxy in both trials and an additional reweighting proxy in the source trial. We propose an estimator which is doubly-robust against misspecifications of the so-called bridge functions and asymptotically normal under mild consistency of estimators for the bridge functions. We use two weight management trials as a context to illustrate selection of proxies and apply our method to compare the weight loss effect of active treatments from these trials.

stat.ME

A Robustness Test for Estimating Total Effects with Covariate Adjustment

Suppose we want to estimate a total effect with covariate adjustment in a linear structural equation model. We have a causal graph to decide what covariates to adjust for, but are uncertain about the graph. Here, we propose a testing procedure, that exploits the fact that there are multiple valid adjustment sets for the target total effect in the causal graph, to perform a robustness check on the graph. If the test rejects, it is a strong indication that we should not rely on the graph. We discuss what mistakes in the graph our testing procedure can detect and which ones it cannot and develop two strategies on how to select a list of valid adjustment sets for the procedure. We also connect our result to the related econometrics literature on coefficient stability tests.

stat.ME