Biometrika最新文献

Linear regression is arguably the most widely used statistical method. With fixed regressors and correlated errors, the conventional wisdom is to modify the variance-covariance estimator to accommodate the known correlation structure of the errors. We depart from existing literature by showing that with random regressors, linear regression inference is robust to correlated errors with unknown correlation structure. The existing theoretical analyses for linear regression are no longer valid because even the asymptotic normality of the least squares coefficients breaks down in this regime. We first prove the asymptotic normality of the $t$ statistics by establishing their Berry-Esseen bounds based on a novel probabilistic analysis of self-normalized statistics. We then study the local power of the corresponding $t$ tests and show that, perhaps surprisingly, error correlation can even enhance power in the regime of weak signals. Overall, our results show that linear regression is applicable more broadly than the conventional theory suggests, and they further demonstrate the value of randomization for ensuring robustness of inference.

In recent years, real-world external controls have grown in popularity as a tool to empower randomized placebo-controlled trials, particularly in rare diseases or cases where balanced randomization is unethical or impractical. However, as external controls are not always comparable to the trials, direct borrowing without scrutiny may heavily bias the treatment effect estimator. Our paper proposes a data-adaptive integrative framework capable of preventing unknown biases of the external controls. The adaptive nature is achieved by dynamically sorting out a comparable subset of external controls via bias penalization. Our proposed method can simultaneously achieve (a) the semiparametric efficiency bound when the external controls are comparable and (b) selective borrowing that mitigates the impact of the existence of incomparable external controls. Furthermore, we establish statistical guarantees, including consistency, asymptotic distribution and inference, providing Type-I error control and good power. Extensive simulations and two real-data applications show that the proposed method leads to improved performance over the trial-only estimator across various bias-generating scenarios.

In geostatistical problems with massive sample size, Gaussian processes can be approximated using sparse directed acyclic graphs to achieve scalable $O\left(n\right)$ computational complexity. In these models, data at each location are typically assumed conditionally dependent on a small set of parents which usually include a subset of the nearest neighbors. These methodologies often exhibit excellent empirical performance, but the lack of theoretical validation leads to unclear guidance in specifying the underlying graphical model and sensitivity to graph choice. We address these issues by introducing radial neighbors Gaussian processes (RadGP), a class of Gaussian processes based on directed acyclic graphs in which directed edges connect every location to all of its neighbors within a predetermined radius. We prove that any radial neighbors Gaussian process can accurately approximate the corresponding unrestricted Gaussian process in Wasserstein-2 distance, with an error rate determined by the approximation radius, the spatial covariance function, and the spatial dispersion of samples. We offer further empirical validation of our approach via applications on simulated and real world data showing excellent performance in both prior and posterior approximations to the original Gaussian process.

Many proposals for the identification of causal effects require an instrumental variable that satisfies strong, untestable unconfoundedness and exclusion restriction assumptions. In this paper, we show how one can potentially identify causal effects under violations of these assumptions by harnessing a negative control population or outcome. This strategy allows one to leverage subpopulations for whom the exposure is degenerate, and requires that the instrument-outcome association satisfies a certain parallel trend condition. We develop semiparametric efficiency theory for a general instrumental variable model, and obtain a multiply robust, locally efficient estimator of the average treatment effect in the treated. The utility of the estimators is demonstrated in simulation studies and an analysis of the Life Span Study.

Given a collection of features available for inclusion in a predictive model, it may be of interest to quantify the relative importance of a subset of features for the prediction task at hand. For example, in HIV vaccine trials, participant baseline characteristics are used to predict the probability of HIV acquisition over the intended follow-up period, and investigators may wish to understand how much certain types of predictors, such as behavioural factors, contribute to overall predictiveness. Time-to-event outcomes such as time to HIV acquisition are often subject to right censoring, and existing methods for assessing variable importance are typically not intended to be used in this setting. We describe a broad class of algorithm-agnostic variable importance measures for prediction in the context of survival data. We propose a nonparametric efficient estimation procedure that incorporates flexible learning of nuisance parameters, yields asymptotically valid inference and enjoys double robustness. We assess the performance of our proposed procedure via numerical simulations and analyse data from the HVTN 702 vaccine trial to inform enrolment strategies for future HIV vaccine trials.

Functional principal component analysis has been shown to be invaluable for revealing variation modes of longitudinal outcomes, which serve as important building blocks for forecasting and model building. Decades of research have advanced methods for functional principal component analysis, often assuming independence between the observation times and longitudinal outcomes. Yet such assumptions are fragile in real-world settings where observation times may be driven by outcome-related processes. Rather than ignoring the informative observation time process, we explicitly model the observational times by a general counting process dependent on time-varying prognostic factors. Identification of the mean, covariance function and functional principal components ensues via inverse intensity weighting. We propose using weighted penalized splines for estimation and establish consistency and convergence rates for the weighted estimators. Simulation studies demonstrate that the proposed estimators are substantially more accurate than the existing ones in the presence of a correlation between the observation time process and the longitudinal outcome process. We further examine the finite-sample performance of the proposed method using the Acute Infection and Early Disease Research Program study.