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Cluster randomized trials (CRTs) are studies where treatment is randomized at the cluster level but outcomes are typically collected at the individual level. When CRTs are employed in pragmatic settings, baseline population characteristics may moderate treatment effects, leading to what is known as heterogeneous treatment effects (HTEs). Pre-specified, hypothesis-driven HTE analyses in CRTs can enable an understanding of how interventions may impact subpopulation outcomes. While closed-form sample size formulas have recently been proposed, assuming known intracluster correlation coefficients (ICCs) for both the covariate and outcome, guidance on optimal cluster randomized designs to ensure maximum power with pre-specified HTE analyses has not yet been developed. We derive new design formulas to determine the cluster size and number of clusters to achieve the locally optimal design (LOD) that minimizes variance for estimating the HTE parameter given a budget constraint. Given the LODs are based on covariate and outcome-ICC values that are usually unknown, we further develop the maximin design for assessing HTE, identifying the combination of design resources that maximize the relative efficiency of the HTE analysis in the worst case scenario. In addition, given the analysis of the average treatment effect is often of primary interest, we also establish optimal designs to accommodate multiple objectives by combining considerations for studying both the average and heterogeneous treatment effects. We illustrate our methods using the context of the Kerala Diabetes Prevention Program CRT, and provide an R Shiny app to facilitate calculation of optimal designs under a wide range of design parameters.

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We adopt a maximum-likelihood framework to estimate parameters of a stochastic susceptible-infected-recovered (SIR) model with contact tracing on a rooted random tree. Given the number of detectees per index case, our estimator allows to determine the degree distribution of the random tree as well as the tracing probability. Since we do not discover all infectees via contact tracing, this estimation is non-trivial. To keep things simple and stable, we develop an approximation suited for realistic situations (contract tracing probability small, or the probability for the detection of index cases small). In this approximation, the only epidemiological parameter entering the estimator is $R_0$. The estimator is tested in a simulation study and is furthermore applied to covid-19 contact tracing data from India. The simulation study underlines the efficiency of the method. For the empirical covid-19 data, we compare different degree distributions and perform a sensitivity analysis. We find that particularly a power-law and a negative binomial degree distribution fit the data well and that the tracing probability is rather large. The sensitivity analysis shows no strong dependency of the estimates on the reproduction number. Finally, we discuss the relevance of our findings.

There are multiple cluster randomised trial designs that vary in when the clusters cross between control and intervention states, when observations are made within clusters, and how many observations are made at that time point. Identifying the most efficient study design is complex though, owing to the correlation between observations within clusters and over time. In this article, we present a review of statistical and computational methods for identifying optimal cluster randomised trial designs. We also adapt methods from the experimental design literature for experimental designs with correlated observations to the cluster trial context. We identify three broad classes of methods: using exact formulae for the treatment effect estimator variance for specific models to derive algorithms or weights for cluster sequences; generalised methods for estimating weights for experimental units; and, combinatorial optimisation algorithms to select an optimal subset of experimental units. We also discuss methods for rounding weights to whole numbers of clusters and extensions to non-Gaussian models. We present results from multiple cluster trial examples that compare the different methods, including problems involving determining optimal allocation of clusters across a set of cluster sequences, and selecting the optimal number of single observations to make in each cluster-period for both Gaussian and non-Gaussian models, and including exchangeable and exponential decay covariance structures.

Our motivation is to shed light the performance of the widely popular "R-Learner." Like many other methods for estimating conditional average treatment effects (CATEs), R-Learning can be expressed as a weighted pseudo-outcome regression (POR). Previous comparisons of POR techniques have paid careful attention to the choice of pseudo-outcome transformation. However, we argue that the dominant driver of performance is actually the choice of weights. Specifically, we argue that R-Learning implicitly performs an inverse-variance weighted form of POR. These weights stabilize the regression and allow for convenient simplifications of bias terms.

In randomized trials, repeated measures of the outcome are routinely collected. The mixed model for repeated measures (MMRM) leverages the information from these repeated outcome measures, and is often used for the primary analysis to estimate the average treatment effect at the primary endpoint. MMRM, however, can suffer from bias and precision loss when it models intermediate outcomes incorrectly, and hence fails to use the post-randomization information harmlessly. This paper proposes an extension of the commonly used MMRM, called IMMRM, that improves the robustness and optimizes the precision gain from covariate adjustment, stratified randomization, and adjustment for intermediate outcome measures. Under regularity conditions and missing completely at random, we prove that the IMMRM estimator for the average treatment effect is robust to arbitrary model misspecification and is asymptotically equal or more precise than the analysis of covariance (ANCOVA) estimator and the MMRM estimator. Under missing at random, IMMRM is less likely to be misspecified than MMRM, and we demonstrate via simulation studies that IMMRM continues to have less bias and smaller variance. Our results are further supported by a re-analysis of a randomized trial for the treatment of diabetes.

Cluster-randomized experiments are increasingly used to evaluate interventions in routine practice conditions, and researchers often adopt model-based methods with covariate adjustment in the statistical analyses. However, the validity of model-based covariate adjustment is unclear when the working models are misspecified, leading to ambiguity of estimands and risk of bias. In this article, we first adapt two conventional model-based methods, generalized estimating equations and linear mixed models, with weighted g-computation to achieve robust inference for cluster-average and individual-average treatment effects. To further overcome the limitations of model-based covariate adjustment methods, we propose an efficient estimator for each estimand that allows for flexible covariate adjustment and additionally addresses cluster size variation dependent on treatment assignment and other cluster characteristics. Such cluster size variations often occur post-randomization and, if ignored, can lead to bias of model-based estimators. For our proposed efficient covariate-adjusted estimator, we prove that when the nuisance functions are consistently estimated by machine learning algorithms, the estimator is consistent, asymptotically normal, and efficient. When the nuisance functions are estimated via parametric working models, the estimator is triply-robust. Simulation studies and analyses of three real-world cluster-randomized experiments demonstrate that the proposed methods are superior to existing alternatives.

The practical utility of causality in decision-making is widespread and brought about by the intertwining of causal discovery and causal inference. Nevertheless, a notable gap exists in the evaluation of causal discovery methods, where insufficient emphasis is placed on downstream inference. To address this gap, we evaluate seven established baseline causal discovery methods including a newly proposed method based on GFlowNets, on the downstream task of treatment effect estimation. Through the implementation of a distribution-level evaluation, we offer valuable and unique insights into the efficacy of these causal discovery methods for treatment effect estimation, considering both synthetic and real-world scenarios, as well as low-data scenarios. The results of our study demonstrate that some of the algorithms studied are able to effectively capture a wide range of useful and diverse ATE modes, while some tend to learn many low-probability modes which impacts the (unrelaxed) recall and precision.

With the increasing availability of datasets, developing data fusion methods to leverage the strengths of different datasets to draw causal effects is of great practical importance to many scientific fields. In this paper, we consider estimating the quantile treatment effects using small validation data with fully-observed confounders and large auxiliary data with unmeasured confounders. We propose a Fused Quantile Treatment effects Estimator (FQTE) by integrating the information from two datasets based on doubly robust estimating functions. We allow for the misspecification of the models on the dataset with unmeasured confounders. Under mild conditions, we show that the proposed FQTE is asymptotically normal and more efficient than the initial QTE estimator using the validation data solely. By establishing the asymptotic linear forms of related estimators, convenient methods for covariance estimation are provided. Simulation studies demonstrate the empirical validity and improved efficiency of our fused estimators. We illustrate the proposed method with an application.

We study the fundamental problem of fairly allocating a set of indivisible goods among $n$ agents with additive valuations using the desirable fairness notion of maximin share (MMS). MMS is the most popular share-based notion, in which an agent finds an allocation fair to her if she receives goods worth at least her MMS value. An allocation is called MMS if all agents receive at least their MMS value. However, since MMS allocations need not exist when $n>2$, a series of works showed the existence of approximate MMS allocations with the current best factor of $\frac{3}{4} + O(\frac{1}{n})$. The recent work by Akrami et al. showed the limitations of existing approaches and proved that they cannot improve this factor to $3/4 + \Omega(1)$. In this paper, we bypass these barriers to show the existence of $(\frac{3}{4} + \frac{3}{3836})$-MMS allocations by developing new reduction rules and analysis techniques.

The last decade has seen many attempts to generalise the definition of modes, or MAP estimators, of a probability distribution $\mu$ on a space $X$ to the case that $\mu$ has no continuous Lebesgue density, and in particular to infinite-dimensional Banach and Hilbert spaces $X$. This paper examines the properties of and connections among these definitions. We construct a systematic taxonomy -- or `periodic table' -- of modes that includes the established notions as well as large hitherto-unexplored classes. We establish implications between these definitions and provide counterexamples to distinguish them. We also distinguish those definitions that are merely `grammatically correct' from those that are `meaningful' in the sense of satisfying certain `common-sense' axioms for a mode, among them the correct handling of discrete measures and those with continuous Lebesgue densities. However, despite there being 17 such `meaningful' definitions of mode, we show that none of them satisfy the `merging property', under which the modes of $\mu|_{A}$, $\mu|_{B}$ and $\mu|_{A \cup B}$ enjoy a straightforward relationship for well-separated positive-mass events $A,B \subseteq X$.

A bootstrap procedure for constructing prediction bands for a stationary functional time series is proposed. The procedure exploits a general vector autoregressive representation of the time-reversed series of Fourier coefficients appearing in the Karhunen-Loeve representation of the functional process. It generates backward-in-time, functional replicates that adequately mimic the dependence structure of the underlying process in a model-free way and have the same conditionally fixed curves at the end of each functional pseudo-time series. The bootstrap prediction error distribution is then calculated as the difference between the model-free, bootstrap-generated future functional observations and the functional forecasts obtained from the model used for prediction. This allows the estimated prediction error distribution to account for the innovation and estimation errors associated with prediction and the possible errors due to model misspecification. We establish the asymptotic validity of the bootstrap procedure in estimating the conditional prediction error distribution of interest, and we also show that the procedure enables the construction of prediction bands that achieve (asymptotically) the desired coverage. Prediction bands based on a consistent estimation of the conditional distribution of the studentized prediction error process also are introduced. Such bands allow for taking more appropriately into account the local uncertainty of prediction. Through a simulation study and the analysis of two data sets, we demonstrate the capabilities and the good finite-sample performance of the proposed method.

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