Effective surveillance of infectious diseases, cancers, and other deadly diseases is critically important for public health and safety of our society. Incidence data of such diseases are often collected spatially from different clinics and hospitals through a regional, national or global disease reporting system. In such a system, new batches of data keep being collected over time, and a decision needs

In heart failure (HF) trials efficacy is usually assessed by a composite endpoint including cardiovascular death (CVD) and heart failure hospitalizations (HFHs), which has traditionally been evaluated with a time-to-first-event analysis based on a Cox model. As a considerable fraction of events is ignored that way, methods for recurrent events were suggested, among others the semiparametric proportional

One of the key challenges of personalized medicine is to identify which patients will respond positively to a given treatment. The area of subgroup identification focuses on this challenge, that is, identifying groups of patients that experience desirable characteristics, such as an enhanced treatment effect. A crucial first step towards the subgroup identification is to identify the baseline variables

The increasingly widespread use of meta-analysis has led to growing interest in meta-analytic methods for rare events and sparse data. Conventional approaches tend to perform very poorly in such settings. Recent work in this area has provided options for sparse data, but these are still often hampered when heterogeneity across the available studies differs based on treatment group. We propose a permutation-based

There are sometimes cost, scientific, or logistical reasons to allocate individuals unequally in an individually randomized trial. In cluster randomized trials we can allocate clusters unequally and/or allow different cluster size between trial arms. We consider parallel group designs with a continuous outcome, and optimal designs that require the smallest number of individuals to be measured given

Clusterwise statistical inference is the most widely used technique for functional magnetic resonance imaging (fMRI) data analyses. Clusterwise statistical inference consists of two steps: (i) primary thresholding that excludes less significant voxels by a prespecified cut-off (eg, p < . 001 ); and (ii) clusterwise thresholding that controls the familywise error rate caused by clusters consisting of

High-dimensional data are becoming increasingly common in the medical field as large volumes of patient information are collected and processed by high-throughput screening, electronic health records, and comprehensive genomic testing. Statistical models that attempt to study the effects of many predictors on survival typically implement feature selection or penalized methods to mitigate the undesirable

In assessing prediction accuracy of multivariable prediction models, optimism corrections are essential for preventing biased results. However, in most published papers of clinical prediction models, the point estimates of the prediction accuracy measures are corrected by adequate bootstrap-based correction methods, but their confidence intervals are not corrected, for example, the DeLong's confidence

In clinical trials, there often exist multiple historical studies for the same or related treatment investigated in the current trial. Incorporating historical data in the analysis of the current study is of great importance, as it can help to gain more information, improve efficiency, and provide a more comprehensive evaluation of treatment. Enlightened by the unit information prior (UIP) concept

In a quantitative synthesis of studies via meta-analysis, it is possible that some studies provide a markedly different relative treatment effect or have a large impact on the summary estimate and/or heterogeneity. Extreme study effects (outliers) can be detected visually with forest/funnel plots and by using statistical outlying detection methods. A forward search (FS) algorithm is a common outlying

Causal inference methods are gaining increasing prominence in pharmaceutical drug development in light of the recently published addendum on estimands and sensitivity analysis in clinical trials to the E9 guideline of the International Council for Harmonisation. The E9 addendum emphasises the need to account for post-randomization or ‘intercurrent’ events that can potentially influence the interpretation

Chronic medical conditions often necessitate regular testing for proper treatment. Regular testing of all afflicted individuals may not be feasible due to limited resources, as is true with HIV monitoring in resource-limited settings. Pooled testing methods have been developed in order to allow regular testing for all while reducing resource burden. However, the most commonly used methods do not make

We introduce a numerically tractable formulation of Bayesian joint models for longitudinal and survival data. The longitudinal process is modeled using generalized linear mixed models, while the survival process is modeled 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

In prediction model research, external validation is needed to examine an existing model's performance using data independent to that for model development. Current external validation studies often suffer from small sample sizes and consequently imprecise predictive performance estimates. To address this, we propose how to determine the minimum sample size needed for a new external validation study

Since the outbreak of the new coronavirus disease (COVID-19), a large number of scientific studies and data analysis reports have been published in the International Journal of Medicine and Statistics. Taking the estimation of the incubation period as an example, we propose a low-cost method to integrate external research results and available internal data together. By using empirical likelihood method

Gaussian graphical models are usually estimated from unreplicated data. The data are, however, likely to comprise signal and noise. These two cannot be deconvoluted from unreplicated data. Pragmatically, the noise is then ignored in practice. We point out the consequences of this practice for the reconstruction of the conditional independence graph of the signal. Replicated data allow for the deconvolution

A common goal in comparative effectiveness research is to estimate treatment effects on prespecified subpopulations of patients. Though widely used in medical research, causal inference methods for such subgroup analysis (SGA) remain underdeveloped, particularly in observational studies. In this article, we develop a suite of analytical methods and visualization tools for causal SGA. First, we introduce

We show how entropy balancing can be used for transporting experimental treatment effects from a trial population onto a target population. This method is doubly robust in the sense that if either the outcome model or the probability of trial participation is correctly specified, then the estimate of the target population average treatment effect is consistent. Furthermore, we only require the sample

Outcomes from studies assessing exposure often use multiple measurements. In previous work, using a model first proposed by Buonoccorsi (1991), we showed that combining direct (eg, biomarkers) and indirect (eg, self-report) measurements provides a more accurate picture of true exposure than estimates obtained when using a single type of measurement. In this article, we propose a tool for efficient

In the published article entitled “Survival analysis using a 5-step stratified testing and amalgamation routine (5-STAR) in randomized clinical trials” (DOI:10.1002/sim.8750), the Figures 5, 7, 5, 7, and 9 in the first published version should appear as follows: FIGURE 5 Open in figure viewerPowerPoint Results from 5-STAR Step 4 and Step 5 for Example 1. Top: Kaplan-Meier curves by treatment within

Expectile regression can be used to analyze the entire conditional distribution of a response, omitting all distributional assumptions. Among its benefits are computational simplicity, efficiency, and the possibility to incorporate a semiparametric predictor. Due to its advantages in full data settings, we propose an extension to right-censored data situations, where conventional methods typically

Recurrent event data frequently arise in longitudinal studies and observations on recurrent events could be terminated by a major failure event such as death. In many situations, there exist a large fraction of subjects without any recurrent events of interest. Among these subjects, some are unsusceptible to recurrent events, while others are susceptible but have no recurrent events being observed

Bulk and single-cell RNA-seq (scRNA-seq) data are being used as alternatives to traditional technology in biology and medicine research. These data are used, for example, for the detection of differentially expressed (DE) genes. Several statistical methods have been developed for the classification of bulk and single-cell RNA-seq data. These feature genes are vitally important for the classification

In public health research, finite resources often require that decisions be made at the study design stage regarding which individuals to sample for detailed data collection. At the same time, when study units are naturally clustered, as patients are in clinics, it may be preferable to sample clusters rather than the study units, especially when the costs associated with travel between clusters are

The analysis of randomized trials with time-to-event endpoints is nearly always plagued by the problem of censoring. In practice, such analyses typically invoke the assumption of noninformative censoring. While this assumption usually becomes more plausible as more baseline covariates are being adjusted for, such adjustment also raises concerns. Prespecification of which covariates will be adjusted

We present a statistical model that can be employed to monitor the time evolution of the COVID-19 contagion curve and the associated reproduction rate. The model is a Poisson autoregression of the daily new observed cases and dynamically adapt its estimates to explain the evolution of contagion in terms of a short-term and long-term dependence of case counts, allowing for a comparative evaluation of

We thank Krahn et al for their letter1 and welcome the opportunity to discuss this further. When assessing inconsistency, interest lies in the difference between the direct evidence and the network evidence. We believe the difference between our paper and the correction that Krahn et al1 have suggested arises due to the possibility of interpreting “detaching a design” in one of two ways. In their original

A typographical error was made in the name of the second author in our article “Quantifying how diagnostic test accuracy depends on threshold in a meta-analysis”, published in 2019 (https://onlinelibrary.wiley.com/doi/full/10.1002/sim.8301). This should read “Constantine A Gatsonis”. Apologies to Prof Gatsonis for the error.

In biomedical studies, the causal mediation effect might be heterogeneous across individuals in the study population due to each study subject's unique characteristics. While individuals' mediation effects may differ from each other, it is often reasonable and more interpretable to assume that individuals belong to several distinct latent subgroups with similar attributes. In this article, we first

Spectral graph convolutional neural networks (GCN) are proposed to incorporate important information contained in graphs such as gene networks. In a standard spectral GCN, there is only one gene network to describe the relationships among genes. However, for genomic applications, due to condition- or tissue-specific gene function and regulation, multiple gene networks may be available; it is unclear

Most phase I trials in oncology aim to find the maximum tolerated dose (MTD) based on the occurrence of dose limiting toxicities (DLT). Evaluating the schedule of administration in addition to the dose may improve drug tolerance. Moreover, for some molecules, a bivariate toxicity endpoint may be more appropriate than a single endpoint. However, standard dose-finding designs do not account for multiple

We propose a class of alternative estimates and tests to restricted mean survival time (RMST) which improves power in numerous survival scenarios while maintaining a level of interpretability. The industry standards for interpretable hypothesis tests in survival analysis, RMST and logrank tests (LRTs), can suffer from low power in cases where the proportional hazards assumption fails. In particular

Balancing allocation of assigning units to two treatment groups to minimize the allocation differences is important in biomedical research. The complete randomization, rerandomization, and pairwise sequential randomization (PSR) procedures can be employed to balance the allocation. However, the first two do not allow a large number of covariates. In this article, we generalize the PSR procedure and

Obstructive sleep apnea (OSA) is a chronic disease characterized by recurrent pharyngeal collapses during sleep. In most severe cases, continuous positive airway pressure (CPAP) consists in keeping the airways open by administering mild air pressure. This treatment faces adherence issues.

In correlated data settings, analysts typically choose between fitting conditional and marginal models, whose parameters come with distinct interpretations, and as such the choice between the two should be made on scientific grounds. For settings where interest lies in marginal—or population-averaged—parameters, the question of how best to estimate those parameters is a statistical one, and analysts

Binary outcomes are extremely common in biomedical research. Despite its popularity, binomial regression often fails to model this kind of data accurately due to the overdispersion problem. Many alternatives can be found in the literature, the beta-binomial (BB) regression model being one of the most popular. The additional parameter of this model enables a better fit to overdispersed data. It also

In medical research, the development of mediation analysis with a survival outcome has facilitated investigation into causal mechanisms. However, studies have not discussed the death-truncation problem for mediators, the problem being that conventional mediation parameters cannot be well defined in the presence of a truncated mediator. In the present study, we systematically defined the completeness

Diagnostic tests are frequently reliant upon the interpretation of images by skilled raters. In many clinical settings, however, the variability observed between experts' ratings plays a detrimental role in the degree of confidence in these interpretations, leading to uncertainty in the diagnostic process. For example, in breast cancer testing, radiologists interpret mammographic images, while breast

In the published article entitled “Semiparametric mixture cure model analysis with competing risks data: Application to vascular access thrombosis data” (DOI:10.1002/sim.8711), there are typing errors in the affiliation of the second author, Pao-sheng Shen, which should be corrected as “Department of Statistics, Tunghai University, Taichung, Taiwan, R.O.C.”

Multiple public health and medical research studies have applied matched-pair cluster randomization design to the evaluation of the intervention and/or prevention effects. One of the most common and severe problems faced by researchers when conducting cluster randomized trials (CRTs) is incomplete observations, which are associated with various reasons causing the individuals to discontinue participating

A Bayesian phase I-II design is presented that optimizes the dose of a new agent within predefined prognostic subgroups. The design is motivated by a trial to evaluate targeted agents for treating metastatic clear cell renal carcinoma, where a prognostic risk score defined by clinical variables and biomarkers is well established. Two clinical outcomes are used for dose-finding, time-to-toxicity during

The problem of testing multiple hypotheses using a group sequential procedure often arises in clinical trials. We review several group sequential Holm (GSHM) type procedures proposed in the literature and clarify the relationships between them. In particular, we show which procedures are equivalent or, if different, which are more powerful and what are their pros and cons. We propose a step-up group

Individuals differ in how they respond to a given treatment. In an effort to predict the treatment response and analyze the heterogeneity of treatment effect, we propose a general modeling framework by identifying treatment-covariate interactions honoring a hierarchical condition. We construct a single-step l 1 norm penalty procedure that maintains the hierarchical structure of interactions in the

Many epidemiologic studies forgo probability sampling and turn to nonprobability volunteer-based samples because of cost, response burden, and invasiveness of biological samples. However, finite population (FP) inference is difficult to make from the nonprobability sample due to the lack of population representativeness. Aiming for making inferences at the population level using nonprobability samples

The power prior is a popular tool for constructing informative prior distributions based on historical data. The method consists of raising the likelihood to a discounting factor in order to control the amount of information borrowed from the historical data. However, one often wishes to assign this discounting factor a prior distribution and estimate it jointly with the parameters, which in turn necessitates

Meta-analysis of rare event data has recently received increasing attention due to the challenging issues rare events pose to traditional meta-analytic methods. One specific way to combine information and analyze rare event meta-analysis data utilizes confidence distributions (CDs). While several CD methods exist, no comparisons have been made to determine which method is best suited for homogeneous

We propose a ridge-penalized adaptive Mantel test (AdaMant) for evaluating the association of two high-dimensional sets of features. By introducing a ridge penalty, AdaMant tests the association across many metrics simultaneously. We demonstrate how ridge penalization bridges Euclidean and Mahalanobis distances and their corresponding linear models from the perspective of association measurement and

Molecularly targeted agents and immunotherapies have prolonged administration and complicated toxicity and efficacy profiles requiring longer toxicity observation windows and the inclusion of efficacy information to identify the optimal dose. Methods have been proposed to either jointly model toxicity and efficacy, or for prolonged observation windows. However, it is inappropriate to address these

Healthcare researchers are showing renewed interest in the utilization of N-of-1 clinical trials for the individualization of pharmacological treatments. Here, we propose a frequentist approach to conducting treatment individualization in N-of-1 trials that we call “partial empirical Bayes.” We infer the most beneficial treatment for the patient from combining the information provided by a previously

In prognosis studies to evaluate association between a continuous biomarker and a survival outcome, investigators often classify subjects into two subclasses of the high- and low-expression groups and apply simple survival analysis techniques of the Kaplan-Meier method and the logrank test. The high- and low-expressions are defined according to whether or not the observation of the biomarker is higher

Methods for estimating optimal treatment strategies typically assume unlimited access to resources. However, when a health system has resource constraints, such as limited funds, access to medication, or monitoring capabilities, medical decisions must account for competition between individuals in resource usage. The problem of incorporating resource constraints into optimal treatment strategies has

Observational studies usually include participants representing the wide heterogeneous population. The conditional causal effect, treatment effect conditional on baseline characteristics, is of practical importance. Its estimation is subject to two challenges. First, the causal effect is not observable in any individual due to counterfactuality. Second, high-dimensional baseline variables are involved

As the world faced the devastation of the COVID-19 pandemic in late 2019 and early 2020, numerous clinical trials were initiated in many locations in an effort to establish the efficacy (or lack thereof) of potential treatments. As the pandemic has been shifting locations rapidly, individual studies have been at risk of failing to meet recruitment targets because of declining numbers of eligible patients

We propose a practical principal component analysis (PCA) framework that provides a nonparametric means of simultaneously reducing the dimensions of and modeling functional and vector (multivariate) data. We first introduce a Hilbert space that combines functional and vector objects as a single hybrid object. The framework, termed a PCA of hybrid functional and vector data (HFV-PCA), is then based

This article considers how to estimate the accuracy of a diagnostic test when there are repeated observations, but without the availability of a gold standard or reference test. We identify conditions under which the structure of the observed data is rich enough to provide sufficient degrees of freedom, such that a suitable latent class model can be fitted with identifiable accuracy parameters. We