Segmented regression is a standard statistical procedure used to estimate the effect of a policy intervention on time series outcomes. This statistical method assumes the normality of the outcome variable, a large sample size, no autocorrelation in the observations, and a linear trend over time. Also, segmented regression is very sensitive to outliers. In a small sample study, if the outcome variable does not follow a Gaussian distribution, then using segmented regression to estimate the intervention effect leads to incorrect inferences. To address the small sample problem and non-normality in the outcome variable, including outliers, we describe and develop a robust statistical method to estimate the policy intervention effect in a series of longitudinal data. A simulation study is conducted to demonstrate the effect of outliers and non-normality in the outcomes by calculating the power of the test statistics with the segmented regression and the proposed robust statistical methods. Moreover, since finding the sampling distribution of the proposed robust statistic is analytically difficult, we use a nonparametric bootstrap technique to study the properties of the sampling distribution and make statistical inferences. Simulation studies show that the proposed method has more power than the standard t-test used in segmented regression analysis under the non-normality error distribution. Finally, we use the developed technique to estimate the intervention effect of the Istanbul Declaration on illegal organ activities. The robust method detected more significant effects compared to the standard method and provided shorter confidence intervals.
Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times, multiple time-varying confounders, and complex associational relationships simultaneously. Reasons for this include the potential computational burden, technical challenges, restricted modeling options for long follow-up times, and limited practical guidance in the literature. However, LTMLE has desirable asymptotic properties, i.e. it is doubly robust, and can y…
Single subject or n-of-1 research designs have been widely used to evaluate treatment interventions. Many statistical procedures such as split-middle trend lines, regression trend line, Shewart-chart trend line, binomial tests, randomization tests and Tryon C-statistics have been used to analyze single-subject data, but they fail to control Type I error due to serially-dependent time-series observations. The interrupted time series analysis maintains Type I error but assumes that the intervention effect to be a linear trend change from baseline. In this paper, we consider an improved intervent…
Measuring the effect of patient safety improvement efforts is needed to determine their value but is difficult due to the inherent complexities of hospital operations. In this paper, we show by case study how interrupted time series design can be used to isolate and measure the impact of interventions while accounting for confounders often present in complex health delivery systems. We searched for time-stamped data from electronic medical records and operating room information systems associated with perioperative patient flow in a large, urban, academic hospital in Baltimore, Maryland. We li…
Construction of just-in-time adaptive interventions, such as prompts delivered by mobile apps to promote and maintain behavioral change, requires knowledge about time-varying moderated effects to inform when and how we deliver intervention options. Micro-randomized trials (MRT) have emerged as a sequentially randomized design to gather requisite data for effect estimation. The existing literature (Qian et al., 2020; Boruvka et al., 2018; Dempsey et al., 2020) has defined a general class of causal estimands, referred to as "causal excursion effects", to assess the time-varying moderated effect.…
Quantile regression is a powerful statistical methodology that complements the classical linear regression by examining how covariates influence the location, scale, and shape of the entire response distribution and offering a global view of the statistical landscape. In this paper we propose a new quantile regression model for longitudinal data. The proposed approach incorporates the correlation structure between repeated measures to enhance the efficiency of the inference. In order to use the Newton-Raphson iteration method to obtain convergent estimates, the estimating functions are redefin…
Modern longitudinal data, for example from wearable devices, measures biological signals on a fixed set of participants at a diverging number of time points. Traditional statistical methods are not equipped to handle the computational burden of repeatedly analyzing the cumulatively growing dataset each time new data is collected. We propose a new estimation and inference framework for dynamic updating of point estimates and their standard errors across serially collected dependent datasets. The key technique is a decomposition of the extended score function of the quadratic inference function …
Swiss Data Science Center（瑞士数据科学中心）；ETH Zurich（苏黎世联邦理工学院）；Institute for Atmospheric and Climate Science（大气与气候科学研究所）
Fingerprints are key tools in climate change detection and attribution (D&A) that are used to determine whether changes in observations are different from internal climate variability (detection), and whether observed changes can be assigned to specific external drivers (attribution). We propose a direct D&A approach based on supervised learning to extract fingerprints that lead to robust predictions under relevant interventions on exogenous variables, i.e., climate drivers other than the target. We employ anchor regression, a distributionally-robust statistical learning method inspired by cau…
We developed a prediction model based on the evolutionary causal matrices (ECM) and the Markov Chain to predict long-term influences of educational interventions on adolescents development. Particularly, we created a computational model predicting longitudinal influences of different types of stories of moral exemplars on adolescents voluntary service participation. We tested whether the developed prediction model can properly predict a long-term longitudinal trend of change in voluntary service participation rate by comparing prediction results and surveyed data. Furthermore, we examined whic…
In light of recent work studying massive functional/longitudinal data, such as the resulting data from the COVID-19 pandemic, we propose a novel functional/longitudinal data model which is a combination of the popular varying coefficient (VC) model and additive model. We call it Semi-VCAM in which the response could be a functional/longitudinal variable, and the explanatory variables could be a mixture of functional/longitudinal and scalar variables. Notably some of the scalar variables could be categorical variables as well. The Semi-VCAM simultaneously allows for both substantial flexibility…
Physical activity (PA) is significantly associated with many health outcomes. The wide usage of wearable accelerometer-based activity trackers in recent years has provided a unique opportunity for in-depth research on PA and its relations with health outcomes and interventions. Past analysis of activity tracker data relies heavily on aggregating minute-level PA records into day-level summary statistics, in which important information of PA temporal/diurnal patterns is lost. In this paper we propose a novel functional data analysis approach based on Riemann manifolds for modeling PA and its lon…
In learn-as-you-go (LAGO) adaptive studies, the intervention is a complex package consisting of multiple components, and is adapted in stages during the study based on past outcome data. This design formalizes standard practice, and desires for practice, in public health intervention studies. An effective intervention package is sought, while minimizing intervention package cost. When analyzing data from a learn-as-you-go study, the interventions in later stages depend upon the outcomes in the previous stages, violating standard statistical theory. We develop methods for estimating the interve…
This paper studies the generalization of the targeted minimum loss-based estimation (TMLE) framework to estimation of effects of time-varying interventions in settings where both interventions, covariates, and outcome can happen at subject-specific time-points on an arbitrarily fine time-scale. TMLE is a general template for constructing asymptotically linear substitution estimators for smooth low-dimensional parameters in infinite-dimensional models. Existing longitudinal TMLE methods are developed for data where observations are made on a discrete time-grid. We consider a continuous-time cou…
The Drinkers' Intervention to Prevent TB (DIPT) is a randomized controlled trial designed to determine if incentive-based approaches can reduce alcohol use and improve medication adherence to isoniazid (INH) preventive therapy in persons with HIV (PWH) co-infected with tuberculosis (TB) who engage in heavy drinking in Uganda. This statistical analysis plan (SAP) provides a detailed descriptions of the primary and secondary outcomes in the study and the corresponding statistical analyses.
Understanding the pathways whereby an intervention has an effect on an outcome is a common scientific goal. A rich body of literature provides various decompositions of the total intervention effect into pathway specific effects. Interventional direct and indirect effects provide one such decomposition. Existing estimators of these effects are based on parametric models with confidence interval estimation facilitated via the nonparametric bootstrap. We provide theory that allows for more flexible, possibly machine learning-based, estimation techniques to be considered. In particular, we establ…
Ron et al (1998) introduced a rich family of models for discrete longitudinal data, called acyclic probabilistic finite automata. These may be described as context-specific graphical models, since they are represented as directed multigraphs that embody context-specific conditional independence relations. Here we develop the methodology from a statistical modelling perspective. We show how likelihood ratio tests may be constructed using standard contingency table methods, and indicate how these may be used in model selection. We also show that the models generalize certain subclasses of conven…
We consider the marginal models of Liang and Zeger [Biometrika 73 (1986) 13-22] for the analysis of longitudinal data and we develop a theory of statistical inference for such models. We prove the existence, weak consistency and asymptotic normality of a sequence of estimators defined as roots of pseudo-likelihood equations.
Longitudinal social network studies can easily suffer from insufficient statistical power. Studies that simultaneously investigate change of network ties and change of nodal attributes (selection and influence studies) are particularly at risk because the number of nodal observations is typically much lower than the number of observed tie variables. This paper presents a simulation-based procedure to evaluate statistical power of longitudinal social network studies in which stochastic actor-oriented models (SAOMs) are to be applied. Two detailed case studies illustrate how statistical power is…
Statistical inference of directed relations given some unspecified interventions (i.e., the intervention targets are unknown) is challenging. In this article, we test hypothesized directed relations with unspecified interventions. First, we derive conditions to yield an identifiable model. Unlike classical inference, testing directed relations requires identifying the ancestors and relevant interventions of hypothesis-specific primary variables. To this end, we propose a peeling algorithm based on nodewise regressions to establish a topological order of primary variables. Moreover, we prove th…
In the field of cardio-thoracic surgery, valve function is monitored over time after surgery. The motivation for our research comes from a study which includes patients who received a human tissue valve in the aortic position. These patients are followed prospectively over time by standardized echocardiographic assessment of valve function. Loss of follow-up could be caused by valve intervention or the death of the patient. One of the main characteristics of the human valve is that its durability is limited. Therefore, it is of interest to obtain a prognostic model in order for the physicians …
Despite of many measures applied for determine the difference between two groups of observations, such as mean value, median value, sample stan- dard deviation and so on, we propose a novel non parametric transformation method based on Mallows distance to investigate the location and variance differences between the two groups. The convexity theory of this method is constructed and thus it is a viable alternative for data of any distribu- tions. In addition, we are able to establish the similar method under other distance measures, such as Kolmogorov-Smirnov distance. The application of our me…
Biosecurity risk material (BRM) presents a clear and significant threat to national and international environmental and economic assets. Intercepting BRM carried by non-compliant international passengers is a key priority of border biosecurity services. Global travel rates are constantly increasing, which complicates this important responsibility, and necessitates judicious intervention. Selection of passengers for intervention is generally performed manually, and the quality of the selection depends on the experience and judgement of the officer making the selection. In this article we report…
It is important to characterize the temporal trajectories of disease-related biomarkers in order to monitor progression and identify potential points of intervention. This is especially important for neurodegenerative diseases, as therapeutic intervention is most likely to be effective in the preclinical disease stages prior to significant neuronal damage. Longitudinal neuroimaging allows for the measurement of structural, functional, and metabolic integrity of the brain over time at the level of voxels. However, commonly used longitudinal analysis approaches, such as linear mixed effects mode…
In many longitudinal microarray studies, the gene expression levels in a random sample are observed repeatedly over time under two or more conditions. The resulting time courses are generally very short, high-dimensional, and may have missing values. Moreover, for every gene, a certain amount of variability in the temporal profiles, among biological replicates, is generally observed. We propose a functional mixed-effects model for estimating the temporal pattern of each gene, which is assumed to be a smooth function. A statistical test based on the distance between the fitted curves is then ca…
Statistical Design of Pragmatic Trials Using Electronic Health Record Data when Outcome Assessments are Uncontrolled and Irregular
Kaiser Permanente Washington Health Research Institute（凯撒永久华盛顿健康研究所）；Kaiser Permanente Center for Health Research Northwest Region（凯撒永久西北区健康研究中心）；Department of Biostatistics, School of Public Health, University of Washington（华盛顿大学公共卫生学院生物统计系）
Although there is much excitement surrounding the use of mobile and wearable technology for the purposes of delivering interventions as people go through their day-to-day lives, data analysis methods for constructing and optimizing digital interventions lag behind. Here, we elucidate data analysis methods for primary and secondary analyses of micro-randomized trials (MRTs), an experimental design to optimize digital just-in-time adaptive interventions. We provide a definition of causal "excursion" effects suitable for use in digital intervention development. We introduce the weighted and cente…
A Machine Learning-Based Framework to Shorten the Questionnaire for Assessing Autism Intervention
Emma Willard School（艾玛威拉德学校）；The Harker School（哈克学校）；Newton South High School（牛顿南高中）；Fairview High School（美景高中）；Massachusetts General Hospital（麻省总医院）；Harvard Medical School（哈佛医学院）；University College London（伦敦大学学院）
The PROmotion of Breastfeeding Intervention Trial (PROBIT) cluster-randomized a program encouraging breastfeeding to new mothers in hospital centers. The original studies indicated that this intervention successfully increased duration of breastfeeding and lowered rates of gastrointestinal tract infections in newborns. Additional scientific and popular interest lies in determining the causal effect of longer breastfeeding on gastrointestinal infection. In this study, we estimate the expected infection count under various lengths of breastfeeding in order to estimate the effect of breastfeeding…
When Method Choice Changes Statistical Inference: A Comparison of a Baseline Two-Stage Approach and Bayesian Joint Modeling for Longitudinal and Survival Data in an HIV Clinical Trial
The generalized g-formula can be used to estimate the probability of survival under a sustained treatment strategy. When treatment strategies are deterministic, estimators derived from the so-called efficient influence function (EIF) for the g-formula will be doubly robust to model misspecification. In recent years, several practical applications have motivated estimation of the g-formula under non-deterministic treatment strategies where treatment assignment at each time point depends on the observed treatment process. In this case, EIF-based estimators may or may not be doubly robust. In thi…
Early detection of clinical outcomes such as cancer may be predicted based on longitudinal biomarker measurements. Tracking longitudinal biomarkers as a way to identify early disease onset may help to reduce mortality from diseases like ovarian cancer that are more treatable if detected early. Two general frameworks for disease risk prediction, the shared random effects model (SREM) and the pattern mixture model (PMM) could be used to assess longitudinal biomarkers on disease early detection. In this paper, we studied the predictive performances of SREM and PMM on disease early detection throu…
The pandemic of COVID-19 has caused severe public health consequences around the world. Many interventions of COVID-19 have been implemented. It is of great public health and societal importance to evaluate the effects of interventions in the pandemic of COVID-19. In this paper, with help of synthetic control method, regression discontinuity and a Susceptible-Infected and infectious without isolation-Hospitalized in isolation-Removed (SIHR) model, we evaluate the horizontal and longitudinal effects of stringent interventions implemented in Wenzhou, a representative urban city of China, where s…
The use of observational time series data to assess the impact of multi-time point interventions is becoming increasingly common as more health and activity data are collected and digitized via wearables, social media, and electronic health records. Such time series may involve hundreds or thousands of irregularly sampled observations. One common analysis approach is to simplify such time series by first discretizing them into sequences before applying a discrete-time estimation method that adjusts for time-dependent confounding. In certain settings, this discretization results in sequences wi…
A new statistical approach for joint modeling of longitudinal outcomes measured in electronic health records with clinically informative presence and observation processes
Modeling Parkinson's Disease Progression Using Longitudinal Voice Biomarkers: A Comparative Study of Statistical and Neural Mixed-Effects Models
Department of Mathematical Sciences（数学科学系）；Naveen Jindal School of Management（奈文·金达管理学院）；Department of Biology（生物系）；University of Texas at Dallas（德克萨斯大学达拉斯分校）；Duke University（杜克大学）；The Second Affiliated Hospital, Zhejiang University School of Medicine（浙江大学医学院第二附属医院）；Department of Neurosurgery（神经外科系）
Forecasting intra-individual changes of affective states taking into account inter-individual differences using intensive longitudinal data from a university student drop out study in math
Technological advancements in mobile devices have made it possible to deliver mobile health interventions to individuals. A novel intervention framework that emerges from such advancements is the just-in-time adaptive intervention (JITAI), where it aims to suggest the right support to the individual "just in time", when their needs arise, thus having proximal, near future effects. The micro-randomized trial (MRT) design was proposed recently to test the proximal effects of these JITAIs. In an MRT, participants are repeatedly randomized to one of the intervention options of various in the inter…
Causal identification of treatment effects for infectious disease outcomes in interconnected populations is challenging because infection outcomes may be transmissible to others, and treatment given to one individual may affect others' outcomes. Contagion, or transmissibility of outcomes, complicates standard conceptions of treatment interference in which an intervention delivered to one individual can affect outcomes of others. Several statistical frameworks have been proposed to measure causal treatment effects in this setting, including structural transmission models, mediation-based partne…
