Recent Past Seminars

 Abstract: In this paper, we consider the Bayesian design of a randomized, double-blind, placebo-controlled superiority clinical trial. To leverage multiple historical data sets to augment the placebo-controlled arm, we develop three conditional borrowing approaches built upon the borrowing-by-parts prior, the hierarchical prior, and the robust mixture prior.  The operating characteristics of the conditional borrowing approaches are examined. Extensive simulation studies are carried out to empirically demonstrate the superiority of the conditional borrowing approaches over the unconditional borrowing or no-borrowing approaches in terms of controlling type I error, maintaining good power, having a large “sweet-spot” region, minimizing bias, and reducing the mean squared error of the posterior estimate of the mean parameter of the placebo-controlled arm.  Computational algorithms are also developed for calculating the Bayesian type I error and power as well as the corresponding simulation errors. This is a joint work with Wenlin Yuan and John Zhong.

Location: Online via Zoom

Abstract: Causal inference with observational longitudinal data and time-varying exposures is complicated due to the potential for time-dependent confounding and unmeasured confounding. Most causal inference methods that handle time-dependent confounding rely on either the assumption of no unmeasured confounders or the availability of an unconfounded variable that is associated with the exposure (e.g., an instrumental variable). Furthermore, when data are incomplete, validity of many methods often depends on the assumption of missing at random. The proposed approach combines a parametric joint mixed-effects model for the study outcome and the exposure with g-computation to identify and estimate causal effects in the presence of time-dependent confounding and unmeasured confounding. G-computation can estimate participant-specific or population-average causal effects using parameters of the joint model. The joint model is a type of shared parameter model where the outcome and exposure-selection models share common random effect(s). The joint model is also extended to handle missing data and truncation by death when missingness is possibly not at random. Performance of the proposed method is evaluated using simulation studies, and the method is compared to both linear mixed- and fixed-effects models combined with g-computation as well as to targeted maximum likelihood estimation. The method is applied to an epidemiologic study of vitamin D and depressive symptoms in older adults and can be implemented using SAS PROC NLMIXED software, which enhances accessibility of the method to applied researchers.

Location: Online via Zoom

Abstract: Randomized clinical trials (RCT) are the gold standard for approvals by regulatory agencies. However, RCT’s are increasingly time consuming, expensive, and laborious with a multitude of bottlenecks involving volunteer recruitment, patient truancy, and adverse events. An alternative that fast tracks clinical trials without compromising quality of scientific results is desirable to more rapidly bring therapies to consumers. We propose a model-based approach using nonparametric Bayesian common atoms models for patient baseline covariates. This specific class of models has two critical advantages in this context: First, the models have full prior support, i.e., allow to approximate arbitrary distributions without unreasonable restrictions or shrinkage in specific parametric families; and second, inference naturally facilitates a re-weighting scheme to achieve equivalent populations. We prove equivalence of the synthetic and other patient cohorts using an independent separate verification. Failure to classify a merged data set using a flexible statistical learning method such as random forests, support vector machines etc. proves equivalence. We implement the proposed approach in two motivating case studies.

Location: Online via Zoom

Abstract: We present a general theoretical and algorithmic analysis of the problem of multiple-source adaptation, a key learning problem in applications such as medical diagnosis, sentiment analysis, speech recognition, and object recognition. We will also report the results of several experiments demonstrating the effectiveness of our algorithms and showing that they outperform all previously known baselines.

Location: Online via Zoom

Abstract: Science applied in a medicines regulatory context (“regulatory science”) sometimes has features that differs from traditional “academic science”. At the centre of regulatory science is that analyses must be decision-relevant, timely, and occasionally must rely on poor data. This seminar will present examples of biostatistical analyses that can support regulatory decision-making in the post-authorisation surveillance phase (e.g. pharmacoepidemiology). Examples will include analyses relying on data from the network of population-based Nordic healthcare databases. Lastly, the challenges posed with the advent of Advanced Therapeutic Medicinal Products (e.g. gene and cell therapies) will be discussed. These therapies have characteristics that are different from traditional medicinal products thereby having implications for approaches to pre- and post-authorisation evaluation.

Location: Online via Zoom

Abstract: Early or late phase clinical trials that aim to enroll a biomarker selected patient population are often initiated using a clinical trial assay (CTA) which may differ in assay components compared to the final companion diagnostic assay (CDx), potentially necessitating further clinical analysis to bridge study conclusions to results based on the CDx.  There may be substantial missing data due to the retrospective nature of CDx sample testing.  Key elements of the ideas behind bridging will be reviewed using a case study conducted for a randomized trial of pembrolizumab in second line metastatic non-small cell lung cancer.  Emphasis is on methods aimed at constructing an imputation model to (1) confirm the robustness of clinical trial conclusions via the Bayesian posterior predictive distribution of the study’s intention-to-treat testing results and (2) conduct sensitivity analysis for estimands of the intention-to-diagnose population, while capturing all sources of variability. 

Location: Online via Zoom

Abstract: Since 2014, synthetic controls, defined as a statistical method used to evaluate the comparative effectiveness of an intervention using a weighted combination of external controls in successful regulatory submissions in rare diseases and oncology is growing. In the next few years, the utilization of synthetic controls is likely to increase within the regulatory space owing to concurrent improvements in medical record collection, statistical methodologies, and sheer demand.  In this talk, I will focus on existing and new strategies from the applications of synthetic controls in the framework of augmented control designs. This will include (1) matching strategies and use of entrophy balancing; (2) distinction of causal estimands in augmented designs; (3) Bayesian methodologies for incorporating external information; (4) novel adaptive designs incorporating external information. 

Location: Online via Zoom

Abstract: Big data is best viewed not in terms of its size but in terms of its purpose:  if we can measure it all, maybe we can describe it all. In a molecular context, big data challenges the biomedical research community to describing all the levels of variation based on hundreds of thousands simultaneous measures and data types of DNA, RNA, and protein function alongside patient and tumor features. The bigger and more molecular data, the bigger the promise of advances and the greater the opportunities and challenges posed to the biomedical research community in our ability to harness the power of such data to obtain quick and reliable insights from it. Cancer research has been witnessed to many opportunities on the analytical front from the use of big data for big advances to usher in the era of precision medicine. We posit that the use of big data for big advances in cancer starts at the DNA-level and requires the synergy with, not replacement of, classical hypothesis-driven methods. We describe several methods, data types and metrics for detection of DNA variation at both the gene-and sample-level within the context of pancreatic cancer and their fit for purpose to improve our understanding of DNA level heterogeneity associated with phenotype diversity.   

Location: Online via Zoom

Abstract: Empirical data are seldom complete. Missing data pose a threat to the validity of statistical inferences when missingness is not a completely random process. Model based multiple imputation (MI) can make uses of all available information in the data file to predict missing information and can produce valid statistical inferences in many scenarios. In this talk, I give an introduction to MI, discuss pros and cons of MI and demonstrate how to use the popular mice package in R to create model based multiple imputations of missing values. Finally, I also show how to specify more advanced imputation models (using further add-ons to the mice package) for example for longitudinal count data based on piecewise growth curve models assuming a zero-inflated Poisson or negative Binomial data generating process.

Location: Online via Zoom

Abstract: In this talk, new computer vision algorithms to learn complex morphologies and phenotypes that are important for human diseases will be presented. I will illustrate this approach with examples that capture physical scales from macro to micro: 1) video-based AI to assess heart function (Ouyang et al Nature 2020), 2) generating spatial transcriptomics from histology images (He et al Nature BME 2020), 3) and learning morphodynamics of immune cells. Throughout the talk I’ll illustrate new design principles/tools for human-compatible and robust AI that we developed to enable these technologies (Ghorbani et al. ICML 2020, Abid et al. Nature MI 2020). 

Location: Online via Zoom

Abstract: Smoothing spline mixed-effects density models are proposed for the nonparametric estimation of density and conditional density functions with clustered data. The random effects in a density model introduce within-cluster correlation and allow us to borrow strength across clusters by shrinking cluster specific density function to the population average, where the amount of shrinkage is decided automatically by data. Estimation is carried out using the penalized likelihood and computed using a Markov chain Monte Carlo stochastic approximation algorithm.  We apply our methods to investigate evolution of hemoglobin density functions over time in response to guideline changes on anemia management for dialysis patients. Smoothing spline mixed-effects density models are proposed for the nonparametric estimation of density and conditional density functions with clustered data. The random effects in a density model introduce within-cluster correlation and allow us to borrow strength across clusters by shrinking cluster specific density function to the population average, where the amount of shrinkage is decided automatically by data. Estimation is carried out using the penalized likelihood and computed using a Markov chain Monte Carlo stochastic approximation algorithm. We apply our methods to investigate evolution of hemoglobin density functions over time in response to guideline changes on anemia management  for dialysis patients.

Location: Online via Zoom

Abstract: Phase I oncology trials aim to identify the optimal dose that will be recommended for phase II trials, but the standard designs are inefficient and inflexible. In this talk, I will introduce two innovative Bayesian adaptive designs we developed to improve the efficiency of the trial or incorporate the complex features of the trial. In the first example, we propose PA-CRM, a design for pediatric phase I trials when concurrent adult trials are being conducted. The design automatically and adaptively incorporate information from the concurrent adult trial into the ongoing pediatric trial, and thus greatly improves the efficiency of the pediatric trial. In the second example, we propose a design for early phase platform trials, where multiple doses of multiple targeted therapies are evaluated in patients with different biomarkers, with an objective to identify the best drug at an efficacious and safe dose for the subpopulation defined by a given biomarker. This design addresses complex issues of such platform trials, incorporates information about toxicity and response outcomes from multiple tested doses and biomarkers, and maximizes potential patients benefit from the targeted therapies.

Location: Online via Zoom

Abstract: A fundamental assumption usually made in causal inference is that of no interference between individuals (or units), i.e., the potential outcomes of one individual are assumed to be unaffected by the treatment assignment of other individuals. However, in many settings, this assumption obviously does not hold. For example, in infectious diseases, whether one person becomes infected may depend on who else in the population is vaccinated. In this talk we will discuss recent approaches to assessing treatment effects in the presence of interference.

Location: Online via Zoom

Abstract: Literature on change point analysis mostly requires a sudden change in the data distribution, either in a few parameters or the distribution as a whole. We are interested in the scenario where the variance of data may make a significant jump while the mean changes in a smooth fashion. The motivation is a liver procurement experiment monitoring organ surface temperature. Blindly applying the existing methods to the example can yield erroneous change point estimates since the smoothly-changing mean violates the sudden-change assumption. We propose a penalized weighted least squares approach with an iterative estimation procedure that integrates variance change point detection and smooth mean function estimation. The procedure starts with a consistent initial mean estimate ignoring the variance heterogeneity. Given the variance components the mean function is estimated by smoothing splines as the minimizer of the penalized weighted least squares. Given the mean function, we propose a likelihood ratio test statistic for identifying the variance change point. The null distribution of the test statistic is derived together with the rates of convergence of all the parameter estimates. Simulations show excellent performance of the proposed method. Application analysis offers numerical support to non-invasive organ viability assessment by surface temperature monitoring. Extension to functional variance change point detection will also be presented if time allows.

Location: Online via Zoom

Abstract: In this talk, we exploit the complementing features of randomized clinical trials (RCT) and real world evidence (RWE) to estimate the average treatment effect of the target population. We will review existing methods in conducting integrated analysis of the data from RCTs and RWEs. We will then discuss in detail new calibration weighting estimators that are able to calibrate the covariate information between RCTs and RWEs. We will briefly review asymptotic results under mild regularity conditions, and confirm the finite sample performances of the proposed estimators by simulation experiments. In a comparison of existing methods, we illustrate our proposed methods to estimate the effect of adjuvant chemotherapy in early-stage resected non–small-cell lung cancer integrating data from a RCT and a sample from the National Cancer Database.

Location: Online via Zoom

Abstract: In 2018, there were 52.4 million Americans aged 65 years and older and represented 16% of the population.  By 2040, it is projected that there will be about 80.8 million people in this age group.  The 85 and older population is projected to more than double from 6.5 million in 2018 to 14.4 million in 2040.  Although people of all ages may need post-acute or long-term care services, the risk of needing these services increases with age.  

The National Post-acute and Long-term Care study monitors trends in the supply, provision, and use of the major sectors of paid, regulated long-term care services. NPALS uses survey data on the residential care community and adult day services sectors, and administrative data on the home health, nursing home, hospice, inpatient rehabilitation, and long-term care hospital sectors.  This presentation will describe the study, methodological issues, some findings from the study, and a brief discussion of future possibilities.

Location: Online via Zoom

Abstract: We have proposed a novel, accurate low-cost method to estimate the incubation-period distribution of COVID-19 by conducting a cross-sectional and forward follow-up study. We identified those pre-symptomatic individuals at their time of departure from Wuhan and followed them until the development of symptoms. The renewal process was adopted by considering the incubation period as a renewal and the duration between departure and symptoms onset as a forward time. Such a method enhances the accuracy of estimation by reducing recall bias and using the readily available data. The estimated median incubation period was 7.76 days [95% confidence interval (CI): 7.02 to 8.53], and the 90th percentile was 14.28 days (95% CI: 13.64 to 14.90). By including the possibility that a small portion of patients may contract the disease on their way out of Wuhan, the estimated probability that the incubation period is longer than 14 days was between 5 and 10%.

This is a joint work with Dr. Andrew Zhou’s group at the Biostatistics Department in Peking University.

Location: Online via Zoom

Abstract: Cluster randomized trials (CRTs) are often used in public health research in which the intervention is naturally applied to clusters, or groups, of individuals. Common examples include schools, medical care practices, and even entire communities. In this talk, we introduce possible study design and statistical analysis options for cluster randomized trial. Utilizing real-life examples, we focus on stepped wedge designs and the use of generalized estimating equations. Furthermore, because CRTs often involve only a small number of clusters, small-sample adjustments with the GEE approach are explored.

Location: Online via Zoom

Abstract:  As nowadays confirmatory clinical trials become increasingly complex pursuing several goals simultaneously, the graphical testing approach is often used to address testing of multiple hypotheses of interest.  This approach for a strong control of the familywise error rate (FWER) has several features that are appealing to clinical teams. For example, it allows for a structured visualized evaluation while developing strategies based on importance of hypotheses and corresponding success likelihoods.

At this presentation we consider recent extensions of the graphical testing procedure to group sequential designs using a case study involving “dual” primary endpoints (pCR and MFS) along with several key secondary endpoints. This constitutes potential multiple paths to establish efficacy based on results at interim and final analyses that needs to be statistically addressed. Furthermore, hypothesis tests might have different numbers of analysis points and different rates of accumulation of statistical information.  Study design optimization  and practical implementations will be explored. 

Location: Online via Zoom

Abstract: Evaluation of medical products needs to consider its totality of evidence for benefits and harms that are measured through multiple relevant endpoints. The importance of these endpoints can vary for different clinical settings, clinicians, and patients. Evans and Follmann (2016) advocated the use the desirability of outcome ranking (DOOR) to integrate multiple outcomes according to their importance for the design and analysis of clinical trials. Wang and Chen (2019) proposed testing procedures for trend in benefit-risk analysis based on the importance of multiple outcomes.  In these approaches, the priority levels can be determined by clinicians or based on survey of patients. In this paper, we proposed a stratified randomization design and a composite win ratio endpoint (Pocock et al. 2012) to evaluate the treatment benefits based on patient individually reported outcomes and importance. We introduce motivation examples to illustrate importance of patient heterogeneity in endpoint importance, discuss mathematical properties and difference of our proposed approach with others, and demonstrate the differences and advantages via design examples. We will also discuss our experience using this approach in the development of a shared decision making trial for AFib stroke prevention. 

This is a joint work with Drs. Qian Zhao, Shiyan Yan, Lu TIan, Min M. Tu, and Jie Chen.

Location: Online via Zoom

Abstract: We propose a generalized empirical likelihood (GEL) method for causal inference based on a moment condition model that balances the treatment groups with respect to the potential confounders (e.g., as indicated by a directed acyclic graph). Allowing the number of moment conditions grow with the sample size, we show the asymptotic normality of the causal effects estimates without relying on regression models for the counterfactuals nor for the propensity scores. In a simulation study, we assess the finite sample properties of the proposed estimators in terms of the mean squared error and coverage of confidence intervals. We illustrate an application of the proposed method to data analysis of a training program study.

Authors: Pierre Chausse, Mihai Giurcanu, and George Luta

Location: Online via Zoom

Abstract:  The talk will concern the role of statistical thinking in the Search for Truth using data. This will bring us to a discussion of P-values, which has been, and still is, a central concept in Statistics and Biostatistics and has become a critical and highly controversial tool of scientific research. Recently it has elicited much, sometimes heated, debates and discussions. The American Statistical Association (ASA) was even compelled to release an official statement in early March 2016 regarding this issue, a psychology journal has gone to the extreme of banning the use of P-values in articles appearing in its journal, and a special issue of The American Statistician this year was fully devoted to this issue. The concerns about P-values has also been in relation to important issues of reproducibility and replicability in scientific research. This issue goes to the core of inductive inference and the different schools of thought (Fisher’s null hypothesis significance testing (NHST) approach, Neyman-Pearson paradigm, Bayesian approach, etc.) on how inductive inference (that is, the process of discovering the Truth through sample data) should be done. Some new perspectives on the use of P-values and on the search for truth through data will be discussed. In particular, we will discuss the representation of knowledge and its updating based on observations, and ask the question: “When given the P-value, what does it provide in the context of the updated knowledge of the phenomenon under consideration, and what additional information should accompany it?” This talk is based on the preprint in the Math ArXiV. (http://arxiv.org/abs/1910.05486 (new window))

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Applied researchers often need to construct confidence sets for policy effects based on functions of estimated parameters, and often these functions are such that the delta method cannot be used. In this case, researchers currently use one of two bootstrap procedures, but we show that these procedures can produce confidence sets that are too small. We provide two alternatives, both of which produce consistent confidence sets under reasonable assumptions that are likely to be met in empirical work. Our second, more efficient method produces consistent confidence sets in cases when the delta method cannot be used, but is asymptotically equivalent to the delta method if the use of the latter is valid. Finally, we show that our second procedure works well when we conduct counterfactual policy analyses using a dynamic model for employment.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Genetic analyses have identified etiological factors for several complex disease but understanding how genetic factors interact to increase risk is challenging. In this talk I describe the development of novel methods for large-scale identification of population-level attributes that may affect genome-wide association studies. Because studies we conduct are planned for hundreds of thousands of samples, we had to develop machine-learning based procedures that could be generalized for identifying ethnic variability. We also evaluated tools for jointly estimating the effects of multiple genetic factors by using machine learning tools including random forests and classification trees. These particular analytical schemes identified novel interactions among alleles at multiple loci influencing risk for a rare autoimmune disease. We are now studying the efficacy of modeling with classification tree based analysis versus more traditional approaches such as logistic regression with lasso for high dimensional SNP studies.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: For oncology clinical trials, time-to-event endpoints, such as overall survival or progression-free survival, are used widely as key endpoints and of great interest. While the classic log-rank test and Cox proportional hazards model have been considered as the “default” analysis methods for statistical inference and for quantifying treatment benefit, we have witnessed many challenges and issues when they cannot be readily or properly applied. Furthermore, in cancer treatment trials we also concurrently observe disease-related longitudinal processes or multiple outcomes that are dependently censored by some “terminal” event like death, and there is increasing need and interest in developing and applying alternative and statistically valid metrics and inference tools to assess the overall disease prognosis and benefit-risk profile more efficiently and in a timely fashion. In recent years, restricted mean survival time (RMST) has gained growing interests as an important alternative metric to evaluate survival data. In this talk we will review and discuss these recent methodological developments, as well as their potential use and implications in oncology clinical trials and drug development.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: In this talk, we highlight the use of causal inference and machine learning methods to reduce bias when assessing disease burden and to improve precision when estimating intervention effects in randomized trials. We illustrate with data from the SEARCH Study, a large (>320,000-person) cluster randomized trial for HIV prevention and improved community health in rural Kenya and Uganda (NCT01864603).

Location: Zoom only

Abstract: Observational medical databases increasingly find uses for comparative effectiveness and safety research. However, the lack of analytic methods that simultaneously handle the issues of missing data and confounding bias along with the onus of model specification, limit the use of these valuable data sources. We derived a novel machine-learning approach based on trees to estimate the average treatment effect. In order to evaluate causal estimation by model-free machine-learning methods in data with incomplete observations, we conducted a simulation study with data generated from known models of exposure, outcome and missing mechanisms. Thus the true causal effect was known and used as the benchmark for evaluations. Two settings were studied. We compared the bias and standard error of causal estimates from our method to a multiply robust parametric method, the complete case analysis (CC) and a regression analysis after multiple imputations (MI). The proposed methods were applied to a real observational data set of implantable cardioverter defibrillator use.

Location: Proctor Harvey Amphitheater, Med-Dent Building C104
3900 Reservoir Rd. NW, Washington, DC 20057

Abstract: This seminar presents applications of statistics and data science in the design and analysis of biomedical research studies including drug combinations, adaptive and/or targeted clinical trials designs, statistical learning and predictive modeling in head and neck cancer with a series of validation in three large randomized studies, and search for patient subgroups in precision medicine. Part I will focus on drug combinations which are the hallmark of therapies for complex diseases such as cancer. A statistical approach for evaluating the joint effect of the combination is necessary because even in vitro experiments often demonstrate significant variation in dose-effect. I will present a novel methodology for efficient design and analysis of preclinical drug combination studies with applications in the combination of Vorinostat and Ara-C and etoposide. Further discussion will be on the utilization of the preclinical data to guide early phase clinical trial design and a novel adaptive phase I design for drug combinations.

Location: Proctor Harvey Amphitheater, Med-Dent Building C104
3900 Reservoir Rd. NW, Washington, DC 20057

Abstract:  Multi-regional clinical trials (MRCTs) help to synchronize drug development globally, whereby the time lag in marketing authorization among different countries is minimized. However, there are statistical concerns associated with analysis and interpretation of MRCTs. The results of certain countries/regions could vary significantly from the overall results. In this case, controversy exists regarding the extent to which country-specific result should be minimized/ignored and medical scientists/regulators should defer to the overall global treatment effect. Rather than analyzing data separately in each region, our discussion today focuses on developing a Bayesian framework for assessing heterogeneity of regional treatment effects that leverages data collected in other regions. The goal is to make scientifically valid judgments about the play of chance versus real regional differences when comparing results to the overall trial outcome.

Location: New Research Building Auditorium
3970 Reservoir Rd. NW, Washington, DC 20057

Abstract: 

Pathological evaluations are frequently reported on an ordinal scale. Moreover, diseases may progress from less to more advanced stages. For example, HCV infection progresses from normal liver tissue to cirrhosis, dysplastic nodules, and potentially to hepatocellular carcinoma. To elucidate molecular mechanisms associated with disease progression, genomic characteristics from samples procured from these different tissue types are often assayed using a high-throughput platform. Such assays result in a high-dimensional feature space where the number of predictors (P) greatly exceeds the available sample size (N). In this talk, various approaches to modeling an ordinal response when P>N will be described including algorithmic and statistical methods.

Location: New Research Building Auditorium
3970 Reservoir Rd. NW, Washington, DC 20057

Abstract: Based on best practices from federal law enforcement officials, this training program is designed to increase awareness of the “run, hide, fight” protocols in case of an active shooter or violent incident. The course, which uses the “See Something, Say Something” concept, as well as detailed steps in an active shooter incident, is taught by the Georgetown University Police Department (GUPD).

Location: New Research Building Auditorium
3970 Reservoir Rd. NW, Washington, DC 20057

Abstract: Modern clinical trials need to be designed with much flexibility and efficiency. Flexibility includes adaptation based on new information while trial is ongoing and being monitored dynamically with cumulative data. Efficiency includes adequate study power and timely decision making regarding the future course of the trial. Both aspects require the protection of trial integrity and validity. Adaptive sequential designs have been proposed for clinical trials for the last decades. However, traditional computing environment could not accommodate trial monitoring at any time in a timely fashion. In this high-speed, AI – (artificial intelligence) – everywhere era, we introduce Dynamic Data Monitoring concept in which the cumulative data are monitored continuously, and the treatment effect is examined timely over the trial duration. Changing frequency and schedules of the interim analyses can be monitored at real time. The accumulating data can be viewed whenever new data is available and the timing of efficacy and futility assessments and sample size adaptation is made very flexibly, and the type I error rate is always controlled. Numerical and real study examples and simulations are presented. (Collaborated with Drs. Gordon Lan, Joe Shih, and Peng Zhang)

Location: Pre-Clinical Science Building, LA4
3900 Reservoir Rd. NW, Washington, DC 20057

Abstract:  We have proposed new algorithms to estimate the rarefaction curve and accordingly the number of species. The key idea in developing the algorithms is based on an interpolated rarefaction curve through quadratic optimization with linear constraints. Our proposed algorithms are easily implemented and show better performances than existing methods in terms of computational speed and accuracy. We also provide a criterion of model selection to choose tuning parameters and the idea of confidence interval. A broad range of numerical studies including simulations and real date examples are also conducted, and the gain that it produces has been compared to existing methods.

Location: Proctor Harvey Amphitheater, Med-Dent Building C104
3900 Reservoir Rd. NW, Washington, DC 20057

Abstract: The stochastic gradient Markov chain Monte Carlo (SGMCMC) algorithms, such as stochastic gradient Langevin dynamics and stochastic gradient Hamilton Monte Carlo, have recently received much attention in Bayesian computing for large-scale data for which the sample size can be very large, or the dimension can be very high, or both. However, these algorithms can only be applied to a small class of problems for which the parameter space has a fixed dimension and the log-posterior density is differentiable with respect to the parameters. We propose a class of extended SGMCMC algorithms which, by introducing appropriate latent variables and utilizing Fisher’s identity, can be applied to more general large-scale Bayesian computing problems, such as those involving dimension jumping and missing data. For a large-scale dataset with sample size N and dimension p, the proposed algorithms can achieve a computational complexity of O(N^{1+\epsilon} p^{1-\epsilon’}) for some small constants \epsilon and \epsilon’, which is quite comparable with the computational complexity O(N p^{1-\epsilon’}) achieved in general by the stochastic gradient descent (SGD) algorithm. The proposed algorithms are illustrated using high-dimensional variable selection, sparse deep learning with large-scale data, and a large-scale missing data problem. The numerical results show that the proposed algorithms have a significant computational advantage over traditional MCMC algorithms and can be highly scalable when mini-batch samples are used in simulations. Compared to frequentist methods, they can produce more accurate variable selection and prediction results, while exhibiting similar CPU costs when the dataset contains a large number of samples. The proposed algorithms have much alleviated the pain of Bayesian methods in large-scale computing.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Extensive research has been conducted in the Multi-Regional Clinical Trial (MRCT) area. To effectively apply an appropriate approach to a MRCT, we need to synthesize and understand the features of different approaches. In this presentation, numerical and real data examples are used to illustrate considerations regarding design, conduct, analysis and interpretation of result of MRCTs. We compare different models as well as their corresponding interpretations of the trial results. We highlight the importance of paying special attention to trial monitoring and conduct to prevent potential issues associated with the final trial results. Besides evaluating the overall treatment effect for the entire MRCT, we also consider other key analyses including quantification of regional treatment effects within a MRCT and the assessment of consistency of these regional treatment effects.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Developing targeted therapies based on patients’ baseline characteristics and genomic profiles such as biomarkers has gained growing interests in recent years. Depending on patients’ clinical characteristics, the expression of specific biomarkers or their combinations, different patient subgroups could respond differently to the same treatment. An ideal design, especially at the proof of concept stage, should search for such subgroups and make dynamic adaptation as the trial goes on. When no prior knowledge is available on whether the treatment works on the all-comer population or only works on the subgroup defined by one biomarker or several biomarkers, it’s necessary to estimate the subgroup effect adaptively based on the response outcomes and biomarker profiles from all the treated subjects at interim analyses. To address this problem, we propose an Adaptive Subgroup-Identification Enrichment Design, ASIED, to simultaneously search for predictive biomarkers, identify the subgroups with differential treatment effects, and modify study entry criteria at interim analyses when justified. More importantly, we construct robust quantitative decision-making rules for population enrichment when the interim outcomes are heterogeneous. Through extensive simulations, the ASIED is demonstrated to achieve desirable operating char- acteristics and compare favorably against the alternatives.  

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Neuroscience has a strong research tradition that employs experimental and observational studies in laboratory settings and controlled testing and evaluation in both clinical, educational and volunteer populations. In the past two decades, there has been increasing interest in conducting population-scale epidemiological studies of early age brain development and functioning as well as later age neurological functioning including cognitive impairment, dementias and Alzheimer’s disease. The data collected in these population-based studies is not restricted to observations on neurological systems and functioning but is collected in parallel with a wide array of information on participants’ life events, medical history, social and environmental exposures, genetics and genomics. This rich array of observational data has the potential to greatly advance our understanding of how complex neurological systems develop, are modified by internal or external factors or otherwise change over the life course. The growing field of epidemiological research also presents many challenging problems in design, measurement, data integration and analysis that those of us trained in biostatistics, bioinformatics and biomathematics will be called on to help to solve.

This presentation will use two cases studies to illustrate the nature of the statistical challenges in conducting population-scale neuroscientific research, describe current best practices and outline opportunities for future research. The first case study will be the Adolescent Brain Cognitive Development project (ABCD, https://abcdstudy.org), a 12-year longitudinal investigation of brain morphology and functional development in U.S. adolescents and teens. The second case study will focus on the challenges in design, measurement and analysis faced in special supplemental investigations of dementia and Alzheimer’s disease conducted under the auspices of the larger Health and Retirement Study (HRS, https://hrs.isr.umich.edu/about). Each case study review will include a description of the specific study challenges and current solutions. The major aim of this presentation is to increase awareness of these emerging lines of research and to promote interest on the part of the next generation of statisticians and data scientists who will be called upon to advance the various methodologies that will be required to better understand complex neurological systems and how they relate to our individual attributes and the world around us.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract:  Similar to its univariate counterpart, multivariate meta-analysis is a method to synthesize multiple outcome effects by taking in to account the available variance-covariance structure. It can improve efficiency over separate univariate syntheses and enables joint inferences across the outcomes. Multivariate meta-analysis is required to address the complexity of the research questions. Multivariate data can arise in meta-analysis due to several reasons.  The primary studies can be multivariate in nature by measuring multiple outcomes for each subject, typically known as multiple-endpoint studies, or it may arise when primary studies involve several comparisons among groups based on a single outcome or measures several parameters. Although it possesses many advantages over the more established univariate counterpart, multivariate meta-analysis has some challenges including modelling and estimating the parameter of interests. Under random-effects model assumption, we discuss the methods of estimating the heterogeneity parameters and effect sizes of the multivariate data and its application by using illustrative example and simulation results. 

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract:  “I see yellow; therefore, there is colocalization.” Is it really so simple when it comes to colocalization studies? Unfortunately, and fortunately, no. Colocalization is in fact a supremely powerful technique for scientists who want to take full advantage of what optical microscopy has to offer: quantitative, correlative information together with spatial resolution. Yet, methods for colocalization have been put into doubt now that images are no longer considered simple visual representations. Colocalization studies have notoriously been subject to misinterpretation due to difficulties in robust quantification and, more importantly, reproducibility, which results in a constant source of confusion, frustration, and error. In this talk, I will share some of our effort and progress to ease such challenges using novel statistical and computational tools.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Causal inference is a key component for comparative effectiveness research in observational studies. The inverse-propensity weighting (IPW) technique and augmented inverse-propensity weighting (AIPW) technique, which is known as a double-robust method, are the common methods for making causal inference in observational studies. However, these methods are known not stable, particularly when the models for propensity score and the study outcome are wrongly specified.  In this work, we propose a model-free approach for causal inference. While possessing standard asymptotic properties, this method also enjoys excellent finite sample performance and robustness. Simulation studies were conducted to compare with the well-known IPW and AIPW methods for causal inference. A real-life example from an ongoing Juvenile Idiopathic Arthritis Study was applied for the illustration of the proposed method.

Location: New Research Building Auditorium
3970 Reservoir Rd. NW, Washington, DC 20057

Abstract: Joint modeling of longitudinal and survival data is an active area of statistics research and becoming increasingly essential in most epidemiological and clinical studies. As a result, a considerable number of statistical models and analysis methods have been suggested for analyzing such longitudinal-survival data. However, the following issues may standout. (i) a common assumption for longitudinal variables is that model errors are normally distributed due to mathematical tractability and computational convenience. This requires the variables to be “symmetrically” distributed. A violation of this assumption could lead to misleading inferences; (ii) in practice, many studies are often to collect multiple longitudinal exposures which may be significantly correlated, ignoring their correlations may lead to bias and reduce efficiency in estimation; (iii) the longitudinal responses may encounter nonignorable missing; (iv) repeatedly measured observations in time are often interrelated with a time-to-event of interest. Inferential procedures may complicate dramatically when one analyzes data with these features together. Under the umbrella of Bayesian inference, this talk explores a multivariate mixed-effects joint models with skewed distributions for longitudinal measures with an attempt to mediate correlation from multiple responses, adjust departure from normality, and tailor accuracy from nonignorable missingness as well as overcome shortage of confidence in specifying a time-to-event model. A data set arising from diabetes study is analyzed to demonstrate the methodology. Simulation studies are conducted to assess the performance of the proposed joint models and method under various scenarios.

Location: Proctor Harvey Amphitheater, Med-Dent Building C105 
3900 Reservoir Rd. NW, Washington, DC 20057

Abstract: In many social science experiments, subjects often interact with each other and as a result one unit’s treatment influences the outcome of another unit. Over the last decade, a significant progress has been made towards causal inference in the presence of such interference between units. Researchers have shown that the two-stage randomization of treatment assignment enables the identification of average direct and spillover effects. However, much of the literature has assumed perfect compliance with treatment assignment. In this paper, we establish the nonparametric identification of the complier average direct and spillover effects in two-stage randomized experiments with interference and noncompliance. In particular, we consider the spillover effect of the treatment assignment on the treatment receipt as well as the spillover effect of the treatment receipt on the outcome. We propose consistent estimators and derive their randomization-based variances under the stratified interference assumption. We also prove the exact relationship between the proposed randomization-based estimators and the popular two-stage least squares estimators. Our methodology is motivated by and applied to the randomized evaluation of the India’s National Health Insurance Program (RSBY), where we find some evidence of spillover effects on both treatment receipt and outcome. The proposed methods are implemented via an open-source software package.  

Location: New Research Building Auditorium
3970 Reservoir Rd. NW, Washington, DC 20057

Abstract: Physicians frequently use N-of-1 (single-patient) trial designs in an informal manner to identify an optimal treatment for an individual patient. An N-of-1 clinical trial that focuses exclusively on optimizing the primary outcome for a specific patient clearly may not be very useful for generalizability to a population of patients. A series or collection of N-of-1 clinical trials, however, could be generalizable. We review current literature on the design and analysis of N-of-1 trials, and this includes Bayesian approaches as well. We next describe the “Best African American Response to Asthma Drugs (BARD)” trial, which invokes a four-way crossover design and has the flavor of a series of N-of-1 trials. We propose a nonlinear mixed-effects model with a quadrinomial logistic regression for the analysis of the BARD data that constructs six pairwise comparisons of the four asthma treatments to (1) assess the optimal treatment for each study participant and (2) estimate population-level treatment comparisons.

Location: New Research Building Auditorium
3970 Reservoir Rd. NW, Washington, DC 20057

Abstract: Probability books sometimes present “cooked” counterexamples to warn students of the lurking dangers of compromising rigor.  Can such anomalies actually occur in practice?  This talk is proof that they can!  I present actual examples from my clinical trials experience in which I either fell into, or almost fell into, probability traps.  These experiences were a major motivation for our book, “Essentials of Probability Theory for Statisticians” (Proschan and Shaw, 2016, CRC Press, Taylor & Francis Group).   

Location: New Research Building Auditorium
3970 Reservoir Rd. NW, Washington, DC 20057

Abstract: In many applications involving large dataset or online updating, stochastic gradient descent (SGD) provides a scalable way to compute parameter estimates and has gained increasing popularity due to its numerical convenience and memory efficiency. While the asymptotic properties of SGD-based estimators have been established decades ago, statistical inference such as interval estimation remains much unexplored. The traditional resampling method such as the bootstrap is not computationally feasible since it requires to repeatedly draw independent samples from the entire dataset. The plug-in method is not applicable when there are no explicit formulas for the covariance matrix of the estimator. In this paper, we propose a scalable inferential procedure for stochastic gradient descent, which, upon the arrival of each observation, updates the SGD estimate as well as a large number of randomly perturbed SGD estimates. The proposed method is easy to implement in practice. We establish its theoretical properties for a general class of models that includes generalized linear models and quantile regression models as special cases. The finite-sample performance and numerical utility is evaluated by simulation studies and two real data applications.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Linear mixed effect models (LMMs) have a long history in genetics, going back at least as far as when R. A. Fisher proposed the polygenic model. They have become a main stay in statistical modeling.  Because these models can be computationally intense, LMMs were dropped in favor of simpler statistical tests in the whole genome era of genetics.  However, quite recently LMMs surged in popularity for -omic studies and in particular for genome wide association studies.  In my talk, I will review what makes these models so popular now in genomics, discuss my groups’ recent work with LMMs to detect maternal gene by offspring gene interactions, and then touch on some open questions that deserve consideration. 

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: I will discuss the National Immunization Survey (NIS) conducted by the Centers for Disease Control and Prevention.  NIS-Child monitors vaccination coverage for the population of children 19-35 months, NIS-Teen focuses on vaccination coverage of adolescents 13-17 years, and NIS-Flu monitors influenza vaccination coverage for the population of children 6 months – 17 years, all living in the U.S.A.  This family of surveys is conducted annually in two phases: 1) a large survey of telephone numbers to identify households with age-eligible children, collect socio-demographic information about the child, and obtain contact information for the child’s immunization providers; and 2) a mail survey to collect immunization histories from identified providers for whom consent has been ob tained to contact providers.  Independent samples are selected quarterly in each of the 50 states and in specified urban areas.  The first-phase sample is obtained by random digit dialing from a national sampling frame consisting of landline and cell-phone numbers.  Because of insufficient validity of estimates derived from household-retained vaccination cards and parental recall, the NIS uses children with adequate provider-reported data to estimate vaccination coverage rates.  I discuss the NIS dual-frame estimation procedure.  

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract:  Dose-response studies play an important role in clinical drug development. In this presentation, I will give an overview of some of my research work on optimal adaptive designs for dose-response studies with time-to-event outcomes. These designs utilize response-adaptive allocation to most informative dose levels according to pre-defined statistical criteria. The designs can significantly improve estimation efficiency of the trial, which can potentially translate into reduction in study sample size. I will also emphasize some open topics in this field which can motivate some interesting research on optimal adaptive designs.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Defining labor progression in women has been a long-standing challenge for obstetricians. Cervical dilation, as integer-valued measurement, is a key indicator of the first stage of labor progression. Assessing the distribution of the time to per-unit increments of cervical dilation is of considerable interest in aiding obstetricians with better management of labor. Given that women are observed only intermittently for cervical dilation after they get admitted to hospital and that the observation frequency is very likely correlated to how fast/slow she dilates, one could view such data as panel count data with informative observation times and unknown time-zero. We propose semiparametric proportional rate models for the cervical dilation process and the observation process, with a multiplicative subject-specific frailty variable capturing the correlation between the two processes. Inference procedures for the gap times between consecutive events are proposed for both the scenarios with known and unknown time-zero using maximum likelihood approach and estimating equations. The methodology is assessed through simulation study and its large sample properties. A detailed analysis using the proposed method applied to the longitudinal cervical dilation data from the National Collaborative Perinatal Project from 1960s and the Consortium of Safe Labor of 2000s will be presented providing interesting comparisons across time. We will discuss other statistical challenges in studying labor progression including second stage of labor as well as neonatal and maternal morbidities.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract:  The correlation coefficient (CC) is a standard measure of a possible linear association between two continuous random variables. The CC plays a significant role in many scientific disciplines. For a bivariate normal distribution, there are many types of confidence intervals for the CC, such as Z-transformation and maximum likelihood-based intervals. However, when the underlying bivariate distribution is unknown, the construction of confidence intervals for the CC is not well-developed. In this paper, we discuss various interval estimation methods for the CC. We propose a generalized confidence interval for the CC when the underlying bivariate distribution is a normal distribution, and two empirical likelihood-based intervals for the CC when the underlying bivariate distribution is unknown. We also conduct extensive simulation studies to compare the new intervals with existing intervals in terms of coverage probability and interval length. Finally, two real examples are used to demonstrate the application of the proposed methods.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract:  In this talk, I will introduce the Bayesian optimal interval (BOIN) design as a novel platform for designing various different types of early phase clinical trials, including single agent, combination, toxicity grades and late-onset toxicity, under a unified framework. The BOIN belongs a class of new designs, known as model-assisted designs, that use a model for efficient decision making like model-based designs, while their dose escalation and de-escalation rules can be tabulated before the onset of a trial as with algorithm-based designs. The BOIN design is easy to implement in a way similar to the 3+3 design, but is more flexible for choosing the target toxicity rate and cohort size and yields a substantially better performance that is comparable to that of more complex model-based designs, such as the continuous reassessment method. The BOIN design possesses intuitive Bayesian and frequentist interpretations with desirable finite-sample and large-sample properties, i.e., long-memory coherence and consistency. The software with graphical user interface will be demonstrated.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Despite the wide use of the design with statistical stopping guidelines to stop a randomized clinical trial early for efficacy, there are unsettled debates of potential harmful consequences of such designs. These concerns include the possible over-estimation of treatment effects in early-stopped trials, and a newer argument of a “freezing effect” that will halt future RCTs on the same comparison since an early-stopped trial represents an effective declaration that randomization to the un-favored arm is unethical. We determine the degree of bias in designs that allow for early stopping, and assess the impact on estimation if indeed future experimentation is “frozen” by an early-stopped trial. We discuss methods to correct for the over-estimate in early-stopped trials. We demonstrate that superiority established in a RCT stopping early and designed with appropriate statistical stopping rules is likely a valid inference, even if the estimate may be slightly inflated. 

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd. NW, Washington, DC 20057

Abstract: Quantile regression has been getting more attention recently in survival analysis due to its robustness and interpretability, and is considered as a powerful alternative to Cox proportional hazards model and accelerated failure time (AFT) model. Allowing a nonlinear relationship between survival time and risk factors, we study a single index model for censored quantile regression, and employ B-spline approximation for estimation. To avoid estimation bias cause by censoring, we consider the redistribution-of-mass to obtain a weighted quantile regression estimator. For high dimensional covariates, dimension reduction approach is adopted to alleviate the “curse of dimensionality”. Furthermore, we penalize the developed estimator for variable selection. The proposed methods can be efficiently implemented using the existing weighted linear quantile regression algorithm. The asymptotic properties of the developed estimators are investigated, and their numerical performance is evaluated in simulation studies. We apply the proposed methods to dataset from a kidney transplant study.

Location: Proctor Harvey Amphitheater, Med-Dent Building C105
3900 Reservoir Rd. NW, Washington, DC 20057

Abstract:
Background: The oral cavity contains a diverse microbiome with over 700 bacterial species, many of which influence human health.
Objective: We hypothesize that features of the salivary microbiome will distinguish gingival health from disease and that these attributes will be more prevalent in those with Type 1 Diabetes (T1D). 1) Characterize the composition of the salivary microbiome from 16s sequencing. 2) Identify features of the salivary microbiome that distinguish those with T1D from those without T1D.
Methods: Passive drool saliva samples and clinical data were obtained from 197 (97 with T1D and 100 without diabetes) adults attending the 12-year visit for the CACTI study.  Salivary DNA was extracted and 16S amplicons were sequenced. 16S reads will be mapped and clustered into operational taxonomic units (OTUs). Multi testing analysis was used to identify associations between the taxonomic microbial profiles and T1D status.
Results: At the phylum level, the main constituents of the salivary microbiome in both T1D and non-T1D were Bacteroidetes, Firmicutes, and Proteobacteria. However, we did find a significant increased abundance of Firmicutes in the saliva from T1D subjects (29%) compared to non-T1D subjects (25%, false-discovery rate (FDR)-adjusted p=0.019). At the genus level, the relative abundances of several genera were higher or lower in T1D compared to non-diabetics. The relative abundance of Prevotella was lower, and the relative abundances of Campylobacter and Streptococcus were higher in those with T1D compared to those without.
Conclusion: The composition of the salivary microbiome was largely made up with Bacteroidetes, Firmicutes, and Proteobacteria. There is association between taxonomic Profiles of the Salivary Microbiome and Type 1 Diabetes. At the phylum level, T1D were enriched with Firmicutes compared to non-T1D. At the genus level, the relative abundances of several genera were higher or lower in T1D compared to non-diabetics.

Location: New Research Building Auditorium
3800 Reservoir Rd. NW, Washington, DC 20057

Abstract:  Meta-analysis has increasingly been used to identify adverse effects of drugs and vaccines, but the results have often been controversial. In one respect, metaanalysis is an especially appropriate tool in these settings. Efficacy studies are often too small to reliably assess risks that become important when a medication is in widespread use, so meta-analysis, which is a statistically efficient way to pool evidence from similar studies, seems like a natural approach. But, as the examples in this paper illustrate, different syntheses can come to qualitatively different conclusions, and the results of any one analysis are usually not as precise as they seem to be. There are three reasons for this: the adverse events of interest are rare, standard meta-analysis methods may not be appropriate for the clinical and methodological heterogeneity that is common in these studies, and adverse effects are not always completely or consistently reported. To address these problems, analysts should explore heterogeneity and use randomeffects or more complex statistical methods, and use multiple statistical models to see how dependent the results are to the choice of models.

Location: New Research Building Auditorium
3800 Reservoir Rd. NW, Washington, DC 20057

Abstract: Statistics, analytics, and data science provide powerful methods, tools, and ways of thinking for solving problems and making decisions, but not everyone who could benefit from applying statistics and data science to their research has the knowledge or skills to apply it correctly. The Laboratory for Interdisciplinary Statistical Analysis (LISA) is a statistical collaboration laboratory recently create at the University of Colorado Boulder that generates, applies, and spreads new knowledge throughout the state, the nation, and the world. LISA’s mission is to train statisticians to become interdisciplinary collaborators, provide research infrastructure to enable and accelerate high impact research, and engage with the community in outreach activities to improve statistical literacy. LISA has learned how to create statistical collaboration laboratories to train students to become effective statistical collaborators and to provide research infrastructure for the university. LISA is spreading this knowledge globally through the LISA 2020 Program to help scientists, government officials, businesses, and NGOs in developing countries discover local solutions to local problems through collaborations with statisticians from newly created statistical collaboration laboratories. The LISA 2020 goal is to build a global network of 20 statistical collaboration laboratories in developing countries by 2020. So far seven stat labs have been created in developing countries to train students to become effective interdisciplinary collaborators and enable researchers and government officials to solve problems and make better decisions.

Location: Proctor Harvey Amphitheater, Med-Dent Building C105
3900 Reservoir Rd. NW, Washington, DC 20057

Abstract: The Rasch Model (RM) is a classic IRT (Item Response Theory) model in psychometrics. RM is used to solve various applied problems including the measurement of a psychological construct, the scoring of patient-reported outcomes, and in understanding the politics in the high court. I will begin with the measurement of aggression as an example on how to fit a Rasch Model using Gibbs sampling. Next, the RM can be extended to quantify the politics of the Supreme Court. These first two examples will be brief. I will spend most of the time investigating a paradox—that many cancer survivors report memory deficits, yet their memory seems intact by standard neurocognitive tests. A Bayesian latent regression RM (Li, et al. 2016) helps to make sense of this apparent contradiction. I will provide a practical guide, on how to fit the Bayesian latent RM, and how to use the MCMC chains to derive empirical estimates that are harder to get with non-Bayesian methods. The overall goal is to show how psychometric methods have many useful applications across diverse disciplines. Hopefully, a brief introduction will stir discussions on how IRT models may be useful in your own research.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: Exposure to particulate matter (PM) air pollution has been associated with increased mortality and morbidity. PM is a complex chemical mixture, and associations between PM and health vary by its chemical composition. Identifying which sources of PM, such as motor vehicles or wildfires, emit the most toxic pollution can lead to a better understanding of how PM impacts health. However, exposure to source-specific PM is not directly observed and must be estimated from PM chemical component data. Source apportionment models aim to estimate source-specific concentrations of PM and the chemical composition of PM emitted by each source. These models, while useful, have some limitations. Specifically, the models are not identifiable without additional information, the estimated source chemical compositions may not match known source compositions, and the models are difficult to apply in multicity studies. In this talk, I introduce source apportionment models and discuss current challenges and opportunities in their application. I estimate sources and their health effects in two studies: a study of commuters in Atlanta, GA and a multicity time series study of four U.S. cities.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: As data sets of related studies become more easily accessible, combining data sets of similar studies is often undertaken in practice to achieve a larger sample size and higher power. A major challenge arising from data integration pertains to data heterogeneity in terms of study population, study design, or study coordination. Ignoring such heterogeneity in data analysis may result in biased estimation and misleading inference. Traditional techniques of remedy to data heterogeneity include the use of interactions and random effects, which are inferior to achieving desirable statistical power or providing a meaningful interpretation, especially when a large number of smaller data sets are combined. In this paper, we propose a regularized fusion learning method that allows us to identify and merge inter-model homogeneous parameter clusters in regression analysis, without the use of hypothesis testing approach. Using the fused lasso, we establish a computationally efficient procedure to deal with large-scale integrated data. Incorporating the estimated parameter ordering in the fused lasso facilitates computing speed with no loss of statistical power. We conduct extensive simulation studies and provide an application example to demonstrate the performance of the new method with a comparison to the conventional methods. This is a joint work with Lu Tang.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: The development of microarray and sequencing technologies enables biomedical researchers to collect and analyze large-scale molecular data. We will introduce our recent studies on the concordant integrative approach to the analysis of multiple related two-sample genome-wide expression data sets. A mixture model is developed and yields concordant integrative differential expression analysis as well as concordant integrative gene set enrichment analysis. As the number of data sets increases, it is necessary to reduce the number of parameters in the model. Motivated by the well-known generalized estimating equations (GEEs) for longitudinal data analysis, we focus on the concordant components and assume some special structures for the proportions of non-concordant components in the mixture model. The advantage and usefulness of this approach are illustrated on experimental data.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: Given the desire to enhance the effectiveness and efficiency of health care systems, it is important to understand and evaluate the risk factors for disease progression, treatment patterns such as medication uses, and utilizations such as hospitalization. Statistical analyses via observational studies and data mining may help evaluate patients’ diagnostic and prognostic outcomes, as well as inform policies to improve patient outcomes and to control costs. In the era of big data, real-world longitudinal patient-level databases containing the insurance claims of commercially insured adults, electronic health records, or cross-sectional surveys, provide useful insights to such analyses. Within the pharmaceutical industry, executing rapid queries to inform development and commercialization strategies, as well as pre-specified non-interventional observation studies, are commonly performed. In addition, pragmatic studies are increasingly being conducted to examine health-related outcomes. In this presentation, selective published examples on real-world data analyses are illustrated. Results typically suggest that paying attention to patient comorbidities and pre-index or at index health care service utilization may help identify patients at higher risk and unmet needs for treatments. Finally, fruitful collaborative opportunities exist across different sectors among academia, industry and the government.

Location: Med-Dent C-104, W. Proctor Harvey Amphitheater
3900 Reservoir Rd, Washington, DC 20057-1484

Abstract: This presentation reviews methods for comparative effectiveness research using observational data. The basic idea is using an observational study to emulate a hypothetical randomised trial by comparing initiators versus non-initiators of treatment. After adjustment for measured baseline confounders, one can then conduct the observational analogue of an intention-to-treat analysis. We also explain two approaches to conduct the analogues of per-protocol and as-treated analyses after further adjusting for measured time varying confounding and selection bias using inverse-probability weighting. As an example, we implemented these methods to estimate the effect of statins for primary prevention of coronary heart disease (CHD) using data from electronic medical records in the UK. Despite strong confounding by indication, our approach detected a potential benefit of statin therapy. The analogue of the intention-to treat hazard ratio (HR) of CHD was 0.89 (0.73, 1.09) for statin initiators versus non-initiators. The HR of CHD was 0.84 (0.54, 1.30) in the per-protocol analysis and 0.79 (0.41, 1.41) in the as-treated analysis for 2 years of use versus no use. In contrast, a conventional comparison of current users versus never users of statin therapy resulted in a HR of 1.31 (1.04, 1.66). We provide a flexible and annotated SAS program to implement the proposed analyses.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: This presentation reviews methods for comparative effectiveness research using Cox regression methods are well known. It has, however, a strong proportional hazards assumption. In many medical contexts, a disease progresses until a failure event (such as death) is triggered when the health level first reaches a failure threshold. I’ll present the Threshold Regression (TR) model for patient’s latent health process that requires few assumptions and, hence, is quite general in its potential application. We use TR to analyze data from a randomized clinical trial of treatment for multiple myeloma. A comparison is made with a Cox proportional hazards regression analysis of the same data.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: Concerns about reproducibility in science are widespread. In response, the National Institutes of Health has changed review procedures and training requirements for applicants (https://www.nih.gov/research-training/rigor-reproducibility). The Director of NIH and his deputy outlined their plans in Collins and Tabak (2014). Key methodological concerns include poor study designs, incorrect statistical analyses, inappropriate sample size selection, and misleading reporting. Planners can avoid the concerns by following four statistical guidelines. 1) Explicitly control both Type I errors (false positives) and Type II errors (false negatives). 2) Align the scientific goals, study design, data analysis plan, and the sample size analysis. 3) Vary inputs to the sample size analysis to determine the sensitivity to the values assumed. 4) Account for statistical uncertainty in inputs to sample size computations. Extending the guidelines to sequences of studies requires careful allocation of exploratory and confirmatory analyses (leapfrog designs) and allows some forms of adaptive designs. We give examples in the talk for a variety of designs and hypotheses. Case studies include a randomized drug trial in kidney disease, an observational study of quality of care in Medicaid, and a neurotoxicology experiment in rats. Analytic and simulation results provide the foundation for the conclusions.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: This talk introduces the three central uses of directed acyclic graphs (DAGs) for causal inference in the observational biomedical and social sciences.  First, DAGs provide clear notation for the researcher’s theory of data generation, against which all causal inferences must be judged. Second, DAGs reveal to what extent the researcher’s data-generating model can be tested. Third, researchers can inspect the DAG to determine whether a given causal question can be answered (“identified”) from the data. After introducing basic building blocks, we will discuss a number of real examples to demonstrate how DAGs help solve thorny practical problems in causal inference.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: Dimensional Analysis (DA) is a fundamental method in the engineering and physical sciences for analytically reducing the number of experimental variables prior to the experimentation. The principle use of dimensional analysis is to reduce from a study of the dimensions of the variables on the form of any possible relationship between those variables. The method is of great generality. In this talk, an overview/introduction of DA will be first given. A basic guideline for applying DA will be proposed, using examples for illustration. Some initial ideas on using DA for Data Analysis and Data Collection will be discussed. Future research issues will be proposed.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: An unmet significant challenge in the treatment of many early-stage cancers is the lack of effective prognostic models to identify patients who are at high risk of disease progression from a large number of potentially cured patients. Semi-parametric mixture cure models can account for latent cure fractions in patient populations thus are more suitable prognostic models than standard survival models such as Cox Proportional Hazard models or Proportional Odds models that ignore the existence of latent cure fractions. Without the requirement of knowing who is surely cured, the semiparametric mixture cure models can be used to evaluate predictive utility of biomarkers on cure probability and on survival of uncured subjects. However, appropriate statistical metrics to evaluate prognostic efficiency in the presence of cured patients have been lacking. In this paper, we introduce concordance-based prognostic metrics for semi-parametric mixture cure models and develop consistent estimates. The asymptotic normality and confidence intervals of these estimates are also established. Finite sample applicability of the developed indices and estimates are investigated using numerical simulations and illustrated using a melanoma data set. This talk is based on joint work with Dr. Yilong Zhang at Merck.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484

Abstract: The analysis of failure time data plays an important and essential role in many studies, especially medical studies such as clinical trials and follow-up studies. One key feature of failure time data that separates the failure time data analysis from other fields, is censoring, which can occur in different forms.  In this talk, we will discuss and review a general form, interval censoring, and the existing literature for the analysis of interval-censored data as well as some research topics.

Location: Warwick Evans Conference Room, Building D
4000 Reservoir Rd, Washington, DC 20057-1484