962 resultados para Medicine Research Statistical methods
Resumo:
Well-established methods exist for measuring party positions, but reliable means for estimating intra-party preferences remain underdeveloped. While most efforts focus on estimating the ideal points of individual legislators based on inductive scaling of roll call votes, this data suffers from two problems: selection bias due to unrecorded votes and strong party discipline, which tends to make voting a strategic rather than a sincere indication of preferences. By contrast, legislative speeches are relatively unconstrained, as party leaders are less likely to punish MPs for speaking freely as long as they vote with the party line. Yet, the differences between roll call estimations and text scalings remain essentially unexplored, despite the growing application of statistical analysis of textual data to measure policy preferences. Our paper addresses this lacuna by exploiting a rich feature of the Swiss legislature: on most bills, legislators both vote and speak many times. Using this data, we compare text-based scaling of ideal points to vote-based scaling from a crucial piece of energy legislation. Our findings confirm that text scalings reveal larger intra-party differences than roll calls. Using regression models, we further explain the differences between roll call and text scalings by attributing differences to constituency-level preferences for energy policy.
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Individual participant data (IPD) meta-analysis is an increasingly used approach for synthesizing and investigating treatment effect estimates. Over the past few years, numerous methods for conducting an IPD meta-analysis (IPD-MA) have been proposed, often making different assumptions and modeling choices while addressing a similar research question. We conducted a literature review to provide an overview of methods for performing an IPD-MA using evidence from clinical trials or non-randomized studies when investigating treatment efficacy. With this review, we aim to assist researchers in choosing the appropriate methods and provide recommendations on their implementation when planning and conducting an IPD-MA. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd.
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When considering data from many trials, it is likely that some of them present a markedly different intervention effect or exert an undue influence on the summary results. We develop a forward search algorithm for identifying outlying and influential studies in meta-analysis models. The forward search algorithm starts by fitting the hypothesized model to a small subset of likely outlier-free studies and proceeds by adding studies into the set one-by-one that are determined to be closest to the fitted model of the existing set. As each study is added to the set, plots of estimated parameters and measures of fit are monitored to identify outliers by sharp changes in the forward plots. We apply the proposed outlier detection method to two real data sets; a meta-analysis of 26 studies that examines the effect of writing-to-learn interventions on academic achievement adjusting for three possible effect modifiers, and a meta-analysis of 70 studies that compares a fluoride toothpaste treatment to placebo for preventing dental caries in children. A simple simulated example is used to illustrate the steps of the proposed methodology, and a small-scale simulation study is conducted to evaluate the performance of the proposed method. Copyright © 2016 John Wiley & Sons, Ltd.
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OBJECTIVES The purpose of the study was to provide empirical evidence about the reporting of methodology to address missing outcome data and the acknowledgement of their impact in Cochrane systematic reviews in the mental health field. METHODS Systematic reviews published in the Cochrane Database of Systematic Reviews after January 1, 2009 by three Cochrane Review Groups relating to mental health were included. RESULTS One hundred ninety systematic reviews were considered. Missing outcome data were present in at least one included study in 175 systematic reviews. Of these 175 systematic reviews, 147 (84%) accounted for missing outcome data by considering a relevant primary or secondary outcome (e.g., dropout). Missing outcome data implications were reported only in 61 (35%) systematic reviews and primarily in the discussion section by commenting on the amount of the missing outcome data. One hundred forty eligible meta-analyses with missing data were scrutinized. Seventy-nine (56%) of them had studies with total dropout rate between 10 and 30%. One hundred nine (78%) meta-analyses reported to have performed intention-to-treat analysis by including trials with imputed outcome data. Sensitivity analysis for incomplete outcome data was implemented in less than 20% of the meta-analyses. CONCLUSIONS Reporting of the techniques for handling missing outcome data and their implications in the findings of the systematic reviews are suboptimal.
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Despite many researches on development in education and psychology, not often is the methodology tested with real data. A major barrier to test the growth model is that the design of study includes repeated observations and the nature of the growth is nonlinear. The repeat measurements on a nonlinear model require sophisticated statistical methods. In this study, we present mixed effects model in a negative exponential curve to describe the development of children's reading skills. This model can describe the nature of the growth on children's reading skills and account for intra-individual and inter-individual variation. We also apply simple techniques including cross-validation, regression, and graphical methods to determine the most appropriate curve for data, to find efficient initial values of parameters, and to select potential covariates. We illustrate with an example that motivated this research: a longitudinal study of academic skills from grade 1 to grade 12 in Connecticut public schools. ^
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Genetic anticipation is defined as a decrease in age of onset or increase in severity as the disorder is transmitted through subsequent generations. Anticipation has been noted in the literature for over a century. Recently, anticipation in several diseases including Huntington's Disease, Myotonic Dystrophy and Fragile X Syndrome were shown to be caused by expansion of triplet repeats. Anticipation effects have also been observed in numerous mental disorders (e.g. Schizophrenia, Bipolar Disorder), cancers (Li-Fraumeni Syndrome, Leukemia) and other complex diseases. ^ Several statistical methods have been applied to determine whether anticipation is a true phenomenon in a particular disorder, including standard statistical tests and newly developed affected parent/affected child pair methods. These methods have been shown to be inappropriate for assessing anticipation for a variety of reasons, including familial correlation and low power. Therefore, we have developed family-based likelihood modeling approaches to model the underlying transmission of the disease gene and penetrance function and hence detect anticipation. These methods can be applied in extended families, thus improving the power to detect anticipation compared with existing methods based only upon parents and children. The first method we have proposed is based on the regressive logistic hazard model. This approach models anticipation by a generational covariate. The second method allows alleles to mutate as they are transmitted from parents to offspring and is appropriate for modeling the known triplet repeat diseases in which the disease alleles can become more deleterious as they are transmitted across generations. ^ To evaluate the new methods, we performed extensive simulation studies for data simulated under different conditions to evaluate the effectiveness of the algorithms to detect genetic anticipation. Results from analysis by the first method yielded empirical power greater than 87% based on the 5% type I error critical value identified in each simulation depending on the method of data generation and current age criteria. Analysis by the second method was not possible due to the current formulation of the software. The application of this method to Huntington's Disease and Li-Fraumeni Syndrome data sets revealed evidence for a generation effect in both cases. ^
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The joint modeling of longitudinal and survival data is a new approach to many applications such as HIV, cancer vaccine trials and quality of life studies. There are recent developments of the methodologies with respect to each of the components of the joint model as well as statistical processes that link them together. Among these, second order polynomial random effect models and linear mixed effects models are the most commonly used for the longitudinal trajectory function. In this study, we first relax the parametric constraints for polynomial random effect models by using Dirichlet process priors, then three longitudinal markers rather than only one marker are considered in one joint model. Second, we use a linear mixed effect model for the longitudinal process in a joint model analyzing the three markers. In this research these methods were applied to the Primary Biliary Cirrhosis sequential data, which were collected from a clinical trial of primary biliary cirrhosis (PBC) of the liver. This trial was conducted between 1974 and 1984 at the Mayo Clinic. The effects of three longitudinal markers (1) Total Serum Bilirubin, (2) Serum Albumin and (3) Serum Glutamic-Oxaloacetic transaminase (SGOT) on patients' survival were investigated. Proportion of treatment effect will also be studied using the proposed joint modeling approaches. ^ Based on the results, we conclude that the proposed modeling approaches yield better fit to the data and give less biased parameter estimates for these trajectory functions than previous methods. Model fit is also improved after considering three longitudinal markers instead of one marker only. The results from analysis of proportion of treatment effects from these joint models indicate same conclusion as that from the final model of Fleming and Harrington (1991), which is Bilirubin and Albumin together has stronger impact in predicting patients' survival and as a surrogate endpoints for treatment. ^
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The discrete-time Markov chain is commonly used in describing changes of health states for chronic diseases in a longitudinal study. Statistical inferences on comparing treatment effects or on finding determinants of disease progression usually require estimation of transition probabilities. In many situations when the outcome data have some missing observations or the variable of interest (called a latent variable) can not be measured directly, the estimation of transition probabilities becomes more complicated. In the latter case, a surrogate variable that is easier to access and can gauge the characteristics of the latent one is usually used for data analysis. ^ This dissertation research proposes methods to analyze longitudinal data (1) that have categorical outcome with missing observations or (2) that use complete or incomplete surrogate observations to analyze the categorical latent outcome. For (1), different missing mechanisms were considered for empirical studies using methods that include EM algorithm, Monte Carlo EM and a procedure that is not a data augmentation method. For (2), the hidden Markov model with the forward-backward procedure was applied for parameter estimation. This method was also extended to cover the computation of standard errors. The proposed methods were demonstrated by the Schizophrenia example. The relevance of public health, the strength and limitations, and possible future research were also discussed. ^
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In recent years, disaster preparedness through assessment of medical and special needs persons (MSNP) has taken a center place in public eye in effect of frequent natural disasters such as hurricanes, storm surge or tsunami due to climate change and increased human activity on our planet. Statistical methods complex survey design and analysis have equally gained significance as a consequence. However, there exist many challenges still, to infer such assessments over the target population for policy level advocacy and implementation. ^ Objective. This study discusses the use of some of the statistical methods for disaster preparedness and medical needs assessment to facilitate local and state governments for its policy level decision making and logistic support to avoid any loss of life and property in future calamities. ^ Methods. In order to obtain precise and unbiased estimates for Medical Special Needs Persons (MSNP) and disaster preparedness for evacuation in Rio Grande Valley (RGV) of Texas, a stratified and cluster-randomized multi-stage sampling design was implemented. US School of Public Health, Brownsville surveyed 3088 households in three counties namely Cameron, Hidalgo, and Willacy. Multiple statistical methods were implemented and estimates were obtained taking into count probability of selection and clustering effects. Statistical methods for data analysis discussed were Multivariate Linear Regression (MLR), Survey Linear Regression (Svy-Reg), Generalized Estimation Equation (GEE) and Multilevel Mixed Models (MLM) all with and without sampling weights. ^ Results. Estimated population for RGV was 1,146,796. There were 51.5% female, 90% Hispanic, 73% married, 56% unemployed and 37% with their personal transport. 40% people attained education up to elementary school, another 42% reaching high school and only 18% went to college. Median household income is less than $15,000/year. MSNP estimated to be 44,196 (3.98%) [95% CI: 39,029; 51,123]. All statistical models are in concordance with MSNP estimates ranging from 44,000 to 48,000. MSNP estimates for statistical methods are: MLR (47,707; 95% CI: 42,462; 52,999), MLR with weights (45,882; 95% CI: 39,792; 51,972), Bootstrap Regression (47,730; 95% CI: 41,629; 53,785), GEE (47,649; 95% CI: 41,629; 53,670), GEE with weights (45,076; 95% CI: 39,029; 51,123), Svy-Reg (44,196; 95% CI: 40,004; 48,390) and MLM (46,513; 95% CI: 39,869; 53,157). ^ Conclusion. RGV is a flood zone, most susceptible to hurricanes and other natural disasters. People in the region are mostly Hispanic, under-educated with least income levels in the U.S. In case of any disaster people in large are incapacitated with only 37% have their personal transport to take care of MSNP. Local and state government’s intervention in terms of planning, preparation and support for evacuation is necessary in any such disaster to avoid loss of precious human life. ^ Key words: Complex Surveys, statistical methods, multilevel models, cluster randomized, sampling weights, raking, survey regression, generalized estimation equations (GEE), random effects, Intracluster correlation coefficient (ICC).^
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Next-generation DNA sequencing platforms can effectively detect the entire spectrum of genomic variation and is emerging to be a major tool for systematic exploration of the universe of variants and interactions in the entire genome. However, the data produced by next-generation sequencing technologies will suffer from three basic problems: sequence errors, assembly errors, and missing data. Current statistical methods for genetic analysis are well suited for detecting the association of common variants, but are less suitable to rare variants. This raises great challenge for sequence-based genetic studies of complex diseases.^ This research dissertation utilized genome continuum model as a general principle, and stochastic calculus and functional data analysis as tools for developing novel and powerful statistical methods for next generation of association studies of both qualitative and quantitative traits in the context of sequencing data, which finally lead to shifting the paradigm of association analysis from the current locus-by-locus analysis to collectively analyzing genome regions.^ In this project, the functional principal component (FPC) methods coupled with high-dimensional data reduction techniques will be used to develop novel and powerful methods for testing the associations of the entire spectrum of genetic variation within a segment of genome or a gene regardless of whether the variants are common or rare.^ The classical quantitative genetics suffer from high type I error rates and low power for rare variants. To overcome these limitations for resequencing data, this project used functional linear models with scalar response to develop statistics for identifying quantitative trait loci (QTLs) for both common and rare variants. To illustrate their applications, the functional linear models were applied to five quantitative traits in Framingham heart studies. ^ This project proposed a novel concept of gene-gene co-association in which a gene or a genomic region is taken as a unit of association analysis and used stochastic calculus to develop a unified framework for testing the association of multiple genes or genomic regions for both common and rare alleles. The proposed methods were applied to gene-gene co-association analysis of psoriasis in two independent GWAS datasets which led to discovery of networks significantly associated with psoriasis.^
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Coalescent theory represents the most significant progress in theoretical population genetics in the past three decades. The coalescent theory states that all genes or alleles in a given population are ultimately inherited from a single ancestor shared by all members of the population, known as the most recent common ancestor. It is now widely recognized as a cornerstone for rigorous statistical analyses of molecular data from population [1]. The scientists have developed a large number of coalescent models and methods[2,3,4,5,6], which are not only applied in coalescent analysis and process, but also in today’s population genetics and genome studies, even public health. The thesis aims at completing a statistical framework based on computers for coalescent analysis. This framework provides a large number of coalescent models and statistic methods to assist students and researchers in coalescent analysis, whose results are presented in various formats as texts, graphics and printed pages. In particular, it also supports to create new coalescent models and statistical methods. ^