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== [[Main_Page | SOCR Wiki]]: Scientific Methods for Health Sciences ==
[[Image:SMHS_EBook.png|250px|thumbnail|right| Scientific Methods for Health Sciences EBook]]

==[[SMHS_Preface| Preface]]==
The ''Scientific Methods for Health Sciences (SMHS) EBook'' is designed to support a [http://www.socr.umich.edu/people/dinov/SMHS_Courses.html 4-course training curriculum] emphasizing the fundamentals, applications and practice of scientific methods specifically for graduate students in the health sciences.

===[[SMHS_Format| Format]]===
Follow the instructions in [[SMHS_Format| this page]] to expand, revise or improve the materials in this EBook.

===[[SMHS_Usage| Learning and Instructional Usage]]===
This section describes the means of traversing, searching, discovering and utilizing the SMHS EBook resources in both formal and informal learning setting.

===[[SMHS_copyright | Copyrights]]===
The SMHS EBook is a freely and openly accessible electronic book developed by [[SOCR]] and the general health sciences community.

==Chapter I: Fundamentals==
===[[SMHS_EDA | Exploratory Data Analysis, Plots and Charts]]===
Review of data types, exploratory data analyses and graphical representation of information.

===[[SMHS_UbiquitousVariation | Ubiquitous Variation]]===
There are many ways to quantify variability, which is present in all natural processes.

===[[SMHS_ParamInference | Parametric Inference]]===
Foundations of parametric (model-based) statistical inference.

===[[SMHS_Probability | Probability Theory]]===
Random variables, stochastic processes, and events are the core concepts necessary to define likelihoods of certain outcomes or results to be observed. We define event manipulations and present the fundamental principles of probability theory including conditional probability, total and Bayesian probability laws, and various combinatorial ideas.

===[[SMHS_OR_RR | Odds Ratio/Relative Risk]]===
The relative risk, RR, (a measure of dependence comparing two probabilities in terms of their ratio) and the odds ratio, OR, (the fraction of one probability and its complement) are widely applicable in many healthcare studies.

===[[SMHS_CenterSpreadShape | Centrality, Variability and Shape]]===
Three main features of sample data are commonly reported as critical in understanding and interpreting the population, or process, the data represents. These include Center, Spread and Shape. The main measures of centrality are Mean, Median and Mode(s). Common measures of variability include the range, the variance, the standard deviation, and mean absolute deviation. The shape of a (sample or population) distribution is an important characterization of the process and its intrinsic properties.

===[[SMHS_ProbabilityDistributions | Probability Distributions]]===
Probability distributions are mathematical models for processes that we observe in nature. Although there are different types of distributions, they have common features and properties that make them useful in various scientific applications. This section presents the Bernoulli, Binomial, Multinomial, Geometric, Hypergeometric, Negative binomial, Negative multinomial distribution, Poisson distribution, and Normal distributions, as well as the concept of moment generating function.

===[[SMHS_ResamplingSimulation | Resampling and Simulation]]===
Resampling is a technique for estimation of sample statistics (e.g., medians, percentiles) by using subsets of available data or by randomly drawing replacement data. Simulation is a computational technique addressing specific imitations of what’s happening in the real world or system over time without awaiting it to happen by chance.

===[[SMHS_DesignOfExperiments | Design of Experiments]]===
Design of experiments (DOE) is a technique for systematic and rigorous problem solving that applies data collection principles to ensure the generation of valid, supportable and reproducible conclusions.

===[[SMHS_IntroEpi | Intro to Epidemiology]]===
Epidemiology is the study of the distribution and determinants of disease frequency in human populations. This section presents the basic epidemiology concepts. More advanced epidemiological methodologies are discussed in [[SMHS_Epidemiology|the next chapter]]. This section also presents the Positive and Negative Predictive Values (PPV/NPV).

===[[SMHS_ExpObsStudies | Experiments vs. Observational Studies]]===
Experimental and observational studies have different characteristics and are useful in complementary investigations of association and causality.

===[[SMHS_Estimation | Estimation]]===
Estimation is a method of using sample data to approximate the values of specific population parameters of interest like population mean, variability or 97<sup>th</sup> percentile. Estimated parameters are expected to be interpretable, accurate and optimal, in some form.

===[[SMHS_HypothesisTesting | Hypothesis Testing]]===
Hypothesis testing is a quantitative decision-making technique for examining the characteristics (e.g., centrality, span) of populations or processes based on observed experimental data. In this section we discuss inference about a mean, mean differences (both small and large samples), a proportion or differences of proportions and differences of variances.

===[[SMHS_PowerSensitivitySpecificity | Statistical Power, Sensitivity and Specificity]]===
The fundamental concepts of type I (false-positive) and type II (false-negative) errors lead to the important study-specific notions of statistical power, sample size, effect size, sensitivity and specificity.

===[[SMHS_DataManagement | Data Management]]===
All modern data-driven scientific inquiries demand deep understanding of tabular, ASCII, binary, streaming, and cloud data management, processing and interpretation.

===[[SMHS_BiasPrecision | Bias and Precision]]===
Bias and precision are two important and complementary characteristics of estimated parameters that quantify the accuracy and variability of approximated quantities.

===[[SMHS_AssociationCausality | Association and Causality]]===
An association is a relationship between two, or more, measured quantities that renders them statistically dependent so that the occurrence of one does affect the probability of the other. A causal relation is a specific type of association between an event (the cause) and a second event (the effect) that is considered to be a consequence of the first event.

===[[SMHS_RateOfChange | Rate-of-change]]===
Rate of change is a technical indicator describing the rate in which one quantity changes in relation to another quantity.

===[[SMHS_ClinicalStatSignificance | Clinical vs. Statistical Significance]]===
Statistical significance addresses the question of whether or not the results of a statistical test meet an accepted quantitative criterion, whereas clinical significance is answers the question of whether the observed difference between two treatments (e.g., new and old therapy) found in the study large enough to alter the clinical practice.

===[[SMHS_CorrectionMultipleTesting | Correction for Multiple Testing]]===
Multiple testing refers to analytical protocols involving testing of several (typically more then two) hypotheses. Multiple testing studies require correction for type I (false-positive rate), which can be done using Bonferroni's method, Tukey’s procedure, family-wise error rate (FWER), or false discovery rate (FDR).

==Chapter II: Applied Inference==
===[[SMHS_Epidemiology| Epidemiology]]===
This section expands the [[SMHS_IntroEpi|Epidemiology Introduction]] from the previous chapter. Here we will discuss numbers needed to treat and various likelihoods related to genetic association studies, including linkage and association, LOD scores and Hardy-Weinberg equilibrium.

===[[SMHS_SLR| Correlation and Regression (ρ and slope inference, 1-2 samples)]]===
Studies of correlations between two, or more, variables and regression modeling are important in many scientific inquiries. The simplest situation such situation is exploring the association and correlation of bivariate data ($X$ and $Y$).

===[[SMHS_ROC| ROC Curve]]===
The receiver operating characteristic (ROC) curve is a graphical tool for investigating the performance of a binary classifier system as its discrimination threshold varies. We also discuss the concepts of positive and negative predictive values.

===[[SMHS_ANOVA| ANOVA]]===
Analysis of Variance (ANOVA) is a statistical method fpr examining the differences between group means. ANOVA is a generalization of the [[SMHS_HypothesisTesting|t-test]] for more than 2 groups. It splits the observed variance into components attributed to different sources of variation.

===[[SMHS_NonParamInference| Non-parametric inference]]===
Nonparametric inference involves a class of methods for descriptive and inferential statistics that are not based on parametrized families of probability distributions, which is the basis of the [[SMHS_ParamInference|parametric inference we discussed earlier]]. This section presents the Sign test, Wilcoxon Signed Rank test, Wilcoxon-Mann-Whitney test, the McNemar test, the Kruskal-Wallis test, and the Fligner-Killeen test.

===[[SMHS_Cronbachs| Instrument Performance Evaluation: Cronbach's α]]===
Cronbach’s alpha (α) is a measure of internal consistency used to estimate the reliability of a cumulative psychometric test.

===[[SMHS_ReliabilityValidity| Measurement Reliability and Validity]]===
Measures of Validity include: Construct validity (extent to which the operation actually measures what the theory intends to), Content validity (the extent to which the content of the test matches the content associated with the construct), Criterion validity (the correlation between the test and a variable representative of the construct), experimental validity (validity of design of experimental research studies). Similarly, there many alternate strategies to assess instrument Reliability (or repeatability) -- test-retest reliability, administering different versions of an assessment tool to the same group of individuals, inter-rater reliability, internal consistency reliability.

===[[SMHS_SurvivalAnalysis| Survival Analysis]]===
Survival analysis is used for analyzing longitudinal data on the occurrence of events (e.g., death, injury, onset of illness, recovery from illness). In this section we discuss data structure, survival/hazard functions, parametric versus semi-parametric regression techniques and introduction to Kaplan-Meier methods (non-parametric).

===[[SMHS_DecisionTheory| Decision Theory]]===
Decision theory helps determining the optimal course of action among a number of alternatives, when consequences cannot be forecasted with certainty. There are different types of loss-functions and decision principles (e.g., frequentist vs. Bayesian).

===[[SMHS_CLT_LLN| CLT/LLNs – limiting results and misconceptions]]===
The Law of Large Numbers (LLT) and the Central Limit Theorem (CLT) are the first and second fundamental laws of probability. CLT yields that the arithmetic mean of a sufficiently large number of iterates of independent random variables given certain conditions will be approximately normally distributed. LLT states that in performing the same experiment a large number of times, the average of the results obtained should be close to the expected value and tends to get closer to the expected value with increasing number of trials.

===[[SMHS_AssociationTests| Association Tests]]===
There are alternative methods to measure association two quantities (e.g., relative risk, risk ratio, efficacy, prevalence ratio). This section also includes details on Chi-square tests for association and goodness-of-fit, Fisher’s exact test, randomized controlled trials (RCT), and external and internal validity.

===[[SMHS_BayesianInference| Bayesian Inference]]===
Bayes’ rule connects the theories of conditional and compound probability and provides a way to update probability estimates for a hypothesis as additional evidence is observed.

===[[SMHS_PCA_ICA_FA| PCA/ICA/Factor Analysis]]===
Principal component analysis is a mathematical procedure that transforms a number of possibly correlated variables into a fewer number of uncorrelated variables through a process known as orthogonal transformation. Independent component analysis is a computational tool to separate a multivariate signal into additive subcomponents by assuming that the subcomponents are non-Gaussian signals and are statistically independent from each other. Factor analysis is a statistical method, which describes variability among observed correlated variables in terms of potentially lower number of unobserved variables.

===[[SMHS_CIs| Point/Interval Estimation (CI) – MoM, MLE]]===
Estimation of population parameters is critical in many applications. In statistics, estimation is commonly accomplished in terms of point-estimates or interval-estimates for specific (unknown) population parameters of interest. The method of moments (MOM) and maximum likelihood estimation (MLE) techniques are used frequently in practice. In this section, we also lay the foundations for expectation maximization and Gaussian mixture modeling.

===[[SMHS_ResearchCritiques| Study/Research Critiques]]===
The scientific rigor in published literature, grant proposals and general reports needs to be assessed and scrutinized to minimize errors in data extraction and meta-analysis. Reporting biases present significant obstacles to collecting of relevant information on the effectiveness of an intervention, strength of relations between variables, or causal associations.

===[[SMHS_CommonMistakesMisconceptions| Common mistakes and misconceptions in using probability and statistics, identifying potential assumption violations, and avoiding them]]===

==Chapter III: Linear Modeling==
===[[SMHS_MLR | Multiple Linear Regression (MLR)]]===
Multiple Linear Regression encapsulated a family of statistical analyses for modeling single or multiple independent variables and one dependent variable. MLR computationally estimates all of the effects of each independent variable (coefficients) based on the data using least square fitting.

===[[SMHS_GLM| Generalized Linear Modeling (GLM)]]===
Generalized Linear Modeling (GLM) is a flexible generalization of ordinary linear multivariate regression, which allows for response variables that have error distribution models other than a normal distribution. GLM unifies statistical models like linear regression, logistic regression and Poisson regression.

===[[SMHS_ANCOVA| Analysis of Covariance (ANCOVA)]]===
Analysis of Variance ([[SMHS_ANOVA|ANOVA]]) is a common method applied to analyze the differences between group means. Analysis of Covariance (ANCOVA) is another method applied to blend ANOVA and regression and evaluate whether population means of a dependent variance are equal across levels of a categorical independent variable while statistically controlling for the effects of other continuous variables.

===[[SMHS_MANOVA| Multivariate Analysis of Variance (MANOVA)]]===
A generalized form of [[SMHS_ANOVA|ANOVA]] is the multivariate analysis of variance (MANOVA), which is a statistical procedure for comparing multivariate means of several groups.

===[[SMHS_MANCOVA| Multivariate Analysis of Covariance (MANCOVA)]]===
Similar to [[SMHS_MANOVA|MANOVA]], the multivariate analysis of covariance (MANOCVA) is an extension of [[SMHS_ANCOVA|ANCOVA]] that is designed for cases where there is more than one dependent variable and when a control of concomitant continuous independent variables is present.

===[[SMHS_rANOVA| Repeated measures Analysis of Variance (rANOVA)]]===
Repeated measures are used in situations when the same objects/units/entities take part in all conditions of an experiment. Given there is multiple measures on the same subject, we have to control for correlation between multiple measures on the same subject. Repeated measures ANOVA (rANOVA) is the equivalent of the one-way [[SMHS_ANOVA|ANOVA]], but for related, not independent, groups. It is also referred to as within-subject ANOVA or ANOVA for correlated samples.

===[[SMHS_PartialCorrelation| Partial Correlation]]===
Partial correlation measures the degree of association between two random variables by measuring variances controlling for certain other factors or variables.

===[[SMHS_TimeSeries| Time Series Analysis]]===
Time series data is a sequence of data points measured at successive points in time. Time series analysis is a technique used in varieties of studies involving temporal measurements and tracking metrics.

===[[SMHS_FixedRandomMixedModels|Fixed, Randomized and Mixed Effect Models]]===
Fixed effect models are statistical models that represent the observed quantities in terms of explanatory variables (covariates) treated as non-random, while random effect models assume that the dataset being analyzed consist of a hierarchy of different population whose differences relate to that hierarchy. Mixed effect models consist of both fixed effects and random effects. For random effects model and mixed models, either all or part of the explanatory variables are treated as if they rise from random causes.

===[[SMHS_HLM| Hierarchical Linear Models (HLM)]]===
Hierarchical linear model (also called multilevel models) refer to statistical models of parameters that vary at more than one level. These are generalizations of linear models and are widely applied in various studies especially for research designs where data for participants are organized at more than one level.

===[[SMHS_MultimodelInference|Multi-Model Inference]]===
Multi-Model Inference involves model selection of a relationship between $Y$ (response) and predictors $X_1, X_2, ..., X_n$ that is simple, effective and retains good predictive power, as measured by the SSE, AIC or BIC.

===[[SMHS_MixtureModeling|Mixture Modeling]]===
Mixture modeling is a probabilistic modeling technique for representing the presence of sub-populations within overall population, without requiring that an observed data set identifies the sub-population to which an individual observation belongs.

===[[SMHS_Surveys|Surveys]]===
Survey methodologies involve data collection using questionnaires designed to improve the number of responses and the reliability of the responses in the surveys. The ultimate goal is to make statistical inferences about the population, which would depend strongly on the survey questions provided. The commonly used survey methods include polls, public health surveys, market research surveys, censuses and so on.

===[[SMHS_LongitudinalData|Longitudinal Data]]===
Longitudinal data represent data collected from a population over a given time period where the same subjects are measured at multiple points in time. Longitudinal data analyses are widely used statistical techniques in many health science fields.

===[[SMHS_GEE| Generalized Estimating Equations (GEE) Models]]===
Generalized estimating equation (GEE) is a method for parameter estimation when fitting [[SMHS_GLM|generalized linear models]] with a possible unknown correlation between outcomes. It provides a general approach for analyzing discrete and continuous responses with marginal models and works as a popular alternative to maximum likelihood estimation (MLE).

===[[SMHS_ModelFitting| Model Fitting and Model Quality (KS-test)]]===
The Kolmogorov-Smirnov Test (K-S test) is a nonparametric test commonly applied to test for the equality of continuous, one-dimensional probability distributions. This test can be used to compare one sample against a reference probability distribution (one-sample K-S test) or to compare two samples (two-sample K-S test).

==Chapter IV: Special Topics==
===[[SMHS_DataSimulation| Data Simulation ]]===
This section demonstrates the core principles of simulating multivariate datasets.
===[[SMHS_LinearModeling| Linear Modeling ]]===
This section is a review of linear modeling.

===Scientific Visualization===
===PCOR/CER methods Heterogeneity of Treatment Effects===
===Big-Data/Big-Science===
===[[SMHS_MissingData|Missing data]]===
Many research studies encounter incomplete (missing) data that require special handling (e.g., teleprocessing, statistical analysis, visualization). There are a variety of methods (e.g., multiple imputation) to deal with missing data, detect missingness, impute the data, analyze the completed dataset and compare the characteristics of the raw and imputed data.

===Genotype-Environment-Phenotype associations===
===Medical imaging===
===Data Networks===
===Adaptive Clinical Trials===
===Databases/registries===
===Meta-analyses===
===Causality/Causal Inference, SEM===
===Classification methods===
===Time-series analysis===
===Scientific Validation===
===Geographic Information Systems (GIS)===
===Rasch measurement model/analysis===
===MCMC sampling for Bayesian inference===
===Network Analysis===

<hr>
* SOCR Home page: http://www.socr.umich.edu

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Test - Revision history

Dinov at 14:30, 1 February 2016

Dinov: Created page with "{| cellspacing="5" cellpadding="0" style="margin:0em 0em 1em 0em; border:1px solid #1DA0E7; background:#B3DDF4;width:100%" | '''The Scientific Methods for Health Sciences EBoo..."