# Time-varying covariate

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A time-varying covariate (also called time-dependent covariate) is a term used in statistics, particularly in survival analysis. [1] It reflects the phenomenon that a covariate is not necessarily constant through the whole study Time-varying covariates are included to represent time-dependent within-individual variation to predict individual responses. [2] For instance, if one wishes to examine the link between area of residence and cancer, this would be complicated by the fact that study subjects move from one area to another. The area of residency could then be introduced in the statistical model as a time-varying covariate. In survival analysis, this would be done by splitting each study subject into several observations, one for each area of residence. For example, if a person is born at time 0 in area A, moves to area B at time 5, and is diagnosed with cancer at time 8, two observations would be made. One with a length of 5 (5 − 0) in area A, and one with a length of 3 (8 − 5) in area B.

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Statistics is the discipline that concerns the collection, organization, analysis, interpretation, and presentation of data. In applying statistics to a scientific, industrial, or social problem, it is conventional to begin with a statistical population or a statistical model to be studied. Populations can be diverse groups of people or objects such as "all people living in a country" or "every atom composing a crystal". Statistics deals with every aspect of data, including the planning of data collection in terms of the design of surveys and experiments.

An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a particular factor is manipulated. Experiments vary greatly in goal and scale but always rely on repeatable procedure and logical analysis of the results. There also exist natural experimental studies.

In survival analysis, the hazard ratio (HR) is the ratio of the hazard rates corresponding to the conditions characterised by two distinct levels of a treatment variable of interest. For example, in a clinical study of a drug, the treated population may die at twice the rate per unit time of the control population. The hazard ratio would be 2, indicating higher hazard of death from the treatment.

Analysis of covariance (ANCOVA) is a general linear model which blends ANOVA and regression. ANCOVA evaluates whether the means of a dependent variable (DV) are equal across levels of a categorical independent variable (IV) often called a treatment, while statistically controlling for the effects of other continuous variables that are not of primary interest, known as covariates (CV) or nuisance variables. Mathematically, ANCOVA decomposes the variance in the DV into variance explained by the CV(s), variance explained by the categorical IV, and residual variance. Intuitively, ANCOVA can be thought of as 'adjusting' the DV by the group means of the CV(s).

Cross-validation, sometimes called rotation estimation or out-of-sample testing, is any of various similar model validation techniques for assessing how the results of a statistical analysis will generalize to an independent data set. Cross-validation is a resampling method that uses different portions of the data to test and train a model on different iterations. It is mainly used in settings where the goal is prediction, and one wants to estimate how accurately a predictive model will perform in practice. In a prediction problem, a model is usually given a dataset of known data on which training is run, and a dataset of unknown data against which the model is tested. The goal of cross-validation is to test the model's ability to predict new data that was not used in estimating it, in order to flag problems like overfitting or selection bias and to give an insight on how the model will generalize to an independent dataset.

Survival analysis is a branch of statistics for analyzing the expected duration of time until one event occurs, such as death in biological organisms and failure in mechanical systems. This topic is called reliability theory or reliability analysis in engineering, duration analysis or duration modelling in economics, and event history analysis in sociology. Survival analysis attempts to answer certain questions, such as what is the proportion of a population which will survive past a certain time? Of those that survive, at what rate will they die or fail? Can multiple causes of death or failure be taken into account? How do particular circumstances or characteristics increase or decrease the probability of survival?

Dependent and independent variables are variables in mathematical modeling, statistical modeling and experimental sciences. Dependent variables receive this name because, in an experiment, their values are studied under the supposition or demand that they depend, by some law or rule, on the values of other variables. Independent variables, in turn, are not seen as depending on any other variable in the scope of the experiment in question. In this sense, some common independent variables are time, space, density, mass, fluid flow rate, and previous values of some observed value of interest to predict future values.

A case–control study is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case–control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have that condition/disease with patients who do not have the condition/disease but are otherwise similar. They require fewer resources but provide less evidence for causal inference than a randomized controlled trial. A case–control study produces only an odds ratio, which is an inferior measure of strength of association compared to relative risk.

A nested case–control (NCC) study is a variation of a case–control study in which cases and controls are drawn from the population in a fully enumerated cohort.

Spatial analysis or spatial statistics includes any of the formal techniques which studies entities using their topological, geometric, or geographic properties. Spatial analysis includes a variety of techniques, many still in their early development, using different analytic approaches and applied in fields as diverse as astronomy, with its studies of the placement of galaxies in the cosmos, to chip fabrication engineering, with its use of "place and route" algorithms to build complex wiring structures. In a more restricted sense, spatial analysis is the technique applied to structures at the human scale, most notably in the analysis of geographic data or transcriptomics data.

The sign test is a statistical method to test for consistent differences between pairs of observations, such as the weight of subjects before and after treatment. Given pairs of observations for each subject, the sign test determines if one member of the pair tends to be greater than the other member of the pair.

Multilevel models are statistical models of parameters that vary at more than one level. An example could be a model of student performance that contains measures for individual students as well as measures for classrooms within which the students are grouped. These models can be seen as generalizations of linear models, although they can also extend to non-linear models. These models became much more popular after sufficient computing power and software became available.

Proportional hazards models are a class of survival models in statistics. Survival models relate the time that passes, before some event occurs, to one or more covariates that may be associated with that quantity of time. In a proportional hazards model, the unique effect of a unit increase in a covariate is multiplicative with respect to the hazard rate. For example, taking a drug may halve one's hazard rate for a stroke occurring, or, changing the material from which a manufactured component is constructed may double its hazard rate for failure. Other types of survival models such as accelerated failure time models do not exhibit proportional hazards. The accelerated failure time model describes a situation where the biological or mechanical life history of an event is accelerated.

In statistics, censoring is a condition in which the value of a measurement or observation is only partially known.

In the statistical area of survival analysis, an accelerated failure time model is a parametric model that provides an alternative to the commonly used proportional hazards models. Whereas a proportional hazards model assumes that the effect of a covariate is to multiply the hazard by some constant, an AFT model assumes that the effect of a covariate is to accelerate or decelerate the life course of a disease by some constant. This is especially appealing in a technical context where the 'disease' is a result of some mechanical process with a known sequence of intermediary stages.

In the statistical analysis of observational data, propensity score matching (PSM) is a statistical matching technique that attempts to estimate the effect of a treatment, policy, or other intervention by accounting for the covariates that predict receiving the treatment. PSM attempts to reduce the bias due to confounding variables that could be found in an estimate of the treatment effect obtained from simply comparing outcomes among units that received the treatment versus those that did not. Paul R. Rosenbaum and Donald Rubin introduced the technique in 1983.

Events are often triggered when a stochastic or random process first encounters a threshold. The threshold can be a barrier, boundary or specified state of a system. The amount of time required for a stochastic process, starting from some initial state, to encounter a threshold for the first time is referred to variously as a first hitting time. In statistics, first-hitting-time models are a sub-class of survival models. The first hitting time, also called first passage time, of the barrier set with respect to an instance of a stochastic process is the time until the stochastic process first enters .

One application of multilevel modeling (MLM) is the analysis of repeated measures data. Multilevel modeling for repeated measures data is most often discussed in the context of modeling change over time ; however, it may also be used for repeated measures data in which time is not a factor.

Hypertabastic survival models were introduced in 2007 by Mohammad Tabatabai, Zoran Bursac, David Williams, and Karan Singh. This distribution can be used to analyze time-to-event data in biomedical and public health areas and normally called survival analysis. In engineering, the time-to event analysis is referred to as reliability theory and in business and economics it is called duration analysis. Other fields may use different names for the same analysis. These survival models are applicable in many fields such as biomedical, behavioral science, social science, statistics, medicine, bioinformatics, medicalinformatics, data science especially in machine learning, computational biology, business economics, engineering, and commercial entities. They not only look at the time to event, but whether or not the event occurred. These time-to-event models can be applied in a variety of applications for instance, time after diagnosis of cancer until death, comparison of individualized treatment with standard care in cancer research, time until an individual defaults on loans, relapsed time for drug and smoking cessation, time until property sold after being put on the market, time until an individual upgrades to a new phone, time until job relocation, time until bones receive microscopic fractures when undergoing different stress levels, time from marriage until divorce, time until infection due to catheter, and time from bridge completion until first repair.

Recurrent event analysis is a branch of survival analysis that analyzes the time until recurrences occur, such as recurrences of traits or diseases. Recurrent events are often analysed in social sciences and medical studies, for example recurring infections, depressions or cancer recurrences. Recurrent event analysis attempts to answer certain questions, such as: how many recurrences occur on average within a certain time interval? Which factors are associated with a higher or lower risk of recurrence?

## References

1. Austin PC, Latouche A, Fine JP (January 2020). "A review of the use of time-varying covariates in the Fine-Gray subdistribution hazard competing risk regression model". Statistics in Medicine. 39 (2): 103–113. doi:10.1002/sim.8399. PMC  . PMID   31660633.
2. Little TD (2013-02-01). The Oxford Handbook of Quantitative Methods, Vol. 2: Statistical Analysis. Oxford University Press. p. 397. ISBN   978-0-19-993490-4.